tbuckley/cabot-search huggingface dataset:
Choosing unwisely: Low-value care in older adults with a diagnosis of myelodysplastic syndrome.
Authors: Sudipto Mukherjee, Weichuan Dong, Kurt C Stange, Jennifer Cullen, Sarah C. Markt, Mikkael A. Sekeres, Siran M. Koroukian
Journal: Journal of Clinical Oncology (2021)

1532 Background: In tandem with the Choosing Wisely initiative, ASCO’s Cost of Care Task Force has proposed a list of low-value (LV) procedures and therapies that may be of limited benefit to patients. Myelodysplastic syndrome (MDS) is the most common myeloid malignancy in the US. A complete diagnostic evaluation (CDE) of MDS requires a bone marrow biopsy, fluorescence in situ hybridization and chromosomal analysis. As a potential LV procedure, we evaluated receipt of CDE in MDS patients with isolated or no cytopenias and no transfusion dependence. Methods: Using national 2011-2014 Medicare data, we identified fee-for-service Medicare patients 66 years of age or older with an MDS diagnosis, one or no cytopenias, and no blood transfusions in the 16 weeks before or after an MDS diagnosis (n = 16,779). We examined the following variables that may have provided a clinical context to (or not to) pursue CDE – demographics (age, race, sex); number of Elixhauser comorbid conditions ( &lt; 5 vs &gt;5); nursing home status, prior history of lymphoma, myeloma, MGUS and other cancers; chronic kidney disease (CKD); colonoscopy; and therapies received including erythropoiesis stimulating agents (ESAs), hypomethylating agents (HMAs) or lenalidomide. We conducted Classification and Regression Tree (CART) analysis, a machine learning approach to identify combinations of factors in patients with little clinical justification for CDE, and Cox proportional hazards regression analysis to compare survival outcomes between those with or without CDE. Results: Over half of our study population (51%) received CDE. Of those, 46.6% were 80 years of age or older, 4.8% were nursing home residents; and 33.6% had 5 or more chronic conditions. Results from CART analysis showed that among patients with an isolated cytopenia (e.g., isolated anemia), 46.0% of patients &gt;80 years (n = 860), and 57.7% (n = 1,156) of those in the 66-79 age group underwent CDE in the absence of CKD, colonoscopy, HMA, or ESA. Among those with no cytopenia (n = 3890), 866 patients received CDE in the absence of HMA, ESA, or history of lymphoma or progression to leukemia. In adjusted analyses, no survival benefit was associated with receipt of CDE (p = 0.24). Conclusions: A substantial number of patients with an MDS diagnosis, isolated or no cytopenias, and no transfusion dependence received a CDE in the absence of other diagnoses, procedures, or therapies that may have explained the clinical decision to perform CDE. These procedures entail costs, pain and anxiety, but do not appear to yield useful information to guide clinical management, as evidenced by the comparable survival outcomes between patients who did and did not undergo CDE. To promote patient-centered care, careful patient selection that reduces unnecessary CDE in MDS patients should be a priority in clinical decision-making.
Why are oncologists not testing all NSCLC patients for biomarkers in the U.S. market?
Authors: Daniel F. Winkelman, Vaibhav M. Varkhedkar, Holly Stellander-Amato, Lesley Bailey, Anise Kachadourian
Journal: Journal of Clinical Oncology (2021)

e21003 Background: NSCLC has the greatest number of biomarkers of any tumor type. If a patient is not biomarker tested, he or she may not receive access to targeted therapies that often offer greater efficacy through personalized therapy. The purpose of this research study is to examine the reasons certain lung cancer patients are not tested in the United States for biomarkers. Methods: This study followed market research best practices. The study was based on a survey of the BrandImpact Oncology panel conducted on patient visits during Q4 2020 at the point-of-prescribing. Results: The baseline measure of NSCLC patients that were being treated but had a biomarker status that was unknown ranges from 9% to 12% of patient visits. The biomarkers examined included ALK, ROS-1, EGFR and PD-L1. The Oncologists who treat NSCLC patients received the following question: When treating patients in your practice with NSCLC cancer what are your top 3 reasons for not conducting biomarker testing? As outlined in the table below which reflects all survey responses, the top four reasons for not conducting biomarker testing are: not enough tumor sample for testing purposes, patient has early stage of disease, patient is not healthy enough and patient cost associated with testing. Conclusions: The overall results indicate the absence of biomarker testing for lung cancer patients is mainly due to two different patient types. The early-stage patient was a key reason for not testing despite advances in early stage indications and diagnostic technology which provide increasing evidence that testing should be done earlier in the treatment journey. The late-stage patient which is seen more often in Academic institutions and who often has more aggressive cancer. The speed of receiving the biomarker test results for these more severe patients likely needs to be addressed. In the Community, setting cost of branded therapies can be an issue and in some cases biomarker testing is not readily available in all practices. It should also be noted that “not enough tumor sample for testing” was the number one reason for not conducting biomarker testing, but this issue can now be addressed through liquid NGS technology.[Table: see text]
Health outcomes and resource utilization associated with postsurgical opioid use among cancer patients undergoing curative-intent surgery.
Authors: Na Lin, Yuan Xu, Winson Y. Cheung, May Lynn Quan
Journal: Journal of Clinical Oncology (2021)

6515 Background: To date, it remains unclear whether new persistent post-surgical opioid use is associated with subsequent opioid overdose, higher mortality and greater consumption of healthcare resources among cancer patients. To fill this gap, a population-based cohort study by applying real-world data has been performed to compare the long-term outcomes and healthcare resource use between new persistent and non-persistent opioid users among cancer patients after curative-intent surgery. Methods: This retrospective cohort study included all adult cancer patients with solid tumours who received curative-intent surgery in Alberta between 2011 and 2015, with a follow-up period until December 31, 2019. Patients who had multiple tumors, or had a follow-up &lt; 6 months, or &gt; 30 days of hospitalization were excluded. A new persistent post-surgical opioid user was defined as a patient who was opioid-naïve before surgery (no opioid prescription filled prior to the surgery) and subsequently filled at least one opioid prescription between 60 and 180 days after surgery. The outcomes (opioid overdose and mortality within 3 years) and health resource use (emergency department visits and hospitalization within the first year) after surgery were evaluated by applying multivariable logistic and Cox regressions. Results: A total of 19,219 patients received curative-intent surgery with a median follow-up of 47 months, of which 1,530 (8.0%) were identified as postoperative new persistent opioid users. Compared with the non-persistent group, a higher rate of opioid overdose (OR = 1.81, 95% CI: 1.49-2.2) within 3 years of surgery has been observed for new persistent opioid users, who were also associated with a greater likelihood of being hospitalized (OR = 2.52, 95% CI: 2.21-2.87) and visiting an emergency room (OR = 2.0, 95% CI: 1.78-2.24) within the first year after surgery. A higher overall (HR = 1.37, 95% CI: 1.2-1.57) and non-cancer caused mortality (HR = 1.39, 95% CI: 1.18-1.65) has also been detected for new persistent opioid users during the study follow-up period. Conclusions: For cancer patients undergoing curative-intent surgery, reducing new persistent opioid use is imperative to improve subsequent outcomes and health resource utilization.
Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals
Authors: Talia Kustin, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi, Rachel Levy, Michael Leshchinsky, Shifra Ken Dror, Galit Bergerzon, Hala Gadban, Faten Gadban, Eti Eliassian, Orit Shimron, Loulou Saleh, Haim Ben-Zvi, Elena Keren Taraday, Doron Amichay, Anat Ben-Dor, Dana Sagas, Merav Strauss, Yonat Shemer Avni, Amit Huppert, Eldad Kepten, Ran D. Balicer, Doron Netzer, Shay Ben-Shachar, Adi Stern
Journal: Nature Medicine (2021)

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.
Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease
Authors: Mary M. McDermott, Sudarshan Dayanidhi, Kate Kosmac, Sunil Saini, Joshua Slysz, Christiaan Leeuwenburgh, Lisa Hartnell, Robert Sufit, Luigi Ferrucci
Journal: Circulation Research (2021)

Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of walking exercise on lower extremity skeletal muscle in PAD. In older people without PAD, aerobic exercise improves mitochondrial activity, muscle mass, capillary density, and insulin sensitivity in skeletal muscle. However, walking exercise increases lower extremity ischemia in people with PAD, and therefore, mechanisms by which this exercise improves walking may differ between people with and without PAD. Compared with people without PAD, gastrocnemius muscle in people with PAD has greater mitochondrial impairment, increased reactive oxygen species, and increased fibrosis. In multiple small trials, walking exercise therapy did not consistently improve mitochondrial activity in people with PAD. In one 12-week randomized trial of people with PAD randomized to supervised exercise or control, supervised treadmill exercise increased treadmill walking time from 9.3 to 15.1 minutes, but simultaneously increased the proportion of angular muscle fibers, consistent with muscle denervation (from 7.6% to 15.6%), while angular myofibers did not change in the control group (from 9.1% to 9.1%). These findings suggest an adaptive response to exercise in PAD that includes denervation and reinnervation, an adaptive process observed in skeletal muscle of people without PAD during aging. Small studies have not shown significant effects of exercise on increased capillary density in lower extremity skeletal muscle of participants with PAD, and there are no data showing that exercise improves microcirculatory delivery of oxygen and nutrients in patients with PAD. However, the effects of supervised exercise on increased plasma nitrite abundance after a treadmill walking test in people with PAD may be associated with improved lower extremity skeletal muscle perfusion and may contribute to improved walking performance in response to exercise in people with PAD. Randomized trials with serial, comprehensive measures of muscle biology, and physiology are needed to clarify mechanisms by which walking exercise interventions improve mobility in PAD.
Regulation and Impact of BCR Induced Autophagy in Chronic Lymphocytic Leukemia
Authors: Lindsay D Smith, Laura I Karydis, Margaret Ashton-Key, Jonathan C Strefford, Freda K. Stevenson, Graham Packham, Mark Cragg, David A Tumbarello, Matthew D Blunt, Francesco Forconi, Andrew J Steele
Journal: Blood (2017)
Comparison of outcomes with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus real-world standard of care (RW SOC) for patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM).
Authors: Thomas G. Martin, Amrita Y. Krishnan, Kwee Yong, Katja Weisel, Maneesha Mehra, Sandhya Nair, Keqin Qi, Anil Londhe, Joris Diels, Concetta Crivera, Carolyn Chang Jackson, Yunsi Olyslager, Martin Vogel, Jordan Mark Schecter, Arnob Banerjee, Satish Valluri, Saad Zafar Usmani, Jesus G. Berdeja, Sundar Jagannath
Journal: Journal of Clinical Oncology (2021)

8045 Background: Pts with RRMM who are triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and an anti-CD38 antibody) cycle through multiple salvage regimens with progressively worse outcomes. CARTITUDE-1 (NCT03548207) is a single-arm phase 1b/2 study evaluating cilta-cel, a chimeric antigen receptor T-cell therapy with 2 B-cell maturation antigen–targeting single-domain antibodies, in pts with RRMM who received ≥3 prior lines of therapy (LOT) or were double refractory to an IMiD and PI, were triple-class exposed, had ECOG score of 0 or 1, and had disease progression ≤12 mo after the last LOT. Here, we compare efficacy outcomes for pts who received cilta-cel in CARTITUDE-1 (N = 97) with pts treated with SOC in a synthetic cohort from RW clinical practice. Methods: The Flatiron database, a primarily US community-based MM registry (Sep 2020 data cutoff), was used to identify a RW pt cohort who met CARTITUDE-1 (Sep 2020 data cutoff) eligibility criteria, including organ function. Progression-free/overall survival (PFS/OS) were compared between the cilta-cel–treated US pts and RW SOC cohort, using inverse probability of treatment (tx) weighting (IPTW) propensity scores adjusting for unbalanced baseline covariates of prognostic significance. Sensitivity analyses were conducted using multivariate Cox regression models and propensity score matching. Results: Baseline characteristics were similar between the 2 cohorts after propensity score weighting (Table). SOC tx regimens in the RW cohort primarily included pomalidomide (33%), carfilzomib (32%), daratumumab (13%), elotuzumab (16%), and ixazomib (8%). Pts had improved PFS and OS with cilta-cel (N = 97; median follow-up 12.4 mo) vs RW SOC (N = 196; median follow-up 9.2 mo) with a reduction in risk of progression/death and death by 84% and 78%, respectively (Table). Cilta-cel treatment benefit was robust across sensitivity analyses. Conclusions: Cilta-cel shows significantly better efficacy outcomes over RW SOC for PFS and OS, highlighting its potential as an effective tx option in pts with triple-class exposed RRMM. Clinical trial information: NCT03548207. [Table: see text]
Impact of tobacco and illicit drug use in the care of adolescent and young adults with sarcoma.
Authors: Rushad Machhi, Amanda Marie Parkes
Journal: Journal of Clinical Oncology (2021)

e18657 Background: Despite adolescent and young adults (AYAs) representing the patient population most likely to initiate and use tobacco and illicit drugs, studies of their impact have thus far focused on older cancer patients or those in survivorship. As sarcomas often serve as a model for AYA care and are associated with poor psychosocial function, frequent delays in diagnosis, and outcomes related to chemotherapy dose density, we sought to understand the impact of tobacco and illicit drug use on diagnosis, chemotherapy delays and dose reductions, and no-show rates in AYAs with sarcoma. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with sarcoma seen at least once in 2019 at the University of Wisconsin, identifying documentation of tobacco, marijuana, and other illicit drug use and comparing to pre-identified cancer outcomes including days from symptom onset to tissue diagnosis (with delay defined as &gt; 120 days from symptoms to diagnosis), chemotherapy delays &gt; 1 week and dose reductions, and appointment no-show rates. Current substance use was defined as use following cancer diagnosis. Results: We identified 46 AYAs with sarcoma, with documented tobacco use in 20% as current (9/46), 13% as former (6/46) and 67% as none (31/46). Marijuana and illicit drug use were less frequent at 17% (8/46) and 7% (3/46) respectively. Delayed diagnoses were more common in patients with current tobacco use (6/9, 67%) as compared with former or non-smokers (12/37, 32%, p = 0.12) and were seen in all patients with illicit drug use (3/3, 100%), as compared with only 35% without illicit drug use (15/43, p = 0.05). Of the 24 patients who received chemotherapy, chemotherapy delays and dose reductions were more common in current tobacco users at 86% (6/7) and 29% (2/7) respectively, as compared with patients with former or no tobacco use at 71% (12/17) and 18% (3/17) respectively. Chemotherapy dose reductions were also more common in patients with illicit drug use (2/3, 67%) versus no illicit drug use (3/21, 14%, p = 0.10). Appointment no-show rates were higher in current tobacco users versus former or non-smokers, with 44% (4/9) versus 27% (10/37) with a no-show rate &gt; 5%. In patients with documented substance use, oncology providers documented 93% of tobacco use (14/15) but only 38% marijuana use (3/8) and 33% illicit drug use (1/3) and no oncology providers documented a cessation plan. Conclusions: Current tobacco and illicit drug use in AYAs with sarcoma were associated with delays in diagnosis, increased chemotherapy delays and dose reductions, and higher no-show rates, highlighting modifiable risk factors. Even more strikingly, oncology providers had low rates of documentation of marijuana and illicit drug use in AYAs and no documentation of plans for cessation, highlighting a lost opportunity and the need for more standardized substance use assessment and evidence-based cessation interventions for AYAs with cancer.
A retrospective study of efficacy and safety of mechlorethamine, vindesine, liposomal doxorubicin, and prednisone (MODP) in relapsed/refractory classical Hodgkin lymphoma.
Authors: Min-Hang Zhou, Chunmeng Wang, Yang Liu, Wenjing Ku, Qingming Yang, Weidong Han
Journal: Journal of Clinical Oncology (2021)

e19516 Background: There are few optimized therapeutic options for relapsed and/or refractory classic Hodgkin’s lymphoma (r/rCHL), especially in patients who failed in treatments of autologous stem cell transplantation (ASCT), brentuximab vedotin or even immune checkpoint blockage. Therefore, we developed a chemotherapeutic scheme to evaluate the efficacy in r/rCHL patients with previous various lines of therapies. Methods: Between January, 2014 and December, 2019, a retrospective study was performed on r/rCHL patients from Chinese PLA general hospital who were treated with MOAP regimen consisting of mechlorethamine 6mg/m 2 , vindesine 4mg, liposomal doxorubicin 15mg/m 2 on days 1 and 8, prednisone 1mg/kg per day on days 1 to 10 (MOAP) every 4 weeks. CT or PET/CT were done every two cycles to assess the response. Patients treated with MOAP regimen and complete clinical data were included. Patients with less than two cycles of MOAT or unavailable response assessment were excluded. The primary endpoint were complete remission (CR) and progression-free survival (PFS). Results: A total of 87 patients were included and five patients were excluded, so 82 patients were eligible in the study. The median previous lines and cycles of chemotherapy was 2 (range, 1-7), and 9 (range, 3-31), respectively. All the eligible patients received MOAP regimen for a median 4 cycles (range from 2 to 8), and overall response rate (ORR) was 87.8% including 40 patients in CR (48.8%) and 32 in PR (39.0%). In patients with ≥ 3 lines or ≥ 10 cycles of chemotherapy, up to 50.0% and 41.0% of patients achieved CR, respectively. In patients with previous ASCT, 31.6% of patients also achieved CR. Patients with previous checkpoint inhibitors had even higher CR than those without checkpoint inhibitors, though not significantly (51.6% vs. 47.1%, p = 0.689). Median PFS in patients with CR, PR and SD/PD were 43.8 months, 9.6 months and 6.1 months, respectively (p = 0.000).Patients with &lt; 3 previous lines of chemotherapy had a favorable PFS than those with ≥ 3 previous lines (not reached vs. 14.4 months, (p = 0.032). No differences in PFS were observed in terms of previous cycles of chemotherapy, ASCT and checkpoint inhibitors. Grade ≥ 3 adverse events included 37 leukopenia (45.1%), 16 lung infection (19.5%), 11 anemia (13.4%), 4 thrombocytopenia (4.9%), 3 febrile neutropenia (3.7%) and 3 increased transaminase (3.7%). Conclusions: The MOAP combination regimen produced a favorable CR in r/rCHL failing or progressing on ASCT, checkpoint inhibitors, multiple cycles or lines of chemotherapies. It is an effective salvage regimen in heavily pretreated r/r CHL.