bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: Long-term results of KDOG1001 trial.
Authors: Hosoda Kei , Azuma Mizutomo , Katada Chikatoshi , Ishido Kenji , Niihara Masahiro , Ushiku Hideki , Sakuraya Mikiko , Washio Marie , Wada Takuya , Watanabe Akinori , Koizumi Wasaburo , Tanabe Satoshi , Yamashita Keishi , Hiki Naoki 
Published: May 2020

4521 Background: In the phase 2, open-label, KDOG1001 (UMIN000003642) study, neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and S-1 (DCS), followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer showed feasibility of DCS therapy with an enough R0 resection rate of 90%. Here we present long-term results after a minimum follow-up of 3 years. Methods: Patients with bulky node metastasis (bulky N), linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy. This analysis presents the final preplanned assessment of outcomes after 3 years. Primary endpoint was R0 resection rate. Secondary endpoints included overall survival (OS), progression free survival (PFS), completion rate of the protocol treatment, and pathological response rate (pRR) of DCS NAC. Results: Of 40 patients enrolled from May 2010 through January 2017, 7 (17.5%) had bulky N, 18 (45.0%) had type 4, and 16 (40%) had large type 3 with 1 (2.5%) having both large type 3 and bulky N2. All included patients underwent preoperative DCS chemotherapy followed by surgery with D2 lymphadenectomy with 32 (80%) completed postoperative S-1 therapy for 1 year. After a median follow-up for surviving patients of 67 mo (range, 36 mo to 110 mo) at the last follow-up in January 2020, 3-year OS was 78% [95% confidence interval (CI) 62–88%], while 3-year PFS was 63% (95% CI 47–76%). Completion rate of the protocol treatment was 62.5% (25/40) with pRR of 57.5% (23/40). In bulky N2, 3-y OS was 86% and 3-y PFS was 71% with pRR of 100%. In type 4, 3-y OS was 67% and 3-y PFS was 50% with pRR of 44%. In large type 3, 3-y OS was 88% and 3-y PFS was 75% with pRR of 56%. Patients with type 4 had significantly worse OS and PFS than those with the other types [HR 7.20 (95% CI 2.23–32.21) and HR 3.00 (95% CI 1.21–8.19)]. Conclusions: Preoperative chemotherapy with up to four cycles of DCS followed by gastrectomy plus adjuvant S-1 therapy is a promising treatment strategy for patients with bulky node metastasis, type 4 and large type 3 gastric cancers. For type 4 cancer, further improvement of treatment strategy is needed. Clinical trial information: 000003642 .
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric adenocarcinoma: A phase II clinical trial.
Authors: Song Yan , Li Ning , Mu Lan , Zhang Shu , Fan Qingxia , Liang Xinjun , Yin Xianli , Zhuang Zhixiang , Liu Yunpeng , Zhang Jingdong , Kou Xiaoge , Zhong Haijun , Huang Jing 
Published: May 2020

4524 Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We investigated HX008, an Anti-PD1 Antibody, with irinotecan in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and/or fluoropyrimidine. Methods: This study is a multicenter, open, phase II clinical study of recombinant humanized anti-pd-1 monoclonal antibody HX008 injection plus Irinotecan that was conducted at 11 hospitals in China. Eligible patients are adults with histologically confirmed advanced gastric or gastro-oesophageal junction cancer. Subjects participating in this study are required to submit a archived tumor tissue specimen or newly obtained biopsy of tumor lesions at the site of no previous radiotherapy and peripheral blood (2mL) for detection of PD-L1 and MSI/MMR expression. The samples will be tested for expression of PD-L1 and MMR by immunohistochemistry (IHC) in the central laboratory, and MSI levels will be determined by polymerase chain reaction (PCR) and gel electrophoresis. Subjects received PD-1 monoclonal antibody HX008 at 200mg (d1, intravenous drip, once every 3 weeks) plus irinotecan at 160mg/m2 (d1, intravenous drip, 60 ~ 120min, once every 2 weeks). Response was assessed every 6 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Primary endpoints was objective remission rate (ORR). Results: Between October 2018 and September 2019, a total of 58 patients with advanced gastric or gastro-oesophageal junction cancer were enrolled in this study. Median (range) age was 61 (27-71) years, and most patients were male (72.4%). Among 53 patients who were evaluated, 15 (28.3%) experienced objective response and 22 (41.5%) experienced stable disease (SD). The median progression free survival (PFS) was 5.4 months, the one-year survival rate was 71.3%. The most common treatment-related adverse events of grade 3 or 4 included neutropenia(31.0%), anemia(15.5%), loss of appetite (6.9%), vomiting(5.2%), nausea(3.4%), diarrhea (1.7%) and fatigue (1.7%). There were no treatment-related deaths. Conclusions: HX008 injection plus Irinotecan demonstrated promising activity and manageable safety in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Clinical trial information: NCT03704246 .
The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061.
Authors: Shitara Kohei , Özgüroğlu Mustafa , Bang Yung-Jue , Di Bartolomeo Maria , Mandalà Mario , Ryu Min-hee , Vivaldi Caterina , Olesinski Tomasz , Chung Hyun Cheol , Muro Kei , Van Cutsem Eric , Kobie Julie , Cristescu Razvan , Aurora-Garg Deepti , Lu Jia , Shih Chie-Schin , Adelberg David , Cao Z. Alexander , Fabrizio David , Fuchs Charles S. 
Published: May 2020

4537 Background: KEYNOTE-061 (NCT02370498) was a randomized, open-label, phase 3 study of pembrolizumab vs paclitaxel in pts with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with tumor progression after first-line therapy (N = 592). In this analysis, we evaluated tTMB using FoundationOne CDx (F1CDx; Foundation Medicine) in pts with gastric or GEJ cancer in KEYNOTE-061. Methods: In pts with evaluable F1CDx tTMB data (n = 204), we analyzed the association of tTMB with confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) within each treatment arm using one-sided (pembrolizumab) and two-sided (paclitaxel) Wald test nominal P for logistic regression (ORR) and Cox proportional hazards regression (PFS; OS) adjusted for ECOG performance status; significance was prespecified at 0.05. The clinical utility of tTMB was assessed using the prespecified cutoff of 10 mut/Mb for F1CDx. Clinical data cutoff: Oct 26, 2017. Results: tTMB was positively associated with ORR ( P < 0.001; AUROC, 0.68), PFS ( P < 0.001), and OS ( P = 0.003) with pembrolizumab but not paclitaxel (ORR, P = 0.047; AUROC, 0.30; PFS, P = 0.605; OS, P = 0.084). Pt outcomes by tTMB cutoff are reported in the Table; prevalence of TMB ≥10 mut/Mb was 17%. In pts with microsatellite stable disease-only, HRs (95% CI) by treatment arm for OS by F1CDx cutoff were 0.40 (0.14-1.17) for tTMB ≥10 mut/Mb (n = 21) vs 0.97 (0.70-1.34) for tTMB <10 mut/Mb (n = 168). Conclusions: In this exploratory analysis from KEYNOTE-061, tTMB as determined by F1CDx demonstrated a positive association with clinical outcomes with pembrolizumab, but not paclitaxel, in pts with GC; these findings are consistent with those reported with whole exome sequencing. Pembrolizumab demonstrated an OS benefit vs paclitaxel in the subgroup with tTMB ≥10 mut/Mb, which remained when pts with microsatellite instability-high disease were excluded. Clinical trial information: NCT02370498 . [Table: see text]
PILGRIM: Phase III clinical trial in evaluating the role of hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer patients after radical gastrectomy with D2 lymphadenectomy(HIPEC-01).
Authors: Cui Shu-zhong , Liang Han , Li Yong , Zhou Yanbing , Tao Kaixiong , Zhou Zhiwei , Li Guoxin , Li Peiyu , Zhou Baojun , Yao Hongliang , Peng Zheng , Xiong Bin , Pang Minghui , Cai Shirong , Li Yong , Wan Jin , Liang Bin , Lei Ziying , Wang Jiping ,   Chinese Peritoneal Oncology Study Group
Published: May 2020

4538 Background: Gastric cancer remains the 3rd leading cancer related death worldwide due to early disease recurrence. We hypothesize that hyperthermic intraperitoneal chemotherapy (HIPEC) may effectively prevent local regional recurrence for locally advanced gastric cancer patients who received curative intent surgery. Methods: Pathology proven gastric cancer patients with clinical T3/T4NxM0 disease are eligible for the study and will be randomized to either control group, who will receive standard radical gastrectomy and D2 lymph node dissection or HIPEC group, who will receive the same surgery and HIPEC with paclitaxel x 2 within the first week after surgery. All patients will receive either XELOX or SOX adjuvant chemotherapy. The primary end point is overall survival. Results: 648 patients from 16 high volume gastric medical centers were enrolled between May, 2015 and March, 2019. 331 and 317 patients were randomized to control and HIPEC groups respectively. The median follow-up time is 12.1 months. The common grade 3/4 toxicities ( > 5%) in control and HIPEC groups are anemia 6% vs. 4.1%, intraabdominal infection 5.4% vs. 3.8%, pneumonia 9.7% vs. 9.8%, fever 10.6% vs. 11.4% and hypoalbunemia 15.1% vs. 16.7% respectively. All three perioperative death (within 30 days after surgery) occurred in control group. One patient died from duodenum stump leak which led to multiple organ failure. One patient died from anastomotic led to intraabdominal infection and shock. The 3rd death was suicide caused by severe depression. At the time of this report, the number of event has not reached for final efficacy analysis. Conclusions: It is safe to administer HIPEC to patients received radical gastrectomy with D2 lymph node dissection within one week of surgery. The primary analysis will be expected in one year. Clinical trial information: NCT02356276 .
Durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Updated survival and early translational results from Big Ten Cancer Research Consortium Study.
Authors: Mamdani Hirva , Schneider Bryan J. , Kasi Pashtoon Murtaza , Abushahin Laith I. , Birdas Thomas J. , Kesler Kenneth , Burney Heather , Perkins Susan , Jalal Shadia Ibrahim 
Published: May 2020

4572 Background: Concurrent chemoradiation(CRT) followed by esophagectomy is a standard of care for locally advanced esophageal(LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients(pts) experience disease relapse within the 1st yr after treatment(tx) completion. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown radiation +/- chemotherapy upregulates PD-1/PD-L1 pathway. Methods: We conducted a phase II trial evaluating safety and efficacy of PD-L1 inhibitor durvalumab(durva) in pts with LA-EAC and GEJ adenocarcinoma who had residual disease in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: Initially 24 pts were enrolled, study was expanded to enroll additional 13 pts. Median age: 61yrs (range, 43-73). 31 received carbo/paclitaxel and 6 received cis/5-FU concurrently with RT. 24(64.9%) pts had positive lymph nodes(LN) at the time of surgery following CRT: N3(n = 3,8.1%), N2(n = 10, 27%), N1(n = 11,29.7%).17 pts relapsed: 11 on tx, 6 had late relapses. 3/5 late relapses were locoregional and were re-treated with chemo-RT. Remaining relapses were systemic with lung and LN being the most common sites. 2 of 3 pts who developed grade 3 irAEs are alive and disease free at 17 and 23 mo. RFS/OS:1 yr- 79.2%/95.5%, 2yr-55.5%/67.4%. 20/37 pts have HER-2 status available: 5/6 HER2 positive pts had disease relapse, 1 is undergoing tx. Molecular profiling is available on 8 relapsed pts: all were microsatellite stable with low TMB and PD-L1 < 10% CPS. Mutations in DNA repair genes ( ARID1A, ATM, ATR, CHEK2), and PIK3CA E542K were more prevalent among late relapsing pts. Circulating tumor cells (CTCs) analysis is available for 10/37 pts. 4/5 pts where CTCs increased from C1 to C4 had disease relapse. Molecular profiling of the remaining pts and correlation of PD-L1 expression, TMB, specific genes mutations, CTCs, and Immunoscore with outcomes with durva is being evaluated will be presented at the meeting. Conclusions: Adjuvant durva following trimodality therapy for LA-EAC and GEJ adenocarcinoma improved 1-yr RFS to 79.2% compared to historical rate of 50%.2-yr RFS and OS data are encouraging in this high risk pt population. HER-2 positivity may be associated with lack of benefit from durva. Mutations in DNA repair genes are prevalent in pts with delayed relapse. Rise in CTCs during durva tx may be an early marker of disease relapse. Clinical trial information: NCT02639065 .
A multicenter nonrandomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF cohort trial).
Authors: Tateishi Ryosuke , Hasegawa Kiyoshi , Kawaguchi Yoshikuni , Takayama Tadatoshi , Izumi Namiki , Yamanaka Naoki , Kudo Masatoshi , Shimada Mitsuo , Inomata Masafumi , Kaneko Shuichi , Koike Kazuhiko , Omata Masao , Makuuchi Masatoshi , Matsuyama Yutaka , Kokudo Norihiro 
Published: May 2020

4581 Background: In parallel with a multicenter randomized controlled trial that reported an equal recurrence-free survival (RFS) of early-stage hepatocellular carcinoma (HCC) patients who underwent either surgery (SUR) or radiofrequency ablation (RFA), we also enrolled HCC patients who fulfilled the enrollment criteria but did not give consent to participate in the RCT. Methods: All patients gave informed consent to participate in this study. Inclusion criteria were as follows: primary HCC with less than or equal to 3 tumors, each measuring 3 cm or smaller; without vascular invasion or extrahepatic metastasis; Child-Pugh score of 7 or less; and ages between 20 and 79 years. The feasibility for both treatments was confirmed by a joint chart review by surgeons and hepatologists. The primary endpoint was RFS and overall survival. A pre-specified interim analysis was performed to compare RFS. Results: Between April 2009 and August 2015, 740 patients (371 in SUR, 369 in RFA) were enrolled from 49 participating hospitals in Japan. The SUR group had significantly fewer patients with chronic hepatitis C (56.6% vs. 69.4%), higher median value of platelet count (145 vs. 120 × 109/L), and more patients with > 2 cm tumors (49.9% vs. 27.9%); most patients had a single tumor (91.1% vs. 88.3%). During the median follow-up period of 5 years, tumor recurrence was observed in 192 of SUR and 218 of RFA with 3-year RFS being 66.0% and 61.7%, respectively ( P = 0.091). In subgroup analysis, RFS was significantly better in SUR in patients with ≤ 2 cm tumors (62.9% vs. 51.7% in 3 years; hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.56-0.93; P = 0.014), whereas the difference was not significant in those with > 2 cm tumors (52.7% vs. 46.4%; HR 0.85, 95% CI 0.63-1.18; P = 0.34). The adjusted HR for RFS using inversed probability of treatment weighting was 0.89 (95% CI, 0.72-1.10; P = 0.287). Conclusions: The imbalance in patient characteristics reflected a real-world practice. Factors related to background liver disease rather than tumor characteristics might have a larger impact on the recurrence in early HCC. Clinical trial information: C000001796 .
Genome-wide plasma cell-free DNA methylation profiling to identify high-performing biomarkers for early detection of hepatocellular carcinoma.
Authors: Yang Xin-Rong , Huang Ao , Wang Yuying , Peng Jiaxi , Jiang Ruijingfang , Li Zhilong , Jie Yuan , Fan Jia , Zhou Jian 
Published: May 2020

4600 Background: Hepatocellular carcinoma (HCC) represents the second most common cause of cancer deaths worldwide. □-fetoprotein (AFP) is the most common serological test used for screening and diagnosis of HCC. However, it is widely recognized that AFP has lower sensitivity with sub-optimal specificity. Tumor-originated circulating cell-free DNA (cfDNA) provides new opportunity for non-invasive detection of liver cancer. Methods: HCC-specific differentially methylated regions (DMRs) were identified by whole genome bisulfite sequencing (WGBS) in 44 pairs of HCC tissues and adjacent tissues. We then performed methylome profiling on cfDNA from HCC patients and healthy individuals by targeted bisulfite sequencing covering genome-wide CpG islands, shelves, and shores. We employed machine learning approaches to build diagnostic models based on cfDNA regional methylation level to classify the plasma of HCC (n = 140) from that of healthy individuals (n = 84). Further analyses were performed in the validation cohort, including 155 HCC patients, and a control group with 96 healthy individuals, 21 chronic hepatitis B infection (CHB)/liver cirrhosis (LC) patients and 34 patients with benign hepatic lesions (BHL). Area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate diagnostic performance. Results: A random forest classifier achieved an AUC of 0.97 (sensitivity: 92.9%; specificity: 89.4%) with 10-fold cross-validation using a panel of 39 DMR markers. The AUC of the diagnostic panel was 0.93 (sensitivity: 81.3%; specificity: 90.7%) in validation cohort, and it performed equally well in detecting BCLC stage 0+A (AUC = 0.90; sensitivity: 74.7%) and AFP negative (AUC = 0.92; sensitivity: 79.4%) HCC, as well as differentiating HCC from CHB/LC and BHL. Based on these results, we have further developed a small targeted bisulfite sequencing panel covering 127 CpG sites for non-invasive diagnosis of HCC. The panel had similar performance in training and validation cohorts, an AUC of 0.96 (sensitivity: 90.7%, specificity: 88.2%) in the training set, and 0.91 (sensitivity: 80.0%, specificity: 88.7%) in the validation set. Conclusions: Our diagnostic panel with 39 DMR markers showed high sensitivity and specificity in HCC diagnosis as well as surveillance in high-risk populations for developing HCC. More importantly, simple diagnostic model show similar diagnostic performance for early HCC diagnosis, which was easily to transfer to clinical application in the future.
Health-related quality-of-life results from SANET-ep: A phase III study of surufatinib versus placebo for advanced extrapancreatic neuroendocrine tumors.
Authors: Bai Chunmei , Xu Jianming , Shen Lin , Li Jie , Zhou Zhiwei , Chi Yihebali , Li Zhiping , Xu Nong , LI Enxiao , Liu Tianshu , Bai Yuxian , Yuan Ying , Li Xingya , Wang Xiuwen , Chen Jia , Ying Jieer , Li Jing , Fan Songhua , Peng Mengye , Su Weiguo 
Published: May 2020

4613 Background: In the phase 3 study (SANET-ep, NCT02588170), surufatinib significantly prolonged progression free survival compared with placebo in patients with progressive, well-differentiated advanced extrapancreatic neuroendocrine tumors (epNETs) (ESMO 2019 Abs. LBA76). Here, we report the results of health-related quality-of-life (HRQoL) from this study. Methods: Eligible patients were randomized in a 2:1 ratio to receive surufatinib or placebo, 300 mg, orally, once daily, until disease progression or intolerable adverse events. Patient-reported outcome questionnaires, including the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the QLQ-G.I.NET-21, were collected at baseline, Day 15 of the first cycle (28 Days/cycle), and Day 1 of every cycle thereafter and at discontinuation. Time until definitive deterioration (TUDD) was defined as time from randomization to deterioration of 10 points in domain score compared with baseline score (without subsequent observations of deterioration of less than 10 point or any improvement as compared to baseline score), or death due to any cause. TUDD and mean change from baseline based on a longitudinal repeated measures analysis of each domain were analyzed retrospectively. Significance testing was at two-sided 0.05 without adjustment for multiplicity. Results: Of 198 pts randomized (surufatinib n = 129; placebo n = 69), 197 (99.5%) patients completed HRQoL questionnaires at baseline. The questionnaire compliance rate was >90% for most on-treatment assessments. The TUDD was significantly longer in the surufatinib arm versus the placebo arm in the dyspnea domain (hazard ratio [HR] 0.52, p = 0.0103) and social function scale (HR 0.58, p = 0.0222), while the TUDD of diarrhea was significantly shorter in the surufatinib arm compared to placebo (HR 2.68, p = 0.0074). There was no significant difference of TUDD in the remaining domains of QLQ-C30 and G.I.NET-21. There was also no significant difference of the mean change of scores from baseline by repeated measures in the domains between the two arms except diarrhea (increase of 14.0 points [95% CI 9.6, 18.4] in the surufatinib arm versus 2.1 points [95% CI -4.1, 8.4] in the placebo arm, p = 0.0007). Conclusions: Treatment with surufatinib resulted in superior efficacy, acceptable toxicity, while generally maintaining HRQoL, which support surufatinib as a treatment option in this patient population that was previously treated with available therapies for epNETs. Clinical trial information: NCT02588170 .
Circulating tumor DNA is prognostic and potentially predictive of eryaspase efficacy in patients with advanced pancreatic adenocarcinoma.
Authors: Bachet Jean-Baptiste , Blons Helene , Hammel Pascal , El Hariry Iman , Portales Fabienne , Mineur Laurent , Metges Jean-Philippe , Mulot Claire , Bourreau Camille , Cain Jason , Cros Jerome , Laurent-Puig Pierre 
Published: May 2020

4617 Background: Eryaspase is composed of L-asparaginase encapsulated in erythrocytes. It has demonstrated significant efficacy in combination with chemotherapy in a randomized phase 2 trial in second-line in patients with advanced pancreatic adenocarcinoma. We assessed, in this study, the prognostic and predictive value of circulating tumor DNA (ctDNA) in plasma samples of patients included in the eryaspase phase 2 trial. Methods: Samples prospectively collected pre-treatment at each 28-day cycle were centrally analyzed by next-generation sequencing (BPER method). Prognostic values of baseline ctDNA and ctDNA early changes between day 0 and 28 were assessed in both arms combined on objective response rate (ORR), progression free survival (PFS) and overall survival (OS). We conducted interaction test between ctDNA positivity and treatment arm, and the predictive value of ctDNA for eryaspase efficacy was investigated. Results: Patients with at least one available plasma sample have been included (n = 122/141). The presence of ctDNA at baseline was identified in 68% (77/113) of patients and was an independent negative prognostic factor for OS (4.6 vs 8.8 months; p = 0.0025) and PFS (1.6 vs 3.3 months; p = 0.00043). Early change in ctDNA levels was assessed by separating patients into three categories (one without detectable ctDNA, and two according to radio median value between day 0 and day 28) that were significantly correlated with ORR, PFS and OS. A significant interaction was observed between the presence of ctDNA and eryaspase efficacy. In patients with ctDNA detectable at baseline, eryaspase was associated with better PFS (HR = 0.53; 95% CI: 0.3-0.94) and OS (HR = 0.52; 95% CI: 0.29-0.91). Conclusions: We confirm from a prospective randomized trial that 1/ the presence of ctDNA at baseline is a major prognostic factor, 2/ the early change of ctDNA correlates with treatment outcome and 3/ the ctDNA could be a predictive biomarker of eryaspase efficacy. Clinical trial information: NCT02195180 .