tbuckley/cabot-search huggingface dataset:
An open-label phase II trial of G-FLIP (low doses of gemcitabine, 5-FU, leucovorin, irinotecan &amp; oxaliplatin), followed by G-FLIP-DM (G-FLIP + low doses of docetaxel &amp; mitomycin C), used concurrently with ascorbic acid (AA), in patients with advanced pancreatic cancer.
Authors: Azriel Hirschfeld, Howard Bruckner
Journal: Journal of Clinical Oncology (2016)

e15745 Background: G-FLIP is a low dose combination chemotherapeutic regimen which utilizes drugs at approximately 1/2 of the standard doses. G-FLIP has synergistic anti-cancer activity according to lab and early clinical studies, and clinical practice in ~200 patients. AA has been reported to have anti-cancer activity, is safe, and can achieve high plasma levels (up to 5,000 μmol/L) when given iv. The combination of G-FLIP+AA may be a relatively well tolerated treatment option for patients with advanced pancreatic cancer. Methods: This study evaluated the response rate, overall survival (OS) and safety of G-FLIP+AA (75 or 100 g) in patients with advanced pancreatic cancer. Key eligibility criteria include metastatic (Stage IV), locally advanced unresectable, or recurrent pancreatic adenocarcinoma; with or without prior chemotherapies; ECOG 0-2; 18 and older of both genders; and adequate hematologic, hepatic, renal and coagulation functions. Results: 22 patients were screened, and 18 treated with G-FLIP+AA. Median age was 66 and range was 40-80. All patients, except one who was 40, were > 60 years old. Disease Control Rate (DCR, % CR, PR or SD) was 73%. OS at 11 months was 75%. Hematologic adverse events (AEs) were mostly mild (Grade 1 or 2), with some Grade 3, and no Grade 4. Grade 3 neutropenia was 15% and no febrile neutropenia, and Grade 3 thrombocytopenia was 5%. Non-hematologic AEs were also mostly Grade 1 or 2, with Grade 3 diarrhea and thromboembolism (both 6%). There was no grade 3 or 4 nausea, vomiting, or neuropathy. Conclusions: G-FLIP+AA has a favorable toxicity profile and should be explored further as an option for advanced pancreatic cancer, particularly in the elderly and patients who are not candidates for standard high dose combination therapy. Clinical trial information: NCT01905150.Adverse Events Severity Level Grade 1 Grade 2 Grade 3 Grade 4 Hematologic Anemia 9 (47%) 10 (53%) Thrombocytopenia 8 (42%) 4 (21%) 1 (5%) Neutropenia 4 (21%) 3 (16%) 3 (16%) Non-Hematologic Fatigue 13 (72%) 5 (28%) Vomiting 4 (22%) 1 (6%) Diarrhea 3 (17%) 1 (6%) Neuropathy 1 (6%) 2 (11%) Thromboembolism 1 (6%) 1 (6%) 1 (6%)
Bone targeted therapy and skeletal related events in the era of modern therapies for castration resistant prostate cancer with bone metastases.
Authors: Li Zhang, Kathryn P. Gray, Grace Shaw, Carolyn Evan, Edoardo Francini, Christopher Sweeney
Journal: Journal of Clinical Oncology (2018)

5049 Background: Bone metastases in castration resistant prostate cancer (CRPC) is associated with serious morbidity and costs. The optimal timing of initiation and duration of bone targeted therapy (BTT) Zoledronic acid and Denosumab is unknown in the current era with four classes of therapy for CRPC prolonging overall survival (OS). We sought to define the practice patterns of BTT use and outcomes (skeletal related events - SRE and OS) in a high-volume center in the modern era of metastatic CRPC management. Methods: A retrospective cohort of patients (pts) who have received Abiraterone and/or Enzalutamide for CRPC from 2007 to 2017 was identified based on a single-institution’s clinical database. The database and electronic medical record review was used for data collection, including pts’ characteristics and pattern of BTT uses. Kaplan Meier method and Cox proportional hazards model assessed association of BTT use with time to first SRE and OS, respectively. Results: 197 pts were identified, and 79(40%) had ≥ 4 bone metastases (BM) and median follow-up was 4.7 (95%CI: 4.2-5.9) years. More pts with ≥ 4 BM received BTT with first line therapy (49% vs 32% - p-int < 0.01). Pts with ≥ 4 BM, receiving BTT with first line therapy for CRPC had a 19% reduced risk of developing SRE - HR 0.81 (95%CI: 0.45-1.45). Pts with < 4 BM did not have a lower HR when starting BTT with first line CRPC therapy. No OS difference was noted in pts who received BTT with first line therapy or not, regardless of the volume of bone metastases. Conclusions: Our cohort suggested that in the modern era, with more effective and greater number of CRPC therapies, pts with ≥ 4 BM still benefit from starting BTT with first line CRPC therapy.
TCT-394 Efficacy and safety of ‘Fisherman's knot’ technique to achieve venous haemostasis after removal of large sheath (&gt;12-Fr).
Authors: Santosh Sinha, Vinay Krishna, Amit Goel, Mukesh Jha, Karandeep Sayal, Ramesh Thakur, Mahmodula Razi, Puneet Aggarwal, Kumar Himanshu
Journal: Journal of the American College of Cardiology (2018)
Abstract P312: Stress Related to Family Member(s) With Legal/Police Problems and BodyMass Index in the Study of Women’s Health Across the Nation (SWAN)
Authors: Miriam E Van Dyke, Tiffany Lemon, Karen A Matthews, Emma Barinas-Mitchell, Tené T Lewis
Journal: Circulation (2018)

Introduction: Millions of Americans encounter the legal system each year, although persons of low socioeconomic status and racial/ethnic minorities are disproportionately impacted. The health implications of having legal or police problems have been well-documented, especially among incarcerated populations. Missing from the literature, however, is an insight into the health of those closest to the individuals facing legal and/or police problems—their family. Hypothesis: Using data from the Study of Women’s Health Across the Nation (SWAN), we examined the hypothesis that stress related to family member(s) with legal/police problems (FLPP) is associated with higher body mass index (BMI, kg/m 2 ) across 12 years and examined whether this association varied by education or race. Methods: Participants were 1,550 white, 935 Black, 281 Japanese, and 250 Chinese middle-aged women. Data from baseline through year 13 were analyzed using generalized estimating equations with a year fixed effect. Models were adjusted for site, year, age, race/ethnicity, education, menopausal status, smoking, alcohol use, physical activity, caloric intake, and depressive symptoms. Results: Of the 3,016 women included at baseline, 16.1% of women reported any FLPP, although lower educated women reported more FLPP (20.4%) than higher educated (12.3%) women, and slightly more FLPP than middle educated women (18.9%). Similarly, Black women reported more FLPP (23.8%) than white (14.3%), Japanese (8.5%), and Chinese (7.6%) women. EducationxFLPP interaction was observed such that among lower, but not middle or higher educated women, FLPP that were reported to be very upsetting were on average associated with higher BMI in age, year, race/ethnicity, menopausal status, and site-adjusted models (beta=0.35, p=0.03), although this association became marginal in fully-adjusted models (beta=0.31, p=0.09). Although race/ethnicityxFLPP interaction was not observed, in race-stratified models, very upsetting FLPP were on average marginally associated with increased levels of BMI among Black women only, in both minimally (beta=0.21, p=0.06) and fully-adjusted (beta=0.21, p=0.08) models. Conclusions: Our findings based on 12 years of data suggest that lower educated women and Black women who report having a family member with legal or police problems and who find this very upsetting on average have higher BMI. SWAN has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The content of this abstract is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH.
Genetic heterogeneity and survival among pancreatic adenocarcinoma (PDAC) patients with positive family history.
Authors: Gloria M. Petersen, Kari G. Chaffee, Robert R. McWilliams, Neil Majithia, Brian Allen, John Kidd, Nanda Singh, Anne-Renee Hartman, Ann L. Oberg
Journal: Journal of Clinical Oncology (2016)

4108 Background: Availability of cancer gene mutation panel-based screening will identify increasing numbers of patients who carry diverse germline mutations. Prevalence of mutations and survival by carrier status among PDAC patients has not been well described. Methods: Using a hereditary cancer panel, we sequenced 25 cancer susceptibility genes in lymphocyte DNA from 303 well-characterized PDAC patients (47% female, mean age (+SD) 64.9+10.3 years, 98% White, 3% Ashkenazi Jewish heritage) in the Mayo Clinic Familial Pancreatic Cancer Registry. Kindreds that contained at least two first degree relatives (FDR) with PDAC met criteria for Familial Pancreatic Cancer (FPC), while the remaining were familial, but not FPC. Results: Overall, 35 of 303 (12%) patients carried a deleterious mutation in one of 10 genes in the 25-gene panel. Of the 186 FPC patients, 24 (13%) were carriers, and 11/117 (9%) patients with family history not meeting FPC criteria were carriers. Prevalence of (n) in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2. Among individuals with deleterious mutations in genes associated with breast cancer, 13/27 (48%) had a FDR with breast cancer vs non-carriers (76/276 (28%); p = .02); among only women with these deleterious mutations, the proportions were 9/12 (75%) and 39/129 (30%), respectively; p = .003). There was no significant difference in median survival overall or by stage among mutation carriers versus non-carriers: Overall sample: 14.2 months (mos) vs 12.7 mos, respectively; p = 0.78; Resectable: 32.4 mos, n = 10 vs 27.3 mos, n = 78; Locally Advanced: 14.5 mos, n = 6 vs 10.6 mos, n = 72; Metastatic: 8.8 mos, n = 15 vs 7.8 mos, n = 98). Conclusions: With 12% prevalence of deleterious mutations, susceptibility gene testing in PDAC patients with a positive family history is warranted regardless of meeting FPC criteria. These findings will inform genetic risk counseling for family members. While survival did not differ, further analysis is warranted. The diversity of genetic susceptibility offers future opportunities for targeted therapies.
Effect of JS001, a monoclonal antibody targeting programed death-1 (PD-1), on responses and disease control in patients with advanced or refractory alveolar soft part sarcoma: Results from a phase 1 trial.
Authors: Sheng Yang, Jianliang Yang, Xiaohong Han, Ying Han, Shiyu Jiang, Jiarui Yao, Zhishang Zhang, Shuxiang Zhang, Peng Liu, Yan Qin, Hui Feng, Sheng Yao, Yan Sun, Yuankai Shi
Journal: Journal of Clinical Oncology (2018)

11572 Background: Alveolar soft part sarcoma (ASPS) is a rare and lethal malignancy mainly affecting youth, with no effective standard systemic treatment. Checkpoint inhibitors has showed efficacy in a variety of tumors, but its role in ASPS remains elusive. Here we report data of JS001, a humanized IgG4 anti-PD-1 antibody developed by Shanghai Junshi Biosciences Co., Ltd., China, in advanced or refractory alveolar ASPS from a phase 1 trial. Methods: After a dramatic tumor shrinkage with a single injection of JS001 in a patient with ASPS, we decided to expand a cohort in this tumor. Following patients(pts) were planned to receive JS001 at 3mg/kg or 10mg/kg, repeated every 2 weeks (up to 6 doses). The diagnosis was confirmed with central histological review. PD-L1 and CD8 IHC were performed when tissue sample available. Results: From October 2016 to June 2017, 12 pts were enrolled and all are efficacy-evaluable. One achieved CR and 2 had PR, with a response rate of 25%. Two additional pts had some degree of tumor shrinkage. Response heterogeneity was common: some lesions enlarged while others reduced in a same patient. In three pts with responses, the time to responses were 5.7, 7.7 and 23.9 weeks, respectively and the durations of response were 48.3, 31.1+ and 36.0+ weeks, respectively. Six pts remained under disease control at 6 months, and 4 at 12 months. The estimated median progression-free survival was 12.4 months. Toxicities were mostly grade 1-2. Grade 1 pneumonia and hepatitis, each in 1, were considered immune-related. No DLT or treatment-related death occurred. Tissue samples were available in 10 pts. In 4 PD-L1 positive cases, there were 2 PR, 1 SD and 1 PD; while in 2 pts with minimal CD8+ T-cell infiltration, there were 1 SD and 1 PD. In-depth biomarker analysis is in progress. Conclusions: In this first prospective cohort of PD-1 antibody in ASPS, JS001 showed satisfactory response rate and prolonged disease control. Responses heterogeneity highlights the importance of biomarker and microenvironment study in ASPS. Our findings may prelude a new option for advanced ASPS. Clinical trial information: NCT02836834.
Squamous-Cell Carcinoma of the Lung
Authors: Luca Conti, Simon Gatt
Journal: New England Journal of Medicine (2018)

A 63-year-old man presented with cough and a history of recent weight loss of 10 kg. Computed tomography revealed a 5.6-cm mass in the right lower lobe and a pack of cigarettes and a lighter in his right breast pocket. A diagnosis of squamous-cell carcinoma was made.
High-Risk Clonal Hematopoiesis as the Origin of AITL and <i>NPM1</i>-Mutated AML
Authors: Enrico Tiacci, Alessandra Venanzi, Stefano Ascani, Andrea Marra, Valeria Cardinali, Giovanni Martino, Veronica Codoni, Gianluca Schiavoni, Maria Paola Martelli, Brunangelo Falini
Journal: New England Journal of Medicine (2018)

Two Cancers in CHIP A patient with clonal hematopoiesis of indeterminate potential (CHIP) received the diagnosis of lymphoma with activation of RHOA. Approximately 1 year later, NPM1-mutated acute ...
Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study
Authors: Guifeng Xu, Buyun Liu, Yangbo Sun, Yang Du, Linda G Snetselaar, Frank B Hu, Wei Bao
Journal: BMJ (2018)

To estimate the prevalence of diagnosed total diabetes, type 1 diabetes, and type 2 diabetes in the US general population and the proportions of each among US adults with a diagnosis of diabetes.Nationwide, population based, cross sectional survey.National Health Interview Survey, 2016 and 2017.Adults aged 20 years or older (n=58 186), as a nationally representative sample of the civilian, non-institutionalized US population.Prevalence of diagnosed diabetes, type 1 diabetes, and type 2 diabetes in the US general population, and the proportions of each subtype in participants with a diagnosis of diabetes.Among the 58 186 included adults, 6317 had received a diagnosis of diabetes. The weighted prevalence of diagnosed diabetes, type 1 diabetes, and type 2 diabetes among US adults was 9.7% (95% confidence interval 9.4% to 10.0%), 0.5% (0.5% to 0.6%), and 8.5% (8.2% to 8.8%), respectively. Type 1 diabetes was more prevalent among adults with lower education level, and type 2 diabetes was more prevalent among older adults, men, and those with lower educational level, lower family income level, and higher body mass index (BMI). Among adults with a diagnosis of diabetes, the weighted percentage of type 1 and type 2 diabetes was 5.6% (4.9% to 6.4%) and 91.2% (90.4% to 92.1%), respectively. The percentage of type 1 diabetes was higher among younger adults (age 20-44 years), non-Hispanic white people, those with higher education level, and those with lower BMI, whereas the percentage of type 2 diabetes was higher among older adults (age ≥65 years), non-Hispanic Asians, those with lower education level, and those with higher BMI.This study provided benchmark estimates on the national prevalence of diagnosed type 1 diabetes (0.5%) and type 2 diabetes (8.5%) among US adults. Among US adults with diagnosed diabetes, type 1 and type 2 diabetes accounted for 5.6% and 91.2%, respectively.
Early response rates and Curie scores at end of induction: An update from a phase II study of an anti-GD2 monoclonal antibody (mAb) with chemotherapy (CT) in newly diagnosed patients (pts) with high-risk (HR) neuroblastoma (NB).
Authors: Wayne Lee Furman, Barry L. Shulkin, Sara Michele Federico, Mary B McCarville, Andrew M. Davidoff, Matthew J. Krasin, Jianrong Wu, Rachel Christine Brennan, Michael William Bishop, Sara E. Helmig, Fariba Navid, Victor M. Santana, Gwendolyn Anthony, Jacquelyn A Hank, Stephen D Gillies, Paul M. Sondel, Wing H. Leung, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2017)

10534 Background: We are conducting a Phase II trial of the anti-GD2 mAb hu14.18K322A given concomitantly with CT in newly diagnosed pts with HR NB. Our primary objective is to compare the response rate (RR; defined as ≥ PR) after two courses of CT with cyclophosphamide (CTX)/topotecan (TPT) and hu14.18K322A with GM-CSF and IL-2 to the RR reported by Park et al. (JCO 29:4351, 2011), using identical CT with GCSF only, in a two-stage group sequential design. Semiquantitative MIBG scoring (Curie; CS) has been shown to be a prognostic indicator of outcome in pts with HR NB (Yanik et al, J Nucl Med, 2013), particularly, those with CS &gt; 2 at end of induction (EoI) CT have inferior outcomes. Here we update the RR and report the CS at EoI CT. Methods: Pts received induction CT (6 cycles) as described by Park et al, with the addition of hu14.18K332A (on d 2-5; 40mg/m 2 /d x 4d), daily sc GM-CSF and sc IL-2 (1 x 10 6 IU/m 2 /dose) qod x 6. 123 I-MIBG scans and scoring (CS) were obtained on all pts at diagnosis, after second course of CT and at EoI. Results: 42 evaluable pts completed the first two courses of CT (24 male, median age 2.9 yrs (range 6 m -15.2 yrs), 36 INSS 4, 19 MYCNamplified); 40/42 evaluable pts had measurable reductions in primary tumor volume after two courses of CT (median 79%, average 69%, range +5 – 100%). Responses (≥ PR) after two courses were seen in 32/42 (76.2%; 95% CI 61.3 – 87.9%); No mAb dose-reductions were made but 20/43 (47%) pts had infusion times extended. The development of human anti-human antibody reactivity (HAHA) to hu14.18K322A in the first 22 pts is minimal. Of the 36 INSS 4 pts, 1 withdrew prior to EoI and 2 are too early. The median CS at diagnosis for the 33 stage 4 pts who have completed induction CT was 18 (range 1 – 28). At EoI the median CS was 0 (range 0 -23); 29/33 INSS 4 pts had EoI CS ≤ 2. Conclusions: The addition of hu14.18K322A to two courses of CTX/TPT significantly improves the RR compared to two courses of CTX/TPT alone (32/42 vs 12/30 as reported by Park et al,; P = 0.000004). The improved median CS of the stage 4 patients from 18 at diagnosis to 0 at EoI suggest the improvement in early RR may translate into improved EFS as well. Clinical trial information: NCT01857934.
Hypothyroidism to predict for long term survival in patients with fosbretabulin treated anaplastic thyroid carcinoma.
Authors: Deborah Blythe Doroshow, Hari Anant Deshpande, Scot C. Remick, Aarti K. Bhatia
Journal: Journal of Clinical Oncology (2018)

e18108 Background: Anaplastic thyroid cancer (ATC) is considered a systemic disease at the time of diagnosis and has a poor prognosis. A long-term survivor (Case #1) treated with combretastatin (fosbretabulin) a vascular disrupting agent has been previously reported [ii]. We report the survival of a second patient treated initially with fosbretabulin. Methods: Retrospective chart review. Results: A 53 year old man (Case #2) was diagnosed with unresectable ATC at the time of attempted surgery. He was treated with fosbretabulin in combination with paclitaxel and carboplatin, for 31 months. Further treatment included palliative radiation, efatutazone plus paclitaxel, lenvatinib and pembrolizumab. He expired 8 years after diagnosis with progression of disease. TSH levels were noted to be elevated despite increasing levels of levothyroxine replacement. Conclusions: This represents the second long-term survivor with unresectable ATC treated with fosbretabulin. A randomized phase II trial of fosbretabulin plus paclitaxel and carboplatin versus carboplatin and paclitaxel alone, failed to meet its endpoint of improved overall survival[i]. However a previously reported patient, aged 55 at diagnosis, survived for 10 years after treatment with combretastatin for locally advanced disease[ii]. In both cases TSH levels were markedly elevated and indicative of profound suppression of thyroid function. In patients with differentiated thyroid cancer, a therapeutic objective is to suppress TSH levels, whereas in ATC patients this practice is not customary. Hypothyroidism has been associated with improved survival in other cancers [ii]. Further work up including tumor profiling is being planned to see if there are any mutations that may have predicted a good response to treatment. [i] Sosa JA, et al. Thyroid. 2014 Feb;24(2):232-40 [ii] Mohapatra S, et al (2016) Anaplastic Thyroid Carcinoma - Long Term Survival in a Man with Uncorrected Primary Hypothyroidism: A Case Report with Review of Literature. Int J Endocrinol Metab Disord 2(2) Table 1. TSH levels for each case Case 1 Case 2 Maximum TSH (uIU/ml) 138 57.26 Range TSH (uIU/ml) 0.056 - 138 0.33 – 57.26 Survival (months) 96 120
Survivorship experience for patients (pts) with metastatic melanoma (MM) on long-term targeted therapy (TT).
Authors: Chloe Chia Hoey Khoo, Julia Elizabeth Lai-Kwon, Serigne Lo, Donna Milne, Mustafa Abdi Mohamed, Jeanette Raleigh, Kortnye Maureen Smith, Michael Jefford, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2018)

9556 Background: TT has improved survival for pts with MM. The lived experience for long-term responders remains under-studied. We characterised pt issues using a cross-sectional survey. Methods: Eligible pts had MM, aged > 18, ≥ 6 months post initiation of TT, and had a complete response. A 72-item survey including items from validated measures and custom questions covering physical and psychological effects, impact on lifestyle, access to information, satisfaction with care, and availability of support was administered. Impact of treatment duration (≤12 / > 12 months) on pt experience was assessed. Results: 36/42 (86%) pts responded from Aug-Dec 2017: median age 59 (range 30-84); 18 (50%) male; 21 (58%) had M1c disease; 34 (94%) were receiving TT as 1st line therapy. The majority (31, 86%) were still on treatment; most (22, 74%) had been on treatment for > 12 months. Long-term toxicities including fatigue (33, 92%), dry/itchy skin (25, 69%) and arthralgias (23, 64%) were common. Typical acute toxicities, such as fevers, rashes and gastrointestinal toxicities, were minimal. Psychological morbidity was high, including fear of cancer recurrence (31, 86%), concern regarding long-term toxicities (30, 83%), anxiety awaiting results (29, 81%), concern regarding ongoing sun exposure (28, 78%) and fear of death (26, 72%). The prevalence of both physical and psychological issues was higher among pts on treatment > 12 months, and persisted in 5 (14%) who ceased treatment. Patients reported difficulties with finances (19, 53%), undertaking recreational activities (23, 64%), and performing domestic tasks (14, 39%). Most would value screening for skin cancers (35, 97%), for other cancers (34, 94%), and a survivorship care plan (SCP) to guide management (34, 94%). Conclusions: Physical, psychological and functional issues exist in long-term responders to TT. These issues may increase with increasing duration on treatment. Pts may benefit from ongoing toxicity management, tailored psychological support and an SCP.