bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigatory study of biomarkers for gastric cancer based on a cDNA bank.
Authors: Oshima Takashi , Imada Toshio , Kunisaki Chikara , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka 
Published: March 2020

4070 Background: We have constructed a cDNA bank using mRNA extracted from frozen specimens of gastric cancer tissue and adjacent normal gastric mucosa and studied biomarkers for the individualized therapy of gastric cancer and the identification of new treatment targets. We report currently available results. Methods: We studied 227 patients in whom at least 5 years had elapsed since surgery for gastric cancer. The disease stage was IB in 29 patients, II in 66, III in 103, and IV in 29. Among the 139 patients who postoperatively received fluoropyrimidine anticancer agents, 82 with stage II or III disease were given adjuvant chemotherapy with S-1. A total 116 genes were selected as candidate biomarkers on the basis of the results of comprehensive DNA microarray analysis, extraction from a serial analysis of gene expression (SAGE) database, and other studies. The relative expression levels of these 116 genes in gastric cancer tissue and adjacent normal mucosa were measured in each case by a quantitative polymerase chain reaction assay using the cDNA databank described above, and the relations between clinical histopathological factors and treatment outcomes were examined. Results: In patients who underwent gastrectomy, high expression levels of the secreted protein acidic and rich in cysteine (SPARC), sulfatase 1 (SULF1), and inhibin, beta A (INHBA) genes were significantly associated with poor outcomes. In patients with stage II or III disease who received adjuvant chemotherapy with S-1, high expression levels of the insulin-like growth factor receptor 1 (IGF-1R), KIAA1199, thymidylate synthase (TS), and regenerating IV (Reg IV) genes were significantly associated with poor survival. Conclusions: Investigatory studies using a cDNA bank of biomarkers for gastric cancer suggested that expression levels of the SPARC, SULFI, and INHBA genes are useful prognostic factors in patients who undergo gastrectomy for gastric cancer. Expression levels of the IGF-1R, KIAA1199, TS, Reg IV, and INHBA genes may be useful biomarkers in patients who receive adjuvant chemotherapy with S-1.
Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab in inoperable gastric cancer: First efficacy results of a multicenter phase II trial (AGMT Gastric-3) of the Arbeitsgemeinschaft Medikamentöse Tumortherapie.
Authors: Woell Ewald , Thaler Josef , Keil Felix , Eisterer Wolfgang , Fridrik Michael A. , Gruenberger Birgit , Hejna Michael , Romeder Franz , Greil Richard 
Published: March 2020

4074 Background: In our previous phase II trials (AGMT-Gastric-1 and AGMT Gastric-2) efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab was shown. Time to progression however was short suggesting acquired chemotherapy resistance. Therefore sequential chemotherapy combined with bevacizumab is investigated in the presented trial. Methods: Oxaliplatin 85 mg/m2 biweekly (q2w) and irinotecan 125 mg/m2 q2w are administered for the first three months followed by docetaxel 50mg/m2 q2w for three months. Chemotherapy for 6 months is combined with bevacizumab 5 mg/kg q2w which is administered until progression. For this abstract 36 patients (pt.) with histologically proven unresectable and/or metastatic gastric adenocarcinoma have been evaluated in a first line setting. Median age: 62.5 years (range 26-80 years), PS 0: 25 patients, PS 1: 10 patients, missing: 1 patient, single metastatic site: 24 patients, multiple metastases: 10 patients, missing: 2. Results: Frequently reported adverse events (more than 20% of pt.) were predominantly grade 1 or 2 and included diarrhea (25/36, 69%), polyneuropathy (17/36, 47%), nausea (17/36, 47%), fatigue (15/36, 42%), neutropenia (13/36, 36%), abdominal pain (11/36, 31%), hypokalemia (9/36, 25%). Grade 3 and 4 toxicities included neutropenia (6/36, 17%), diarrhea (3/36, 8%), hypokalemia (3/36, 8%), anemia in (2/36, 6%), leucopenia (2/36, 6%), thrombocytopenia (1/36, 3%), nausea in (1/36, 3%). Objective response rate after 3 cycles was available in 25 patients: CR 1/25 (4%), PR 14/25 (56%), SD 8/25 (32%), PD 2/25 (8%). After 6 cycles there were 12 evaluable patients with CR 2/12 (16.7%), PR 5/12 (41.7%), SD 4/12 (33.3%) and PD 1/12 (8.3%). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and very active in advanced gastric cancer.
Post-recurrence survival in patients with previously resected esophageal adenocarcinoma (EAC).
Authors: Lewis Mark , Yoon Harry H. , Shi Qian , Diasio Robert B. , Sinicrope Frank A. 
Published: March 2020

4075 Background: EAC recurrence after surgery with curative intent is believed to carry a uniformly dismal prognosis that may discourage further therapy. To date, the post-recurrence survival of patients has not been examined in EAC. Our aim was to examine site of recurrence in relation to outcome in EAC patients after surgery. Methods: Among EAC patients (N = 796) rendered margin-free at surgery performed at Mayo Clinic, most were T3-4 and lymph node (LN)-positive; none received neoadjuvant therapy. The patient subset who had documented disease recurrence (N = 401) formed the current study population. Cox models were used to examine overall survival (OS) post-recurrence. Results: Among patients with recurrence, median time to recurrence (TTR) was 11 months. Site of recurrence included loco-regional (regional LNs, esophagogastric, anastomosis), chest, abdomen, or distant sites in 97 (27%), 144 (40%), 181 (50%), and 88 (24%) patients, respectively. Most recurrences (66%) were limited to one site. Chest-involved recurrence was significantly associated with improved OS (hazard ratio [HR] 0.78, P = .047), even after adjusting for TTR, number of recurrence sites, tumor pathology, and palliative chemotherapy. This result was confirmed when multivariate analysis was restricted to patients who had only 1 recurrence site (Table) or who had biopsy-proven recurrence (P = .080). In separate models, abdomen-involved (HR = 1.3, P = .016) or bone-involved (HR = 1.6, P= .008) recurrences were independently associated with worse OS. Conclusions: Chest-involved recurrence of EAC independently predicts for improved survival, whereas abdominal and bony sites of recurrence predict for worse outcome. Primary tumor grade and node number were durable prognosticators after recurrence. These novel data provide useful prognostic information and have the potential to influence clinical decision-making. [Table: see text]
Interim safety results from a phase II/III trial with 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/oesophagogastric junction (OGJ) cancer: A study of the AIO.
Authors: Koock Ulrike , Pauligk Claudia , Luley Kim Barbara , Mayer Frank , Schulmann Karsten , Homann Nils , Schmalenberg Harald , Hozaeel Wael , Hofheinz Ralf , Probst Stephan , Mahlberg Rolf , Koenigsmann Michael , Haag Georg Martin , Meiler Johannes , Prasnikar Nicole , Behringer Dirk M. , Trojan Jorg , Egger Matthias , Jäger Elke , Al-Batran Salah-Eddin 
Published: March 2020

4083 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remain below 40%. The FLOT regime is an effective new combination with pathologic response rates in the 15% range. This phase II/III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by Capecitabine in the ECF-arm (ECX). This is a preplanned toxicity analysis after 200 pts in order to decide whether to continue to a phase III trial. Results: 202 pts have been randomized so far. Median age is 62 yrs; 79% of pts are male. The Primaries were Gastric in 43.4%, OGJ in 53.2% and not evaluable/documented in 3.4% of pts. 190 pts were eligible for the safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, and 68.7% vs. 66.0% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct). Grade 3/4 side effects were observed in 52.1% of ECF/ECX and 59.6% of FLOT pts with no significant differences between arms regarding individual grade 3/4 toxicities. Thromboembolic events occurred in 14.5% vs. 8.5% in pts with ECF/ECX vs. FLOT (p=.25). Serious adverse events occurred in 60.3% vs. 39.7% of pts with ECF/ECX vs. FLOT. Preoperative delay/interruptions of ct were observed in 74.0% vs. 61.7% of pts with ECF/ECX vs. FLOT (p=.07). Dose modifications of preoperative ct were performed in 28.1% vs. 22.3% of treatment cycles with ECF/ECX vs. FLOT, respectively. 121 pts underwent surgery. Severe surgical morbidity was similar in both arms (ECF/ECX, 15.8%; FLOT, 14.1%). Surgical mortality was observed in 2 and 1 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. This supports the continuation of the trial as a phase III.
Neoadjuvant chemoradiotherapy with 5-fluorouracil-cisplatin combined with cetuximab in patients with resectable locally advanced esophageal carcinoma: A prospective phase I/II trial (FFCD-PRODIGE 3)—Preliminary phase II results.
Authors: Dahan Laetitia , Mariette Christophe , Ychou Marc , Nguyen Tan Dat , Guimbaud Rosine , Aparicio Thomas , Vendrely Veronique , d'Journo Xavier , Subtil Fabien , Bonnetain Franck , Adenis Antoine , Seitz Jean Francois 
Published: March 2020

4091 Background: Chemoradiotherapy (CRT) for locally advanced esophageal cancer is based on 5FU combined with cisplatin. The anti-EGFR antibody cetuximab increases the efficacy of RT-based regimen for patients (pts) with cancer of the head and neck. This phase I/II trial was evaluating MTD, safety and pathologic complete response (pCR) rate of the combination of cetuximab with platinum-based CRT in esophageal cancer. Methods: Inclusion criteria: squamous cell carcinoma or adenocarcinoma of the esophagus, stage II-III, WHO PS 0-1. A radiotherapy of 45 grays (1.8 Gy/25F) was given over 5 weeks. During phase I, four patients experienced limited toxicity to dose level 0, and treatment was desescalated to dose level -1: weekly cetuximab (400 mg/m2 one week before start of radiotherapy and 250 mg/m2 during radiotherapy), and 5 FU (500 mg/m2 per day D1-D4) combined with cisplatin (40 mg/m2 D1) on week 1 and 5. Nine pCR over 27 resections were needed to show a pCR rate>20% (α=5%, power = 90% ). Thirty three patients were included in the phase II. Results: From 07-2007 to 01-2011, 33 pts were enrolled, 20 squamous cell carcinoma (60.6%), 13 adenocarcinoma (39.4%), 25 (75.8%) stage III and 8 (24.2%) stage II. Among 32 pts who received CRT, the main grade 3-4 toxicities were esophagitis (4 pts), leucopenia (1 pt), anaphylaxis reaction (1 pt), rash (1 pt). Resection was achieved in 27 pts (25 R0)/31 who underwent surgery. Complete or near complete pathologic response (TRG grades 1 and 2 to Mandard) was achieved respectively in 5 (18.5%) and 6 (22.2%) pts. There were 4 deaths at 30 days post surgery. Severe postoperative complications were pulmonary complications (8), anastomotic stricture (4), gastric necrosis (1) and infection (7). The median overall survival was 15.7 months [11.01-.], and the median relapse free survival was 13.7 months [5.47-.]. Conclusions: Adding cetuximab to preoperative chemoradiotherapy including 5FU and cisplatin did not increase pCR. The recommended dose level of chemotherapy determined during phase I could explain those disappointing results. We won’t initiate a phase III trial.
Randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1 and oxaliplatin in patients with resectable esophageal cancer.
Authors: Yoon Dok Hyun , Jang Geundoo , Kim Jong Hoon , Kim Yong Hee , Son Seyoung , KIM Jiyoun , Park Seung-Il , Kim Hyeong Ryul , Jung Hwoon-Yong , Lee Gin-Hyug , Choi Kee Don , Song Ho June , Song Ho Young , Shin Ji Hoon , Cho Kyung-Ja , Kim Sung-Bae 
Published: March 2020

4093 Background: The value of adding induction chemotherapy (ICT) to preoperative chemoradiotherapy followed by surgery has not been delineated well. Methods: Patients with stage II, III or IVA (by AJCC 6th ed.) esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m2 on day 1 and S-1 at 40 mg/m2 bid on days 1-14, every 3 weeks), followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/day with oxaliplatin 130 mg/m2 on day 1 and 21 and S-1 30 mg/m2 bid, 5 days/week during radiotherapy) and surgery (arm A, n=48), or the same chemoradiotherapy followed by surgery without ICT (arm B, n=49). Primary outcome was to compare pathologic complete response (pCR). Results: Thirty six and 35 patients underwent surgery with or without ICT, respectively. pCR rate among those who underwent surgery was significantly lower in arm A (30.6% vs. 54.3%, p=0.043). However, no difference in progression-free survival (PFS) and overall survival (OS) was observed with a median follow-up of 19.5 mo (95% CI, 19.1-22.4). Two-year PFS rate was 63.8% in arm A and 55.2% in arm B (p=0.626) and 2-year OS rate was 70.1% and 62.6%, respectively (p=0.515). While 47 (arm A) and 48 (arm B) patients received at least 44 Gy of radiotherapy, relative dose intensity (RDI) for oxaliplatin during CCRT was significantly lower in arm A vs. arm B (92.7% ± 19.6% vs. 99.7 ± 1.8%, p=0.017). RDI for S1 did not significantly differ (94.1% ± 17.3% vs. 98.5% ± 5.9%, p=0.095). G3/4 thrombocytopenia was significantly common in arm A (37.5% vs. 4.1%, p <0.001), which contributed to lower RDI of oxaliplatin. Three patients in arm A, compared to none in arm B, failed to survive for 90 days after surgery. Conclusions: Adding this ICT to preoperative chemoradiotherapy seems to cause lower pCR rate and higher toxicity during CCRT.
Multicenter phase II study combining panitumumab with chemoradiation followed by surgery for patients with operable esophageal cancer (PACT-study).
Authors: Kordes Sil , Richel Dirk , van Berge Henegouwen Mark I. , Hulshof Maarten C. , Meijer Sybren L. , Wilmink Johanna 
Published: March 2020

4094 Background: A consistent finding in many studies in patients with operable esophageal and gastro-esophageal junction cancer is that response to preoperative therapy, particularly the absence of residual disease in the surgical specimen, is an indicator of better disease-free and overall survival. One of the potential strategies to improve these local effects of preoperative chemoradiation (CRT) is the concurrent inhibition of the epidermal growth factor receptor (EGFR). Therefore in our trial we evaluated the pathologic response of panitumumab in combination with neoadjuvant CRT as first line treatment of operable adenocarcinomas or squamous cell carcinomas of the esophagus. Methods: Patients with resectable cT1N1M0 or cT2-3N0-2M0 tumors received preoperative CRT consisting of 3 administrations of panitumumab (6mg/kg) in weeks 1-3-5, weekly administrations of carboplatin (AUC = 2) and paclitaxel (50 mg·m2) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery. The primary endpoint was the percentage of pathologic complete responses (pCR). Results: From January 2010 till December 2011, 91 patients were enrolled. 3 patients were not resected due to the development of metastatic disease during CRT. Results of all patients will be presented at ASCO. The majority of the 74 patients operated thus far had T3 (85%) and node positive (77%) tumors. 21.6% reached pCR and 13.5% had less than 10% viable tumor cells in the resected specimen. R0-resection was achieved in 98.6%. There were 58 patients with adenocarcinoma and 11 patients with squamous cell carcinoma. The pCR of these patients were 15.5% and 45.5%, respectively. Main grade 3 toxicities were esophagitis, fatigue, rash and anorexia. 1 postoperative death occurred due to ischemia of the esophageal reconstruction. Conclusions: The addition of panitumumab to chemoradiotherapy with carboplatin and paclitaxel was feasible without increasing postoperative mortality, but did not improve the rate of pathologic complete responses compared to historical data.
A phase II study of capecitabine-oxaliplatin and cetuximab in patients (pts) with advanced/metastatic gastric cancer (G) or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Iqbal Syma , El-Khoueiry Anthony B. , Yang Dongyun , Páez David , Duddalwar Vinay , Zhang Wu , Agafitei Raluca Dana , Lujan Ramona , Cole Sarah , Ning Yan , El-Khoueiry Rita , Loupakis Fotios , Wakatsuki Takeru , Lenz Heinz-Josef 
Published: March 2020

4096 Background: There have been limited advances in the treatment (tx) of pts with metastatic G or GEJ adenocarcinoma. The combination of fluroropyrimidines and platinums are standard regimens for this disease. The epidermal growth factor receptor pathway has been identified as a target and KRAS mutations are rare. Methods: The primary objective was to assess the proportion of pts with progression within 4 months. Secondary objectives include response (RR), progression free survival (PFS) overall survival (OS), toxicity and molecular correlates. A two-stage Simon phase II design was used to distinguish between a 30% vs. 50% 4 month PFS; with analysis planned at 27 and 53 pts. Eligible pts were chemonaive, metastatic/unresectable with measurable disease. Pts received capecitabine 850 mg/m2 BID D1-14, oxaliplatin 130 mg/m2 IV D1, cetuximab 400 mg/m2 (load) then 250 mg/m2 IV D1, 8, 15, q21 days. Blood and tissue were analyzed for genes in the DNA repair and EGFR pathways. Results: 61 pts were accrued, 2 GEJ and 59 G; 42 male, 19 female; median age 56 years (28-86); 54 pts were evaluable. The 4 month PFS rate 61% (95%CI 47-73%), PFS 5.4 months (95% CI 3.5-6.7); RR 50% (95%CI: 36-64%), 1 (1.9%) complete, 26 (48.1%) partial, 22 (40.7%) stable disease; 2 (3.7%) pts became resectable; median OS 14.9 months (95% CI 8.8-22.2) with median follow-up of 21.8 months. 65% (39/60) of pts had grade 3 (36 pts) or 4 (3 pts) toxicity; most common, anorexia (13.3%), diarrhea (13.3%), fatigue (13.3%), nausea (15%), vomiting (15%); grade 3 hand/foot (5.3%), acneiform rash (3.3%). SNP’s in LRIG4, (regulator of EGF signaling) and PAI1 (tumor angiogenesis, cell proliferation, migration and adhesion) were significantly associated with RR (67% G/G vs 17% A/A ,p=0.044) and PFS (5.8 months 5G/4G vs 3.4 months 5G/5G, p=0.017) respectively. Conclusions: XELOX and cetuximab has promising activity, comparable to existing regimens. Novel SNP’s were identified correlating with RR and PFS which may allow for optimization of pt selection.
Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by oxaliplatin, folinic acid, 5-fluorouracil, and irinotecan (COFFI) in locally advanced or metastatic gastric cancer (MGC).
Authors: Tomasello Gianluca , Liguigli Wanda , Poli Rossana , Negri Federica , Brighenti Matteo , Toppo Laura , Curti Alessandra , Lazzarelli Silvia , Panni Stefano , Donini Maddalena , Maltese Mariangela , Ratti Margherita , Passalacqua Rodolfo 
Published: March 2020

4097 Background: MGC is a chemosensitive tumour. According to the Norton-Simon hypothesis, a reduction of tumor burden could best be achieved by shortening the interval between the cycles, and the resistance might be overcome by switching from initial chemotherapy to a new, non cross-resistant one. We previously reported on the high efficacy of a new strategy using 2 sequential, non cross-resistant chemotherapy regimens in MGC (Cancer Chemother Pharmacol 11 Jan; 67 (1): 41-8). Aim of this study is to evaluate this therapeutic approach in a larger case series. Methods: 43 patients (pts) treated at our centre from November 04 to April 11 were included. All pts were chemo-naïve and received 4 cycles of TCF-dd (see reference above for doses) every 2 weeks. Subsequently and irrespective of their response, they received 4 cycles of COFFI (see reference above ) every 2 weeks. In both regimens pegfilgrastim 6 mg sc on day 3 was included. Results: Median age: 63; 74% male. PS 0-1. After the first regimen (TCF-dd) 43 pts were evaluable for response.We registered 3 CR, 27 PR, 7 SD, 5 PD and 1 not evaluable for an ORR at ITT of 70% (95% CI, 58-85). All pts proceeded to the second regimen (COFFI) and 40 pts were evaluable for response. The 3 CR observed after TCF-dd were maintained. Among the 27 pts with PR after TCF-dd, 2 achieved CR, 14 improved the response, 6 maintained PR, 3 progressed. Among the 7 pts with SD after TCF-dd, 1 achieved CR, 3 achieved PR, 2 progressed and 1 is not valuable. Among the 5 pts with PD after TCF-dd, 1 achieved CR, 4 achieved RP. After COFFI we observed 5 CR, 21 PR, 9 SD and 5 PD. The ORR in the 40 pts was 60% (95% CI, 50-80). Considering both regimen ORR was 93%. mTTP was 12.1 months (95% CI, 8,1-16,2). mOS was 16.1 months (95% CI, 12.7-21.6). At Dec '11, 4 out of 8 pts who achieved CR are alive and disease free. Most frequent G3-4 toxicities were: astenia (32%), neutropenia (35%), anemia (14%), neurotoxicity (21%). Conclusions: The study confirms that a sequential dose-dense strategy using TCF-dd followed by COFFI is feasible and highly effective and deserves to be tested in a randomized study which is on going.