Carol Marquez, MD

All Publications

• A phase 2 single-arm trial of high-dose precision targeted radiotherapy added to immunotherapy for patients with metastatic non-small cell lung cancer. International journal of radiation oncology, biology, physics Gensheimer, M. F., Kotha, N. V., Vitzthum, L. K., Chin, A. L., Jackson, S., 't Erve, I. v., Pratapneni, A., Le-Budka, M. L., Wong, S., Brown, E., Barnick, K., Wakelee, H. A., Das, M., Ramchandran, K. J., Myall, N. J., Padda, S., Marquez, C. M., Million, L., Chen, T. T., Man, M. C., Cabebe, E. C., Chen, M. C., Hiniker, S., Hancock, S. L., Swift, P. S., Diehn, M., Loo, B. W., Neal, J. W. 2024

  Abstract

  For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS).In this single arm phase 2 trial, 45 patients with metastatic NSCLC who had received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017-May 2021. Patients received high-dose RT to 1-4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing to a historical control rate of 35%.Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1 positive. Median number of treated tumors was two and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI 44-75%), higher than the historical control rate (p<0.001). Median PFS was 6.9 months (95% CI 4.0-13.5 mo) and median OS was 27.4 months (95% CI 20.4-not reached). Several patients with pre-study disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis.The strategy improved 24-week PFS compared to historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.

  View details for DOI 10.1016/j.ijrobp.2024.09.038

  View details for PubMedID 39357790

• INVESTIGATING THE PREDICTIVE UTILITY OF DOSIMETRY AND IMAGING FOR GRADE ≥3 CARDIAC EVENTS AFTER BREAST CANCER RADIOTHERAPY Guo, F., No, H., Butler, S., Jackson, S., Rhee, J., Clark, D., Marquez, C., Horst, K., Binkley, M. ELSEVIER SCIENCE INC. 2024: 2658

  View details for Web of Science ID 001324901502692

• An affordable platform for virtual reality-based patient education in radiation therapy. Practical radiation oncology Schulz, J. B., Dubrowski, P., Blomain, E., Million, L., Qian, Y., Marquez, C., Yu, A. S. 2023

  Abstract

  The goal of this study is to develop and assess the effectiveness of an affordable smartphone-based Virtual Reality (VR) patient education platform with 360-degree videos produced depicting a first-person patient perspective during the radiation therapy (RT) care path to reduce patient anxiety.and Materials Three disease site-specific (breast, pelvis, head and neck) VR-videos were filmed using a 360-degree camera to portray the first-person perspective of a patient's standard RT appointments: including a Computed Tomography (CT) simulation and the first RT treatment session. Instruction is given for possible clinical implementation. Patient participation was divided into two groups: 1) Group-A (n=28) included patients participating before simulation and later after the first treatment, and 2) Group-B (n=33) included patients participating only while undergoing treatment. Patients viewed their disease site-specific video using an inexpensive cardboard VR-viewer and their smartphone, emulating an expensive VR-headset. Surveys were administered assessing patient anxiety, comfort, satisfaction, and knowledge of RT on a 5-point Likert-type scale.Patients in Group-A and Group-B while undergoing treatment both selected their anxiety "decreased a little" in the survey, after watching the VR-video (Group-A, median on a 5-point Likert-type scale, 4 [interquartile range {IQR}, 4-5]; Group-B, 4 [IQR 4-4]). The VR aspect of the videos was especially liked by patients while undergoing treatment, with 96.4% in Group-A and 90.9% in Group-B reporting that the VR aspect of the videos was helpful. All Group-A participants believed that the VR-videos would be beneficial to new patients.Our affordable VR patient education platform effectively immerses a patient in their care path from simulation through initial treatment delivery, reducing anxiety and increasing familiarity with the treatment process.

  View details for DOI 10.1016/j.prro.2023.06.008

  View details for PubMedID 37482182

• Call for action: expanding global access to hereditary cancer genetic testing. The Lancet. Oncology Bychkovsky, B., Rana, H. Q., Ademuyiwa, F., Plichta, J., Anderson, K., Nogueira-Rodrigues, A., Santa-Maria, C. A., Coffman, L. G., Marquez, C., Das, A., Taghian, A., Koeller, D. R., Sandoval, R. L., Park, B. H., Dizon, D. S. 2022; 23 (9): 1124-1126

  View details for DOI 10.1016/S1470-2045(22)00378-3

  View details for PubMedID 36055301

• ASTRO Editorial: ONS Guidelines for Cancer Treatment-Related Radiodermatitis. Practical radiation oncology Marquez, C. M., Wong, W. 2021; 11 (5): 352-353

  View details for DOI 10.1016/j.prro.2021.05.005

  View details for PubMedID 34479660

• CT-less electron radiotherapy simulation and planning with a consumer 3D camera. Journal of applied clinical medical physics Skinner, L., Knopp, R., Wang, Y., Dubrowski, P., Bush, K. K., Limmer, A., Trakul, N., Million, L., Marquez, C. M., Yu, A. S. 2021

  Abstract

  PURPOSE: Electron radiation therapy dose distributions are affected by irregular body surface contours. This study investigates the feasibility of three-dimensional (3D) cameras to substitute for the treatment planning computerized tomography (CT) scan by capturing the body surfaces to be treated for accurate electron beam dosimetry.METHODS: Dosimetry was compared for six electron beam treatments to the nose, toe, eye, and scalp using full CT scan, CT scan with Hounsfield Unit (HU) overridden to water (mimic 3D camera cases), and flat-phantom techniques. Radiation dose was prescribed to a depth on the central axis per physician's order, and the monitor units (MUs) were calculated. The 3D camera spatial accuracy was evaluated by comparing the 3D surface of a head phantom captured by a 3D camera and that generated with the CT scan in the treatment planning system. A clinical case is presented, and MUs were calculated using the 3D camera body contour with HU overridden to water.RESULTS: Across six cases the average change in MUs between the full CT and the 3Dwater (CT scan with HU overridden to water) calculations was 1.3% with a standard deviation of 1.0%. The corresponding hotspots had a mean difference of 0.4% and a standard deviation of 1.9%. The 3D camera captured surface of a head phantom was found to have a 0.59mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213±8cGy) agreed with the 3D-camera planned dose of 209±6cGy, compared to 192±6cGy for the flat-phantom calculation (same MUs).CONCLUSIONS: Electron beam dosimetry is affected by irregular body surfaces. 3D cameras can capture irregular body contours which allow accurate dosimetry of electron beam treatment as an alternative to costly CT scans with no extra exposure to radiation. Tools and workflow for clinical implementation are provided.

  View details for DOI 10.1002/acm2.13283

  View details for PubMedID 34042253

• Locoregional and Distant Outcomes in Women With cT1-3N1 Breast Cancer Treated With Neoadjuvant Chemotherapy With or Without Adjuvant Radiotherapy. Clinical breast cancer Kozak, M. M., von Eyben, R., Gutkin, P. M., Vemuri, M., Jacobson, C. E., Karl, J. J., Walck, E., Marquez, C., Horst, K. C. 2021

  Abstract

  BACKGROUND: We evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC).PATIENTS AND METHODS: We retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0.RESULTS: After excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P < .001) and/or lymphovascular invasion (P=.03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P=.04) and/or if they had ypN+ disease (P=.01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n=98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P=.23).CONCLUSION: Recommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.

  View details for DOI 10.1016/j.clbc.2021.02.008

  View details for PubMedID 33766533

• ONS Guidelines for Cancer Treatment-Related Radiodermatitis. Oncology nursing forum Gosselin, T., Ginex, P. K., Backler, C., Bruce, S. D., Hutton, A., Marquez, C. M., McGee, L. A., Shaftic, A. M., Suarez, L. V., Moriarty, K. A., Maloney, C., Vrabel, M., Morgan, R. L. 2020; 47 (6): 654–70

  Abstract

  PURPOSE: Radiodermatitis is a side effect of radiation therapy. Evidence-based interventions to minimize severity or delay progression are important for clinical care. This guideline intends to support individuals with cancer, clinicians, and others in decisions regarding radiodermatitis treatment.METHODOLOGIC APPROACH: A panel of healthcare professionals with patient representation was convened to develop a national clinical practice guideline for the management of radiodermatitis. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and the National Academies of Sciences, Engineering, and Medicine criteria for trustworthy guidelines were followed. The Cochrane Collaboration risk-of-bias tool was used, and certainty of the evidence was assessed using the GRADE approach. A quantitative and narrative synthesis of the evidence was completed.FINDINGS: The panel agreed on eight recommendations and made a conditional recommendation for deodorant/antiperspirant. Aloe vera and oral curcumin had knowledge gaps and were recommended only in the context of a clinical trial. The panel suggested against emu oil, calendula, and nonsteroidal interventions.IMPLICATIONS FOR NURSING: This guideline summarizes evidence-based interventions for the management of radiodermatitis to guide clinical care.SUPPLEMENTARY MATERIAL CAN BE FOUND AT&NBSP;HTTPS: //bit.ly/2GEwJtT.

  View details for DOI 10.1188/20.ONF.654-670

  View details for PubMedID 33063779

• A randomized phase II study comparing surgical excision versus NeOadjuvant Radiotherapy followed by delayed surgical excision of Ductal carcinoma In Situ (NORDIS) Wapnir, I., DeMartini, W., Allison, K., Stone, K., Dirbas, F., Marquez, C., Ikeda, D., Pal, S., Tsai, J., Yang, R., West, R., McMillan, A., Telli, M., Horst, K. AMER ASSOC CANCER RESEARCH. 2020

  View details for DOI 10.1158/1538-7445.SABCS19-OT3-09-04

  View details for Web of Science ID 000527012500151

• Representation of Women Among Invited Speakers at Medical Specialty Conferences. Journal of women's health (2002) Larson, A. R., Sharkey, K. M., Poorman, J. A., Kan, C. K., Moeschler, S. M., Chandrabose, R., Marquez, C. M., Dodge, D. G., Silver, J. K., Nazarian, R. M. 2019

  Abstract

  Background: Gender-related differences have been found among invited speakers in select professional and medical societies. We examined whether similar disparities existed among keynote speakers, plenary speakers, and invited lecturers in a broad range of medical specialty conferences from 2013 to 2017. Materials and Methods: A cross-sectional study was performed on 27 U.S. medical specialty conferences for which data were available on plenary speakers, keynote speakers, and/or invited lecturers. For each speaker, gender and degree(s) were determined. Fisher's exact test was performed to compare proportions of women among speakers to Association of American Medical Colleges' (AAMC) physician workforce data on gender distribution. Results: In aggregate, we identified 246 women among 984 speakers, significantly lower than expected when compared with 2015 AAMC data (25.0% vs. 34.0%; p<0.00001). Compared with AAMC data reported in 2013, 2015, and 2017, women were significantly underrepresented in 2013 (p=0.0064) and 2015 (p=0.00004). In 2017, the proportion of women among invited speakers trended lower than AAMC active women physicians but did not reach significance (p=0.309). Analysis of individual conference data stratified by year indicated that, while the representation of women among all speakers improved between 2015 and 2017, the representation of women among keynote speakers, plenary speakers, and invited lectureships was variable (including zero levels some years during the study period) and remained lower than expected as compared with workforce data for specific medical specialties. Conclusions: Evaluating for and improving disparities is recommended to ensure gender equity among invited speakers across all medical specialty conferences.

  View details for DOI 10.1089/jwh.2019.7723

  View details for PubMedID 31687866

• Observe, and Keep Chemotherapy Up the Sleeve INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Marquez, C. 2018; 100 (3): 550

  View details for PubMedID 29413268

• Treatment of hormone-refractory prostate cancer with Y-90-CYT-356 monoclonal antibody CLINICAL CANCER RESEARCH Deb, N., Goris, M., Trisler, K., Fowler, S., Saal, J., Ning, S. C., Becker, M., Marquez, C., Knox, S. 1996; 2 (8): 1289-1297

  Abstract

  A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving

  View details for Web of Science ID A1996VB19900006

  View details for PubMedID 9816299

• Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma CLINICAL CANCER RESEARCH Knox, S. J., Goris, M. L., Trisler, K., Negrin, R., Davis, T., Liles, T. M., GRILLOLOPEZ, A., Chinn, P., Varns, C., Ning, S. C., Fowler, S., Deb, N., Becker, M., Marquez, C., Levy, R. 1996; 2 (3): 457-470

  Abstract

  A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with

  View details for Web of Science ID A1996TY62000004

  View details for PubMedID 9816191

• Treatment of cutaneous T-Cell lymphoma with chimeric anti-CD4 monoclonal antibody BLOOD Knox, S., Hoppe, R. T., Maloney, D., Gibbs, I., Fowler, S., Marquez, C., Cornbleet, P. J., Levy, R. 1996; 87 (3): 893-899

  Abstract

  Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.

  View details for Web of Science ID A1996TT48400008

  View details for PubMedID 8562959

• MUSCLE CRAMPING IN PHASE-I CLINICAL-TRIALS OF TIRAPAZAMINE (SR-4233) WITH AND WITHOUT RADIATION 8th International Conference on Chemical Modifiers of Cancer Treatment Doherty, N., Hancock, S. L., Kaye, S., Coleman, C. N., Shulman, L., Marquez, C., Mariscal, C., Rampling, R., Senan, S., ROEMELING, R. V. PERGAMON-ELSEVIER SCIENCE LTD. 1994: 379–82

  Abstract

  Tirapazamine (SR 4233) is a benzotriazine di-N-oxide which acts as a hypoxic cytotoxic agent and as a radiation enhancer when given shortly before or after radiation. Three Phase I clinical trials were designed to determine the maximum tolerated dose, toxicities, pharmacokinetics, and effects on irradiated tumors and normal tissues.Tirapazamine 9 mg/m2 to 21 mg/m2 was given i.v. 1/2 to 1 h prior to irradiation on a multiple dose schedule of 10 consecutive doses. This was later revised to a three times-per-week schedule for 12 doses. In a second clinical trial, tirapazamine was given in a single dose of 18 mg/m2 to 293 mg/m2 i.v. after irradiation. In a third trial, tirapazamine was administered without irradiation in single doses of 36 mg/m2 to 250 mg/m2, with an option for retreatment.Subjects reported muscle cramping of varying degrees of severity on all three dose schedules. One patient experienced Grade 3 cramping and treatment was discontinued. The most frequent site of cramping were the lower extremities. Creatine phosphokinase (CPK) values were elevated in three patients with associated muscle soreness in one patient. MB (cardiac) isoenzymes were elevated in one patient with no evidence of cardiac muscle damage, and returned to baseline at drug completion. No consistent abnormalities in clinical laboratory values were found. Stretching of the muscle was most effective in relieving the cramping.Muscle cramping has been the most frequently reported toxicity in Phase I studies of tirapazamine, though it does not appear to be dose limiting. Dose escalation on the three clinical trials continues. In vitro studies to investigate the cramping are ongoing.

  View details for Web of Science ID A1994NN51200028

  View details for PubMedID 8195037

• EFFECT OF FILGRASTIM (G-CSF) IN HODGKINS-DISEASE PATIENTS TREATED WITH RADIATION INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Knox, S. J., Fowler, S., Marquez, C., Hoppe, R. T. 1994; 28 (2): 445-450

  Abstract

  To evaluate the effect of filgrastim (recombinant human G-CSF) on radiation-induced neutropenia in a well defined, homogenous patient population.Seven patients who were to receive large field subdiaphragmatic irradiation after thoracic "mantle" fields for treatment of Hodgkin's disease entered this study. They received daily subcutaneous (SC) injections of filgrastim during subdiaphragmatic irradiation. Total white blood cell (WBC) and absolute neutrophil cell (ANC) counts were measured and compared to a historical series of patients, and hematological toxicity was assessed. The endpoints of the study were nadir WBC and ANC counts and time to WBC and ANC recovery.Compared to the historical series, filgrastim significantly increased the WBC and ANC throughout the period of subdiaphragmatic irradiation. Nadir WBC (5.98 +/- 1.24/mm3) and ANC (4.71 +/- 1.07/mm3) in the Filgrastim group were approximately two times those of the historical series (3.32 +/- 1.06/mm3 and 2.39 +/- 0.97/mm3 respectively; p < 0.002). Nadir platelet counts were not affected by filgrastim therapy. Three of seven patients reported mild musculoskeletal pain, but there was no other apparent toxicity.Compared to the historical series, filgrastim therapy significantly increased WBC and ANC during extended field radiation therapy and was well tolerated. It may be clinically useful in other groups of patients who are likely to develop profound neutropenia during large field irradiation.

  View details for Web of Science ID A1994MP98100015

  View details for PubMedID 7506247