bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative therapy for gastric adenocarcinoma in relation to oncologic outcomes in patients with complications after gastrectomy.
Authors: Vicente Diego , Ikoma Naruhiko , Chiang Y. Sabrina , Fournier Keith , Mansfield Paul F. , Ajani Jaffer A. , Badgwell Brian D. 
Published: January 2019

107 Background: Postoperative complications (POC) are associated with poor oncologic outcomes in gastric cancer, however, it is unknown if preoperative therapy has any impact on this association. We sought to evaluate the impact of POC on survival in patients with gastric cancer treated with upfront surgery versus those treated with preoperative therapy. Methods: We analyzed data from a prospectively maintained database of patients who had undergone resection of their gastric cancer at our institution between 1995 and 2015. Patients with T1N0 or M1 lesions, recurrent disease, mortality within 90 days, and GEJ tumors were excluded. Cox regression analyses were used to examine factors associated with overall survival (OS) and disease free survival (DFS). Interaction terms between complications and preoperative therapy were used in the multivariate model to determine their impact on OS and DFS. Results: 421 patients underwent resection of gastric cancer: 30% underwent upfront surgery, and 51% had a POC. Variables associated with POCs included total gastrectomy (p = 0.02) and additional organ resection (p = 0.05). Among patients who had POCs, 71% were infectious, 41% experienced multiple complications, and 55% were classified as Clavien-Dindo grade III or IV. On multivariable analysis, the presence of a POC had the strongest association with diminished OS (HR 3.5, 95% CI 1.9-6.5). Among patients who underwent upfront surgery, patients with a POC had shorter OS (5-year, 85% vs. 47%; p < 0.001) and DFS (5-year, 76% vs. 46%; p < 0.001) than those without a POC. In contrast, there was no difference in OS (5-year, 63% vs. 57%; p = 0.77) and DFS (5-year, 52% vs. 52%; p = 0.52) between patients with and without POC who received preoperative therapy. Interaction terms between preoperative therapy and complication in the multivariable Cox regression model were significant on OS (3.53 [95%CI: 1.92-6.52]) and DFS (2.84 [95%CI: 1.59-5.08]), which indicated that the negative impact of complications were reduced if patients received preoperative therapy. Conclusions: The use of preoperative therapy negated the impact of POCs on OS and DFS in patients undergoing resection for gastric cancer.
A survival analysis of a prospective multicenter observational study of surgical palliation in patients treated for malignant gastric outlet obstruction caused by incurable advanced gastric cancer.
Authors: Terashima Masanori , Fujitani Kazumasa , Ando Masahiko , Sakamaki Kentaro , Kawabata Ryohei , Ito Yuichi , Yoshikawa Takaki , Kondo Masato , Kodera Yasuhiro , Kaji Masahide , Oka Yoshio , Imamura Hiroshi , Kawada Junji , Takagane Akinori , Shimada Hideaki , Tanizawa Yutaka , Yamanaka Takeharu , Morita Satoshi , Ninomiya Motoki , Yoshida Kazuhiro 
Published: January 2019

113 Background: We previously reported that surgical palliation maintained patients’ quality of life (QOL) while improving the solid food intake with an acceptable surgical safety in patients with malignant gastric outlet obstruction (GOO) caused by advanced gastric cancer. To elucidate the impact of the improvement in the QOL on the survival, we performed a survival analysis according to the changes in the QOL. Methods: Eligibility criteria included (1) no or liquids-only oral intake, (2) aged ≥20 , (3) surgically fit, (4) ECOG PS of 0-2, and (5) written informed consent. Patients underwent either palliative gastrectomy or gastrojejunostomy. Validated QOL instruments (EORTC QLQ-STO22 and EuroQol-5D) assessed the QOL at baseline, 2 weeks, 1 month, and 3 months following surgical palliation, and postoperative improvement in the oral intake was also evaluated. Univariate and multivariate survival analyses were performed according to baseline characteristics and changes in QOL 2 weeks, 1 month, and 3 months after the operation. Results: The median survival time in the 104 patients was 11.30 months. In the univariate analysis, the survival was significantly better in the patients who received gastrectomy, received adjuvant chemotherapy, had a better PS, and had a worse baseline EQ5D score. Changes in the QOL scores had no marked impact on the survival at 2 weeks and 1 month after operation. However, in patients with an improved or stable EQ5D score at 3 months post-surgery, the survival was significantly better (p = 0.0043). An improved oral intake on the GOO score system (GOOSS) had a positive impact on the survival. A multivariate analysis in the patients survived more than 3 months after the operation revealed that adjuvant chemotherapy, a better baseline PS, a worse baseline EQ5D, an improved or stable EQ5D score, and an improved oral intake on the GOOSS at 3 months after surgical palliation were independent prognostic factors. Conclusions: In patients who received surgical palliation for malignant GOO caused by advanced gastric cancer, an improved oral intake and QOL score at 3 months after operation predicted a good survival. Clinical trial information: 000023494.
Histopathological tumor regression or ypN: Which better predicts survival of patients who received neoadjuvant chemotherapy and surgery for non-type 4 locally advanced gastric cancer?
Authors: Fujitani Kazumasa , Nakamura Kenichi , Mizusawa Junki , Kuwata Takeshi , Shimoda Tadakazu , Katayama Hiroshi , Kushima Ryoji , Taniguchi Hirokazu , Yoshikawa Takaki , Boku Narikazu , Terashima Masanori , Fukuda Haruhiko 
Published: January 2019

114 Background: Histopathological tumor regression with < 10% residual tumor is a globally accepted prognostic factor in gastric cancer patients who received neoadjuvant chemotherapy (NAC) and curative surgery, however, impact of ypN remains unclear. Methods: Previously, Japan Clinical Oncology Group (JCOG) had conducted 3 phase II trials to evaluate NAC with irinotecan/CDDP (JCOG0001) and S-1/CDDP (JCOG0405) for extensive nodal disease, and with S-1/CDDP (JCOG0210) for large type 3 and type 4 (linitis plastica) disease. Prognostic factors, including ypN and histopathological tumor regression with < 10% residual tumor, were analyzed in patients with curative resection excluding type 4 advanced gastric cancer in these trials by univariable and multivariable analyses using the Cox proportional hazards model. Results: Among 85 patients, 5-year OS was 46.0% (95% CI, 35.0-56.4). Median OS was not reached in patients with < 10% residual tumor (n = 26), whereas that was 2.7 years (95% CI, 1.4-4.5) in patients with > 10% residual tumor (n = 59) (p = 0.008). Median OS was not reached in patients with ypN0-1 (n = 25), whereas that was 2.6 years (95% CI, 1.5-4.0) in patients with ypN2-3 (n = 60) (p = 0.003). On multivariable analysis, only ypN2-3 was an independent predictor of OS (hazard ratio, 3.67; 95% CI, 1.55 to 8.69), whereas < 10% residual tumor was not (hazard ratio, 2.24; 95% CI, 0.98 to 5.10). Conclusions: It is suggested that ypN may have greater impact on the survival than histopathological tumor regression in patients who received NAC and surgery for AGC.
Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for local advanced gastric or Siewert II/III GEJ cancer: A retrospective analysis.
Authors: Li Guichao , Wo Jennifer Y , Blaszkowsky Lawrence Scott , Zheng Hui , Clark Jeffrey W. , Mullen John , Rattner David W , Berger David L. , Eyler Christine , Keane Florence K. , Zhu Andrew X. , Murphy Janet E. , Goyal Lipika , Parikh Aparna Raj , Allen Jill N. , Ryan David P. , Zhang Zhen , Hong Theodore S. 
Published: January 2019

115 Background: Radiation therapy has improved survival in gastric cancer in some randomized trials. However, post-operative fields have been difficult tolerate, and completion rates have been low. Preoperative therapy may afford the opportunity to radical therapy, and potentially improve the resectability in advanced patients. Methods: Patients with Siewert II/III GE junction or gastric cancer treated at Massachusetts General Hospital were evaluated with Institutional Review Board approval. Clinical parameters and prognostic factors including gender, age, clinical stage, pathological stage, radiation parameters, concurrent chemotherapy, non-radiation chemotherapy, toxicity and survival were included in the analysis. Results: From Jul 2005 to Jan 2017, we enrolled 88 patients had chemoradiotherapy (CRT) and surgery, 48 preoperative and 40 postoperative CRT patients. In the preoperative group, 16.7% (8/48) had nodes outside a standard D2 dissection range, and the pathologic complete regression (pCR) rate was 18.8% (9/48). Median preoperative and postoperative radiation dose was 50.4 Gy and 45 Gy. Two-drug regimen was the most commonly used preoperative concurrent chemotherapy: 60.5% and single drug was the most commonly used postoperative concurrent chemotherapy: 97.5%. Except concurrent chemotherapy, 25 preoperative CRT patients received induction FOLFOX (median 8 cycles); 9 postoperative CRT patients also received 5-FU and 23 received FOLFOX (or EOX) chemotherapy. The estimated 3-year relapse-free survival (RFS) and overall survival (OS) in the preoperative and postoperative group was 51% vs. 34.3% (p = 0.286), and 71.2% vs. 45.9% (p = 0.179), respectively. In preoperative CRT group, there was more hematological toxicity but less gastrointestinal toxicity than postoperative CRT group, more distant metastasis but less peritoneal recurrence rate. Conclusions: Compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy option has the trend of better tolerance, higher RFS and OS in patients with local advanced gastric cancer. Different chemoradiotherapy strategy may lead to different recurrence patterns.
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced esophageal squamous cell carcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.
Authors: Xu Rui-hua , Wang Fenghua , Shi Jianhua , Feng Ji Feng , Shen Lin , Yang Shujun , Hu Xi-Chun , Dai Guanghai , Xu Nong , Jiang Yi , Yongqian Shu , Zhang Qingyuan , Chen Ye , Yuan Xianglin , Lin Xiaoyan , Ba Yi , Li Qi , Li Wei , Huang Haixin , Yao Sheng 
Published: January 2019

116 Background: Patients with Esophageal squamous cell carcinoma (EC) often present with advanced and metastatic stage disease, which has poor prognosis and limited treatment options, and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic EC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic EC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19 2017 and Sep 11 2017, 56 EC pts (84.9% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11 2017, 34 EC pts have been evaluated for clinical efficacy. Among these pts, 8 PR (partial response) and 14 SD (stable disease) were observed (ORR 23.5% and DCR 64.7%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell [TC] or on Immune Cell [IC] by SP142) in EC tumor tissue was 21.4% (12/56). 2/10 (20%) PD-L1+ patients and 6/24 (25%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic EC pts with a manageable safety profile. Clinical response was not correlated with PD-L1 expression. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.
Updated results of phase 1 study of DS-8201a in subjects with HER2-expressing gastric cancer.
Authors: Iwasa Satoru , Shitara Kohei , Takahashi Shunji , Park Haeseong , Kadowaki Shigenori , Modi Shanu , Nonagase Yoshikane , Tamura Kenji , Yamaguchi Kensei , Muro Kei , Tsurutani Junji , Shahidi Javad , Lee Caleb C. , Sugihara Masahiro , Kawaguchi Yoshinori , Doi Toshihiko 
Published: January 2019

118 Background: DS-8201a is a HER2 targeting antibody-drug conjugate of high drug to antibody ratio (7 to 8) with a novel linker and topoisomerase I inhibitor. In preclinical studies, DS-8201a demonstrated a broad antitumor spectrum including efficacy against low HER2 expressing cancers. Interim results of the first-in-human phase 1 trial reported an overall confirmed response rate of 40.2% across several tumor types including breast and gastric (data cutoff of May 11, 2017). Here, we present updated results focusing on HER2 expressing gastric cancer (GC) subjects as of August 1, 2017. Methods: The trial consists of part 1, dose-escalation, and part 2, dose expansion cohorts. Part 2 included the cohort for subjects with HER2 expressing GC previously treated with trastuzumab. HER2 status was determined by IHC, and/or FISH according to ASCO CAP guidelines. Results: Seven GC subjects were enrolled in Part 1and 41 subjects were enrolled in Part 2. The median number of prior anticancer treatment was 3. In Part 1, confirmed ORR across doses was 43% (3/7). One out of two subjects with HER2 low (IHC2+/ISH-) showed PR. In Part 2, confirmed ORR and DCR were 44% (16/36) and 78% (28/36), respectively with 83% of subjects experiencing tumor shrinkage. Currently, the median DoR and PFS are ≥31 weeks and 25 weeks, respectively. For subjects enrolled in part2b, the most common AEs of any grades were nausea (All 71%; ≥Gr3 2%), decreased appetite (All 61%; ≥Gr3 10%), vomiting (All 22%; ≥Gr3 0%) and platelet count decreased (All 32%; ≥Gr3 17%). Five subjects (10%) discontinued drug treatment due to AE. Conclusions: DS-8201a demonstrated promising antitumor activity in heavily pretreated subjects with HER2 expressing GC. Clinical trial information: NCT02564900.
Clinical significance of lymphatic flows around pylorus identified by sentinel node mapping in patients with gastric cancer.
Authors: Aoyama Junya , Kawakubo Hirofumi , Mayanagi Shuhei , Fukuda Kazumasa , Suda Koichi , Nakamura Rieko , Wada Norihito , Kitagawa Yuko 
Published: January 2019

12 Background: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries. The suprapyloric lymph nodes (No. 5) and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin, and the subpyloric lymph nodes (No. 6) are classified in the right gastroepiploic artery (r-GEA) basin. The aim of this study is to analyze the lymphatic flows between these lymph nodes and basins. Methods: Five hundred and fourty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. Results: We detected SN No. 5 in 36 (6.6 %) patients. In these patients, we detected SN No. 5 with SNs that belonged to the left gastric artery (l-GA) basin (69 %), r-GA basin (14 %), and r-GEA basin (44 %). No. 6 was detected as SN significantly more frequently with SN No. 5. We detected SN No. 6 in 100 (18.2 %) patients. In these patients, we detected SN No. 6 with SNs that belonged to the l-GA basin (42 %), left gastroepiploic artery (l-GEA) basin (4 %), r-GA basin (28 %), and r-GEA basin (41 %). No. 4d, No. 5 and No. 8a were detected as SNs significantly more frequently with SN No. 6. We detected SN No. 8a in 43 (7.8 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the l-GA basin (65 %), l-GEA basin (7 %), r-GA basin (21 %), r-GEA basin (58 %), and posterior gastric artery (p-GA) basin (7 %). No. 6 and No. 9 were detected as SNs significantly more frequently with SN No. 8a. SN No. 5 and No. 8a were tend to be detected with not SNs that belonged to the r-GA basin but No. 6, and SN No. 6 was detected significantly more frequently with No. 4d, No. 5 and No. 8a. Conclusions: Our findings show that lymphatic flows exist not only between lymph nodes which are belonged to the same basin, but also between No. 5 and No.6, and No.6 and No. 8a. On the other hand, the lymphatic flows between No. 5 and No. 8a seem to be limited. Our results suggest that the lymph node dissection of No. 6 given lymphatic flows from lesser curvature side and retroperitoneal side is important for surgery of gastric cancer.
Potentially curable gastric adenocarcinoma (GAC) patients treated without surgery.
Authors: Mizrak Kaya Dilsa , Nogueras-Gonzalez Graciela M. , Estrella Jeannelyn , Harada Kazuto , Ghazanfari Amlashi Fatemeh , Lin Quan , Blum Murphy Mariela A. , Lee Jeffrey H , Weston Brian , Bhutani Manoop S. , Matamoros Aurelio , Sagebiel Tara L. , Devine Catherine E , Patnana Madhavi , Minsky Bruce D. , Das Prajnan , Badgwell Brian D. , Ajani Jaffer A. 
Published: January 2019

120 Background: Surgery is the best option to cure localized GAC. When surgery is not possible due to comorbidities or patient refusal, definitive chemoradiation is an option. We report on one of the largest cohorts of GAC patients who did not have surgery. Methods: We identified 71 patients with localized GAC who received chemo/chemoradiation therapy but did not have surgery. We assessed various endpoints (overall survival [OS] and recurrence-free survival [RFS]). Clinical complete response (cCR; negative post therapy biopsy and no evidence of cancer by imaging) was also assessed. Results: The median follow-up time was 1.8 years (range; 0.4-10.6). Most of the patients were men (64.8%) and the median age was 73 years (range; 30-96). Reason for not having surgery included comorbidities in 34 (47.9%), poor performance status 14 (19.7%), and patient refusal 23 (32.4%). Most of the patients (80.3%) received chemoradiation and 14 (19.7%) could receive only chemotherapy. Of all 71 patients, 32 (45.1%) achieved to a cCR. For the entire cohort, the median OS was 2.1 years (95% Cl 0.98-1.02). The estimated OS rates at 2 and 5 years were 46.5% and 11.3%, respectively. The median OS and the median RFS for patients with cCR were 2.3 and 1.8 years (95% Cl 0.97-1.01), respectively. Female gender (HR 0.47, 95% Cl 0.25-0.91, p = 0.024) and chemoradiation (HR 0.36, 95% Cl 0.16-0.85; p = 0.019) were independently associated with longer OS in the multivariate analysis. Histologic grade and the presence of signet ring cell had no effect on OS. Conclusions: Our data show that patients with localized GAC who do not undergo surgery have a low but measurable 5-year OS rate of 11.3%.
Fluoropyrimidine (F) alone versus F plus platinum (P) as first-line chemotherapy in patients (pts) with advanced gastric cancer (AGC) and severe peritoneal metastasis (SPM): A multicenter observational study.
Authors: Arai Hiroyuki , Iwasa Satoru , Boku Narikazu , Kawahira Masahiro , Yasui Hirofumi , Masuishi Toshiki , Muro Kei , Hironaka Shuichi , Fukuda Naoki , Takahari Daisuke , Nakajima Takako Eguchi 
Published: January 2019

121 Background: The standard 1st-line chemotherapy for AGC pts with SPM has not been established. F alone is generally used for their treatment because of difficulty of hydration for dosing of cisplatin (CDDP) in pts with massive ascites, and has shown limited efficacy. It is unclear whether a combination of F and P (CDDP or oxaliplatin): FP improves their clinical outcome. We therefore investigated the efficacy and safety of FP in comparison with F alone. Methods: This retrospective study comprised of AGC pts with SPM and HER2 negative or unknown tumors who received FP or F as 1st-line chemotherapy between Jul 2010 and Sep 2016 at 6 institutions in Japan. SPM was defined as having massive ascites and/or inadequate oral intake requiring intravenous nutrition support. Overall survival (OS), progression-free survival (PFS), response rate of ascites, improvement rate of oral intake, and safety were compared between two treatment groups. Results: A total of 129 pts (64 in FP group, 65 in F group) were included. Patient characteristics (FP vs F) were as follows: median age, 62 vs 67; PS 0/1/2/3/4 (%), 6/64/25/3/2 vs 8/42/42/8/0; massive ascites/inadequate oral intake/both (%), 61/25/14 vs 35/29/35; number of metastatic sites 1-2/3-5 (%), 77/23 vs 78/22; median serum albumin level (g/ml), 3.1 vs 3.1. OS was significantly longer in FP group than F group (median, 9.0 vs 5.0 months; HR 0.56, 95%CI 0.39-0.82; log-rank p < 0.01); it remained significant upon multivariate analysis adjusting for prognostic variables (HR 0.48, 95% CI 0.32-0.73, p < 0.01). Pts in FP group had significantly better PFS in both uni- and multivariate analyses (median, 4.3 vs 2.3 months; HR 0.44, p < 0.01 and HR 0.40, p < 0.01, respectively). Response rate of ascites (51% vs 17%) and improvement rate of oral intake (64% vs 43%) also were better in FP group (p < 0.01 and p = 0.09, respectively). Toxicities were tolerable in both groups, but grade ≥3 neutropenia was more frequent in FP group (36% vs 11%). Conclusions: FP showed significantly better efficacy than F alone, and it could be a promising option as 1st-line treatment for AGC pts with SPM.