tbuckley/cabot-search huggingface dataset:
Transitions across different lines of therapy in Medicare-enrolled patient populations with multiple myeloma.
Authors: Akeem Yusuf, Tanya Natwick, Diana Felici, Winifred Werther
Journal: Journal of Clinical Oncology (2016)

8043 Background: Multiple myeloma (MM) patients are often treated with multiple lines of therapy (LOT). However, transition rates and reasons for not transitioning across LOT have not been well characterized. Methods: Using a validated algorithm, adult MM patients (2008-2011) were identified from the 100% Medicare hematologic cancer file. Patients receiving treatments were identified for LOT up to 5 lines. Patients advanced LOT after a 90 day gap in all treatments (break) or when a drug was added to a regimen after 90 days (direct switch). Claims-based transition across LOT was determined using a previously developed algorithm. LOT transition rates, reasons for advancing to the next line and disposition of those who did not advance were determined. Results: 15474, 8308, 3878, 1608 and 604 MM patients initiated LOT 1, 2, 3, 4 and 5, respectively; accounting for transition rates of 54%, 47%, 42% and 38% from lines 1 - 4. Of those who initiated a 1st line treatment and advanced to 2nd line treatment (N=8308), 4293(52%) had a break in current treatment before line advancement while 4015(48%) switched directly. Similar patterns of advancement were observed for the other LOT. The reasons for not advancing from 1st to 2ndLOT were death (52%), censoring due to study end (41%), and cessation of Medicare coverage (7%). Conclusions: Transition rates across LOT decreased with increasing LOT as expected. While half of patients advance LOT directly, the other half experience a break in treatment between LOTs. Transitions across lines of therapy in Medicare-enrolled multiple myeloma patients. Therapy Advanced to next line n (%) Pathway for advancing to next line n (%) Reason for not advancing to next line n (%) 1st line 15474 (100.0) Advanced 53.7% 8308(100.0) Break in therapy 51.7% Direct switch 48.3% Did not advance 46.3% 7166 (100.0) Died 52.3% Lost coverage 6.9% Censored 40.8% 2nd line 8308 (100) Advanced 46.7% 3878 (100.0) Break in therapy 48.3% Direct switch 51.8% Did not advance 53.3% 4430 (100.0) Died 40.0% Lost coverage 4.6% Censored 55.4% 3rd line 3878 (100.0) Advanced 41.7% 1608 (100.0) Break in therapy 51.3% Direct switch 48.6% Did not advance 58.5% 2270 (100.0) Died 37.6% Lost coverage 2.9% Censored 59.5%
A FARETES study of the efficacy and safety of testosterone in metastatic renal cell carcinoma patients with fatigue.
Authors: Ilya Tsimafeyeu, Ruslan Zukov, Pavel Borisov, Anastasia Bondarenko, Kristina Zakurdaeva, Yulia Tishova
Journal: Journal of Clinical Oncology (2018)

4569 Background: Fatigue is a frequent symptom of metastatic renal cell carcinoma (mRCC), and most common adverse event of treatment with tyrosine kinase inhibitors. The aim of this multicenter randomized phase 2 study was to determine efficacy and safety of testosterone undecanoate (T) in mRCC patients with fatigue developed during targeted therapy. Methods: Sixty male patients with clear cell mRCC, normal PSA level, low testosterone level and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either T and targeted therapy or targeted therapy alone (control group). T (1,000 mg) was injected intramuscular deeply on Day 1 of a new treatment cycle. The primary endpoint of the study was the difference in mean change of fatigue according to Functional Assessment of Cancer Therapy-Fatigue (FACIT-F). Secondary endpoints were safety, FKSI-19 score, testosterone serum concentrations, red blood cells (RBC) count and hemoglobin level. The assessments were performed at baseline and Day 28 of a treatment cycle. Results: T was well tolerated. No unexpected toxicity was observed. The health-related quality-of-life scores in the T group were better than those in the control group (Table). The current study did achieve its primary endpoint based on the significant differences favored T over targeted therapy alone regarding fatigue (all P≤0.012). Clinical trial information: NCT03379012.Conclusions: Male patients with mRCC receiving targeted therapy had significantly less fatigue and better symptom control with T. There was non-significant positive trend in hemoglobin level between 2 groups. T therapy was safe. Long-term outcomes will be reported. Baseline Day 28 T group, N=30 Control group, N=30 T group, N=30 Control group, N=30 Age (years), mean (range) 52 (33-71) 55 (42-69) - - Sunitinib, N(%) 28 (93) 28 (93) - - IMDC poor risk factors, 0-2, N(%) 21 (70) 22 (73) - - FACIT-F, mean (SD) 37 (4.7) 35.3 (3.1) 20.3 (8.1) 42.5 (8.4) FKSI-19, mean (SD) 46.5 (12.2) 44.2 (9.4) 27.5 (12.5) 39.9 (9.8) Total testosterone serum, nmol/l, mean (SD) 6.21 (1.78) 8.56 (2) 33.2 (14.3) - RBC, 1012/l, mean (SD) 3.7 (0.5) 3.9 (0.2) 4.4 (0.4) 3.6 (0.15) Hemoglobin, g/l, mean (SD) 124.5 (11.7) 119 (10.4) 133 (13.5) 108 (17)
Outcome of young patients with blastoid variant mantle cell lymphoma: An analysis of 138 patients.
Authors: James Gerson, Elizabeth A. Handorf, Stefan K. Barta
Journal: Journal of Clinical Oncology (2018)

e19548 Background: Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with heterogeneous outcomes. Small studies have shown that the blastoid variant has a particularly poor prognosis. We previously described the outcome of a cohort of 1031 young patients (pts) with MCL. Herein we sought to characterize the subset of pts with blastoid variant. Methods: We retrospectively studied transplant eligible adults with newly diagnosed MCL treated with induction chemotherapy from 2000-2015. 25 US and Canadian academic medical centers contributed. Data on prognostic markers, induction therapy, and survival were collected. Primary objectives were to assess progression free survival (PFS) and overall survival (OS). Secondary objectives included determination of differences in pt characteristics and treatments. Results: Of the 1031 pt cohort, 13% (n = 138) had blastoid variant MCL. As compared to the non-blastoid cohort, pts with blastoid variant were older (mean age 57 vs 55 years, p < 0.01), had a higher mean Ki67 index (64% vs 34%, p < 0.01), had a greater frequency of high risk MIPI (24% vs 13%, p < 0.05), and more often had TP53 mutations (6% (n = 114 due to missing data) vs 3% (n = 680 due to missing data), p < 0.05). Comparing pts with blastoid variant to pts with non-blastoid variant, 64% vs 41% were treated with intensive, cytarabine containing induction (HyperCVAD, DHAP/RCHOP, or Nordic regimen) (p < 0.01); response to induction did not differ (66% vs 74% CR; 18% vs 24% PR, p = 0.5); and fewer pts underwent consolidative autologous hematopoietic cell transplantation (HCT) (56% vs 65%, p < 0.05). At a median follow up of 76 months (mo), the median PFS for blastoid and non-blastoid MCL was 36 and 67 mo, respectively (p < 0.01), and median OS was 91 and 145 mo (p < 0.01). For pts with blastoid variant, autologous HCT after induction was associated with improved median PFS (52 mo vs 25 mo; p < 0.01). Autologous HCT was also associated with improved median OS (109 mo vs 71 mo; p < 0.01). Conclusions: In this large retrospective cohort, pts with blastoid variant MCL had higher rates of poor risk features and worse outcome as compared to non-blastoid pts. Receipt of autologous HCT after induction was associated with improved survival for eligible pts.
Stepping On: Cancer Edition: A fall-prevention intervention adapted for older adults with cancer.
Authors: Tanya Marya Wildes, Theresa Cordner, Brittany Depp, Tamara Coyne, Jan Hungerford, Heidi Tymkew, Scott Vouri, Marian Keglovits, Susan Stark
Journal: Journal of Clinical Oncology (2018)

e22020 Background: 20-50% of older patients (pts) with cancer have fallen in the past 6 months. Stepping On, a 7-week group-based self-management fall-prevention program addressing exercise, medications, and environmental hazards, reduces falls in community-dwelling older adults. Its effectiveness in older adults with cancer is unknown. Methods: In this mixed-methods study, pts aged ≥65 receiving systemic cancer therapy or experiencing side effects of cancer/cancer treatment who reported a fall or fear-of-falling were enrolled. We used an iterative process, based on participant feedback, to adapt Stepping On to the needs of cancer pts during the first 3 program waves. Next, we pilot-tested the adapted program for feasibility and preliminary efficacy. Efficacy included pre- and post-testing using the Falls Behavior Scale (FAB; a measure of behaviors that increase fall-risk) and the Falls-Efficacy Scale-International (FES-I; a measure of fear of falling in various situation). Here, we report pre-and post-test data from 2 pilot-testing program waves. Change scores were analyzed using a one-sample t-test. Results: 20 pts enrolled, with a mean age of 74.6 (range 66-85). 60% were female. Cancer types included breast (35%), prostate (15%), myeloma (15%), genitourinary (10%), and other (25%). Most (60%) had stage IV disease. All but 1 were on treatment (50% chemotherapy, 30% targeted agents, 15% endocrine). Participants were highly satisfied with the program: 100% were satisfied with the program format & weekly session length; 11.1% of respondents said the 7-week program was ‘too short’; 88.9% said it was ‘just right’. Over the course of the program, participants reported behavior change (mean baseline FAB 2.88±0.54; mean post-program FAB 3.21±0.43; mean change 0.32±0.38, p = 0.002, indicating more behaviors to decrease fall-risk). The mean FES-I did not change significantly (mean baseline FES-I 29.6±11.8; Mean post-program FES-I 30.1±11.1, mean change 0.056±9.5, p = 0.98). Conclusions: Participation in Stepping On: Cancer Edition was associated with a change in Falls Behavior Scale scores among older adults with cancer. Future study will be required to determine if the program prevents falls in this population. Clinical trial information: NCT02737839.
Risk-adjustment models for breast, lung, and colorectal cancer cost, utilization, and outcomes in a commercially insured population.
Authors: Bhuvana Sagar, Yu Shen Lin, Liana Desharnais Castel
Journal: Journal of Clinical Oncology (2017)

e18340 Background: Advances in oncology have led to rising costs which are unsustainable, necessitating value-based arrangements that maximize quality and overall outcomes. Our objective was to identify clinical and patient factors that predict higher costs and utilization among breast, lung, and colorectal cancer in a commercial population. Methods: We conducted a longitudinal analysis of claims in a sample of 9,748 commercially insured patients with breast, lung, and colorectal cancer, to measure costs and utilization based on presence of metastases, proxies for clinical biomarkers, patient demographics, and treatments. Results: Episode Risk Group (ERG) risk score, metastasis, and facility provider affiliation were cost drivers for all three types of cancer (breast, lung, and colorectal). Hypertension and younger age were cost drivers for breast cancer. In addition, HER2 positive status (β = 68,946, SE = 2,104, p &lt; .0001) was significant in breast cancer, and VEGF in both lung (β = 56,975, SE = 10,138, p &lt; .0001) and colorectal (β = 24,400, SE = 5,671, p &lt; .0001) cancers. Metastasis also was associated with greater hospital admissions and hospital length of stay in all three cancers. Chemotherapy and supportive drug therapies accounted for the highest proportions of total medical costs among beneficiaries observed. Conclusions: Value-based reimbursement models in oncology should appropriately risk adjust by accounting for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, we recommend adjusting for the factors we identified in models to predict costs and outcomes in breast, lung, and colorectal cancers.
Nonconventional responses and survival benefit of immunotherapy in advanced lung cancer.
Authors: Meera Yogarajah, Brian S Kuszyk, Chipman Robert Geoffrey Stroud, Cynthia R. Cherry, Paul R. Walker
Journal: Journal of Clinical Oncology (2017)

e14572 Background: Objective response rates (ORR) utilizing RECIST or WHO criteria have been traditionally used as clinical endpoints to assess efficacy of cytotoxic chemotherapy. However in the era of immunotherapeutic agents, response rate assessment can be misleading due to nonconventional responses resulting in premature discontinuation of treatment. Wolchok et al proposed immune-related response criteria (irRC) to assess immune responses in melanoma. He also noted that stable disease which is not indicative of antitumor activity could be a potential surrogate marker of better clinical outcome. Brahmer et al reported nonconventional pattern of responses with Nivolumab in lung cancer. Methods: A retrospective chart review was done to assess differences in responses utilizing both RECIST v1.1 and irRC criteria in lung cancer patients treated with Nivolumab. Patients who received minimum of 4 cycles of Nivolumab were included in the study. The CT scans were reviewed by a senior radiologist. We reviewed 64 patients treated with Nivolumab between 4/30/2015 to 6/21/2016 and 30 patients were found eligible. Results: Patient characteristics. Male 53%; median age 61 years; squamous 47%; adeno 40%; small cell 13%; Median cycles of Nivolumab 6. Response rates utilizing both criteria was essentially similar with only 2 patients showing dis-concordant responses (6.6%). We utilized RECIST responses criteria for further analysis. Partial response (PR) 2/30; stable disease (SD) 12/30; progressive disease (PD) 15/30 and not evaluable (NE) 1/30. ORR 6.6%. Kaplan–Meier curve was used to analyze difference in survival between patients with PR+SD and PD. The median survival for PD was 9 months and PR+SD was not reached at median follow up of 1 year. Overall survival at 1 year for PD 33% and PR+SD 60% (p = 0.048). Hazard ratio for PD was 3.060 (p = 0.60). Conclusions: Patients with stable disease had a better survival and should be considered as responders though traditionally not included in the ORR. However irRC did not help in differentiating nonconventional immune responses in lung cancer patients. [Table: see text]
Characterization of complete responders to combination nivolumab (nivo) and ipilimumab (ipi) in patients (pts) with advanced, unresectable melanoma.
Authors: Allison Betof Warner, Alexander Noor Shoushtari, Sean Houghton, Katherine Panageas, Paul B. Chapman, Jedd D. Wolchok, Michael A. Postow
Journal: Journal of Clinical Oncology (2018)

9552 Background: Among pts who discontinue treatment with nivo + ipi due to toxicity with a partial response or complete response (CR), ~30% ultimately progress. Less is known about whether pts who achieve CR to nivo + ipi maintain the CR after discontinuing treatment and how progression occurs. Methods: We conducted a single-institution (Memorial Sloan Kettering Cancer Center), retrospective analysis of checkpoint inhibitor naïve pts with advanced, unresectable melanoma treated with at least one dose of nivo + ipi and ≥6 months of follow-up from time of first treatment (n = 201). Pts with acral, uveal and mucosal melanoma were excluded. CR was defined by absence of radiographically apparent disease or after a biopsy showed no viable melanoma in radiographically apparent residual tissue. Overall survival (OS) was calculated by the Kaplan-Meier method. Results: Of the 201 pt cohort with a median follow-up of 27 months (mos) among survivors, the median OS has not been reached. Estimated 24-month OS is 74.5%. 56 pts (28%) achieved CR. Estimated 24-month OS among the pts in CR is 93.5%. Of the 56 pts with CR, only 2 (4%) remain on anti-PD-1 maintenance. 34 (61%) discontinued immunotherapy for toxicity, and 20 (36%) discontinued for reasons other than toxicity (i.e. protocol completion, CR, pt preference). Among the CR pts who discontinued therapy, 50 remain in CR (longest duration of CR = 71 mos) with a median follow-up of 20.5 mos from time of CR. 4 of the 56 pts ultimately had disease progression (PD); none of these pts was on treatment at time of PD (range of treatment duration: 1-16 mos). Two patients had PD within 3 months of CR, one in the bladder/pelvis and the other in bone. One patient had PD in the brain 18 months after CR, and one had PD in a regional lymph node after 41 months. Conclusions: Patients with advanced, unresectable melanoma can have durable CR, even after discontinuing therapy. OS and CR rates in our large dataset are similar to published trials yet follow-up time for some pts exceeds that reported in clinical trials. The incidence of disease progression after CR to nivo + ipi is low after 3 months. The need for ongoing systemic and intracranial surveillance requires further study
Abstract 453: <i>FADS2</i> Overexpression Exacerbates Myocardial Ischemia-reperfusion Injury in Mice: Role of Mitochondria
Authors: Lance C Li Puma, Kalyn S Specht, Adam J Chicco
Journal: Circulation Research (2017)

Common FADS2 haplotypes associated with hyperactivity of its gene product, delta-6-desaturase (D6D), predict cardiovascular morbidity and mortality in humans. D6D is the rate-limiting enzyme in essential polyunsaturated fatty acid (PUFA) metabolism, but its role in the pathogenesis of cardiovascular disease is unclear. To investigate this, we generated mice with global (CMV promoter) transgenic overexpression of FADS2 and evaluated their cardiometabolic phenotype. FADS2 -tg mice exhibit mild glucose intolerance and aortic stiffening with advancing age, but no overt cardiac pathology. However, when challenged with ischemia-reperfusion (I/R) ex vivo , FADS2 -tg mouse hearts have greater infarct sizes compared to their wild-type (WT; FVB) counterparts. Mitochondrial phospholipid analyses revealed a 65% increase in the membrane arachidonic/linoleic acid (AA/LA) ratio of FADS2- tg versus WT hearts, consistent with previous work in our lab linking D6D hyperactivity with mitochondrial phospholipid remodeling and disease progression in heart failure. Thus, we hypothesized that FADS2 might exacerbate myocardial injury by altering mitochondrial responses to ischemia-reperfusion. To examine this further, mitochondria were isolated from FADS2 -tg or WT mouse hearts for functional studies following 45/90 minutes of global I/R ex vivo . FADS2- tg - I/R mitochondria exhibited lower ADP-stimulated respiration and higher H 2 O 2 emission per O 2 consumed compared to WT-I/R and non-ischemic controls , suggesting impaired cardiac energetics and greater oxidant burden following ischemia. I/R augmented Ca 2+ -induced swelling in both WT and FADS2 -tg mitochondria. This was attenuated in the presence of K + in WT, but not FADS2 -tg, implicating FADS2 -dependent alterations post-ischemic in mitochondrial K + handling. Interestingly, ischemia led to a 38% depletion of mitochondrial membrane AA in FADS2 -tg, but not WT hearts, suggesting an interaction of FADS2 and mitochondrial membrane AA liberation following ischemia. Ongoing studies in our laboratory are investigating the potentially novel links between FADS2 expression with mitochondrial phospholipases, AA signaling, and mitoK ATP channel activity in the pathogenesis of myocardial I/R injury.
Abstract 14197: The Impact of Comorbid Atrial Fibrillation on the Incidence and Outcome of Fracture in Patients With Osteoporosis: A Propensity Score Matched Analysis
Authors: Pil-sung Yang, Dong Geum Shin, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Circulation (2016)

Introduction: Both atrial fibrillation (AF) and osteoporosis are common in elderly. AF is associated with dizziness, weakness, and decreased cerebral perfusion, and these in turn may increase the l...
Molecular classification of Japanese gastric adenocarcinoma.
Authors: Masanori Terashima, Rie Makuuchi, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Makoto Hikage, Keiichi Hatakeyama, Keiichi Oshima, Shunpei Ohnami, Kennichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
Journal: Journal of Clinical Oncology (2016)

e15565 Background: Gastric cancer is well known as having heterogeneous features. Recently, TGCA project had successfully established a molecular classification of gastric adenocarcinoma. In addition, another group (Asian Cancer Research Group; ACRG) had proposed a new classification based on the gene expression profile that reflects tumor progression and prognosis. We started a comprehensive molecular profiling study that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from 2014 (High-tech Omics-based Patient Evaluation; HOPE). We already had evaluated more than 2,000 samples from various type of cancer. We validated the ACRG classification using Japanese cohort registered to HOPE project. Methods: A total of 104 patients were included in this study. Fresh surgically resected tumor/normal samples and peripheral blood were obtained and whole-exome sequencing (Ion Proton System, Termo Fisher Scientific) and gene expression profiling (DNA microarray, Agilent Technologies) were performed. Patients were divided into subgroups based on the gene expression profile according to AGRG classification, and clnicopathological features were compared among the group. Results: Patients were classified into MSI in 14, MSS/EMT in 15, MSS/TP53+ in 38 and MSS/TP53- in 37, respectively. There was no significant difference of sex among the group. Age was significantly younger in MSS/EMT and MSS/TP53-. In MSI, tumor tended to be located at antrum, and differentiated type tumor was predominant. In MSS/EMT, advanced T stage (T4) and undifferentiated type of tumor was predominant. In MSS/TP53+, relatively less advanced stage and localized macroscopic type tumor was predominant. In MSS/TP53-, relatively advanced stage and invasive macroscopic type tumor was predominant. Cause-specific survival was the worst in MSS/EMT and no patient died in MSI. Conclusions: Molecular classification of gene expression profiling based on ACRG was well validated in Japanese gastric cancer cohort. Distribution and tumor characteristics were almost identical to ACRG cohort. Gene-expression profiling will be comprehensively used for tumor classification and further clinical trials of molecular targeting agents.