Academic Appointments


Administrative Appointments


  • Unit-based Medical Director, F-Ground, Stanford Hospital and Clinics (2009 - 2012)
  • Chair, Scientific Review Committee, Stanford Cancer Institute (2009 - 2012)

Current Research and Scholarly Interests


Clinical investigations in breast cancer include institutional and NSABP studies of chemoprevention, adjuvant therapy, psychosocial interventions, treatment of metastatic disease, methods of decreasing anthracycline cardiotoxicity, and modulation of multidrug resistance. Research in meta-analysis includes the performance of meta-analysis in a wide variety of settings in cancer treatment by the international Meta-Analysis Group in Cancer.

Computer science research efforts focus on computer-based systems for patient care. These include: the development of expert systems to assist in the care of patients with cancer (ONCOCIN) or AIDS (T-Helper); the development of computer-based systems using speech and pen-based input for medical records to access sources of medical knowledge; the design of three-dimensional methods of performing and representing literature searches; and the development of standards for implementing of medical computer-based systems; the development of smart agents and medical ontologies.

Clinical Trials


  • A Clinical Trial Comparing the Combination of TC Plus Bevacizumab to TC Alone and to TAC for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer Not Recruiting

    The main purpose of this study is to learn if adding bevacizumab to standard treatment with chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) for early stage HER2-negative breast cancer will prevent breast cancer from returning. A second purpose of this study is to learn if adding bevacizumab to treatment with chemotherapy will help women with HER2-negative breast cancer live longer. The researchers also want to learn about the side effects of the combination of drugs used in this study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer Not Recruiting

    The investigators propose to conduct a Phase I/randomized Phase II study design in order to test the tolerability and efficacy of AZD0530 (also called saracatinib) when used together with anastrozole in therapy for ER+ and/or PR+, postmenopausal breast cancer. The Phase I pharmacokinetic (PK) cohort of the study (cohort A) in postmenopausal women with metastatic breast cancer 2008-2009 showed initial safety,tolerability and good bioavailability of both drugs and determined the doses for use in the ongoing Phase II trial. In the randomized Phase II cohort of the study (cohort B), postmenopausal women with newly diagnosed, previously untreated ER+, HER2 negative breast cancer that is at least 2 cm or more in diameter by clinical exam or radiology will be randomized to either neoadjuvant treatment with anastrozole plus placebo, or anastrozole in combination with AZD0530 (saracatinib). The Phase II cohort will permit extended assays of tolerability, initial estimates of efficacy, and the investigation of molecular predictors of drug efficacy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Annabel Castaneda, 650-498-7977.

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  • A Phase 2 Study of Standard Chemotherapy Plus BSI-201 (a PARP Inhibitor) in the Neoadjuvant Treatment of Triple Negative Breast Cancer Not Recruiting

    This study will investigate whether the neoadjuvant combination of gemcitabine, carboplatin, and BSI-201 will cause a high percentage of triple negative breast cancer patients to achieve a pathologic complete response prior to surgery. Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pei-Jen Chang, (650) 725 - 0866.

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  • A Phase 3, Multi-Center Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer Not Recruiting

    The goal of this study was to determine the effect on overall survival and progression free survival by adding iniparib (BSI-201/SAR240550) to the combination of gemcitabine/carboplatin in adult patients with triple negative breast cancer (estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative). Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the poly (ADP-ribose) polymerase (PARP) inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Charlene Kranz, (650) 498 - 7977.

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  • A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Breast Cancer After Adjuvant Therapy Not Recruiting

    The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with HER-2-positive breast cancer. The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Breast Cancer After Adjuvant Therapy Not Recruiting

    The current trial, BNIT-BR-003, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2 following adjuvant chemotherapy in patients with HER-2-positive breast cancer. The intent of vaccination is to induce a combined antibody and T-cell anti-HER-2 immune response, which is intended to target HER-2-expressing tumor cells, and may induce tumor regression or slow progression of disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Metastatic Breast Cancer Not Recruiting

    The current trial, BNIT-BR-002, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2, with and without Herceptin, following 1st- or 2nd-line chemotherapy in patients with Her-2-positive metastatic breast cancer. The intent of vaccination is to induce anti-Her-2 immune responses, both antibody and T cell, that will then attack the Her-2 expressing tumors, and may induce tumor regression or slow progression of disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer Not Recruiting

    The primary purpose of this study is to determine whether breast cancer tumors respond (as measured by pathologic complete response: the absence of microscopic evidence of invasive tumor cells in the breast) to combined chemotherapy of AC(doxorubicin and cyclophosphamide) followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with HER2-positive breast cancer. Trastuzumab will also be given to all patients after surgery. The study will also evaluate the toxic effects of the chemotherapy combination, including effects on the heart, and will determine survival and progression-free survival 5 years after treatment. Also, the study will look at whether there are gene expression profiles in the tumor tissue that can predict pathologic complete response.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Adjuvant Chemotherapy in Treating Women Who Have Undergone Resection for Relapsed Breast Cancer; Chemotherapy as Adjuvant for LOcally Recurrent Breast Cancer Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether chemotherapy is effective in treating women who have undergone surgery and radiation therapy for relapsed breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of adjuvant chemotherapy in treating women who have undergone resection for local and/or regional relapsed breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Anastrozole and ZD1839 Compared With Fulvestrant and ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer Not Recruiting

    This randomized phase II trial is studying how well giving gefitinib together with anastrozole works compared to giving gefitinib together with fulvestrant in treating postmenopausal women with recurrent or metastatic breast cancer. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using anastrozole and fulvestrant may fight breast cancer by blocking the use of estrogen. Gefitinib (ZD1839) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It is not yet known whether gefitinib is more effective when combined with anastrozole or fulvestrant in treating breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nancy Mori, (650) 724 - 0201.

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  • Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer Not Recruiting

    This randomized phase III clinical trial studies chemotherapy with or without trastuzumab after surgery to see how well they work in treating women with invasive breast cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving chemotherapy after surgery may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether combination chemotherapy is more effective with trastuzumab in treating breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Amy Isaacson, 650-723-0501.

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  • Comparison of Two Combination Chemotherapy Regimens in Treating Women With Breast Cancer Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as fluorouracil, epirubicin, cyclophosphamide, and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating breast cancer. PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens to compare how well they work in treating women who have undergone surgery for breast cancer that has not spread to the lymph nodes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Docetaxel and Cyclophosphamide Compared to Anthracycline-Based Chemotherapy in Treating Women With HER2-Negative Breast Cancer Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of breast cancer cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different combinations may kill more breast cancer cells. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating women with non-metastatic breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Donna Adelman, 650-724-1953.

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  • Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole Not Recruiting

    There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • Intellectual Impairment in Women With Breast Cancer Not Recruiting

    RATIONALE: Breast cancer and its treatment may cause changes in a patient's ability to think, learn, and remember. Gathering information about a woman's genes, brain function, and personal history may help doctors learn more about the disease and plan the best treatment. PURPOSE: 1. To determine changes in brain function that occur following breast cancer chemotherapy. 2. To gain further understanding of the individual differences in brain function changes and recovery based on demographic, medical and treatment variables.

    Stanford is currently not accepting patients for this trial. For more information, please contact Shelli Kesler, PhD, 650-723-0058.

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  • Ph I/II of Vitamin D on Bone Mineral Density & Markers of Bone Resorption Not Recruiting

    Aromatase inhibitors are potent suppressors of breast cancer growth, but side effects include bone loss, fractures, arthralgias and myalgias. We hypothesize vitamin D administration might be beneficial in treating these symptoms and to protect bone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Charlene Kranz, (650) 498 - 7977.

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  • Phase 2 Anastrozole and Vandetanib (ZD6474) in Neoadjuvant Treatment of Postmenopausal Hormone Receptor-Positive Breast Cancer Not Recruiting

    In this study we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2 with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marcy Chen, (650) 723 - 8686.

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  • Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer Not Recruiting

    This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to determine whether lapatinib combined with chemotherapy was safe and resulted in an increase in pathologic complete response rates.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • Phase 2 Study of Gemzar, Taxol & Avastin Combination as 1st Line Treatment for Metastatic Breast Cancer Not Recruiting

    Single-institution phase 2 trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT Not Recruiting

    This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane staining in > 20% of cells as determined by immunohistochemical methods. A total of 10 patients will be imaged with 124I PET/CT (serial scans over 24 hour period) to determine radioiodide uptake and distribution in tumor tissue. Thyroid iodide uptake and retention will be blocked beginning one week prior to 124I PET/CT scan with thyroid hormone (T3) and methimazole (impedes organification). Tumor, organ and whole body dosimetry will be calculated in each patient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Radiation Therapy (WBI Versus PBI) in Treating Women Who Have Undergone Surgery For Ductal Carcinoma In Situ or Stage I or Stage II Breast Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in different ways may kill any tumor cells that remain after surgery. It is not yet known whether whole breast radiation therapy is more effective than partial breast radiation therapy in treating breast cancer. PURPOSE: This randomized phase III trial is studying whole breast radiation therapy to see how well it works compared to partial breast radiation therapy in treating women who have undergone surgery for ductal carcinoma in situ or stage I or stage II breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • S0307 Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer. Not Recruiting

    RATIONALE: Zoledronate, clodronate, or ibandronate may delay or prevent bone metastases in patients with nonmetastatic breast cancer. It is not yet known whether zoledronate is more effective than clodronate or ibandronate in treating breast cancer. PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to clodronate or ibandronate in treating women who have undergone surgery for stage I, stage II, or stage III breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mary Chen, (650) 723 - 8686.

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  • S0500 Treatment Decision Making Based on Blood Levels of Tumor Cells for Metastatic Breast Cancer Treated With Chemo Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Measuring blood levels of tumor cells may help in learning how well chemotherapy works to kill metastatic breast cancer cells and allow doctors to plan better treatment. When blood levels of tumor cells are high while receiving chemotherapy, it is not yet known whether it is more effective to change chemotherapy regimens at that time or wait until disease progression. PURPOSE: This randomized phase III trial is studying treatment decision making based on blood levels of tumor cells in women with metastatic breast cancer receiving chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pei-Jen Chang, (650) 725 - 0866.

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  • Sleep, Circadian Hormonal Dysregulation, and Breast Cancer Survival Not Recruiting

    Recent research provides evidence that disrupted circadian rhythms, including hormonal patterns and sleep, are associated with increased risk of breast cancer incidence and faster progression to mortality. We have observed that a loss of normal diurnal cortisol rhythm associated with more awakenings during the night predicts early mortality with metastatic breast cancer. Other recent studies have shown that nighttime shift work is associated with higher breast cancer incidence, and in a murine model disrupting circadian cortisol cycles produced a doubling of implanted tumor growth. There is also recent evidence that abnormal clock genes are associated with cancer. However, it is not clear whether sleep disruption per se affects breast cancer progression, or whether such an effect is mediated by hormonal and immune dysregulation of this prevalent and hormone-mediated cancer. We propose to study sleep disruption as a prognostic factor in the progression of metastatic breast cancer. We will also examine sleep patterns in association with disrupted circadian rhythms of cortisol, ACTH, and melatonin as well as measures of immune function known to be salient to breast cancer progression. These are natural killer cell cytoxicity and specific cytokine, IL-6. We plan to recruit 105 women 45 years through 75 years with metastatic or recurrent breast cancer and 20 age and SES-matched controls for a two-week at home sleep study with Actiwatch and two nights of in-home EEG monitoring, followed by 28 hours of continuous blood sampling and one night of EEG sleep monitoring in our lab at Stanford. This will provide a full examination of circadian hormones associated with sleep patterns. We will relate these assessments to the subsequent course of breast cancer progression. Results of this study will provide specific evidence regarding how improved sleep management may affect the course of breast cancer. Aim 1: To study 24-hr diurnal rhythms of HPA axis hormones and melatonin in women with metastatic or recurrent breast cancer. Hypothesis 1: Women with metastatic or recurrent breast cancer will have reduced amplitude and disrupted phase of 24-hr diurnal rhythms of cortisol, ACTH, and melatonin. Aim 2: To describe sleep disruption in women with metastatic breast cancer and examine psychosocial, endocrine, and immune factors that may be associated with sleep disruption. Hypothesis 2: Women with metastatic or recurrent breast cancer will have a higher incidence of both at home and laboratory-examined sleep disruption than control women without breast cancer. Hypothesis 3: Poorer sleep quality will be associated with more pain, more emotional suppression in response to stressors, less emotional support, greater depression and anxiety, and greater perceived and traumatic stress. Hypothesis 4: Poorer sleep quality and quantity of sleep and daytime sleepiness and fatigue will be associated with abnormal circadian neuroendocrine (i.e., cortisol, ACTH, and melatonin) and immune patterns (i.e., suppressed day and night time NK activity and loss of NK rhythms; increased day time IL-6 levels and /or loss of IL-6 rhythm). Aim 3: To study the relationship between sleep disruption and survival time among metastatic and recurrent breast cancer patients. Hypothesis 5: Poorer sleep quality and quantity of sleep will predict shorter survival. Hypothesis 6: Reduced diurnal amplitude and an abnormal phase of cortisol will predict shorter survival. Explanatory Aim 4: To investigate whether sleep disruption mediates the relation of psychosocial factors to health outcomes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Bita Nouriani, (650) 723 - 8479.

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  • Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer Not Recruiting

    RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer. PURPOSE: This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Vitamin D and Breast Cancer: Does Weight Make a Difference? Not Recruiting

    This is a research study of the effect of Vitamin D on breast cancer. We hope to learn whether Vitamin D can change characteristics of certain genes in a breast cancer tumor that affect its growth. We believe some of these characteristics may be influenced by body weight.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sumita Sood, 650-723-0186.

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2023-24 Courses


All Publications


  • The Value and Process of Inclusion: Using Sensitive, Respectful, and Inclusive Language and Images in NCCN Content. Journal of the National Comprehensive Cancer Network : JNCCN Freedman-Cass, D. A., Fischer, T., Alpert, A. B., Obedin-Maliver, J., Kunz, P. L., Koh, W. J., Carlson, R. W. 2023; 21 (5): 434-441

    Abstract

    A core component of NCCN's mission is to improve and facilitate equitable cancer care. Inclusion and representation of diverse populations are essential toward this goal of equity. Within NCCN's professional content, inclusivity increases the likelihood that clinicians are prepared to provide optimal oncology care to all patients; within NCCN's patient-facing content, it helps ensure that cancer information is relevant and accessible for all individuals. This article describes changes that have been made in the language and images used in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Guidelines for Patients to promote justice, respect, and inclusion for all patients with cancer. The goals are to use language that is person-first, nonstigmatizing, inclusive of individuals of all sexual orientations and gender identities, and anti-racist, anti-classist, anti-misogynist, anti-ageist, anti-ableist, and anti-fat-biased. NCCN also seeks to incorporate multifaceted diversity in images and illustrations. NCCN is committed to continued and expanding efforts to ensure its publications are inclusive, respectful, and trustworthy, and that they advance just, equitable, high-quality, and effective cancer care for all.

    View details for DOI 10.6004/jnccn.2023.7025

    View details for PubMedID 37156485

  • The NCCN 2022 Annual Conference JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Koh, W. 2022; 20 (5.5): 549-550

    View details for DOI 10.6004/jnccn.2022.5001

    View details for Web of Science ID 000814420100001

    View details for PubMedID 35660572

  • Development and evaluation of safety and effectiveness of novel cancer screening tests for routine clinical use with applications to multicancer detection technologies. Cancer Doubeni, C. A., Lau, Y. K., Lin, J. S., Pennello, G. A., Carlson, R. W. 2022; 128 Suppl 4: 883-891

    Abstract

    Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.

    View details for DOI 10.1002/cncr.33954

    View details for PubMedID 35133658

  • Reply to A. Pfob and C. Sidey-Gibbons. JCO clinical cancer informatics Barcenas, C. H., Song, J., Murthy, R. K., Raghavendra, A. S., Li, Y., Hsu, L., Carlson, R. W., Tripathy, D., Hortobagyi, G. N. 2022; 6: e2100171

    View details for DOI 10.1200/CCI.21.00171

    View details for PubMedID 35175860

  • The NCCN 2021 Virtual Congress: Hematologic Malignancies JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2021; 19 (11.5): 1323

    View details for DOI 10.6004/jnccn.2021.5100

    View details for Web of Science ID 000731434000001

    View details for PubMedID 34818626

  • Prognostic Model for De Novo and Recurrent Metastatic Breast Cancer. JCO clinical cancer informatics Barcenas, C. H., Song, J., Murthy, R. K., Raghavendra, A. S., Li, Y., Hsu, L., Carlson, R. W., Tripathy, D., Hortobagyi, G. N. 2021; 5: 789-804

    Abstract

    PURPOSE: Metastatic breast cancer (MBC) has a heterogeneous clinical course. We sought to develop a prognostic model for overall survival (OS) that incorporated contemporary tumor and clinical factors for estimating individual prognosis.METHODS: We identified patients with MBC from our institution diagnosed between 1998 and 2017. We developed OS prognostic models by Cox regression using demographic, tumor, and treatment variables. We assessed model predictive accuracy and estimated annual OS probabilities. We evaluated model discrimination and prediction calibration using an external validation data set from the National Comprehensive Cancer Network.RESULTS: We identified 10,655 patients. A model using age at diagnosis, race or ethnicity, hormone receptor and human epidermal growth factor receptor 2 subtype, de novo versus recurrent MBC categorized by metastasis-free interval, Karnofsky performance status, organ involvement, frontline biotherapy, frontline hormone therapy, and the interaction between variables significantly improved predictive accuracy (C-index, 0.731; 95% CI, 0.724 to 0.739) compared with a model with only hormone receptor and human epidermal growth factor receptor 2 status (C-index, 0.617; 95% CI, 0.609 to 0.626). The extended Cox regression model consisting of six independent models, for < 3, 3-14, 14-20, 20-33, 33-61, and ≥ 61 months, estimated up to 5 years of annual OS probabilities. The selected multifactor model had good discriminative ability but suboptimal calibration in the group of 2,334 National Comprehensive Cancer Network patients. A recalibration model that replaced the baseline survival function with the average of those from the training and validation data improved predictions across both data sets.CONCLUSION: We have generated and validated a robust prognostic OS model for MBC. This model can be used in clinical decision making and stratification in clinical trials.

    View details for DOI 10.1200/CCI.21.00020

    View details for PubMedID 34351787

  • The NCCN 2021 Virtual Annual Conference JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2021; 19 (5.5): 581-582
  • The NCCN 2020 Virtual Congress: Hematologic Malignancies JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2020; 18 (12): 1741

    View details for DOI 10.6004/jnccn.2020.5030

    View details for Web of Science ID 000605166600001

    View details for PubMedID 33302257

  • The NCCN 2020 Virtual Annual Conference JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2020; 18 (7): 917–18
  • Comment on "Replacing the NCCN's Blocks with Wheels: How Should Consideration of Societal Spending be Incorporated into Oncology Practice?" PharmacoEconomics Koh, W., Carlson, R. W. 2020

    View details for DOI 10.1007/s40273-020-00938-y

    View details for PubMedID 32588390

  • NCCN resource-stratified and harmonized guidelines: A paradigm for optimizing global cancer care. Cancer Koh, W. J., Anderson, B. O., Carlson, R. W. 2020; 126 Suppl 10: 2416–23

    Abstract

    Clinical practice guidelines in oncology lead to improved outcomes in care. However, the most frequently used guidelines are developed for highly resourced systems. Recognizing the significant and increasing burden of cancer in low- and middle-income countries, the National Comprehensive Cancer Network (NCCN) has developed resource-stratified framework and harmonization processes that allow the NCCN Guidelines to be tailored and optimized for specific geographical areas, resource levels, and settings. The critical need for local expertise and involvement in successful development and uptake is emphasized, and the promise of this collaboration for advancement in oncology programs is illustrated.

    View details for DOI 10.1002/cncr.32880

    View details for PubMedID 32348572

  • The NCCN 2019 Annual Congress: Hematologic Malignancies JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2019; 17 (11): 1407

    View details for DOI 10.6004/jnccn.2019.5025

    View details for Web of Science ID 000499644200001

    View details for PubMedID 31766015

  • Policy Challenges and Opportunities to Address Changing Paradigms in Cancer Care Delivery. Journal of the National Comprehensive Cancer Network : JNCCN Winckworth-Prejsnar, K., McCanney, J., Schatz, A. A., Smedley, W., Platanias, L. C., Benitez, C. M., Newcomer, L. N., Fitzgerald, C. L., Carlson, R. W. 2019; 17 (5): 424–31

    Abstract

    Multiple factors are forcing the healthcare delivery system to change. A movement toward value-based payment models is shifting these systems to team-based integration and coordination of care for better efficiencies and outcomes. Workforce shortages are stressing access and quality of care for patients with cancer and survivors, and their families and caregivers. Innovative therapies are expensive, forcing payers and employers to prioritize resources. Patients are advocating for care models centered on their needs rather than those of providers. In response, payment policies have recently focused on the promotion of alternative payment models that incentivize coordinated, high-quality care with consideration for value and controlling the increasing overall costs associated with cancer and its treatment. Given the multitude of factors confounding cancer care, NCCN convened a multistakeholder working group to examine the challenges and opportunities presented by changing paradigms in cancer care delivery. The group identified key challenges and developed policy recommendations to address 4 high-visibility topics in cancer care delivery. The findings and recommendations were then presented at the NCCN Policy Summit: Policy Challenges and Opportunities to Address Changing Paradigms in Cancer Care Delivery in September 2018, and multistakeholder roundtable panel discussions explored these findings and recommendations along with additional items. This article encapsulates the discussion from the NCCN Working Group meetings and the NCCN Policy Summit, including multistakeholder policy recommendations on delivery issues in cancer care designed to help inform national policies moving forward.

    View details for DOI 10.6004/jnccn.2019.7299

    View details for PubMedID 31085764

  • The NCCN 2019 Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W. 2019; 17 (5): 529–30

    View details for DOI 10.6004/jnccn.2019.5001

    View details for Web of Science ID 000468988700001

    View details for PubMedID 31117029

  • Breast Cancer Diagnosis and Treatment in Low- and Mid-Resource Settings: the Role of Resource-Stratified Clinical Practice Guidelines CURRENT BREAST CANCER REPORTS El Saghir, N. S., El Tomb, P. A., Carlson, R. W. 2018; 10 (3): 187–95
  • Tumor BRCA1 Reversion Mutation Arising During Neoadjuvant Platinum-Based Chemotherapy in Triple-Negative Breast Cancer Is Associated with Therapy Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research Afghahi, A., Timms, K. M., Vinayak, S., Jensen, K. C., Kurian, A. W., Carlson, R. W., Chang, P., Schackmann, E. A., Hartman, A., Ford, J. M., Telli, M. L. 2017

    Abstract

    In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy.PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80). All patients underwent comprehensive BRCA1/2 genotyping. For mutation carriers with moderate or extensive residual disease after neoadjuvant therapy, BRCA1/2 status was re-sequenced in the residual surgical breast tumor tissue.Nineteen patients had a deleterious germline BRCA1/2 mutation and 4 had moderate residual disease at surgery. BRCA1/2 sequencing of residual tissue was performed on three patients. These patients had BRCA1 1479delAG, 3374insGA and W1712X mutations, respectively, with loss of heterozygosity at these loci in the pre-treatment tumors. In the first case, a new BRCA1 mutation was detected in the residual disease. This resulted in a 14 amino acid deletion and restoration of the BRCA1 reading frame. A local relapse biopsy four months later revealed the identical reversion mutation, and the patient subsequently died of metastatic breast cancer.We report a BRCA1 reversion mutation in a newly diagnosed triple-negative breast cancer patient that developed over 18 weeks of platinum-based neoadjuvant therapy. This was associated with poor therapy response, early relapse and death.

    View details for DOI 10.1158/1078-0432.CCR-16-2174

    View details for PubMedID 28087643

  • Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors. JAMA oncology Carlson, R. W., McClure, J. S. 2016

    View details for DOI 10.1001/jamaoncol.2016.4919

    View details for PubMedID 27787555

  • Emerging Issues and Opportunities in Health Information Technology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Nardi, E. A., Lentz, L. K., Winckworth-Prejsnar, K., Abernethy, A. P., Carlson, R. W. 2016; 14 (10): 1226-1233

    Abstract

    When used effectively, health information technology (HIT) can transform clinical care and contribute to new research discoveries. Despite advances in HIT and increased electronic health record adoption, many challenges to optimal use, interoperability, and data sharing exist. Data standardization across systems is limited, and scanned medical note documents result in unstructured data that make reporting on quality measures for reimbursement burdensome. Different policies and initiatives, including the Health Information Technology for Economic and Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the National Cancer Moonshot initiative, among others, all recognize the impact that HIT can have on cancer care. Given the growing role HIT plays in health care, it is vital to have effective and efficient HIT systems that can exchange information, collect credible data that is analyzable at the point of care, and improves the patient-provider relationship. In June 2016, NCCN hosted the Emerging Issues and Opportunities in Health Information Technology Policy Summit. The summit addressed challenges, issues, and opportunities in HIT as they relate to cancer care. Keynote presentations and panelists discussed moving beyond Meaningful Use, HIT readiness to support and report on quality care, the role of HIT in precision medicine, the role of HIT in the National Cancer Moonshot initiative, and leveraging HIT to improve quality of clinical care.

    View details for Web of Science ID 000385057100004

    View details for PubMedID 27697977

  • NCCN Framework for Resource Stratification: A Framework for Providing and Improving Global Quality Oncology Care. Journal of the National Comprehensive Cancer Network Carlson, R. W., Scavone, J. L., Koh, W., McClure, J. S., Greer, B. E., Kumar, R., McMillian, N. R., Anderson, B. O. 2016; 14 (8): 961-969

    Abstract

    More than 14 million new cancer cases and 8.2 million cancer deaths are estimated to occur worldwide on an annual basis. Of these, 57% of new cancer cases and 65% of cancer deaths occur in low- and middle-income countries. Disparities in available resources for health care are enormous and staggering. The WHO estimates that the United States and Canada have 10% of the global burden of disease, 37% of the world's health workers, and more than 50% of the world's financial resources for health; by contrast, the African region has 24% of the global burden of disease, 3% of health workers, and less than 1% of the world's financial resources for health. This disparity is even more extreme with cancer. NCCN has developed a framework for stratifying the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to help health care systems in providing optimal care for patients with cancer with varying available resources. This framework is modified from a method developed by the Breast Health Global Initiative. The NCCN Framework for Resource Stratification (NCCN Framework) identifies 4 resource environments: basic resources, core resources, enhanced resources, and NCCN Guidelines, and presents the recommendations in a graphic format that always maintains the context of the NCCN Guidelines. This article describes the rationale for resource-stratified guidelines and the methodology for developing the NCCN Framework, using a portion of the NCCN Cervical Cancer Guideline as an example.

    View details for PubMedID 27496112

  • Value, Access, and Cost of Cancer Care Delivery at Academic Cancer Centers JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Nardi, E. A., Wolfson, J. A., Rosen, S. T., Diasio, R. B., Gerson, S. L., Parker, B. A., Alvarnas, J. C., Levine, H. A., Fong, Y., Weisenburger, D. D., Fitzgerald, C. L., Egan, M., Stranford, S., Carlson, R. W., Benz, E. J. 2016; 14 (7): 837-847

    Abstract

    Key challenges facing the oncology community today include access to appropriate, high quality, patient-centered cancer care; defining and delivering high-value care; and rising costs. The National Comprehensive Cancer Network convened a Work Group composed of NCCN Member Institution cancer center directors and their delegates to examine the challenges of access, high costs, and defining and demonstrating value at the academic cancer centers. The group identified key challenges and possible solutions to addressing these issues. The findings and recommendations of the Work Group were then presented at the Value, Access, and Cost of Cancer Care Policy Summit in September 2015 and multi-stakeholder roundtable panel discussions explored these findings and recommendations along with additional items.

    View details for Web of Science ID 000380175200005

    View details for PubMedID 27407124

  • Clinical Breast Examination and Breast Cancer Screening Guideline. JAMA Anderson, B. O., Bevers, T. B., Carlson, R. W. 2016; 315 (13): 1403-1404

    View details for DOI 10.1001/jama.2016.0686

    View details for PubMedID 27046372

  • Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105. Journal of clinical oncology Telli, M. L., Jensen, K. C., Vinayak, S., Kurian, A. W., Lipson, J. A., Flaherty, P. J., Timms, K., Abkevich, V., Schackmann, E. A., Wapnir, I. L., Carlson, R. W., Chang, P., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B., Dakhil, S. R., Reid, J. E., Hartman, A., Manola, J., Ford, J. M. 2015; 33 (17): 1895-1901

    Abstract

    This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor-negative (≤ 5%), progesterone receptor-negative (≤ 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

    View details for DOI 10.1200/JCO.2014.57.0085

    View details for PubMedID 25847929

  • Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105 JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Jensen, K. C., Vinayak, S., Kurian, A. W., Lipson, J. A., Flaherty, P. J., Timms, K., Abkevich, V., Schackmann, E. A., Wapnir, I. L., Carlson, R. W., Chang, P., Sparano, J. A., Head, B., Goldstein, L. J., Haley, B., Dakhil, S. R., Reid, J. E., Hartman, A., Manola, J., Ford, J. M. 2015; 33 (17): 1895-U57

    Abstract

    This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor-negative (≤ 5%), progesterone receptor-negative (≤ 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

    View details for DOI 10.1200/JCO.2014.57.0085

    View details for Web of Science ID 000355999800009

    View details for PubMedID 25847929

  • Phase III Study of Iniparib Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin in Patients With Metastatic Triple-Negative Breast Cancer JOURNAL OF CLINICAL ONCOLOGY O'Shaughnessy, J., Schwartzberg, L., Danso, M. A., Miller, K. D., Rugo, H. S., Neubauer, M., Robert, N., Hellerstedt, B., Saleh, M., Richards, P., Specht, J. M., Yardley, D. A., Carlson, R. W., Finn, R. S., Charpentier, E., Garcia-Ribas, I., Winer, E. P. 2014; 32 (34): 3840-U232

    Abstract

    There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial.Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression.Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC.The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.

    View details for DOI 10.1200/JCO.2014.55.2984

    View details for Web of Science ID 000345904300012

    View details for PubMedID 25349301

  • Solid Malignancies in Individuals With Down Syndrome: A Case Presentation and Literature Review JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Bratman, S. V., Horst, K. C., Carlson, R. W., Kapp, D. S. 2014; 12 (11): 1537-1545

    Abstract

    Individuals with Down syndrome (DS) are at elevated risk for acute leukemia, whereas solid tumors are uncommon, and most types, including breast cancers, have significantly lower-than-expected age-adjusted incidence rates. This article reports on a man with DS and breast cancer, thought to be the first in the literature, and presents the management of his cancer. The literature on malignancies in patients with DS is reviewed and the major epidemiologic studies that have examined the spectrum of cancer risk in individuals with DS are summarized. Potential environmental and genetic determinants of cancer risk are discussed, and the potential role of chromosomal mosaicism in cancer risk among patients with DS is explored. Trisomy of chromosome 21, which causes DS, provides an extra copy of genes with tumor suppressor or repressor functions. Recent studies have leveraged mouse and human genetics to uncover specific candidate genes on chromosome 21 that mediate these effects. In addition, global perturbations in gene expression programs have been observed, with potential effects on proliferation and self-renewal.

    View details for Web of Science ID 000344516200007

  • NCCN Working Group report: designing clinical trials in the era of multiple biomarkers and targeted therapies. Journal of the National Comprehensive Cancer Network Venook, A. P., Arcila, M. E., Benson, A. B., Berry, D. A., Camidge, D. R., Carlson, R. W., Choueiri, T. K., Guild, V., Kalemkerian, G. P., Kurzrock, R., Lovly, C. M., Mckee, A. E., Morgan, R. J., Olszanski, A. J., Redman, M. W., Stearns, V., McClure, J., Birkeland, M. L. 2014; 12 (11): 1629-1649

    Abstract

    Defining treatment-susceptible or -resistant populations of patients with cancer through the use of genetically defined biomarkers has revolutionized cancer care in recent years for some disease/patient groups. Research continues to show that histologically defined diseases are diverse in their expression of unique mutations or other genetic alterations, however, which presents opportunities for the development of personalized cancer treatments, but increased difficulty in testing these therapies, because potential patient populations are divided into ever smaller numbers. To address some of the growing challenges in biomarker development and clinical trial design, NCCN assembled a group of experts across specialties and solid tumor disease types to begin to define the problems and to consider alternate ways of designing clinical trials in the era of multiple biomarkers and targeted therapies. Results from that discussion are presented, focusing on issues of clinical trial design from the perspective of statisticians, clinical researchers, regulators, pathologists, and information developers.

    View details for PubMedID 25361808

  • NCCN Working Group Report: Designing Clinical Trials in the Era of Multiple Biomarkers and Targeted Therapies JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Venook, A. P., Arcila, M. E., Benson, A. B., Berry, D. A., Camidge, D. R., Carlson, R. W., Choueiri, T. K., Guild, V., Kalemkerian, G. P., Kurzrock, R., Lovly, C. M., Mckee, A. E., Morgan, R. J., Olszanski, A. J., Redman, M. W., Stearns, V., McClure, J., Birkeland, M. L. 2014; 12 (11): 1629-1649
  • International Adaptations of NCCN Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Larsen, J. K., McClure, J., Fitzgerald, L., Venook, A. P., Benson, A. B., Anderson, B. O. 2014; 12 (5): 643-648

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) are evidence- and consensus-based clinical practice guidelines addressing malignancies that affect more than 97% of all patients with cancer in the United States. The NCCN Guidelines are used extensively in the United States and globally. Use of the guidelines outside the United States has driven the need to adapt the guidelines based on local, regional, or national resources. The NCCN Guidelines Panels created, vetted, and continually update the NCCN Guidelines based on published scientific data on cancer detection, diagnosis, and treatment efficacy. The guidelines are developed within the context of commonly available resources, methods of payment, societal and cultural expectations, and governmental regulations as they exist in the United States. Although many of the cancer management recommendations contained in the NCCN Guidelines apply broadly from a global perspective, not all do. Disparities in availability and access to health care exist among countries, within countries, and among different social groups in the same country, especially regarding resources for cancer prevention, early detection, and treatment. In addition, different drug approval and payment processes result in regional variation in availability of and access to cancer treatment, especially highly expensive agents and radiation therapy. Differences in cancer risk, predictive biomarker expression, and pharmacogenetics exist across ethnic and racial groups, and therefore across geographic locations. Cultural and societal expectations and requirements may also require modification of NCCN Guidelines for use outside the United States. This article describes the adaptation process, using the recent Latin American adaptation of the 2013 NCCN Guidelines for Colorectal Cancer as an example.

    View details for Web of Science ID 000335718600006

    View details for PubMedID 24812133

  • Survivorship: Sexual Dysfunction (Male), Version 1.2013 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (3): 356-363

    Abstract

    Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.

    View details for Web of Science ID 000332777600009

    View details for PubMedID 24616541

  • Survivorship: Sexual Dysfunction (Female), Version 1.2013 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (2): 184-192

    Abstract

    Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.

    View details for Web of Science ID 000332213600005

    View details for PubMedID 24586080

  • Survivorship: introduction and definition. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (1): 34-45

    Abstract

    Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.

    View details for PubMedID 24453291

  • Tumor boards: optimizing the structure and improving efficiency of multidisciplinary management of patients with cancer worldwide. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting El Saghir, N. S., Keating, N. L., Carlson, R. W., Khoury, K. E., Fallowfield, L. 2014: e461-6

    Abstract

    Multidisciplinary management tumor boards are now conducted worldwide for the management of patients with cancer. Studies evaluating their influence on decision making and patient outcome are limited; however, single-center studies have reported significant changes in diagnosis and treatment plans. A survey from Arabic countries showed widespread use and reliance on tumor boards for decision making. A recent multi-institutional survey of veteran affairs (VA) hospitals in the United States found limited association between the presence of tumor boards and care and outcomes. The Cancer Care Outcomes Research and Surveillance Consortium looked at the association between tumor board features and measures of quality of care. Results of overall survival among the patients of these physicians participating in tumor boards is ongoing, but preliminary results are outlined along with a recent ASCO survey of international members on the presence, utilization, and influence of tumor boards in this article. Tumor boards allow for implementation of clinical practice guidelines and may help capture cases for clinical trials. Efforts to improve preparations, structure, and conduct of tumor boards, research methods to monitor their performance, teamwork, and outcomes are outlined also in this article. The concept of mini-tumor boards and more efficient methods for MDM in countries with limited resources are also discussed. In suboptimal settings, such as small community hospitals, rural areas, and areas with limited resources, boundaries in diagnosis and management can be overcome, or at least improved, with tumor boards, especially with the use of video-conferencing facilities. Studies from the United Kingdom showed that special training of multidisciplinary teams (MDT) led to better team dynamics and communication, improved patient satisfaction, and improved clinical outcome. The weight of the benefits versus the time and effort spent to improve efficiency, patient care, and better time management in the United States and in the international oncology community is also reviewed in this article.

    View details for DOI 10.14694/EdBook_AM.2014.34.e461

    View details for PubMedID 24857140

  • Survivorship: Introduction and Definition JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (1): 34-45

    Abstract

    Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.

    View details for Web of Science ID 000330333200005

    View details for PubMedID 24453291

  • Breast Cancer, Version 3.2013 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Theriault, R. L., Carlson, R. W., Allred, C., Anderson, B. O., Burstein, H. J., Edge, S. B., Farrar, W. B., Forero, A., Giordano, S. H., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Isakoff, S. J., Ljung, B. E., Mankoff, D. A., Marcom, P. K., Mayer, I. A., McCormick, B., Pierce, L. J., Reed, E. C., Schwartzberg, L. S., Smith, M. L., Soliman, H., Somlo, G., Ward, J. H., Wolff, A. C., Zellars, R., Shead, D. A., Kumar, R. 2013; 11 (7): 753-761

    Abstract

    These NCCN Guidelines Insights highlight the important updates specific to the management of HER2-positive metastatic breast cancer in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. These include new first-line and subsequent therapy options for patients with HER2-positive metastatic breast cancer.

    View details for Web of Science ID 000321614400003

    View details for PubMedID 23847214

  • mTOR Inhibitors in the Treatment of Breast Cancer ONCOLOGY-NEW YORK Vinayak, S., Carlson, R. W. 2013; 27 (1): 38-?

    Abstract

    The phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly dysregulated in breast cancer. In preclinical studies, hyperactivation of the PI3K pathway has been linked to resistance to both endocrine therapy and trastuzumab (Herceptin). Rapalogs, agents that primarily inhibit mTOR-raptor complex 1, have been studied in combination with endocrine therapy to overcome endocrine resistance.Trials of combination endocrine therapy and rapalogs in metastatic hormone receptor-positive breast cancer have demonstrated variable results. However, two independent trials have recently shown that combination everolimus (Afinitor) and tamoxifen or combination everolimus and exemestane (Aromasin) is more effective than either endocrine agent alone. These trials selected patients with cancer refractory to endocrine therapy, which may be important in sensitizing tumors to inhibition of this pathway. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the early clinical data with combinations of PI3K/mTOR inhibitors and anti-HER2 therapies are encouraging. Efforts to identify clinical biomarkers of response or resistance to mTOR inhibitors are ongoing. This review will summarize results of preclinical and clinical studies aswell as ongoing clinical trials with mTOR or dual PI3K/mTOR inhibitors.

    View details for Web of Science ID 000314141000003

    View details for PubMedID 23461041

  • Metastatic Breast Cancer, Version 1.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Allred, D. C., Anderson, B. O., Burstein, H. J., Edge, S. B., Farrar, W. B., Forero, A., Giordano, S. H., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Isakoff, S. J., Ljung, B. E., Mankoff, D. A., Marcom, P. K., Mayer, I. A., McCormick, B., Pierce, L. J., Reed, E. C., Smith, M. L., Soliman, H., Somlo, G., Theriault, R. L., Ward, J. H., Wolff, A. C., Zellars, R., Kumar, R., Shead, D. A. 2012; 10 (7): 821-829

    Abstract

    These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.

    View details for Web of Science ID 000306303900006

    View details for PubMedID 22773798

    View details for PubMedCentralID PMC3753191

  • A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer BREAST CANCER RESEARCH AND TREATMENT Carlson, R. W., O'Neill, A., Vidaurre, T., Gomez, H. L., Badve, S. S., Sledge, G. W. 2012; 133 (3): 1049-1056

    Abstract

    EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. The primary endpoint was clinical benefit (complete responses plus partial responses plus stable disease for 6 months or longer). 141 eligible subjects were enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44% [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI 29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus 5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+) versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity.

    View details for DOI 10.1007/s10549-012-1997-5

    View details for Web of Science ID 000305914900022

    View details for PubMedID 22418699

    View details for PubMedCentralID PMC3587179

  • Effect of stimulation of natural killer cells with an anti-CD137 mAb on the efficacy of trastuzumab, cetuximab, and rituximab 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Kohrt, H. E., Houot, R., Weiskopf, K., Goldstein, M., Lund, P., Scheeren, F., Czerwinski, D., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., Sunwoo, J., Tedder, T., Chen, L., Levy, R. AMER SOC CLINICAL ONCOLOGY. 2012
  • Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines PLOS ONE Powell, A. A., Talasaz, A. H., Zhang, H., Coram, M. A., Reddy, A., Deng, G., Telli, M. L., Advani, R. H., Carlson, R. W., Mollick, J. A., Sheth, S., Kurian, A. W., Ford, J. M., Stockdale, F. E., Quake, S. R., Pease, R. F., Mindrinos, M. N., Bhanot, G., Dairkee, S. H., Davis, R. W., Jeffrey, S. S. 2012; 7 (5)

    Abstract

    To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy.For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery.

    View details for DOI 10.1371/journal.pone.0033788

    View details for PubMedID 22586443

  • Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer JOURNAL OF CLINICAL INVESTIGATION Kohrt, H. E., Houot, R., Weiskopf, K., Goldstein, M. J., Scheeren, F., Czerwinski, D., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., Stockdale, F. E., Mollick, J. A., Chen, L., Levy, R. 2012; 122 (3): 1066-1075

    Abstract

    Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2(+) breast cancer. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including NK cells, may improve the efficacy of trastuzumab. Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. CD137 activation, which was dependent on NK cell expression of the FcγRIII receptor, occurred both in vitro and in the peripheral blood of women with HER2-expressing breast cancer after trastuzumab treatment. Stimulation of trastuzumab-activated human NK cells with an agonistic mAb specific for CD137 killed breast cancer cells (including an intrinsically trastuzumab-resistant cell line) more efficiently both in vitro and in vivo in xenotransplant models of human breast cancer, including one using a human primary breast tumor. The enhanced cytotoxicity was restricted to antibody-coated tumor cells. This sequential antibody strategy, combining a tumor-targeting antibody with a second antibody that activates the host innate immune system, may improve the therapeutic effects of antibodies against breast cancer and other HER2-expressing tumors.

    View details for DOI 10.1172/JCI61226

    View details for Web of Science ID 000301021500029

    View details for PubMedID 22326955

    View details for PubMedCentralID PMC3287235

  • Breast Medical Oncologists' Use of Standard Prognostic Factors to Predict a 21-Gene Recurrence Score ONCOLOGIST Kamal, A. H., Loprinzi, C. L., Reynolds, C., Dueck, A. C., Geiger, X. J., Ingle, J. N., Carlson, R. W., Hobday, T. J., Winer, E. P., Goetz, M. P. 2011; 16 (10): 1359-1366

    Abstract

    Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX®; Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit. We explored the ability of oncologists to predict the RS using standard prognostic criteria.Standard demographic and tumor prognostic criteria were obtained from patients with an available RS. Two academic pathologists provided tumor grade, histologic type, and hormone receptor status. Six academic oncologists predicted the RS category (low, intermediate, or high) and provided a recommendation for therapy. The oncologists were then given the actual RS and provided recommendations for therapy. Analysis for agreement was performed.Thirty-one cases, including nine additional cases with variant pathology reads, were presented. There was substantial agreement in oncologists' ability to discriminate between true low or true intermediate and true high (κ = 0.75; p < .0001). Predictions between low and intermediate were not consistent. The most common discrepancies were predictions of a low RS risk when cases were true intermediate and predictions of an intermediate RS risk when cases were true low. The actual RS resulted in a change in the treatment recommendations in 19% of cases. Of the 186 scenarios and six oncologists in aggregate, five fewer chemotherapy recommendations resulted with the actual RS.Oncologists are able to differentiate between a low or intermediate RS and a high RS using standard prognostic criteria. However, provision of the actual RS changed the treatment recommendations in nearly 20% of cases, suggesting that the RS may reduce chemotherapy use. This effect was observed in particular in intermediate-risk cases. Prospective clinical trials are necessary to determine whether decisions based on the RS change outcomes.

    View details for DOI 10.1634/theoncologist.2011-0048

    View details for Web of Science ID 000296557500003

    View details for PubMedID 21934103

  • Treating Asymptomatic Chemotherapy-Induced Cardiac Dysfunction A Chance That Cardiologists and Oncologists Should Not Miss Reply JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Witteles, R. M., Yoon, G., Telli, M., Kao, D. P., Matsuda, K. Y., Carlson, R. W. 2011; 57 (17): 1790-1791
  • Breast cancer management in low resource countries (LRCs): Consensus statement from the Breast Health Global Initiative BREAST El Saghir, N. S., Adebamowo, C. A., Anderson, B. O., Carlson, R. W., Bird, P. A., Corbex, M., Badwe, R. A., Bushnaq, M. A., Eniu, A., Gralow, J. R., Harness, J. K., Masetti, R., Perry, F., Samiei, M., Thomas, D. B., Wiafe-Addai, B., Cazap, E. 2011; 20: S3-S11

    Abstract

    The Breast Health Global Initiative (BHGI) brought together international breast cancer experts to discuss breast cancer in low resource countries (LRCs) and identify common concerns reviewed in this consensus statement. There continues to be a lack of public and health care professionals' awareness of the importance of early detection of breast cancer. Mastectomy continues to be the most common treatment for breast cancer; and a lack of surgeons and anesthesia services was identified as a contributing factor in delayed surgical therapy in LRCs. Where available, radiation therapy is still more likely to be used for palliation rather than for curative treatment. Tumor receptor status is often suboptimally performed due to lack of advanced pathology services and variable quality control of tissue handling and processing. Regional pathology services can be a cost-effective approach and can serve as reference, training and research centers. Limited availability of medical oncologists in LRCs often results in non-specialist providing chemotherapeutic services, which requires additional supervision and training. Palliative care is an emerging field in LRCs that requires investment in training and infrastructure development. A commitment and investment in the development of breast cancer care services by LRC governments and health authorities remains a critical need in LRCs.

    View details for DOI 10.1016/j.breast.2011.02.006

    View details for Web of Science ID 000290194000002

    View details for PubMedID 21392996

  • Invasive Breast Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Allred, C., Anderson, B. O., Burstein, H. J., Carter, W. B., Edge, S. B., Erban, J. K., Farrar, W. B., Forero, A., Giordano, S. H., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Ljung, B., Mankoff, D. A., Marcom, P. K., Mayer, I. A., McCormick, B., Pierce, L. J., Reed, E. C., Sachdev, J., Smith, M. L., Somlo, G., Ward, J. H., Wolff, A. C., Zellars, R. 2011; 9 (2): 136-222

    View details for Web of Science ID 000287942900002

    View details for PubMedID 21310842

  • Left Ventricular Dysfunction in Patients Receiving Cardiotoxic Cancer Therapies Are Clinicians Responding Optimally? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Yoon, G. J., Telli, M. L., Kao, D. P., Matsuda, K. Y., Carlson, R. W., Witteles, R. M. 2010; 56 (20): 1644-1650

    Abstract

    The purpose of this study was to examine treatment practices for cancer therapy-associated decreased left ventricular ejection fraction (LVEF) detected on echocardiography and whether management was consistent with American College of Cardiology/American Heart Association guidelines.Patients treated with anthracyclines or trastuzumab are at risk of cardiotoxicity. Decreased LVEF represents a Class I indication for drug intervention according to American College of Cardiology/American Heart Association guidelines.Patients receiving anthracycline or trastuzumab at Stanford University from October 2005 to October 2007 and who had undergone echocardiography before and after receiving an anthracycline or trastuzumab were identified. Chart review examined chemotherapy regimens, cardiac risk factors, imaging results, concomitant medications, and cardiology consultations.Eighty-eight patients received therapy with an anthracycline or trastuzumab and had a pre-treatment and follow-up echocardiogram. Ninety-two percent were treated with anthracyclines, 17% with trastuzumab after an anthracycline, and 8% with trastuzumab without previous treatment with anthracycline. Mean baseline LVEF was 60%, with 14% having a baseline <55%. Forty percent had decreased LVEF (<55%) after anthracycline and/or trastuzumab treatment. Of these patients, 40% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 51% beta-blocker therapy, and 54% cardiology consultation. Of patients with asymptomatic decreased LVEF, 31% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 35% beta-blocker therapy, and 42% cardiology consultation. Of those with symptomatic decreased LVEF, 67% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 100% beta-blocker therapy, and 89% cardiology consultation.Many cancer survivors are not receiving treatment consistent with heart failure guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of oncology patients receiving cardiotoxic therapy.

    View details for DOI 10.1016/j.jacc.2010.07.023

    View details for PubMedID 21050974

  • Breast Cancer: Noninvasive and Special Situations JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Allred, D. C., Anderson, B. O., Burstein, H. J., Carter, W. B., Edge, S. B., Erban, J. K., Farrar, W. B., Forero, A., Giordano, S. H., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Ljung, B., Marcom, P. K., Mayer, I. A., McCormick, B., Pierce, L. J., Reed, E. C., Smith, M. L., Som, G., Topham, N. S., Ward, J. H., Winer, E. P., Wolff, A. C. 2010; 8 (10): 1182-1207

    View details for Web of Science ID 000283403400006

    View details for PubMedID 20971842

  • Breast Cancer Risk Reduction JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Bevers, T. B., Armstrong, D. K., Arun, B., Carlson, R. W., Cowan, K. H., Daly, M. B., Fleming, I., Garber, J. E., Gemignani, M., Gradishar, W. J., Krontiras, H., Kulkarni, S., Laronga, C., Loftus, L., MacDonald, D. J., Mahoney, M. C., Merajver, S. D., Meszoely, I., Newman, L., Pritchard, E., Seewaldt, V., Sellin, R. V., Shapiro, C. L., Ward, J. H. 2010; 8 (10): 1112-1146

    View details for Web of Science ID 000283403400002

    View details for PubMedID 20971838

  • Phase II Trial of Anastrozole Plus Goserelin in the Treatment of Hormone Receptor-Positive, Metastatic Carcinoma of the Breast in Premenopausal Women JOURNAL OF CLINICAL ONCOLOGY Carlson, R. W., Theriault, R., Schurman, C. M., Rivera, E., Chung, C. T., Phan, S., Arun, B., Dice, K., Chiv, V. Y., Green, M., Valero, V. 2010; 28 (25): 3917-3921

    Abstract

    To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin.Premenopausal women with estrogen and/or progesterone receptor-positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity.Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities.The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor-positive metastatic breast cancer.

    View details for DOI 10.1200/JCO.2009.24.9565

    View details for Web of Science ID 000281502500006

    View details for PubMedID 20679610

  • Ensuring Optimal Interdisciplinary Breast Care in the United States BREAST JOURNAL Anderson, B. O., Carlson, R. W., Kaufman, C. S., Kiel, K. D. 2009; 15 (6): 569-570
  • NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Allred, C., Carlson, R. W., Berry, D. A., Burstein, H. J., Edge, S. B., Goldstein, L. J., Gown, A., Hammond, M. E., Iglehart, J. D., Moench, S., Pierce, L. J., Ravdin, P., Schnitt, S. J., Wolff, A. C. 2009; 7: S1-S21

    Abstract

    The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.

    View details for Web of Science ID 000270360600001

    View details for PubMedID 19755043

  • Impaired interferon signaling is a common immune defect in human cancer PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Critchley-Thorne, R. J., Simons, D. L., Yan, N., Miyahira, A. K., Dirbas, F. M., Johnson, D. L., Swetter, S. M., Carlson, R. W., Fisher, G. A., Koong, A., Holmes, S., Lee, P. P. 2009; 106 (22): 9010-9015

    Abstract

    Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-alpha)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-gamma)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction.

    View details for DOI 10.1073/pnas.0901329106

    View details for PubMedID 19451644

  • First-Line Chemotherapy for Metastatic Breast Cancer CLINICAL BREAST CANCER Telli, M. L., Carlson, R. W. 2009; 9: S66-S72

    Abstract

    The selection of first-line chemotherapy for metastatic breast cancer (MBC) is complex because of the myriad of treatment options available and the inherent biologic heterogeneity of the disease. The potential treatment options are greatly influenced by estrogen and progesterone receptor and HER2 status of the tumor, and biopsy with reassessment of these markers at the time of disease recurrence is strongly recommended. Metastatic breast cancer is generally an incurable disease, with survival that could range from months to several years. Important but modest improvements in overall survival (OS) have been observed for women with MBC over the past few decades, in part because of improvements in systemic therapy. For women with endocrine-responsive disease, hormonal therapy is the appropriate initial treatment choice at the time of disease recurrence with rare exception. Initiation of systemic chemotherapy is appropriate for women with disease that is either hormone receptor negative, endocrine therapy refractory, or rapidly progressive with visceral involvement. The addition of trastuzumab to chemotherapy for women with HER2-positive breast cancer represents a clear standard of care. For HER2-negative MBC, sequential single-agent chemotherapy is preferred over combination therapy as a result of the more favorable toxicity profile and absence of a clinically significant improvement in survival with combination treatment. Many single-agent chemotherapeutic agents have activity in MBC, with most data supporting an anthracycline- or taxane-based approach. Bevacizumab in combination with chemotherapy prolongs progression-free survival in women with MBC, though its position in the first-line treatment of MBC relative to standard chemotherapy remains unclear at this time because of lack of OS benefit.

    View details for DOI 10.3816/CBC.2009.s.007

    View details for Web of Science ID 000267527100003

    View details for PubMedID 19596645

  • Randomized phase II trial of gefitinib plus anastrozole or fulvestrant in postmenopausal, metastatic breast cancer 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Carlson, R. W., O'Neill, A., Vidaurre, T., Gomez, H. L., Badve, S., Sledge, G. AMER SOC CLINICAL ONCOLOGY. 2009
  • Breast Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carlson, R. W., Allred, D. C., Anderson, B. O., Burstein, H. J., Carter, W. B., Edge, S. B., Erban, J. K., Farrar, W. B., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Jahanzeb, M., Kiel, K., Ljung, B., Marcom, P. K., Mayer, I. A., McCormick, B., Nabell, L. M., Pierce, L. J., Reed, E. C., Smith, M. L., Somlo, G., Theriault, R. L., Topham, N. S., Ward, J. H., Winer, E. P., Wolff, A. C. 2009; 7 (2): 122-?

    View details for Web of Science ID 000270264400005

    View details for PubMedID 19200416

  • Predictors and Temporal Trends of Adjuvant Aromatase Inhibitor Use in Breast Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Svahn, T. H., Niland, J. C., Carlson, R. W., Hughes, M. E., Ottesen, R. A., Theriault, R. L., Edge, S. B., Schott, A. F., Bookman, M. A., Weeks, J. C. 2009; 7 (2): 115-121

    Abstract

    After the first report of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, adjuvant aromatase inhibitor use increased rapidly among National Comprehensive Cancer Network member institutions. Increased aromatase inhibitor use was associated with older age, vascular disease, overexpression of human epidermal growth factor receptor 2 (HER2), or more advanced stage, and substantial variation was seen among institutions. This article examines adjuvant endocrine therapy in postmenopausal women after the first report of the trial, identifies temporal relationships in aromatase inhibitor use, and examines characteristics associated with choice of endocrine therapy among 4044 postmenopausal patients with hormone receptor-positive nonmetastatic breast cancer presenting from July 1997 to December 2004. Multivariable logistic regression analysis examined temporal associations and characteristics associated with aromatase inhibitor use. Time-trend analysis showed increased aromatase inhibitor and decreased tamoxifen use after release of ATAC results (P < .0001). In multivariable regression analysis, institution (P <. 0001), vascular disease (P <. 0001), age (P = .0002), stage (P = .0002), and HER2 status (P = .0009) independently predicted aromatase inhibitor use. Institutional rates of use ranged from 15% to 66%. Adjuvant aromatase inhibitor use increased after the first report of ATAC, with this increase associated with older age, vascular disease, overexpression of HER2, or more advanced stage. Substantial variation was seen among institutions.

    View details for Web of Science ID 000270264400004

    View details for PubMedID 19200415

  • A mufti-center phase II study of three doses of TAS-108 in postmenopausal women with advanced breast carcinoma following first or second line endocrine therapy. 31st Annual Meeting of the San Antonio Breast Cancer Symposium Buzdar, A., Tan-Chiu, E., Schwartzberg, L., Perez, A., Ellis, M., Garin, A., Ingle, J., Carlson, R. AMER ASSOC CANCER RESEARCH. 2009: 195S–195S
  • The Decline in Breast Cancer Incidence: Real or Imaginary? CURRENT ONCOLOGY REPORTS Kurian, A. W., Clarke, C. A., Carlson, R. W. 2009; 11 (1): 21-28

    Abstract

    Breast cancer is a major global problem, with nearly 1 million cases occurring each year. Over the past several decades, the disease's incidence has risen worldwide, increasing in developing and developed countries. This rise in breast cancer incidence has been attributed to changes in lifestyle and reproductive factors and to the dissemination of population-wide mammographic screening, which facilitates diagnosis. Recently, a decline in breast cancer incidence was reported in the United States and several other developed countries, and a substantial reduction in menopausal hormone therapy use was proposed as a possible cause. However, significant controversy remains as to the timing, causes, generalizability, and longevity of this reported decline in incidence.

    View details for Web of Science ID 000207843700006

    View details for PubMedID 19080738

  • Guideline Implementation for Breast Healthcare in Low-income and Middle-income Countries Overview of the Breast Health Global Initiative Global Summit 2007 CANCER Anderson, B. O., Yip, C., Smith, R. A., Shyyan, R., Sener, S. F., Eniu, A., Carlson, R. W., Azavedo, E., Harford, J. 2008; 113 (8): 2221-2243

    Abstract

    Breast cancer outcomes in low- and middle-income countries (LMCs) correlate with the degree to which 1) cancers are detected at early stages, 2) newly detected cancers can be diagnosed correctly, and 3) appropriately selected multimodality treatment can be provided properly in a timely fashion. The Breast Health Global Initiative (BHGI) invited international experts to review and revise previously developed BHGI resource-stratified guideline tables for early detection, diagnosis, treatment, and healthcare systems. Focus groups addressed specific issues in breast pathology, radiation therapy, and management of locally advanced disease. Process metrics were developed based on the priorities established in the guideline stratification. The groups indicated that cancer prevention through health behavior modification could influence breast cancer incidence in LMCs. Diagnosing breast cancer at earlier stages will reduce breast cancer mortality. Programs to promote breast self-awareness and clinical breast examination and resource-adapted mammographic screening are important early detection steps. Breast imaging, initially with ultrasound and, at higher resource levels with diagnostic mammography, improves preoperative diagnostic assessment and permits image-guided needle sampling. Multimodality therapy includes surgery, radiation, and systemic therapies. Government intervention is needed to address drug-delivery problems relating to high cost and poor access. Guideline dissemination and implementation research plays a crucial role in improving care. Adaptation of technology is needed in LMCs, especially for breast imaging, pathology, radiation therapy, and systemic treatment. Curricula for education and training in LMCs should be developed, applied, and studied in LMC-based learning laboratories to aid information transfer of evidence-based BHGI guidelines.

    View details for DOI 10.1002/cncr.23844

    View details for Web of Science ID 000260198200003

    View details for PubMedID 18816619

  • Locally Advanced Breast Cancer Treatment Guideline Implementation With Particular Attention to Low- and Middle-Income Countries CANCER El Saghir, N. S., Eniu, A., Carlson, R. W., Aziz, Z., Vorobiof, D., Hortobagyi, G. N. 2008; 113 (8): 2315-2324

    Abstract

    The management of locally advanced breast cancer (LABC) is guided by scientific advances but is limited by local resources and expertise. LABC remains very common in low-resource countries. The Systemic Therapy Focus Group met as part of the Breast Health Global Initiative (BHGI) Summit in Budapest, Hungary, in October 2007 to discuss management and implementation of primary systemic therapy (PST) for LABC. PST is standard treatment for large operable breast cancer in enhanced-resource settings and, in all resource settings, should be standard treatment for inoperable breast cancer and for LABC. Standard PST includes anthracycline-based chemotherapy. The addition of sequential taxanes after anthracycline improves pathologic responses and breast-conservation rates and is appropriate at enhanced-resource levels; however, costs and lack of clear survival benefit do not justify their use at limited-resource levels. It remains to define better the role of endocrine therapy as PST, but it is acceptable in elderly women. Aromatase inhibitors have produced better results than tamoxifen in postmenopausal patients and are used in enhanced-resource settings. The less expensive tamoxifen remains useful in low-resource countries. Trastuzumab combined with chemotherapy yields high pathologic response rates in patients with HER2/neu-overexpressing tumors; its use in low-resource countries is limited by high costs. Most studies on PST of LABC were conducted in countries with enhanced resources. BHGI encourages conducting clinical trials in countries with limited resources.

    View details for DOI 10.1002/cncr.23836

    View details for Web of Science ID 000260198200010

    View details for PubMedID 18837023

  • Guideline Implementation for Breast Healthcare in Low- and Middle-income Countries: Treatment Resource Allocation CANCER Eniu, A., Carlson, R. W., El Saghir, N. S., Bines, J., Bese, N. S., Vorobiof, D., Masetti, R., Anderson, B. O. 2008; 113 (8): 2269-2281

    Abstract

    A key determinant of breast cancer outcome is the degree to which newly diagnosed cancers are treated correctly in a timely fashion. Available resources must be applied in a rational manner to optimize population-based outcomes. A multidisciplinary international panel of experts addressed the implementation of treatment guidelines and developed process checklists for breast surgery, radiation treatment, and systemic therapy. The needed resources for stage I, stage II, locally advanced, and metastatic breast cancer were outlined, and process metrics were developed. The ability to perform modified radical mastectomy is the mainstay of locoregional treatment at the basic level of breast healthcare. Radiation therapy allows for consideration of breast-conserving therapy, postmastectomy chest wall irradiation, and palliation of painful or symptomatic metastases. Systemic therapy with cytotoxic chemotherapy is effective in the treatment of all biologic subtypes of breast cancer, but its provision is resource intensive. Although endocrine therapy requires few specialized resources, it requires knowledge of hormone receptor status. Targeted therapy against human epidermal growth factor receptor 2 (anti-HER-2) is very effective in tumors that overexpress HER-2/neu receptors, but cost largely prevents its use in resource-limited environments. Incremental allocation of resources can help address economic disparities and ensure equity in access to care. Checklists and allocation tables can support the objective of offering optimal care for all patients. The use of process metrics can facilitate the development of multidisciplinary, integrated, fiscally responsible, continuously improving, and flexible approaches to the global enhancement of breast cancer treatment.

    View details for DOI 10.1002/cncr.23843

    View details for Web of Science ID 000260198200006

    View details for PubMedID 18837019

  • Breast Pathology Guideline Implementation in Low- and Middle-income Countries CANCER Masood, S., Vass, L., Ibarra, J. A., Ljung, B., Stalsberg, H., Eniu, A., Carlson, R. W., Anderson, B. O. 2008; 113 (8): 2297-2304

    Abstract

    The quality of breast healthcare delivery and the ultimate clinical outcome for patients with breast cancer are directly related to the quality of breast pathology practices within the healthcare system. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary from October 1 to 4, 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for the early detection, diagnosis, and treatment in low-income and middle-income countries (LMCs). From this group, a subgroup of experts met to address the specific needs and concerns related to breast pathology program implementation in LMCs. Specific recommendations were made by the group and process indicators identified in the areas of personnel and training, cytology and histopathology interpretation, accuracy of pathology interpretation, pathology reporting, tumor staging, causes of diagnostic errors, use of immunohistochemical markers, and special requirements to facilitate breast conservation therapy. The group agreed that the financial burden of establishing and maintaining breast pathology services is counterbalanced by the cost savings from decreased adverse effects and excessive use of treatment resources that result from incorrect or incomplete pathologic diagnosis. Proper training in breast pathology for pathologists and laboratory technicians is critical and provides the underpinnings of programmatic success for any country at any level of economic wealth.

    View details for DOI 10.1002/cncr.23833

    View details for Web of Science ID 000260198200008

    View details for PubMedID 18837021

  • Selecting high priority quality measures for breast cancer quality improvement Geological-Society-of-America Penrose Conference Hassett, M. J., Hughes, M. E., Niland, J. C., Ottesen, R., Edge, S. B., Bookman, M. A., Carlson, R. W., Theriault, R. L., Weeks, J. C. LIPPINCOTT WILLIAMS & WILKINS. 2008: 762–70

    Abstract

    Although many quality measures have been created, there is no consensus regarding which are the most important. We sought to develop a simple, explicit strategy for prioritizing breast cancer quality measures based on their potential to highlight areas where quality improvement efforts could most impact a population.Using performance data for 9019 breast cancer patients treated at 10 National Comprehensive Cancer Network institutions, we assessed concordance relative to 30 reliable, valid breast cancer process-based treatment measures. We identified 4 attributes that indicated there was room for improvement and characterized the extent of burden imposed by failing to follow each measure: number of nonconcordant patients, concordance across all institutions, highest concordance at any 1 institution, and magnitude of benefit associated with concordant care. For each measure, we used data from the concordance analyses to derive the first 3 attributes and surveyed expert breast cancer physicians to estimate the fourth. A simple algorithm incorporated these attributes and produced a final score for each measure; these scores were used to rank the measures.We successfully prioritized quality measures using explicit, objective methods and actual performance data. The number of nonconcordant patients had the greatest influence on the rankings. The highest-ranking measures recommended chemotherapy and hormone therapy for hormone-receptor positive tumors and radiation therapy after breast-conserving surgery.This simple, explicit approach is a significant departure from methods used previously, and effectively identifies breast cancer quality measures that have broad clinical relevance. Systematically prioritizing quality measures could increase the efficiency and efficacy of quality improvement efforts and substantially improve outcomes.

    View details for Web of Science ID 000258014400002

    View details for PubMedID 18665055

  • New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients 30th Annual San Antonio Breast Cancer Symposium Kohrt, H., Olshen, R., Bermas, H., GOODSON, W., Henry, S., Rouse, R., Bailey, L., Philben, V., Dirbas, F., Dunn, J., Johnson, D., Wapnir, I., Carlson, R., STOCKDALE, F., Hansen, N., JEFFREY, S. SPRINGER. 2008: 588–88
  • New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients BMC CANCER Kohrt, H. E., Olshen, R. A., Bermas, H. R., Goodson, W. H., Wood, D. J., Henry, S., Rouse, R. V., Bailey, L., Philben, V. J., Dirbas, F. M., Dunn, J. J., Johnson, D. L., Wapnir, I. L., Carlson, R. W., Stockdale, F. E., Hansen, N. M., Jeffrey, S. S. 2008; 8

    Abstract

    Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.

    View details for DOI 10.1186/1471-2407-8-66

    View details for PubMedID 18315887

  • Interdisciplinary coordination for breast healthcare - A rational approach to detection, diagnosis, and treatment DISEASE MANAGEMENT & HEALTH OUTCOMES Anderson, B. O., Kaufman, C. S., Kiel, K. D., Carlson, R. W. 2008; 16 (1): 7-11
  • NCCN Task Force Report: breast cancer in the older woman. Journal of the National Comprehensive Cancer Network Carlson, R. W., Moench, S., Hurria, A., Balducci, L., Burstein, H. J., Goldstein, L. J., Gradishar, W. J., Hughes, K. S., Jahanzeb, M., Lichtman, S. M., Marks, L. B., McClure, J. S., McCormick, B., Nabell, L. M., Pierce, L. J., Smith, M. L., Topham, N. S., Traina, T. A., Ward, J. H., Winer, E. P. 2008; 6: S1-25

    Abstract

    Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.

    View details for PubMedID 18597715

  • MagSweeper: an automated system for high efficiency and specificity capture of live circulating tumor cells 30th Annual San Antonio Breast Cancer Symposium Powell, A. A., Talasaz, A. A., Mindrinos, M., Carlson, R., Pease, F. W., Davis, R. W., Jeffrey, S. S. SPRINGER. 2007: S24–S24
  • Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer - A randomized prospective trial 159th Annual Meeting of the American-Psychiatric-Association Spiegel, D., Butler, L. D., Giese-Davis, J., Koopman, C., Miller, E., DiMiceli, S., Classen, C. C., Fobair, P., Carlson, R. W., Kraemer, H. C. JOHN WILEY & SONS INC. 2007: 1130–38

    Abstract

    This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed.One hundred twenty-five women with confirmed metastatic (n = 122) or locally recurrent (n = 3) breast cancer were randomly assigned either to the supportive-expressive group therapy condition (n = 64), where they received educational materials plus weekly supportive-expressive group therapy, or to the control condition (n = 61), where they received only educational materials for a minimum of 1 year. The treatment, 90 minutes once a week, was designed to build new bonds of social support, encourage expression of emotion, deal with fears of dying and death, help restructure life priorities, improve communication with family members and healthcare professionals, and enhance control of pain and anxiety.Overall mortality after 14 years was 86%; median survival time was 32.8 months. No overall statistically significant effect of treatment on survival was found for treatment (median, 30.7 months) compared with control (median, 33.3 months) patients, but there was a statistically significant intervention site-by-condition interaction. Exploratory moderator analysis to explain that interaction revealed a significant overall interaction between estrogen-receptor (ER) status and treatment condition (P = .002) such that among the 25 ER-negative participants, those randomized to treatment survived longer (median, 29.8 months) than ER-negative controls (median, 9.3 months), whereas the ER-positive participants showed no treatment effect.The earlier finding that longer survival was associated with supportive-expressive group therapy was not replicated. Although it is possible that psychosocial effects on survival are relevant to a small subsample of women who are more refractory to current hormonal treatments, further research is required to investigate subgroup differences.

    View details for DOI 10.1002/cncr.22890

    View details for Web of Science ID 000249191100025

    View details for PubMedID 17647221

  • Stress history and breast cancer recurrence JOURNAL OF PSYCHOSOMATIC RESEARCH Palesh, O., Butler, L. D., Koopman, C., Giese-Davis, J., Carlson, R., Spiegel, D. 2007; 63 (3): 233-239

    Abstract

    There is mixed evidence regarding the possible association between a history of stressful or traumatic life events and more rapid breast cancer progression.Retrospective reports of past experiences of traumatic life events were assessed among 94 women with metastatic or recurrent breast cancer. A traumatic event assessment was conducted using the event-screening question from the posttraumatic stress disorder (PTSD) module of the Structured Clinical Interview for the DSM-IV-TR (SCID; 2002). Each reported event was judged by two independent raters to determine whether it met DSM-IV-TR PTSD A1 criteria for a traumatic event. Those events that did not meet such criteria were designated "stressful events."Nearly 42% of the women in the sample were judged to have experienced one or more traumatic events; 28.7% reported only stressful events. A Kruskal-Wallis test found significant differences in disease-free interval among the three groups [chi2 (2, N=94)=6.09, P<.05]. Planned comparisons revealed a significantly longer disease-free interval among women who had reported no traumatic or stressful life events (median=62 months) compared to those who had experienced one or more stressful or traumatic life events (combined median=31 months).A history of stressful or traumatic life events may reduce host resistance to tumor growth. These findings are consistent with a possible long-lasting effect of previous life stress on stress response systems such as the hypothalamic-pituitary-adrenal (HPA) axis.

    View details for DOI 10.1016/jjpsychores.2007.05.012

    View details for Web of Science ID 000249309300003

    View details for PubMedID 17719359

    View details for PubMedCentralID PMC2094358

  • Trastuzumab-related cardiotoxicity: Calling into question the concept of reversibility JOURNAL OF CLINICAL ONCOLOGY Telli, M. L., Hunt, S. A., Carlson, R. W., Guardino, A. E. 2007; 25 (23): 3525-3533

    Abstract

    To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials.The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context.Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%.Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2-positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

    View details for DOI 10.1200/JCO.2007.11.0106

    View details for Web of Science ID 000248744300023

    View details for PubMedID 17687157

  • Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer - The Women's Healthy Eating and Living (WHEL) Randomized Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pierce, J. P., Natarajan, L., Caan, B. J., Parker, B. A., Greenberg, E. R., Flatt, S. W., Rock, C. L., Kealey, S., Al-Delaimy, W. K., Bardwell, W. A., Carlson, R. W., Emond, J. A., Faerber, S., Gold, E. B., Hajek, R. A., Hollenbach, K., Jones, L. A., Karanja, N., Madlensky, L., Marshall, J., Newman, V. A., Ritenbaugh, C., Thomson, C. A., Wasserman, L., Stefanick, M. L. 2007; 298 (3): 289-298

    Abstract

    Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the "5-A-Day" dietary guidelines.Invasive breast cancer event (recurrence or new primary) or death from any cause.From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.clinicaltrials.gov Identifier: NCT00003787.

    View details for Web of Science ID 000248086700023

    View details for PubMedID 17635889

  • NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer. Journal of the National Comprehensive Cancer Network Podoloff, D. A., Advani, R. H., Allred, C., Benson, A. B., Brown, E., Burstein, H. J., Carlson, R. W., Coleman, R. E., Czuczman, M. S., Delbeke, D., Edge, S. B., Ettinger, D. S., Grannis, F. W., Hillner, B. E., Hoffman, J. M., Kiel, K., Komaki, R., Larson, S. M., Mankoff, D. A., Rosenzweig, K. E., Skibber, J. M., Yahalom, J., Yu, J. M., Zelenetz, A. D. 2007; 5: S1-22

    Abstract

    The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology.

    View details for PubMedID 17509259

  • A longitudinal study of depression, pain, and stress as predictors of sleep disturbance among women with metastatic breast cancer BIOLOGICAL PSYCHOLOGY Palesh, O. G., Collie, K., Batiuchok, D., Tilston, J., Koopman, C., Perlis, M. L., Butler, L. D., Carlson, R., Spiegel, D. 2007; 75 (1): 37-44

    Abstract

    Sleep disturbances are common among women with breast cancer and can have serious consequences. The present study examined depression, pain, life stress, and participation in group therapy in relation to sleep disturbances in a sample of women with metastatic breast cancer.Ninety-three women with metastatic breast cancer participated in a large intervention trial examining the effect of the group therapy on their symptoms. They completed measures of depression, pain, life stress, and sleep disturbance at baseline, 4, 8 and 12 months.The results showed that higher initial levels of depression at baseline predicted problems associated with getting up in the morning, waking up during the night, and daytime sleepiness. Increases in depression over the course of 12 months were associated with fewer hours of sleep, more problems with waking up during the night and more daytime sleepiness. Higher levels of pain at baseline predicted more problems getting to sleep. Increases in pain predicted more difficulty getting to sleep and more problems waking up during the night. Greater life stress at baseline predicted more problems getting to sleep and more daytime sleepiness.Depression, pain, and life stress scores were each associated with different types of negative change in self-reported sleep disturbances. Depression, especially worsening depression, was associated with the greatest number of types of negative change. The relationships found between sleep disturbance and depression, pain, and life stress suggest specific ways to address the problem of sleep disturbance for women with metastatic breast cancer and show how different types of disturbed sleep may be clinical markers for depression, pain, or life stress in this population.

    View details for DOI 10.1016/j.biopsycho.2006.11.002

    View details for Web of Science ID 000245832000006

    View details for PubMedID 17166646

    View details for PubMedCentralID PMC1894689

  • Phyllodes tumors of the breast: natural history, diagnosis, and treatment. Journal of the National Comprehensive Cancer Network Telli, M. L., Horst, K. C., Guardino, A. E., Dirbas, F. M., Carlson, R. W. 2007; 5 (3): 324-330

    Abstract

    Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a wide range of clinical behavior. These tumors are categorized as benign, borderline, or malignant based on a combination of histologic features. The prognosis of phyllodes tumors is favorable, with local recurrence occurring in approximately 15% of patients overall and distant recurrence in approximately 5% to 10% overall. Wide excision with a greater than 1 cm margin is definitive primary therapy. Adjuvant systemic therapy is of no proven value. Patients with locally recurrent disease should undergo wide excision of the recurrence with or without subsequent radiotherapy.

    View details for PubMedID 17439760

  • Invasive breast cancer. Journal of the National Comprehensive Cancer Network Carlson, R. W., Anderson, B. O., Burstein, H. J., Carter, W. B., Edge, S. B., Farrar, W. B., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C. A., Jahanzeb, M., Ljung, B., Kiel, K., Marks, L. B., McCormick, B., Nabell, L. M., Pierce, L. J., Reed, E. C., Silver, S. M., Smith, M. L., Somlo, G., Theriault, R. L., Ward, J. H., Winer, E. P., Wolff, A. C. 2007; 5 (3): 246-312

    View details for PubMedID 17439758

  • Guidelines for improving breast health care in limited resource countries: the Breast Health Global Initiative. Journal of the National Comprehensive Cancer Network Anderson, B. O., Carlson, R. W. 2007; 5 (3): 349-356

    Abstract

    Breast cancer is an increasingly urgent problem in low- and mid-level resource regions of the world. Despite knowing the optimal management strategy based on guidelines developed in wealthy countries, clinicians are forced to provide less-than-optimal care when diagnostic or treatment resources are lacking. For this reason, it is important to identify which resources most effectively fill health care needs in limited-resource regions, where patients commonly present with more advanced disease at diagnosis, and to provide guidance on how new resource allocations should be made to maximize improvement in outcome. Established in 2002, the Breast Health Global Initiative (BHGI) created an international health alliance to develop evidence-based guidelines for countries with limited resources to improve breast health outcomes. The BHGI serves as a program for international guideline development and as a hub for linkage among clinicians, governmental health agencies, and advocacy groups to translate guidelines into policy and practice. The BHGI collaborated with 12 national and international health organizations, cancer societies, and nongovernmental organizations to host 2 BHGI international summits. The evidence-based BHGI guidelines, developed at the 2002 Global Summit, were published in 2003 as a theoretical treatise on international breast health care. These guidelines were then updated and expanded at the 2005 Global Summit into a fully comprehensive and flexible framework to permit incremental improvements in health care delivery, based on outcomes, cost, cost-effectiveness, and use of health care services.

    View details for PubMedID 17439764

  • Supportive-expressive group therapy and survival in patients with metastatic breast cancer: A randomized clinical intervention trial 45th Annual Meeting of the American-College-of-Neuropsychopharmacology Spiegel, D., Butler, L. D., Giese-Davis, J., Koopman, C., Miller, E., DiMiceli, S., Classen, C., Fobair, P., Carlson, R. W., Kraemer, H. C. NATURE PUBLISHING GROUP. 2006: S134–S134
  • A pilot phase II trial of valspodar modulation of multidrug resistance to paclitaxel in the treatment of metastatic carcinoma of the breast (E1195): A trial of the eastern cooperative oncology group CANCER INVESTIGATION Carlson, R. W., O'Neill, A. M., Goldstein, L. J., Sikic, B. I., Abramson, N., Stewart, J. A., Davidson, N. E., Wood, W. C. 2006; 24 (7): 677-681

    Abstract

    To assess the activity and toxicity of valspodar (PSC-833) in combination with paclitaxel in women with anthracycline refractory, metastatic breast cancer.Limited, multi-institutional, Phase II trial of valspodar at 5 mg/kg/dose orally every 6 hours for 12 doses in combination with paclitaxel 70 mg/m2 administered intravenously as a 3-hour infusion beginning 4 hours after the fifth dose of valspodar, every 3 weeks. Eligible patients had bi-dimensionally measurable metastatic carcinoma of the breast, prior anthracycline therapy or a medical contraindication to anthracycline therapy, no more than one prior chemotherapy for recurrent or metastatic breast cancer, and adequate organ function. Treatment was continued until disease progression or unacceptable toxicity.Thirty-four patients are evaluable for response and 37 for toxicity. Two (6 percent) patients achieved a complete response and 5 (15 percent) a partial response for an objective response rate of 21 percent (95 percent confidence interval of 9 to 38 percent). Median duration of response was 9.7 months (95 percent confidence interval 8.0-17.2 months), median time to progression was 3.3 months (95 percent confidence interval 2.0-4.2 months), and median survival was 12 months (95 percent confidence interval 8.1-17.3 months). The toxicity experienced was acceptable.Combination valspodar plus paclitaxel is an active regimen and has acceptable toxicity. The combination is not clearly more active than single agent paclitaxel.

    View details for DOI 10.1080/07357900600981349

    View details for Web of Science ID 000242207700003

    View details for PubMedID 17118777

  • Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. Journal of the National Comprehensive Cancer Network Carlson, R. W., Hudis, C. A., Pritchard, K. I. 2006; 4 (10): 971-979

    Abstract

    Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.

    View details for PubMedID 17112447

  • Breast cancer followed by corpus cancer: Is there a higher risk for aggressive histologic subtypes? GYNECOLOGIC ONCOLOGY Chan, J. K., Manuel, M. R., Cheung, M. K., Osann, K., Husain, A., Teng, N. N., Rao, A., Carlson, R. W., Whittemore, A. S. 2006; 102 (3): 508-512

    Abstract

    To analyze corpus cancer patients with a breast cancer history for risk of developing aggressive uterine histologic types.Corpus cancer patients with a history of breast cancer were identified from the Surveillance Epidemiology and End Results database from 1988 to 2001. Demographics, clinico-pathologic, and survival data were analyzed using Kaplan-Meier and logistic regression analyses.Of 52,109 women diagnosed with corpus cancer, 1922 had a history of breast cancer. Women with a history of breast cancer had a significantly higher proportion of uterine papillary serous carcinomas (UPSC) and sarcomas compared to those without a breast cancer history (9.4% vs. 6.3% for UPSC and 10.3% vs. 8.4% for sarcoma; P < 0.001). Patients with endometrioid or sarcoma of the uterus after breast cancer had significantly worse 5-year survivals than patients without a breast cancer history (84.4% vs. 90.5%; P < 0.001 and 49.0% vs. 63.6%, P < 0.001, respectively). Older age, advanced stage, lack of surgery and radiation treatment, poor histologic types, and history of breast cancer were independent prognostic factors for poorer survival.In this study, the proportional incidence of UPSC and sarcoma was significantly higher in women with a breast cancer history. These findings highlight the association of breast cancer and high-risk corpus cancer subtypes.

    View details for DOI 10.1016/j.ygyno.2006.01.014

    View details for Web of Science ID 000240871000017

    View details for PubMedID 16483640

  • HER2 testing in breast cancer: NCCN Task Force report and recommendations. Journal of the National Comprehensive Cancer Network Carlson, R. W., Moench, S. J., Hammond, M. E., Perez, E. A., Burstein, H. J., Allred, D. C., Vogel, C. L., Goldstein, L. J., Somlo, G., Gradishar, W. J., Hudis, C. A., Jahanzeb, M., Stark, A., Wolff, A. C., Press, M. F., Winer, E. P., Paik, S., Ljung, B. 2006; 4: S1-22

    Abstract

    The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

    View details for PubMedID 16813731

  • Predicting non-sentinel lymph node involvement in breast cancer patients. 42nd Annual Meeting of the American-Society-of-Clinical-Oncology Kohrt, H. E., Olshen, R. A., Goodson, W. H., Rouse, R. V., Bailey, L., Philben, V., Dirbas, F. M., Stockdale, F. E., Carlson, R. W., Jeffrey, S. S. AMER SOC CLINICAL ONCOLOGY. 2006: 10S–10S
  • NCCN Task Force Report: Adjuvant Therapy for Breast Cancer. Journal of the National Comprehensive Cancer Network Carlson, R. W., Brown, E., Burstein, H. J., Gradishar, W. J., Hudis, C. A., Loprinzi, C., Mamounas, E. P., Perez, E. A., Pritchard, K., Ravdin, P., Recht, A., Somlo, G., Theriault, R. L., Winer, E. P., Wolff, A. C. 2006; 4: S1-26

    Abstract

    The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

    View details for PubMedID 16507275

  • Development of a new device for high throughput isolation of live circulating tumor cells. 29th Annual San Antonio Breast Cancer Symposium Talasaz, A. A., Powell, A. A., Mindrinos, M., Carlson, R. W., Pease, F. W., Davis, R. W., Jeffrey, S. S. SPRINGER. 2006: S213–S213
  • Breast cancer in limited-resource countries: Treatment and allocation of resources BREAST JOURNAL Eniu, A., Carlson, R. W., Aziz, Z., Bines, J., Hortobagyi, G. N., Bese, N. S., Love, R. R., Vikram, B., Kurkure, A., Anderson, B. O. 2006; 12 (1): S38-S53

    Abstract

    Treating breast cancer under the constraints of significantly limited health care resources poses unique challenges that are not well addressed by existing guidelines. We present evidence-based guidelines for systematically prioritizing cancer therapies across the entire spectrum of resource levels. After consideration of factors affecting the value of a given breast cancer therapy (contribution to overall survival, disease-free survival, quality of life, and cost), we assigned each therapy to one of four incremental levels--basic, limited, enhanced, or maximal--that together map out a sequential and flexible approach for planning, establishing, and expanding breast cancer treatment services. For stage I disease, basic-level therapies are modified radical mastectomy and endocrine therapy with ovarian ablation or tamoxifen; therapies added at the limited level are breast-conserving therapy, radiation therapy, and standard-efficacy chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF], or doxorubicin and cyclophosphamide [AC], epirubicin and cyclophosphamide [EC], or 5-fluorouracil, doxorubicin, and cyclophosphamide [FAC]); at the enhanced level, taxane chemotherapy and endocrine therapy with aromatase inhibitors or luteinizing hormone-releasing hormone (LH-RH) agonists; and at the maximal level, reconstructive surgery, dose-dense chemotherapy, and growth factors. For stage II disease, the therapy allocation is the same, with the exception that standard-efficacy chemotherapy is a basic-level therapy. For locally advanced breast cancer, basic-level therapies are modified radical mastectomy, neoadjuvant chemotherapy (CMF, AC, or FAC), and endocrine therapy with ovarian ablation or tamoxifen; the therapy added at the limited level is postmastectomy radiation therapy; at the enhanced level, breast-conserving therapy, breast-conserving whole-breast radiation therapy, taxane chemotherapy, and endocrine therapy with aromatase inhibitors or LH-RH agonists; and at the maximal level, reconstructive surgery and dose-dense chemotherapy and growth factors. For metastatic or recurrent disease, basic-level therapies are total mastectomy for ipsilateral in-breast recurrence, endocrine therapy with ovarian ablation or tamoxifen, and analgesics; therapies added at the limited level are radiation therapy and CMF or anthracycline chemotherapy; at the enhanced level, chemotherapy with taxanes, capecitabine, or trastuzumab, endocrine therapy with aromatase inhibitors, and bisphosphonates; and at the maximal level, chemotherapy with vinorelbine, gemcitabine, or carboplatin, growth factors, and endocrine therapy with fulvestrant. Compared with the treatment of early breast cancer, the treatment of advanced breast cancer is more resource intensive and generally has poorer outcomes, highlighting the potential benefit of earlier detection and diagnosis, both in terms of conserving scarce resources and in terms of reducing morbidity and mortality. Use of the scheme outlined here should help ministers of health, policymakers, administrators, and institutions in limited-resource settings plan, establish, and gradually expand breast cancer treatment services for their populations.

    View details for Web of Science ID 000235660400005

    View details for PubMedID 16430398

  • Breast cancer in limited-resource countries: An overview of the breast health global initiative 2005 guidelines BREAST JOURNAL Anderson, B. O., Shyyan, R., Eniu, A., SMITH, R. A., Yip, C. H., Bese, N. S., Chow, L. W., Masood, S., Ramsey, S. D., Carlson, R. W. 2006; 12 (1): S3-S15

    Abstract

    Breast cancer is the most common cause of cancer-related death among women worldwide, with case fatality rates highest in low-resource countries. Despite significant scientific advances in its management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence-based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence-based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited-resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels-basic, limited, enhanced, and maximal-based on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost-effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound +/- diagnostic mammography) can facilitate cost-effective tissue sampling techniques for cytologic or histologic diagnosis. Breast-conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited-resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node-positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low-resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor-negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited-resource settings.

    View details for Web of Science ID 000235660400002

    View details for PubMedID 16430397

  • Supportive-expressive group therapy and survival in patients with metastatic breast cancer: A randomized clinical intervention trial. 29th Annual San Antonio Breast Cancer Symposium Spiegel, D., Butler, L. D., Giese-Davis, J., Koopman, C., Miller, E., DiMiceli, S., Classen, C. C., Fobair, P., Carlson, R. W., Kraemer, H. C. SPRINGER. 2006: S240–S240
  • Update: NCCN breast cancer Clinical Practice Guidelines. Journal of the National Comprehensive Cancer Network Carlson, R. W., McCormick, B. 2005; 3: S7-11

    View details for PubMedID 16280118

  • Final results of a phase II trial of preoperative TAC (docetaxel/doxorubicin/cyclophosphamide) in stage III breast cancer. Clinical breast cancer O'Regan, R. M., Von Roenn, J. H., Carlson, R. W., Malik, U., Sparano, J. A., Staradub, V., Khan, S., Jovanovic, B., Morrow, M., Gradishar, W. J. 2005; 6 (2): 163-168

    Abstract

    The use of preoperative chemotherapy for breast cancer has been demonstrated to result in similar disease-free survival (DFS) and overall survival (OS) as postoperative adjuvant chemotherapy. Additionally, the rate of pathologic complete response (pCR) in the breast after preoperative chemotherapy has been shown to correlate with survival. The objective of this study was to determine the pCR rate in patients with stage III breast cancer treated with 4 cycles of TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) on day 1 before surgery.From November 1998 through August 2001, we treated 40 patients (mean age, 47 years) with stage III breast cancer with TAC administered every 3 weeks for 4 cycles.We now report follow-up at 24 months. Responses were seen in 83% of patients, with 25% experiencing a clinical complete response, of which 4 patients (10%) had pCRs. At a follow-up of 2 years, data on DFS and OS are available on 37 patients: 12 patients (38%) had disease progression, and 7 patients (21%) had died. Despite the use of prophylactic ciprofloxacin, some degree of myelosuppression was seen in all patients, with 24 patients (63%) experiencing grade 3/4 neutropenia.Based on the pCR rate seen in this trial, docetaxel given concomitantly with AC (doxorubicin/cyclophosphamide) for 4 cycles does not appear to be superior to 4 cycles of AC as preoperative treatment for stage III breast cancer. Based on other trials, longer durations of therapy and/or sequencing of AC and docetaxel may result in a higher pCR rate.

    View details for PubMedID 16001995

  • Breast cancer. Journal of the National Comprehensive Cancer Network Carlson, R. W., Anderson, B. O., Burstein, H. J., Cox, C. E., Edge, S. B., Farrar, W. B., Goldstein, L. J., Gradishar, W. J., Hayes, D. F., Hudis, C., Jahanzeb, M., Ljung, B., Marks, L. B., McCormick, B., Nabell, L. M., Pierce, L. J., Reed, E. C., Silver, S. M., Smith, M. L., Somlo, G., Theriault, R. L., Ward, J. H., Winer, E. P., Wolff, A. C. 2005; 3 (3): 238-289

    View details for PubMedID 16002000

  • The history and mechanism of action of fulvestrant. Clinical breast cancer Carlson, R. W. 2005; 6: S5-8

    Abstract

    Fulvestrant is a pure antiestrogen that emerged from a systematic medicinal chemistry strategy of modification of long-chain alkyl substitutes in the 7a-position of estradiol. Fulvestrant has no uterotrophic effects on the immature or ovariectomized rat and blocks the agonistic effects of estradiol and tamoxifen in a dose-dependent manner. In in vivo and in vitro breast cancer models, fulvestrant has anticancer activity at least as good as tamoxifen and is superior to tamoxifen in some models. Fulvestrant requires intramuscular administration in a proprietary formulation of castor oil and alcohols. When fulvestrant binds to estrogen receptor monomers it inhibits receptor dimerization, activating function 1 (AF1) and AF2 are rendered inactive, translocation of receptor to the nucleus is reduced, and degradation of the estrogen receptor is accelerated. This results in pure antiestrogenic effects. There is substantial preclinical evidence that the nonsteroidal hormone-dependent mechanisms of estrogen receptor activation and regulation via growth factor receptors and their signal transduction pathways are important in the development of breast cancer hormonal resistance. Methods of exploiting the interactions between these nonsteroidal hormone-dependent mechanisms of resistance and hormonal agents such as fulvestrant are an active area for drug development and clinical investigation.

    View details for PubMedID 15865849

  • Predictors of local recurrence after breast-conservation therapy. Clinical breast cancer Horst, K. C., Smitt, M. C., Goffinet, D. R., Carlson, R. W. 2005; 5 (6): 425-438

    Abstract

    Breast-conserving therapy (BCT) is a proven local treatment option for select patients with early-stage breast cancer. This paper reviews pathologic, clinical, and treatment-related features that have been identified as known or potential predictors for ipsilateral breast tumor recurrence in patients treated with BCT. Pathologic risk factors such as the final pathologic margin status of the excised specimen after BCT, the extent of margin involvement, the interaction of margin status with other adverse features, the role of biomarkers, and the presence of an extensive intraductal component or lobular carcinoma in situ all impact the likelihood of ipsilateral breast tumor recurrence. Predictors of positive repeat excision findings after conservative surgery include young age, presence of an extensive intraductal component, and close or positive margins in prior excision. Finally, treatment-related factors predicting ipsilateral breast tumor recurrence include extent of breast radiation therapy, use of a boost to the lumpectomy cavity, use of tamoxifen or chemotherapeutic agents, and timing of systemic therapy with irradiation. The ability to predict for an increased risk of ipsilateral breast tumor recurrence enhances the ability to select optimal local treatment strategies for women considering BCT.

    View details for PubMedID 15748463

  • Update: NCCN breast cancer clinical practice guidelines. Journal of the National Comprehensive Cancer Network Carlson, R. W., Edge, S. B. 2004; 2: S-1 4

    View details for PubMedID 23570090

  • Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? Clinical breast cancer Chung, C. T., Carlson, R. W. 2004; 5: S18-23

    Abstract

    Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.

    View details for PubMedID 15347435

  • Cytotoxic T lymphocyte count and survival time in women with metastatic breast cancer. breast journal Blake-Mortimer, J. S., Sephton, S. E., Carlson, R. W., Stites, D., Spiegel, D. 2004; 10 (3): 195-199

    Abstract

    While prognostic factors in early stage breast cancer are well documented, few studies have examined predictors of the rate of metastatic progression. The purpose of this study was to examine cytotoxic T-cell lymphocyte (CTL) count as a marker of disease status in women with metastatic breast cancer. This study examined CTL subset counts as predictors of subsequent survival in 113 women with metastatic or recurrent breast cancer. Samples were measured by flow cytometry using monoclonal antibodies for cell surface antigens for percentages and absolute numbers of CTLs (CD3/CD8), total lymphocytes, T cells (CD3), helper T cells (CD3/CD4), and total white blood cell (TWC) count. Higher CTL counts emerged as a significant predictor of longer survival up to 7 years later (Wald = 7.40, p = 0.007; Cox regression model). The relationship of higher CTL count with enhanced survival was independent of the effects of medical treatment. CTLs were significantly associated with TWC count (r = 0.42, p < 0.001). However, TWC count was not associated with subsequent survival time. Higher CTL count was associated with Karnofsky performance status (r = 0.27, p = 0.004). However, after adjustment for the Karnofsky score, the CTL count/survival relationship remained significant (Wald = 4.33, p = 0.038). In conclusion, there is a robust relationship between CTL count and survival that is independent of the effects of medical treatments, TWC count, and Karnofsky performance status. Moreover, a reduced CTL count may be a mediator or marker of more rapid disease progression in metastatic breast cancer.

    View details for PubMedID 15125744

  • High-dose chemotherapy and stem cell transplantation does not improve relapse-free or overall survival in women with high-risk breast cancer. Cancer treatment reviews Carlson, R. W., Wheatley, K. 2004; 30 (1): 131-137

    View details for PubMedID 14766131

  • Central carbon metabolism genes that predict disease-free survival in hormone receptor negative tumors. 27th Annual San Antonio Breast Cancer Symposium Funari, V. A., Tibshirani, R., Ji, Y., Nicolau, M., Carlson, R. W., Brown, P. O., Noh, D. Y., Jeffrey, S. S. SPRINGER. 2004: S115–S115
  • Rational surveillance programs for early stage breast cancer patients after primary treatment. Breast disease Mollick, J. A., Carlson, R. W. 2004; 21: 47-54

    Abstract

    The majority of women with early stage breast cancers are successfully treated with surgery, radiation therapy and adjuvant systemic therapy. However, 30% of all Stage I and Stage II patients can be expected to experience a relapse. The belief that early detection of recurrences can lead to an increase in survival has been used to justify intensive follow-up regimens following primary treatment of patients with early stage disease. However, the vast majority of data support a program of scheduled surveillance visits and demonstrate that a comprehensive history and physical examination is as efficacious as programs utilizing intensive testing and imaging procedures in the asymptomatic patient. Screening mammography to detect ipsilateral in-breast recurrence or a new primary cancer in the contralateral breast is the only imaging study that is recommended for routine surveillance. Knowledge of the natural history of breast cancer, risk factors for relapse, and the symptoms and physical findings commonly associated with recurrence are central to efficiently and effectively monitoring this cohort of women in clinical practice.

    View details for PubMedID 15687722

  • Goserelin plus anastrozole for the treatment of premenopausal women with hormone receptor positive, recurrent/metastatic breast cancer 27th Annual San Antonio Breast Cancer Symposium Carlson, R. W., Schurmann, C. M., Rivera, E., Chung, C. T., Phan, S. C., Dice, E. K., Arun, B., Thomas, E., Valero, V. SPRINGER. 2004: S237–S238
  • Predictors of reexcision findings and recurrence after breast conservation 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Smitt, M. C., Nowels, K., Carlson, R. W., Jeffrey, S. S. ELSEVIER SCIENCE INC. 2003: 979–85

    Abstract

    To identify predictors of reexcision findings and local recurrence in the setting of breast-conserving therapy with radiation.The records of 535 patients who underwent breast-conserving surgery followed by radiation for Stage I or II cancer between 1972 and 1996 were reviewed. The mean follow-up period for surviving patients without evidence of recurrence is 6 years. Various clinical and pathologic prognostic factors were examined for significance with regard to reexcision findings and recurrence rates. Pathologic margin status was classified as negative, close (

    View details for DOI 10.1016/S0360-3016(03)00740-5

    View details for Web of Science ID 000186293800010

    View details for PubMedID 14575828

  • Phase I trial of uracil-ftorafur, leucovorin, and etoposide: an active all-oral regimen for metastatic breast cancer BREAST CANCER RESEARCH AND TREATMENT Hartman, A. R., Grekowicz, A., Lum, B. L., Carlson, R. W., Schurman, C., Sikic, B. I., Shapiro, R., Stockdale, F. E. 2003; 82 (1): 61-69

    Abstract

    To determine the maximum tolerated doses, toxicities, and therapeutic effect of an oral chemotherapy regimen consisting of uracil-ftorafur, etoposide, and leucovorin for metastatic breast cancer.The regimen consists of 28-day cycles of uracil-ftorafur, etoposide, and leucovorin administered orally on days 1-14. The dose of etoposide was fixed at 50 mg/m2/day, and uracil-ftorafur was escalated in 50 mg/m2/day increments from 200 to 350 mg/m2. Leucovorin, was used at a dose of 90 mg/day. Eligibility criteria required prior treatment with a taxane or anthracycline.A total of 23 patients were enrolled. Twenty patients are assessable for toxicity and 16 patients are assessable for response. All non-hematologic toxicities were grade 1 or 2. Three hematologic dose-limiting toxicities (DLTs) were observed. Partial responses were seen in 6 of 16 (37.5%, 95% confidence interval 15%, 85%) of assessable patients with durations ranging from 4 to 20 months. Stable disease was observed in 4 of 16 (25%) of patients with durations from 4 to 12 months. Median time to progression was 10.5 months. An intent to treat analysis revealed a response of 26%.The recommended dose and schedule of this combination is uracil-ftorafur 350 mg/m2, leucovorin 90 mg/day, and etoposide 50 mg/m2 for two consecutive weeks in a 4-week cycle. This all-oral regimen is well tolerated and demonstrates encouraging efficacy in a cohort of heavily pretreated patient with metastatic breast cancer.

    View details for Web of Science ID 000186609000008

    View details for PubMedID 14672404

  • Treatment of breast cancer in countries with limited resources. breast journal Carlson, R. W., Anderson, B. O., Chopra, R., Eniu, A. E., Jakesz, R., Love, R. R., Masetti, R., Schwartsmann, G. 2003; 9: S67-74

    Abstract

    Early and accurate diagnosis of breast cancer is important for optimizing treatment. Local treatment of early stage breast cancer involves either mastectomy or breast-conserving surgery followed by whole-breast irradiation. The pathologic and biologic properties of a woman's breast cancer may be used to estimate her probability for recurrence of and death from breast cancer, as well as the magnitude of benefit she is likely to receive from adjuvant endocrine therapy or cytotoxic chemotherapy. Ovarian ablation or suppression with or without tamoxifen is an effective endocrine therapy in the adjuvant treatment of breast cancer in premenopausal women with estrogen receptor (ER)-positive or ER-unknown breast cancer. In postmenopausal women with ER- and/or progesterone receptor (PR)-positive or PR-unknown breast cancer, the use of tamoxifen or anastrozole is effective adjuvant endocrine therapy. The benefit of tamoxifen is additive to that of chemotherapy. Cytotoxic chemotherapy also improves recurrence rates and survival, with the magnitude of benefit decreasing with increasing age. Substantial support systems are required to optimally and safely use breast-conserving approaches to local therapy or cytotoxic chemotherapy as systemic therapy. Locally advanced breast cancer (LABC) accounts for at least half of all breast cancers in countries with limited resources and has a poor prognosis. Initial treatment of LABC with anthracycline-based chemotherapy is standard and effective. Addition of a sequential, neoadjuvant taxane thereafter increases the rate of pathologic complete responses. Neoadjuvant endocrine therapy may benefit postmenopausal women with hormone receptor-positive LABC. After an initial response to neoadjuvant chemotherapy, the use of local-regional surgery is appropriate. Most women will require a radical or modified radical mastectomy. In those women in whom mastectomy is not possible after neoadjuvant chemotherapy, the use of whole-breast and regional lymph node irradiation alone is appropriate. In those women who cannot receive neoadjuvant chemotherapy because of resource constraints, mastectomy with node dissection, when feasible, may still be considered in an attempt to achieve local-regional control. After local-regional therapy, most women should receive additional systemic chemotherapy. Women with LABC that has a positive or unknown hormone receptor status benefit from endocrine therapy with tamoxifen. The treatment of LABC requires multiple disciplines and is resource intensive. Efforts to reduce the number of breast cancers diagnosed at an advanced stage thus have the potential to improve rates of survival while decreasing the use of limited resources.

    View details for PubMedID 12713499

  • The role of aromatase inhibitors in early breast cancer. Current treatment options in oncology Chung, C. T., Carlson, R. W. 2003; 4 (2): 133-140

    Abstract

    The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptor-positive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.

    View details for PubMedID 12594939

  • NCCN breast cancer clinical practice guidelines in oncology: an update. Journal of the National Comprehensive Cancer Network Carlson, R. W. 2003; 1: S61-3

    Abstract

    The 2002 NCCN Breast Cancer Clinical Practice Guidelines in Oncology represent the 7th annual update produced by a multidisciplinary panel of breast cancer experts from the NCCN member institutions. The Breast Cancer Panel uses an objective, evidence-based method when high-level evidence from clinical trials exists. In clinical situations in which high-level evidence is lacking, recommendations are generated through a multidisciplinary consensus development process. The NCCN institutions also review the complete guideline on an annual basis. In this update, several of the modifications in the 2002 Breast Cancer Guidelines are highlighted, including the use of aromatase inhibitors and leuteinizing hormone-releasing hormone agonists plus tamoxifen in the first-line therapy of metastatic breast cancer and the use of anastrozole in the adjuvant setting. The new guidelines for axillary lymph node staging are reported on in a companion article in this issue.

    View details for PubMedID 19795577

  • Goals and objectives in the management of metastatic breast cancer ONCOLOGIST Chung, C. T., Carlson, R. W. 2003; 8 (6): 514-520

    Abstract

    Patients with metastatic breast cancer consist of a heterogeneous group of patients whose prognoses and clinical courses can vary depending on host factors, such as comorbidity and age, and on tumor factors, such as hormone-receptor status, grade, and anatomical site of disease. Although the median survival time for patients with metastatic breast cancer is 2-4 years, subsets of patients with either indolent or limited metastatic disease may have prolonged survival times. Further, expectations of treatment, both in terms of efficacy and of toxicity, vary greatly based upon the specific treatment, patient characteristics, and tumor characteristics. Thus, the goals of treatment for patients with metastatic breast cancer are influenced by estimates of prognoses as well as a balance between physician and patient preferences regarding efficacy and toxicity considerations. Traditionally, objective measures of response and survival have been the targeted end points in clinical trial design and in physician selection of therapy for metastatic breast cancer. More recently, issues of quality of life have surfaced as important end points, especially from the perspective of the patient. The decision-making process in selecting the optimal treatment for patients with metastatic breast cancer is, therefore, a multidimensional process involving subjective as well as objective goals of treatment. Ultimately, the benefits of treatment must justify the risks and toxicities of the treatment, and the impact of treatment should be measured in relation to specified goals. Both physician and patient perspectives are important in establishing the objectives of treatment, and this process is optimally an interactive and ongoing process throughout the course of disease.

    View details for Web of Science ID 000186862900005

    View details for PubMedID 14657529

  • Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole BREAST CANCER RESEARCH AND TREATMENT Carlson, R. W., Henderson, I. C. 2003; 80: S19-S26

    Abstract

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.

    View details for Web of Science ID 000184961200004

    View details for PubMedID 14535531

  • Sequencing of endocrine therapies in breast cancer - integration of recent data BREAST CANCER RESEARCH AND TREATMENT Carlson, R. W. 2002; 75 (1): S27-S32

    Abstract

    A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.

    View details for Web of Science ID 000177727200006

    View details for PubMedID 12353821

  • NCCN: Breast cancer. Cancer control Carlson, R. W., Edge, S. B., Theriault, R. L. 2001; 8 (6): 54-61

    Abstract

    The 2001 NCCN Breast Cancer Guidelines reflect the results of 5 generations of NCCN Breast Cancer Guidelines. Evidence-based guidelines, such as the NNCN Breast Cancer Guidelines, are possible only because of the availability of high-level evidence at multiple decision points in treatment. The continued performance of high quality clinical trials is central to our ability to further improve the treatment of breast cancer. The panel believes that participation in high quality clinical trials is the preferred treatment at all points in breast cancer therapy.

    View details for PubMedID 11760559

  • Is the placebo powerless? NEW ENGLAND JOURNAL OF MEDICINE Spiegel, D., Kraemer, H., Carlson, R. W. 2001; 345 (17): 1276-1276

    View details for Web of Science ID 000171773100011

    View details for PubMedID 11680452

  • Supportive-expressive group therapy and distress in patients with metastatic breast cancer - A randomized clinical intervention trial Annual Meeting of the American-Psychological-Association Classen, C., Butler, L. D., Koopman, C., Miller, E., DiMiceli, S., Giese-Davis, J., Fobair, P., Carlson, R. W., Kraemer, H. C., Spiegel, D. AMER MEDICAL ASSOC. 2001: 494–501

    Abstract

    Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population.Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition.Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

    View details for Web of Science ID 000168479100010

    View details for PubMedID 11343530

  • Locally advanced breast cancer: is surgery necessary? breast journal Favret, A. M., Carlson, R. W., Goffinet, D. R., Jeffrey, S. S., Dirbas, F. M., Stockdale, F. E. 2001; 7 (2): 131-137

    Abstract

    A retrospective analysis of the treatment of locally advanced breast cancer (LABC) was undertaken at Stanford Medical Center to assess the outcome of patients who did not undergo surgical removal of their tumors. Between 1981 and 1998, 64 patients with locally advanced breast cancer were treated with induction chemotherapy, radiation with or without breast surgery, and additional chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was followed by local radiotherapy in 59 (92%) patients. Based on the clinical response to chemotherapy and patient preference, 44 (69%) patients received no local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin-containing chemotherapy in all patients. The mean age of patients was 49 years. Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph nodes only). Response to induction chemotherapy was seen in 59 patients (92%), with 29 (45%) achieving a complete clinical response and 30 (47%) a partial clinical response. With a mean follow-up of 51 months (range 7-187 months), 43 patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial 5-year survival is 75%, disease-free survival is 58%, and local control rate is 87.5%. These data indicate that the routine inclusion of breast surgery in a combined modality treatment program for LABC does not appear necessary for the majority of patients who experience a response to induction chemotherapy.

    View details for PubMedID 11328324

  • NCCN Practice Guidelines for breast cancer ONCOLOGY-NEW YORK Carlson, R. W., Anderson, B. O., Bensinger, W., Cox, C. E., Davidson, N. E., Edge, S. B., Farrar, W. B., Goldstein, L. J., Gradishar, W. J., Lichter, A. S., McCormick, B., Nabell, L. M., Reed, E. C., Silver, S. M., Smith, M. L., Somlo, G., Theriault, R., Ward, J. H., Winer, E. P., Wolff, A. 2000; 14 (11A): 33-49

    Abstract

    The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients.

    View details for Web of Science ID 000166713700003

    View details for PubMedID 11195418

  • New bilateral microcalcifications at mammography in a postlactational woman: Case report RADIOLOGY Stucker, D. T., Ikeda, D. M., Hartman, A. R., George, T. I., Nowels, K. W., Birdwell, S. L., Goffinet, D., Carlson, R. W. 2000; 217 (1): 247-250

    Abstract

    A 33-year-old woman with a strong family history of breast cancer who was referred for mammography 5 weeks after completing lactation was found to have new diffuse bilateral microcalcifications in the breast ducts. Contrast material-enhanced magnetic resonance imaging of the breast showed bilateral patchy areas of abnormal enhancement. Large-core needle biopsy showed diffuse calcifications within expanded benign ducts in a background of lactational change, without evidence of malignancy. To the authors' knowledge, these calcifications have not been previously reported and are possibly related to milk stasis or apoptosis associated with lactation.

    View details for PubMedID 11012452

  • Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis LANCET Buyse, M., Thirion, P., Carlson, R. W., Burzykowski, T., Molenberghs, G., Piedbois, P. 2000; 356 (9227): 373-378

    Abstract

    Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint.This meta-analysis was done on individual data from 3791 patients enrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous infusion, or hepatic-arterial infusion of floxuridine). Analyses were by intention to treat.Compared with bolus fluoropyrimidines, experimental fluoropyrimidines led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p<0.0001) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival benefits could be explained by the higher tumour response rates. However, a treatment that lowered the odds of failure to respond by 50% would be expected to decrease the odds of death by only 6%. In addition, less than half of the variability of the survival benefits in the 25 trials could be explained by the variability of the response benefits in these trials.These analyses confirm that an increase in tumour response rate translates into an increase in overall survival for patients with advanced colorectal cancer. However, in the context of individual trials, knowledge that a treatment has benefits on tumour response does not allow accurate prediction of the ultimate benefit on survival.

    View details for Web of Science ID 000088486000009

    View details for PubMedID 10972369

  • Meta-analysis: Methods, strengths, and weaknesses ONCOLOGY-NEW YORK Buyse, M., Piedbois, P., Piedbois, Y., Carlson, R. W. 2000; 14 (3): 437-443

    Abstract

    Meta-analysis is a systematic, quantitative approach to the combination of data from several clinical trials that address the same question. This analytic approach can help resolve questions that remain unclear from the results of individual trials. Meta-analysis is of particular interest in oncology because of the small differences in efficacy between therapeutic alternatives. The large number of patients included in meta-analyses permit small to moderate benefits of a treatment to be reliably detected and larger treatment benefits to be quantified more accurately. Despite these apparent benefits, the use of meta-analysis has met with a great deal of resistance and has generated much controversy in clinical journals. After a brief description of the basic methods of conducting meta-analyses, this article will explore both their advantages and disadvantages.

    View details for Web of Science ID 000090128900022

    View details for PubMedID 10742969

  • Management of breast cancer after Hodgkin's disease 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Wolden, S. L., Hancock, S. L., Carlson, R. W., Goffinet, D. R., Jeffrey, S. S., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 2000: 765–72

    Abstract

    To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease.Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed.The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero.The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

    View details for Web of Science ID 000085401800008

    View details for PubMedID 10673517

  • Economic implications of hepatic arterial infusion versus intravenous chemotherapy or symptom palliation in the treatment of nonresectable colorectal liver metastases CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY Durand-Zaleski, I., Roche, B., Buyse, M., Carlson, R., O'Connell, M., Rougier, P., Chang, A. E., Sondak, V. K., Kemeny, M., Allen-Mersh, T., Fagniez, P. L., Le Bourgeois, J. P., Piedbois, P. 1999; 32 (2): 125-131

    View details for Web of Science ID 000083740300007

    View details for PubMedID 10612012

  • NCCN breast cancer risk-reduction guidelines ONCOLOGY-NEW YORK Carlson, R., Barakat, R., Bevers, T., Daly, M. B., Edge, S., Garber, J. E., Gradishar, W., Mahoney, M., Sellin, R. V., Shapiro, C., Singletary, E., Theriault, R., Ward, J., Whittemore, A., Williams, C., Winer, E. 1999; 13 (11A): 241-254
  • Update: NCCN practice guidelines for the treatment of breast cancer ONCOLOGY-NEW YORK Carlson, R. W., Anderson, B. O., Bensinger, W., Cox, C., Davidson, N. E., Edge, S. B., Farrar, W. B., Goldstein, L. J., Gradishar, W. J., Lichter, A. S., McCormick, B., Nabell, L. M., Reed, E. C., Silver, S. M., Smith, M. L., Somlo, G., Theriault, R. L., Winer, E. P. 1999; 13 (11A): 187-212
  • Multidisciplinary Management of Locally Advanced Breast Cancer. breast journal Carlson, R. W., Favret, A. M. 1999; 5 (5): 303-307

    Abstract

    The treatment of locally advanced breast cancer is aimed at achieving long-term local control with local surgery and/or radiation therapy and at improving disease-free and overall survival through the application of systemic cytotoxic chemotherapy and hormonal therapy. Studies of local therapy alone with surgery or radiotherapy have demonstrated high rates of local recurrence and low rates of long-term survival. The application of anthracycline-based neoadjuvant chemotherapy has resulted in rates of response ranging from 72% to 97%, clinical complete responses of 12-52%, and pathologic complete responses of 4-33%. Multidisciplinary treatment with neoadjuvant therapy, followed by local surgery and/or radiation therapy, followed by additional chemotherapy, has resulted in rates of local control that exceed 80%, and 5-year survival rates exceeding 50% are not unusual. The use of anthracycline-based neoadjuvant chemotherapy in the treatment of locally advanced breast cancer is thus now firmly established. Research in the treatment of locally advanced breast cancer is needed to further define the optimal method of local therapy and the role of new agents such as the taxanes.

    View details for PubMedID 11348306

  • Toxicity of fluorouracil in patients with advanced colorectal cancer: Effect of administration schedule and prognostic factors JOURNAL OF CLINICAL ONCOLOGY Levy, E., Piedbois, P., Buyse, M., Pignon, J. P., Rougier, P., Ryan, L., Hansen, R., Zee, B., Weinerman, B., Pater, J., Leichman, C., MacDonald, J., Benedetti, J., Lokich, J., Fryer, J., Brufman, G., Isacson, R., Laplanche, A., Quinaux, E., Thirion, P., Ryan, L., Hansen, R., Harrington, D., McFadden, E., Ribble, A., Jacobson, R., Zee, B., Weinerman, B., Pater, J., Leichman, C., MacDonald, J., Benedetti, J., Lokich, J., Fryer, J., Pignon, J. P., Laplanche, A., Luboinski, M., Rougier, P., Brufman, G., Isacson, R., Vaitkevicius, V., Piedbois, P., Le Bourgeois, J. P., Piedbois, Y., Gauthier, E., Levy, E., Thirion, P., Durand-Zalenski, I., Buyse, M., Quinaux, E., Wolmark, N., Piedbois, P., Buyse, M., Carlson, R., Rustum, Y., Erlichman, C. 1998; 16 (11): 3537-3541
  • Quality of life issues in the treatment of metastatic breast cancer ONCOLOGY-NEW YORK Carlson, R. W. 1998; 12 (3): 27-31

    Abstract

    The treatment of metastatic breast cancer involves the sequential selection and delivery of hormonal therapies and cytotoxic chemotherapies. The available therapies for metastatic breast cancer are rarely curative, although high rates of response and modest prolongation of survival may be achieved in association with varying degrees of treatment-related toxicity. Therefore, the selection of appropriate therapy requires a reasoned consideration of the likelihood of benefit from therapy balanced with the impact of therapy on the patient's quality of life. Several instruments have been developed to measure quality of life in cancer patients, but none has been universally accepted, and they require time and resources to administer. Few randomized clinical trials have incorporated quality of life assessments. Thus, the clinician must balance antitumor activity, performance status, and the usual toxicity measures, (e.g., nausea, myelosuppression, asthenia) as surrogates for quality of life associated with each specific therapy. Studies have confirmed the clinical impression that antitumor activity of treatment generally correlates with quality of life outcome. The hormonal therapies have the quality of life advantages of limited and non-threatening acute toxicity, rare chronic toxicity, need for infrequent visits to health care providers, oral administration, and, in appropriately selected patients, response and duration of response rates equivalent to those of the cytotoxic agents. A number of cytotoxic agents have activity in the treatment of metastatic breast cancer. Although the active single agents differ substantially in their toxicity profiles, the dose-limiting toxicity is usually myelosuppression. Recently, several agents with substantial activity against breast cancer have become available, including the taxanes (paclitaxel and docetaxel), vinorelbine, and gemcitabine. Oral formulations of vinorelbine are being studied that may provide the additional advantages of not requiring intravenous access, requiring fewer visits to the health care professional, and providing patients with a greater sense of control of their treatment.

    View details for Web of Science ID 000073005300005

    View details for PubMedID 9556780

  • Knowledge architectures for patient access to breast-cancer information IEEE INTELLIGENT SYSTEMS & THEIR APPLICATIONS Crangle, C., Carlson, R., Fagan, L., Erlbaum, M., Sherertz, D., Langford, L. 1998; 13 (1): 26-31
  • Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer JOURNAL OF CLINICAL ONCOLOGY Wolmark, N., Piedbois, P., Rougier, P., Buyse, M., Pignon, J. P., Ryan, L., Hansen, R., Zee, B., Weinerman, B., Pater, J., Leichman, C., MacDonald, J., Benedetti, J., Lokich, J., Fryer, J., Brufman, G., Isacson, R., Laplanche, A., Levy, E., Harrington, D., McFadden, E., Ribble, A., Jacobson, R., Luboinski, M., Vaitkevicius, V., Le Bourgeois, J. P., Piedbois, Y., Gauthier, E., Durand-Zaleski, I., Carlson, R., Rustum, Y., Erlichman, C. 1998; 16 (1): 301-308
  • Effects of medical and psychotherapeutic treatment on the survival of women with metastatic breast carcinoma CANCER KOGON, M. M., Biswas, A., Pearl, D., Carlson, R. W., Spiegel, D. 1997; 80 (2): 225-230

    Abstract

    The authors previously reported a statistically significant effect of psychosocial intervention on survival time of women with metastatic breast carcinoma. In this study, the authors investigated whether this effect could be explained by differences in the medical treatment patients received subsequent to their group participation or differences in causes of death.Of the original 86 study participants, medical treatment charts for 61 and death certificates for 83 were available for further analysis. The authors reviewed the course of the medical treatment they received subsequent to their entry into the randomized psychotherapy trial.Although there were no statistically significant differences with regard to chemotherapy and hormone therapy between the control and treatment groups, women in the control group tended to have received more adrenalectomies, although this procedure did not account for the difference in survival time between the control group and the treatment group. Furthermore, women in the control group developed more bone and lung metastases than the women in the treatment group.Differences in disease course between the control and treatment groups appeared to be independent of any differences in medical treatment received.

    View details for Web of Science ID A1997XJ01600009

    View details for PubMedID 9217034

  • Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE DURANDZALESKI, I., Roche, B., Buyse, M., Carlson, R., OCONNELL, M. J., Rougier, P., Chang, A. E., Sondak, V. K., Kemeny, M. M., ALLENMERSH, T. G., Fagniez, P. L., LeBourgeois, J. P., Piedbois, P. 1997; 89 (11): 790-795

    Abstract

    Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response.Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy.The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications.The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto.The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

    View details for Web of Science ID A1997XC09400013

  • Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer. Journal of the National Cancer Institute Durand-Zaleski, I., Roche, B., Buyse, M., Carlson, R., O'Connell, M. J., Rougier, P., Chang, A. E., Sondak, V. K., Kemeny, M. M., Allen-Mersh, T. G., Fagniez, P. L., Le Bourgeois, J. P., Piedbois, P. 1997; 89 (11): 790-795

    Abstract

    Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response.Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy.The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications.The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto.The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

    View details for PubMedID 9182977

  • Scientific review of tamoxifen. Overview from a medical oncologist. Seminars in oncology Carlson, R. W. 1997; 24 (1): S1-151 S1 7

    Abstract

    Tamoxifen is a widely used, effective, and well-tolerated agent in the treatment of primary and recurrent breast cancer. In the adjuvant setting, tamoxifen decreases the annual odds of recurrence and death by 25% and 16%, respectively. The toxicities of tamoxifen are of minor concern in the poor-prognosis group of women with metastatic breast cancer. In the more favorable group of women with early breast cancer, the benefits of tamoxifen appear to substantially outweigh the known toxicities. In retrospective analysis, tamoxifen has been consistently demonstrated to decrease the occurrence of contralateral second breast cancer and to be associated with an increased frequency of diagnosis of endometrial carcinoma. It is not known whether tamoxifen is promoting the growth of pre-existing, clinically occult endometrial carcinomas or is truly etiologic for the development of new cancers. The endometrial carcinomas that are associated with tamoxifen appear to have a biology and natural history similar to non-tamoxifen-associated endometrial carcinomas. There is no evidence supporting an association between hepatocellular carcinomas and tamoxifen in humans. Retrospective analysis of the association of colorectal carcinoma and gastric carcinoma provides little convincing evidence of a causal relationship, although further study is warranted.

    View details for PubMedID 9045312

  • NCCN Breast Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Williston Park, N.Y.) Carlson, R. W., Goldstein, L. J., Gradishar, W. J., Lichter, A. S., McCormick, B., Moe, R. E., Theriault, R. L. 1996; 10 (11): 47-75

    View details for PubMedID 8953596

  • Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Journal of the National Cancer Institute Piedbois, P., Buyse, M., Kemeny, N., Rougier, P., Carlson, R., Allen-Mersh, T., O'Connell, M., Chang, A., Sondak, V., Kemeny, M., Levy, E. 1996; 88 (5): 252-258

    Abstract

    Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear.A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival.The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two-trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of stratified logrank test. Multivariate analyses were performed with use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators.The tumor response rate was 41% for patients allocated to HAI with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 10 (-10)). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14).These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer.The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.

    View details for PubMedID 8614003

  • Toward reusable software components at the point of care. Proceedings : a conference of the American Medical Informatics Association / ... AMIA Annual Fall Symposium. AMIA Fall Symposium Tuttle, M. S., Sherertz, D. D., Olson, N. E., Nelson, S. J., Erlbaum, M. S., Keck, K. D., Davis, A. N., Suarez-Munist, O. N., Lipow, S. S., Cole, W. G., Fagan, L. M., ACUFF, R. D., Crangle, C. E., Musen, M. A., Tu, S. W., Wiederhold, G. C., Carlson, R. W. 1996: 150-154

    Abstract

    An architecture built from five software components -a Router, Parser, Matcher, Mapper, and Server -fulfills key requirements common to several point-of-care information and knowledge processing tasks. The requirements include problem-list creation, exploiting the contents of the Electronic Medical Record for the patient at hand, knowledge access, and support for semantic visualization and software agents. The components use the National Library of Medicine Unified Medical Language System to create and exploit lexical closure-a state in which terms, text and reference models are represented explicitly and consistently. Preliminary versions of the components are in use in an oncology knowledge server.

    View details for PubMedID 8947646

  • Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer Journal of the National Cancer Institute Piedbois P, Buyse M, Kemeny N, Rougier P, Carlson R, Allen-Mersh T, O'Connel M, Change A, Sondak V, Kemeny M, Levy 1996; 88: 252-258
  • Trade-offs between survival and breast preservation for three initial treatments of ductal carcinoma-in-situ of the breast JOURNAL OF CLINICAL ONCOLOGY Hillner, B. E., Desch, C. E., Carlson, R. W., Smith, T. J., Esserman, L., Bear, H. D. 1996; 14 (1): 70-77

    Abstract

    To assess the trade-offs between survival and breast preservation of currently accepted approaches for ductal carcinoma-in-situ (DCIS) of the breast.Decision analysis was performed using the Markov model of hypothetical cohorts of 55-year-old white women with nonpalpable mammographic abnormalities found to be DCIS. Strategies were breast-conserving surgery (BCS), BCS with 50-Gy radiation (RT) or initial mastectomy. Recurrence rates were derived from the published literature. Main outcomes were overall, breast cancer-free, and event-free survival plus years of both breasts preserved.Using the conditions defined in this model, the actuarial survival rates at 10 and 20 years were 91.7% and 74.1% for the initial mastectomy strategy, 91.0% and 72.1% for BCS plus RT, and 89.6% and 68.2% for BCS alone. At 20 years, the initial mastectomy strategy also had a greater breast cancer-free survival rate of 74.5%, compared with 63.3% for BCS plus RT, or 46.8% for BCS alone. However, BCS alone had the highest survival rate with both breasts preserved (64.2%) compared with BCS plus RT (56.0%) or initial mastectomy (0%). Of the breast-conserving strategies at 20 years, the breast event-free survival rate (no invasive cancer or DCIS) was greater for BCS plus RT (47.2%) compared with BCS alone (28.4%). Using just survival as the primary end point, mastectomy is the optimal strategy by a small margin. However, if quality-adjusted survival is at issue, mastectomy is the choice only if the yearly reduction in quality of life due to mastectomy is less than 1%.BCS with or without radiation compared with mastectomy as initial management of DCIS of the breast trades a slight decrease in survival rates for the value of breast preservation. This model should aid clinicians in matching treatments to their patients' preferences.

    View details for Web of Science ID A1996TP68700011

    View details for PubMedID 8558224

  • THE IMPORTANCE OF THE LUMPECTOMY SURGICAL MARGIN STATUS IN LONG-TERM RESULTS OF BREAST-CONSERVATION CANCER Smitt, M. C., Nowels, K. W., ZDEBLICK, M. J., JEFFREY, S., Carlson, R. W., Stockdale, F. E., Goffinet, D. R. 1995; 76 (2): 259-267

    Abstract

    The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear.The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years.The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors.The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.

    View details for Web of Science ID A1995RH15100015

    View details for PubMedID 8625101

  • Computer-based screening of patients with HIV/AIDS for clinical-trial eligibility. The Online journal of current clinical trials Carlson, R. W., Tu, S. W., Lane, N. M., Lai, T. L., Kemper, C. A., Musen, M. A., Shortliffe, E. H. 1995; Doc No 179: [3347 words, 32 paragraphs]

    Abstract

    To assess the potential effect of a computer-based system on accrual to clinical trials, we have developed methodology to identify retrospectively and prospectively patients who are eligible or potentially eligible for protocols.Retrospective chart abstraction with computer screening of data for potential protocol eligibility.A county-operated clinic serving human immunodeficiency virus (HIV) positive patients with or without acquired immune deficiency syndrome (AIDS).A randomly selected group of 60 patients who were HIV-infected, 30 of whom had an AIDS-defining diagnosis.Using a computer-based eligibility screening system, for each clinic visit and hospitalization, patients were categorized as eligible, potentially eligible, or ineligible for each of the 17 protocols active during the 7-month study period. Reasons for ineligibility were categorized.None of the patients was enrolled on a clinical trial during the 7-month period. Thirteen patients were identified as eligible for protocol; three patients were eligible for two different protocols; and one patient was eligible for the same protocol during two different time intervals. Fifty-four patients were identified as potentially eligible for a total of 165 accrual opportunities, but important information, such as the result of a required laboratory test, was missing, so that eligibility could not be determined unequivocally. Ineligibility for protocol was determined in 414 (35%) potential opportunities based only on conditions that were amenable to modification, such as the use of concurrent medications; 194 (17%) failed only laboratory tests or subjective determinations not routinely performed; and 346 (29%) failed only routine laboratory tests.There are substantial numbers of eligible and potentially eligible patients who are not enrolled or evaluated for enrollment in prospective clinical trials. Computer-based eligibility screening when coupled with a computer-based medical record offers the potential to identify patients eligible or potentially eligible for clinical trial, to assist in the selection of protocol eligibility criteria, and to make accrual estimates.

    View details for PubMedID 7719564

  • Accessing oncology information at the point of care: experience using speech, pen, and 3-D interfaces with a knowledge server. Medinfo. MEDINFO Sherertz, D. D., Tuttle, M. S., Olson, N. E., Hsu, G. T., Carlson, R. W., Fagan, L. M., ACUFF, R. D., Cole, W. G., Nelson, S. J. 1995; 8: 792-795

    Abstract

    Oncologists' information needs arise at diverse times and settings. For example: "Is superior vena cava syndrome a medical emergency?" Our collaborative group is developing a system that supports an interface with combinations of spoken, gestural, and simulated three-dimensional manipulation to help an oncologist focus on the information need, not the system. The system requires a small amount of input from the oncologist, and then anticipates what information is pertinent to the patient at hand, based on the sources it has available. The system makes use of a "Knowledge Server" to find relevant information. The Knowledge Server uses selected data for the particular patient from a Computer-based Patient Record (CPR) to provide context for the information needs. The Knowledge Server leverages the Unified Medical Language System (UMLS) resources as well as relevant communications standards. A layered, interaction protocol is used to help manage the fulfillment of information needs. Each of the oncology knowledge sources is transformed into a uniform representation that utilizes both its formal schema (e.g., its table of contents) and its concepts and words indexed through the UMLS Metathesaurus. Our focus on the appropriate use of information from a CPR, and on anticipating oncologists' information needs, resulted from our study of several longitudinal patient scenarios. We believe that our use of scenario-based design techniques will help to ensure the system's success.

    View details for PubMedID 8591330

  • Semantic visualization of oncology knowledge sources. Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care Cole, W. G., Sherertz, D. D., Tuttle, M. S., Hsu, G. T., Fagan, L. M., Carlson, R. W. 1995: 67-71

    Abstract

    Visualization of knowledge sources can have a substantial impact on the use of such sources at the point of care. This is because barriers to use at the point of care include hours required to master the electronic interfaces to those sources, and minutes required to master the electronic interfaces to those sources, and minutes required to accomplish any one retrieval. For a system to be used regularly at the point of care, therefore, it must be intuitive and fast. This paper presents a three dimensional interface to oncology knowledge sources that aims to meet this challenge.

    View details for PubMedID 8563371

  • METAANALYSIS OF RANDOMIZED TRIALS TESTING THE BIOCHEMICAL MODULATION OF FLUOROURACIL BY METHOTREXATE IN METASTATIC COLORECTAL-CANCER JOURNAL OF CLINICAL ONCOLOGY Piedbois, P., Buyse, M., Blijham, G., Glimelius, B., Herrmann, R. B., Valone, F., Carlson, R., Machiavelli, M., Delfino, C., Abad, A., Petrelli, N. 1994; 12 (5): 960-969
  • Toward a patient-centered knowledge-server standard for CPRs. Proceedings of the 1994 Annual Healthcare Information and Management Systems Society Conference Tuttle MS, Sheretz DD, Fagan LM, Carlson RW, Cole WG, Schipma PB, Nelson SJ. 1994; 88: 114-128
  • INTEGRATION OF PEN-BASED COMPUTER-TECHNOLOGY IN CLINICAL SETTINGS 18th Annual Symposium on Computer Applications in Medical Care - Transforming Information, Changing Health Care ACUFF, R. D., Fagan, L. M., Rindfleisch, T. C., Carlson, R. W., Tuttle, M. S., Sherertz, D. D. BMJ PUBLISHING GROUP. 1994: 1042–1042

    View details for Web of Science ID A1994QF21600245

    View details for PubMedID 7949880

  • IMPACT OF OMEPRAZOLE ON THE PLASMA-CLEARANCE OF METHOTREXATE CANCER CHEMOTHERAPY AND PHARMACOLOGY Reid, T., Yuen, A., CATOLICO, M., Carlson, R. W. 1993; 33 (1): 82-84

    Abstract

    Omeprazole inhibits the gastric hydrogen pump and is an effective treatment for peptic ulcers. Methotrexate is a chemotherapeutic agent that inhibits dihydrofolate reductase and is eliminated by a hydrogen-ion-dependent mechanism in the kidney. We present evidence that omeprazole inhibits methotrexate clearance and may result in potentially toxic methotrexate levels.

    View details for Web of Science ID A1993MC70700014

    View details for PubMedID 8269594

  • A METHODOLOGY FOR DETERMINING PATIENTS ELIGIBILITY FOR CLINICAL-TRIALS METHODS OF INFORMATION IN MEDICINE Tu, S. W., Kemper, C. A., Lane, N. M., Carlson, R. W., Musen, M. A. 1993; 32 (4): 317-325

    Abstract

    The task of determining patients' eligibility for clinical trials is knowledge and data intensive. In this paper, we present a model for the task of eligibility determination, and describe how a computer system can assist clinical researchers in performing that task. Qualitative and probabilistic approaches to computing and summarizing the eligibility status of potentially eligible patients are described. The two approaches are compared, and a synthesis that draws on the strengths of each approach is proposed. The result of applying these techniques to a database of HIV-positive patient cases suggests that computer programs such as the one described can increase the accrual rate of eligible patients into clinical trials. These methods may also be applied to the task of determining from electronic patient records whether practice guidelines apply in particular clinical situations.

    View details for Web of Science ID A1993LQ71400012

    View details for PubMedID 8412828

  • T-HELPER - AUTOMATED SUPPORT FOR COMMUNITY-BASED CLINICAL RESEARCH 16th Annual Symposium on Computer Applications in Medical Care Musen, M. A., Carlson, R. W., Fagan, L. M., Deresinski, S. C., Shortliffe, E. H. MCGRAW-HILL BOOK CO. 1993: 719–723
  • Toward an interim standard for patient-centered knowledge-access. Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care Tuttle, M. S., Sherertz, D. D., Fagan, L. M., Carlson, R. W., Cole, W. G., SCHIPMA, P. B., Nelson, S. J. 1993: 564-568

    Abstract

    Most care-giver "knowledge" needs arise at the point of care and are "patient-centered." Many of these knowledge needs can be met using existing on-line knowledge sources, but the process is too time-consuming, currently, for even the computer-proficient. We are developing a set of public domain standards aimed at bringing potentially relevant knowledge to the point of care in a straight-forward and timely fashion. The standards will a) make use of selected items from a Computer-based Patient Record (CPR), e.g., a diagnosis and measure of severity, b) anticipate certain care-giver knowledge needs, e.g., "therapy," "protocols," "complications," and c) try to satisfy those needs from available knowledge sources, e.g., knowledge-bases, citation databases, practice guidelines, and on-line textbooks. The standards will use templates, i.e., fill-in-the-blank structures, to anticipate knowledge needs and UMLS Metathesaurus enhancements to represent the content of knowledge sources. Together, the standards will form the specification for a "Knowledge-Server" (KS) designed to be accessed from any CPR system. Plans are in place to test an interim version of this specification in the context of medical oncology. We are accumulating anecdotal evidence that a KS operating in conjunction with a CPR is much more compelling to users than either a CPR or a KS operating alone.

    View details for PubMedID 8130537

  • Reducing the cardiotoxicity of the anthracyclines. Oncology (Williston Park, N.Y.) Carlson, R. W. 1992; 6 (6): 95-?

    Abstract

    Most patients are not at risk for anthracycline-associated cardiotoxicity, since the cancer usually develops resistance before a dangerously high cumulative dose can be given. However, select patients may benefit from continued therapy. The physician's goal is to continue to treat these patients without risking drug-related cardiomyopathy. A simple maneuver is to switch from bolus administration to a weekly low-dose or continuous-infusion schedule. Pretreatment with ICRF-187, a new cardioprotective agent currently under investigation, may prove highly useful in the near future. Perhaps most important, the physician must be able to spot the early signs of drug-related cardiac injury. This can be accomplished with radionuclide ventriculography to determine both resting and exercise ejection fractions. Patients shown to be at high risk can then be withdrawn from the drug or further monitored with endomyocardial biopsy and right heart catheterization.

    View details for PubMedID 1535212

  • MODULATION OF FLUOROURACIL BY LEUCOVORIN IN PATIENTS WITH ADVANCED COLORECTAL-CANCER - EVIDENCE IN TERMS OF RESPONSE RATE JOURNAL OF CLINICAL ONCOLOGY Piedbois, P., Buyse, M., Rustum, Y., Machover, D., Erlichman, C., Carlson, R. W., Valone, F., Labianca, R., Doroshow, J. H., Petrelli, N. 1992; 10 (6): 896-903
  • T-HELPER: automated support for community-based clinical research. Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care Musen, M. A., Carlson, R. W., Fagan, L. M., Deresinski, S. C., Shortliffe, E. H. 1992: 719-723

    Abstract

    There are increasing expectations that community-based physicians who care for people with HIV infection will offer their patients opportunities to enroll in clinical trials. The information-management requirements of clinical investigation, however, make it unrealistic for most providers who do not practice in academic centers to participate in clinical research. Our T-HELPER computer system offers community-based physicians the possibility of enrolling patients in clinical trials as a component of primary care. T-HELPER facilitates data management for patients with HIV disease, and can offer patient-specific and situation-specific advice concerning new protocols for which patients may be eligible and the treatment required by those protocols in which patients currently are enrolled. We are installing T-HELPER at three county-operated AIDS clinics in the San Francisco Bay Area, and plan a comprehensive evaluation of the system and its influence on clinical research.

    View details for PubMedID 1482965

  • LATE CONSOLIDATIVE RADIATION-THERAPY IN THE TREATMENT OF LIMITED-STAGE SMALL-CELL LUNG-CANCER CANCER Carlson, R. W., Sikic, B. I., Gandara, D. R., HENDRICKSON, C. G., WITTLINGER, P. S., Shields, J. A., Wong, P. P., WHITE, J. E., MEAKIN, C. J., MCWHIRTER, K. M., Lamborn, K. R., Phillips, T. L. 1991; 68 (5): 948-958

    Abstract

    Two hundred twenty-three patients were enrolled on this randomized Phase III trial testing the value of late consolidative involved-field radiation therapy in the treatment of limited-stage small cell lung cancer (SCLC). Patients were treated with induction chemotherapy consisting of alternating cycles of procarbazine, vincristine, lomustine, and cyclophosphamide (POCC) and etoposide, doxorubicin, and methotrexate (VAM) for 6 to 9 months. Responding patients were then randomized at 6 or 9 months to chemotherapy alone or to involved-field radiation therapy. All partial and complete responders received prophylactic cranial irradiation. Of the 180 eligible and evaluable patients, 80 (44%) achieved a complete response and 39 (22%) achieved a partial response (overall rate of response, 66%). Actuarial median survival time was 11.6 months, with 16% of patients surviving 2 years and 11% surviving 5 years. Forty-eight patients were randomized to chemotherapy alone (24 patients) versus chemotherapy plus involved-field radiation therapy (24 patients). There were no significant differences in time to progression or survival between those patients receiving or not receiving involved-field radiation therapy. The thorax was the site of first relapse in 58% of patients randomized to chemotherapy alone versus 29% in patients randomized to chemotherapy plus involved-field radiation therapy (P equals 0.042). The major acute toxicity was reversible myelosuppression, and the major late toxicity was chronic central nervous system dysfunction. The authors conclude that the addition of late consolidative radiation therapy to induction chemotherapy in the treatment of limited-stage SCLC is well tolerated and improves local control, but does not improve time to progression or rates of survival.

    View details for Web of Science ID A1991GD02500006

    View details for PubMedID 1655219

  • SUCCESSFUL TREATMENT OF METASTATIC THYMIC CARCINOMA WITH CISPLATIN, VINBLASTINE, BLEOMYCIN, AND ETOPOSIDE CHEMOTHERAPY CANCER Carlson, R. W., Dorfman, R. F., Sikic, B. I. 1990; 66 (10): 2092-2094

    Abstract

    Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.

    View details for Web of Science ID A1990EH74500007

    View details for PubMedID 1699650

  • TRIMETREXATE IN LOCALLY ADVANCED OR METASTATIC ADENOCARCINOMA OF THE PANCREAS - A PHASE-II STUDY OF THE NORTHERN CALIFORNIA ONCOLOGY GROUP INVESTIGATIONAL NEW DRUGS Carlson, R. W., Doroshow, J. H., ODUJINRIN, O. O., Flam, M. S., Malec, M., Lamborn, K. R. 1990; 8 (4): 387-389

    View details for Web of Science ID A1990EJ35100009

    View details for PubMedID 2150672

  • A PHASE-II TRIAL OF CARBETIMER FOR THE TREATMENT OF COLORECTAL-CANCER - A TRIAL OF THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS AUDEH, M. W., Jacobs, C. D., Davis, T. E., Carlson, R. W. 1990; 13 (4): 324-326

    Abstract

    Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer.

    View details for Web of Science ID A1990DT05600012

    View details for PubMedID 2198795

  • A MULTIINSTITUTIONAL EVALUATION OF THE ANALGESIC EFFICACY AND SAFETY OF KETOROLAC TROMETHAMINE, ACETAMINOPHEN PLUS CODEINE, AND PLACEBO IN CANCER PAIN PHARMACOTHERAPY Carlson, R. W., BORRISON, R. A., SHER, H. B., Eisenberg, P. D., MOWRY, P. A., WOLIN, E. M. 1990; 10 (3): 211-216

    Abstract

    Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined.

    View details for Web of Science ID A1990DM69100006

    View details for PubMedID 2196536

  • HIGH-DOSE CISPLATIN AND MITOMYCIN-C IN ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II STUDY OF THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP CANCER CHEMOTHERAPY AND PHARMACOLOGY Gandara, D. R., Perez, E. A., WOLD, H., Caggiano, V., Malec, M., Ahn, D. K., Meyers, F., Carlson, R. W. 1990; 27 (3): 243-247

    Abstract

    To investigate chemotherapeutic dose intensity in advanced non-small-cell lung cancer (NSCLC), we evaluated a pharmacokinetically designed schedule of high-dose cisplatin (200 mg/m2 per 28-day cycle) plus mitomycin C. Between March 1987 and March 1989, 62 patients were registered for a phase II study of the Northern California Oncology Group (NCOG). The treatment schedule consisted of cisplatin in hypertonic saline given on a divided days 1 and 8 schedule (100 mg/m2 on each day) plus mitomycin C given at a dose of 8 mg/m2 on day 1 of each cycle. In 61 patients evaluable for response analysis, the overall response rate was 39% (24/61), with a complete response being achieved in 6% (4/61) of cases and a partial response, in 33% (20/61). The response according to reviewed histologic subtype included squamous, 53% of patients (10/19); large cell, 31% (4/13); and adenocarcinoma, 34% (10/29). The median survival for all patients was 29.3 weeks. The mean cisplatin and mitomycin C delivered dose intensities in this study were 45 mg/m2 per week (90% of the projected dose) and 1.5 mg/m2 per week (75%). The toxicity of this combination regimen in the 62 enrolled patients was significant but manageable. Leukopenia (WBC, less than 1,000/mm3) and thrombocytopenia (platelets, less than 25,000/mm3) occurred in 3% and 8% of patients treated, respectively. Dose-limiting renal toxicity and clinically significant ototoxicity developed in 8 patients each (13%), and a peripheral sensory neuropathy was observed in 17 cases (27%). Whether this type of dose-intensive therapy results in an improved therapeutic index in NSCLC is currently being evaluated in a randomized comparative trial versus standard-dose cisplatin therapy.

    View details for Web of Science ID A1990EN24500013

    View details for PubMedID 2176134

  • ENHANCEMENT OF THE CLINICAL ACTIVITY OF MELPHALAN BY THE HYPOXIC CELL SENSITIZER MISONIDAZOLE CANCER RESEARCH Coleman, C. N., Carlson, R. W., Halsey, J., Kohler, M., Gribble, M., Sikic, B. I., Jacobs, C. 1988; 48 (12): 3528-3532

    Abstract

    One hundred patients with non-small cell lung cancer were entered by members of the Northern California Oncology Group into a randomized Phase II trial of i.v. melphalan versus i.v. melphalan with concomitant oral misonidazole. The patients had not received prior chemotherapy. Eighty-five patients were evaluable for assessment of response and 89 were evaluable for toxicity analysis. The melphalan/misonidazole group had a superior response rate (two complete and four partial responses among 42 patients or 14%) compared to the melphalan group in which there were no responses among 43 patients (p = 0.024, two-sided Fisher exact test). Since hematological toxicity was equivalent in the two groups, there was an improvement in therapeutic index. Data from 12 patients undergoing pharmacological studies demonstrated that the plasma concentration of melphalan was 25% higher in the misonidazole group, a difference that is not statistically significant. Although the mechanism of interaction has not been fully established, this randomized trial demonstrates that a chemosensitizer can enhance the clinical antitumor activity of an alkylating agent and suggests that chemosensitizers in combination with alkylating agents should be investigated in further clinical trials.

    View details for Web of Science ID A1988N713400041

    View details for PubMedID 2836059

  • THE CLINICAL BIOLOGY OF BREAST-CANCER ANNUAL REVIEW OF MEDICINE Carlson, R. W., Stockdale, F. E. 1988; 39: 453-464

    Abstract

    Breast cancers present as a spectrum of neoplasms. The natural histories of the neoplasms are tied to the biological properties of the neoplastic cells that compose them. We review the histological, cytological, kinetic, and other parameters that best characterize the clinical biology of breast cancer.

    View details for Web of Science ID A1988M825500037

    View details for PubMedID 2835930

  • PHASE-II EVALUATION OF ORAL MEDROXYPROGESTERONE ACETATE IN ADVANCED BREAST-CANCER - A NORTHERN CALIFORNIA ONCOLOGY GROUP-STUDY CANCER TREATMENT REPORTS Tan, Y. O., Hendrickson, C., MCWHIRTER, K., Kohler, M., Hannigan, J. F., Carlson, R. W. 1987; 71 (10): 969-970

    View details for Web of Science ID A1987K718800015

    View details for PubMedID 2958131

  • ESOPHAGEAL-CARCINOMA - MODEST BENEFITS FROM COMBINED MODALITY THERAPY RADIOLOGY Hancock, S. L., Goffinet, D. R., Carlson, R. W., Mark, J. B. 1987; 164 (3): 603-606

    Abstract

    Between 1969 and 1986, 109 consecutive patients with esophageal carcinoma were studied. Of the 77 patients who had squamous cell carcinoma, 62 received definitive treatment for disease confined to the esophagus and regional nodes. Survival was equivalent whether they were treated with radiation alone (n = 18), preoperative radiation and esophagectomy (n = 19), postoperative radiation (n = 5), or a combination of chemotherapy and radiation with or without esophagectomy (n = 20). Fifteen patients had significantly poorer survival after palliative irradiation for overt metastatic disease or severe debility. The pathologic specimens from four of the nine patients who underwent resection showed no histologic evidence of residual tumor; however, tumor recurred in three in the mediastinum, and only one remains alive and free of disease. Four of the 11 patients who received chemotherapy and radiation therapy without resection remain alive and free of disease after further mediastinal irradiation, suggesting a benefit from additional regional therapy. Chemotherapy improved median survival duration and complete response rate but did not produce a significant improvement in survival, as reported in other recent series.

    View details for Web of Science ID A1987J665300003

    View details for PubMedID 3112863

  • Combined modality therapy of locally advanced breast cancer. One institution's experience and a review of the literature. Anticancer research Hu, E., Stockdale, F. E., Turner, B., Carlson, R. W., Levine, J., KUSHLAN, P. 1987; 7 (4B): 733-736

    Abstract

    Fourteen patients with locally advanced breast cancer were treated at Stanford University Medical Center with a combined modality approach. Treatment consisted of an initial 5 day course of cyclophosphamide followed by three cycles of combination chemotherapy (CAF or CMF). Patients subsequently received radiation therapy to the involved breast and regional nodal areas, followed by mastectomy if resistant disease was present following irradiation. Additional chemotherapy (CMF) was administered for 6 cycles. With a median follow up of 42 months, all fourteen patients are free of local disease. Five out of the fourteen patients have experienced distant relapses and two patients died. We conclude that an aggressive combined modality approach to treatment of locally advanced breast cancer can result in excellent local control and survival even in poor prognosis patients. A review of pertinent studies on multimodality treatment for locally advanced breast cancer confirms our findings.

    View details for PubMedID 3314673

  • PHASE-II TRIAL OF ESORUBICIN IN THE TREATMENT OF METASTATIC CARCINOMA OF THE KIDNEY - A STUDY OF THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP CANCER TREATMENT REPORTS Carlson, R. W., Williams, R. D., Billingham, M. E., Kohler, M., Torti, F. M. 1987; 71 (7-8): 767-768

    View details for Web of Science ID A1987J624500020

    View details for PubMedID 3607787

  • COMBINED MODALITY THERAPY OF LOCALLY ADVANCED BREAST-CANCER - ONE INSTITUTIONS EXPERIENCE AND A REVIEW OF THE LITERATURE ANTICANCER RESEARCH Hu, E., Stockdale, F. E., Turner, B., Carlson, R. W., Levine, J., KUSHLAN, P. 1987; 7 (4): 733-736
  • BLEOMYCIN, MITOMYCIN, AND CISPLATIN THERAPY FOR ADVANCED SQUAMOUS CARCINOMA OF THE UTERINE CERVIX - A PHASE-II STUDY OF THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP CANCER TREATMENT REPORTS Picozzi, V. J., Sikic, B. I., Carlson, R. W., Koretz, M., Ballon, S. C. 1985; 69 (7-8): 903-905

    Abstract

    Twenty-eight patients with advanced squamous carcinoma of the uterine cervix received cisplatin, bleomycin, and mitomycin after failure of surgery and/or irradiation to control disease. Six patients (21%) achieved responses (two complete; four partial), ranging from 3 to 7+ months. Toxicity was acceptable for most patients; however, dose reduction because of myelosuppression was frequently required. Bleomycin was delivered by continuous iv infusion, and no significant pulmonary toxicity was observed. Although this combination of drugs has activity in advanced squamous carcinoma of the uterine cervix, the addition of cisplatin to bleomycin and mitomycin did not significantly increase the clinical response rate.

    View details for Web of Science ID A1985APC8900032

    View details for PubMedID 2410123

  • IMPROVEMENTS IN DATA-COLLECTION THROUGH PHYSICIAN USE OF A COMPUTER-BASED CHEMOTHERAPY TREATMENT CONSULTANT JOURNAL OF CLINICAL ONCOLOGY Kent, D. L., Shortliffe, E. H., Carlson, R. W., BISCHOFF, M. B., Jacobs, C. D. 1985; 3 (10): 1409-1417

    Abstract

    The impact of a computer-based data management system on the completeness of clinical trial data was studied before and after the system's introduction in an oncology clinic. Physicians use the system, termed ONCOCIN, to record data during patient visits and to receive advice about treatment and tests required by experimental cancer protocols. Although ONCOCIN does not force the user to enter all data expected by the protocol, after its introduction there was improvement in the recording frequency of such data. The percentage of expected physical findings recorded increased from 74% to 91% (P less than .05), toxicity history from less than 1% to 45% (P less than .01), general chemistry results from 36% to 82% (P less than .01), x-ray results from 44% to 73% (P less than .01), and physicians' assessments of overall disease activity and Karnofsky performance status from 73% to 91% (P less than .05). Analysis of the steps in data collection and their contribution to loss of data suggests that observations or test ordering which are dependent on the physician are most improved by the system. Furthermore, analysis of post-ONCOCIN visits when the system was unavailable suggests that the recording of physician-dependent data (physical findings and assessments of disease activity and performance status) is likely to revert to pre-ONCOCIN levels if the system is not used routinely. The results show that ONCOCIN can greatly enhance recovery of those data expected for chemotherapy protocol patients. The program's interaction with the physician is central to its effectiveness in data collection, especially for data that arise directly from the patient-physician encounter.

    View details for Web of Science ID A1985ART2400018

    View details for PubMedID 3840200

  • EVALUATION OF COMPUTER-BASED INTERACTIVE DATA MANAGEMENT FOR CLINICAL-TRIALS Kent, D. L., Carlson, R. W., Jacobs, C. D., Shortliffe, E. H. SLACK INC. 1984: A31–A31
  • CONTINUOUS INFUSION OR BOLUS INJECTION IN CANCER-CHEMOTHERAPY ANNALS OF INTERNAL MEDICINE Carlson, R. W., Sikic, B. I. 1983; 99 (6): 823-833

    Abstract

    Continuous intravenous infusion of anticancer drugs is being incorporated into more experimental chemotherapy protocols. The rationale for use of continuous infusions generally includes the restriction of cytotoxic mechanisms of a drug to a specific phase of the cell cycle and the short half-life of some drugs. Two such agents are cytarabine and bleomycin; continuous exposure to these drugs greatly increases their antitumor effects in cell cultures and animal models. Toxicity to normal tissues may also be reduced by continuous infusion, notably the pulmonary toxicity of bleomycin, the cardiac toxicity of doxorubicin, and the myelosuppression of fluorouracil. Recent advances in infusion pump technology have made continuous intravenous infusion therapy more practical. Unfortunately, most clinical studies of the continuous infusion of anticancer drugs have been uncontrolled. Further randomized, controlled clinical trials comparing schedules of drug administration are necessary before definitive recommendations can be made.

    View details for Web of Science ID A1983RU40300016

    View details for PubMedID 6197002

  • COMBINATION CISPLATIN, VINBLASTINE, AND BLEOMYCIN CHEMOTHERAPY (PVB) FOR MALIGNANT GERM-CELL TUMORS OF THE OVARY JOURNAL OF CLINICAL ONCOLOGY Carlson, R. W., Sikic, B. I., Turbow, M. M., Ballon, S. C. 1983; 1 (10): 645-651

    Abstract

    Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.

    View details for Web of Science ID A1983RM39600009

    View details for PubMedID 6199468

  • CLINICAL INTEGRATION TO PROMOTE USE AND ACCEPTANCE OF A COMPUTER-BASED CONSULTANT Shortliffe, E. H., BISCHOFF, M. B., Carlson, R. W., Jacobs, C. D. HANLEY & BELFUS INC. 1983: 358–58