tbuckley/cabot-search huggingface dataset:
Influence of radiation therapy on the outcome of T1-2N0M0 triple-negative breast cancer: A SEER population-based retrospective analysis.
Authors: Xiaoxiang Guan, Huan Li, Yajuan Chen, Xin Wang, Lin Tang, Yucai Wang, Yongqian Shu
Journal: Journal of Clinical Oncology (2019)

e12073 Background: For T1-2N0M0 breast cancer after surgery and axillary staging, the current NCCN guideline recommends radiation therapy (RT) after lumpectomy but not total mastectomy unless there is a positive or less than 1 mm negative margin. This recommendation is regardless of hormonal status. Triple-negative breast cancer is a generally considered more aggressive compared with hormone positive breast cancer. We sought to investigate whether there is a survival benefit of RT in T1-2N0M0 TNBC. Methods: A Population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into three groups according to surgery modality and RT: breast conservation therapy (BCT, i.e., lumpectomy + RT), mastectomy alone, and mastectomy + RT. The survival endpoints were breast cancer-specific survival (BCSS) and overall survival (OS), and survival analysis was performed using the Kaplan-Meier method. Results: A total of 22473 female with T1-2N0M0 TNBC diagnosed between 2010 and 2015 were included, with 13395 (60%) T1 and 9078 (40%) T2 cases. Surgery, RT and chemotherapy was done in 21674 (96%), 9633 (43%) and 14651 (65%) patients, respectively. Patients who underwent RT were older ( &gt; 50 years, 78% vs 72%, P&lt; 0.001), had fewer T2 (35% vs 44%, P&lt; 0.001) tumor, and had more chemotherapy utilization (72% vs 60%, P&lt; 0.001). 8807 patients had BCT; 8329 had mastectomy alone and 635 had mastectomy + RT. The 5-year BCSS rate was 94.3% for BCT, 93.3% for mastectomy alone ( P= 0.009 vs BCT), and 83.7% for mastectomy + RT ( P&lt; 0.001 vs BCT and P&lt; 0.001 vs mastectomy alone), respectively. The 5-year OS rate was 88.6% for BCT, 83.0 % for mastectomy alone ( P&lt; 0.001 vs BCT), and 79.6% for mastectomy + RT ( P&lt; 0.001 vs BCT and P= 0.190 vs mastectomy alone), respectively. Conclusions: In patients with T1-2N0M0 TNBC, BCT was associated with superior BCSS and OS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT, with worse BCSS and similar OS.
Differences in prescribing and patient demographics of cki agents among United States patients &lt; 65 and 65+ years old.
Authors: William H Angel, Alessandra Franceschetti
Journal: Journal of Clinical Oncology (2019)

e14097 Background: Since FDA approval, immune checkpoint inhibitors (CKIs) have become increasingly important in treating NSCLC, particularly among mutation-negative patients who did not benefit from biomarker testing. Because clinical trials typically recruit healthy patients, little information is available to understand the role of CKIs in treating older patients, who also face immunosenescence. This study explores differences in prescribing behavior of CKIs for mutation-negative NSCLC patients &lt; 65 y/o and 65+ y/o in the US and satisfaction with results. Methods: The Ipsos Global Oncology Monitor: an online multi-center medical chart review study of stage IIIb-IV NSCLC patients currently receiving drug treatments seen in consultation from June – November 2018. 170 US physicians provided de-identified data on 1484 patients negative or untested for EGFR, ALK, ROS1 and BRAF. Results: Compared to patients &lt; 65 y/o (n = 539), those 65+ y/o (n = 945) were prescribed a CKI significantly more often, 63% vs 70% (p &lt; 0.01), driven by CKI monotherapy (CKIm) use, 47% vs 55% (p &lt; 0.01). This trend was seen among patients on 1L therapy (n = 1015), with 42% of patients &lt; 65 y/o and 50% of patients 65+ y/o on CKIm (p &lt; 0.05), and on 2L therapy (n = 337), with 62% of patients &lt; 65 y/o and 76% of patients 65+ y/o on CKIm (p &lt; 0.01). In both lines, this was due to more use of nivolumab among 65+ y/o patients (p &lt; 0.01), while among 2L patients &lt; 65 y/o there was also greater use of pembrolizumab (p &lt; 0.05). Physicians’ stated satisfaction with 1L CKI results was similar in both cohorts but, at 2L, greater among patients 65+ y/o (μ = 8.45; σ x̅ = 1.26) vs patients &lt; 65 y/o (μ = 8.01; σ x̅ = 1.38) (p &lt; 0.05). Older 2L CKIm patients were more likely to be ECOG 2+ (18% vs 5%; p &lt; 0.01) and to have 2+ concomitant conditions (60% vs 36%p &lt; 0.01). Conclusions: Satisfaction with 2L CKIs is higher in older vs younger patients, despite the former’s association with poorer outcomes. Potentially, lower expectations at treatment initiation caused higher satisfaction for similar treatment success, but this may also be due to immunosenescence, one study suggesting CKIs are more effective in older melanoma patients ( https://dx.doi.org/10.2147%2FOTT.S165368 ). The role of age in CKIs’ efficacy in NSCLC merits further investigation.
Apatinib inhibits tumor progression and promotes antitumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma.
Authors: Yanyan Chi, Feng Wang, Xiangrui Meng, Zhengzheng Shan, Yan Sun, Qingxia Fan
Journal: Journal of Clinical Oncology (2019)

e15554 Background: Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumors. The function and mechanism of Apatinib in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: The expression of VEGFR-2 in ESCC cell lines (KYSE450, EC1, KYSE410, KYSE70) were detected by western blot. KYSE450 and EC1 cell lines were treated with Apatinib, or combined with cytotoxic drugs: paclitaxel (TAX), 5-fluorouracil (5-FU) or cisplatin (DDP) respectively. Cell proliferation was then measured using CCK-8 assay; cell apoptosis was analyzed by flow cytometry; cell migration and invasion were evaluated by wound healing and transwell assays. The expression of VEGFR-2, Bcl2, MMP-2/MMP-9, p-Akt and p-mTOR in KYSE450 and EC1 cell lines were determined by western blot. Esophageal cancer xenografts model was established and used to evaluate the antitumor effects of combination of Apatinib and cytotoxic drugs in vivo. Immunohistochemistry was used to detect the expression of Ki67, VEGFR-2 and CD31 in tumor tissues of esophageal cancer xenografts model. Results: We found that Apatinib efficiently inhibited cell growth, metastasis and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that Apatinib significantly increased Bax protein levels, decreased VEGFR-2, Bcl2, MMP-2/MMP-9, p-Akt and p-mTOR protein levels in ESCC cells. Moreover, Apatinib enhanced chemosensitivity of cytotoxic drugs TAX, 5-FU and DDP by upregulating expression of Bax protein, and downregulating expression of VEGFR-2, Bcl2, MMP-2/MMP-9 protein in vitro. Compared with single agent groups, the combination of Apatinib with each chemotherapeutic drug significantly repressed tumor growth and angiogenesis through blocking the expression of Ki67, VEGFR-2 and CD31 in vivo. Conclusions: Taken together, Apatinib suppressed cell growth, migration and invasion, and promoted antitumor effect of chemotherapeutic agents in ESCC.
Cycling and cardiovascular disease risk factors including body composition, blood lipids and cardiorespiratory fitness analysed as continuous variables: Part 2—systematic review with meta-analysis
Authors: Solveig Nordengen, Lars Bo Andersen, Ane K Solbraa, Amund Riiser
Journal: British Journal of Sports Medicine (2019)

Objectives We aimed to examine the relationship between cycling (particularly commuter cycling) and risk factors associated with cardiovascular diseases (CVDs) including body composition, blood lipids and cardiorespiratory fitness. This study differed from our recent (Part 1) systematic review in that risk factors for CVD were analysed as continuous variables rather than being present or absent. Design Systematic review and meta-analysis. Eligibility criteria We searched four databases (Web of Science, MEDLINE, SPORTDiscus and Scopus). All quantitative studies, published until August 2017, were included when a general population was investigated, cycling was assessed either in total or as a transportation mode, and CVD risk factors were reported. Methods We analysed body composition, physical activity (PA), cardiorespiratory fitness (CRF), blood lipids and blood pressure (BP). Skinfold, waist circumference and body mass index were analysed and prioritised in that order when more than one measure were available. PA included measures of counts per minutes, moderate-to-vigorous PA or minutes per week. CRF included results of maximal tests with or without expired air or submaximal test. For blood lipids and BP, separate analyses were run for low-density and high-density lipoprotein, triglycerides, total cholesterol, systolic BP and diastolic BP. Studies were excluded when reporting dichotomous outcomes or when cycling and walking were combined. Heterogeneity was investigated using I 2 . Results Fifteen studies were included; the majority reported commuter cycling. In total, we included 5775 cyclists and 39 273 non-cyclists. Cyclists had more favourable risk factor levels in body composition −0.08 (95% CI −0.13 to −0.04), PA 0.13 (95% CI 0.06 to 0.20), CRF 0.28 (95% CI 0.22 to 0.35) and blood lipids compared with non-cyclists. There was no sex difference in risk reduction. Conclusion/implication Cycling mitigated the risk factor profile for CVD. A strength of this systematic review is that all the risk factors were analysed as continuous variables. These data provide evidence for practitioners, stakeholders, policy-makers and city planners to accommodate and promote cycling. Systematic review registration PROSPERO CRD42016052421.
Identifying actionable somatic mutations in lung cancer using cell-free DNA from bronchial washing fluid.
Authors: Xin Zhang, Xinyu Zhang, Weiran Wang, Jian'An Huang, Min Zhou, Chun Li, Maosong Ye, Yancheng Zhao, Yuhua Gong, Yaping Xu, Qin Hu, Yanfang Guan, Ling Yang, Xuefeng Xia, Hua Zhang, Tao Ren, Qian Shen, Kai Wang, YY Hou, Xin Yi
Journal: Journal of Clinical Oncology (2019)

8528 Background: Bronchial washing is the most common technique for sampling the components of the alveolar space. Here, we evaluated the potential use of bronchial washing fluid (BWF) in liquid biopsy in lung cancer. Methods: This study enrolled 65 lung cancer patients. BWF (separated supernatant and precipitate) samples, peripheral blood lymphocytes (PBL) and formalin-fixed paraffin-embedded tissues were obtained and subjected to next-generation sequencing using a 1021-gene panel. Results: Mutations were identified in 58 (89.2%) of BWF precipitate (BWFp) samples and 64 (98.5%) of BWF supernatant (BWFs) samples, comparing with 61 (93.8%) of tumor tissues. In total, 461 somatic mutations were identified in tissues, of which 331 (71.8%) and 381 (82.6%) were detected in the matched BWFp and BWFs samples. In addition, there were 44.6% of patients carrying actionable variants identified in tissue DNA, including EGFR, ALK, ROS1, RET, etc. (Table). Similarly, there were 40.0% of BWFp samples and 44.6% of BWFs samples identified actionable variants. Moreover, tumor mutation burden (TMB) was also calculated. Nearly 9% of BWFp samples and 23% of BWFs samples were TMB-H (more than 9 mutations per megabase), comparing with 20% of tissues. Significantly, the combined results of three types of samples showed that, 49.2% of patients carrying actionable variants and 24.6% of patients with TMB-H, which suggested more patients benefit from targeted therapy or immunotherapy. Conclusions: In summary, liquid biopsy using BWF showed high potential to identify actionable mutations and to calculate TMB grade of patients with lung cancer, which might be implemented and standardized into clinical use. [Table: see text]
Meta-analysis of prognostic biomarkers for pancreatic neuroendocrine tumors (PNETs).
Authors: Mojun Zhu, Thorvardur Ragnar Halfdanarson, Bonnie Elyssa Gould Rothberg
Journal: Journal of Clinical Oncology (2019)

e15688 Background: PNETs are marked by histological heterogeneity and variable clinical outcomes. Other than Ki67 index, reliable circulating or tissue biomarkers for prognosis do not exist. Methods: PubMed was searched through 01/31/2017. Inclusion criteria were: 1) prospective/retrospective cohort with defined source population, boundary dates, and justifications for exclusions; 2) assay of primary tumors; 3) clear descriptions of methods including techniques and controls; 4) use of multivariate proportional hazards modeling adjusted for prognostic factors including but not limited to stage or grade; and 5) reporting adjusted hazard ratios (HR) with 95 % confidence intervals and P values. Studies with &lt; 50 % PNETs were excluded. PNET-specific data was summarized in the table. Results: A total of 2958 manuscripts were identified and 462 manuscripts were reviewed. Only 23 multivariate studies met all inclusion criteria. These altogether analyzed 24 unique targets and 14 were associated with survival. Conclusions: This meta-analysis identified 14 markers associated with survival of PNET patients. Future studies should adhere to the REMARK criteria and incorporate the 2017 WHO grading system for multivariate analysis. 1. I-immunohistochemistry, F-fluorescence in situ hybridization, E-enzyme linked immunosorbent assay, M- methylation specific PCR, P-polymerase chain reaction; 2. O-overall survival, F-disease free survival, S-disease specific survival, P- progression free survival.[Table: see text]
Factors predicting poor survival in early gastric cancer: A SEER analysis.
Authors: Yanal Mufeed Alnimer, Ayman Qasrawi, Khalil Katato
Journal: Journal of Clinical Oncology (2019)

e15548 Background: The benefit of adjuvant treatment in gastric adenocarcinoma patients with muscularis propria involvement but not beyond is unclear. We aim to establish a model that identifies the factors that could adversely affect the prognosis in these patients, whom could potentially benefit from adjuvant treatment. Methods: We used the Surveillance, Epidemiology, and End Results Program (SEER) database to identify subjects with stage T2aN0M0 gastric adenocarcinoma according to the 6 th AJCC TNM staging system who underwent tumor resection between 2004-2015. The effect of the following factors on the 5-year overall survival (OS) was evaluated using Kaplan-Meier analysis: demographics, tumor size, grade and site, number of lymph nodes (LNs) being examined and extent of surgery. Factors with a P value &lt; 0.1% in log-rank test were entered in a Cox proportional hazard ratio (HR) model. Results: We identified 1337 patients who met the inclusion criteria. After a median follow-up of 42 months (1-60), the 5-year OS was 64% with the median being unreached. The following factors were significantly associated with shorter OS in univariate analysis: Age &gt; 60 years with a HR = 1.86 (95% CI 1.49-2.32), Non-Hispanics excluding non-Hispanic Asian and Pacific Islanders with a HR = 1.87 (95% CI 1.54-2.28), patients with less than 15 lymph nodes examined at the time of surgery with a HR = 1.86 (95% CI 1.52-2.26), tumors at the fundus and cardia of the stomach compared to other sites with a HR = 1.73 (95% CI 1.37-2.15), those who underwent endoscopic resection with a HR = 2.27 (95% CI 1.16-4.4) and those who didn’t receive chemotherapy with a HR = 1.23 (95%CI 1.001-1.52) . On multivariate analysis; the following factors were predictors for worse OS; Age &gt; 60 years with a HR = 1.97 (95% CI 1.46-2.65), Non-Hispanics excluding non-Hispanic Asian and Pacific Islanders with a HR = 1.45 (95%CI 1.10-2.00), those in whom less &lt; 15 LNs were examined at the time of surgery with a HR = 1.75 (95% 1.38-2.22) and gastric adenocarcinoma at the cardia and fundus with a HR = 1.50 (95%CI 1.20-1.86). Conclusions: Patients with T2aN0M0 gastric adenocarcinoma, and one of the adverse prognostic factors in our Cox-proportional hazard ratio model need to be studied for possible benefit of adjuvant treatment.
Abstract 15777: Preconditioning With Whole Body Periodic Acceleration (pGz) Protects Cardiomyocytes From Hypoxia-Reoxygenation Injury
Authors: Jose R Lopez, Juan Kolster, Arkady Uryash, Francisco Altamirano, Jose A Adams
Journal: Circulation (2015)

Hypoxia and Reoxygenation (H-R) injury of the heart induces increase in diastolic Ca 2+ ([Ca 2+ ] d , and reactive oxygen species (ROS) leading to cellular death and myocardial dysfunction. pGz is the repetitive head-foot motion of the body inducing pulsatile shear stress, activating endothelial nitric oxide synthase (eNOS) to produce small quantities of eNO. eNO is cardioprotective and active in varied signaling pathways. We showed that preconditioning with pGz (pre-pGz) decreased myocardial injury from focal myocardial injury (MI) and cardiac arrest and increases the level and activity of endogenous antioxidants Hypothesis: pre-pGz confers cardioprotection in a cellular model of H-R injury. Methods: Mice (n=30) were randomized to pGz (f=480cpm, Gz 3.0mt/sec 2 ,1 hr /d for 8 days) or none (CONT). Cardiomyocytes were isolated and exposed to 45 min hypoxia, followed by 15min reoxygenation (H-R). Resting membrane potentials (Vm) and [Ca 2+ ] d were measured with microelectrodes. Intracellular ROS and glutathione peroxidase activity (GPx) were measured during normoxia and after H-R. In a separate group of mice, L-NAME was administered for 5 days along with pre-pGz prior to H-R (L-NAME+pGz+H-R). Results: Resting membrane potentials (Vm) were decreased by H-R and restored by pre-pGz. A 15x (fold) increase in [Ca 2+ ] d and 5x increase in ROS production occurred in H-R that was blunted by pre-pGz. GPx activity was decreased but pre-pGz restored it. Pretreatment with L-NAME to pre-pGz animals abolished the effects of pGz. (FigureM±SD***p&lt;0.001) Conclusion: Cardioprotection by pGz from H-R injury is in part due to a decrease in membrane depolarization, improved Ca 2+ homeostasis and reduction of ROS as well as increasing the level and activity of antioxidants. Such benefits are partially mediated via NO pathway. pGz is a novel, method of eliciting cardioprotection in hypoxic injury.
Results of NGS panel of hereditary breast and ovarian cancer in Lebanese women.
Authors: Joseph Al Ajami, Nadine Jalkh, Ghadi Moubarak, Roland Eid, Fady Haddad, Joseph Gergi Kattan, Marwan Ghosn, David M. Atallah, Eliane Chouery Khoury, Hampig Raphael Kourie
Journal: Journal of Clinical Oncology (2019)

e13045 Background: Hereditary breast (BC) and ovarian cancer (OC) genetic alterations are considered the most prevalent among familial cancer. To date, four studies have exposed the mutations related to hereditary BC predisposition in the Lebanese population , with percentage of BRCA-related pathogenic mutations ranging between 5 % and 15 %. Methods: Between 2017 and 2019, 117 patients with high risk hereditary breast and ovarian cancer were referred to undergo the testing at the Unité de Génétique médicale (UGM) of Saint-Joseph University of Beirut, Lebanon. The sequencing was accomplished by using the 21-panel Next-Generation Sequencing (NGS) method for all of our patients, to which we also added the MLPA technique followed by the Sanger sequencing for validation whenever a genetic alteration was found. Results: From 117 Lebanese women with high-risk hereditary breast and ovarian cancer predisposition, 19 pathogenic mutations were identified in this study: 11 BRCA1, 1 BRCA2, 2 PALB2, 1 ATM, 1 CDH1, 1 MSH6, 1 RAD51C, and 1 BRIP1. Among those, 13 patients had BC, one had OC and five were healthy individuals. Five similar mutations were found within the BRCA1 gene, the p.C44F mutation, accounting for 45.4 %, thus suggesting a founder effect. Average age at diagnosis in the BC patients carrying a mutation was 41 years and 38.5% had a triple negative BC. Conclusions: The overall pathogenic mutation rate was equal to 16.2% while the BRCA deleterious mutation rate was 10.3% lower to those reported in the literature. The p.C44F mutation appeared five times suggesting a founder effect. [Table: see text]
Comparison of two dose calculation methods of intra-arterial carboplatin in the treatment of recurrent glioblastoma multiforme.
Authors: Brigitte Boilard, Alexandra Hinse, Karianne Beaulieu, Florence Marcotte, David Fortin, Marie-Constance Lacasse, Thomas joly-Mischlich, Gabrielle Ferland
Journal: Journal of Clinical Oncology (2019)

e13503 Background: Glioblastoma is a deadly brain cancer, and as part of the natural evolution, its relapses will mostly occur 32 to 36 weeks after the initial diagnosis. The standard of care for recurrent glioblastomas is not well defined and multiple options exist. Intra-arterial chemotherapy as one option is currently practiced at the Centre hospitalier universitaire de Sherbrooke, the only center doing this procedure in Canada. The aim of this study is to evaluate the impact of using the area under the curve (AUC) or body surface area (BSA) dosing formula to guide intra-arterial carboplatin administration. It was designed to explore the relation of two dose calculation methods on efficacy and toxicity, determined by progression-free survival (PFS) and hematologic toxicity, respectively. Methods: A retrospective observational study was conducted, which includes adult in-patients who received intra-arterial carboplatin for recurrent glioblastoma from June 1st, 2000 to December 31st, 2017. It examined the associations of the method used to calculate the doses, in mg or mg/mL x min-1, with clinical outcomes. Results: One hundred ninety patients were included in the analysis. For the primary endpoint, an exposure greater than 6 of AUC was found potentially harmful in terms of efficacy compared to AUC under 6 (HR 0.529, p = 0.0044). In terms of toxicity, a higher AUC is highlighted to correlate with a slightly higher incidence of thrombocytopenia and neutropenia (OR 1.051 p = 0.0271; OR 1.072 p = 0.049). No significant association between toxicity and dose calculated with BSA could be established. Conclusions: AUC greater than 6 is detrimental in terms of effectiveness according to progression free survival. Moreover, AUC could be used to predict neutropenia and thrombocytopenia. However no significant predictions were found using BSA method. We recommend the use of AUC method in intra-arterial carboplatin instead of BSA method since the latter was not statistically related to toxicity. A prospective trial comparing the two dosage methods would be needed.