Kavitha Ramchandran

All Publications

• Automated patient selection and care coaches to increase advance care planning for cancer patients. Journal of the National Cancer Institute Gensheimer, M. F., Teuteberg, W., Patel, M. I., Gupta, D., Noroozi, M., Ling, X., Fardeen, T., Seevaratnam, B., Lu, Y., Alves, N., Rogers, B., Asuncion, M. K., Denofrio, J., Hansen, J., Shah, N. H., Chen, T., Cabebe, E., Blayney, D. W., Colevas, A. D., Ramchandran, K. 2024

  Abstract

  Advance care planning/serious illness conversations can help clinicians understand patients' values and preferences. There are limited data on how to increase these conversations, and their effect on care patterns. We hypothesized that using a machine learning survival model to select patients for serious illness conversations, along with trained care coaches to conduct the conversations, would increase uptake in cancer patients at high risk of short-term mortality.We conducted a cluster-randomized stepped wedge study on the physician level. Oncologists entered the intervention condition in a random order over six months. Adult patients with metastatic cancer were included. Patients with <2 year computer-predicted survival and no prognosis documentation were classified as high-priority for serious illness conversations. In the intervention condition, providers received automated weekly emails highlighting high-priority patients and were asked to document prognosis for them. Care coaches reached out to these patients to conduct the remainder of the conversation. The primary endpoint was proportion of visits with prognosis documentation within 14 days.6,372 visits in 1,825 patients were included in the primary analysis. The proportion of visits with prognosis documentation within 14 days was higher in the intervention condition than control condition: 2.9% vs 1.1% (adjusted odds ratio 4.3, p < .0001). The proportion of visits with advance care planning documentation was also higher in the intervention condition: 7.7% vs 1.8% (adjusted odds ratio 14.2, p < .0001). In high-priority visits, advance care planning documentation rate in intervention/control visits was 24.2% vs 4.0%.The intervention increased documented conversations, with contributions by both providers and care coaches.

  View details for DOI 10.1093/jnci/djae243

  View details for PubMedID 39348179

• 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

• Using Patient-Related Outcomes Data to Inform About a Novel Exercise Program in Oncology Patients. Journal of cancer education : the official journal of the American Association for Cancer Education Sibley, A., Schapira, L., Ramchandran, K. 2024

  View details for DOI 10.1007/s13187-024-02470-5

  View details for PubMedID 38954163

• Survivorship in Advanced Lung Cancer: Understanding a New Landscape and Opportunities. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Presley, C. J., Dalal, N., Davenport, A. P., Gounden, A., Ramchandran, K., Tonorezos, E. 2024; 44 (3): e433298

  Abstract

  People with advanced lung cancer represent a distinct group whose needs remain understudied, especially compared with people diagnosed with limited-stage disease. Fortunately, novel treatments such as tyrosine kinase inhibitors and immune checkpoint inhibitors are leading to significant advances in prognosis and survival, even among those with advanced disease at the time of diagnosis. However, there are known gaps in symptom management, psychosocial and nutritional support, complex care coordination, health behavior coaching, and health care delivery efforts among patients living with advanced lung cancer. Many of these patients would benefit from survivorship and palliative care approaches. In particular, survivorship care may include health care maintenance, treatment of immune-related adverse events and late- or long-term effects, frailty assessment and rehabilitation, and care coordination. Palliative care may be best suited to discuss ongoing symptom management, advanced care planning, and end-of-life considerations, as well as psychosocial well-being. To this end, we share a review of the current status of the palliative and survivorship care infrastructure for patients with advanced lung cancer and provide suggestions across the care continuum for this diverse group of patients and families.

  View details for DOI 10.1200/EDBK_433298

  View details for PubMedID 38768420

• Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial. Clinical lung cancer Hui, C., Brown, E., Wong, S., Das, M., Wakelee, H., Neal, J., Ramchandran, K., Myall, N. J., Pham, D., Xing, L., Yang, Y., Kovalchuk, N., Yuan, Y., Lu, Y., Xiang, M., Chin, A., Diehn, M., Loo, B. W., Vitzthum, L. K. 2023

  Abstract

  Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint.PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.

  View details for DOI 10.1016/j.cllc.2023.11.004

  View details for PubMedID 38040540

• Lessons Learned from a Multi-Site, Team-Based Serious Illness Care Program Implementation at an Academic Medical Center. Journal of palliative medicine Seevaratnam, B., Wang, S., Fong, R., Hui, F., Callahan, A., Chobot, S., Gensheimer, M. F., Li, R. C., Nguyen, D., Ramchandran, K., Shah, N. H., Shieh, L., Zeng, J. G., Teuteberg, W. 2023

  Abstract

  Background: Patients with serious illness benefit from conversations to share prognosis and explore goals and values. To address this, we implemented Ariadne Labs' Serious Illness Care Program (SICP) at Stanford Health Care. Objective: Improve quantity, timing, and quality of serious illness conversations. Methods: Initial implementation followed Ariadne Labs' SICP framework. We later incorporated a team-based approach that included nonphysician care team members. Outcomes included number of patients with documented conversations according to clinician role and practice location. Machine learning algorithms were used in some settings to identify eligible patients. Results: Ambulatory oncology and hospital medicine were our largest implementation sites, engaging 4707 and 642 unique patients in conversations, respectively. Clinicians across eight disciplines engaged in these conversations. Identified barriers that included leadership engagement, complex workflows, and patient identification. Conclusion: Several factors contributed to successful SICP implementation across clinical sites: innovative clinical workflows, machine learning based predictive algorithms, and nonphysician care team member engagement.

  View details for DOI 10.1089/jpm.2023.0254

  View details for PubMedID 37935036

• Study of Patient and Physician Attitudes Toward Automated Prognostic Models for Patients With Metastatic Cancer. JCO clinical cancer informatics Hildebrand, R. D., Chang, D. T., Ewongwoo, A. N., Ramchandran, K. J., Gensheimer, M. F. 2023; 7: e2300023

  Abstract

  For patients with cancer and their doctors, prognosis is important for choosing treatments and supportive care. Oncologists' life expectancy estimates are often inaccurate, and many patients are not aware of their general prognosis. Machine learning (ML) survival models could be useful in the clinic, but there are potential concerns involving accuracy, provider training, and patient involvement. We conducted a qualitative study to learn about patient and oncologist views on potentially using a ML model for patient care.Patients with metastatic cancer (n = 15) and their family members (n = 5), radiation oncologists (n = 5), and medical oncologists (n = 5) were recruited from a single academic health system. Participants were shown an anonymized report from a validated ML survival model for another patient, which included a predicted survival curve and a list of variables influencing predicted survival. Semistructured interviews were conducted using a script.Every physician and patient who completed their interview said that they would want the option for the model to be used in their practice or care. Physicians stated that they would use an AI prognosis model for patient triage and increasing patient understanding, but had concerns about accuracy and explainability. Patients generally said that they would trust model results completely if presented by their physician but wanted to know if the model was being used in their care. Some reacted negatively to being shown a median survival prediction.Patients and physicians were supportive of use of the model in the clinic, but had various concerns, which should be addressed as predictive models are increasingly deployed in practice.

  View details for DOI 10.1200/CCI.23.00023

  View details for PubMedID 37478393

• Patient-reported distress at a cancer center during the COVID-19 pandemic. Scientific reports Shah, M. P., Rosenthal, S. W., Roy, M., Khaki, A. R., Hernandez-Boussard, T., Ramchandran, K. 2023; 13 (1): 9581

  Abstract

  Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.

  View details for DOI 10.1038/s41598-023-36025-3

  View details for PubMedID 37311790

  View details for PubMedCentralID 7450263

• Pulmonary Hemorrhage in Patients Treated with Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Lau, B., Wu, Y. F., No, H. J., Ko, R. B., Devine, M., Das, M. S., Neal, J. W., Wakelee, H. A., Ramchandran, K., Gensheimer, M. F., Diehn, M., Chin, A. L., Loo, B. W., Vitzthum, L. K. 2023

  Abstract

  Severe pulmonary hemorrhage can occur in patients treated with thoracic stereotactic ablative radiotherapy (SABR) and vascular endothelial growth factor inhibitors (VEGFi). There is limited understanding of which patients are at risk for toxicity with the combination of thoracic SABR and VEGFis or how the risk differs over either therapy alone.We evaluated a prospectively maintained cohort of 690 patients with 818 pulmonary tumors treated with highly conformal SABR. Rates of any grade and grade-three-plus (G3+) pulmonary hemorrhage were compared between patients treated with or without VEGFi therapy across tumor locations. Outcomes were compared between patients treated with SABR + VEGFi and a propensity-matched cohort of those treated with VEGFi therapy alone.Treatment with VEGFi + SABR was associated with higher rates of G3+ pulmonary hemorrhage compared to those treated with SABR alone for the overall cohort (3-year incidence: 7.9% vs 0.6%, p<0.01) and those with central tumors (19.1% vs 3.3%, p=0.04). When further subdivided, there were significantly higher toxicity rates with VEGFi for the ultracentral (9.0% vs 45.0%, p = 0.044), but not central non-abutting tumors (0.0% vs 1.3% p = 0.69). There was an increased incidence of G3+ hemorrhage in patients treated with VEGFi + SABR compared to VEGFi alone (9.6 vs 1.3%, p=0.04).The combination of VEGFi and SABR was associated with an increased risk of high-grade pulmonary hemorrhage over either therapy alone. Low rates of toxicity were observed when excluding patients with SABR to ultracentral tumors and applying highly conformal SABR techniques.

  View details for DOI 10.1016/j.jtho.2023.04.007

  View details for PubMedID 37085030

• Real-world risk of brain metastases in stage III non-small cell lung cancer in the era of PET and MRI staging. Frontiers in oncology Alhusaini, S., Lanman, T. A., Ko, R. B., Therkelsen, K. E., Eyben, R. V., Diehn, M., Soltys, S. G., Pollom, E. L., Chin, A., Vitzthum, L., Wakelee, H. A., Padda, S. K., Ramchandran, K., Loo, B. W., Neal, J. W., Nagpal, S. 2023; 13: 1139940

  Abstract

  The 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC.Using a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment.We identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses [adenocarcinoma (n = 96), squamous cell carcinoma (n = 53), other histology subtype (n = 11)]. The median OS for the entire cohort was 41 months (95% CI, 28-53), while the median time from BrMs to death was 19 months (95% CI, 9-21). Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% (95% CI, 11-23). A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma (p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%).At our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence.

  View details for DOI 10.3389/fonc.2023.1139940

  View details for PubMedID 37035171

  View details for PubMedCentralID PMC10080021

• Adoption of Patient-Generated Health Data in Oncology: A Report From the NCCN EHR Oncology Advisory Group JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Stetson, P. D., McCleary, N. J., Osterman, T., Ramchandran, K., Tevaarwerk, A., Wong, T., Sugalski, J. M., Akerley, W., Mercurio, A., Yamzon, J., Stillman, R. C., Gabriel, P. E., Heinrichs, T., Kerrigan, K., Patel, S. B., Gilbert, S. M., Weiss, E. 2022; 20 (13)

  Abstract

  Collecting, monitoring, and responding to patient-generated health data (PGHD) are associated with improved quality of life and patient satisfaction, and possibly with improved patient survival in oncology. However, the current state of adoption, types of PGHD collected, and degree of integration into electronic health records (EHRs) is unknown.The NCCN EHR Oncology Advisory Group formed a Patient-Reported Outcomes (PRO) Workgroup to perform an assessment and provide recommendations for cancer centers, researchers, and EHR vendors to advance the collection and use of PGHD in oncology. The issues were evaluated via a survey of NCCN Member Institutions. Questions were designed to assess the current state of PGHD collection, including how, what, and where PGHD are collected. Additionally, detailed questions about governance and data integration into EHRs were asked.Of 28 Member Institutions surveyed, 23 responded. The collection and use of PGHD is widespread among NCCN Members Institutions (96%). Most centers (90%) embed at least some PGHD into the EHR, although challenges remain, as evidenced by 88% of respondents reporting the use of instruments not integrated. Forty-seven percent of respondents are leveraging PGHD for process automation and adherence to best evidence. Content type and integration touchpoints vary among the members, as well as governance maturity.The reported variability regarding PGHD suggests that it may not yet have reached its full potential for oncology care delivery. As the adoption of PGHD in oncology continues to expand, opportunities exist to enhance their utility. Among the recommendations for cancer centers is establishment of a governance process that includes patients. Researchers should consider determining which PGHD instruments confer the highest value. It is recommended that EHR vendors collaborate with cancer centers to develop solutions for the collection, interpretation, visualization, and use of PGHD.

  View details for DOI 10.6004/jnccn.2021.7088

  View details for Web of Science ID 001045234400008

  View details for PubMedID 35042190

• Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer. JCO oncology practice Gensheimer, M. F., Gupta, D., Patel, M. I., Fardeen, T., Hildebrand, R., Teuteberg, W., Seevaratnam, B., Asuncion, M. K., Alves, N., Rogers, B., Hansen, J., DeNofrio, J., Shah, N. H., Parikh, D., Neal, J., Fan, A. C., Moore, K., Ruiz, S., Li, C., Khaki, A. R., Pagtama, J., Chien, J., Brown, T., Tisch, A. H., Das, M., Srinivas, S., Roy, M., Wakelee, H., Myall, N. J., Huang, J., Shah, S., Lee, H., Ramchandran, K. 2022: OP2200128

  Abstract

  Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures.In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis.In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures (P = .04).Combining a computer prognosis model with care coaches increased ACP documentation.

  View details for DOI 10.1200/OP.22.00128

  View details for PubMedID 36395436

• Plasma Exchange for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Therapy: Implications for Clinical Care and Clinical Trial Design Giri, V. K., Yunce, M., Muppidi, S., Ramchandran, K. J., Katsumoto, T. R., Martin-Kool, B. A. AMER SOC HEMATOLOGY. 2022: 2835-2836

  View details for DOI 10.1182/blood-2022-171037

  View details for Web of Science ID 000893223202381

• Local Control of Brain Metastases with Osimertinib Alone in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Hui, C., Qu, V., Wang, J. Y., Von Eyben, R., Chang, Y. C., Chiang, P. L., Liang, C. H., Lin, J. Y., Lu, J. T., Li, G., Hayden, M., Myall, N., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2022: E54-E55

  View details for Web of Science ID 000892639300120

• Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. Journal of neuro-oncology Hui, C., Qu, V., Wang, J. Y., von Eyben, R., Chang, Y. C., Chiang, P. L., Liang, C. H., Lu, J. T., Li, G., Hayden-Gephart, M., Wakelee, H., Neal, J., Ramchandran, K., Das, M., Nagpal, S., Soltys, S., Myall, N., Pollom, E. 2022

  Abstract

  Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone.We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB.We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB.Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.

  View details for DOI 10.1007/s11060-022-04145-x

  View details for PubMedID 36227422

• Racial diversity and reporting in United States Food and Drug Administration registration trials for thoracic malignancies from 2006-2020. Cancer investigation Chiang, R. S., Desai, A., Glover, M. J., Hui, G., Ramchandran, K. J., Wakelee, H., Lythgoe, M. P., Khaki, A. R. 2022: 1-6

  Abstract

  There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006-2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

  View details for DOI 10.1080/07357907.2022.2131808

  View details for PubMedID 36197034

• Feasibility of large scale distress screening at an academic center and associated network sites using an adapted patient-reported outcome instrument and reflexive suicide screening. Gupta, D., Savadamuthu, V., Qin, F., Roy, M., Herring, J., Robinson, A., Terrell, C., Neal, J. W., Lahijani, S., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: 278

  View details for Web of Science ID 000891944700277

• Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Mao, J. J., Ismaila, N., Bao, T., Barton, D., Ben-Arye, E., Garland, E. L., Greenlee, H., Leblanc, T., Lee, R. T., Lopez, A. M., Loprinzi, C., Lyman, G. H., MacLeod, J., Master, V. A., Ramchandran, K., Wagner, L. I., Walker, E. M., Bruner, D. W., Witt, C. M., Bruera, E. 2022: JCO2201357

  Abstract

  PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other health care providers on integrative approaches to managing pain in patients with cancer.METHODS: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included pain intensity, symptom relief, and adverse events. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations.RESULTS: The literature search identified 227 relevant studies to inform the evidence base for this guideline.RECOMMENDATIONS: Among adult patients, acupuncture should be recommended for aromatase inhibitor-related joint pain. Acupuncture or reflexology or acupressure may be recommended for general cancer pain or musculoskeletal pain. Hypnosis may be recommended to patients who experience procedural pain. Massage may be recommended to patients experiencing pain during palliative or hospice care. These recommendations are based on an intermediate level of evidence, benefit outweighing risk, and with moderate strength of recommendation. The quality of evidence for other mind-body interventions or natural products for pain is either low or inconclusive. There is insufficient or inconclusive evidence to make recommendations for pediatric patients. More research is needed to better characterize the role of integrative medicine interventions in the care of patients with cancer.Additional information is available at https://integrativeonc.org/practice-guidelines/guidelines and www.asco.org/survivorship-guidelines.

  View details for DOI 10.1200/JCO.22.01357

  View details for PubMedID 36122322

• Characterization of ERBB2 (HER2) Alterations in Metastatic Non-small Cell Lung Cancer and Comparison of Outcomes of Different Trastuzumab-based Regimens. Clinical lung cancer Waliany, S., Wakelee, H., Ramchandran, K., Das, M., Huang, J., Myall, N., Li, C., Pagtama, J., Tisch, A. H., Neal, J. W. 2022

  Abstract

  About 3%-5% of mNSCLC have ERBB2 (HER2) alterations, but currently, there are no FDA-approved targeted therapies for this indication. We compared treatment response between trastuzumab-based and non-targeted regimens in ERBB2-mutant mNSCLC.This retrospective, single-institution study included patients with mNSCLC with ERBB2 alterations identified by next-generation sequencing. Best overall response was determined using Response Evaluation Criteria in Solid Tumors 1.1.We identified 3 groups of patients: ERBB2-mutant/EGFR-wildtype mNSCLC (n = 33), ERBB2-amplified/EGFR-wildtype mNSCLC without concurrent ERBB2 mutations (n = 6), and ERBB2-altered/EGFR-mutant mNSCLC (n = 8). Observed mutations included A775_G776insYVMA (n = 23), Gly778_Pro780dup (n = 4), Ser310Phe (n = 3), and others (n = 5). Among the 33 with ERBB2-mutant/EGFR-wildtype mNSCLC, those with and without A775_G776insYVMA had significantly different median overall survival (OS) of 17.7 and 52.9 months, respectively (Cox regression multivariable HR: 5.03, 95% CI: 1.37-18.51, P = .02). In those with mNSCLC with A775_G776insYVMA, trastuzumab-based therapies were associated with greater OS (20.3 vs. 9.8 months; multivariable HR: 0.19, 95% CI: 0.04-0.87, P = .032). Objective response and disease control rates (median tumor size change) in the 33 patients with ERBB2-mutant/EGFR-wildtype mNSCLC were 40.0% and 80.0% (-35.8%), respectively, for patients treated with trastuzumab deruxtecan; 0% and 30.0% (-5.2%) for trastuzumab emtansine; and 7.1% and 50.0% (-13.0%) for trastuzumab/chemotherapy combinations.In ERBB2-mutant/EGFR-wildtype mNSCLC, while most trastuzumab-based regimens had modest activity in this real-world analysis, trastuzumab deruxtecan had highest response rates and best tumor size reduction. Receipt of any trastuzumab-based regimen was associated with greater OS with A775_G776insYVMA. There remains an unmet need for approved targeted therapies for ERBB2-mutant/EGFR-wildtype NSCLC.

  View details for DOI 10.1016/j.cllc.2022.05.015

  View details for PubMedID 35753988

• Patient-reported distress at a cancer center during the COVID-19 pandemic. Shah, M. P., Rosenthal, S., Roy, M., Khaki, A., Hernandez-Boussard, T., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: E18644

  View details for Web of Science ID 000863680303793

• Plasma exchange for severe immune-related adverse events from checkpoint inhibitors: an early window of opportunity? Immunotherapy advances Katsumoto, T. R., Wilson, K. L., Giri, V. K., Zhu, H., Anand, S., Ramchandran, K. J., Martin, B. A., Yunce, M., Muppidi, S. 2022; 2 (1): ltac012

  Abstract

  Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several advanced malignancies leading to durable remission in a subset of patients. Their rapidly expanding use has led to an increased frequency of immune-related adverse events (irAEs). The pathogenesis of irAEs is poorly understood but may involve aberrant activation of T cells leading to inflammatory cytokine release or production of pathogenic antibodies leading to organ damage. Severe irAEs can be extremely debilitating and, in some cases, life threatening. IrAEs may not always be corticosteroid responsive or may require excessively high, often toxic, corticosteroid doses. Therapeutic plasma exchange (PLEX) is a treatment modality that has shown promising results for the management of certain severe irAEs, including irAEs that are not mentioned in current treatment guidelines. PLEX may attenuate ongoing irAEs and prevent delayed irAEs by accelerating clearance of the ICI, or by acutely removing pathogenic antibodies, cytokines, and chemokines. Here, we summarize examples from the literature in which PLEX was successfully used for the treatment of irAEs. We posit that timing may be a critical factor and that earlier utilization of PLEX for life-threatening irAEs may result in more favorable outcomes. In individuals at high risk for irAEs, the availability of PLEX as a potential therapeutic mitigation strategy may encourage life-saving ICI use or rechallenge. Future research will be critical to better define which indications are most amenable to PLEX, particularly to establish the optimal place in the sequence of irAE therapies and to assess the ramifications of ICI removal on cancer outcomes.

  View details for DOI 10.1093/immadv/ltac012

  View details for PubMedID 35814850

  View details for PubMedCentralID PMC9257781

• Considerations in the reliability and fairness audits of predictive models for advance care planning Frontiers in Digital Health Lu, J., Sattler, A., Wang, S., Khaki, A. R., Callahan, A., Fleming, S., Fong, R., Ehlert, B., Li, R., Shieh, L., Ramchandran, K., Gensheimer, M., Chobot, S., Pfohl, S., Li, S., Shum, K., Parikh, N., Desai, P., Seevaratnam, B., Hanson, M., Smith, M., Xu, Y., Gokhale, A., Lin, S., Shah, N. 2022: 943768

  View details for DOI 10.3389/fdgth.2022.943768

• Chemotherapy Plus Immunotherapy Versus Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone in EGFR-Mutant NSCLC After Progression on Osimertinib. Clinical lung cancer White, M. N., Piper-Vallillo, A. J., Gardner, R. M., Cunanan, K., Neal, J. W., Das, M., Padda, S. K., Ramchandran, K., Chen, T. T., Sequist, L. V., Piotrowska, Z., Wakelee, H. A. 2021

  Abstract

  INTRODUCTION: Patients with EGFR-mutant lung cancer who have had disease progression on osimertinib commonly receive platinum doublet chemotherapy, but whether adding immunotherapy or bevacizumab provides additional benefit is unknown.MATERIALS AND METHODS: This was a retrospective analysis at 2 university-affiliated institutions. Patients with EGFR-mutant lung cancer who had progression on osimertinib and received next-line therapy with platinum doublet chemotherapy (chemo), platinum doublet chemotherapy plus immunotherapy (chemo-IO), or platinum doublet chemotherapy plus bevacizumab (chemo-bev), were identified; patients who continued osimertinib with these regimens were included. Efficacy outcomes including duration on treatment (DOT) and overall survival (OS) from the start of chemotherapy were assessed. Associations of treatment regimen with outcomes were evaluated using adjusted Cox regression models, using pairwise comparisons between groups.RESULTS: 104 patients were included: 57 received chemo, 12 received chemo-IO, and 35 received chemo-bev. In adjusted models, patients who received chemo-IO had worse OS than did those who received chemo (hazard ratio (HR) 2.66, 95% CI 1.25-5.65; P= .011) or those who received chemo-bev (HR 2.37, 95% CI 1.09-5.65; P= .030). A statistically significant difference in OS could not be detected in patients who received chemo-bev versus those who received chemo (HR 1.50, 95% CI 0.84-2.69; P= .17).CONCLUSION: In this retrospective study, giving immunotherapy with platinum doublet chemotherapy after progression on osimertinib was associated with a worse OS compared with platinum doublet chemotherapy alone. Platinum doublet chemotherapy without immunotherapy (with consideration of continuation of osimertinib, in selected cases) is a reasonable choice in this setting, while we await results of clinical trials examining optimal next-line chemotherapy-based regimens in EGFR-mutant lung cancer.

  View details for DOI 10.1016/j.cllc.2021.11.001

  View details for PubMedID 34887193

• Palliative Care Always: Hepatology-Virtual Primary Palliative Care Training for Hepatologists. Hepatology communications DeNofrio, J. C., Verma, M., Kosinski, A. S., Navarro, V., Taddei, T. H., Volk, M. L., Bakitas, M., Ramchandran, K. 2021

  Abstract

  Palliative care (PC) benefits patients with serious illness including end-stage liver disease (ESLD). As part of a cluster randomized trial, hepatologists were trained to deliver primary palliative care to patients with ESLD using an online course, Palliative Care Always: Hepatology (PCA:Hep). Here we present a multimethod formative evaluation(feasibility, knowledge acquisition, self-efficacy, and practice patterns) of PCA:Hep. Feasibility was measured by completion of coursework and achieving a course grade of >80%. Knowledge acquisition was measured through assessments before and throughout the course. Pre/post-course surveys were conducted to determine self-efficacy and practice patterns. The hepatologists (n=39) enrolled in a 12-week online course and spent 1-3hours on the course weekly. The course was determined to be feasible as 97% successfully completed the course and 100% passed. The course was acceptable to participants; 91.7 % reported a positive course experience and satisfaction with knowledge gained (91.6%). The pre/post knowledge assessment showed an improvement of 6.0% (pre 85.9% to post 91.9%, 95% CI [2.8, 9.2], P=0.001). Self-efficacy increased significantly (P<0.001) in psychological symptom management, hospice, and psychosocial support. A year after training, over 80% of the hepatologists reported integrating a variety of PC skills into routine patient care. Conclusion: PCA:Hep is feasible, acceptable, and improves learner knowledge and confidence in palliative care skills. This is a viable method to teach primary PC skills to specialists caring for patients with ESLD.

  View details for DOI 10.1002/hep4.1849

  View details for PubMedID 34719137

• Impact of Tumor Suppressor Gene Co-Mutations on Differential Response to EGFR TKI Therapy in EGFR L858R and Exon 19 Deletion Lung Cancer. Clinical lung cancer Hellyer, J. A., White, M. N., Gardner, R. M., Cunanan, K., Padda, S. K., Das, M., Ramchandran, K., Neal, J. W., Wakelee, H. A. 2021

  Abstract

  BACKGROUND: In most studies, patients with EGFR L858R mutant non-small cell lung cancer (NSCLC) have a shorter duration of response to EGFR tyrosine kinase inhibitor (TKI) therapy than do patients with EGFR exon 19 deletion NSCLC. The role that co-mutations play in this observation is unknown.METHODS: We performed a single-institution retrospective analysis of patients with EGFR-mutant NSCLC (exon 19 deletion or L858R mutation) who received frontline EGFR TKI for metastatic disease between 2014 and 2019, and who had STAMP next-generation sequencing (NGS), a 130-gene platform. Time to treatment failure (TTF) and overall survival were calculated using Cox models adjusted for age, race, and brain metastases. Co-mutations in key tumor suppressor genes (TP53, RB1, KEAP1, CDKN2A, or CTNNB1) were identified and their effects on outcomes were evaluated. Analyses were stratified according to receipt of osimertinib versus nonosimertinib as frontline EGFR TKI.RESULTS: Of 137 patients, 72 (57%) had EGFR exon 19 deletions and 65 (43%) had EGFR L858R mutations. Median TTF and OS on frontline TKI was shorter for the L858R cohort versus the exon 19 deletion cohort in univariate analysis. In adjusted models, this difference persisted for TTF but was no longer significant for OS. The difference in TTF in L858R mutant tumors was driven by the presence of co-mutations in key tumor suppressor genes.CONCLUSION: Patients with metastatic NSCLC with mutations in EGFR L858R had shorter TTF on frontline TKI compared to patients with EGFR exon 19 deletions. Co-mutations in tumor suppressor genes may play an important role in the differential response to TKI therapy.

  View details for DOI 10.1016/j.cllc.2021.09.004

  View details for PubMedID 34838441

• Use of a computer model and care coaches to increase advance care planning conversations for patients with metastatic cancer Gupta, D., Fardeen, T., Teuteberg, W., Seevaratnam, B., Asuncion, M., Alves, N., Rogers, B., Neal, J. W., Fan, A. C., Parikh, D., Patel, M. I., Shah, S., Srinivas, S., Huang, J. E., Reddy, S. A., Ganjoo, K. N., Bui, N., Hansen, J., Gensheimer, M. F., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.8

  View details for Web of Science ID 000707130200008

• Patients' perception of meaning of life and needed support before and after cancer treatment initiation Roy, M., Rosenthal, S., Shah, M., Khaki, A., Hernandez-Boussard, T., Ramchandran, K. SPRINGER. 2021: S156-S157

  View details for Web of Science ID 000712224700339

• Association of telemedicine use with disparities in cancer distress screening for patients with limited English proficiency Roy, M., Fardeen, T., Cabot, A., Bruzzone, B., Savadamuthu, V., Kasprick, D., Cheung, L., Teske, E., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.147

  View details for Web of Science ID 000707130200146

• Association of treatment type with patient-reported quality of life in cancer distress screening Roy, M., Rosenthal, S., Shah, M. P., Khaki, A., Bozkurt, S., Seto, T., Blayney, D. W., Hernandez-Boussard, T., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.178

  View details for Web of Science ID 000707130200177

• Implementation of a cloud-based electronic patient-reported outcome (ePRO) platform in patients with advanced cancer. Journal of patient-reported outcomes Generalova, O., Roy, M., Hall, E., Shah, S. A., Cunanan, K., Fardeen, T., Velazquez, B., Chu, G., Bruzzone, B., Cabot, A., Fisher, G. A., Srinivas, S., Fan, A. C., Haraldsdottir, S., Wakelee, H. A., Neal, J. W., Padda, S. K., Johnson, T., Heestand, G. M., Hsieh, R. W., Ramchandran, K. 2021; 5 (1): 91

  Abstract

  BACKGROUND: Patient reported outcomes (PROs) have been associated with improved symptom management and quality of life in patients with cancer. However, the implementation of PROs in an academic clinical practice has not been thoroughly described. Here we report on the execution, feasibility and healthcare utilization outcomes of an electronic PRO (ePRO) application for cancer patients at an academic medical center.METHODS: We conducted a randomized trial comparing an experimental ePRO arm to standard of care in patients with advanced cancer in the thoracic, gastrointestinal, and genitourinary oncology groups at Stanford Cancer Center from March 2018 to November 2019. We describe the pre-implementation, implementation, and post-implementation phases of the ePRO arm, technological barriers, electronic health record (EHR) integration, clinician burden, and patient data privacy and security. Feasibility was pre-specified to be at least 70% completion of all questionnaires. Acceptability was based on patient and clinician feedback. Ambulatory healthcare utilization was assessed by reviewing numbers of phone messages, electronic portal messages, and referrals for supportive care.RESULTS: Of 617 ePRO questionnaires sent to 72 patients, 445 (72%) were completed. Most clinicians (87.5%) and patients (93%) felt neutral or positive about the ePRO tool's ease of use. Exposure to ePRO did not cause a measurable change in ambulatory healthcare utilization, with a median of less than two phone messages and supportive care referrals, and 5-6 portal messages.CONCLUSIONS: Web-based ePRO tools for patients with advanced cancer are feasible and acceptable without increasing clinical burden. Key lessons include the importance of pilot testing, engagement of stakeholders at all levels, and the need for customization by disease group. Future directions for this work include completion of EHR integration, expansion to other centers, and development of integrated workflows for routine clinical practice.

  View details for DOI 10.1186/s41687-021-00358-2

  View details for PubMedID 34524558

• Feasibility Study Integrating Electronic Patient-Reported Outcomes (PROs) and Palliative Care for High-Risk Acute Myeloid Leukemia (AML) Patients Tan, I., Choi, J., Cunanan, K., Fronk, J., Zhang, T., Mannis, G. N., Ramchandran, K. CIG MEDIA GROUP, LP. 2021: S279-S280

  View details for Web of Science ID 000691910500447

• Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Waliany, S., Zhu, H., Wakelee, H., Padda, S. K., Das, M., Ramchandran, K., Myall, N. J., Chen, T., Witteles, R. M., Neal, J. W. 2021

  Abstract

  INTRODUCTION: Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung carcinoma (NSCLC). We compared cardiovascular adverse events between and within targeted therapy classes.METHODS: We used WHO pharmacovigilance database VigiBase to compare odds of heart failure, conduction disease, QT prolongation, supraventricular tachycardia (SVT), and ventricular arrhythmias between inhibitors of EGFR (erlotinib, gefitinib, afatinib, osimertinib), BRAF (dabrafenib), MEK (trametinib), and ALK ± ROS1 (alectinib, brigatinib, ceritinib, crizotinib, lorlatinib).RESULTS: Of 98,765 adverse reactions reported with NSCLC targeted therapies, 1,783 (1.8%) were arrhythmias and 1,146 (1.2%) were heart failure. ALK/ROS1 inhibitors were associated with increased odds of conduction disease (reporting odds ratio [ROR] 12.95, 99% CI: 10.14-16.55) and QT prolongation (ROR 5.16, 99% CI: 3.92-6.81) relative to BRAF and EGFR inhibitors. Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00). Dabrafenib (ROR 2.24, 99% CI: 1.86-2.70) and trametinib (ROR 2.44, 99% CI: 2.03-2.92) had higher odds of heart failure than other targeted therapies. Osimertinib was strongly associated with QT prolongation (ROR 6.13, 99% CI: 4.43-8.48), heart failure (ROR 3.64, 99% CI: 2.94-4.50), and SVT (ROR 1.90, 99% CI: 1.26-2.86) relative to other targeted therapies.CONCLUSIONS: ALK/ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than other targeted therapies. Osimertinib is strongly associated with QT prolongation, SVT, and heart failure relative to other EGFR inhibitors and targeted therapies. Monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib.

  View details for DOI 10.1016/j.jtho.2021.07.030

  View details for PubMedID 34418561

• EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy. Clinical lung cancer Shah, M. P., Aredo, J. V., Padda, S. K., Ramchandran, K. J., Wakelee, H. A., Das, M. S., Neal, J. W. 2021

  Abstract

  INTRODUCTION: In classical EGFR mutant non-small-cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitor (TKI) therapy yields better outcomes than platinum-based chemotherapy. However, EGFR exon 20 insertion (ex20ins) NSCLC is relatively resistant to currently available EGFR TKIs. Though platinum-based chemotherapy is the frontline standard of care for EGFR ex20ins NSCLC, its efficacy is not fully described.STUDY DESIGN: A retrospective, single-center, case series METHODS: Patients were identified through an electronic research database at a single institution and included if they had advanced EGFR ex20ins NSCLC, received platinum-based chemotherapy for metastatic disease, and had scans evaluable for response. Each patient's demographics, tumor characteristics, and clinical course were recorded. Treatment response was evaluated using RECIST v1.1 criteria, and the PFS was calculated by the Kaplan-Meier method.RESULTS: Among 27 patients identified with EGFR ex20ins NSCLC at our institution, 18 (67%) received platinum-based chemotherapy for metastatic disease and had scans evaluable for response. These patients received platinum-based chemotherapy in the first-line (N=17, 94%) and second-line settings (N=1, 6%). The objective response rate (ORR) to platinum-based chemotherapy was 39% (7 of 18 patients; 95% confidence interval [CI] 16-61). The median PFS with platinum-based chemotherapy was 7.1 months (95% CI, 6.3 -13.7), and the median overall survival was 3.2 years (95% CI, 1.92 - NR).CONCLUSIONS: The efficacy of platinum-based chemotherapy in EGFR ex20ins NSCLC is similar to that expected for TKI sensitive EGFR mutant NSCLC. Novel agents designed to specifically target ex20ins mutant EGFR should additionally improve outcomes.

  View details for DOI 10.1016/j.cllc.2021.07.001

  View details for PubMedID 34391686

• Investigating gene expression profiles associated with clinical radiation resistance in KEAP1/NFE2L2 wildtype lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D., Yoo, C., Kurtz, D. M., Owen, S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000641160600087

• Circulating tumor DNA kinetics to identify genomic predictors of rapid response to chemoradiation in non-small cell lung cancer. Moding, E. J., Liu, Y., Hui, A. B., He, J., Qiao, Y., Xu, T., Yao, L., Gandhi, S., Liao, Z., Das, M., Ramchandran, K. J., Padda, S. K., Neal, J. W., Wakelee, H. A., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000641160600097

• How could we forget? The Lancet. Respiratory medicine Ramchandran, K. 2021

  View details for DOI 10.1016/S2213-2600(21)00041-2

  View details for PubMedID 33581078

• End-of-Life Practice Patterns in Head and Neck Cancer. The Laryngoscope Vukkadala, N., Fardeen, T., Ramchandran, K., Divi, V. 2021

  Abstract

  OBJECTIVE/HYPOTHESIS: Despite the importance of symptom management and end-of-life (EOL) care in head and neck cancers (HNC), there is little literature on care practices in this population. This study examines EOL care practice patterns using nationally established metrics.STUDY DESIGN: Retrospective chart review.METHODS: Review of HNC patients who were actively followed and treated (defined as one clinic note within 90days, two within preceding 9months, and having received treatment at our institution) and died between January 1, 2017 and December 31, 2018. The cohort was reviewed for performance on Quality Oncology Practice Initiative (QOPI) and other metrics.RESULTS: Of 133 patients identified, 52 met inclusion criteria. The average age at death was 69.8years. About 59% had distant metastases, 30% had locoregional disease, 11% were undergoing primary treatment. Twenty-three percentage received chemotherapy within the last 14days of life. Fifty percentage of patients were admitted in the last 30days of life, and 33% died in the hospital. Fifty-four percentage of patients had either Physician Orders for Life-Sustaining Treatment or Advanced Directive on file. Eighty-one percentage of patients had any type of goals of care discussion documented. Sixty-five percentage of all patients received referrals to palliative care and 46% of all patients enrolled in hospice. The median days in hospice was 12. Having a goals of care discussion was significantly associated with utilization of palliative and hospice care.CONCLUSIONS: Provider-documented goals of care discussions were strongly correlated to referrals and enrollment in palliative and hospice care. Areas for improvement include better documentation of treatment directives and reducing low-utility treatments.LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

  View details for DOI 10.1002/lary.29423

  View details for PubMedID 33491219

• Distress Screening Through Patient-Reported Outcomes Measurement Information System (PROMIS) at an Academic Cancer Center and Network Site: Implementation of a Hybrid Model. JCO oncology practice Neal, J. W., Roy, M. n., Bugos, K. n., Sharp, C. n., Galatin, P. S., Falconer, P. n., Rosenthal, E. L., Blayney, D. W., Modaressi, S. n., Robinson, A. n., Ramchandran, K. n. 2021: OP2000473

  Abstract

  Cancer care guidelines recommend regular distress screening of patients, with approximately one in three patients with cancer experiencing significant distress. However, the implementation of such programs is variable and inconsistent. We sought to assess the feasibility of implementing a hybrid electronic and paper screening tool for distress in all patients coming to a large academic cancer center and an associated integrated network site.Patients at an academic cancer center (Stanford Cancer Center) and its associated integrated network site received either an electronic or on-paper modified Patient-Reported Outcomes Measurement Information System-Global Health questionnaire, to assess overall health and distress. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance implementation framework to test and report on the feasibility of using this questionnaire. Iterative workflow changes were made to implement the questionnaire throughout the healthcare system, including processes to integrate with existing electronic health records.From June 2015 to December 2017, 53,954 questionnaires representing 26,242 patients were collected. Approximately 30% of the questionnaires were completed before the visit on an electronic patient portal. The number of patients meeting the positive screen threshold remained around 40% throughout the study period. Following assessment, there were 3,763 referrals to cancer supportive services. Of note, those with a positive screen were more likely to have a referral to supportive care (odds ratio, 6.4; 95% CI, 5.8 to 6.9; P < .0001).The hybrid electronic and on-paper use of a commonly available patient-reported outcome tool, Patient-Reported Outcomes Measurement Information System-Global Health, as a large-scale distress screening method, is feasible at a large integrated cancer center.

  View details for DOI 10.1200/OP.20.00473

  View details for PubMedID 33830852

• NCCN Guidelines Insights: Palliative Care, Version 2.2021. Journal of the National Comprehensive Cancer Network : JNCCN Dans, M., Kutner, J. S., Agarwal, R., Baker, J. N., Bauman, J. R., Beck, A. C., Campbell, T. C., Carey, E. C., Case, A. A., Dalal, S., Doberman, D. J., Epstein, A. S., Fecher, L., Jones, J., Kapo, J., Lee, R. T., Loggers, E. T., McCammon, S., Mitchell, W., Ogunseitan, A. B., Portman, D. G., Ramchandran, K., Sutton, L., Temel, J., Teply, M. L., Terauchi, S. Y., Thomas, J., Walling, A. M., Zachariah, F., Bergman, M. A., Ogba, N., Campbell, M. 2021; 19 (7): 780-788

  Abstract

  Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

  View details for DOI 10.6004/jnccn.2021.0033

  View details for PubMedID 34340208

• Brief Report: Role of Consolidation Durvalumab in patients with EGFR and HER2 Mutant Unresectable Stage III NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Hellyer, J. A., Aredo, J. V., Das, M. n., Ramchandran, K. n., Padda, S. K., Neal, J. W., Wakelee, H. A. 2021

  Abstract

  Despite the recent advance of consolidation durvalumab in the treatment of unresectable stage III non-small cell lung cancer (NSCLC), not every patient benefits from durvalumab and predictive markers of response have been difficult to identify.We performed a retrospective analysis of patients with unresectable stage III NSCLC treated with consolidation durvalumab following definitive chemoradiation from January 2018 to March 2020.Thirty-six patients with unresectable stage III NSCLC were treated with consolidation durvalumab. Fourteen of these patients had tumor mutations in the ERBB family including 11 EGFR and 3 ERBB2. The ERBB2/EGFR tumor mutation cohort was more likely to be non-smokers; otherwise the two groups were similar in age, sex, PD-L1 expression and type of prior chemotherapy regimen. Patients in the ERBB2/EGFR cohort had a significantly shorter disease free survival compared to the EGFR/ERBB2 wildtype cohort (7.5 months vs NR, p= 0.04).Consolidation durvalumab appears to be less efficacious in patients with ERBB2/EGFR mutant tumors. Future work should seek to evaluate this in the prospective setting and provide insight into the optimal treatment of ERBB2/EGFR-mutant stage III NSCLC.

  View details for DOI 10.1016/j.jtho.2020.12.020

  View details for PubMedID 33539970

• Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases. Journal of neuro-oncology Zhang, M. n., Rodrigues, A. J., Pollom, E. L., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Neal, J. W., Padda, S. K., Ramchandran, K. J., Wakelee, H. A., Chang, S. D., Lim, M. n., Hayden Gephart, M. n., Li, G. n. 2021

  Abstract

  Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

  View details for DOI 10.1007/s11060-020-03686-3

  View details for PubMedID 33415659

• End-of-Life Cost Trajectories in Cancer Patients Treated by Medicare versus the Veterans Health Administration. Journal of the American Geriatrics Society Gidwani, R., Asch, S. M., Needleman, J., Faricy-Anderson, K., Boothroyd, D. B., Illarmo, S., Lorenz, K. A., Patel, M. I., Hsin, G., Ramchandran, K., Wagner, T. H. 2020

  Abstract

  BACKGROUND/OBJECTIVES: To evaluate differences in end-of-life cost trajectories for cancer patients treated through Medicare versus by the Veterans Health Administration (VA).DESIGN: A retrospective analysis of VA and Medicare administrative data from FY 2010 to 2014. We employed three-level generalized estimating equation to evaluate monthly cost trajectories experienced by patients in their last year of live, with patients nested within hospital referral region.SETTING: Care received at VA facilities or by Medicare-reimbursed providers nationwide.PARTICIPANTS: A total of 36,401 patients dying from cancer and dually enrolled in VA and Medicare.MEASUREMENTS: We evaluated trajectories for total, inpatient, outpatient, and drug costs, using the last 12months of life. Cost trajectories were prioritized as costs are not directly comparable across Medicare and VA. Patients were assigned to be VA-reliant, Medicare-reliant or Mixed-reliant based on their healthcare utilization in the last year of life.RESULTS: All three groups experienced significantly different cost trajectories for total costs in the last year of life. Inpatient cost trajectories were significantly different between Medicare-reliant and VA-reliant patients, but did not differ between VA-reliant and Mixed-reliant patients. Outpatient and drug cost trajectories exhibited the inverse pattern: they were significantly different between VA-reliant and Mixed-reliant patients, but not between VA-reliant and Medicare-reliant patients. However, visual examination of cost trajectories revealed similar cost patterns in the last year of life among all three groups; there was a sharp rise in costs as patients approach death, largely due to inpatient care.CONCLUSION: Despite substantially different financial incentives and organization, VA- and Medicare-treated patients exhibit similar patterns of increasing end-of-life costs, largely driven by inpatient costs. Both systems require improvement to ensure quality of end-of-life care is aligned with recommended practice.

  View details for DOI 10.1111/jgs.16941

  View details for PubMedID 33368171

• DEVELOPMENT, FEASIBILITY AND ACCEPTABILITY OF AN ONLINE COURSE TO TEACH PRIMARY PALLIATIVE CARE SKILLS TO HEPATOLOGY PROVIDERS. Verma, M., Denofrio, J., Ramchandran, K., Taddei, T. H., Volk, M., Navarro, V. J. WILEY. 2020: 1156–57

  View details for Web of Science ID 000574027004356

• A noninvasive approach for early prediction of therapeutic benefit from immune checkpoint inhibition for lung cancer Nabet, B. Y., Esfahani, M. S., Hamilton, E. G., Chabon, J. J., Moding, E. J., Rizvi, H., Steen, C. B., Chaudhuri, A. A., Liu, C., Hui, A. B., Stehr, H., Goljenola, L., Jin, M. C., Jeon, Y., Tseng, D., Merghoub, T., Neal, J. W., Wakelee, H. A., Padda, S. K., Ramchandran, K. J., Das, M., Bonilla, R. F., Yoo, C., Chen, E. L., Ko, R. B., Newman, A. M., Hellmann, M. D., Alizadeh, A. A., Diehn, M. AMER ASSOC CANCER RESEARCH. 2020

  View details for DOI 10.1158/1538-7445.AM2020-5666

  View details for Web of Science ID 000590059306446

• The role of palliative care in the management of patients with lung cancer LUNG CANCER MANAGEMENT Tan, I., Ramchandran, K. 2020

  View details for DOI 10.2217/lmt-2020-0016

  View details for Web of Science ID 000553560300001

• Distress screening through PROMIS at an academic cancer center and network site: Implementation of a hybrid model. Roy, M., Neal, J. W., Bugos, K., Sharp, C., Falconer, P., Rosenthal, E., Blayney, D. W., Modaressi, S., Robinson, A., Ramchandran, K. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368301136

• A mid-chemoradiation dynamic risk model integrating tumor features and ctDNA analysis for lung cancer outcome prediction. Moding, E. J., Esfahani, M., Nabet, B., Liu, Y., Chabon, J. J., He, J., Qiao, Y., Xu, T., Yao, L., Gandhi, S., Liao, Z. X., Das, M., Ramchandran, K., Padda, S., Neal, J. W., Wakelee, H. A., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368303378

• KEAP1/NFE2L2 mutations to predict local recurrence after radiotherapy but not surgery in localized non-small cell lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D. S., Yoo, C., Kurtz, D., Owen, S., Backhus, L., Berry, M. F., Shrager, J. B., Ramchandran, K., Padda, S., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020

  View details for Web of Science ID 000560368303348

• Circulating Tumor DNA Dynamics Predict Benefit from Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer. Nature cancer Moding, E. J., Liu, Y., Nabet, B. Y., Chabon, J. J., Chaudhuri, A. A., Hui, A. B., Bonilla, R. F., Ko, R. B., Yoo, C. H., Gojenola, L., Jones, C. D., He, J., Qiao, Y., Xu, T., Heymach, J. V., Tsao, A., Liao, Z., Gomez, D. R., Das, M., Padda, S. K., Ramchandran, K. J., Neal, J. W., Wakelee, H. A., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. 2020; 1 (2): 176-183

  Abstract

  Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.

  View details for DOI 10.1038/s43018-019-0011-0

  View details for PubMedID 34505064

  View details for PubMedCentralID PMC8425388

• Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell Nabet, B. Y., Esfahani, M. S., Moding, E. J., Hamilton, E. G., Chabon, J. J., Rizvi, H. n., Steen, C. B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Almanza, D. n., Stehr, H. n., Gojenola, L. n., Bonilla, R. F., Jin, M. C., Jeon, Y. J., Tseng, D. n., Liu, C. n., Merghoub, T. n., Neal, J. W., Wakelee, H. A., Padda, S. K., Ramchandran, K. J., Das, M. n., Plodkowski, A. J., Yoo, C. n., Chen, E. L., Ko, R. B., Newman, A. M., Hellmann, M. D., Alizadeh, A. A., Diehn, M. n. 2020

  Abstract

  Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

  View details for DOI 10.1016/j.cell.2020.09.001

  View details for PubMedID 33007267

• KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer discovery Binkley, M. S., Jeon, Y. J., Nesselbush, M. n., Moding, E. J., Nabet, B. Y., Almanza, D. n., Kunder, C. n., Stehr, H. n., Yoo, C. H., Rhee, S. n., Xiang, M. n., Chabon, J. J., Hamilton, E. n., Kurtz, D. M., Gojenola, L. n., Owen, S. G., Ko, R. B., Shin, J. H., Maxim, P. G., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M. n., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. n. 2020

  Abstract

  Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in KEAP1/NFE2L2 mutation tumors, indicating they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1 mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations.

  View details for DOI 10.1158/2159-8290.CD-20-0282

  View details for PubMedID 33071215

• Symptom relief and palliative care in gynecologic oncology. Current opinion in obstetrics & gynecology Roy, M., Ramchandran, K. 2019

  Abstract

  PURPOSE OF REVIEW: Patients with gynecologic malignancies experience varied and often difficult-to-manage symptoms through their disease course, along with decisions surrounding preferences for advance care planning. This review focuses on evidence-based symptom management for these patients and offers a framework for conversations regarding goals of therapy.RECENT FINDINGS: There is increasing literature on palliative care specifically in gynecologic oncology, including barriers and possible solutions for early palliative care use, along with updated guidelines on postoperative pain management and tools for communication.SUMMARY: Integration of early palliative care and focus on symptom management is an important and multidisciplinary approach to help patients with gynecologic malignancies.

  View details for DOI 10.1097/GCO.0000000000000601

  View details for PubMedID 31851044

• Palliative care clinicians and online education in India: a survey BMJ SUPPORTIVE & PALLIATIVE CARE Kiss-Lane, T., Spruijt, O., Day, T., Lam, V., Ramchandran, K. J., Chan, S., Hsin, G., Vallath, N., Bhatnagar, S., Rajagopal, M. R., Lorenz, K. A. 2019; 9 (4)

  View details for DOI 10.1136/bmjspcare-2018-001546

  View details for Web of Science ID 000505622500010

• Feasibility and design of a cloud-based digital platform in patients with advanced cancer. Roy, M., Hall, E., Velazquez, B., Shah, S., Fardeen, T., Cunanan, K., San Pedro-Salcedo, M., Wakelee, H. A., Neal, J. W., Padda, S., Das, M., Fan, A. C., Srinivas, S., Fisher, G. A., Haraldsdottir, S., Johnson, T., Chu, G., McMillan, A., Ramchandran, K. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.27_suppl.211

  View details for Web of Science ID 000518223100208

• Introducing Palliative Care within the Treatment of End-Stage Liver Disease: The Study Protocol of a Cluster Randomized Controlled Trial. Journal of palliative medicine Verma, M., Kosinski, A. S., Volk, M. L., Taddei, T., Ramchandran, K., Bakitas, M., Green, K., Green, L., Navarro, V. 2019; 22 (S1): 34–43

  Abstract

  Introduction: Patients with end-stage liver disease (ESLD) suffer from myriad symptoms due to the systemic effects of the disease and unpredictable acute episodes, which contribute to progressive deterioration in quality of life (QOL). Despite clear evidence that palliative care (PC) improves QOL in other serious illnesses, PC is underutilized and delayed for ESLD patients. Through a comparative effectiveness trial of specialist led consultative PC (Model 1) versus trained hepatologist led PC (Model 2), we aim to build evidence on introducing PC into the routine outpatient care of ESLD patients. Objective: We hypothesize that trained hepatologist led PC model will have a better improvement in QOL compared to consultative PC model. Methods: This two-arm, multicenter cluster-randomized trial assesses the effectiveness of two PC models for patients with ESLD. Fourteen clinical centers will recruit 1260 patient-caregiver dyads. Each center is the unit of randomization. Hepatologists at sites randomized to the Model 2 have undergone web-based training in the principles of PC as pertained to ESLD. PC intervention is delivered over four visits (initial, one, two, and three months). Follow-up assessments occur at 6, 9, and 12 months. Eligible patients are those with new onset or ongoing complications of ESLD with a caregiver willing to participate. Outcomes: The primary outcome is change in patients' QOL from baseline to three months. Secondary outcomes include symptom burden, depression, distress, satisfaction with care, caregiver burden and QOL, goal concordant care, and health care utilization. Challenges and Contributions Engagement: A research advisory board has been developed with representatives from the participating centers, who have provided active feedback on the protocol, outcomes, study methods, and training program. Intervention Fidelity: Intervention fidelity will be maintained by adherence to a visit agenda and providers in both models completing a PC checklist after each study visit.

  View details for DOI 10.1089/jpm.2019.0121

  View details for PubMedID 31486722

• Automated Survival Prediction in Metastatic Cancer Patients Using High-Dimensional Electronic Medical Record Data JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Gensheimer, M. F., Henry, A., Wood, D. J., Hastie, T. J., Aggarwal, S., Dudley, S. A., Pradhan, P., Banerjee, I., Cho, E., Ramchandran, K., Pollom, E., Koong, A. C., Rubin, D. L., Chang, D. T. 2019; 111 (6): 568–74

  View details for DOI 10.1093/jnci/djy178

  View details for Web of Science ID 000474267400007

• ctDNA analysis for personalization of consolidation immunotherapy in localized non-small cell lung cancer. Moding, E. J., Liu, Y., Nabet, B., Chabon, J. J., Chaudhuri, A., Hui, A. B., He, J., Qiao, Y., Heymach, J., Tsao, A. S., Liao, Z. X., Gomez, D., Ramchandran, K., Neal, J. W., Wakelee, H. A., Loo, B. W., Lin, S. H., Alizadeh, A. A., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.2547

  View details for Web of Science ID 000487345804497

• Randomized phase II study of adjuvant afatinib for three months versus two years in patients with resected stage I-III EGFR mutant NSCLC. Chaft, J. E., Costa, D., Muzikansky, A., Shrager, J. B., Lanuti, M., Huang, J., Ramchandran, K., Rangachari, D., Huberman, M., Piotrowska, Z., Kris, M. G., Azzoli, C. G., Sequist, L. V., Neal, J. W. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345806385

• Impact of KEAP1/NFE2L2/CUL3 mutations on duration of response to EGFR tyrosine kinase inhibitors in EGFR mutated non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) Hellyer, J. A., Stehr, H. n., Das, M. n., Padda, S. K., Ramchandran, K. n., Neal, J. W., Diehn, M. n., Wakelee, H. A. 2019; 134: 42–45

  Abstract

  For patients with Epidermal Growth Factor Receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), frontline EGFR-tyrosine kinase inhibitor (TKI) therapy compared to chemotherapy improves outcomes. However, resistance to these agents uniformly develops. Recently, mutations in the KEAP1-NFE2L2 pathway have been implicated as a potential mechanism of acquired EGFR TKI resistance.We examined all patients with metastatic NSCLC with mutations in both EGFR and KEAP1/NFE2L2/CUL3 identified on next generation sequencing from 2015 - 2018. These patients were compared to a NSCLC control cohort with mutations in EGFR and wild type in KEAP1/NFE2L2/CUL3 matched on the basis of sex, smoking status, age and race. Time to treatment failure on EGFR TKI therapy and overall survival were examined.Among 228 EGFR mutant NSCLCs, 17 (7%) also carried mutations in KEAP1, NFE2L2, or CUL3. The most common co-mutation in both the KEAP1/NFE2L2/CUL3 mutant and wild-type cohort was TP53. Patients with KEAP1/NFE2L2/CUL3 mutations had a shorter median time to treatment failure on EGFR TKI (4.7 months) compared with the wild-type matched cohort (13.0 months), p= 0.0014. There was no difference in overall survival.For NSCLC patients with mutations in EGFR, co-mutations in KEAP1/NFE2L2/CUL3 are associated with significantly decreased time to treatment failure. Our results suggest that these mutations represent a mechanism of intrinsic resistance to TKI treatment.

  View details for DOI 10.1016/j.lungcan.2019.05.002

  View details for PubMedID 31319993

• Health System and Beneficiary Costs Associated With Intensive End-of-Life Medical Services. JAMA network open Gidwani-Marszowski, R. n., Asch, S. M., Mor, V. n., Wagner, T. H., Faricy-Anderson, K. n., Illarmo, S. n., Hsin, G. n., Patel, M. I., Ramchandran, K. n., Lorenz, K. A., Needleman, J. n. 2019; 2 (9): e1912161

  Abstract

  Despite recommendations to reduce intensive medical treatment at the end of life, many patients with cancer continue to receive such services.To quantify expected beneficiary and health system costs incurred in association with receipt of intensive medical services in the last month of life.This retrospective cohort study used data collected nationally from Medicare and the Veterans Health Administration for care provided in fiscal years 2010 to 2014. Participants were 48 937 adults aged 66 years or older who died of solid tumor and were continuously enrolled in fee-for-service Medicare and the Veterans Health Administration in the 12 months prior to death. The data were analyzed from February to August 2019.American Society of Clinical Oncology metrics regarding medically intensive services provided in the last month of life, including hospital stay, intensive care unit stay, chemotherapy, 2 or more emergency department visits, or hospice for 3 or fewer days.Costs in the last month of life associated with receipt of intensive medical services were evaluated for both beneficiaries and the health system. Costs were estimated from generalized linear models, adjusting for patient demographics and comorbidities and conditioning on geographic region.Of 48 937 veterans who received care through the Veterans Health Administration and Medicare, most were white (90.8%) and male (98.9%). More than half (58.9%) received at least 1 medically intensive service in the last month of life. Patients who received no medically intensive service generated a mean (SD) health system cost of $7660 ($1793), whereas patients who received 1 or more medically intensive services generated a mean (SD) health system cost of $23 612 ($5528); thus, the additional financial consequence to the health care system for medically intensive services was $15 952 (95% CI, $15 676-$16 206; P < .001). The biggest contributor to these differences was $21 093 (95% CI, $20 364-$21 689) for intensive care unit stay, while the smallest contributor was $3460 (95% CI, $2927-$3880) for chemotherapy. Mean (SD) expected beneficiary costs for the last month of life were $133 ($50) for patients with no medically intensive service and $1257 ($408) for patients with at least 1 medically intensive service (P < .001).Given the low income of many elderly patients in the United States, the financial consequences of medically intensive services may be substantial. Costs of medically intensive services at the end of life, including patient financial consequences, should be considered by both physicians and families.

  View details for DOI 10.1001/jamanetworkopen.2019.12161

  View details for PubMedID 31560384

• Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies. Lung cancer (Amsterdam, Netherlands) Hellyer, J. A., Gubens, M. A., Cunanan, K. M., Padda, S. K., Burns, M. n., Spittler, A. J., Riess, J. W., San Pedro-Salcedo, M. n., Ramchandran, K. J., Neal, J. W., Wakelee, H. A., Loehrer, P. J. 2019; 137: 71–75

  Abstract

  There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor.This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1-3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients.A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%-32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient.Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

  View details for DOI 10.1016/j.lungcan.2019.09.015

  View details for PubMedID 31557562

• Role of KEAP1/NFE2L2 mutations in the chemotherapeutic response of non-small cell lung cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research Jeong, Y. n., Hellyer, J. A., Stehr, H. n., Hoang, N. T., Niu, X. n., Das, M. n., Padda, S. K., Ramchandran, K. n., Neal, J. W., Wakelee, H. A., Diehn, M. n. 2019

  Abstract

  Activation of NFE2L2 has been linked to chemoresistance in cell line models. Recently, somatic mutations which activate NFE2L2, including mutations in NFE2L2,KEAP1, or CUL3,have been found to be associated with poor outcomes in patients with non-small cell lung cancer (NSCLC). However, the impact of these mutations on chemoresistance remains incompletely explored.We investigated the effect of Keap1 deletion on chemoresistance in cell lines from Trp53-based mouse models of lung squamous cell carcinoma (LSCC) and lung adenocarcinoma (LUAD). Separately, we identified 51 stage IV NSCLC patients with KEAP1, NFE2L2, or CUL3mutations and a matched cohort of 52 wildtype patients. Time to treatment failure after front line platinum doublet chemotherapy and overall survival was compared between the two groups.Deletion of Keap1 in Trp53-null murine LUAD and LSCC resulted in increased clonogenic survival upon treatment with diverse cytotoxic chemotherapies. In NSCLC patients, median time to treatment failure (TTF) after first line chemotherapy for the KEAP1/NFE2L2/CUL3-mutant cohort was 2.8 months compared to 8.3 months in the control group (p < 0.0001) Median overall survival (OS) was 11.2 months in the KEAP1/NFE2L2/CUL3-mutant group and 36.8 months in the control group (p = 0.006). Conclusions: Keap1 deletion confers chemoresistance in murine lung cancer cells. Patients with metastatic NSCLC with mutations in KEAP1, NFE2L2, or CUL3 have shorter time to treatment failure and overall survival after first line platinum doublet chemotherapy compared with matched controls. Novel approaches for improving outcomes in this subset of NSCLC patients are therefore needed.

  View details for DOI 10.1158/1078-0432.CCR-19-1237

  View details for PubMedID 31548347

• Feasibility of a massive online open course to teach skills in primary palliative care for a global audience. Kerkar, A., DeNofrio, J., Tribett, E., Ramchandran, K. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.34_suppl.111

  View details for Web of Science ID 000464876100107

• Automated Survival Prediction in Metastatic Cancer Patients Using High-Dimensional Electronic Medical Record Data. Journal of the National Cancer Institute Gensheimer, M. F., Henry, A. S., Wood, D. J., Hastie, T. J., Aggarwal, S., Dudley, S. A., Pradhan, P., Banerjee, I., Cho, E., Ramchandran, K., Pollom, E., Koong, A. C., Rubin, D. L., Chang, D. T. 2018

  Abstract

  Background: Oncologists use patients' life expectancy to guide decisions and may benefit from a tool that accurately predicts prognosis. Existing prognostic models generally use only a few predictor variables. We used an electronic medical record dataset to train a prognostic model for patients with metastatic cancer.Methods: The model was trained and tested using 12588 patients treated for metastatic cancer in the Stanford Health Care system from 2008 to 2017. Data sources included provider note text, labs, vital signs, procedures, medication orders, and diagnosis codes. Patients were divided randomly into a training set used to fit the model coefficients and a test set used to evaluate model performance (80%/20% split). A regularized Cox model with 4126 predictor variables was used. A landmarking approach was used due to the multiple observations per patient, with t0 set to the time of metastatic cancer diagnosis. Performance was also evaluated using 399 palliative radiation courses in test set patients.Results: The C-index for overall survival was 0.786 in the test set (averaged across landmark times). For palliative radiation courses, the C-index was 0.745 (95% confidence interval [CI] = 0.715 to 0.775) compared with 0.635 (95% CI = 0.601 to 0.669) for a published model using performance status, primary tumor site, and treated site (two-sided P<.001). Our model's predictions were well-calibrated.Conclusions: The model showed high predictive performance, which will need to be validated using external data. Because it is fully automated, the model can be used to examine providers' practice patterns and could be deployed in a decision support tool to help improve quality of care.

  View details for PubMedID 30346554

• Palliative care clinicians and online education in India: a survey. BMJ supportive & palliative care Kiss-Lane, T., Spruijt, O., Day, T., Lam, V., Ramchandran, K. J., Chan, S., Hsin, G., Vallath, N., Bhatnagar, S., Rajagopal, M. R., Lorenz, K. A. 2018

  Abstract

  BACKGROUND: Whether online resources can facilitate spread of palliative care knowledge and skills in India is an urgent question given few providers and a large, ageing population.OBJECTIVES: We surveyed needs and feasibility regarding e-learning.METHODS: Indian, Australian and North American palliative care experts developed an electronic survey using Qualtrics, emailed to all registrants of the 2017 Indian Association of Palliative Care (IAPC) conference and distributed during the conference.RESULTS: Of 60 respondents (66% men, 60% doctors), most worked in hospitals and had oncology backgrounds, and 35% were from Kerala and Tamil Nadu. Most (90.9%) received palliative care training in India or overseas with 41% trained in a Trivandrum Institute of Palliative Sciences residential course (4-6 weeks). 17% completed the IAPC essential certificate and 22% had undertaken various distance learning courses. Interest in online training was substantial for most aspects of palliative care.CONCLUSION: There was a high level of interest and reported feasibility in taking a case-based online course. This pilot survey provides support for online case-based education in India, particularly among physicians.

  View details for PubMedID 30301753

• Oncologists' Views on Using Value to Guide Cancer Treatment Decisions VALUE IN HEALTH Gidwani-Marszowski, R., Nevedal, A. L., Blayney, D. W., Patel, M., Kelly, P., Timko, C., Ramchandran, K., Murrell, S. S., Asch, S. M. 2018; 21 (8): 931–37

  Abstract

  Cancer costs have increased substantially in the past decades, prompting specialty societies to urge oncologists to consider value in clinical decision making. Despite oncologists' crucial role in guiding cancer care, current literature is sparse with respect to the oncologists' views on value. Here, we evaluated oncologists perceptions of the use and measurement of value in cancer care.We conducted in-depth, open-ended interviews with 31 US oncologists practicing nationwide in various environments. Oncologists discussed the definition, measurement, and implementation of value. Transcripts were analyzed using matrix and thematic analysis.Oncologists' definitions of value varied greatly. Some described versions of the standard health economic definition of value, that is, cost relative to health outcomes. Many others did not include cost in their definition of value. Oncologists considered patient goals and quality of life as important components of value that they perceived were missing from current value measurement. Oncologists prioritized a patient-centric view of value over societal or other perspectives. Oncologists were inclined to consider the value of a treatment only if they perceived treatment would pose a financial burden to patients. Oncologists had differing opinions regarding who should be responsible for determining whether care is low value but generally felt this should remain within the purview of the oncology community.Oncologists agreed that cost was an important issue, but disagreed about whether cost was involved in value as well as the role of value in guiding treatment. Better clarity and alignment on the definition of and appropriate way to measure value is critical to the success of efforts to improve value in cancer care.

  View details for PubMedID 30098670

• Quality Of End-Of-Life Care Is Higher In The VA Compared To Care Paid For By Traditional Medicare HEALTH AFFAIRS Gidwani-Marszowski, R., Needleman, J., Mor, V., Faricy-Anderson, K., Boothroyd, D. B., Hsin, G., Wagner, T. H., Lorenz, K. A., Patel, M. I., Joyce, V. R., Murrell, S. S., Ramchandran, K., Asch, S. M. 2018; 37 (1): 95–103

  Abstract

  Congressional and Veterans Affairs (VA) leaders have recommended the VA become more of a purchaser than a provider of health care. Fee-for-service Medicare provides an example of how purchased care differs from the VA's directly provided care. Using established indicators of overly intensive end-of-life care, we compared the quality of care provided through the two systems to veterans dying of cancer in fiscal years 2010-14. The Medicare-reliant veterans were significantly more likely to receive high-intensity care, in the form of chemotherapy, hospital stays, admission to the intensive care unit, more days spent in the hospital, and death in the hospital. However, they were significantly less likely than VA-reliant patients to have multiple emergency department visits. Higher-intensity end-of-life care may be driven by financial incentives present in fee-for-service Medicare but not in the VA's integrated system. To avoid putting VA-reliant veterans at risk of receiving lower-quality care, VA care-purchasing programs should develop coordination and quality monitoring programs to guard against overly intensive end-of-life care.

  View details for PubMedID 29309227

• The Appropriate Provision of Primary versus Specialist Palliative Care to Cancer Patients: Oncologists' Perspectives JOURNAL OF PALLIATIVE MEDICINE Gidwani, R., Nevedal, A., Patel, M., Blayney, D. W., Timko, C., Ramchandran, K., Kelly, P. A., Asch, S. M. 2017; 20 (4): 395-403

  Abstract

  Many cancer patients do not receive recommended palliative care (PC). Oncologists' perspectives about PC have not been adequately described qualitatively and may explain some of the gaps in the delivery of PC.To characterize U.S. oncologists' perceptions of: primary and specialist PC; experiences interacting with PC specialists; and the optimal interface of PC and oncology in providing PC.In-depth interviews with practicing oncologists.Oncologists working in: the general community, academic medical centers (AMC), and Veterans Health Administration.Semistructured telephone interviews with 31 oncologists analyzed using matrix and thematic approaches.Seven major themes emerged: PC was perceived as appropriate throughout the disease trajectory but due to resource constraints was largely provided at end of life; oncologists had three schools of thought on primary versus specialist PC; there was an under-availability of outpatient PC; poor communication about prognosis and care plans created tension between providers; PC was perceived as a "team of outsiders"; PC had too narrow a focus of care; and AMC-based PC evidence did not generalize to community practices. Oncologists noted three ways to improve the interface between oncologists and PC providers: a clear division of responsibility, in-person collaboration, and sharing of nonphysician palliative team members.Oncologists in our sample were supportive of PC, but they reported obstacles related to care coordination and inpatient PC. Inpatient PC posed some unique challenges with respect to conflicting prognoses and care practices that would be mitigated through the increased availability and use of outpatient PC.

  View details for DOI 10.1089/jpm.2016.0399

  View details for Web of Science ID 000398452000016

• The Appropriate Provision of Primary Versus Specialist Palliative Care to Cancer Patients: Oncologists' Perspectives. Journal of palliative medicine Gidwani, R., Nevedal, A., Patel, M., Blayney, D. W., Timko, C., Ramchandran, K., Kelly, P. A., Asch, S. M. 2016

  Abstract

  Many cancer patients do not receive recommended palliative care (PC). Oncologists' perspectives about PC have not been adequately described qualitatively and may explain some of the gaps in the delivery of PC.To characterize U.S. oncologists' perceptions of: primary and specialist PC; experiences interacting with PC specialists; and the optimal interface of PC and oncology in providing PC.In-depth interviews with practicing oncologists.Oncologists working in: the general community, academic medical centers (AMC), and Veterans Health Administration.Semistructured telephone interviews with 31 oncologists analyzed using matrix and thematic approaches.Seven major themes emerged: PC was perceived as appropriate throughout the disease trajectory but due to resource constraints was largely provided at end of life; oncologists had three schools of thought on primary versus specialist PC; there was an under-availability of outpatient PC; poor communication about prognosis and care plans created tension between providers; PC was perceived as a "team of outsiders"; PC had too narrow a focus of care; and AMC-based PC evidence did not generalize to community practices. Oncologists noted three ways to improve the interface between oncologists and PC providers: a clear division of responsibility, in-person collaboration, and sharing of nonphysician palliative team members.Oncologists in our sample were supportive of PC, but they reported obstacles related to care coordination and inpatient PC. Inpatient PC posed some unique challenges with respect to conflicting prognoses and care practices that would be mitigated through the increased availability and use of outpatient PC.

  View details for DOI 10.1089/jpm.2016.0399

  View details for PubMedID 27997278

• The Current State of Palliative Care for Patients Cared for at Leading US Cancer Centers: The 2015 NCCN Palliative Care Survey. Journal of the National Comprehensive Cancer Network Calton, B. A., Alvarez-Perez, A., Portman, D. G., Ramchandran, K. J., Sugalski, J., Rabow, M. W. 2016; 14 (7): 859-866

  Abstract

  ASCO and IOM recommend palliative care (PC) across health care settings for patients with serious illnesses, including cancer. This study provides an overview of the current availability, structure, and basic quality of PC services within NCCN Member Institutions.A PC survey was developed by NCCN staff and a working group of PC experts from 11 NCCN Member Institutions under the auspices of the NCCN Best Practices Committee. The survey was piloted and refined by 3 working group members and sent electronically to all 26 NCCN Member Institutions. NCCN staff and working group leaders analyzed the survey data.A total of 22 of 26 institutions responded (85%). All respondents (100%) reported an inpatient PC consult service (staffed by an average of 6.8 full-time equivalents [FTEs], seeing 1,031 consults/year with an average length of stay [LOS] of 10 days). A total of 91% of respondents had clinic-based PC (with an average of 469 consults/year, staffed by an average of 6.8 FTEs, and a 17-day wait time). For clinics, a comanagement care delivery model was more common than strict consultation. Home-based PC (23%) and inpatient PC units (32%) were less prevalent. Notably, 80% of institutions reported insufficient PC capacity compared with demand. Across PC settings, referrals for patients with solid tumors were more common than for hematologic malignancies. Automatic or "triggered" referrals were rare. The most common services provided were symptom management (100%) and advance care planning (96%). Most programs were funded through fee-for-service billing and institutional support. Partnerships with accountable care organizations and bundled payment arrangements were infrequent. PC program data collection and institutional funding for PC research were variable across institutions.Despite the prevalence of PC inpatient and clinic services among participating NCCN Member Institutions, PC demand still exceeds capacity. Opportunities exist for expansion of home-based PC and inpatient PC units, optimizing referrals, research, and payer collaborations.

  View details for PubMedID 27407126

• Integrated Palliative Care and Oncologic Care in Non-Small-Cell Lung Cancer. Current treatment options in oncology Chandrasekar, D., Tribett, E., Ramchandran, K. 2016; 17 (5): 23-?

  Abstract

  Palliative care integrated into standard medical oncologic care will transform the way we approach and practice oncologic care. Integration of appropriate components of palliative care into oncologic treatment using a pathway-based approach will be described in this review. Care pathways build on disease status (early, locally advanced, advanced) as well as patient and family needs. This allows for an individualized approach to care and is the best means for proactive screening, assessment, and intervention, to ensure that all palliative care needs are met throughout the continuum of care. Components of palliative care that will be discussed include assessment of physical symptoms, psychosocial distress, and spiritual distress. Specific components of these should be integrated based on disease trajectory, as well as clinical assessment. Palliative care should also include family and caregiver education, training, and support, from diagnosis through survivorship and end of life. Effective integration of palliative care interventions have the potential to impact quality of life and longevity for patients, as well as improve caregiver outcomes.

  View details for DOI 10.1007/s11864-016-0397-1

  View details for PubMedID 27032645

  View details for PubMedCentralID PMC4819778

• Integrating Palliative Care Into Oncology: A Way Forward CANCER CONTROL Ramchandran, K., Tribett, E., Dietrich, B., Von Roenn, J. 2015; 22 (4): 386-395

  View details for Web of Science ID 000368051500003

• Implementation of supportive care and best supportive care interventions in clinical trials enrolling patients with cancer†. Annals of oncology Lee, R. T., Ramchandran, K., Sanft, T., Von Roenn, J. 2015; 26 (9): 1838-1845

  Abstract

  With the growing and evolving role of palliative care in oncology, we examined how supportive care (SC) and best supportive care (BSC) are implemented in clinical trials when used as a comparison treatment arm.We conducted a systematic review of the literature for clinical trials published between 1980 and 2012 in which systemic anticancer therapy was compared with an SC-only arm and compared SC implementation with World Health Organization (WHO) published guidelines.Our search identified 189 articles, 73 of which met our inclusion criteria with the following cancer types: 29 lung, 7 colorectal, 6 pancreatic, 5 gastric and 26 others. Fifty-five studies (75%) provided some definition of SC, and 48 studies (66%) used the term BSC. Twenty-one of the 55 studies that provided a definition described the use of palliative therapies as being 'at the discretion of the treating physician' without standardization. Only two studies provided SC that incorporated routine physical, psychological and social assessments including rapid referral to SC specialists. SC interventions most commonly included analgesics (47%) and radiotherapy (44%). Trials using the term BSC versus SC were more likely to include blood transfusions (P = 0.002) and antibiotics (P = 0.033), but less likely to include steroids (P = 0.05) and palliative specialists (P = 0.047).The implementation of SC in clinical trials in this systematic review is highly variable. The vast majority of the studies did not meet the WHO guidelines on SC because palliative care therapies were not recommended or integrated into care. Future clinical trials utilizing a SC intervention arm should define these interventions in a standardized approach that meets current guidelines such as the WHO recommendations.

  View details for DOI 10.1093/annonc/mdv207

  View details for PubMedID 25922064

• Prolonged survival of patients with non-small-cell lung cancer with leptomeningeal carcinomatosis in the modern treatment era. Clinical lung cancer Riess, J. W., Nagpal, S., Iv, M., Zeineh, M., Gubens, M. A., Ramchandran, K., Neal, J. W., Wakelee, H. A. 2014; 15 (3): 202-206

  Abstract

  Leptomeningeal carcinomatosis (LM) is a severe complication of non-small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM.Patients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3.LM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007).In this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication.

  View details for DOI 10.1016/j.cllc.2013.12.009

  View details for PubMedID 24524822

• A predictive model to identify hospitalized cancer patients at risk for 30-day mortality based on admission criteria via the electronic medical record. Cancer Ramchandran, K. J., Shega, J. W., von Roenn, J., Schumacher, M., Szmuilowicz, E., Rademaker, A., Weitner, B. B., Loftus, P. D., Chu, I. M., Weitzman, S. 2013; 119 (11): 2074-2080

  Abstract

  This study sought to develop a predictive model for 30-day mortality in hospitalized cancer patients, by using admission information available through the electronic medical record.Observational cohort study of 3062 patients admitted to the oncology service from August 1, 2008, to July 31, 2009. Matched numbers of patients were in the derivation and validation cohorts (1531 patients). Data were obtained on day 1 of admission and included demographic information, vital signs, and laboratory data. Survival data were obtained from the Social Security Death Index.The 30-day mortality rate of the derivation and validation samples were 9.5% and 9.7% respectively. Significant predictive variables in the multivariate analysis included age (P < .0001), assistance with activities of daily living (ADLs; P = .022), admission type (elective/emergency) (P = .059), oxygen use (P < .0001), and vital signs abnormalities including pulse oximetry (P = .0004), temperature (P = .017), and heart rate (P = .0002). A logistic regression model was developed to predict death within 30 days: Score = 18.2897 + 0.6013*(admit type) + 0.4518*(ADL) + 0.0325*(admit age) - 0.1458*(temperature) + 0.019*(heart rate) - 0.0983*(pulse oximetry) - 0.0123 (systolic blood pressure) + 0.8615*(O2 use). The largest sum of sensitivity (63%) and specificity (78%) was at -2.09 (area under the curve = -0.789). A total of 25.32% (100 of 395) of patients with a score above -2.09 died, whereas 4.31% (49 of 1136) of patients below -2.09 died. Sensitivity and positive predictive value in the derivation and validation samples compared favorably.Clinical factors available via the electronic medical record within 24 hours of hospital admission can be used to identify cancer patients at risk for 30-day mortality. These patients would benefit from discussion of preferences for care at the end of life. Cancer 2013;119:2074-2080. © 2013 American Cancer Society.

  View details for DOI 10.1002/cncr.27974

  View details for PubMedID 23504709

• Palliative Care Always ONCOLOGY-NEW YORK Ramchandran, K., Von Roenn, J. H. 2013; 27 (1): 13-?

  Abstract

  Palliative cancer care is the integration into oncologic care of therapies that address the issues that cause physical and psychosocial suffering for the patient and family. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all settings (home, inpatient, and outpatient). There is clear evidence for improved outcomes in multiple domains-symptoms, quality of end-of-life care, provider satisfaction, cost of care-with the integration of palliative care into cancer care. As a result, there are now guideline-based recommendations for incorporating palliative care into cancer care. Unfortunately there continue to be barriers to effective integration; these include gaps in education and research, and a cultural stigma that equates palliative care with end-of-life care. These barriers will need to be addressed in order to achieve seamless palliative care integration across the continuum of cancer care for all patients and their families.

  View details for Web of Science ID 000314141000002

  View details for PubMedID 23461040

• Emerging Concepts in the Pathology and Molecular Biology of Advanced Non-Small Cell Lung Cancer AMERICAN JOURNAL OF CLINICAL PATHOLOGY Kulesza, P., Ramchandran, K., Patel, J. D. 2011; 136 (2): 228-238

  Abstract

  Non-small cell lung cancer (NSCLC) is traditionally classified histologically, but until recently, the histologic subtype has had little impact on the selection of therapy. Drugs such as pemetrexed and bevacizumab are indicated for specific NSCLC subtypes, and this type of stratification represents the first step toward individualizing therapy in NSCLC. Beyond histologic features, the status of molecular targets, such as the epidermal growth factor receptor (EGFR) gene, has been shown to correlate with response to treatment with EGFR tyrosine kinase inhibitors in patients with relapsed or refractory disease and in the first-line therapy setting. New therapies targeting the EGFR and other molecular aberrations are under way to help define specific subsets of patients responsive to certain molecularly targeted treatments. The role of pathologists in guiding treatment decisions will increase because molecular profiling, together with pathologic and histologic analysis, represents the future of personalizing medicine for patients with NSCLC.

  View details for DOI 10.1309/AJCPO66OIRULFNLZ

  View details for Web of Science ID 000292905000006

  View details for PubMedID 21757595

• Phantom Limb Pain #212 JOURNAL OF PALLIATIVE MEDICINE Ramchandran, K., Hauser, J. 2010; 13 (10): 1285-1286

  View details for DOI 10.1089/jpm.2010.9775

  View details for Web of Science ID 000282953900020

  View details for PubMedID 20942763

• Sex Differences in Susceptibility to Carcinogens SEMINARS IN ONCOLOGY Ramchandran, K., Patel, J. D. 2009; 36 (6): 516-523

  Abstract

  Lung cancer has reached epidemic proportions in women, and is now the most common cause of cancer death among both men and women in the United States. While smoking rates have declined marginally in women, the rising impact of lung cancer in women may imply that women are at higher risk from carcinogens secondary to underlying factors related to sex. These factors include differences in female physiology such as bronchial responsiveness and airway size, sex-based differences in nicotine metabolism via the cytochrome p450 system driven by hormones, and differences in DNA repair capacity, as well as the evolution of cigarettes. These hypotheses will be explored in depth in this article.

  View details for DOI 10.1053/j.seminoncol.2009.09.005

  View details for Web of Science ID 000278079100006

  View details for PubMedID 19995643

• My Friend, My Patient JOURNAL OF PALLIATIVE MEDICINE Ramchandran, K. 2009; 12 (1): 95-96

  View details for DOI 10.1089/jpm.2009.9688

  View details for Web of Science ID 000262827900026

  View details for PubMedID 19284274