tbuckley/cabot-search huggingface dataset:
Determinants of spending for metastatic breast, lung, and colorectal cancer in SEER-Medicare.
Authors: Michael J. Hassett, Matthew P. Banegas, Hajime Uno, Shicheng Weng, Angel M. Cronin, Maureen Cecelia O'Keeffe-Rosetti, Nikki Carroll, Mark C Hornbrook, Debra P. Ritzwoller
Journal: Journal of Clinical Oncology (2017)

6621 Background: A substantial proportion of cancer spending is directed towards patients with metastatic disease. Past efforts to characterize spending for metastatic cancer have been limited, because they have not included patients with recurrent disease or analyzed spending across the entire episode of care. Spending for stage IV and recurrent metastatic cancer patients may differ. Methods: Using SEER-Medicare data from 2008-13, we identified breast (BC), colorectal (CRC), and lung (LC) cancer patients who were continuously enrolled in parts A, B and D, and had either stage IV or recurrent disease (i.e., return of cancer after resection of stage I-III disease). Mean total Medicare spending/patient per month and per year (2012$US) were estimated from 12 months prior to 12 months after diagnosis, and described for relevant patient sub-groups. Results: In a cohort of 27,847 patients, total spending for stage IV vs. recurrent cancer was 61-73% lower in the year before diagnosis ($11,339 vs. $28,796 for BC; $13,359 and $49,804 for CRC; $15,118 and $49,555 for LC), and 28-88% higher in the year after diagnosis ($68,787 and $42,091 for BC; $111,304 and $58,657 for CRC; $92,181 and $72,354 for LC). When considering the 2 year-period spanning the diagnosis, spending was similar (≤14%) between groups. The primary drivers of spending differences between patients with stage IV and recurrent disease were cancer type and time from diagnosis (Table). Younger age, higher comorbidity, and SEER region were also drivers of higher spending, especially after diagnosis. Conclusions: Spending patterns differ for patients with stage IV vs. recurrent cancer, suggesting different patterns of care that warrant further investigation. Spending differences after diagnosis were driven largely by part B spending, which was due in part to differential chemotherapy use. [Table: see text]
Patient-reported outcomes (PRO) in cancer trials submitted to the FDA from 2012-2015.
Authors: Bindu Kanapuru, Harpreet Singh, Janice Kim, Paul Gustav Kluetz
Journal: Journal of Clinical Oncology (2017)

e14024 Background: PRO measures are commonly assessed in cancer trials. We reviewed the PRO strategy, tools and trial designs for new drug applications (NDA) and biologics license applications (BLA) submitted to FDA over a 4 year period. Methods: A review of protocols and clinical study reports for original NDA and BLA applications submitted to the Office of Hematology and Oncology Products between 2012 and 2015 to support initial approval for adult malignant hematology and oncology conditions was done. We reviewed applications for inclusion of PRO data, trial design, type of PRO measure employed and statistical analysis methods. Results: Forty three trials were submitted to support 40 original NDA or BLA approvals targeting adult malignancies between 2012 and 2015. Of these 43 trials, 17/43 (40%) were accelerated approval, 26/43 (60%) were randomized, 17/43 (40%) were single arm and 27/43 (63%) were open label trials. Sponsors documented the incorporation of PRO assessments in 28/43 (65%) trials. For trials that included PRO assessments, 22/28 (79%) were randomized controlled trials, 6/28 (21%) were single arm and 17/28 (61%) were open label studies. The most common PRO instruments used were the EORTC-QLQ-C30 (15/28; 54%), EQ-5D (13/28; 46%) and various FACIT measures (8/28; 29%). Although 20/28 (71%) trials had PRO measures listed as a secondary endpoint, only 1 trial included PRO endpoints in the statistical testing hierarchy. Conclusions: PRO measures are often employed in randomized controlled cancer trials; however accelerated approval is common in oncology and trial designs are increasingly open label and single arm. Patient-focused drug development efforts will need to identify clinical trial objectives and analysis methods for PRO measures to describe symptoms and function that are suitable for these contexts. Descriptive PRO data on the tolerability of an anti-cancer agent may be one objective that is relevant across trial contexts. To support a claim of superiority, PRO endpoints should be adjusted for multiplicity by inclusion in the statistical hierarchy.
Results of randomized, placebo (PL)-controlled phase II study evaluating efficacy and safety of regorafenib (REG) in patients (pts) with metastatic osteosarcoma (metOS), on behalf of the French Sarcoma Group (FSG) and Unicancer.
Authors: Florence Duffaud, Jean-Yves Blay, Olivier Mir, Pascaline Boudou-Rouquette, Sophie Piperno-Neumann, Nicolas Penel, Emmanuelle Bompas, Corinne Delcambre, Elsa Kalbacher, Antoine Italiano, Olivier Collard, Christine Chevreau, Antoine Thyss, Nicolas Isambert, Jessy Delaye, Nicolas De Sousa Carvalho, Camille Schiffler, Corinne Bouvier, Vincent Vidal, Sylvie Chabaud
Journal: Journal of Clinical Oncology (2018)

11504 Background: Oral multikinase inhibitor REG has shown activity in GIST and non-adipocytic soft tissue sarcomas. We designed REGOBONE as a non-comparative phase II, double-blind, PL-controlled trial to study the efficacy and safety of REG for pts with metOS and other types of bone sarcomas. This trial consisted of 4 independent cohorts : metOS, Ewing sarcoma, chondrosarcoma, and chordoma. We report here the metOS cohort results. Methods: metOS pts were randomized (2:1) to receive either REG (160 mg/d, 21/28d) or PL with optional cross-over at the time of confirmed central review of progressive disease (PD). Key-eligibility criteria were age ≥10 years, histologically confirmed diagnosis of OS, confirmed measurable PD not amenable to curative-intent, 1-2 previous chemotherapy (CT) regimen(s) for metastatic disease, and ECOG 0-1. 24 pts were planned in the REG arm based on A’Hern’s single-stage design for phase II trials (1-sided α = 0.05, and 80% power) to detect a 27% benefit in the progression-free rate at 8 weeks (P0 = 40%). Major secondary endpoints were PFS (per modified RECIST1.1), OS and safety. Results: From June 2014 to April 2017, 43 metOS pts were included. Five pts were not eligible for efficacy analysis. Of 38 efficacy-evaluable pts (12 in PL arm and 26 in REG arm) ; 24 were men, median age was 33 (18-74) years, 28 (74%) had 1 previous CT regimen. 17 pts (65.4% ; one-sided CI95% = [47.4%-]) were non-progressive at 8 weeks in the REG arm vs. 0 in the PL arm. Median PFS was 13.7 (CI95% = 8.0-27.3) vs. 4 (CI95% = 3.0-5.7) weeks for REG and PL arms, respectively. PFS rate at 24 weeks was 35% (CI95% = 17-52) in the REG arm vs. 0 in the PL arm. 1-year OS was 53% (CI95% = 31-71) and 33% (CI95% = 10-59) for REG and PL arms, respectively. Ten pts crossed-over to REG after centrally-confirmed PD on PL. The most common ≥Gr3 REG-related AEs during the double blind period were hypertension (24%), hand-foot skin reaction (17%), asthenia (10%) and diarrhea (7%). Conclusions: REG demonstrates very promising activity, with acceptable toxicity, in metOS after failure of conventional chemotherapy, justifying confirmatory trials. Clinical trial information: NCT02389244.
Qualitative study of patient perspectives on B-cell non-Hodgkin lymphoma: Impact of patient education.
Authors: Anne Roc, Alexandra Howson, Wendy Turell, Matthew Alexander Lunning
Journal: Journal of Clinical Oncology (2017)

e18109 Background: This qualitative study explored the impact of an online, patient-focused education activity on B-cell NHL ( http://www.cancercoachlive.com/ ), developed by the Leukemia and Lymphoma Society, University of Nebraska, and PlatformQ Health, to improve patient knowledge on B-cell NHL and offer strategies to enhance quality of life through better disease and side effect management. Methods: 12 qualitative interviews were conducted using a semi-structured interview guide. Questions focused on knowledge of B-cell NHL epidemiology, prognosis, and typical presentation; diagnostic and imaging tests; efficacy and side effects of treatments used to treat B-cell NHLs; and actions to improve quality of life and overall health. Interviews were recorded and transcribed verbatim, and analyzed using constant comparative method with software support (NVivo 11, QSR International). Results: Participants, aged 43-78 (mean 60 years, 8 female), were diagnosed with a B-cell NHL 2-24 years prior to interview. Participants demonstrated understanding of B-cell NHL, with good recall on typical presentation of B-cell lymphoma, the importance of blood tests and laboratory/diagnostic procedures and what to expect during these tests. Six participants recalled traumatic experiences with bone marrow biopsy and suggest additional education for newly diagnosed patients. Participants were knowledgeable about treatment options covered by the program (i.e. active surveillance, chemotherapy, radiation therapy, stem cell transplant), and were interested in more information on treatment options across the B-cell disease trajectory. Not all participants could recall information on targeted therapies from the program, and there was low awareness about clinical trials as a treatment option, indicating need for further education. Conclusions: Overall, participants had a positive impression of the education activity. They judged the content to be comprehensive, accurate, and realistic. Participant descriptions suggest that education continues to play a role in allaying fears and anxieties even among patients who have learned to live with B-cell NHL and who have been managing their disease for several years.
Health plan selection and out-of-pocket costs for cancer patients in the health insurance exchange.
Authors: Callie Lynne Gable, Donald H. Taylor, Yousuf Zafar
Journal: Journal of Clinical Oncology (2016)

6504 Background: Little is known about variation in out-of-pocket costs for cancer patients in exchange-based health insurance plans. Despite annual maximums, it is unclear to what extent the Affordable Care Act limits out-of-pocket costs, and what role indicators like metal tier and annual maximums should play in consumer plan selection. Methods: This was a
Treatment response and prognosis according to pre and post treatment Ebstein-Barr virus DNA level in nasopharyngeal carcinoma patients.
Authors: Aysel Ahmedova, Kubra Ozkaya, Makbule Tambas, Ugur Gezer, Emre Ozgur, Dilek Sahin, Yasemin Sanli, Musa Altun
Journal: Journal of Clinical Oncology (2017)

e17544 Background: To evaluate pre and post-treatment Epstein-Barr virus (EBV) DNA copy numbers, to investigate changes with treatment and the possibility of using it as a follow-up marker in nasopharyngeal carcinoma (NPC) patients. Methods: Blood samples were obtained before (0-3 weeks) and after treatment (mean 6 weeks) and number of EBV DNA copies were determined by PCR . Treatment was administered as concomittant chemoradiotherapy ± induction chemotherapy. MRI and PET-CT were performed prior (0-4 weeks) and after (6-16 weeks) treatment. Mann Whitney test was used for 2 group comparisons of parameters with no normal distribution and comparison of quantitative data. Fisher-Freeman-Halton and Wilcoxon Signed Ranks tests were used for comparison of qualitative data and intra-group comparison of parameters with non-normal distribution. Kaplan Meier Survival analysis was used to assess survival. Results: The study included 50 NPC patients treated between 2011 and 2015. Median follow-up is 25.3 (27.5 ± 14) months. 12 patients had residual-recurrent or metastatic (3 patients initially had distant metastasis) disease. Mean survival is 49.77 ± 2.4 months. Median posttreatment EBV DNA level is lower than pretreatment EBV DNA level (p = 0.001). Pretreatment EBV DNA copy numbers are higher in patients with residual-recurrent or metastatic disease (RRM) than those without RRM (p=0.05). Mortal patients had higher pre (p = 0.015) and post (p = 0.043) treatment EBV DNA levels than those who survived. Overall survival (OS) is higher in patients with undetectable (n:41) than those with detectable (n:9) EBV DNA levels after treatment (p = 0.02). Conclusions: The OS is lower in patients with higher pretreatment and detectable posttreatment EBV DNA levels. This study implies that pre and post treatment serum EBV DNA levels can be used as prognostic indicators and also be beneficial as a follow up marker in NPC patients. [Table: see text]
Long-term efficacy and outcomes with sequential crizotinib followed by alectinib in <i>ALK</i>+ NSCLC.
Authors: Jessica Jiyeong Lin, Beow Y. Yeap, Lorin A Ferris, Satoshi Yoda, Ibiayi Dagogo-Jack, Jochen K Lennerz, Justin F. Gainor, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2018)

9093 Background: Alectinib was recently approved for first-line treatment of advanced ALK+ NSCLC based on the ALEX trial, which demonstrated improved PFS with first-line alectinib compared to crizotinib. However, crossover was not allowed in ALEX. As standard therapy for ALK+ patients relapsing on crizotinib is treatment with a second-generation ALK inhibitor, such as alectinib, a more appropriate control arm would have been sequential crizotinib and alectinib, rather than crizotinib alone. We therefore evaluated outcomes of patients sequentially treated with crizotinib and alectinib. Methods: We identified 94 ALK+ NSCLC patients treated with crizotinib followed by alectinib. Medical records were reviewed to determine clinical outcomes and post-alectinib resistance mechanisms. Results: The median PFS on crizotinib and alectinib were 8.1 months (95% CI, 6.4-10.6) and 13.1 months (95% CI, 8.2-19.4), respectively. The median interval from crizotinib discontinuation to initiation of alectinib was 8 days (range, 1-304). Five patients (5.3%) switched to alectinib due to toxicity, 1 (1.1%) due to patient preference, and 88 (93.6%) due to progression (pattern: CNS only, n = 39; extracranial only, n = 37; both CNS/extracranial, n = 12). The median combined PFS for sequential crizotinib and alectinib was 22.9 months (95% CI, 17.1-30.5). Of note, among 68 patients who received crizotinib as first-line and alectinib as second-line therapy, the median combined PFS was shorter at 17.1 months (95% CI, 13.3-23.6). The 5-year OS for the overall cohort from the diagnosis of metastatic disease or from initiation of crizotinib was 66% (95% CI, 51-77%) and 59% (95% CI, 44-72%), respectively. Twenty-nine patients underwent a tumor biopsy following progression on alectinib. Of these, 20 (69%) had an ALK resistance mutation, including: 10 (50%) G1202R, 6 (12%) I1171N, 1 (5%) I1171S, 1 (5%) I1171T, and 2 (10%) V1180L. Conclusions: These findings serve as a historical comparator for first-line alectinib trials including ALEX. While sequential therapy with crizotinib and alectinib can provide significant benefit, this analysis suggests patients may derive greater benefit from first-line alectinib, supporting upfront use of alectinib.
Microwave weapon caused syndrome in diplomats in Cuba, US medical team believes
Authors: Owen Dyer
Journal: BMJ (2018)

A directional microwave weapon was the most likely cause of debilitating neurological symptoms reported by US diplomats in Cuba who heard strange, unexplained sounds at the onset of their symptoms, says the lead author of a medical team that examined the diplomats and reported preliminary findings in JAMA in March.1 That article noted evidence of brain injury but did not offer an explanation of the cause.

Microwave weapons were a recurring theme at a House Foreign Affairs Committee hearing on Cuba policy on 6 September, although State Department officials, while still characterising the events of November 2016 as an “attack,” were unwilling to support any particular theory of how it was carried …
Low-coverage, genome-wide sequencing of cell-free DNA developed for noninvasive prenatal testing (NIPT) to enable genomic characterization that can be used to monitor immunotherapy response in cancer patients.
Authors: Taylor J. Jensen, Aaron Goodman, Shumei Kato, Christopher K Ellison, Gregory A. Daniels, Lisa Tran, Erin McCarthy, Prachi Nakashe, Amin Mazloom, Graham McLennan, Daniel S. Grosu, Mathias Ehrich, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

e24050 Background: DNA harboring tumor-specific mutations has been detected in the blood of cancer patients and may be a representative surrogate of the primary tumor and metastases. While most liquid biopsies are performed using deep targeted sequencing ( > 8000x) of a subset of genes, we hypothesized that we could utilize low-coverage sequencing of cell-free DNA (cfDNA) to detect copy number alterations (CNAs) genome-wide. This method was used to evaluate the frequency, distribution, and persistence of CNAs in the cfDNA of cancer patients and determine whether these aberrations could be used as a biomarker of treatment response. Methods: Data are presented from the first 433 plasma aliquots obtained from 141 patients with diverse cancers. The cfDNA from each patient was assayed with low-coverage (~0.3X) genome-wide sequencing and CNA events were identified using analytical methods previously developed for NIPT. To quantify the level of CNAs present in the cfDNA of cancer patients, we developed a genomic instability number (GIN) defined as the sum of deviations of CNAs in a sample relative to an euploid genome. A threshold for the positivity of a GIN was determined through the evaluation of 6014 cfDNA samples submitted for NIPT. Results: An elevated GIN was detected in 68/141 patients (48.2%). CNAs were detected covering > 95% of the evaluable genome, highlighting the breadth of information obtained using genome-wide data. Finally, two clinical questions in this cohort were evaluated. In patients where tissue biopsy was not medically recommended, CNAs were characterized in 31/80 patients with a clear relationship to tumor site. In addition, we utilized the GIN to distinguish responses of cancer patients to immunotherapy (checkpoint blockade). By ~week 6, serial testing differentiated patients with a clinical response from those with progression, hyperprogression, and pseudoprogression. Conclusions: These data demonstrate the technical feasibility of using low-coverage, genome-wide sequencing of cfDNA to provide genetic information about the tumor and to monitor response to immune checkpoint inhibitors.
A phase 1, first-in-human, open label, dose escalation study of MGD007, a humanized gpA33 x CD3 DART molecule, in patients with relapsed/refractory metastatic colorectal carcinoma.
Authors: John D. Powderly, Herbert Hurwitz, David P. Ryan, Daniel A. Laheru, Naimish B. Pandya, Joanna Lohr, Paul A. Moore, Ezio Bonvini, Jon M. Wigginton, Todd S. Crocenzi
Journal: Journal of Clinical Oncology (2016)

TPS3628 Background: Colorectal (CRC) cancer is the fourth most commonly diagnosed cancer in the U.S. and the second most common cause of cancer related deaths. Recent advances in immunotherapy for multiple malignancies benefit only a specific minority of patients with colorectal cancer but serve as proof of principle. The Dual-Affinity Re-Targeting, or DART, technology, is a proprietary antibody-based platform that has been designed to engage multiple targets with a single molecule. MGD007 is a novel gpA33 x CD3 DART protein that targets gpA33-positive cells for recognition and elimination by co-engagement of CD3-expressing T lymphocytes. Glycoprotein A33 (gpA33) is a 43 kDa membrane-bound glycoprotein normally restricted to the surface of normal human colon and small bowel epithelial cells. In addition, the gpA33 antigen is homogeneously expressed at high levels in > 95% of primary and metastatic human CRC. MGD007 mediates redirected T cell killing of gpA33-expressing CRC cell lines in vitro and blocks transplantable CRC cell line xenografts in preclinical tumor models. These observations suggest that gpA33 that could be an attractive target for the immunotherapy of CRC. This study represents the first clinical evaluation of DARTmolecules in patients with solid tumors. Methods: The Phase I dose-escalation two-arm study of MGD007 will enroll patients with metastatic relapsed/refractory CRC. The study will employ a 3+3+3 design to explore the safety, PK, immuno-regulatory activity and preliminary anti-tumor activity of MGD007. Patients will receive either weekly infusions of MGD007 (Arm A) or every three-week infusions (Arm B) in 6-week cycling until confirmed disease progression or intolerable toxicity. Two dose expansion cohorts will be initiated once dose and schedule are established from dose escalation. Response will be assessed every 6 weeks per RECIST v1.1 and immune RECIST to account for response patterns observed with immunotherapies. The study is ongoing in the U.S. Clinical trial information: NCT02248805.
TCT-180 Incidence and Outcomes of Cardiogenic Shock Complicating Inferior versus Anterior ST-elevation Myocardial Infarction
Authors: Tanush Gupta, Michael Weinreich, Dhaval Kolte, Sahil Khera, Pedro Villablanca, Anna Bortnick, Jose Wiley, None mark menegus, Deepak Bhatt, Giora Weisz
Journal: Journal of the American College of Cardiology (2018)
Outcomes of elderly treated with pembrolizumab for metastatic melanoma comparing with younger patients.
Authors: Caroline Dutriaux, Philippe Saiag, Nicolas Meyer, Amir Khammari, Lynda Benmahammed, Abir Tadmouri, Catherine Hunault, Marie Thérèse Leccia, Laurent Mortier
Journal: Journal of Clinical Oncology (2018)

e21508 Background: Pembrolizumab (PBZ), a monoclonal anti-PD-1, is approved in France since Oct 2015, as a first-line treatment of patients with advanced melanoma. Although this treatment was shown to significantly improve survival, data regarding effectiveness and tolerability across age groups are limited, particularly in the elderly being subject to age-related immune dysfunction. Methods: Horizon is a real-life setting analysis of patients treated with PBZ from June 2014 to Sept 2015 within the French national early access program and followed up to 5 yrs. We present the results of PBZ in two cohorts: under 45 yrs (n = 82) and over 80 yrs old (n = 78). Results: A total of 663 patients were included with a median follow-up of 12.95 mo. Median age was 38.5 yrs in the younger and 84.0 yrs in the elderly. Prior to PBZ, 43.6% of elderly were treatment-naïve (vs. 7.3% of the younger, p < 0.001). At PBZ initiation, 15.3% of elderly were presenting with > 3 metastatic sites (vs. 39.9%, p = 0.004). Other baseline characteristics were similar between groups. Mean number of PBZ infusions received was comparable between groups (13.7 vs. 10.8 infusions, p = 0.163). The median PFS was 2.59 mo (95%CI [2.2-3.21]) in the younger and 5.02 mo (2.75-7.54) in the elderly. The median OS was 11.41 mo (95%CI: [6.4-19.7]) in the younger and 15.44 mo (95%CI: [8.6 -19.2]) in the elderly. The 2-year OS rates were 30.5% and 35.2% in the younger and elderly, respectively. No significant differences were observed in ORR or DCR. Elderly patients treated with PBZ had a better PFS and OS than younger patients; the significance level was not reached in univariate analyses (p = 0.335 and 0.9121, respectively), nor after adjusting on prognosis covariates such as baseline LDH and number of metastatic sites (p = 0.112 and 0.360, respectively). A total of 59 adverse reactions were reported of which 21 (35.6%) were considered as serious: 9 (29%) occurred in younger patients, and 12 (42.9%) in elderly (p = 0.0657). No difference in toxicity profile was observed between groups. Conclusions: Age might be associated with better clinical outcomes after PBZ in the real-life setting. Further studies are required to confirm our results and describe the underlying mechanisms involved.
TIMIフレーム・カウント方法の使用際してtako-tsuboのような左室機能不全患者の障害性の多血管性冠状血流の記録
Authors: Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Umemura T, Nakamura S, Yoshida M
Journal: Circulation (2002)