bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of induction epirubicin, oxaliplatin, and flourouracil, surgery and post-operative concurrent cisplatin and fluorouracil chemoradiotherapy (CRT) in patients (pts) with loco-regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).
Authors: McNamara Michael J. , Rice Thomas W. , Rybicki Lisa A. , Rodriguez Cristina P. , Videtic Gregory M. M. , Saxton Jerrold P. , Stephans Kevin L. , Greskovich John , Sohal Davendra , Mason David P. , Murthy Sudish C. , Ives Denise I. , Bodmann Joanna , Adelstein David J. 
Published: March 2020

4087 Background: In pts with LRA ACA of the E/GEJ, CRT and surgery results in excellent locoregional control. Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This single arm phase II study investigated the addition of induction chemotherapy to surgery and post-operative CRT. Methods: Pts with an ultrasound-based clinical stage of T3, N1 or M1a (AJCC 6th) ACA of the E/GEJ were eligible. Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and flourouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy at 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and flourouracil (1000mg/m2/d) given as 96 hour infusions during weeks 1 and 4 of radiotherapy. Results: Between 2/08 and 1/12, 60 evaluable pts enrolled; 95% male, 97% white and 78% with GEJ tumors. Resection was accomplished in 54 pts (90%) and adjuvant CRT in 48 (80%). Toxicity included 1 death during induction (2%), and 2 post-operative deaths (4%). Unplanned hospitalization was required in 18% of pts during induction and 19% during adjuvant CRT. Induction chemotherapy produced a symptomatic response in 79% of pts, a clinical (ultrasound) response in 48% and a pathologic response in 41% (5% complete). With a median follow-up of 31 months, the Kaplan-Meier 3-year projected locoregional control (LRC) is 84%, distant metastatic control (DMC) 44%, relapse-free survival (RFS) 39%, and overall survival (OS) 42%. Symptomatic response to induction and the percentage of remaining viable tumor at surgery proved the strongest predictors of DMC, RFS, and OS. Conclusions: Induction chemotherapy, surgery and adjuvant CRT is feasible and produces outcomes similar to other multimodality treatment schedules in LRA E/GEJ ACA. Despite excellent LRC, projected DMC and OS remain poor. A symptomatic response to induction and less residual viable tumor at surgery are associated with improved outcomes. Clinical trial information: NCT00601705.
PI3K pathway as a major determinant of resistance to HER2-targeted therapy in advanced gastric cancer.
Authors: Kim Hyo Song , Zhang Xianglan , Park Kyu Hyun , Park Ji Soo , Kim Ki Hyang , Chung Hyun Cheol , Rha Sun Young 
Published: March 2020

4089 Background: Despite the improvement of survival with trastuzumab treatment, it is still unclear why majority of patients are initially nonresponsive or eventually become resistant to HER2-based therapy. To evaluate resistant mechanism and stimulate the development of rational drug, we investigated the role of phosphoinisitide 3-kinase (PI3K) pathway activation. Methods: With tumor tissues from HER2-overexpressing advanced gastric cancer, PIK3CA mutation status (by pyrosequencing of exon 9 and 20) and phosphatase and tensin homolog (PTEN) expression levels (using immunohistochemical analysis) were evaluated for the therapeutic response to HER2-based therapy. Results: Forty nine patients received trastuzuamb (n=39) or lapatinib (n=10) in combination with chemotherapy regimen. The age at diagnosis was 61 years and all the cases were HER2 positive and/or amplified. PTEN-loss was found in 67% (n=33) and all the patients showed PIK3CA wild-type tumors. Twenty nine patients (59%) responded to HER2-based therapy (complete and partial response), without significant difference between PTEN-loss and normal tumors (61% vs 62%). Among the patients with responsive disease, time to best response was not different but duration of response was shorter for the PTEN deficient patients (155 vs 244 days, P=0.016). In addition, PTEN-deficient patients have significantly shorter progression-free survival (median 160 vs 286 days, P=0.018), which implying the functional role of PTEN for the acquired resistance to HER2-based therapy. Conclusions: This data suggests PTEN as an important predictor for the early progression and acquired resistance to HER2-based therapy. Activated PI3K pathway may provide a biomarker to identify patients who may need additional or alternative therapies.
Surgery-induced peritoneal metastasis and its intraoperative treatment.
Authors: Murata Satoshi , Takebayashi Katsushi , Kojima Masatsugu , Yamamoto Hiroshi , Yamaguchi Tsuyoshi , Naitoh Hiroyuki , Ishida Mitsuaki , Mekata Eiji , Shimizu Tomoharu , Shiomi Hisanori , Sonoda Hiromichi , Naka Shigeyuki , Mori Tsuyoshi , Akabori Hiroya , Murakami Koichiro , Ueki Tomoyuki , Mizuno Aya , Abe Hajime , Okabe Hidetoshi , Tani Tohru 
Published: March 2020

4092 Background: A large number of advanced gastric cancer patients undergoing curative gastrectomy with D2 lymph node dissection (D2 gastrectomy) show peritoneal metastasis. The source of these metastatic cells and their treatment remain unclear. We examined the mechanism of surgery-induced peritoneal metastasis and determined the appropriate intraoperative treatment. Methods: (1) Curative gastrectomy was performed for 102 gastric cancer patients. Peritoneal lavage fluid was collected before and after gastrectomy. Cytology, RT-PCR, and cell culture were used to determine the presence of cancer cells. Proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. (2) Fifty clinical T3(SE) or T4(SI) advanced gastric cancer patients undergoing curative D2 gastrectomy prospectively received intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in a phase II trial. HIPEC comprised 50 mg CDDP, 10 mg MMC, and 1000 mg 5-FU in 5 L saline maintained at 42–43C° for 30 min. Results: (1) Of 102 peritoneal lavage fluid samples obtained before gastrectomy, 57 from both early and advanced cancer patients did not contain CEA or CK20 mRNA amplification products or cancer cells. Of these 57 samples, CEA or CK20 mRNA was detected in 35 and viable cancer cells were identified in 24 after gastrectomy. Viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells developed into peritoneal tumor nodules after spill over into the peritoneal cavity in NOD/ShiJic-scid mice. (2) Fifty patients were eligible for the phase II clinical trial. The overall 5-year survival rate for all patients was 92.4%. This rate in patients with pT2(ss) (n = 12), pT3(se) (n = 35), and pT4(si) (n = 3) disease was 90.0%, 92.3%, and 100%, respectively. Only 2 patients (4%) showed peritoneal relapse. Conclusions: Viable tumorigenic cancer cells spilled over the peritoneal cavity during curative gastrectomy. Intraoperative HIPEC following curative D2 gastrectomy effectively prevented peritoneal metastasis, thereby potentially improving the prognosis of patients with advanced gastric cancer.
Multicenter, phase II study of trastuzumab and paclitaxel to treat HER2-positive, metastatic gastric cancer patients naive to trastuzumab (JFMC45-1102).
Authors: Iwasa Satoru , Nishikawa Kazuhiro , Miki Akira , Noshiro Hirokazu , Tsuburaya Akira , Nishida Yasunori , Miwa Hiroto , Masuishi Toshiki , Yoshida Kazuhiro , Kodera Yasuhiro , Boku Narikazu , Yamada Yasuhide , Morita Satoshi , Sakamoto Junichi , Saji Shigetoyo , Kitagawa Yuko 
Published: March 2020

4096 Background: The ToGA study indicated that first-line treatment using trastuzumab (T-mab) combined with capecitabine and cisplatin conferred a survival (OS) benefit to patients with HER2-positive metastatic gastric cancer (mGC). However, no reports have described the efficacy and safety of second-line treatment of HER2-positive mGC patients with T-mab who were naïve to the drug. Methods: JFMC45-1102 was a multicenter, Phase II study. Patients positive for HER2 (IHC3+ or IHC2+/FISH+) with gastric adenocarcinoma confirmed histologically; older than ≥ 20 y; who received one or more prior chemotherapies but no prior therapy with T-mab; and normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Patients received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg initial dose, followed by 6 mg/kg q3w). Treatment continued until their disease progressed; there was unacceptable toxicity or patient’s refused further treatment. The primary endpoint was overall response rate (ORR) evaluated according to RECIST ver. 1.0. Threshold and expected ORR were estimated at 15% and 30%, and secondary endpoints included progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: Fourty-six patients were enrolled between September 2011 and March 2012. Patients characteristics were: gender (M/F) 37/9; median age 69; ECOG PS0/1/2, 35/10/1; unresectable/recurrence 25/21; number of prior treatments (1/2), 41/5. The ORR was 37.2% (95% CI: 23.0-53.3%). The median PFS and TTF were 5.2 months (95% CI 3.9-6.6) and 5.2 months (95% CI 3.9-6.6), respectively. The protocol was discontinued for 27 patients (87.1%) for disease progression, and one patient each (3.2%) for severe adverse events, physician’s recommendation, patient refusal, and treatment related death. Conclusions: Combination chemotherapy of paclitaxel plus T-mab showed promising activity and was tolerated well by patients naïve to T-mab who were positive for HER2 and treated previously for mGC. Clinical trial information: UMIN000006223.
Nimotuzumab plus paclitaxel and cisplatin as first-line treatment for esophageal squamous cell cancer: A single center prospective clinical trial.
Authors: Zhang Xiaodong , Lu Ming , Wang Xicheng , Li Jie , Li Yan , Li Jian , Zhang Xiaotian , Gao Jing , Zhou Jun , Lu Zhihao , Gong Jifang , Jia Jun , Cui Yan , Yu Jing , Shen Lin 
Published: March 2020

4097 Background: The aim of this present phase II study is to explore the safety and efficacy of paclitaxel (T), cisplatin (C), and nimotuzumab (N), a humanized anti-EGFR monoclonal antibody combination (TCN) as first-line treatment in advanced esophageal squamous cell cancer (ESCC). Methods: Patients with histologically confirmed advanced ESCC, measureable tumor, and no prior chemotherapy and radiotherapy except adjuvant treatment were enrolled. Patients were given cisplatin 60mg/m2, paclitaxel 175mg/m2per 21 days for at least 2 cycles. The nimotuzumab was given 200mg weekly. Radiotherapy was admitted for patients with unresectable local advanced disease after 4 cycle of TCN treatment. The primary endpoints were safety and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and over-all survival (OS). The expression of EGFR and ERCC1 were also analyzed by histoimmunochemical staining. Results: Between Mar. 2011 and Dec. 2012, 55 patients with advanced ESCC were enrolled and 53 (96.4%) were eligible for evaluation. The ORR was 54.7% (29/53) and the DCR was 94.3% (50/53). The expression of EGFR and ERCC1 were detected in 46 and 31 patients respectively. The ORR had no relation to both the expression of EGFR (55.3% vs 62.5%, p=0.71) and ERCC1 (41.7% vs 58.3%, p=0.47). As a median follow-up of 15months, the median PFS was 10.5 months (95% CI 8.7 to 12.3 months).The TCN combination treatment was well tolerated and the most common adverse events were alopecia (86.8%), leukopenia (84.9%), anorexia (84.9%), vomiting (73.6%), fatigue (73.6%), pain (66.0%), and anaemia (39.6%). And 18 (34%) patients had Grade 3 to 4 leukopenia. The median OS have not yet been reached. Conclusions: In this study, the ORR, DCR and PFS are superior to previous published studies. The addition of anti-EGFR treatment of nimotuzumab to standard chemotherapy was well tolerated with no serious AEs. But the expression of EGFR by IHC could not predict the outcome of nimotuzumab treatment. A phase III study of TCN followed by radiotherapy in unresectable local advanced ESCC had been designed to explore the survival benefits. Clinical trial information: NCT01336049.
Preoperative chemotherapy plus bevacizumab with early salvage therapy based on FDG-PET response in locally advanced gastroesophageal junction and gastric adenocarcinoma.
Authors: Ku Geoffrey Yuyat , Kelsen David Paul , Strong Vivian E. , Schöder Heiko , Janjigian Yelena Yuriy , Shah Manish A. , Coit Daniel G. , Brennan Murray F. , Capanu Marinela , Ilson David H. 
Published: March 2020

4101 Background: Response on FDG-PET scan during preoperative chemotherapy has prognostic significance. We performed a phase II trial to examine the effectiveness of FDG-PET directed early switching to salvage chemotherapy measured by 2-year disease free survival (DFS). Methods: Pts with PET avid, endoscopic ultrasound and laparoscopically staged T3 or N+ resectable gastric or GEJ adenocarcinoma received induction epirubicin 50mg/m2, cisplatin 60mg/m2 Day 1, capecitabine 625mg/m2 BID Days 1-21 (ECX) and bevacizumab 15mg/kg Day 1. PET scan was repeated at Week 3. PET responders (≥35% decline in SUV) continued with ECX for 2 more cycles. PET non-responders were switched to 2 cycles of salvage therapy: docetaxel 30mg/m2 and irinotecan 50mg/m2Days 1 and 8 q21 days and bevacizumab 15mg/kg Day 1. All pts went to surgery 4 weeks after Cycle 3. Results: Twenty of planned 60 pts were enrolled before the study closed for poor accrual. Eleven (55%) had a PET response after induction. Ten of 11 underwent R0 resection: 1/10 path complete response, 3/10 path partial response. Nine PET non-responders were switched to the salvage regimen. Seven of 9 non-responders had R0 resection, none achieved a pathological response. The median DFS for PET responders was 27.8 mos (95% CI 10.3-27.8) and DFS in salvage group has not been reached. There was no significant difference in DFS between the two groups (p= 0.4). Follow up for overall survival is ongoing. Conclusions: Response on PET scan during induction chemotherapy can identify early treatment failures. The results for therapy cross-over indicate a potentially improved DFS with salvage chemotherapy. Results from this trial are hypothesis generating and merit evaluation in a larger clinical trial. Updated survival data will be presented. Clinical trial information: NCT00737438.
Early results of a randomized phase II, compass trial to compare regimen and duration of neoadjuvant chemotherapy for gastric cancer.
Authors: Yoshikawa Takaki , Tanabe Kazuaki , Nishikawa Kazuhiro , Ito Yuichi , Matsui Takanori , Kimura Yutaka , Morita Satoshi , Miyashita Yumi , Tsuburaya Akira , Sakamoto Junichi 
Published: March 2020

4102 Background: Prognosis for stage III gastric cancer was not satisfactory even by D2 gastrectomy and adjuvant chemotherapy. Neoadjuvant chemotherapy is another promising approach. This study investigated the outcomes of two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. Methods: Patients with stage II schirrhous/junctional tumors, stage III, or resectable stage IV, received S-1 (80 mg/m2 for 21 days with 1 week rest)/cisplatin (60 mg/m2 at day 8) or paclitaxel/cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest). The primary endpoint was 3-year OS. Key secondary endpoints included pathological/clinical response, R0 resection, and adverse events. Sample size was set at 60 to 80 to achieve 10% improvement of 3-year OS by four courses or by PC with approximately 80% probability of the correct selection. Results: Between Oct 2009 and July 2011, 83 patients were assigned to arm A (2 courses of SC, n=21), arm B (4 courses of SC, n=20), arm C (2 courses of PC, n=21), and arm D (4 courses of PC, n=21). Clinical response (arm A/B/C/D) was 29%/40%/33%/24%. R0 resection (arm A/B/C/D) was 76%/75%/57%/76%. Pathological response (arm A/B/C/D), defined as tumor regression more than two third in the primary tumor, was 43%/40%/29%/38%. Pathological complete response (arm A/B/C/D) was 0%/10%/0%/10%. Major grade 3/4 toxicities (arm A/B/C/D) were anemia (14%/15%/0%/28.6%), neutropenia (10%/15%/14%/33%), nausea (0%/10%/5%/5%), and appetite loss (5%/10%/0%/5%). Pathological complete response by per-protocol analysis (arm B/D) was 17% and 12%. Treatment discontinuation (number of patients, arm A/B/C/D) was disease progression (1/3/0/1), toxicities (1/4/0/3), and others (0/1/0/0). No surgical mortality was observed. Grade 3 morbidity classified by Clavien-Dindo was leakage in 5% (arm A), pancreatic fistula in 5% (arm C), and postoperative hemorrhage in 5% (arm B). Conclusions: Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen. Clinical trial information: UMIN000002595.
Prognostic outcome of gastric cancer patients with cancer stem cell SNPs in Asian versus western countries.
Authors: Labonte Melissa Janae , Wakatsuki Takeru , Zhang Wu , Yang Dongyun , Azuma Mizutomo , Gerger Armin , Stotz Michael , Ning Yan , Volz Nico Benjamin , Stintzing Sebastian , Li Joseph Ethan , El-Khoueiry Rita Elie , Wilson Peter M. D. , Koizumi Wasaburo , Watanabe Masahiko , Maus Martin K. H. , Barzi Afsaneh , Iqbal Syma , El-Khoueiry Anthony B. , Lenz Heinz-Josef 
Published: March 2020

4110 Background: The clinical significance of cancer stem cells (CSC) has been well established; however, its prognostic role remains controversial. CD44 is recognized as a CSC marker in gastric cancer (GC) and, recently, the clinical impact of CD166 in GC was reported. Our group previously reported SNPs of CD44 and CD166 are associated with outcome in US patients (pts) with adjuvant GC and colorectal cancer, respectively. Since GC has regional differences in epidemiology and clinicopathology, we hypothesized that ethnicity and regional differences in GC could influence the prognostic role of CD44 and CD166. Methods: A total of 369 pts with histopathologically-confirmed localized (stage Ib to IV; AJCC-6th) GC were enrolled from Japan (n=169), the US (n=137), and Austria (n=63) between 2002 and 2010. CD44 rs187116 G>A and CD166 rs1157 G>A were analyzed. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Results: Pts homozygous for A/A CD44rs187116 (n=20) showed a median OS of 2.0 yrs vs not reached for patients harboring at least one-G allele (n=144) (HR: 2.87 [95%CI: 1.61-5.13], p<0.001) in Japanese cohort, while pts homozygous A/A (n=30) showed a median OS of 7.3 yrs vs 4.1 yrs for pts harboring at least one-G allele (n=94) (HR: 2.0 [95%CI: 0.90-4.55], p=0.079) in the US cohort. There were no significant differences in Austrian cohort alone or in combination with US cohort. In CD166 rs1157, pts harboring at least one-A allele (n=27) showed a median OS of 3.9 yrs vs not reached for pts homozygous G/G (n=142) (HR: 1.81 [95%CI: 1.05-3.12], p=0.033) in Japanese cohort., Although there were no significant differences in the US or Austrian cohort when analyzed separately, combining cohorts demonstrated that pts homozygous A/A (n=12) showed a median OS of not reached yrs vs 4.7 yrs for pts harboring at least one-G allele (n=179) (HR: 5.00 [95%CI: 0.70-35.95], p=0.073). Conclusions: SNP profiles in CSC markers predicted opposite prognostic outcomes in patients with GC among Asian and Western countries. This is the first report suggesting that the prognostic role of CSC markers in GC may differ based on ethnic groups or etiology differences.
Association of transcription factor 7-like 2 (TCF7L2) polymorphisms with worse survival in three independent cohorts from the United States, Austria, and Japan in patients with gastric cancer.
Authors: El-Khoueiry Rita Elie , Wakatsuki Takeru , Ning Yan , Zhang Wu , Yang Dongyun , Azuma Mizutomo , Gerger Armin , Stotz Michael , Labonte Melissa Janae , Wilson Peter M. D. , Volz Nico Benjamin , Stintzing Sebastian , Maus Martin K. H. , Sunakawa Yu , Koizumi Wasaburo , Watanabe Masahiko , Li Joseph Ethan , Barzi Afsaneh , El-Khoueiry Anthony B. , Lenz Heinz-Josef 
Published: March 2020

4111 Background: The Wnt/β-catenin signaling pathwaycontrols cell proliferation and differentiation. Disruption of this pathway has been shown in the majority of colorectal (CRC) and gastric cancer (GC). The TCF7L2 complex plays a critical role in this pathway. Interaction of TCF7L2 and β-catenin results in translocation to the nucleus and leads to up-regulation of target genes, including c-myc and cyclin D1. Previous reports have shown that TCF7L2 polymorphism rs7903146 C/T is associated with CRC risk and outcome; however, the prognostic role of this polymorphism in GC is unknown. Therefore, we tested the hypothesis of whether this polymorphism could predict outcome in GC in three independent cohorts. Methods: A total of 369 patients (pts) with histopathologically-confirmed localized GC were enrolled from Japan (n=169), the US (n=137), and Austria (n=63) between 2002 and 2010. Results: In the US cohort, pts with at least one-T allele ((T/T or C/T; n=46) showed a median TTR of 1.7 yrs vs. 4.4 yrs compared to pts homozygous C/C (n=76) (HR: 2.09 95%CI: 1.21- 3.59, p=0.0053). A similar trend was shown in the Austrian cohort, where pts harboring at least one-T allele (n=25) showed a median DFS of 2.08 yrs vs. 5.42 yrs for pts homozygous C/C (n=38) (HR: 1.79 [95%CI: 0.90-3.55], p=0.092). Moreover, in the Japanese cohort, pts homozygous for T/T demonstrated (n=2) a median DFS of 0.15 yrs vs. 4.82 yrs for pts harboring at least one-C allele (n=165) (HR: 10.5 [95%CI: 2.46-45.5], p=0.001). These results were confirmed in the OS in the US and Japanese cohorts. Pts at least one-T allele (n=46) showed a median OS of 3.3 yrs vs. 5.5 yrs for pts homozygous C/C (n=76) (HR: 2.41 95%CI: 1.28-4.53, p=0.0043) in the US cohort, while pts homozygous T/T showed (n=2) a median OS of 0.22 yrs vs 5.76 yrs for pts harboring at least one-C allele (n=165) (HR: 15.2 [95%CI: 3.50-66.7], p<0.001). Conclusions: TCF7L2 polymorphism was associated with worse prognosis in recurrence in pts with GC in three independently global cohorts. This polymorphism may be negative prognostic factor in GC regardless of ethnicity and etiology, suggesting the importance role of Wnt/β-Catenin signaling in GC.