tbuckley/cabot-search huggingface dataset:
Impact of postoperative complications on recurrence in pathological stage II/III gastric cancer patients who received curative resection followed by adjuvant S-1 chemotherapy.
Authors: Hayato Watanabe, Tsutomu Hayashi, Keisuke Koumori, Kazuki Kano, Yota Shimoda, Hirohito Fujikawa, Takanobu Yamada, Yasushi Rino, Munetaka Masuda, Takashi Ogata, Takashi Oshima
Journal: Journal of Clinical Oncology (2020)

320 Background: Postoperative complications increased recurrence in gastric cancer (GC) patients. However, there was no study evaluating impact of postoperative complication among patients receiving adjuvant chemotherapy. The aim of present study was to investigate the impact of postoperative complications in pStage II/III GC patients who received adjuvant S-1 chemotherapy. Methods: The present study retrospectively examined GC patients who received curative gastrectomy followed by adjuvant S-1 chemotherapy between January 2000 and December 2011 at Kanagawa Cancer Center. The patients with postoperative complications were classified into PC group, and those without postoperative complications were into NC group. Clinicopathological characteristics and recurrence-free survival (RFS) were compared between the groups. Results: 226 patients were included in this study. Postoperative complication occurred in 30 patients (13.3%). Age (Median, range) is significantly higher in NC group (64, 24-86) than in PC group (59, 36-82) (p = 0.033). Total gastrectomy was predominant type of surgery in the PC group (73.3%) than in NC group (52.0%) (p = 0.031). There was no difference in gender, ASA score, tumor location, pathological stage (TNM 7th) and pathological type between two groups. Conclusions: Postoperative complications were an independent risk factor for RFS in pStage II/III GC patients who received curative gastrectomy followed by adjuvant S-1 chemotherapy.
How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018
Authors: Ine Wouters, Stefanie Desmet, Liesbet Van Heirstraeten, Sereina A Herzog, Philippe Beutels, Jan Verhaegen, Herman Goossens, Pierre Van Damme, Surbhi Malhotra-Kumar, Heidi Theeten
Journal: Eurosurveillance (2020)

Background The current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium. Aim This observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D. Methods A total of 2,615 nasopharyngeal swabs from children (6–30 months old) attending day care were collected in three periods over 2016–2018. Children’s demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A). Results The carriage prevalence of Sp (&gt; 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017–2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017–2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017–2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (&gt; 44%). Conclusions During and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.
Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020
Authors: Jantien A Backer, Don Klinkenberg, Jacco Wallinga
Journal: Eurosurveillance (2020)

A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.
Survival by line of therapy of older patients with advanced biliary tract cancer (BTC).
Authors: Sarah Bobiak, Mark D. Danese, Deborah P. Lubeck, Michelle L. Gleeson
Journal: Journal of Clinical Oncology (2020)

497 Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.
The potential in artificial intelligence-driven radiomic signature to predict survival in patients with metastatic colorectal cancer treated with cetuximab-based therapy.
Authors: Laurent Dercle, Lin Lu, Lawrence Howard Schwartz, Min Qian, Sabine Tejpar, Peter Eggleton, Binsheng Zhao, Hubert Piessevaux
Journal: Journal of Clinical Oncology (2020)

247 Background: This analysis was undertaken to forecast survival and enhance treatment decisions for patients (pts) with colorectal cancer (CRC) with liver metastases sensitive to folinic acid, fluorouracil and irinotecan (FOLFIRI) alone [F] or in combination with cetuximab [FC] using simple quantitative radiomic changes between CT scans at baseline and 8 weeks. Methods: We retrospectively analyzed 667 pts with KRAS-unselected metastatic CRC in NCT00154102 treated with F and FC. CT quality was classified as high (HQ) or standard (SQ), and four data sets were created and named by treatment quality. Pts were randomly assigned 1:2 to training or validation sets: FC HQ , 38/78 pts; FC SQ , 62/124 pts; F HQ , 51/78 pts; F SQ , 78/158 pts. A machine-learning signature was trained using data set FC HQ to classify pts as treatment-sensitive or treatment-insensitive using just 4 of 3,499 potential radiomic imaging features. Performance was calibrated/validated using ROC curves. Hazard ratios (HRs) and Cox regression models were used to evaluate association with overall survival (OS). Results: The signature used decrease in tumor heterogeneity plus boundary infiltration to successfully predict sensitivity to FC (FC HQ : AUC, 0.80; FC SQ : AUC, 0.72) but failed with non-cetuximab regimens (F HQ : AUC, 0.59; F SQ : AUC, 0.55). The radiomic signature outperformed existing biomarkers ( KRAS mutational status and tumor shrinkage by RECIST 1.1) for sensitivity to cetuximab-based therapy and was strongly associated with OS in the cetuximab-containing sets FC HQ (HR, 44.3; p = 0.0001) and FC SQ (HR, 6.5; p = 0.005). Conclusions: This signature, derived from simple radiomic analysis of tumor imaging phenotype using only standard-of-care CT scans, appeared to be treatment-specific and was superior to all tested prognostic biomarkers. The signature provided early prediction of sensitivity and survival and could be used to guide treatment continuation decisions.
Clinical and genomic factors associated with outcome following ablative radiotherapy for oligometastatic and oligoprogressive liver tumors.
Authors: Danielle Sara Bitterman, Andrzej Niemierko, Emily E. Van Seventer, Daniel W. Kim, Motaz Qadan, Lawrence Scott Blaszkowsky, Jeffrey William Clark, Andrew X. Zhu, Lipika Goyal, Florence Keane, Christine Elissa Eyler, Aparna Raj Parikh, Ryan Bruce Corcoran, Jennifer Yon-Li Wo, Theodore S. Hong
Journal: Journal of Clinical Oncology (2020)

515 Background: There is increasing use of ablative radiotherapy (RT) for oligometastatic and/or oligoprogressive cancer, but the population who may benefit from this more aggressive treatment remains poorly defined. We aimed to identify factors associated with improved outcomes following ablative RT for oligometastatic/oligoprogressive liver tumors. Methods: We retrospectively analyzed 106 patients who had tumor genomic profiling and received a 5, 6, or 15-fraction course of ablative RT for liver metastases from 2008-2019. The interval off systemic therapy post-RT was calculated for patients who did not continue treatment through RT. Overall survival (OS) was estimated using the Kaplan-Meier method. The association between clinical and genomic variables and OS were assessed using uni- and multivariable Cox regression. Results: Median follow-up was 12.6 months. Median age was 61.3 years and 57% were male. The most common primary site was colorectum (42%), followed by pancreas (25%) and non-small cell lung cancer (10%). 42% had colorectal adenocarcinoma, 46% had other adenocarcinoma, and 12% had other histology. A BRAF/RAS family mutation (KRAS, NRAS, and/or BRAF) was present in 41%, 69% had &gt; 1 metastasis, and 38% had extra-hepatic disease. Median biological effective dose (α/β = 10) (BED) was 92 Gy. The RT field encompassed all liver metastases in 91%, and 11% received radiosensitizing chemotherapy. Median time off systemic agents was 5 months. Patients with 1 vs &gt; 1 metastasis had a longer interval off systemic therapy (9 vs 4 months, p = 0.026). Median OS was 12.6 months. The table shows the multivariable Cox model for OS. Conclusions: Presence of a BRAF/RAS family mutation, extra-hepatic metastases, exclusion of liver metastases from RT fields, lower BED, and concurrent radiosensitizing chemotherapy were associated with worse OS. This may inform patient selection and RT delivery for aggressive local therapy for liver metastases. [Table: see text]
Impact of population center (PC) size on access to care in advanced hepatocellular carcinoma (HCC).
Authors: Irene S. Yu, Shiru Lucy Liu, Valeriya O. Zaborska, Tyler Raycraft, Janine Marie Davies
Journal: Journal of Clinical Oncology (2020)

489 Background: To evaluate access to subspecialists, local therapies, treatment at a specialized HCC center, and survival in advanced HCC patients (pts) based on geographical distribution. Methods: Retrospective chart review was performed on HCC pts who received sorafenib in British Columbia from 2008 to 2016. Pts were stratified by Statistics Canada PC size criteria: large urban PC (LUPC), medium urban PC (MUPC), and small urban PC (SUPC). Chi-square tests and Kaplan Meier were used to analyze the groups. Results: Of 288 pts, geographical distribution was: LUPC 75%, MUPC 16%, SUPC 8%, and rural 0.3%. Age, gender, and ECOG performance status were similar; a higher proportion of Asians (50 vs 9 vs 4%), Child Pugh A (93 vs 83 vs 83%), and hepatitis B (37 vs 15 vs 4%) was observed in LUPC vs MUPC and SUPC, respectively. SUPC pts were less likely to see a hepatologist (p=0.04, Table); access to other subspecialists was similar. Pts from LUPC were more likely to have transarterial chemoembolization compared to MUPC and SUPC (38 vs 20 vs 21%; p=0.04); receipt of other local therapies was similar. Sixty percent were treated at a specialized HCC center and were more likely to see a hepatologist (83 vs 19%), hepatobiliary surgeon (57 vs 42%), and/or interventional radiologist (32 vs 13%) (all p&lt;0.01). Median OS was higher for pts treated at a HCC center (24.7 vs 13.2 mo, p&lt;0.01), but similar when stratified by PC size (overall mOS 19.3 mo, p=0.59). Conclusions: Geography did not significantly impact access to care or survival, but pts treated at a specialized HCC center have improved survival. Further research is needed to better understand social and clinical factors that influence these findings. [Table: see text]
Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease
Authors: Esther Lutgens, Tom T.P. Seijkens
Journal: Journal for ImmunoTherapy of Cancer (2020)

The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger arteries, is commonly present in cancer patients. A major concern is the adverse effect of ICI on atherosclerosis-related cardiovascular disease, resulting in cardiovascular events, such as myocardial infarction or ischaemic stroke. The effects of ICI on atherosclerosis in cancer patients are incompletely understood, but it is well known that immune checkpoint proteins orchestrate the inflammatory response underlying atherogenesis. This paper addresses the hypothesis that ICI therapy puts cancer patients at an increased risk for atherosclerosis-related cardiovascular disease, that might only become apparent years after ICI therapy. Until clinical and experimental studies have addressed this hypothesis, optimal cardiovascular risk management in ICI-treated patients is opportune to reduce the occurrence of cardiovascular disease in cancer patients and long-term cancer survivors.
A phase Ib study of troriluzole (BHV-4157) in combination with nivolumab.
Authors: Ann W. Silk, Biren Saraiya, Roman Groisberg, Nancy Chan, Kristen Renee Spencer, Eugenia Girda, Weichung Shih, Veeraswamy Manne, Marisa Palmeri, Robert Berman, Vlad Coric, Joshua Vieth, Suzie Chen, Janice M. Mehnert, Jyoti Malhotra
Journal: Journal of Clinical Oncology (2020)

79 Background: The Metabotropic Glutamate Receptor 1 (GRM1) is overexpressed in many solid tumors. It activates MAPK and PI3K/AKT pathways and promotes an immune-suppressive tumor microenvironment. In an immunocompetent melanoma mouse model, GRM1 blockade using riluzole or its pro-drug troriluzole (BHV-4157) and PD-1 blockade inhibit tumor growth in an additive manner. We conducted a phase Ib trial of troriluzole and the PD-1 antibody nivolumab. Methods: Patients with advanced or refractory solid tumors were treated with increasing doses of troriluzole. Troriluzole monotherapy was given for a 14-day lead-in period and then patients received troriluzole in combination with nivolumab 240 mg IV every 2 weeks. Results: We enrolled 14 patients with advanced solid tumors (melanoma=3, NSCLC=3, renal cell cancer=2, NSCLC=2, head and neck cancer=2). Eleven patients had prior therapy with anti-PD-(L)1. PK sampling demonstrated that the prodrug was cleaved efficiently without regard to food (Table). The most common TEAEs (all grades) occurring in &gt;40% of patients were transaminitis, increased lipase and nausea. DLT occurred in 3 patients: 1) grade 3 anorexia, 2) grade 3 fatigue and, 3) atrial fibrillation. The MTD was determined to be troriluzole 140 mg QAM + 280 mg PO QHS. The response rate was 7 % (1/14); this occurred in a PD-L1 treated patient. The 6-month PFS rate was 21%. Correlative studies will be presented. Conclusions: The combination of troriluzole and nivolumab was safe and well-tolerated in this highly PD-1 refractory population. Clinical trial information: NCT03229278. [Table: see text]
Neuropeptide regulation of secretion and inflammation in human airway gland serous cells
Authors: Derek B. McMahon, Ryan M. Carey, Michael A. Kohanski, Charles C.L. Tong, Peter Papagiannopoulos, Nithin D. Adappa, James N. Palmer, Robert J. Lee
Journal: European Respiratory Journal (2020)

Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO 3 − ), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15–20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pH i ), reflecting activation of Cl − and HCO 3 − secretion, respectively. HCO 3 − secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl − /HCO 3 − secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO 3 − secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl − and HCO 3 − secretion.
Plasma PD-L1 levels according to histologic grade and IDH status in patients with gliomas.
Authors: Santiago Cabezas-Camarero, Vanesa García-Barberán, Rebeca Pérez-Alfayate, María L. Gandía, Isabel Díaz-Millán, Pedro Pérez-Segura
Journal: Journal of Clinical Oncology (2020)

69 Background: Plasma immune biomarkers such as soluble plasma PD-L1 (sPD-L1) may serve as surrogates of the immune condition of cancer patients and be potential markers of response to different immunotherapy modalities. Very few data exist regarding sPD-L1 in patients with primary brain tumors. Our aim was to study the levels of sPD-L1 in patients with gliomas according to histologic grade and IDH mutation status. Methods: Patients (pts) with grade II to IV gliomas were prospectively enrolled. Single-time-point plasma samples were obtained prior to adjuvant radiotherapy +/- chemotherapy. sPD-L1 determined using ELISA with a rabbit polyclonal anti-PDL1/CD274 antibody as capture reagent. Results: Between February 2017 and August 2019, 44 patients (pts) with gliomas and 12 healthy controls (HC) were enrolled. N=11 grade II, n=9 grade III, n=24 grade IV; n=26 IDHwt, n=18 IDHmut. Higher sPD-L1 levels in glioma pts compared to HC (60.8 vs 47.8 ng/ml, p=0.05). Higher sPD-L1 levels in grade II vs grades III-IV (73.3 vs 60 ng/ml, p=0.09). Higher sPD-L1 in IDHmut grades II-III vs IDHwt grades II-III + IDHmut/wt grade IV (73 vs 59 ng/ml, p=0.07). Non-significantly higher sPD-L1 in grades II-III vs grade IV (73 vs 59 ng/ml, p=0.46). No difference in sPD-L1 in IDHmut vs IDHwt (63.3 vs 59.1 ng/ml, p=0.496), nor in IDHwt vs HC (59.1 vs 47.8 ng/ml, p=0.109). Trend to significance in IDHmut vs HC (63.3 vs 47.8, p=0.062). Conclusions: sPD-L1 levels were significantly higher in glioma pts compared to HC. A trend was seen towards higher sPD-L1 levels in lower-grade (grades II, III) IDHmut gliomas. These findings may indicate a different systemic immune profile for currently defined glioma groups based on histologic grade and IDH status and merit confirmation in a larger sample.
Prognostic significance of familial pancreatic cancer after surgery.
Authors: Koji Tezuka, Yukiyasu Okamura, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Katsuhisa Ohgi, Katsuhiko Uesaka
Journal: Journal of Clinical Oncology (2020)

772 Background: Familial pancreatic cancer (FPC) is defined as two first-degree relatives with pancreatic cancer. It is known that the risk of developing pancreatic cancer increases in those who have a family history of pancreatic cancer in first-degree relatives. However, prognostic significance of FPC after surgery is not fully understood. Methods: Patients who underwent pancreatectomy for pancreatic ductal carcinoma between January 2008 and December 2016 were retrospectively reviewed. The prognostic significance of FPC was analyzed. Results: A total of 423 patients underwent pancreatectomy for pancreatic ductal carcinoma. FPC was identified in 32 (7.6%) patients. Recurrence occurred in 72% of all resected cases and in 88% of resected FPC cases. Multivariate analysis revealed FPC (hazard ratio [HR] 1.60; P=0.026), CA19-9 ≥300 U/ml (HR 1.54; P=0.001), lymph node metastasis (HR 2.10; P&lt;0.001), microscopic venous invasion (HR 1.64; P&lt;0.001), nerve plexus invasion (HR 1.39; P=0.010), R1 resection (HR 1.65; P=0.010), and lack of adjuvant chemotherapy (HR 2.27; P&lt;0.001) as independent predictors for recurrence-free survival (RFS). The univariate analysis revealed that FPC is significantly associated with worse overall survival (OS) (P=0.018). The multivariate analysis showed that FPC was not an independent predictor of OS. This cohort was divided into 314 patients (FPC: 18 patients, non-FPC: 296 patients) who received adjuvant chemotherapy (AC group) and 109 patients (FPC: 14 patients, non-FPC: 95 patients) received no adjuvant chemotherapy (no AC group). In AC group, FPC is an independent predictor for RFS (HR 3.03; P&lt;0.001) and OS (HR 2.23; P=0.018). In no AC group, FPC is not a predictor for RFS and OS. Conclusions: This study may show that FPC has a significant impact on RFS and OS after resection in patients who received adjuvant chemotherapy.
Diagnosis of severe respiratory infections in immunocompromised patients
Authors: Elie Azoulay, Lene Russell, Andry Van de Louw, Victoria Metaxa, Philippe Bauer, Pedro Povoa, José Garnacho Montero, Ignacio Martin Loeches, Sangeeta Mehta, Kathryn Puxty, Peter Schellongowski, Jordi Rello, Djamel Mokart, Virginie Lemiale, Adrien Mirouse
Journal: Intensive Care Medicine (2020)