tbuckley/cabot-search huggingface dataset:
A pilot study of durvalumab/tremelimumab (durva/treme) and radiation (XRT) for metastatic biliary tract cancer (mBTC): Preliminary safety and efficacy.
Authors: Theodore S. Hong, Lipika Goyal, Aparna Raj Parikh, Beow Y. Yeap, Christine A. Ulysse, Lorraine C. Drapek, Jill N. Allen, Jeffrey William Clark, Benjamin Christopher, Christine Bolton, David P. Ryan, Ryan Bruce Corcoran, Jeffrey A. Meyerhardt, Jennifer Yon-Li Wo, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2020)

547 Background: Metastatic biliary tract cancer (mBTC) is a lethal malignancy with median 5 year OS of less than 10%. Immunotherapy, particularly single agent anti-PD-1/PD-L1, has limited efficacy in mBTC with ORR~9-15%. Recently presented data shows responses in metastatic MSS pancreatic or colon cancer with combination anti-PD-1/CTLA-4 and radiation (XRT) to produce systemic response (abscopal effect) (Parikh A, GI ASCO 2019, ASCO 2019.). We evaluate safety and efficacy of dual PD-1/CTLA-4 inhibition with XRT in MSS mBTC. Methods: 15 of a planned 15 mBTC patients were enrolled. Eligible pts had histologically-confirmed mBTC, ECOG-PS 0/1, and must have progressed on at least one line of previous therapy or refused standard therapy. Safety cohort of 6 pts of durva 1500 mg/treme 75 mg q4w was enrolled. If &gt; 2 DLTs, patients were enrolled subsequently to dose level -1 (durva 1125 mg/ treme 75 mg q4w). 3 fractions of 8 Gy of radiation at C2D1 every other day to a single metastatic site. Durva/treme continued for 4 cycles, followed by 4 cycles of maintenance durva until progressive disease, discontinuation or withdrawal. Endpoints include disease control rate (DCR (SD+PR+CR)), PFS and OS and safety. Radiological evaluations were done q2 mo. Results: 15 mBTC pts enrolled and evaluable from May 2018 to March 2019. Median age 63 years (range 48-75), 47% male. DLTs occurred in 3 patients during the safety run-in. One patient experienced DLT at dose level -1 and subsequent expansion. 3 patients did NOT reach radiation therapy. DCR was 27% with a 13% PR and 7% CR. Of those who reached radiation, DCR was 33% with a 17% PR and 8% CR. At time of analysis, median PFS was 54 days for ITT mBTC. Duration of response for 4 patients with DCR was 26, 52, 122, 254+ days. Treatment-related adverse events were reported in 12/15 patients (80%). Grade ≥3 toxicities were seen in 9/15 pts (60%) with lymphopenia (5 grade 3) and elevated LFTs (2 grade 4 and 4 grade 2) being the main adverse events. All patients with disease control were not MSI. Conclusions: Combination of durva/treme XRT is feasible and shows preliminary activity in metastatic BTC. An expansion cohort is being planned to confirm activity. Clinical trial information: NCT03482102.
Abstract 180: Nursing Roles for In-Hospital Cardiac Arrest Response: A Qualitative Study
Authors: Timothy C Guetterman, Joan Kellenberg, Sarah Krein, Jessica Lehrich, Molly Harrod, Steven Kronick, Paul S Chan, Saket Girotra, Theodore J Iwashyna, Brahmajee K Nallamothu
Journal: Circulation (2018)

Introduction: Survival and favorable clinical outcomes for in-hospital cardiac arrest (IHCA) are highly dependent on a skilled resuscitation team, prompt initiation of high quality CPR and defibrillation, and organizational structures to support resuscitation care. While nurses are generally involved in resuscitation efforts, the purpose of this study was to examine their specific roles and factors that affect their contributions during an IHCA response. Methods: We conducted a qualitative study at 9 hospitals participating in the AHA Get-With-The-Guidelines Resuscitation registry. Purposeful sampling was used to select hospitals that vary in terms of geography, academic status, and risk-standardized IHCA survival. Participants included nurses, physicians, respiratory therapists, pharmacists, quality improvement staff, hospital administrators, and other staff, yet discussion of the nursing function was prominent across all stakeholder groups. Qualitative thematic text analysis was used to identify the distinct types of nursing roles in relation to IHCA and how these roles were supported across sites. Results: We conducted semi-structured interviews with 158 individuals at 9 hospitals. Nurses were identified as an integral part of the IHCA response at all sites, with three major IHCA nursing roles identified: bedside first responder, rapid response or code team member, and leader. There were distinct differences across sites in support for nurses in these different roles with regard to educational training and competency, organizational engagement, and empowerment (Table). Conclusion: Nurses are a critical component of effective IHCA response and processes, including diverse roles as bedside first responders, code team members, and leadership for resuscitation care. Mentoring and empowering frontline nurses and ensuring that clinical competency and training needs for IHCA care specific for nurses is essential for resuscitation care.
High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts
Authors: Alexandre Roux, Johan Pallud, Raphaël Saffroy, Myriam Edjlali-Goujon, Marie-Anne Debily, Nathalie Boddaert, Marc Sanson, Stéphanie Puget, Steven Knafo, Clovis Adam, Thierry Faillot, Dominique Cazals-Hatem, Emmanuel Mandonnet, Marc Polivka, Georges Dorfmüller, Aurélie Dauta, Mathilde Desplanques, Albane Gareton, Mélanie Pages, Arnault Tauziede-Espariat, Jacques Grill, Franck Bourdeaut, François Doz, Frédéric Dhermain, Karima Mokhtari, Fabrice Chretien, Dominique Figarella-Branger, Pascale Varlet
Journal: Neuro-Oncology (2020)

Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification.Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
Pembrolizumab plus allogeneic NK cells in advanced non–small cell lung cancer patients
Authors: Mao Lin, Haihua Luo, Shuzhen Liang, Jibing Chen, Aihua Liu, Lizhi Niu, Yong Jiang
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.
A phase III study of nivolumab (NIVO), NIVO + ipilimumab (IPI), or chemotherapy (CT) for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): Checkmate 8HW.
Authors: Sandzhar Abdullaev, Thierry André, Ming Lei, Heinz-Josef Lenz, James Novotny, Andrew Scott Paulson, Sabine Tejpar, Kentaro Yamazaki, Jean-Marie Ledeine
Journal: Journal of Clinical Oncology (2020)

TPS266 Background: Patients (pts) with MSI-H/dMMR mCRC treated with CT have poorer outcomes than pts with microsatellite stable/MMR proficient mCRC. NIVO (anti–programmed death [PD]-1) and IPI (anti–cytotoxic T lymphocyte antigen-4 [CTLA-4]) are immune checkpoint inhibitors that act synergistically and promote antitumor immune response by complementary mechanisms. NIVO±IPI received accelerated US FDA approval for MSI-H/dMMR mCRC that progressed after fluoropyrimidine, oxaliplatin, and irinotecan treatment based on the phase 2, non-randomized, multicohort CheckMate 142 study. Indirect comparisons suggest that NIVO (3 mg/kg) + low-dose IPI (1 mg/kg) provides improved clinical benefit vs NIVO (investigator-assessed [INV] objective response rate [ORR] 55% vs 31%; 12-month [mo] INV progression-free survival [PFS] rate 71% vs 50%; 12-mo overall survival [OS] rate 85% vs 73%) with a favorable benefit-risk profile for previously treated MSI-H/dMMR mCRC (Overman et al. JCO 2018). NIVO+low-dose IPI also demonstrated robust and durable clinical benefit in first-line MSI-H/dMMR mCRC (INV ORR 64%; 12-mo INV PFS rate 77%; 12-mo OS rate 84%; Lenz et al. ASCO 2019, #3521). To date, no prospective phase 3 studies have reported results for anti–PD-1, anti–PD-1 + anti–CTLA-4, or CT in MSI-H/dMMR mCRC; these treatments will be evaluated in the international, multicenter, open-label, randomized, phase 3 CheckMate 8HW (NCT04008030) study. Methods: Approximately 494 pts aged ≥18 years with histologically confirmed recurrent or mCRC, irrespective of prior treatment with CT and/or targeted agents, not amenable to surgery, and with known tumor MSI-H or dMMR status, and Eastern Cooperative Oncology Group performance status ≤1 will be randomized to receive NIVO, NIVO+IPI, or investigator’s choice CT (pts in the CT arm can receive NIVO+IPI upon progression). The primary endpoint is PFS, assessed by blinded independent central review (BICR). Secondary endpoints include PFS by INV, ORR and disease control rate by BICR and INV, OS, time to and duration of response. Exploratory endpoints include safety. Clinical trial information: NCT04008030.
Clinical outcome for gastrointestinal cancers with polymerase epsilon mutations treated with immunotherapy.
Authors: Limin Zhu, Funda Meric-Bernstam, Vijaykumar Holla, Taebeom Kim, Kenna Rael Shaw, Ken Chen, Mark Routbort, Scott Kopetz, Michael J. Overman
Journal: Journal of Clinical Oncology (2020)

828 Background: Predictive factors for immunotherapy benefit across gastrointestinal (GI) cancers are limited to those with deficient mismatch repair (dMMR). Mutations in DNA polymerase E (POLE) can cause a hypermutated phenotype irrespective of MMR status and may serve as a predictor factor for immunotherapy. Methods: All POLE-mutant GI cancers with tumor mutation burden (TMB) measured at MD Anderson Cancer Center were identified (N = 58) from 2014 to 2019 and those that had received immunotherapy (N = 18) were studied. TMB was measured by genomic profiling assays FoundationOne or STGA 2018. Samples were analyzed using Kaplan-Meier method and compared using log rank test, with a predefined high TMB threshold of 20 muts/mb. Results: Of the 58 POLE-mutant GI tumors a high TMB was present in 50% of the cases. 18 patients (median age 64, female gender 16.7%, median prior lines of therapy 2) with locally advanced (N = 4) or metastatic (N = 14) POLE-mutant GI cancers (13 colorectal, 1 small intestine, 1 esophageal, 1 pancreatic, and 2 gallbladder) were identified. Immunotherapy agents were PD-1/PD-L1 based in 17 and CTLA-4 based in 1. High TMB was present in 11 patients. dMMR was present in 7 patients, all with high TMB. Treatment response was seen in 3 patients (2 CR and 1 PR), all TMB high and dMMR. Progression-free survival (PFS) was significantly longer in those with high TMB (median: 10.1 months vs. 3 months, p = 0.048). Of the 11 pMMR patients median PFS was 9.3 months in high TMB and 3 months in low TMB (p = 0.246). Conclusions: POLE mutations in GI cancers were associated with a high TMB ( &gt; 20muts/mb) in 50% of patients. Within POLE mutant GI cancers a high TMB may identify patients who benefit from immunotherapy irrespective of mismatch repair status.
Association of ascitic neutrophil to lymphocyte ratio with prognosis in patients with advanced gastric cancer
Authors: Jae-Joon Kim, So Yeon Oh, Kwonoh Park, Sang-Bo Oh
Journal: Journal of Clinical Oncology (2020)

443 Background: Approximately 40% of metastatic gastric cancer patients develop peritoneal carcinomatosis, and this condition leads patients to grave prognosis. Blood neutrophil to lymphocyte ratio (NLR) is associated with prognosis in various solid tumors, such as non-small cell lung cancer, colorectal cancer, and gastric cancer. We performed this study to investigate the prognostic significance of NLR of ascitic fluid. Methods: This is retrospective study. Patients were consecutive included if they; 1) had histologically confirmed gastric adenocarcinoma, poorly cohesive carcinoma, or poorly differentiated carcinoma, 2) were relapsed after curative resection or initially metastatic, 3) had ascites due to peritoneal metastases of gastric cancer, 4) had received paracentesis at least once and the result of ascites exam is available. Patients with clinically active infection in the time of paracentesis is excluded. If multiple times of paracentesis was done, we used initial result. Results: From March 2012 to August 2018, total 157 patients who were visited in Pusan National University Yangsan Hospital met the inclusion criteria. Median age is 58 (29-86) years and male patients was 63% (n = 99). In 38.9% (n = 61) patients, gastric cancer was diagnosed in primary site and in ascites synchronously. At the time of first paracentesis, 47.1% (n = 74) of patients had already been received palliative chemotherapy due to metastatic gastric cancer. In the ascites, mean and median NLR is 2.2±6.8 and 0.3 (0-65). All except 3 patients were expired, and the median survival time form paracentesis was 47 (95% confidence interval 38.6-55.4) days. In the Kaplan-Meier survival analysis, patients with higher NLR (≥0.33) have shorter survival from paracentesis (39 days, 95% CI 32.5-45.4) in compared to lower NLR ( &lt; 0.33) (61 days, 95% CI 29.4-92.6, log-rank p = 0.011). In the additional analyses, higher neutrophil count (41 vs 72 days, p = 0.045) and lower protein level (32 vs 61 days, p = 0.018) of ascites are also poor prognostic factor. Conclusions: High NLR of malignant ascites is poor prognostic factor in patients with gastric cancer. The role of neutrophil in the malignant ascites should be tested in a new perspective.
Levels of oncofetal proteins in pathological tissues of patients with gastric cancer.
Authors: Oleg Ivanovich Kit, Elena M. Frantsiyants, Yuriy A. Gevorkyan, Natalya V. Soldatkina, Nikolay S. Samoylenko
Journal: Journal of Clinical Oncology (2020)

449 Background: Spread to the peritoneal cavity and lymphatic system is the most important factor of gastric cancer prognosis. Successful implantation of cancer cells in a distant place is possible only when cancer cells accept a special kind of molecular invitation sent by some organs. Our purpose was to study levels of CA-19.9, CA-125, CA-72.4 and He-4 in tissues of tumors, peritoneum and omentum in patients with gastric cancer (GC) T 3-4 a N 0-3 M 1 and T 3-4 a N 0-3 M 0 . Methods: Levels of CA-19.9, CA-125 and CA-72.4 were determined by ELISA in primary tumors, the omentum and peritoneum of patients from main groups 1 (M 0 ) – GC T 3-4 a N 0-3 M 0 (n = 24) and 2 (M 1 ) – GC T 3-4 a N 0-3 M 1 (n = 21) and in the stomach, omentum and peritoneum of non-cancer controls (n = 17). Results: Levels of CA-19.9, CA-125 and CA-72.4 were increased, compared to control values, in all studied samples from 1.6 times (CA-72.4) to 180.1 times (СA-19.9). Only CA-19.9 levels differed depending on the metastatic spread: 1.8 times (p˂0.05) higher in T 3-4 a N 0-3 M 1 than in T 3-4 a N 0-3 M 0 . In the omentum tissues, CA-19.9 levels in T 3-4a N 0-3 M 1 exceeded the control values by 20 times; in 20 patients with T 3-4 a N 0-3 M 0 , the value was only 4.1 times higher than in controls and 4.8 times lower than in T 3-4 a N 0-3 M 1 , while in 4 patients it did not differed significantly from the value in T 3-4 a N 0-3 M 1 . In the peritoneal tissues, CA-19.9 levels in T 3-4 a N 0-3 M 1 exceeded the control values by 19.2 times; in 21 patients with T 3-4 a N 0-3 M 0 , the value was only 2.2 times higher than in controls and 8.5 times lower than in T 3-4 a N 0-3 M 1 , while in 3 patients it did not differed significantly from the value in T 3-4 a N 0-3 M 1 . Conclusions: Saturation of peritoneal and omentum tissues with marker oncoproteins is one of the factors associated with metastatic characteristics of gastric cancer, while the CA-19.9 level can serve as informative laboratory tests to predict the nature of the further disease development.
Measuring Clinical Importance in a Trial of Interventions for Mixed Urinary Incontinence—Reply
Authors: Vivian W. Sung, Marie G. Gantz
Journal: JAMA (2020)

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Organ Donation after Medical Assistance in Dying — Canada’s First Cases
Authors: Ian M. Ball, Andrew Healey, Sean Keenan, Fran Priestap, John Basmaji, Kimia Honarmand, Jeanna Parsons Leigh, Sam Shemie, Prosanto Chaudhury, Jeffrey M. Singh, Jeffrey Zaltzman, Stephen Beed, Matthew Weiss
Journal: New England Journal of Medicine (2020)

To the Editor: In 2016, following the Supreme Court of Canada's Carter Decision, 1 medical assistance in dying (MAID became possible with individual court orders.However, owing to the lack of a centrally coordinated Canadian response to the requests of some patients for voluntary euthanasia, as well as concern for individual repercussions, many Canadian providers of assisted dying operate largely independently.With 3 years now passed since euthanasia was approved, it is important to ensure our understanding of current practice for the purpose of quality assurance, provider education, and future research opportunities geared to improve patientcentered practice.Among the practices related to the legalization of euthanasia, organ donation raises challenging issues.We performed a historical cohort study of completed MAID organ-donation cases using data
Analysis of consensus molecular subtypes (CMS) classification in the TRICOLORE trial: A randomized phase III trial of S-1 and irinotecan (IRI) plus bevacizumab (Bmab) versus mFOLFOX6 or CapeOX plus Bmab as first-line treatment for metastatic colorectal cancer (mCRC).
Authors: Satoshi Yuki, Makio Gamoh, Tadamichi Denda, Atsuo Takashima, Shin Takahashi, Masato Nakamura, Hisatsugu Ohori, Tatsuro Yamaguchi, Yoshimitsu Kobayashi, Hideo Baba, Masanori Kotake, Kenji Amagai, Hitoshi Kondo, Ken Shimada, Atsushi Sato, Chikashi Ishioka, Keigo Komine, Kota Ouchi, Satoshi Morita, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2020)

169 Background: The TRICOLORE trial previously demonstrated that S-1+IRI+Bmab (Arm B) was non-inferior to mFOLFOX6/CapeOX+Bmab (Arm A) in terms of progression-free survival (PFS) as first-line treatment for mCRC, irrespective of RAS status. CMS was reported to be a prognostic factor for mCRC. Previously, it was reported that the CMS could be a predictive factor for the efficacy of oxaliplatin (OX) and IRI (Okita A, et al. Oncotarget. 2018). In this exploratory study of TRICOLORE trial, we examined if the CMS could be a predictive factor of OX and IRI regimen. Methods: We collected formalin-fixed paraffin-embedded (FFPE) primary tumor tissues and performed gene expression analysis by microarray. The subtype of CMS was determined by the CMS classifier (Guinney et al. Nature Med. 2015). PFS and overall survival (OS) were compared between arm A and B in each subtypes of CMS. Results: Total of 308 FFPE samples from 487 cases who were enrolled in the TRICOLORE study were collected. Number of patients classified into CMS1 to CMS4 were 47, 72, 99 and 90, respectively. Similar to the previous reports, the proportion of RAS mutant cases was highest in CMS3 and the most of BRAF mutant cases were classified into CMS1. The median PFS (mPFS) of arm A and B were almost same in CMS2 (16.1m vs. 17.6m, HR = 1.10, p = 0.79) and CMS3 (10.6 vs. 11.4, HR = 0.95, p = 0.81). In CMS1, mPFS of arm A was worse than that of arm B, although not statistically significant (7.4m vs. 13.2m, HR = 0.73, p = 0.35). In CMS4, mPFS of arm B was better than that of arm A, although not statistically significant again (9.7m vs. 14.1m, HR = 0.72, p = 0.15). The median OS (mOS) of both arm in CMS2-CMS4 and arm B in CMS1 were good and were 29.0m or more. On the other hand, mOS of arm A in CMS1 (18.1m) was worse than the others. Conclusions: From these results, it was not concluded that CMS was a predictor of mFOLFOX6/CapeOX+Bmab and S-1+IRI+Bmab. However, mPFS and mOS of mFOLFOX6/CapeOX+Bmab in CMS1 were poor unlike other CMS subtypes, and these were consistent with a previous report. Whereas S-1+IRI+Bmab was effective in all subtypes of CMS. Clinical trial information: UMIN000007834.