tbuckley/cabot-search huggingface dataset:
Risk factors for hospitalization for cancer patients with SARS-CoV-2 infection.
Authors: Zainab Shahid, Emily Baldrige, Sally Trufan, Courtney Schepel, Antoinette R. Tan, Jimmy J. Hwang, Laura W. Musselwhite, Edward S. Kim, Seungjean Chai, Ashley Love Sumrall, Brittany K. Ragon, Peter Michael Voorhees, Michael Richard Grunwald, Nilanjan Ghosh, Saad Zafar Usmani, Edward Alan Copelan, Derek Raghavan
Journal: Journal of Clinical Oncology (2021)

e18753 Background: Cancer patients are more susceptible to developing severe disease associated with SARS-CoV-2 infection. Herein, data from a high-volume cancer center is presented highlighting risk factors associated with hospitalization with COVID-19 disease. Methods: Cancer patients in the Levine Cancer Institute COVID19 database who were tested for SARS-CoV-2 due to clinical illness from March 1, 2020 to October 29, 2020 with 90 days follow-up are described here. Patients’ demographic and clinical information were retrospectively entered into a REDCap database from chart reviews. Differences in distributions were identified between hospitalized and non-hospitalized patients using the chi-squared test with uni- and multivariable logistic regression models. Statistical significance was set at p&lt;0.05. Results: 228 patients with SARS-CoV-2 infection were identified, of whom 103 (45%) were hospitalized. Median age was 63 years (range 28-95). Race distribution for infection showed White 65%, followed by Black 26.8% and Hispanic ethnicity 16.7% , with a similar distribution for hospital admission. Median length of stay was 10 days (range 1-91) with no readmissions within 90 days. The most common underlying malignancies were breast (29.8%), hematologic (21.1%) and genitourinary (12.3%). The most common preexisting conditions included hypertension (55.7%), diabetes (27.2%) and cardiac disease (3.9%). The most common presenting symptoms were cough (50.2%), fever (38.4%), fatigue (37.8%) and shortness of breath (36.4%). Maximum oxygen requirements for hospitalized patients were ambient air (34%), nasal canula (34%), high/medium flow nasal canula (10%), non-invasive ventilation (13%) and mechanical ventilation (10%). Case fatality rate was 10% with diagnosis of COVID-19, including 21.4% of those admitted to the hospital and 51.7% of those admitted to the ICU. Univariable logistic regression analysis showed that age, sex, prior chemotherapy, upper gastrointestinal cancers, hematologic cancers, number of medical conditions, cardiac disease, chronic lung diseases, hypertension, and diabetes increased risk of hospitalization. Table shows results of multivariate analysis. Conclusions: The COVID-19 pandemic has caused high case fatality rates in our cancer patients. We identified age, cardiac disease, hematologic malignancy and receipt of chemotherapy within 4 weeks of diagnosis as risk factors for hospitalization. These data may help in prioritizing early intervention in vulnerable subgroups to improve survival outcomes. [Table: see text]
Cemiplimab monotherapy as first-line (1L) treatment of patients with brain metastases from advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥ 50%: EMPOWER-Lung 1 subgroup analysis.
Authors: Mustafa Ozguroglu, Ahmet Sezer, Saadettin Kilickap, Mahmut Gumus, Igor Bondarenko, Miranda Gogishvili, Haci M. Turk, Irfan Cicin, Dmitry Bentsion, Oleg Gladkov, Philip R. Clingan, Virote Sriuranpong, Naiyer A. Rizvi, Jennifer McGinniss, Jean-Francois Pouliot, Sue Lee, Frank A. Seebach, Israel Lowy, Giuseppe Gullo, Petra Rietschel
Journal: Journal of Clinical Oncology (2021)

9085 Background: In the Phase 3, EMPOWER-Lung 1 study, cemiplimab monotherapy provided significant survival benefit and an acceptable safety profile vs chemotherapy in patients with advanced NSCLC and PD-L1 ≥50%. EMPOWER-Lung 1 included patients with brain metastases at baseline who are typically underrepresented in clinical trials. Other published exploratory analyses in single-cohort studies suggest benefit from immunotherapy in this patient population. Here, we present subgroup analysis of patients with brain metastasis from EMPOWER-Lung 1. Methods: Patients were randomized 1:1 to cemiplimab 350 mg IV every 3 weeks or investigator’s choice of chemotherapy (NCT03088540). Patients with treated, clinically stable brain metastases (radiological stability not required) were eligible to enroll and are the focus of this subgroup analysis from the PD-L1 ≥50% population (n=563) of the EMPOWER-Lung 1 study. Results: A total of 68 of 563 (12.1%) cases had treated stable brain metastases at time of randomization. Patients were evenly distributed between cemiplimab (n=34) and chemotherapy (n=34), with similar median duration of follow-up (Table). Baseline characteristics were generally similar; median (range) age: 60.0 (45–76 ) vs 62.0 (48–77); male: 97.1% vs 85.3%; and non-squamous histology: 85.3% vs 76.5%; between cemiplimab vs chemotherapy, respectively. Per independent review committee, median overall survival (OS, 18.7 vs 11.7 months), median progression-free survival (PFS, 10.4 vs 5.3 months), and objective response rate (ORR, 41.2% vs 8.8%) were superior with cemiplimab vs chemotherapy (Table). After baseline, central nervous system (CNS) disease progression occurred in 2 (5.9%) patients with cemiplimab vs 4 (11.8%) patients with chemotherapy; extra-CNS disease progression occurred in 9 (26.5%) patients with cemiplimab vs 15 (44.1%) patients with chemotherapy. Conclusions: 1L cemiplimab monotherapy improved OS, PFS, and ORR vs chemotherapy, in patients with advanced NSCLC with PD-L1 ≥50%, and clinically stable brain metastases at baseline. Cemiplimab monotherapy represents a suitable option for this subgroup of patients. Clinical trial information: NCT03088540. [Table: see text]
Beyond steroids: Immunosuppressants in steroid-refractory/resistant immune related adverse events.
Authors: Jia Luo, Jason Beattie, Paige Fuentes, Hira Rizvi, Jacklynn V. Egger, Jeffrey Kern, Donald Y. M. Leung, Mario E. Lacouture, Mark G. Kris, Maya Gambarin, Bianca Santomasso, David M. Faleck, Matthew D. Hellmann
Journal: Journal of Clinical Oncology (2021)

9092 Background: The optimal management for immune related adverse events (irAEs) in patients who do not respond or become intolerant to steroids is unclear. Guidelines suggest additional immunosuppressants based on case reports and expert opinion. Methods: We examined patients with advanced lung cancers at MSK treated with immune checkpoint blockade (ICB) from 2011-2020. Pharmacy records were queried to identify patients who received systemic steroids as well as an additional immunosuppressant (eg TNFα inhibitor, mycophenolate mofetil). Patient records were manually reviewed to examine baseline characteristics, management, and outcomes. Results: Among 2,750 patients with lung cancers treated with ICB, 51 (2%) received both steroids and an additional immunosuppressant for a severe irAE (TNFα inhibitor (73%), mycophenolate mofetil (20%)). The most common events were colitis (53%), pneumonitis (20%), hepatitis (12%), and neuromuscular (10%). At 90 days after start of an additional immunosuppressant, 57% were improved from their irAE, 18% were unchanged, and 25% were deceased. Improvement was more common in hepatitis (5/6) and colitis (18/27) but less common in neuromuscular (1/5) and pneumonitis (3/10). All patients with hepatitis received mycophenolate mofetil 500-1000mg BID for a median of 3 months, range 2-5 months. Of the 18 patients with colitis who improved with a TNFα inhibitor, 10 needed just one dose. Of 13 patients who died, 4 were related to toxicity from immunosuppression (3, infection-related deaths; 1, drug-induced liver injury leading to acute liver failure). Those who died from immunosuppressive therapy received higher amounts of systemic steroids than those who did not (max median 525 vs 132 mg prednisone equivalent, Mann Whitney U p = 0.004, total median 5.9k vs 2.3k mg prednisone equivalent, p = 0.004). Of 31 patients who received at least 3 weeks of prednisone ≥ 20mg, most (90%, 28/31) had at least one side effect that was brought to clinical attention (most commonly altered mood/ sleep, 52%, increase in BMI &gt; 1kg/m2, 45%, and infection, 32%). Conclusions: Steroid-refractory/resistant immune related adverse events are rare. While existing treatments help patients with hepatitis and colitis, most patients with other irAEs remain refractory and/or experience toxicities from immunosuppression. Systemic steroid use likely contributed to side effects and mortality. A more precise understanding of the pathophysiology of specific irAEs is needed to guide biologically informed treatment regimens for severe irAEs to realize the true benefit of ICB therapy.
Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity
Authors: Andrew Chow, Sara Schad, Michael D. Green, Matthew D. Hellmann, Viola Allaj, Nicholas Ceglia, Giulia Zago, Nisargbhai S. Shah, Sai Kiran Sharma, Marissa Mattar, Joseph Chan, Hira Rizvi, Hong Zhong, Cailian Liu, Yonina Bykov, Dmitriy Zamarin, Hongyu Shi, Sadna Budhu, Corrin Wohlhieter, Fathema Uddin, Aditi Gupta, Inna Khodos, Jessica J. Waninger, Angel Qin, Geoffrey J. Markowitz, Vivek Mittal, Vinod Balachandran, Jennifer N. Durham, Dung T. Le, Weiping Zou, Sohrab P. Shah, Andrew McPherson, Katherine Panageas, Jason S. Lewis, Justin S.A. Perry, Elisa de Stanchina, Triparna Sen, John T. Poirier, Jedd D. Wolchok, Charles M. Rudin, Taha Merghoub
Journal: Cancer Cell (2021)
Novel methods to assess cell-free circulating tumor DNA in acute lymphoblastic leukemia.
Authors: Meghan G Haney, Shilpa Sampathi, Yelena Chernyavskaya, Henry Moore, Tom C. Badgett, Jessica S Blackburn
Journal: Journal of Clinical Oncology (2021)

10034 Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with a relatively high relapse rate, which is associated with poor prognosis. Currently, minimal residual disease (MRD) at the end of induction and consolidation therapy is the best predictor of patient relapse, however obtaining bone marrow aspirate is invasive and not always accurate. Another major concern in ALL is the presence of central nervous system (CNS) disease, which is often present long before clinical diagnosis can be made by flow cytometry. To circumvent these clinical challenges, we developed a new assay quantifying cell-free, circulating tumor (cfDNA) as a biomarker of disease progression, which can be correlated with MRD status as a predictor of relapse. cfDNA is frequently used to monitor progression of solid tumors, but pediatric leukemias lack common mutations that can be used to distinguish leukemic cfDNA from normal cfDNA. Methods: We examined two possible methods for using ctDNA as a biomarker: leukemia cell clonality and DNA methylation profiling. We developed a novel workflow for identifying VDJ rearrangements in leukemia cells and tracking their presence in cfDNA. We collected bone marrow, blood, and CSF samples from newly diagnosed patients, and cfDNA was isolated from blood and CSF samples throughout treatment. Invivoscribe Lymphotrack PCR assays combined with MinION (Oxford Nanopore Technologies) sequencing were used to identify the VDJ sequence of the immunoglobulin (B-ALL) or T-cell receptor (T-ALL) rearrangements of leukemic clones in genomic DNA. The MinION assay relies on patient-specific sequencing. We are also in the process of developing a universal assay that utilizes recurrent methylation changes in ALL to identify leukemic cfDNA in patient samples. Results: The MinION workflow was used to follow leukemic cfDNA throughout the course of treatment, and accurately identified MRD and CNS disease in patients. This workflow performed equivalent or better at detecting leukemic clones compared to MiSeq and droplet digital polymerase chain reaction (ddPCR), and is faster and less expensive than traditional Illumina sequencing. Methylation analysis of 865 ALL and 79 healthy samples yielded 55 regions and 19 specific methylation sites that were uniquely present in ALL samples. We are validating these sites by ddPCR to establish a panel of biomarkers to track ALL over time via cfDNA. Conclusions: The end goal of our study is provide a more sensitive and less invasive method for tracking MRD and CNS disease than current approaches. Results will ultimately be correlated with patient response to therapy, the presence of relapse or CNS disease, and overall outcomes determined by standard clinical diagnostic procedures.
Abstract 12603: Nonischemic Left Ventricular Aneurysms With Undetermined Etiology Are Frequently Due to Cardiac Sarcoidosis
Authors: Steve Guo, Sandhya Murthy, Omar Saeed, Patricia Chavez, Snehal R Patel, Sasha Vukelic, Jooyoung Shin, Ulrich P Jorde, Daniel B Sims
Journal: Circulation (2019)

Introduction: Left ventricular (LV) aneurysms are commonly due to coronary artery disease (CAD). The differential diagnosis of nonischemic LV aneurysm includes cardiac sarcoidosis, Chagas disease, ...
Electricity auto-generating skin patch promotes wound healing process by activation of mechanosensitive ion channels
Authors: Tae-Hyun Kim, Won-Yong Jeon, Yunseong Ji, Eun Ju Park, Dong Suk Yoon, Na-Hyun Lee, Sung-Min Park, Nandin Mandakhbayar, Jung-Hwan Lee, Hae-Hyoung Lee, Hae-Won Kim
Journal: Biomaterials (2021)
Cancer specialists in the VA as early adopters of clinical genetic services.
Authors: Maren Theresa Scheuner, Paloma Sales, Mary Whooley, Katherine Hoggatt, Michael Kelley
Journal: Journal of Clinical Oncology (2021)

11029 Background: Genetic testing has become essential to delivery of cancer treatment, risk assessment, surveillance, and prevention. We sought to understand the use of genetic tests by clinicians in the Department of Veterans Affairs (VA). Methods: We administered a web-based survey to clinicians at 20 VA facilities with precision oncology programs. We excluded respondents if they were: not at one of the 20 VA facilities; not seeing patients in VA; not a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist; a medical geneticist or specialty was not reported; or if the survey was incomplete. Using multiple logistic regression, we assessed the association between genetic test ordering, genetics referral, and clinician characteristics. Results: There were 909 (909/11,442, 8%) eligible respondents with 61% women and 64% under age 55. There were 571 physicians (63%), 200 NPs (22%), 93 pharmacists (10%), and 45 PAs 5(%). There were 361 (40%) primary care providers (PCPs), 90 (10%) cancer specialists, and 458 (50%) non-cancer specialists. Only 21% of clinicians reported feeling prepared to use genetic tests in their practice. In the past year, only 8% had ordered at least one multi-gene cancer test (germline, tumor or both), 12% a pharmacogenetic test, and 0.2%, an exome. Compared to physicians, NPs were 60% less likely (OR = 0.42, 0.23-0.77, p = 0.005), pharmacists, 80% less likely (OR = 0.22, 0.08-0.62, p = 0.005), and PAs, 90% less likely (OR = 0.08, 0.01-0.58, p = 0.01) to have ordered a genetic test. Compared to PCPs, cancer specialists were almost 5 times more likely to order a genetic test (OR = 4.74, 2.57-8.73, p &lt; 0.0001); there was no difference in genetic test ordering between PCPs and non-cancer specialists. Among clinicians (n = 72) who had ordered cancer genetic tests, only about two-thirds were confident in knowing the indications for testing; discussing the potential benefits, harms and limitations of testing; understanding the test report; and knowing implications of results on disease management and prevention. Clinicians (n = 106) who had ordered pharmacogenetic tests had lower frequencies of confidence in these tasks. About half (52%) of the cancer specialists had referred patients to genetics in the past year; they were 1.8 times more likely than PCPs to refer (OR = 1.82, 1.10-3.03, p = 0.02), and non-cancer specialists were about 50% less likely than PCPs to refer (OR = 0.46, 0.33-0.64, p &lt; 0.0001). Conclusions: In the VA, cancer specialists are integrating genetic testing and genetics referral into their practice more than PCPs and other specialists. However, genetic testing is underutilized, and many clinicians remain unprepared to use genetic tests in their practice. These results will inform workforce planning, clinician education, and development of clinical decision support to facilitate genetic risk assessment, informed consent, and ordering of genetic tests.
Investigating the prevalence and risk of chemotherapy-induced neuropathy among cancer patients.
Authors: Philip Jordache, Keith Danahey, Natalie Marie Reizine, Peter H. O'Donnell
Journal: Journal of Clinical Oncology (2021)

12078 Background: Neuropathy is a common side effect of some chemotherapies. Clinical and other factors may confer neuropathy risk, but rates and risk factors across neuropathy-causing chemotherapies are incompletely understood. Methods: We examined 15 chemotherapy drugs known to confer neuropathy. Within a broad population of cancer patients who underwent treatment with these agents at the University of Chicago Medicine between 2012-2018, we determined prevalence of chemotherapy-induced neuropathy, defined as patients with initiation of a neuropathy treatment medication (amitriptyline, carbamazepine, duloxetine, gabapentin, or pregabalin) after starting chemotherapy. We then analyzed chemotherapy-induced neuropathy risk for different drugs and based on clinical demographic factors. Results: We analyzed 7,866 patients (65.3% White, 53.7% Female, 27.6% Black/African-American, 5.6% Hispanic or Latino, 3.1% Asian/Mideast Indian, 2.4% More than one Race, 0.2% American Indian or Alaska Native, 0.2% Native Hawaiian/Other Pacific Islander). The overall prevalence of chemotherapy-induced neuropathy was 24.3% across our patient population. Black/African-American patients had an increased risk of chemotherapy-induced neuropathy compared to the rest of the patient cohort (OR 1.4, 95% CI 1.3-1.6, P = 1.6e-10). Females also exhibited an increased risk of chemotherapy-induced neuropathy compared to males (OR 1.2, 95% CI 1.1-1.3, P = 1.5e-3). Conclusions: Certain chemotherapy agents confer substantial risk of chemotherapy-induced neuropathy, and risk is increased in Blacks and females. Future work will investigate additional risk-modifying factors including the potential role of germline polymorphisms on chemotherapy neuropathy risk.[Table: see text]
Advance care planning billing practices and documentation quality for cancer patients requiring hospitalization.
Authors: Callie Berkowitz, Jessica Ma, Jared Richard Lowe, Rowena Dolor
Journal: Journal of Clinical Oncology (2021)

e24000 Background: Advance Care Planning (ACP) is an important component of comprehensive cancer care, yet barriers exist to successful implementation. In 2016, Medicare introduced billing codes to provide reimbursement for ACP discussions. Our aim was to evaluate the usage of ACP billing codes and quality of accompanying documentation in patients with a prior oncology admission at an academic medical center. Methods: Using an electronic health record data warehouse tool, we identified a cohort of cancer patients who had been admitted to the inpatient oncology service and had an ACP billing encounter (CPT codes 99497 or 99498) over a 4-year period (8/1/2016 to 8/1/2020). We collected patient and provider demographics and performed descriptive statistics. We assessed ACP documentation quality for 30 patients selected at random based on 5 domains (healthcare proxy, health values or goals, scope of treatment/code status, prognosis/illness understanding, and end of life [EOL]care planning/hospice) previously identified from a literature review. Results: We identified 170 unique patients (180 ACP encounters), representing a small fraction (170/5636, 0.03%) of hospitalized oncology patients over the study period. Patients were 52% female with mean age of 64 (SD 12.9). Mean number of oncology hospitalizations was 2.6 (SD 1.96). ACP encounters took place in both inpatient (135/180; 75%) and outpatient (45/180; 25%) settings. In the outpatient setting, the majority of billing encounters were in palliative care (27/45; 60%), followed by oncology (12/45;27%) and primary care (5/45;11%). Of the sample of patient charts reviewed (n = 30), provider documentation frequently included scope of treatment (27/30; 90%), prognosis (27/30; 90%), EOL planning (21/30; 70%), and health values (19/30, 63%); healthcare proxy was infrequently included (4/30, 13%). Conclusions: ACP billing remains infrequently utilized for a cohort of oncology patients requiring hospitalization at a large academic center. In cases for which an ACP discussion is billed, the accompanied documentation is of high clinical utility and meets several key quality domains. This work lays a foundation for future research and quality improvement efforts to improve ACP and documentation.[Table: see text]
Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.
Authors: Rodrigo Sanchez-Bayona, Pablo Tolosa, Ana Sanchez de Torre, Alicia Castelo, Elsa Bernal-Hertfelder, Laura Lema, Eva M. Ciruelos, Luis Manso
Journal: Journal of Clinical Oncology (2021)

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m 2 ) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p &lt; 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.