bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-1+oxaliplatin with pembrolizumab for advanced gastric cancer: The cohort 1 in a phase IIb KEYNOTE-659 study.
Authors: Yasui Hisateru , Kawazoe Akihito , Yamaguchi Kensei , Negoro Yuji , Azuma Mizutomo , Amagai Kenji , Hara Hiroki , Baba Hideo , Tsuda Masahiro , Hosaka Hisashi , Kawakami Hisato , Oshima Takashi , Omuro Yasushi , Machida Nozomu , Esaki Taito , Yoshida Kazuhiro , Nishina Tomohiro , Komatsu Yoshito , Han Shi Rong , Shitara Kohei 
Published: February 2020

382 Background: The KEYNOTE-059 study showed the preliminary antitumor activity and tolerability of chemotherapy with pembrolizumab (P) for advanced gastric cancer (AGC). In Japan, S-1 + platinum regimen is a standard chemotherapy for AGC. The KEYNOTE-659 study (NCT03382600) investigated the efficacy and safety of S-1 + oxaliplatin (SOX; cohort 1) or cisplatin (SP; cohort 2) with P as the first line treatment in patients (pts) with human epidermal growth factor receptor 2 (HER2)-negative, programmed death-ligand 1 (PD-L1)-positive AGC. Here, we report the results of cohort 1. Methods: The key inclusion criteria were as follows: age ≥18 to ≤75 years; an ECOG performance status of 0 or 1; and chemotherapy-naïve, HER2-negative and PD-L1-positive AGC. PD-L1 positivity was defined as a combined positive score of ≥1 using the IHC 22C3 PharmDx assay. An S-1 dose of 40-60 mg per dose was orally administered, twice daily, for the first 2 weeks of a 3-week cycle. P (200 mg) and oxaliplatin (OX; 130 mg/m2) were administered on day 1 of each cycle. The primary endpoint was overall response rate (ORR) that was assessed by a blinded independent central review (BICR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. Results: From April to September 2018, 54 pts were enrolled at 25 sites in Japan. The median follow-up time was 10.1 months. The median number of P doses and cycles in SOX were 9 (range, 2-18) and 6 (range, 2-13), respectively. The relative dose intensities of S-1 and OX were 73% and 60%, respectively. The ORR and DCR assessed by BICR were 72.2% (95% CI 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. The median PFS was 9.4 months (95% CI 6.6-NR). Median DOR and OS were not reached. Grade ≥3 adverse events (AEs) were reported in 31 pts (57.4%). The most common treatment-related AEs of grade ≥3 were thrombocytopenia (14.8%), neutropenia (13.0%), colitis (7.4%), and adrenal insufficiency (5.6%). There were no treatment-related deaths. Conclusions: This study showed the encouraging efficacy and manageable safety of SOX with P therapy as a first line in pts with HER2-negative, PD-L1-positive AGC. Clinical trial information: NCT03382600.
Comparison of efficacy of aspirin plus epirubicin, oxaliplatin, and capecitabine versus epirubicin, oxaliplatin, and capecitabine alone in patients with locally advanced and metastatic gastric cancer: A randomized clinical trial.
Authors: Jafa Esha , Dubashi Biswajit , Kayal Smita , Kate Vikram , Ganesh Rajesh Nachiappa , C. Sunitha V. , L. Charles , Nisha Yadav 
Published: February 2020

384 Background: Aspirin was long known to prevent cancer, the last decade revealed its therapeutic role via varied mechanisms like inhibition of platelet activation, COX and PI3K pathway. Since PI3K/AKT/mTOR is one of the pathways activated in gastric cancer and Giampieri et al (2016) showed improved response rates, PFS and OS with addition of aspirin to capecitabine in heavily pretreated metastatic colorectal cancer,a cancer in which efficacy of aspirin is related to presence of PI3K mutations,we aimed to compare the efficacy of aspirin added to a standard regime EOX with EOX alone in locally advanced and metastatic gastric cancer. Methods: All patients with advanced gastric cancer coming to JIPMER,Department of Medical oncology between march 2017 to may 2019 were screened for eligibility in the trial.Those eligible were randomly assigned to standard EOX or standard EOX plus 150 mg of daily aspirin.Tumor measurements were performed at baseline,then after 3-4 cycles (interim response) and the response to treatment was assessed by the radiologist who was blinded to treatment arms according to RECIST1.1 criteria.Toxicity profiles were recorded as per CTCAE v 4.03.In per protocol analysis,response rates, PFS(progression free survival) and OS (overall analysis) were analysed for patients who received ≥3 cycles and had an evaluable interim response. Results: 95 patients were randomised.In per protocol analysis, 70 patients were included. The results are shown in table. Conclusions: No statistically significant difference was seen with respect to response rates, PFS, OS and toxicity, although there was a higher ORR (overall response rate=complete response,CR +partial response, PR) and OS seen in EOX plus aspirin arm. Clinical trial information: CTRI/2017/11/010651. JIPMER,Puducherry,India [Table: see text]
Treatment efficacy of ramucirumab-based chemotherapy in patients with alpha-fetoprotein producing gastric cancer (AFPGC).
Authors: Kamiimabeppu Daisaku , Wakatsuki Takeru , Takahari Daisuke , Fukuda Naoki , Osumi Hiroki , Nakayama Izuma , Ogura Mariko , Sato Tarou , Ooki Akira , Shinozaki Eiji , Suenaga Mitsukuni , Chin Keisho , Yamaguchi Kensei 
Published: February 2020

389 Background: AFPGC is an aggressive subgroup of gastric cancer and is associated with a worsened survival because of a high incidence of liver metastasis. Ramucirumab-based chemotherapy is the standard treatment as a second line in advanced gastric cancer. Recently ramucirumab has showed survival benefit in hepatocellular carcinoma, but only those with higher AFP levels. However, the efficacy of ramucirumab in AFPGC is unknown. Methods: We retrospectively assessed 283 patients who received paclitaxel or nab-paclitaxel combined with ramucirumab between July 2015 and December 2018. AFPGC was defined when serum AFP levels were elevated and correlated with the disease state during treatment. Non-AFPGC was defined when serum AFP levels were normal when diagnosed. Other patients were excluded. Patients’ demographics, progression-free survival (PFS), overall survival (OS) and objective response rates (ORR) were compared between the two groups. Results: Among the 283 patients, 24 patients were AFPGC and 189 patients were non-AFPGC. AFPGC was associated with high incidences of intestinal histology (46%) and liver metastasis (63%), while AFPGC was associated with a low incidence of peritoneal metastasis (21%), compared with non-AFPGC. There was no significant difference in PFS and OS between the two groups. Median PFS were 5.4 (95%CI 3.6-6.7) months in AFPGC and 4.1 (3.7-5.1) months in non-AFPGC (HR 0.93 95%CI 0.60-1.46, p = 0.788), respectively. Median OS were 19.0 (95%CI 13.2-NA) months in AFPGC and 19.3 (17.9-20.1) months in non-AFPGC (HR 1.21 95%CI 0.70-2.10, p = 0.494), respectively. Regarding with ORR, AFPGC showed higher ORR with 52.6% (95%CI 30.2-75.1), while 37.3% (95%CI 26.4-48.3) in non-AFPGC (p = 0.296), although this was not statistically significant. Conclusions: Ramucirumab showed comparable survival and higher ORR in AFPGC than in non-AFPGC. Considering the generally poor prognosis of AFPGC, it is speculated that ramucirumab may have compensated for disadvantage in survival.
Durvalumab (D) and PET-directed chemoradiation (CRT) after induction FOLFOX for esophageal adenocarcinoma.
Authors: Ly Michele , Molena Daniela , Sihag Smita , Wu Abraham Jing-Ching , Shah Pari M. , Gu Ping , Sugarman Ryan , Maron Steven Brad , Chalasani Sree Bhavani , Shcherba Marina , Yeh Randy , Tang Laura H. , Alterman Carly , Collins Paige , Cowie Kendall , Janjigian Yelena Yuriy , Ilson David H. , Ku Geoffrey Yuyat 
Published: February 2020

394 Background: We previously presented safety data for the combination of D with carboplatin/paclitaxel (C/P) and RT for locally advanced esophageal cancer (J Clin Oncol 2018;36:172 [abstr]). Based on the positive results of the CALGB 80803 study (J Clin Oncol 2017;35:1 [abstr]), we amended the study to administer induction FOLFOX prior to PET assessment. Here, we present updated results. Methods: Patients (Pts) had TanyN+ or T3-4NanyM0 esophageal and Siewert Type I-III GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received mFOLFOX6 ×2 prior to repeat PET/CT. PET responders (PETr) received 5-FU or capecitabine and oxaliplatin with RT to 50.4Gy, while PET non-responders (PETnr) received C/P with RT. All Pts received D 1,500 mg q4W ×2 starting 2 wks prior to and during CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg q4W ×6. Results: 20 Pts have been enrolled: 16 GEJ, 4 esophageal; 3 T1-2N+, 8 T3-4N0, 1 T3Nx, 8 T3-4N+. 13 of 20 Pts (65%) are PETr. Of 13 Pts who have had surgery (8 PETr, all R0), pathologic complete response (pCR) was seen in 3 (23%; 2 PETr); 3 Pts (23%; all PETr) had ypT1bN0 tumors with 99% response and 1 Pt (8%; PETnr) had ypT0N1 (1/30 LN) with profound response in LN. 2 Pts had MSI tumors (1 PETr; 1 pCR, 1 ypT2N0 with 90% response). Notable gd 3/4 adverse events (AEs) observed were lymphopenia in 16 Pts (80%), neutropenia in 4 Pts (20%) and diarrhea and dysphagia in 1 Pt each (5%). Notable gd 1/2 AEs in ≥20%: thrombocytopenia (18 Pts), fatigue (13 Pts), anemia (12 Pts), increased AST (12 Pts), constipation (11 Pts), nausea (11 Pts), diarrhea (7 Pts) and odynophagia (7 Pts). Immune-related AEs noted were gd 3 hepatitis and gd 2 dermatitis in 1 Pt and gd 1 hypothyroidism in 1 Pt. Median length of post-op stay is 8 days, with 18% anastomotic complication rate. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT is safe and feasible. pCR and near-pCR in ½ of Pts is encouraging and compares favorably to our historical pCR rate of 15% in PETr (Cancer 2016:122:2083) and pCR rate of 31% in CALGB 80803 Pts who received induction FOLFOX. Accrual to 36 Pts continues and updated outcomes and immune correlative data will be presented. Clinical trial information: NCT02962063.
Neoadjuvant chemotherapy with docetaxel plus oxaliplatin and S-1 for locally advanced, resectable gastric or gastro-esophageal junction adenocarcinoma: Short-term results from a phase II trial.
Authors: Kawase Tomono , Kurokawa Yukinori , Kobayashi Noboru , Takeno Atsushi , Kawabata Ryohei , Takahashi Tsuyoshi , Yamasaki Makoto , Doki Yuichiro 
Published: February 2020

397 Background: In locally advanced, resectable gastric or gastro-oesophageal junction (EGJ) adenocarcinoma, perioperative the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) is the standard chemotherapy in Europe. However, there is no evidence of neoadjuvant chemotherapy for resectable gastric cancer in Japan. Therefore, we conducted a phase II trial of neoadjuvant chemotherapy with docetaxel plus oxaliplatin, and S-1 (DOS) for locally advanced, resectable gastric or EGJ adenocarcinoma. Methods: Eligible patients had histologically confirmed gastric or EGJ adenocarcinoma of a clinical Stage III according to the 14th Edition of Japanese Classification of Gastric Carcinoma. DOS was administered for two or three preoperative cycles followed by eight postoperative cycles of S-1. Each 3-week cycle of DOS consisted of docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 plus S-1 80-120 mg/body on days 1 to 14. Primary endpoint was 3-year progression-free survival rate, and secondary endpoints included overall survival, progression-free survival, response rate, histological response rate, R0 resection rate, and adverse events. Results: Of 50 enrolled patients, 48 (37 gastric and 11 EGJ) were eligible for the analysis. 42 (88%) patients completed two or three preoperative cycles of DOS. The most common grade 3-4 adverse events of DOS were neutropenia (69%), leukopenia (56%), diarrhea (19%), and febrile neutropenia (13%). Of 45 patients who underwent gastrectomy, postoperative morbidities (Clavien-Dindo ≥Grade II) occurred in 12 (27%) patients. R0 resection could be achieved in 43 (90%) patients. 12 (27%) and 30 (67%) of 45 patients achieved pathological response rate of Grade2-3 and Grade1b-3, respectively. There was no treatment-related death. Conclusions: Neoadjuvant DOS for locally advanced, resectable gastric or EGJ adenocarcinoma might be favorable. Long-term results will be published in two years. Clinical trial information: 000017652.
Enhanced microbial diversity and chemoradiation response in HPV+ anal cancer.
Authors: Kouzy Ramez , Lin Daniel , Noticewala Sonal Suresh , Colbert Lauren Elizabeth , Taniguchi Cullen M. 
Published: February 2020

4 Background: Anal cancer is a rare, but treatable, malignancy caused by the human papilloma virus (HPV). Because anal cancer is uncommon and carries a significant social stigma, this disease has rarely been studied in a prospective fashion, creating a large knowledge gap of which biological factors can improve treatment responses, particularly the microbiome which regulates many facets of oncobiology. Methods: We collected microbiome samples before, during, and after definitive chemoradiation for localized anal cancer as part of an IRB-approved institutional clinical trial (2017-0606). Samples were collected by a non-invasive swab biopsy that enabled collection of tumor cells and microbiome during standard-of-care treatment visits. Bacterial genomic DNA is extracted using MO BIO PowerSoil DNA Isolation Kit (MO BIO Laboratories) and the 16S rDNA V4 region is amplified by PCR and sequenced on the MiSeq platform (Illumina) using the 2x250 bp paired-end protocol, yielding pair-end reads that overlapped almost completely. Sequence read pairs are demultiplexed using unique molecular barcodes, and reads are merged using USEARCH version 7.0.1090 and grouped by organizational taxonomy units (OTU’s) representative of unique bacterial species. Responders are were those patients who had more than 60% tumor shrinkage by MRI at the midpoint of treatment, and all others were considered non-responders. Results: As of June 2019 we enrolled 17 patients and analyzed 14. The majority of patients (10/14, 71.4%) were responders but unfortunately, 4 patients developed in-field recurrences of their anal cancer within a year after their treatment ended and were all T3 or T4 tumors. We found that alpha-diversity of the microbiome did not change during chemoradiation, but non-responders exhibited a lower alpha diversity compared to responders at baseline. Furthermore, specific taxa were correlated with treatment response, which imply a basis for future therapy. Conclusions: The alpha diversity of the microbiome is correlated with treatment response in HPV+ anal cancer. The idenitification of specific bacterial species between responders and non-responder might pave the way for more effective therapeis in the future.
Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.
Authors: Kim Yu Jin , Kim Won Shik , Kim Sang Woo , Jung Woon Yong 
Published: February 2020

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.
Transcriptional profile of immune microenvironment and their prediction role for the prognosis of esophageal squamous cell carcinoma.
Authors: Guo Jianji , Liu Tao , Shi Xinying , Mao Beibei , Zhang Jiao , Zhang Henghui , Xian Lei 
Published: February 2020

416 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer in China. The genetic characterizations have already been described in many studies, but the immune microenvironment features were seldom reported. Our study was aimed to explore the relationship between the immune profile in stage IIIa ESCC and patients’ prognosis. Methods: 20 eligible stage IIIa ESCC patients with received surgery and radiotherapy (19 with and 1 without radiotherapy). RNA targeted sequencing was performed on 20 primary tumor specimens. Transcripts of 395 immune-related genes expressed in tumor were analyzed. The univariate and multivariate Cox proportional hazards analyses were examined the relations of 395 genes’ expression and the prognosis. Results: Patients were divided into two groups based on the median expression values of 395 genes. The univariate analyses showed 20 genes were significantly associated with overall survival (OS). Unsupervised hierarchical clustering analysis using 20 gene expression data revealed two distinct clusters (cluster 1 and 2). The cluster1 patients had high level expression of AXL, ADGRE5, CD40, CXCR6, MPO, etc., which were associated with tumor proliferation and migration. However, the cluster2 patients expressed higher NOS2, IL15, IKZF2, TNFRSF18 which were related with T lymphocyte activated. Therefore, the cluster2 patients had significantly longer OS than cluster 1. Moreover, the combined expression of 10 genes (CD40, ADGRE5, CSF1R, CCR1, IGSF6, MPO, MRC1, SRGN, CD63, LRP1) which had high correlation among 20 genes were significantly related to OS and DFS (disease free survival) in univariate analysis. The multivariate analyses demonstrated that 10 genes signature expression was the independent high risk factor for OS, and the low signature value was associated with better prognosis. Conclusions: In IIIa ESCC, the 20 genes can profile the tumor immune microenvironment, and were independently associated with the patients’ OS. The 10 genes’ signature which represents the malignancy and immune activation of tumor was an independent predictive factor for OS, which can identify the patients with favorable or poor prognosis.
Neutrophil-to-lymphocyte ratio as a prognostic factor and its relationship to patient (pt) outcomes in the RAINBOW trial.
Authors: Muro Kei , Ajani Jaffer A. , Wainberg Zev A. , Knoderer Holly , Wei Ran , Chatterjee Anindya , Abada Paolo , Ohtsu Atsushi 
Published: February 2020

438 Background: Neutrophil-to-lymphocyte ratio (NLR/N) reflects underlying levels of systemic inflammation and has prognostic value in advanced gastric cancer (G/GEJ). We investigated the relationship between pretreatment NLR and clinical outcomes in the RAINBOW study of ramucirumab (R) with paclitaxel (P) in G/GEJ. Methods: NLR is defined as the ratio of absolute neutrophil count and absolute lymphocyte count from peripheral blood. Pts in ITT population with baseline NLR were analyzed. As no clear NLR cutoff is established in G/GEJ, multiple cutoffs (4, 5, 6) were evaluated and relationships between baseline NLR and efficacy endpoints examined. Median OS, PFS were estimated using Kaplan Meier method; prognostic effects on OS/PFS of baseline NLR subgroups (sg) and treatment effects on OS/PFS within each baseline NLR sg were evaluated using univariate Cox PH models. Results: Baseline characteristics were generally balanced between high NLR sg. Higher baseline NLR groups were associated with worse outcomes regardless of cutoff [mOS N < 4 vs ≥4: 9.2 (8.1, 10.3) vs 5.6 (4.8, 6.6), HR = 0.61 (0.49, 0.75); N < 5 vs ≥5: 8.6 (7.8, 9.6) vs 5.3 (4.5, 6.5), HR = 0.59 (0.47, 0.75); N < 6 vs ≥6: 8.6 (7.8, 9.6) vs 4.7 (4.2, 5.9), HR = 0.55 (0.43, 0.70)]. Consistent treatment benefits (R+P vs Placebo (PB)+P) were observed within high baseline NLR sg (Table). No new safety signals were observed. Conclusions: In this exploratory analysis of RAINBOW, pretreatment NLR ( < 4, 5, 6) were independent prognostic factors of improved survival. Treatment benefits with R+P was preserved within high baseline NLR levels defined by different cutoffs and was consistent with ITT results. Clinical trial information: NCT01170663. [Table: see text]
Epstein-Barr virus associated gastric carcinoma at the United States-Mexico border: A single institution study.
Authors: Gaur Sumit , Subramani Ramadevi , Mcalice Meghan , Padilla Osvaldo , Castillo Brenda Sofia , Alshaban Ahmed , Laxmanswamy Rajkumar 
Published: February 2020

440 Background: Globally, gastric cancer (GC) is the fourth most prevalent cancer, and the second leading cause of cancer related deaths. Epstein-Barr virus is implicated in the pathogenesis of 5-10% of gastric cancers. Based upon the results obtained from of the cancer genome atlas, EBV related GC is characterized by promoter hypermethylation, PIK3CA mutations (80%) and increased expression of PD-1 and PD-L1, making it an attractive target for molecularly targeted therapy and immunotherapeutic options. As such, a case can be made for routine testing for EBV in all GC patients. University medical center, El Paso is a tax payer funded safety net health system in El Paso country, TX. We conducted a pilot study to characterize the prevalence of EBV associated gastric cancer seen at this facility. Methods: After obtaining institutional review board (IRB) approval, we identified cases of GC that were diagnosed between January 1, 2008- and December 31-2017. A total of 104 cases were identified of which 17 samples were randomly selected. Pathology specimens were reviewed to identify grade, subtype (intestinal vs diffuse), degree of lymphocytic infiltration and presence/absence of H. pylori. Representative sections from archived tumors were used to perform in-situ hybridization to look for the presence of Epstein-Barr virus. Samples were analyzed using the Rembrandt In situ Hybridization and Detection Universal RISH& HRP Detection Kit for Epstein-Barr early RNA. Results: The median age of the 17 patients is 63 years with 59% being males. 95% self identified as Hispanic. 41% were smokers, 18% used alcohol. The mean BMI was 27.3. Forty one percent of gastric cancer cases were found in the body, 29% in the antrum, 12% in the cardia, and 6% in the fundus. Forty one percent of cases were Stage IV, 24% stage II, 17% Stage III and 17% Stage I. 95% of cases were high grade, 53% of them had signet ring features. 18% of samples were H. pylori positive. None of the seventeen samples tested positive for EBV. Conclusions: EBV does not seem to contribute significantly to the pathogenesis of gastric cancer in our local population. As such routine testing for EBV in all gastric cancer patients may not be a cost effective utilization of resources at our hospital.