bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change of clinical features and outcomes of adolescents and young adults (AYA) with colorectal cancer over time: Pooled analysis of 26,768 patients in the National Cancer Database (NCDB).
Authors: Trufan Sally Jeanne , Worrilow William Mills , Kadakia Kunal C. , Nazemzadeh Reza , Musselwhite Laura W. , Chai Seungjean , Salmon Stuart , Hill Joshua , Salo Jonathan C. , Kim Edward S. , Hwang Jimmy J. , Salem Mohamed E. 
Published: February 2020

256 Background: The incidence of colorectal cancer (CRC) in younger patients (pts) is rising. The underlying etiology is unknown, and it is uncertain if disease biology and clinical features are changing over time. Methods: A retrospective study of pts data in the NCDB was performed to compare the clinicopathological features and outcomes of AYA with CRC over a 12-year period. Pts diagnosis period was dichotomized into older (2004 – 2009) and newer (2010 – 2015) eras. Uni- and multi-variable chi-square, logistic regression, and survival analyses were used for comparisons. Survival differences were assessed using Kaplan-Meier curves. Results: In total, 26,768 AYA (18-40yrs) with CRC were identified and included in the analysis: 45.8% (n = 12,268) from the older and 54.2% (n = 14,500) from the newer era. There were no differences between the 2 groups in gender distribution or levels of income and education. However, in the newer vs. older era, there was a greater proportion of non-white, non-black pts (7.2% vs. 6%; p = 0.0005) and pts diagnosed between the ages of 18-30 (21.1% vs. 18.8%; p < .0001). Pts in the newer era tended to have more comorbidities (8.6 vs 7.5%; p = 0.0012), left-sided tumors (77.5% vs. 76.1%; p = 0.04), and well-differentiated histology (12.0% vs. 8.3%; p < 0.0001). Newer era pts also had lower rates of metastatic disease at presentation (15.3% vs. 18.2%; p < 0.001%) and nodal involvement (54.9 vs. 58.4%; p < 0.001%). Median OS of pts with stage IV disease appears to have improved over time (24.1 vs. 22.5 mos; p = 0.014). After controlling for age, race, primary tumor site and grade, presence of comorbidities, and health insurance status, older era pts with stage IV CRC were at a 15.1% greater risk of all-cause death by year 5 compared to newer era pts (HRadj= 1.15 (1.07-1.24, p = 0.0001). Conclusions: Our data suggest that AYA with CRC in more recent years tend to present at a younger age and have a lower rate of metastatic disease. They also have improved survival. Further investigation of AYA disease etiology and biology are warranted. Continued efforts to increase awareness, promote early detection, and improve treatment options are essential.
Extensive peritoneal lavage after curative gastrectomy for gastric cancer study (EXPEL): An international multicenter randomized controlled trial.
Authors: So Jimmy Bok Yan , Ji Jiafu , Han Sang Uk , Terashima Masanori , Li Guoxin , Kim Hyung-Ho , Law Simon , Shabbir Asim , Song Kyo Young , Hyung Woo Jin , Kosai Nik Ritza , Kono Koji , Misawa Kazunari , Yabusaki Hiroshi , Kinoshita Takahiro , Lau Peng Choong , Kim Young Woo , Rao Jaideepraj , Tai Bee Choo , Yang Han-Kwang ,   EXPEL Study Group
Published: February 2020

279 Background: Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Preliminary studies suggest extensive intraoperative peritoneal lavage (EIPL) may reduce the risk of peritoneal recurrence and improve survival. We sought to perform a randomized phase III study to definitively establish the role of performing EIPL after gastrectomy. Methods: This is a prospective, open-label, phase 3 multicentre randomised controlled trial involving 22 hospitals from Korea. China, Japan, Malaysia and Singapore. Patients aged between 21 to 80 years with cT3/4 stomach cancer undergoing curative resection were randomized to either surgery and EIPL (lavage with 10 litres of saline) or surgery alone. Comparison of DFS and OS were made via log-rank test. The cumulative incidence of peritoneal recurrence was compared using competing risks approach. All analyses were performed based on intention-to-treat. Results: Between March 2015 to August 2018, 800 patients were randomly assigned to surgery alone ( n= 402) or EIPL ( n= 398). Based on a median follow-up duration of 29 months, the 3-year cumulative incidence of all-cause mortality was 23.1% and 23.3% for EIPL and surgery alone respectively (hazard ratio [HR] = 1.09, 95% CI: 0.78 to 1.52, p = 0.615). Similarly, the 3-year cumulative incidence of recurrence were 28.0% and 25.9% respectively (HR = 1.01, 95% CI: 0.74 to 1.37, p = 0.947), and 7.9% and 6.6% respectively for peritoneal recurrence (Subdistribution HR = 1.33, 95% CI: 0.73 to 2.42, p = 0.347). Overall, the risk of adverse events was higher in EIPL as compared to surgery alone (relative risk = 1.58, 95% CI 1.07 to 2.33, p = 0.019). The most common adverse events were anastomotic leak, bleeding and intra-abdominal abscess. At the planned third interim analysis on 28 August 2019, the predictive probability of achieving even a 5% difference in 3-year OS in favour of EIPL at final analysis was < 0.4%. The trial was thus recommended to terminate on the basis of futility. Conclusions: EIPL does not show any survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for cancer. Clinical trial information: NCT02140034.
Evaluating maintenance therapies in advanced oesophago-gastric adenocarcinoma (OGA): Interim analysis and biomarker results from the PLATFORM study.
Authors: Cunningham David , Fong Caroline Yean Kit , Peckitt Clare , Anandappa Gayathri , Davidson Michael , Patel Bijal , Turner Andrea , Begum Ruwaida , Cafferkey Catherine , von Loga Katharina , Rebelatto Marlon , Petty Russell D. , Hewish Madeleine , Roques Tom , Coxon Fareeda Y. , Morgan Carys , Wadsley Jonathan , Waddell Tom , Starling Naureen , Chau Ian 
Published: February 2020

282 Background: Advanced OGA patients (pts) are treated with platinum-based 1st line chemotherapy but the role of maintenance therapy once disease control is obtained is unknown. Methods: PLATFORM is a prospective, open-label, adaptive phase II trial assessing maintenance therapy in OGA. HER2 negative pts with advanced OGA achieving response or stable disease on completion of 1st line platinum-based chemotherapy were initially randomised to surveillance (A1), capecitabine (A2) and durvalumab (A3). Rucaparib (A4) and capecitabine+ramucirumab (A5) were subsequently added as part of adaptive design. Primary endpoint is progression-free survival with target recruitment of 154pts/arm. A pre-planned futility interim analysis (IA) is triggered when 61 pts/arm are recruited and evaluable using 12-week progression-free rate (PFR). Individual arms will continue accrual if the upper limit of 1-sided 95% CI difference is > 0 when compared to A1. Biomarker analyses of A1 and A3 IA patients include: PDL1 as tumour and immune cell combined proportion (TIP), multiplex IHC of tumour infiltrating lymphocytes (TILs), TMB and MSI status by whole exome sequencing. Results: To date, 1053 pts have registered prior to or during 1st line therapy and 356 pts randomised. Primary attrition was due to disease progression. Baseline demographics in the IA population (arms A1 to A3, n = 183) were male (81%); median age 65 yrs; metastatic disease (92%); oesophageal (40%), OG junction (28%) and gastric (32%) primary. 12-week PFR were A1: 51% (95%CI: 38-64%); A2: 52% (95%CI: 40-65%); A3: 49% (95%CI: 36-62%). PFR differences to arm A1 were A2: 1.6% (95%CI: -13.2 to 16.5%); A3: -1.6% (95%CI: -16.5 to 13.3%). In A1, PFR was 53% vs 43% in PDL1 TIP < 10% and ≥10% respectively. In A3, PFR was 51% vs 100% in PDL1 TIP < 10% and ≥10% respectively. 3 pts in A3 had partial response; none were seen in A1 and A2. Density of TILs subsets, TMB and MSI data will be presented. Conclusions: PLATFORM IA did not indicate futility in maintenance capecitabine or durvalumab compared to surveillance in advanced OGA and will continue to target accrual. Incremental radiological responses were observed with maintenance durvalumab only. Clinical trial information: NCT02678182.
Comparing the accuracy of EUS and CT in staging of esophageal cancer.
Authors: Shim Hyun Ik , Lee Dong Ho , Cho Jae Ho , Shin Cheol Min , Yoon Hyuk , Park Young Soo , Kim Nayoung 
Published: February 2020

286 Background: Endoscopic ultrasound (EUS) is a suitable device for staging of esophageal cancers. However, chest computed tomography (CT) has traditionally been the standard diagnostic modality for malignancies. This study aimed was to compare the accuracies of EUS and chest CT in T and N staging of esophageal cancers. Methods: We retrospectively analyzed 149 patients who had undergone EUS examination and 275 patients who had undergone chest CT before cancer surgery. The inclusion criteria were: 1) patients diagnosed with esophageal cancer on biopsy, 2) patients who had undergone EUS examination or chest CT before cancer surgery, and 3) patients who underwent cancer surgery at the Seoul National University Bundang Hospital from May 2003 to December 2018. We determined the accuracy of T and N staging on EUS examination and chest CT with the biopsy specimens. Results: The overall accuracies of EUS examination and chest CT were 72.5% (108/149) and 68.7% (189/275), respectively, for T staging ( p = 0.487) and 64.4% (96/149) and 61.5% (169/275), respectively, for N staging, which was not statistically different ( p = 0.596). For the substaging, the accuracy of EUS examination was not statistically different than that of chest CT for the T, N stage. Conclusions: EUS examination is not superior to chest CT for diagnosing T stage in esophageal cancers, whereas chest CT is not superior to EUS examination for diagnosing N stage in esophageal cancers. EUS examination and chest CT are not satisfactory for diagnosing T, N stage in esophageal cancers. Futher study is needed for accurate T, N stage diagnosis in esophageal cancer.
Prediction of lymph node metastasis in early gastric cancer using artificial intelligence technology.
Authors: Irino Tomoyuki , Kawakubo Hirofumi , Matsuda Satoru , Mayanagi Shuhei , Nakamura Rieko , Wada Norihito , Kamiya Satoshi , Tanizawa Yutaka , Bando Etsuro , Terashima Masanori , Kitagawa Yuko 
Published: February 2020

289 Background: Early gastric cancer shows lymph node involvement in about 10-15% of patients. Despite the fact, we perform radical lymphadenectomy for all patients because predicting lymph node metastasis has yet to be successful. In this study, we hypothesize that image analysis using artificial intelligence (AI) technology may help solve the problem. Methods: We retrospectively collected 82 patients with clinical T1N0 and pathological node negative and 82 patients with clinical T1N0 and pathological node positives and then divided the 164 patients into a training:validation set in ratio of 9:1. Endoscopic images of the early tumors were analyzed by transfer learning using AlexNet, a deep neural network containing 5 convolutional layers and 3 fully-connected layers. The model was validated with newly-collected 40 images from 20 clinical T1N0 and pathological node negative and 20 patients with clinical T1N0 and pathological node positives as a test set. For comparison, three methods of prediction were implemented: prediction at random, by logistic regression, and by skilled endoscopists. Results: The AI predicted LNM with accuracy of 80.9% in the validation set and 66.9% in the test set. (48.3% for node negative cancers and 85.4% for node positive cancers) On the other hand, prediction at random, by logistic regression, and by 2 endoscopists resulted in 50.3%, 50.0%, and 47.5%, respectively. Conclusions: Although the accuracy still needs to be improved, image analysis using the AI technology resulted in the best prediction of lymph node metastasis, indicating that AI is a promising technology for the diagnosis of lymph node metastasis in early gastric cancer.
Health-related quality-of-life results from JCOG0912: A phase III noninferiority trial comparing open and laparoscopy-assisted distal gastrectomy for stage I gastric cancer.
Authors: Yoshikawa Takaki , Ando Masahiko , Mizusawa Junki , Katai Hitoshi , Yamada Takanobu , Ito Seiji , Fukagawa Takeo , Bando Etsuro , Misawa Kazunari , Katayama Hiroshi , Terashima Masanori , Sasako Mitsuru ,   JCOG Stomach Cancer Study Group
Published: February 2020

293 Background: Laparoscopy-assisted distal gastrectomy (LADG) was non-inferior to open (ODG) in patients with stage I gastric cancer in randomized phase 3 non-inferiority trial (JCOG0912). Here, we present the results of health-related quality of life (HRQoL) which was a secondary endpoint in JCOG0912. Methods: Among 33 institutions participated in JCOG0912, 4 major cancer centers were selected for HRQOL assessment. HRQoL was assessed using EORTC QLQ-C30 and the EORTC-STO22 before (baseline) and at 1, 3, 12, and 36 months after surgery. The primary HRQOL scale was QLQ-C30 global health status. We defined clinically meaningful decrease of HRQoL as decrease in 10 points or more from the baseline. Missing data were regarded as decrease. Assuming that expected %decrease of global health status at 3 months was 61% in ODG and 45% in LADG with 80% power and two-sided alpha of 0.05, sample size for HRQOL assessment was calculated to be 304. When this hypothesis at 3 months was confirmed, statistical comparison was tested in turn at 12 and 36 months. Results: Among 921 enrolled patients in JCOG0912 from Mar 2010 to Nov 2013, 592 were enrolled from the 4 centers in this HRQoL study. The %decrease of global health status at 3 months was different between ODG and LADG (37.2% (109/293) in ODG vs 29.2% (86/295) in LADG, odds ratio [OR] 0.65 (95% CI: 0.45-0.93, p = 0.020)), but was not different in 1 month (56.0% (164/293) vs 55.3% (163/295), OR 0.92 (0.61-1.32)), 12 months (26.3% (77/293) vs 27.8% (82/295) (OR 1.07 (0.73-1.56))and 36 months (31.4% (91/293)vs 30.8% (91/295) (odds ratio, 0.96 (0.67-1.37))). Among the other subscales, LADG had significantly better symptom scores for pain at 1 and 3 months, constipation at 3 and 12 months, and eating restrictions at 3 months. Conclusions: Decrease of HRQoL was less frequently observed in LADG than ODG especially in the early phase after surgery. Considering non-inferiority and better HRQoL of LADG, LADG is strongly recommended for stage I gastric cancer. However, we have to be careful to expand the indication of LADG for advanced gastric cancer until a solid evidence is obtained. Clinical trial information: UMIN000003319.
Improved efficacy to cytotoxic agents chemotherapy after immune checkpoint inhibitors exposure in metastatic gastric cancer.
Authors: Sagawa Tamotsu , Sato Yasushi , Hamaguchi Kyoko , Hirakawa Masahiro , Nagashima Hiroyuki , Waga Eriko , Fujikawa Koshi , Takahashi Yasuo 
Published: February 2020

297 Background: An association between improved responses to chemotherapy after exposure to vaccine-based immunotherapy has been previously reported in other cancers. However, it is unclear whether the chemotherapy response improves after exposure to immunotherapy, such as immune checkpoint inhibitors (ICIs). The objective of this retrospective study was to evaluate whether chemotherapy (4th-line) would yield improved efficacy when given after exposure to anti-PD-1 antibody in metastatic gastric cancer (mGC). Methods: We investigated retrospectively clinical characteristics at baseline of mGC patients who received chemotherapy after progression of anti-PD-1 antibody (Nivolumab) between February 2018 and July 2019. Anti-PD-1 antibody was adapted as third-line therapy. Inclusion criteria for the analysis reported herein: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received chemotherapy including 5-fluoropyrimidines (5-FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, DCR by RECIST version 1.1, PFS, and OS. Results: Out of 27 treated with anti-PD-1 antibody, 10 patients were evaluable for responses and eligible to be included in this analysis. Patient characteristics were as follows: median age (range), 72 (50-88) years; male/female, 8/2; ECOG PS (0/1/2), 4/5/1; HER2 (+/-), 5/5; histology (differentiated/undifferentiated), 5/5; metastatic lesions (LN/peritoneum/liver/lung), 5/3/1/3; number of metastatic sites (1/≥2), 5/5; number of prior CTx regimens (3/4/5), 10/0/0; median period (range) from first line CTx, 18.8 (7.9-47.1) months; and CTx regimens (CPT-11/PTX/S-1+Oxaliplatin), 7/2/1; Among the 10 patients, 1 achieved a partial response, giving an ORR of 10.0%. Six patients had stable disease and three had progressive disease. The DCR was 70%. Median PFS and OS were 5.5M and 8.5M, respectively. These were no new irAEs appeared during CTx. Conclusions: In mGC patients, our study demonstrated that increased efficacy to cytotoxic agents chemotherapy given after exposure to ICI was higher as compared to our historical data from the pre-anti-PD1 era. Updated results will be presented.
Impact of gastric cancer treatment pathways on patient outcomes in a community oncology practice setting.
Authors: Paulson Andrew Scott , Hess Lisa M. , Baidoo Bismark , Waycaster Curtis , Chatterjee Anindya , Liepa Astra M. 
Published: February 2020

299 Background: Gastric cancer (GC, including gastroesophageal junction adenocarcinoma) pathways have been implemented and refined since 2010 in the US Oncology Network (USON), a community-practice-based network. This study was designed to evaluate the impact of 4 pathway periods (PP): pre-pathway: pre-Aug ‘10; Level 1: Sept ‘10-Nov ‘14; Clear Value, Dec ‘14-Feb ‘17; Value: After Mar ‘17, on treatment heterogeneity, treatment duration, and overall survival (OS). Methods: Adult patients were eligible if they were treated at a participating USON site and were diagnosed with and treated for GC; follow up was through Mar 2019. Heterogeneity was measured by the Herfindahl-Hirschman Index (HHI), which is evaluated from 0.0 to 1.0 (complete to no heterogeneity). Time to treatment failure (TTF) was defined as initiation of the line of therapy until start of the subsequent line of therapy or death. OS was estimated from start of first-line (1L) therapy. Time-to-event outcomes were estimated using Kaplan-Meier. Results: Of 3191 eligible patients, 2297 received treatment for advanced/metastatic disease. Of these, patient median age was 65.3 years, 60% were male, 70% were initially diagnosed with stage IV disease. Pre-pathway, common 1L regimens were single-agent fluorouracil (15%) and docetaxel-cisplatin-fluorouracil (14%); FOLFOX (45%) was most frequent during the value PP, 941 (41%) received second-line (2L) therapy. During Level 1 PP, single-agent irinotecan (11%) was most common during 2L, whereas in Value PP, ramucirumab+paclitaxel (43%) was most common. HHI and TTF are presented in the table. Median OS was 12.6 months (95% confidence interval, CI: 11.9, 13.5), which did not change significantly over PPs. Conclusions: 1L and 2L heterogeneity was initially high, and was reduced over time; TTF showed modest increase. OS data are limited by high levels of censoring in the latter PPs, which reduces the ability to evaluate changes in more recent years. [Table: see text]
SOURCE: Prediction models for overall survival in patients with metastatic and potentially curable esophageal and gastric cancer.
Authors: van den Boorn Héctor G. , Abu-Hanna Ameen , Haj Mohammad Nadia , Hulshof Maarten C.C.M. , Gisbertz Suzanne S. , Klarenbeek Bastiaan R. , Slingerland Marije , Beerepoot Laurens Victor , Rozema Tom , Sprangers Mirjam A.G. , Verhoeven Rob H. A. , Zwinderman Aeilko H. , van Oijen Martijn G.H. , Van Laarhoven Hanneke W.M. 
Published: February 2020

301 Background: Prediction models in cancer care can provide personalized prediction outcomes and can aid in shared decision making. Existing prediction models for esophageal and gastric cancer (EGC), however, are mostly aimed at predicting survival after a curative treatment has already been completed. The aim of this study is to develop prediction models, called SOURCE, to predict overall survival at diagnosis in potentially curable and metastatic EGC patients. Methods: The data from 12,756 EGC patients diagnosed between 2014-2017 were retrieved from the prospective Netherlands Cancer Registry. Four Cox regression models were created for potentially curable and metastatic cancers of the esophagus and stomach. Predictors, including treatment type, were selected using the Akaike Information Criterion. The models were validated with temporal cross-validation on their concordance-index (c-index) and calibration. Results: The validated model’s c-index is 0.76 for potentially curable cancer. For the metastatic models, the c-indices are 0.71 and 0.70 for esophageal and gastric cancer, respectively. The calibration intercepts and slopes lie in the 95% confidence interval of 0 and 1, respectively. The included model variables are given in Table. Conclusions: The SOURCE prediction models show fair c-indices and an overall good calibration. The models are the first in EGC to include treatment as a predictor. The models predict survival at diagnosis for a variety of treatments and therefore could have a high clinical applicability. Future research is needed to demonstrate the effect on shared decision making in clinical practice. [Table: see text]
Induction oxaliplatin capecitabine followed by switch to carboplatin-paclitaxel based RT versus continuing oxaliplatin capecitabine RT in operable esophageal adenocarcinoma: Survival analysis of the randomized phase II neoscope trial.
Authors: Mukherjee Somnath , Hurt Chris , Cox Catrin , Radhakrishna Ganesh , Gwynne Sarah , Bateman Andrew Rea , Gollins Simon , Hawkins Maria A. , Canham Jo , Grabsch Heike I. , Falk Stephen , Sharma Ricky A. , Ray Ruby , Roy Rajarshi , Wade Wendy , Maggs Rhydian , sebag-Montefiore David joseph , Maughan Tim , Griffiths Gareth Owen , Crosby Tom David Lewis 
Published: February 2020

373 Background: Initial results of the NEOSCOPE trial comparing pre-operative CarPac vs OxCap based chemoradiotherapy (CRT) in patients with adenocarcinoma of the oesophagus or oesophagogastric junction showed comparable toxicity and improvement in pathological complete response (pCR) in favour of the CarPacRT. Here we report survival after a median follow-up of 40.7 months (95% CI: 45.1-53.6). Methods: NEOSCOPE was an open, randomised, ‘pick a winner’ phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m2 day 1, 15, 29; capecitabine 625 mg/m2 bd on days of RT) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 day 1, 8, 15, 22, 29). RT dose was 45 Gy/25 fractions/5 weeks. Induction OxCap (2 cycles) was given prior to CRT. Surgery was performed 6–8 weeks after CRT.The primary endpoint was pCR, secondary endpoints were toxicity, PFS and OS. Results: Between Oct 2013 and Feb 2015, 85 patients were recruited from 17 UK centres. Median OS was not reached in the CarPacRT group and was 41.72 months (95% CI 19.58-.)in the OxCap group (HR 0.56[95% CI 0.29-1.07]; p=0.079). 3-year and 5-year OS rates were 74% (95% CI 58%-85%) and 54% (95% CI 34%-71%) (CarPacRT), and 52% (95% CI 35%-67%) and 39% (95% CI 21%-56%) (OxCapRT). Median PFS (not reached vs 35.3 months, HR=0.61 [95% CI 0.33-1.12]; p=0.111) and metastatic PFS (not reached vs 39.0 months, HR=0.61 [95% CI 0.32-1.14], p=0.118) both favoured the CarPacRT arm. Local recurrence rate was low (OxCapRT= 10%; CarPacRT= 7%). The OS benefit for CarPacRT was consistent across subgroups but not statistically significant. Conclusions: In this longer term analysis there was some evidence that induction OxCap followed by switch to CarPacRT was superior to continuing OxCapRT, with efficacy similar to that seen in other published studies such as ‘CROSS’ and ‘FLOT’. Taken together with the previously published pCR results CarPacRT rather than OxCapRT warrants inclusion in future trials. Funding: Cancer Research UK (C44694/A14614). Clinical trial information: NCT01843829.