bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of postoperative complications on oncologic outcomes after rectal cancer surgery: An analysis of the United States Rectal Cancer Consortium.
Authors: Gamboa Adriana C. , Lee Rachel M. , Turgeon Michael K. , Varlamos Christopher , Regenbogen Scott E. , Hrebinko Katherine , Holder-Murray Jennifer , Wiseman Jason T. , Ejaz Aslam , Feng Michael P. , Hawkins Alexander , Bauer Philip , Silviera Matthew , Maithel Shishir K. , Balch Glen C. 
Published: February 2020

41 Background: Postoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not known. Methods: The US Rectal Cancer Consortium (2007-17) was reviewed for patients with primary rectal adenocarcinoma who underwent R0/R1 low anterior resection (LAR) or abdominoperineal resection (APR). 90-day POCs were categorized as major vs minor and grouped into infectious, cardiopulmonary (CP), thromboembolic (TE), renal, or intestinal dysmotility. Primary outcomes were 5-yr overall survival (OS) and recurrence-free survival (RFS). Results: Of 1136 pts, median age was 59 yrs (IQR 51-67), 61% were male (n = 693), median f/u was 31 mos (IQR 13-54). 70% underwent LAR (n = 799) and 30% APR (n = 337). Complication rate was 46% (n = 527), with 63% minor (n = 330) and 32% major (n = 170). Of all POCs, infectious complications comprised 20% (n = 105), cardiopulmonary 3% (n = 14), thromboembolic 5% (n = 25), renal 9% (n = 46) and intestinal dysmotility 19% (n = 100). When compared to minor or no POCs, major POCs were associated with both worse RFS (48 vs 63 vs 76% p < 0.01) and OS (64 vs 76 vs 80% p < 0.01). While a single POC was associated with worse RFS (61 vs 76% p < 0.01), multiple POCs were associated with worse OS (62% vs 79% p = 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (56 vs 76% p < 0.01) while CP and TE POCs were associated with worse OS (CP 40 vs 78% p < 0.01; TE 63 vs 78% p < 0.01). Postoperative renal dysfunction was associated with both worse RFS (26 vs 76%, p < 0.001) and OS (62 vs 78% p = 0.01). This persisted on MV analysis for OS when accounting for pathologic stage, receipt of neoadjuvant therapy, and final margin status (CP: HR 3.6 p = 0.01; TE: HR 19.4 p < 0.01; renal: HR 2.4 p = 0.01) and for RFS (infectious: HR 2.1 p < 0.01; renal: HR 3.2 p < 0.01). Conclusions: Major complications after proctectomy for cancer are associated with decreased recurrence-free and overall survival. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.
Correlation of tumor mutation with efficacy in patients with gastric cancer who received nivolumab and ramucirumab combination therapy.
Authors: Nakayama Izuma , Shoji Hirokazu , Hara Hiroki , Esaki Taito , Machida Nozomu , Nagashima Kengo , Aoki Kazunori , Honda Kazufumi , Takahari Daisuke , Miyamoto Takahiro , Boku Narikazu , Kato Ken 
Published: February 2020

413 Background: Nivolumab (Nivo) plus ramucirumab (Ram) showed promising efficacy in the second-line chemotherapy for advanced gastric cancer (AGC) in NIVORAM study with the 44% of objective response rate (ORR) and 38.6% of 6-month progression free survival (PFS) rate. We investigated the correlation of tumor mutation load and efficacy. Methods: Patients received Nivo (3mg/kg, Q2W) in combination with Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. Tissue samples were collected before the treatment, and analyzed for tumor mutation load using Oncomine Tumor Mutation Load Assay. Efficacy included ORR, overall survival (OS), PFS and duration of response. OS and PFS curves were estimated using the Kaplan-Meier method. Hazard ratio (HR) was estimated using the Cox proportional hazards model. Results: By the data cut off of December 15, 2018, the median follow duration on therapy was 13.7 month. Thirty AGC pts who obtained tissue sample were analyzed. Median tumor mutation load (TML) was 6.755 mutation/Mb (range 0.84-19.67). Higher TML (cut-off median) related to better tendency of efficacy with ORR (40.0% vs 20.0%), PFS (5.32 vs 2.33 months) and OS (18.1 vs 10.6 months). 6-month PFS rate was better in TML higher group (48%) compared to TML lower group (18%). In multivariate analysis, higher TML showed 2.030 of hazard ratio (95% CI; 0.849-4.855, p-0.112) for PFS, and 1.915 (95% CI; 0.578-6.343, p=0.287) for OS. Conclusions: The patients with higher tumor mutation load have a better tendency for OS and PFS, among AGC patients who received Nivo and Ram combination therapy. Clinical trial information: NCT02999295.
Molecular landscape of gastric cancer (GC) harboring mutations of histone methyltransferases.
Authors: Wang Jingyuan , Xiu Joanne , Baca Yasmine , Goldberg Richard M. , Philip Philip Agop , Seeber Andreas , Battaglin Francesca , Arai Hiroyuki , Soni Shivani , Tokunaga Ryuma , Zhang Wu , Hwang Jimmy J. , Shields Anthony Frank , Marshall John , Astsaturov Igor A. , Lockhart Albert Craig , Gatalica Zoran , Korn W. Michael , Lenz Heinz-Josef 
Published: February 2020

418 Background: Alteration of histone modifications participating in transcription and genomic instability, has been recognized as an important role in tumorigenesis. Aberrant expression of histone-lysine N-methyltransferase 2 ( KMT2) family, which methylate histone H3 on lysine 4, is significantly correlated with poor survival in GC. Understanding how gene mutations of KMT2 family interact to affect cancer progression could lead to new treatment strategies. Methods: A total of 1,245 GC were analyzed using next-generation sequencing (NGS) and immunohistochemistry (IHC; Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous mutations, and MSI status was evaluated by a combination of IHC, fragment analysis and NGS. PD-L1 status was analyzed by IHC (SP142). Gene fusions were detected by Archer (N = 59) or whole-transcriptome sequencing (N = 129). Results: The overall mutation rate of genes in KMT2 family was 10.6% ( KMT2A: 1.7 %, KMT2C: 4.7%, KMT2D: 7.1%). Overall, the mutation rates were significantly higher in KMT2-mutated (MT) GC than KMT2-wild type (WT) GC, except for TP53 (43% vs 63%, p < .0001). Interestingly, among the genes with significant higher mutation rates in KMT2-MT GC, 28% (21/76) of them were related to DNA damage repair (including BRCA1/ 2, RAD50) and 33% (25/76) of them were related to chromatin remodeling (including ARID1A/ 2, SMARCA4). Overexpression of HER2, amplifications of KRAS, CDK6 and HER2 were significant lower, while PCM1 and BCL3 amplifications were significant higher in KMT2-MT, compared to KMT2-WT GC ( p < .05). Significantly higher prevalence of TMB-high ( > 17mut/MB) (49% vs 3%), MSI-H (53% vs 2%), and PD-L1 overexpression (20% vs 7%) were present in KMT2-MT GC, compared to KMT2-WT GC ( p < .001). The rates of fusions involving ARHGAP26 (19% vs 3%, p < .01)and RELA (29% vs 0%, p < .0001) were significantly higher in KMT2-MT than those in KMT2-WT GC. Conclusions: This is the largest study to investigate the distinct genomic landscape between KMT2-MT and WT GC. Our data indicates that KMT2-MT GC patients could potentially benefit from agents targeting DNA damage repair and immunotherapy, which warrants further in-vitro and in-vivo investigation.
Utility of PET-CT CMR after neoadjuvant chemotherapy with DCF for esophageal cancer as a predictive factor of recurrence.
Authors: Kosuke Suzuki , Tomotaka Shibata , Kohei Nishiki , Shoichi Fumoto , Takahiro Hirarsuka , Kohei Kono , Tomonori Akagi , Manabu Tojigamori , Yoshitake Ueda , Hidefumi Shiroshita , Tsuyoshi Etoh , Norio Shiraishi , Masafumi Inomata 
Published: February 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.
Etiological involvement of weak acid reflux in the development of esophageal carcinoma.
Authors: Kono Toru , Sadatomi Daichi , Fujitsuka Naoki , Miyashita Tomoharu , Kaneko Atsushi , Yamamoto Masahiro 
Published: February 2020

435 Background: Patients with gastroesophageal reflux disease (GERD) with mixed gastric acid–bile acid reflux are at a high risk of developing reflux-induced esophageal cancer. Increased local production of prostaglandin E2 (PGE2) is etiologically associated with reflux-induced esophageal cancer pathogenesis; however, the underlying mechanism remains unclear. Our aim was to investigate the relationship between PGE2 production in esophageal cells and reflux fluids, particularly gastric acid. The effect of the Kampo medicine Hangeshashinto (HST), which reduced the incidence of reflux-induced esophageal cancer in rats (Surgery 2018), on PGE2 production was also examined. Methods: Esophageal squamous cell carcinoma were treated for 2 h with acidic culture condition (pH 3.5 – 6.5) and chenodeoxycholic acid (CDCA; 200, 400 μmol/L), followed by measurement of PGE2 production in the culture medium for the additional 6 h by enzyme-linked immunosorbent assay. Results: CDCA induced PGE2 production and significantly increased cyclooxygenase-2 (cox-2) expression. However, in weak acidic conditions (pH 4–5), a pH-specific and significant increase in PGE2 production with no increase in cox-2 expression was observed. cPLA2 inhibitor decreased the effect of weak acid stimulation, indicating that the mechanism underlying PGE2 production differs between weak acid and CDCA. In addition, HST significantly inhibited both weak acid- and CDCA-induced PGE2 production. Conclusions: The synergistic effect of bile acid-induced cox-2 expression and weak acid-induced arachidonic acid production via cPLA2 can cause excessive PGE2 production. Therefore, mixed reflux showing pH 4–5 could contribute to the high incidence of esophageal cancer, which might be prevented by HST treatment. Weak acid reflux around pH 4–5 has been observed in PPI-treated patients, who could exhibit excessive PGE2 production as well as increased risk of reflux-induced esophageal cancer.
Genomic correlates of extreme pathologic response following neoadjuvant chemotherapy in locally advanced gastric cancer to reveal distinct vulnerabilities.
Authors: Datta Jashodeep , Walch Henry S. , Russo Ashley , Chatila Walid Khaled , Vos Elvira , Bhanot Umesh , Janjigian Yelena Yuriy , Schultz Nikolaus , Tang Laura H. , Strong Vivian E. 
Published: February 2020

441 Background: Clinical factors associated with pathologic response (PResp) following neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) are well studied; however, genomic correlates of such response have not been previously investigated. Methods: Evaluable pre-NCT tumor samples from patients with LAGC who underwent resection and demonstrated extreme pathologic response (EPR; ≤10% PResp: n = 21, ≥80% PResp: n = 19) were sequenced using a targeted exome capture platform. Gene- and signaling pathway-level correlates of EPR and disease-specific survival (DSS) were examined. Results: Of 40 patients, a majority had ≥cT2/N+ disease and were treated with predominantly platinum (98%) or 5-FU (88%) based NCT regimens. Two patients with MSI-high tumors had ≤10% PResp and were excluded from analysis. The EPR cohorts did not differ significantly in demographic or clinical (i.e., tumor location, cT/N status, NCT regimen, extent of gastrectomy, number of lymph nodes examined, or margin status) characteristics. Although EPR cohorts did not differ with respect to tumor differentiation/grade, Lauren classification, proportions of TCGA consensus CIN or GS subtypes, tumors with ≤10% PResp were more likely to have vascular (P < 0.001) and perineural (P = 0.007) invasion. At median follow-up of 31m (IQR 21-57), ≥80% PResp was associated with improved DSS compared with ≤10% PResp (median NR vs. 32m, P = 0.04). On gene-level analysis, tumors with ≤10% PResp were significantly more likely to be ERBB2-altered (32% vs 5%, P = 0.04) compared with ≥80% PResp tumors. Conversely, ARID1A truncating mutations were enriched in tumors with ≥80% vs ≤10% PResp (32% vs 5%, P = 0.04). There was no difference in pathway-level alteration frequency between EPR cohorts. While frequency of oncogenic TP53 alterations was similar between EPR cohorts, TP53-altered tumors were associated with worse DSS vs TP53-wildtype tumors (median 80m vs 24m, P = 0.005) in patients demonstrating ≤10%, but not ≥80%, PResp. Conclusions: Genomic comparison of cohorts demonstrating EPR after NCT in LAGC reveal molecular vulnerabilities with distinct prognostic and therapeutic implications.
Abdominal obesity and risk for esophageal cancer: A nationwide population-based cohort study of South Korea.
Authors: Lee Dong Ho , Cho Jae Ho , Shin Cheol Min , Han Kyungdo , Yoon Hyuk , Park Young Soo , Kim Nayoung 
Published: February 2020

446 Background: The relationship between overall obesity, as measured by body mass index (BMI), and risk of esophageal squamous cell carcinoma (ESCC) has been reported, and it has a negative correlation. However, the relationship with abdominal obesity, as measured by waist circumference, may be different. We investigated the association between abdominal obesity and ESCC. Methods: Retrospective cohort study with 22,809,722 individuals who had undergone regular health check-ups provided by the National Health Insurance Corporation between 2009 and 2012 (median follow-up period was 6.4 years) in South Korea. Abdominal obesity was defined as a waist circumference over 90 cm for men and 85 cm for women. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Chi-squared test and Cox proportional hazard model adjusted for confounding factors. Primary outcome was newly developed esophageal cancer. Results: After adjusting for BMI, abdominal obesity increased the risk of ESCC (HR 1.29, 95% CI 1.23–1.36). Waist circumference is associated with increased risk of ESCC in a dose-dependent manner ( P for trend < 0.0001). We analyzed individuals divided into five categories of BMI. Among individuals with overweight (BMI 23–24.9 kg/m2) and obese I (BMI 25–29.9 kg/m2), abdominal obesity was a risk factor associated with developing ESCC (HR 1.22, 95% CI 1.11–1.34; HR 1.28, 95% CI 1.18–1.39, respectively). Conclusions: Abdominal obesity, not BMI itself, is associated with an increased risk for ESCC. Therefore, reducing abdominal obesity may affect decreasing the development of ESCC.
Levels of oncofetal proteins in pathological tissues of patients with gastric cancer.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Samoylenko Nikolay S. 
Published: February 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) T3-4aN0-3M1 and T3-4aN0-3M0. 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 (M0) – GC T3-4aN0-3M0 (n = 24) and 2 (M1) – GC T3-4aN0-3M1 (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 T3-4aN0-3M1 than in T3-4aN0-3M0. In the omentum tissues, CA-19.9 levels in T3-4aN0-3M1 exceeded the control values by 20 times; in 20 patients with T3-4aN0-3M0, the value was only 4.1 times higher than in controls and 4.8 times lower than in T3-4aN0-3M1, while in 4 patients it did not differed significantly from the value in T3-4aN0-3M1. In the peritoneal tissues, CA-19.9 levels in T3-4aN0-3M1 exceeded the control values by 19.2 times; in 21 patients with T3-4aN0-3M0, the value was only 2.2 times higher than in controls and 8.5 times lower than in T3-4aN0-3M1, while in 3 patients it did not differed significantly from the value in T3-4aN0-3M1. 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.
Prognostic factors in patients with nonmetastatic gastric cancer treated with contemporary multimodality strategies.
Authors: Alfaro Ariceli , Hoang Tuyen , Huynh Jasmine , Ji Jingran , Ko Andrew H. , Cho May Thet , Hiyama Darryl , Dayyani Farshid 
Published: February 2020

451 Background: We conducted a retrospective study to evaluate clinical outcomes in patients with non-metastatic gastric adenocarcinoma (nmGA) treated at two high-volume academic institutions within the University of California (UC) system. Methods: Electronic Health Records and California Cancer Registry of demographic and clinical data were collected for pts with nmGA who underwent surgery with curative intent from 2010-2017. Medical chart reviews were conducted to validate outcomes. We used multivariate Cox regression to determine prognostic factors for cancer recurrence and overall survival. Results: Demographics of study cohort (n = 406): mean age 65 years; 71% male; 58% Caucasian, 26% Asian, 13% Latino. There was an even distribution between pts with locoregionally advanced (defined as pT4 or pN1+) vs. localized (pT1-3, pN0) disease. Tumor histology: 49% intestinal, 19% diffuse, 13% mixed, 19% unknown. Type of surgery: 27% open gastrectomy, 59% laparoscopic, 14% unknown. Multimodality therapy: 29% received perioperative systemic rx alone (48% adjuvant only, 52% neoadjuvant +/- adjuvant), 35% received perioperative systemic rx plus radiation (40% adjuvant only, 60% neoadjuvant +/- adjuvant), 36% underwent surgery only. With median f/u time after surgery of 5 years, 21% of pts developed cancer recurrence and 43% had died. Weight loss prior to diagnosis, locoregional stage, and positive resection margins were a/w recurrence (HR = 1.6-2.5, p < .05). Only locoregional stage was prognostic for worse survival (HR = 2.7, p < .0001). Positive resection margins were seen in 6% of pts and were a/w diffuse histology and tumor size > 4cm (odds ratio = 2.9-8.8, p < .02). Multimodality therapy was not a/w recurrence but was a/w longer survival after adjusting for stage (HR = 0.3, p < .0001). Addition of radiation to systemic rx did not confer further improvements in either recurrence or survival. Conclusions: This study highlights contemporary practice patterns for pts with nmGA and demonstrates a survival benefit with multimodality rx. Additional data are being gathered from other UC medical centers to confirm these findings and explore differences across institutions and ethnicities.
Relationship between PET response and pathologic response in distal esophageal/gastroesophageal junction (DE/GEJ) cancers.
Authors: Yu Irene S. , Liu Shiru Lucy , Zhao Yizhou , Lau Sally CM , Lim Howard John 
Published: February 2020

452 Background: The utility of PET scans (PETs) to predict outcomes after neoadjuvant treatment of DE/GEJ cancers is unclear. We aimed to explore the relationship between PET response and pathologic/clinical outcomes in a real-world setting. Methods: Patients (pts) with DE/GEJ cancer treated with curative intent perioperative chemotherapy or neoadjuvant chemoradiation followed by surgery in British Columbia from 2009-2018 were included. Retrospective chart review was conducted; pts were stratified into PET responder (R, ≥ 35% decrease in max SUV) and non-responder (NR, < 35%) groups. Chi-square and Kaplan Meier were used to test for associations between variables and outcomes. Results: Of 576 pts identified, 52% had pre- and post-induction PETs; 232 pts proceeded to surgery and were included for analysis. Treatment regimens comprised of CROSS (72%), MAGIC (24%) and FLOT (4%). Median age was 66 (IQR 57-72), 85% male, 91% ECOG 0/1, 62% GEJ involvement, and 81% adenocarcinoma histology. Characteristics and treatment regimens were balanced between the PET-R and PET-NR groups (all p>0.05). Median time from end of treatment to PET was 30 days (IQR 22-36); 67% were PET-R. Pathologic complete response (PCR) rates were similar for PET-R vs. PET-NR (14% vs. 13%, p=0.08). The discordance rate between PET vs. pathologic response was 34% (Table). Aborted surgery rate was higher in the PET-NR group (8% vs. 3%, p=0.03); 70% of aborted cases were due to peritoneal involvement. Median overall survival was similar between the two groups (PET-R 31.5 mo vs. PET-NR 36.1 mo, p=0.62). Conclusions: In our population-based cohort, PET response did not demonstrate prognostic utility and was associated with a significant pathology discordance rate. The role of PET/CT is evolving and the use of post-induction imaging for response assessment and prognostic value may be questionable. [Table: see text]