bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival impact of the response at twelve weeks in patients with advanced gastric cancer received first-line chemotherapy.
Authors: Arakaki Motoko , Aoki Masahiko , Imazeki Hiroshi , Shoji Hirokazu , Honma Yoshitaka , Iwasa Satoru , Okita Natsuko , Takashima Atsuo , Kato Ken , Boku Narikazu 
Published: January 2019

103 Background: The continuation of first-line chemotherapy or the maintenance chemotherapy has been selected for advanced gastric cancer patients who have not progressed after 4 to 6 cycles of first-line chemotherapy. However, survival data about those patients remains unclear. We retrospectively assessed the impact of response at 12 weeks on survival for advanced gastric cancer who received first-line chemotherapy. Methods: Eligible patients had unresectable advanced gastric adenocarcinoma and treated for the combination chemotherapy with fluoropyrimidine and platinum from January 2010 to December 2017 in our hospital. Patients with HER2 positive were excluded. Patients were divided into three groups (PR, SD, or PD group) according to response at 12 weeks of first-line chemotherapy, and their overall survival and progression-free survival were assessed. Results: The total number of the subject was 249 whose median overall survival (mOS) and progression-free survival (mPFS) were 13.8 and 5.4 months. Among 152 patients with measurable lesions, 58, 42, and 52 patients achieved PR, SD, and PD at 12 weeks. mOS was 16.7 months in the PR group, 9.8 months in the SD group, and 5.7 months in the PD group. mPFS was 7.1 months in the PR group, 4.5 months in the SD group, and 1.7 months in the PD group. Among 97 patients without measurable lesions, 90 patients achieved nonCR/nonPD at 12 weeks of first-line chemotherapy whose mOS and mPFS were 17.9 months and 9.2 months while those were 9.6 months and 1.9 months in the remaining 7 patients with PD at 12 weeks. Conclusions: There were clear differences in survival among PR, SD, and PD at 12 weeks in patients with measurable lesions while patients without measurable lesions obtaining nonCR/nonPD at 12 weeks showed similar OS and PFS to those with measurable lesion obtaining PR in first-line chemotherapy for advanced gastric cancer. [Table: see text]
Anatomical topography of the tumor is related to prognostic survival in adenocarcinoma of esophagogastric junction?: Multivariable analysis.
Authors: Takeda Flavio Roberto , Sallum Rubens Antonio Aissar , Ribeiro Ulysses , de Castria Tiago Bianchi , Tustumi Francisco , Rocha Julio Rafael Mariano , Cecconello Ivan 
Published: January 2019

108 Background: The adenocarcinoma of the esophagogastric junction (AJEG) is divided according to its anatomopathological classification (Siewert classification) for the choice of surgical treatment. However, both the Siewert classification and the location of the AJEG are related to different prognoses reported in the literature. Objectives: To compare the survival of patients with AJEG submitted to surgical treatment according to different topographies in the esophagogastric junction. Methods: 147 patients were selected between 2000 and 2016. One hundred and thirty (88%) males, mean age 64 years. Analyzing the retrieved lymph nodes, affected and the relation of resected and affected. AEGG (E: esophagus, E/TEG: gastric esophagus, TEG: gastric esophagus transition, TEG/G: esophageal gastric and stomach transition, and E/TEG/G: esophagus, transition and stomach) were analyzed for global survival, free of disease, and after relapse. Results: In relation to epidemiological data, the mean age was 63.1 years. Of the 147 patients 90 (61.2%) were submitted to neoadjuvant treatment. There was no statistical difference between the groups regarding histological grade, pT, pN, stage, tumor extension, lymphatic, venous and perineural invasion. The mean extension of the tumor was 5.4 cm. The mean number of retrieved lymphnodes were 32. Overall survival was E: 90%, E/TEG: 60%, TEG: 52%, TEG/G: 50% and E/TEG/G: 21%. (p <0.0001). Disease free of survival was E: 78%, E/TEG: 48%, TEG: 43%, TEG/G: 38% and E/TEG/G: 15%. (p <0.001). Conclusions: The survival of the AJEG varies according to the topography of the lesion, the tumors located closer to the stomach present worse survival than those located in the esophagus, except when the tumor is very extensive, from the esophagus to the stomach.
Subgroup analysis of JCOG0501 phase III study to confirm superiority of additional neoadjuvant chemotherapy with S-1 plus cisplatin to D2 gastrectomy with S-1 adjuvant chemotherapy for resectable type IV or large type III gastric cancer.
Authors: Katai Hitoshi , Iwasaki Yoshiaki , Terashima Masanori , Mizusawa Junki , Katayama Hiroshi , Nakamura Kenichi , Yoshikawa Takaki , Boku Narikazu , Yamada Takanobu , Fujiya Tsuneaki , Kawashima Yoshiyuki , Kinoshita Takahiro , Ohashi Manabu , Yamaue Hiroki , Sano Takeshi , Sasako Mitsuru ,   The Stomach Cancer Study Group of Japan Clinical Oncology Group
Published: January 2019

110 Background: We previously reported that the superiority of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin was not demonstrated for schirrhous or similar macroscopic type (type 4 or large type 3) gastric cancer. However, overall survival (OS) in both arms was better than previous reports (3-year OS: 62.4% in gastrectomy plus adjuvant S-1 [arm A] and 60.9% in NAC followed by gastrectomy plus adjuvant S-1 [arm B]). Therefore, we explored whether histology and peritoneal cytology are associated with treatment effect. Methods: After staging laparoscopy, a total of 300 eligible patients with clinically resectable disease were randomized to arm A, or arm B. In this report, treatment effect was explored in key subgroups such as histology and peritoneal cytology using the data from JCOG0501. Cox regression model was used to investigate the interaction between arms and subgroups. Results: Hazard ratio (HR) classified by histology (excluding one missing) was 0.686 (95% CI: 0.414-1.138) for non-signet type (n = 123) and 1.158 (95% CI: 0.805-1.666) for signet type (n = 176) (p = 0.098 for interaction). HR by peritoneal cytology was 0.870 (95%CI: 0.616-1.228) for the negative (n = 240) and 1.051 (95% CI: 0.598-1.845) for the positive (n = 60) (p = 0.513 for interaction). 3 year-OS of signet ring cell histology was 63.2% (95% CI: 52.2-72.4) in arm A and 51.7% (95% CI: 40.9-61.5) in arm B, that of non-signet ring cell histology was 62.3% (95% CI: 48.9-73.1) in arm A and 74.2% (95% CI: 61.4-83.3) in arm B, and that of peritoneal cytology positive was 35.7% (95% CI: 18.9-53.0) in arm A and 25.0% in arm B (95% CI: 11.8-40.7), and that of peritoneal cytology negative was 68.6% (95% CI: 59.5-76.1) in arm A and 70.6% (95% CI: 61.5-77.9) in arm B. Conclusions: NAC might be beneficial for non-signet ring cell histology. Considering the survival results, primary surgery followed by S-1 could be recommended for this disease even though histology was signet ring cell type or peritoneal cytology was positive. Clinical trial information: UMIN000000279.
Evaluation of intratumoral T cells in biopsies from advanced gastric cancer patients treated with andecaliximab and nivolumab.
Authors: Brachmann Carrie , Zhang Yafeng , Elboudwarej Emon , Turner Scott , Thai Dung , Bhargava Pankaj , Metges Jean-Philippe , Cunningham David , Catenacci Daniel V.T. , Van Cutsem Eric , Wainberg Zev A. , Shah Manish A. 
Published: January 2019

118 Background: Preclinical studies suggest that MMP9 inhibition relieves immune suppression and promotes T cell infiltration to potentiate checkpoint blockade. To test this hypothesis, patient tumor samples obtained in a phase 2, open-label, randomized study (NCT02864381) of previously treated advanced gastric cancer comparing the MMP9-specific inhibitor andecaliximab (ADX) plus nivolumab (N) vs N alone were evaluated for T cell biomarkers. Methods: CD8 and PD-L1 (28-8 DAKO) were assessed by immunohistochemistry. IFNg, Teffector (Teff), and activated CD8+ T cell (ActT) gene signatures (GS) were assessed by RNASeq in archival baseline (BL) and biopsies obtained between weeks 5 and 9 (on-treatment; OT). Results: For both N and ADX/N, intratumoral CD8+ cells were significantly increased in OT biopsies relative to BL. The CD8+ OT increase was significantly greater for the ADX/N treatment relative to N in the PD-L1+ subgroup. In the ADX/N group only, IFNg, Teff, and ActT GS were significantly higher in OT biopsies relative to BL. OT change from BL of ≥ 300% vs <300% in CD8+ cells was associated with longer PFS (HR = 0.50, p = 0.032). The percentage of patients with increased CD8+ cells in OT biopsies was higher in the ADX/N arm. Conclusions: In the PD-L1+ ADX/N group, there was a significantly greater magnitude of CD8+ cell density increase, which was associated with gene signatures of T cell activation. More ADX/N-treated patients had an increase in tumor-associated CD8+ cells. Longer PFS was observed for patients in which CD8+ cells increased by ≥ 300%. These results are consistent with the hypothesis that ADX potentiates checkpoint inhibition by favorably altering the tumor immune microenvironment. Clinical trial information: NCT02864381. [Table: see text]
Comparison between S-1 monotherapy and S-1 plus cisplatin as postoperative chemotherapy after R0 resection for stage IV gastric cancer patients with oligometastasis: A multicenter retrospective study.
Authors: Kumagai Koshi , Yamaguchi Toshifumi , Takashima Atsuo , Nagashima Kengo , Kano Yosuke , Terashima Masanori , Yabusaki Hiroshi , Nishikawa Kazuhiro , Tanabe Kazuaki , Yunome Gen , Kawachi Yasuyuki , Yamada Takanobu , Fukunaga Hiroki , Kinoshita Takahiro , Watanabe Masaya , Taniguchi Hiroki , Sakamoto Takeshi , Ishiyama Koshiro , Boku Narikazu 
Published: January 2019

123 Background: Gastric cancer (GC) with liver metastasis (M1: HEP) and para-aortic lymph node metastasis (M1: LYM) is categorized as stage IV. Based on the retrospective reports, surgical resection is weakly recommended for oligo-metastasis (O-Meta), if resectable, in the Japanese GC Treatment Guidelines 2018. Whereas S-1 monotherapy as adjuvant chemotherapy after surgery for stage II/III GC and S-1 plus cisplatin (SP) as palliative chemotherapy for unresectable stage IV GC are standard treatments, there is no consensus about post-operative chemotherapy (Post-Cx) after R0 resection of stage IV GC with O-Meta. Methods: The criteria for this retrospective study were: 1) no prior treatment for GC, 2) R0 resection including O-Meta (HEP or LYM) at 20 institutions in the Stomach Cancer Group of the Japan Clinical Oncology Group between 2007 and 2012, 3) histological confirmation of adenocarcinoma for primary tumor and O-Meta (M1: HEP or LYM), 4) no other distant metastasis such as peritoneal metastasis. Results: A total of 110 patients were collected. Of the 94 eligible patients, 84 patients underwent gastrectomy followed by Post-Cx with S-1 (S-1 group: n = 55), SP (SP group: n = 22) or others (Others group: n = 7), and 10 patients did not receive post-Cx (non-Cx group). Median age for the S-1, SP, Others and non-Cx groups were 66, 60, 61, and 79 years old. Sites of oligo-metastasis (HEP/LYM) was 21/34, 9/13, 2/5, and 7/3 in the S-1, SP, Others and non-Cx groups. The 3- / 5-year overall and relapse free survival (OS and PFS) rates of all the patients were 45.6/31.4% and 24.5/21.3%, respectively. Median OS was 28.5 and 36.5 months in the S-1 and SP groups (HR 0.99; 95% CI 0.54-1.82, p = 0.986). In multivariate analysis, no Post-Cx, over 70 years old were identified as the independent poor prognostic factor for OS (p < 0.05). Conclusions: R0 resection followed by Post-Cx for GC patients with O-Meta showed favorable survival, while there seems no additional benefit of cisplatin to S-1 alone.
Neoadjuvant treatment in patients with locally advanced gastric cancer.
Authors: Gumus Mahmut , Kaya Serap , Eris S , Alan Ozkan , Telli Tuba Akin , Okten Ilker Nihat , Gunaydin Ulug Mutlu , Tuylu Tuba Basoglu , Ay Seval , Ozturk Turkan , Ercelep Ozlem , Aktas Bilge , Akgun Babacan Nalan , Dane Faysal , Yumuk Fulden Perran 
Published: January 2019

127 Background: Although neoadjuvant treatment has been standart approach in gastric cancer with the positive results of randomized controlled studies in recent years, neoadjuvant treatment approach rates are far below the expectations in our country. We aimed to evaluate neoadjuvant treatment approaches and results of gastric cancer patients in this retrospective study. Methods: We evaluated characteristics and survival outcomes of 54 patients that were operated after neoadjuvant systemic treatment out of 1,143 gastric cancer patients recorded in our database. Results: The median follow-up was 12 months in this study. 38% of the patients was female and the median age was 61 (24-78). While 46 % of the tumors were located in gastro-esophagial junction and cardia, others were located distally. All of the patients treated with neoadjuvant treatment had positive lymph nodes. While lymphatic and perineural invasion were detected in 67% of the patients, vascular invasion was detected in 39 % of the patients after the operation. While 43 % of the patients had grade 3 tumors, others had grade 1-2 tumors. R0 resection was achieved in 91% of the patients and D2 dissection was done in 82% of the patients. FOLFOX/XELOX, DCF/DCX, EOX/ECF and FLOT were applied as neoadjuvant treatment regimes in 19%, 50%, 21% and 11% of the patients respectively. The median chemotherapy cycle number was 3 applied pre and postoperatively. The disease control rate (response or stable disease) was achieved in 75,9 % of the patients after the neoadjuvant chemotherapy. In 13 patients progressive disease was detected and these patients were not operated. We found the median disease free survival was 25 months and overall survival was 41 months in survival analysis. Three year DFS was 29 % and 3 year OS was 52 %. Conclusions: Neoadjuvant treatment approach is important both to facilitate operation procedure and to evaluate efficacy of systemic treatment. As the survival advantage was shown in a study last year, FLOT regime is expected to be used more commonly. The patients have to be evaluated and the treatment decisions should be made in a multidisiplinary tumor board including surgeon, radiologist, medical oncologist to provide optimal treatment benefit.
Endoscopic intratumoral injection of OBP-301 (telomelysin) with radiotherapy in esophageal cancer patients unfit for standard treatments.
Authors: Tanabe Shunsuke , Tazawa Hiroshi , Kanaya Nobuhiko , Noma Kazuhiro , Kagawa Shunsuke , Kuroda Shinji , Urata Yasuo , Shirakawa Yasuhiro , Fujiwara Toshiyoshi 
Published: January 2019

130 Background: OBP-301 (telomelysin) is an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase (hTERT) promoter to regulate viral replication. OBP-301 causes selective replication and lysis of a variety of cancer cells, and also inhibits the repair of radiation-induced DNA double-strand breaks, leading to radiosensitization. We aimed to assess intratumoral injection of OBP-301 with radiotherapy in esophageal cancer patients unfit for standard treatments. Methods: An open-label, phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed esophageal cancer patients who deemed unfit to receive surgery or chemotherapy. Study treatment consisted of intratumoral OBP-301 injections on days 1, 18, and 32 of treatment. Radiation therapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Virus administration was performed by intratumoral needle injection of the primary tumor through a flexible endoscope. The primary and secondary end points were incidence of dose-limiting toxicities and objective response rate. Results: Of 13 patients, seven, three, and three patients were treated in the cohorts with 1010, 1011, and 1012 virus particles of OBP-301, respectively. The patients comprised 10 males and 3 females, with median age of 79.7 years (range, 53 to 92 years). Common grade 1 and 2 toxicities included fever, esophagitis, pneumonitis, anorexia, constipation, and gastroesophageal reflux. All patients developed a transient, self-limited lymphopenia. Eight patients had local complete response (CR); all of them exhibited pathologically no viable malignant cells in biopsy specimens, and three had partial response. The objective response rate was 84.6%. The clinical CR rate was 80.0% in stage I and 66.7% in stage II/III, respectively. Histopathologic examination in post-treatment specimens showed massive infiltration of CD8+ cells in three partially responded tumors. Conclusions: Multiple courses of endoscopic OBP-301 injection with radiotherapy were feasible and provided definite clinical benefits in patients with esophageal cancer. Clinical trial information: 000010158.
Prognostic value of nutritional status for esophageal cancer patients undergoing neoadjuvant therapy and resection.
Authors: Saeed Sabrina D , Fontaine Jacques , Pena Luis , Hoffe Sarah E. , Frakes Jessica , Metha Rutika , Gurd Erin , Pimiento Jose Mario 
Published: January 2019

133 Background: Malnutrition, linked to decreased patient tolerance to chemotherapy and increased rates of therapy-related toxicity, negatively affects cancer prognosis. Esophageal carcinomas (EC) frequently present with dysphagia and significant weight loss which may be exacerbated by neoadjuvant chemoradiation, placing EC patients at an increased risk of malnutrition. We therefore aim to assess the prognostic value of pre-operative malnutrition for esophageal cancer patients undergoing neoadjuvant therapy (NAT). Methods: Query of our institution’s IRB approved database of 1113 EC patients (pts) identified 725 individuals who underwent NAT followed by resection from 1994-2018. Seventy-six pts were considered to be at higher nutritional risk during NAT, as indicated by significant weight loss and enteral feeding tube requirement (ETF+), while 644 did not receive pre-operative feeding tube placement (ETF–). Clinicopathologic characteristics, post-operative outcomes, and survival were compared between ETF+ and ETF– using various statistical methods. Results: Of the included pts, 83% were male with a median age of 64.5 (28-86) years. Between ETF+ (n = 76) and ETF– (n = 644), pt characteristics were balanced in terms of initial stage, age, histology and tumor location. A higher percentage of ETF+ pts had > 5% weight loss before NAT (32 vs. 6%; p < .01). ETF+ was associated with a significantly worse median survival (27 vs. 77 m; p < .01), but not with increased post-operative length of hospital stay (p = .69), complications (p = .20) or tumor recurrence (p = .89). Although completion of chemotherapy (p = .46) and radiation (p = .49) were comparable between ETF+ and ETF–, tumor response was worse in the ETF+ group (71 vs. 60% non-complete response; p = .02). Conclusions: Our results suggest that baseline malnutrition is a risk factor for poor survival and negatively impacts the efficacy of neoadjuvant therapy in EC patients. Poor response to NAT in malnourished patients may stem from impaired immune function. Future prospective studies should evaluate other parameters for nutritional assessment to further assess the impact of malnutrition on tumor regression and survival after NAT.
Phase 1b study of andecaliximab (GS-5745, ADX) as monotherapy and in combination with nivolumab (nivo) in Japanese subjects with gastric or GEJ adenocarcinoma.
Authors: Yamaguchi Kensei , Satoh Taroh , Muro Kei , Takashima Atsuo , Ichimura Takashi , Sakai Daisuke , Kadowaki Shigenori , Chin Keisho , Kudo Toshihiro , Mitani Seiichiro , Kitano Shigehisa , Bhargava Pankaj , Zavodovskaya Marianna , Liu JieJane , Fukui Masato , Boku Narikazu 
Published: January 2019

137 Background: Matrix metalloproteinase 9 (MMP9) is a poor prognostic factor in gastric cancer. Preclinical studies suggest that MMP9 inhibition can relieve immune suppression, promote T cell infiltration, and potentiate benefits of checkpoint blockade. ADX is a monoclonal antibody that inhibits the enzymatic activity of MMP9. In this study, safety, PK, exploratory biomarkers, and preliminary efficacy of ADX alone and in combination with nivo were assessed. Methods: Up to 6 Japanese subjects were to be enrolled in Cohort 1 (monotherapy ADX 800 mg IV Q2W), followed by 10 subjects in Cohort 4 (nivo plus ADX). Treatment was continued until PD or unacceptable toxicity. Tumor biopsies were collected before treatment and at week 6. Results: As of August 2018, 8 and 10 subjects were dosed in Cohort 1 & 4, respectively. All subjects received prior chemotherapy (median: 2, range: 1-4). In Cohort 1, Grade 3 AEs included anemia (25%), fatigue, general physical health deterioration, anorexia, and hydronephrosis (each 13%). All were not related to ADX. No DLTs nor responses were observed in Cohort 1. PK of ADX in Japanese subjects was similar to PK previously obtained in a non-Japanese population. The median t1/2 was ~8.1 days after 800 mg dose. All circulating MMP9 was bound to ADX at 2 weeks after dosing in Cohort 1. In Cohort 4, ≥Grade 3 AEs were anemia (20%), DIC, fatigue, anorexia, hypoglycemia, cholangitis, AST increased, neutropenia, and cancer pain (each 10%). ORR was 40% (4/10) and median PFS & OS have not been reached. Cohort 4 biomarker data will be presented. Conclusions: Preliminary safety data demonstrate a manageable safety profile for ADX alone and in combination with nivo. The combination appears to be promising. Clinical trial information: NCT02862535.
Safety of laparoscopic total gastrectomy with splenectomy for upper third advanced gastric cancer.
Authors: Akimoto Eigo , Tokunaga Masanori , Sato Reo , Kaito Akio , Kinoshita Takahiro 
Published: January 2019

139 Background: In patients with locally advanced gastric cancer, total gastrectomy with splenectomy (TGS) is sometimes indicated when a tumor directly infiltrates the spleen or obvious splenic hilar lymph node metastasis exists. However, this procedure is technically demanding and can cause potentially fatal postoperative pancreas-related complications. TGS has increasingly been performed laparoscopically, particularly in East Asia. However, the number of reports regarding laparoscopic TGS (LTGS) is limited, and thus the feasibility of LTGS remains unclear. Methods: The present study included 68 patients with upper-third advanced gastric cancer who underwent LTGS or conventional open TGS (OTGS) between 2012 and 2018. Clinicopathological characteristics and surgical outcomes were retrospectively reviewed and compared between the groups. Results: There were no significant differences in sex, age, tumor size, cN factor, or cStage. cT4 was less frequently included in the LTGS group (21.4 vs 79.6 %, P < 0.01). In the LTGS group, operating time was longer (332 vs 247 min, P < 0.01) and blood loss was less (38 vs 598 ml, P < 0.01). Incidence of Clavien-Dindo grade 3 or higher complication (0 vs 24.1 %, P = 0.05) and median postoperative hospital stay (9 vs 11 days, P = 0.03) were significantly difference between the groups. The median number of harvested No. 10 and No.11d lymph nodes was equivalent between the groups. Conclusions: LTGS can be a safe procedure provided an experienced surgical team performs the surgery. Oncological safety remains unclear, and needs to be confirmed in future trials.