tbuckley/cabot-search huggingface dataset:
PANOVA-3: A phase III study of tumor treating fields with nab-paclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma (LAPC).
Authors: Vincent J. Picozzi, Teresa Macarulla, Philip Agop Philip, Carlos Roberto Becerra, Tomislav Dragovich
Journal: Journal of Clinical Oncology (2020)

TPS792 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma. TTFields at specific frequency (150-200 kHz) are delivered via transducer arrays placed on the skin in proximity to the tumor site. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase 2 PANOVA study, the first trial testing TTFields in pancreatic cancer patients, demonstrated the safety and preliminary efficacy of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and LAPC. The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy and safety of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m2 once weekly). TTFields (150 kHz) will be delivered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Clinical trial information: NCT03377491.
Emergency department use at the end of life in elderly patients with gastrointestinal malignancies and mental health comorbidities.
Authors: Mehr Kashyap, Jeremy Phillip Harris, Daniel Tandel Chang, Erqi L. Pollom
Journal: Journal of Clinical Oncology (2020)

811 Background: Aggressive care at the end-of-life can contradict patients’ wishes, negatively impact patient quality of life, and contribute to overall health care expenditures. Patients with mental disorders (MD) often experience disparities in medical care and have poorer clinical outcomes. We investigated the impact of mental disorders on emergency department (ED) use at the end of life among elderly patients with gastrointestinal (GI) malignancies. Methods: We conducted a retrospective cohort study using the SEER-Medicare database. We identified patients aged 66 years and older with GI malignancies (colorectal, pancreatic, gastric, hepatic, biliary, esophageal, small bowel, and anal cancer) diagnosed between 2004 and 2013 who had recorded death. We assessed the association between MD (depression, bipolar disorder, psychotic disorder, anxiety, dementia, and substance abuse) and ED use within 30 days of death using logistic regression models. Results: Of the 160,367 decedents included, 54,461 (34.1%) had at least one MD diagnosis between one year prior to cancer diagnosis and death. Those with MD were more likely to use the ED more than once in the last 30 days of life (14.7% vs. 12.4% p &lt; 0.01). ED use was highest among decedents with anxiety disorder (15.8%) and substance abuse (16.3%). Among decedents with mental disorders, risk factors associated with ED use at end of life include being male (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.10 – 1.22), younger (aOR 1.14, 95% CI 1.06 - 1.23), and black (aOR 1.33, 95% CI 1.23 – 1.45), living in a lower income zip code (1.21, 95% CI 1.13 – 1.30), and having a higher Charlson comorbidity score (aOR 1.71, 95% CI 1.56 – 1.87). ED use was also associated with pancreatic (aOR 1.16, 95% CI 1.08 - 1.25), hepatic (aOR 1.21, 95% CI 1.11 - 1.33), biliary (aOR 1.16, 95% CI 1.03 - 1.30) and esophageal (aOR 1.16, 95% CI 1.04 - 1.29) cancer compared to colorectal cancer. Conclusions: MD is associated with increased ED use at the end of life among elderly patients with GI cancer. Palliative and supportive care including mental health services early in the disease course may improve quality of end-of-life care in this vulnerable population.
Economics of Palliative Care for Cancer: Interpreting Current Evidence, Mapping Future Priorities for Research
Authors: Peter May, Charles Normand, R. Sean Morrison
Journal: Journal of Clinical Oncology (2020)

The National Cancer Institute estimates that $154 billion will be spent on care for people with cancer in 2019, distributed across the year after diagnosis (31%), the final year of life (31%), and continuing care between those two (38%). Projections of future costs estimate persistent growth in care expenditures. Early research studies on the economics of palliative care have reported a general pattern of cost savings during inpatient hospital admissions and the end-of-life phase. Recent research has demonstrated more complex dynamics, but expanding palliative care capacity to meet clinical guidelines and population health needs seems to save costs. Quantifying these cost savings requires additional research, because there is significant variance in estimates of the effects of treatment on costs, depending on the timing of intervention, the primary diagnosis, and the overall illness burden. Because ASCO guidelines state that palliative care should be provided concurrently with other treatment from the point of diagnosis onward for all metastatic cancer, new and ambitious research is required to evaluate the cost effects of palliative care across the entire disease trajectory. We propose a series of ways to reach the guideline goals.
Efficacy of a Specialized Group Intervention for Compulsive Exercise in Inpatients with Anorexia Nervosa: A Randomized Controlled Trial
Authors: Nina Dittmer, Ulrich Voderholzer, Claudia Mönch, Ulrich Cuntz, Corinna Jacobi, Sandra Schlegl
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Treatment of compulsive exercise is recognized as a key unmet challenge in the treatment of anorexia nervosa (AN). To address this challenge, we developed the manualized group intervention “healthy exercise behavior” (HEB). This study evaluates the efficacy of HEB for the reduction of compulsive exercise as add-on to routine inpatient treatment (treatment as usual [TAU]) in a randomized controlled trial. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Two hundred and seven adolescent and adult female inpatients with (atypical) AN were randomly allocated to TAU or to additional participation in HEB (TAU + HEB). HEB integrates elements of exercise-based therapy into a cognitive-behavioral approach. Assessments took place at admission, pre-intervention, post-intervention, discharge, and 6 months follow-up. Primary outcome was the severity of compulsive exercise assessed by the Commitment to Exercise Scale between pre- and post-intervention; secondary outcomes were additional aspects of compulsive exercise, assessed by the Compulsive Exercise Test, weight gain, eating disorder and general psychopathology, and emotion regulation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In intention-to-treat analysis for the primary outcome, the TAU + HEB group showed significantly stronger reductions in the severity of compulsive exercise compared to the TAU group (&lt;i&gt;z&lt;/i&gt; = –2.81; &lt;i&gt;p&lt;/i&gt; = 0.005; effect size [ES] = –0.3). We also found significantly stronger reductions from admission to discharge (&lt;i&gt;z&lt;/i&gt;= 2.62; &lt;i&gt;p&lt;/i&gt; = 0.009; ES = –0.43), and from admission to follow-up (&lt;i&gt;z&lt;/i&gt; = 2.1; &lt;i&gt;p&lt;/i&gt; = 0.035; ES = –0.39). Regarding secondary outcomes, we found significant group differences between pre- and post-intervention in additional aspects of compulsive exercise (&lt;i&gt;z&lt;/i&gt; = –2.55; &lt;i&gt;p&lt;/i&gt; = 0.011; ES = –0.27). We did not find significant differences regarding weight gain, eating disorder and general psychopathology, and emotion regulation. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our intervention proved efficacious in reducing compulsive exercise in inpatients with (atypical) AN.
Real-world eligibility of advanced pancreatic (APC) patients for maintenance olaparib.
Authors: Atul Batra, Winson Y. Cheung, Patricia A. Tang
Journal: Journal of Clinical Oncology (2020)

653 Background: The POLO trial demonstrated an improvement in progression free survival (PFS, 7.4 months vs. 3.8 months; hazard ratio, HR, 0.53; 95% confidence interval, 95% CI, 0.35 to 0.82; P=0.004) with olaparib compared to placebo, as maintenance therapy in APC patients with germline BRCA 1/2 mutations with disease control after 16 weeks (DC16) of platinum-based first-line therapy. This study aims to identify the proportion of real-world APC patients eligible for olaparib, and to determine the PFS and overall survival (OS) after DC16. Methods: APC patients treated with first-line FFX in Alberta were identified (2011-2018). We conducted an analysis of baseline characteristics to identify factors associated with DC16. Results: We identified 165 APC patients treated with FFX with unknown BRCA 1/2 status, of which 56% were males and median age at diagnosis was 59 years (interquartile range 38-75 years). Of these, 72 (44%) had DC16. Normal LDH and ALP, and albumin more than 35 g/L were associated with a higher likelihood of having DC16 (table). The PFS of patients with DC16 was significantly higher than those with DC&lt;16 weeks (9.3 vs 2.5 months, HR=0.22, 95% CI 0.15-0.32, P&lt;0.001). In patients who had DC16, median PFS and OS from that point were 5.6 months and 17.9 months, respectively. Conclusions: Less than half of real-world patients treated with first-line FFX would be eligible for olaparib by the criteria of DC16 with FFX. Median PFS after DC16 is 5.6 months with FFX in patients with unknown BRCA 1/2 status. This provides a baseline for future trials evaluating maintenance strategies. Patients with APC and higher disease burden (higher ALP and LDH) and low albumin are less likely to have DC16. [Table: see text]
Case series examining somatic test results for patients with hereditary cancer syndromes associated with gastrointestinal cancer risk.
Authors: Kristen Pauley, Cathryn Koptiuch, Samantha Greenberg, Gammon Amanda, Christopher Nevala-Plagemann, Jennie Vagher, Whitney Espinel, Glynn Weldon Gilcrease, Wendy Kohlmann, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2020)

680 Background: Somatic tumor testing may identify germline pathogenic variants (PV) associated with cancer predisposition syndromes. Labs differ whether they offer somatic only or paired germline analysis. Methods used by somatic testing labs, even those that include germline analysis, differ from designated germline labs that have optimized the identification of germline PV. Methods: Chart reviews were performed for patients who had testing through both somatic and designated germline laboratories. Cases with discrepant results in which germline PV were not detected by the somatic laboratory are summarized. Results: Nine cases with discrepant results. Five had paired germline testing and 4 somatic testing only. All 9 patients met the criteria to undergo designated germline testing, either for Lynch syndrome (3) or BRCA1/2 testing (6), based on personal and/or family history. Designated germline testing identified 4 MLH1, 1 BRCA1, 2 ATM, 1 MUTYH and 1 RAD50 PV not reported by the somatic labs’ tumor or germline analysis; 2 MLH1 PV were called variants of uncertain significance by somatic testing but classified as PV by ClinVar and designated germline labs. Three PV identified by designated germline labs are targets for PARP inhibitors and resulted in different treatment options. Three of the MLH1 PV were identified in patients meeting Lynch Syndrome test criteria while 1 was identified in a patient meeting BRCA1/2 criteria. Among the 5 other patients meeting BRCA1/2 test criteria, 3 had PV in breast cancer genes (2 ATM, 1 BRCA1) and 2 had PV in other cancer genes ( MUTYH and RAD50) not reported by the somatic labs, highlighting the importance of panel testing. Conclusions: Methods used by somatic labs, regardless of inclusion of germline analysis, are not equivalent to those of designated germline labs. Overlooked germline PV may miss identification of hereditary syndromes and targeted therapy opportunities (e.g. Anti-PD1 immunotherapy, PARP inhibitors). Patients meeting criteria for genetic evaluation should be referred for designated germline testing regardless of somatic testing outcomes.
Ischaemic cardiomyopathy. Pathophysiological insights, diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology
Authors: Irina Cabac‐Pogorevici, Balazs Muk, Yasmin Rustamova, Andreas Kalogeropoulos, Stylianos Tzeis, Panos Vardas
Journal: European Journal of Heart Failure (2020)
Impact of Higher Insulin Prices on Out-of-Pocket Costs in Medicare Part D
Authors: Chien-Wen Tseng, Camlyn Masuda, Randi Chen, Daniel M. Hartung
Journal: Diabetes Care (2020)

One in three Medicare beneficiaries have diabetes, and 3.1 million require insulin (1). As insulin prices rise (2), one in four people on insulin report reducing use due to cost (3). Insulin price and affordability concerns the 7 in 10 Medicare beneficiaries with Part D drug coverage, which requires significant deductibles and copayments and places no maximum on out-of-pocket costs (4,5).

In particular, Medicare Part D has a coverage gap (doughnut hole) whereby beneficiaries pay a percentage of a drug’s price until reaching catastrophic coverage (4). To lower financial burden, the Affordable Care Act incrementally reduced patients’ cost-sharing during the gap from 100% to 25% of drug price (2010 to 2019) (4). Concurrently, manufacturers had to provide greater price discounts during the gap, reaching a 70% discount by 2019 (4). Although patients now pay a lower percentage of a drug’s price, these savings can be counterbalanced by simultaneous price increases. Patients’ cost-sharing during the gap also uses a drug’s full list price and excludes manufacturer rebates that insulate plans from rising prices (2). We examined how patients’ out-of-pocket costs for insulin would have dropped from 2014 to 2019 due to Part D policy changes and whether higher …
Nivolumab (NIVO) and drug eluting bead transarterial chemoembolization (deb-TACE): Preliminary results from a phase I study of patients (pts) with liver limited hepatocellular carcinoma (HCC).
Authors: James J. Harding, Hooman Yarmohammadi, Kim Anna Reiss, Joanne F. Chou, Marinela Capanu, Richard K. G. Do, Danny Khalil, Imane H. El Dika, Joseph Daniel Giardina, Taha Merghoub, William R. Jarnagin, Gregory Nadolski, Joseph Patrick Erinjeri, Michael C. Soulen, Benjamin R. Tan, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2020)

525 Background: Regional therapies in HCC impact the immune microenvironment and may augment the effects of immune checkpoint inhibitors. Methods: This is a multicenter phase 1 study of NIVO and deb-TACE in unresectable HCC pts (BCLC Stage B) and Child Pugh A cirrhosis (NCT03143270). The primary objective is to assess safety. Secondary objectives include response rate by RECIST v1.1, progression-free and overall survival by Kaplan-Meier methodology, and blood/tumor immune correlates. A 3 + 3 design sequentially evaluates 3 cohorts of differing schedules of NIVO relative to deb-TACE. Deb-TACE (75mg of doxorubicin) is administered on Day 0. NIVO is dosed at 240mg IV every 14 days for 1 year (Cohort 1: NIVO begins day +14 after deb-TACE; Cohort 2, interrupted NIVO dosing begins at Day -28 but is held on the Day 0 then restarted on Day +14; Cohort 3, continuous NIVO dosing begins on Day -28 without interruption). Results: As of July 2019, 9 pts have been treated [median 65 years (range: 54-76), male (89%), viral (44%;1 HBV, 3 HCV), non-viral (56%;2 EtOH, 1 NASH, 2 unknown), prior resection (44%), prior regional therapy (44%), 3 pts in each cohort]. No cases of treatment related liver failure, dose-limiting toxicity, or Grade 5 adverse events (AEs) were observed. Grade ≥3 AEs possibly related to nivolumab, deb-TACE, or both included: transaminase elevation (1 pt: day 1 post TACE resolved in 7 days without treatment; 2 pts: ≥30 days post TACE resolved with steroids between 20-41 days), post-embolization syndrome (1 pt: resolved in 5 days), asymptomatic lipase increase (1 pt: resolved in 14 days), post-procedural groin hematoma (1 pt: resolved in 2 days). All 9 pts were evaluable for efficacy: 2 (22%) confirmed PR and 7 (78%) SD. 4/9 pts remain on study with SD or better—2 pts continue &gt; 18 months post embolization with durable PRs. 12 months OS rate was 71%. Ongoing correlates will be presented at a separate meeting. Conclusions: Nivolumab given at various times relative to deb-TACE appears safe and tolerable. Cohort 3 continues to accrue to provide a better estimate of safety and antitumor activity of the combination. Clinical trial information: NCT03143270.
Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.
Authors: Aiwu Ruth He, Thomas Yau, Chiun Hsu, Yoon-Koo Kang, Tae-You Kim, Armando Santoro, Bruno Sangro, Ignacio Melero, Masatoshi Kudo, Ming-Mo Hou, Ana Matilla, Francesco Tovoli, Jennifer J. Knox, Bassel F. El-Rayes, Mirelis Acosta-Rivera, Jaclyn Neely, Yun Shen, Marina Tschaika, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2020)

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.
Amoxycillin-clavulanate vs azithromycin for respiratory exacerbations of bronchiectasis in children - a multi-centre double blind non-inferiority randomised controlled trial
Authors: V. Goyal, K. Grimwood, C. A. Byrnes, I. B. Masters, J. Marchant, P. Morris, R. Ware, P. Van Asperen, K. O'Grady, P. Torzillo, G. McCallum, A. Champion, H. Buntain, I. Mackay, T. P. Sloots, J. Ungerer, M. Binks, A. B. Chang
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Based on limited available data, amoxycillin‐clavulanate is the current recommended first‐line empirical oral‐antibiotic treatment for non‐severe bronchiectasis exacerbations in children.
The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View
Authors: Joao B. Xavier, Vincent B. Young, Joseph Skufca, Fiona Ginty, Traci Testerman, Alexander T. Pearson, Paul Macklin, Amir Mitchell, Ilya Shmulevich, Lei Xie, J. Gregory Caporaso, Keith A. Crandall, Nicole L. Simone, Filipa Godoy-Vitorino, Timothy J. Griffin, Katrine L. Whiteson, Heather H. Gustafson, Daniel J. Slade, Thomas M. Schmidt, Marina R.S. Walther-Antonio, Tal Korem, Bobbie-Jo M. Webb-Robertson, Mark P. Styczynski, W. Evan Johnson, Christian Jobin, Jason M. Ridlon, Andrew Y. Koh, Michael Yu, Libusha Kelly, Jennifer A. Wargo
Journal: Trends in cancer (2020)

The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology - a systems biology approach.