tbuckley/cabot-search huggingface dataset:
A phase II study to evaluate safety and efficacy of neoadjuvant pembrolizumab and radiotherapy in localized MSS rectal cancer.
Authors: Thibaud Kossler, Buchs Nicolas, Valérie Dutoit, Giacomo Puppa, Petros Tsantoulis, Jean-Louis Frossard, Philippe Bichard, Xavier Montet, Thomas McKee, Mariagrazia Di Marco, Pierre-Yves Dietrich, Arnaud Roth, Thomas Zilli, Frédéric Ris
Journal: Journal of Clinical Oncology (2020)

TPS272 Background: Locally advanced rectal cancer remains a clinical challenge with few improvements noted over the past few decades. Although immunotherapy has no current clinical role in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitors use. This prospective phase II trial will test that hypothesis in addition to confirming safety of this approach using a “window-of-opportunity” study design with the anti-PD-1 agent Pembrolizumab. Methods: This monocentric phase II trial, will enroll patients (pts) with rectal cancer who are undergoing neoadjuvant short course RT (scRT) (25 Gy in 5 fractions). according to the standard of care. Eligible includes pts with MSS stage II-III rectal cancer with adequate organ function and availability of pre-treatment tumor, who are undergoing scRT with intention to proceed to surgical resection. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes 4 doses of Pembrolizumab (200mg IV, once every 3 wks), the first dose being given before the first scRT fraction. Surgery will be performed within 12-16 weeks of the final scRT dose. Primary endpoint is tumor regression grade (TRG) using the Mandard regression grade score targeting a 30% pathological complete response (pCR) compared to 10% in historical controls. Secondary endpoints include OS, DFS, toxicity, local and distant relapse-free survival, negative surgical margins, QoL, quality of surgery and exploratory assessments of tumor infiltrating lymphocytes, profiling of circulating immune cell populations, and molecular predictors of response. A safety stopping rule is planned based on Wald’s sequential probability ratio test for the occurrence of the safety outcome. Enrollment target is 25 pts. Support: MSD. Clinical trial information: NCT04109755 .
Utility of PET-CT CMR after neoadjuvant chemotherapy with DCF for esophageal cancer as a predictive factor of recurrence.
Authors: Suzuki Kosuke, Shibata Tomotaka, Nishiki Kohei, Fumoto Shoichi, Hirarsuka Takahiro, Kono Kohei, Akagi Tomonori, Tojigamori Manabu, Ueda Yoshitake, Shiroshita Hidefumi, Etoh Tsuyoshi, Shiraishi Norio, Inomata Masafumi
Journal: Journal of Clinical Oncology (2020)

434 Background: PET-CT is considered as standard modality for evaluating metastasis of esophageal cancer before treatment. On the other hand, it is unclear whether PET-CT CMR (complete metabolic response) could be useful for assessment after neoadjuvant chemotherapy. To clarify the utility of PET-CT CMR as an adequate modality of prediction for recurrence after neoadjuvant chemotherapy with DCF for esophageal cancer. Methods: Fifty-eight cases of esophageal cancer (cStageII-IVa) who received the esophagectomy with neoadjuvant chemotherapy of DCF since June 2013 in Oita University. We evaluated the clinicopathological factors, RFS and OS between CMR group (n=22, 38%) and non-CMR group (n=36, 62%). Results: In the clinical stage before chemotherapy, T-factor was higher in the non-CMR group (p = 0.044), but there were no significant differences of lymph node metastasis (p = 0.27) and stage (p = 0.94) between the two groups. There was no significant difference of the SUV max (16.4 ± 6.5 vs 15.7 ± 6.5, p = 0.98) of the main lesion before chemotherapy and the FDG accumulation rate of lymph nodes (14 cases (63.6%) vs 21 cases) (58.3%), p = 0.69) between the two groups. There were no significant differences of the surgical procedure, lymph node dissection area, number of harvested lymph nodes, amount of bleeding, operation time, curability, and intra/post-operative complications between the two groups. There were 5 cases (15%) with postoperative recurrence in the CMR group (lung 1 case, extra-regional lymph nodes 3 cases, bone 1 case), 17 cases (47%) in the non-CMR group (local 4 cases, lung 3 cases, livers 5 cases, extra regional lymph nodes 6 cases, bone 4 cases, pleura 2 cases), but there was no significant difference between the two groups (p = 0.062). There were significant differences between the two groups for 3-year RFS (81.3 vs 65.3 months, p=0.021) and 3-year OS (93.8 vs 61.6 months, p=0.011). Conclusions: PET-CR CMR could not predict recurrence at present. PET-CR CMR cases had better prognosis compared to non-CMR cases in terms of 3-year RFS and 3-years OS.
Enhanced microbial diversity and chemoradiation response in HPV+ anal cancer.
Authors: Ramez Kouzy, Daniel Lin, Sonal Suresh Noticewala, Lauren Elizabeth Colbert, Cullen M. Taniguchi
Journal: Journal of Clinical Oncology (2020)

4 Background: Anal cancer is a rare, but treatable, malignancy caused by the human papilloma virus (HPV). Because anal cancer is uncommon and carries a significant social stigma, this disease has rarely been studied in a prospective fashion, creating a large knowledge gap of which biological factors can improve treatment responses, particularly the microbiome which regulates many facets of oncobiology. Methods: We collected microbiome samples before, during, and after definitive chemoradiation for localized anal cancer as part of an IRB-approved institutional clinical trial (2017-0606). Samples were collected by a non-invasive swab biopsy that enabled collection of tumor cells and microbiome during standard-of-care treatment visits. Bacterial genomic DNA is extracted using MO BIO PowerSoil DNA Isolation Kit (MO BIO Laboratories) and the 16S rDNA V4 region is amplified by PCR and sequenced on the MiSeq platform (Illumina) using the 2x250 bp paired-end protocol, yielding pair-end reads that overlapped almost completely. Sequence read pairs are demultiplexed using unique molecular barcodes, and reads are merged using USEARCH version 7.0.1090 and grouped by organizational taxonomy units (OTU’s) representative of unique bacterial species. Responders are were those patients who had more than 60% tumor shrinkage by MRI at the midpoint of treatment, and all others were considered non-responders. Results: As of June 2019 we enrolled 17 patients and analyzed 14. The majority of patients (10/14, 71.4%) were responders but unfortunately, 4 patients developed in-field recurrences of their anal cancer within a year after their treatment ended and were all T3 or T4 tumors. We found that alpha-diversity of the microbiome did not change during chemoradiation, but non-responders exhibited a lower alpha diversity compared to responders at baseline. Furthermore, specific taxa were correlated with treatment response, which imply a basis for future therapy. Conclusions: The alpha diversity of the microbiome is correlated with treatment response in HPV+ anal cancer. The idenitification of specific bacterial species between responders and non-responder might pave the way for more effective therapeis in the future.
Using human genetics to understand the disease impacts of testosterone in men and women
Authors: Katherine S Ruth, Felix R Day, Jessica Tyrrell, Deborah J Thompson, Andrew R Wood, Anubha Mahajan, Robin N Beaumont, Laura Wittemans, Susan Martin, Alexander S. Busch, A. Mesut Erzurumluoglu, Benjamin Hollis, Tracy A. O’Mara, Mark I McCarthy, Claudia Langenberg, Douglas F Easton, Nicholas J Wareham, Stephen Burgess, Anna Murray, Ken K Ong, Timothy M Frayling, John R. B. Perry
Journal: Nature Medicine (2020)
How do social determinants of health impact timeliness of chemotherapy and survival in patients with metastatic colon cancer? A 12-year study.
Authors: Thejus Thayyil Jayakrishnan, Veli Bakalov, Zena Chahine, Gene Grant Finley, Dulabh K. Monga, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

36 Background: Studies have demonstrated disparities in health care driven by socioeconomic factors. Patients with metastatic cancer represent the most vulnerable group of cancer patients. We hypothesized that these factors impact timeliness to chemotherapy in patients with metastatic colon cancer and their treatment outcomes. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic colon cancer (AJCC pathologic stage4) diagnosed from 2004-2016. We selected patients treated with chemotherapy as first line treatment within 90 days of diagnosis. Time to initiation (TTI) was defined as time in days (d) from diagnosis of cancer to initiation of systemic chemotherapy and survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results: We identified 11,764 patients meeting the eligibility criteria. Median age was 62 (range 18-90) years and included 51% males. Median TTI was 9d (range 1-89) and median overall survival was 24.3m. TTI was significantly associated with race - Caucasian 26.4d (95% CI 25.6-27.1) vs. African American 28.9d (26.9-31.0) p-value=0.021, Median income - ≥ $63,000 23.5d (95% CI 22.4 – 24.5) vs.&lt; $38,000 29.2d (27.3 – 31.0) p-value &lt; 0.0001, Facility type – Community cancer center 23.6d (95% CI 21.6-25.6) vs. Academic/research program 26.5d (95% CI 25.5 – 27.4) p-value=0.014. Factors impacting survival in a multivariate model included time to chemotherapy initiation – 24.7m with TTI ≤ 9d vs. 23.8m with TTI &gt; 9d (p-value &lt;0.0001), type of facility – Academic/research program 26.4m vs. community cancer center 21.3 (p-value &lt;0.0001), age (p-value &lt;0.001), comorbidities (p-value &lt;0.0001) and site of primary. Conclusions: Patients with metastatic cancer are not free from disparities driven by social determinants of health that impact their outcomes. The findings suggest that further studies to identify barriers to healthcare access and continued efforts to improve them are warranted.
Therapeutic options for the 2019 novel coronavirus (2019-nCoV)
Authors: Guangdi Li, Erik De Clercq
Journal: Nature Reviews Drug Discovery (2020)

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.
Efficacy and safety of nivolumab and irinotecan as third-line chemotherapy for advanced gastric cancer: A multi-institutional retrospective study.
Authors: Ryosuke Kumanishi, Seiichiro Mitani, Shigenori Kadowaki, TOMOHIRO MATSUSHIMA, Naoki Takahashi, Takatsugu Ogata, Hisateru Yasui, Misato Ogata, Hironaga Satake, Yukiya Narita, Toshiki Masuishi, Hideaki Bando, Hiroki Hara, Kei Muro
Journal: Journal of Clinical Oncology (2020)

396 Background: Although nivolumab (NIVO) and irinotecan (IRI) are currently used as third- or later-line therapy for advanced gastric cancer (AGC), few direct comparisons between them have been available. The present study therefore aims to compare the efficacy and safety of NIVO with IRI and explore clinical factors that predict efficacy. Methods: Patients with AGC who underwent NIVO or IRI treatment between November 2016 and June 2018 at three institution were retrospectively examined, subsequently evaluating response rates (RR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The main inclusion criteria were patients pretreated with fluoropyrimidines and taxanes, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0–2, and no previous NIVO or IRI treatment. Results: A total of 71 and 61 patients received NIVO and IRI, respectively, with both groups having similar baseline characteristics, except for gender. Efficacies were as follows (NIVO/IRI): RR, 20%/6% (p = 0.17); median PFS, 1.6 months (m)/1.8 m (HR 0.93, p = 0.67); median OS, 6.4 m/6.4 m (HR 0.91, p = 0.61); 1-year survival rate, 24.9%/19.3% (p = 0.61), respectively. Interaction analysis found no significant interaction between drugs and various factors such as ECOG PS (p = 0.59) and neutrophile/lymphocyte ratio (p = 0.33) related to OS. Subsequent chemotherapy agents were administered to 32 patients (45%) in the NIVO group (17 patients out of them received IRI) and 36 patients (59%) in the IRI group (23 patients out of them received NIVO) (p = 0.12). NIVO tended to have lower grade 3 or more AEs than IRI, especially neutropenia (3% vs. 28%, respectively; p &lt; 0.01) and febrile neutropenia (1% vs. 8%, respectively; p = 0.09), as well as neutropenia, nausea, diarrhea, constipation, fatigue, and anorexia of any grade. Five patients developed immune-related adverse events in the NIVO group: pneumonitis (n = 1) and rash (n = 4). Conclusions: Although no remarkable differences in efficacy were found between NIVO and IRI for AGC, NIVO had a better safety profile compared to IRI. This study found no clinical factors that predicted efficacy.
A phase Ib study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 117.
Authors: Masatoshi Kudo, Masafumi Ikeda, Kenta Motomura, Takuji Okusaka, Naoya Kato, Corina E. Dutcus, Takashi Hisai, Mayumi Suzuki, Hiroki Ikezawa, Takeyuki Iwata, Hiromitsu Kumada, Masahiro Kobayashi
Journal: Journal of Clinical Oncology (2020)

513 Background: LEN, a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT with immunomodulatory activity, is approved in multiple countries for first-line treatment of uHCC. NIV is an anti-PD-1 monoclonal antibody approved in multiple countries as a second-line treatment for HCC. We report early results from a phase 1b trial of LEN + NIV in pts with uHCC. Methods: In this open-label study, pts with uHCC, BCLC stage B (not eligible for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤ 1 received LEN (bodyweight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day) PO QD and 240 mg NIV IV Q2W. The primary endpoint was tolerability and safety of the combination. Objective response rate (ORR; mRECIST by investigator) was a secondary endpoint. Tolerability was evaluated by assessing dose-limiting toxicities (DLTs) during the first cycle in pts for whom no other appropriate therapy was available (Part 1). Once tolerability was confirmed, additional pts with no prior systemic therapy for uHCC were enrolled (Part 2). Results: At data cutoff (May 17, 2019), 30 pts had received LEN + NIV (Part 1: n=6; Part 2: n=24). Pts had BCLC stage B (n=17) or C (n=13) and Child-Pugh scores of 5 (n=23) or 6 (n=7). 4 pts in Part 1 (66.7%) had received prior anticancer medications (3 pts had 1; 1 pt had ≥3). No DLTs were reported in Part 1. TEAEs leading to discontinuation of LEN were reported in 2 (6.7%) pts; 4 (13.3%) pts had TEAEs leading to discontinuation of NIV. TEAEs occurred in all 30 pts; the most common were palmar-plantar erythrodysesthesia (56.7%) and dysphonia (53.3%). Adverse events were manageable. Efficacy outcomes are reported (Table). Conclusions: LEN + NIV was well tolerated with encouraging anti-tumor activity in pts with uHCC. Clinical trial information: NCT03418922. [Table: see text]
Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China
Authors: Aiping Wu, Yousong Peng, Baoying Huang, Xiao Ding, Xianyue Wang, Peihua Niu, Jing Meng, Zhaozhong Zhu, Zheng Zhang, Jiangyuan Wang, Jie Sheng, Lijun Quan, Zanxian Xia, Wenjie Tan, Genhong Cheng, Taijiao Jiang
Journal: Cell Host & Microbe (2020)
Significance of frailty in prognosis after hepatectomy in older patients with hepatocellular carcinoma.
Authors: Shinichiro Yamada, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Yu Saito, Masato Yoshikawa, Katsuki Miyazaki
Journal: Journal of Clinical Oncology (2020)

590 Background: An aging society has come, and “Frailty” is becoming increasingly important in surgery. Recently, clinical frail scale (CFS), which is simple criteria for frailty, has been reported to be useful for prognostic prediction of non-cardiac surgery (Ann Surg. 2018). Herein we report a new knowledge about frailty for patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. Methods: Eighty-one patients over 75 years who underwent hepatectomy for HCC between 2007 and 2018 were enrolled in this study. Frailty was diagnosed as CFS≥4, and patient were divided into 2 groups, frailty (n = 17) and no frailty (n = 64). Clinicopathological factors were compared between 2 groups. Results: Patients’ background, such as age, gender, preoperative comorbidity, and liver function showed no significant difference between 2 groups. Regarding tumor factors, frailty group showed significant larger tumor diameter, more advanced stage (p &lt; 0.05) and tendency of high PIVKA-II (p = 0.15) compared with no frailty group. Frailty group showed significant high CRP level (p &lt; 0.01), high modified Glasgow prognostic score (mGPS, p = 0.04) and tendency of high neutrophil-lymphocyte ratio (NLR, p = 0.14). Frailty group also showed tendency of higher rate of postoperative complication (p = 0.11) and longer postoperative hospital stay (p = 0.09). Overall and disease-free survival rate were significantly worse in frailty group (p = 0.03). In univariate analysis for overall survival, AFP≥10, PIVKA-II≥400, frailty and mGPS high (1, 2) were prognostic factor. Multivariate analysis revealed that frailty was independent prognostic factor. In univariate analysis of disease-free survival, only frailty was detected as prognostic factor. Conclusions: Frailty is an independent prognostic factor for HCC patients who underwent hepatectomy.
Training curriculum for European thoracic surgeons: a joint initiative of the European Society of Thoracic Surgeons and the European Respiratory Society
Authors: Gilbert Massard, Nathalie Tabin, Lars Konge, Anna Elisabeth Frick, Hasan Batirel, Alessandro Brunelli, Stefano Elia, Martin Huertgen, Laureano Molins, Kostas Papagiannopoulos, Dragan Subotic, Paul van Schil, Gonzalo Varela, Dirk van Raemdonck
Journal: European Respiratory Journal (2020)

In the most recent issue of the European Journal of Cardio-Thoracic Surgery , the joint task force group on training in thoracic surgery, set up by both the European Society of Thoracic Surgeons and the European Respiratory Society (ERS), has published the core document describing the recommended training curriculum [1]. This document takes its roots from the European syllabus published in 2018 [2, 3]. According to a methodology validated by education scientists, the working group has described, for each item, the expected level of competence in terms of knowledge, skills and attitudes, listed possible learning resources, and recommended appropriate tools for assessment of learning outcomes [4]. This consensual curriculum for thoracic surgeons intends to promote homogeneity of training and and its outcome in terms of competence throughout Europe <http://bit.ly/3a2tTZI>
Disease risk and GVHD biomarkers can stratify patients for risk of relapse and nonrelapse mortality post hematopoietic cell transplant
Authors: Mina D. Aziz, Jay Shah, Urvi Kapoor, Christina Dimopoulos, Sarah Anand, Allan Augustine, Francis Ayuk, Mohammed Chaudhry, Yi-Bin Chen, Hannah K. Choe, Aaron Etra, Stephanie Gergoudis, Matthew J. Hartwell, Elizabeth O. Hexner, William J. Hogan, Carrie L. Kitko, Steven Kowalyk, Nicolaus Kröger, Pietro Merli, George Morales, Ryotaro Nakamura, Rainer Ordemann, Michael A. Pulsipher, Muna Qayed, Ran Reshef, Wolf Rösler, Tal Schechter, Elisabeth Schreiner, Hrishikesh Srinagesh, Matthias Wölfl, Kitsada Wudhikarn, Gregory Yanik, Rachel Young, Umut Özbek, James L. M. Ferrara, John E. Levine
Journal: Leukemia (2020)
Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis
Authors: Michael Walsh, Peter A. Merkel, Chen-Au Peh, Wladimir M. Szpirt, Xavier Puéchal, Shouichi Fujimoto, Carmel M. Hawley, Nader Khalidi, Oliver Floßmann, Ron Wald, Louis P. Girard, Adeera Levin, Gina Gregorini, Lorraine Harper, William F. Clark, Christian Pagnoux, Ulrich Specks, Lucy Smyth, Vladimir Tesar, Toshiko Ito-Ihara, Janak Rashme de Zoysa, Wojciech Szczeklik, Luis Felipe Flores-Suárez, Simon Carette, Loïc Guillevin, Charles D. Pusey, Alina L. Casian, Biljana Brezina, Andrea Mazzetti, Carol A. McAlear, Elizabeth Broadhurst, Donna Reidlinger, Samir Mehta, Natalie Ives, David R.W. Jayne
Journal: New England Journal of Medicine (2020)

More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.
Screening and treatment strategy for double cancer for esophageal cancer surgery patients.
Authors: Takashi Ogata, Yota Shimoda, Kazuki Kano, Keisuke Koumori, Hayato Watanabe, Hirohito Fujikawa, Takanobu Yamada, Takashi Oshima
Journal: Journal of Clinical Oncology (2020)

336 Background: Esophageal cancer treatment, especially esophagectomy, is highly invasive, so treatment strategies are considered in view of existing double cancers. On the other hand, in Japan, 90% of esophageal cancers are squamous cell carcinoma, and it is known that there are a large proportion of head and neck cancers for double cancers as field cancerization. Methods: The aim of this study is to investigate the types of double cancer, simultaneous/metachronous, and the frequency and treatment policy of head and neck cancer as a particularly high coexistence rate for esophageal cancer surgery patient. The subjects were 304 patients who underwent esophagectomy performed from April 2010 to December 2017. All patients were examined with high-definition endoscopy with NBI by certificated endoscopist at the first visit as a search for simultaneous double cancer from the pharynx to the stomach. And after esophagectomy, endoscopy was also performed to check for metachronous double cancers in the remaining esophagus, gastric tube, and pharynx at least every 2 years. Results: The number of double cancer cases was found in 94 cases (30.9%), and the total number of double cancer cases was 122. Head and neck cancer(33 cases), stomach cancer(16 cases), and colon cancer(12 cases) were observed as the main course of double cancers. In double cancer cases, 47cases(50.0%) were metachronous, 35cases(37.2%) were simultaneous, and 12cases(12.8%) were both synchronous. The most common double cancer was head and neck cancer(33 cases:35.1%), and 23 cases were simultaneous, 10 cases were metachronous. As treatment strategy for head and neck cancer, endoscopic laryngo-pharyngo surgery(ELPS) were 19 cases. 10 cases(52.7%) were synchronous cancers, and 9 cases (47.3%) were metachronous cancers which were detected during follow-up after esophagectomy. Conclusions: Head and neck cancer associated with esophageal cancer surgery is the most common type of double cancer, and 1/3 of ELPS cases have been detected by follow-up endoscopy after esophagectomy, so endoscopic surveillance was also considered important.