bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG 9912)
Authors: Fuse N. , Fukuda H. , Yamada Y. , Sawaki A. , Koizumi W. , Suzuki Y. , Yamaguchi K. , Takiuchi H. , Ohtsu A. , Boku N. ,   Gastrointestinal Oncology Study Group/Japan Clinical Oncology Group
Published: August 2020

4514 Background: We reported the primary results of JCOG9912 in ASCO 2007. In the planning, this study with 230 patients (pts) per arm had 80% power to demonstrate 10% superiority of CP and non-inferiority with 5% margin (HR=1.16) of S-1 at 6 months in overall survival (OS) and 0.05 study-wise 1-sided alpha. Primary analysis was conducted in Feb 2007, one year after the last patient accrual with 601 deaths (85%) of all randomized 704 pts. S-1 showed statistically significant non-inferiority to 5-FU (p<0.001), but after adjusting for multiplicity either S-1 or CP failed to show statistically significant superiority to 5-FU (CP, hazard ratio (HR)=0.85 (95% CI, 0.70–1.04), p=0.055 and S-1, HR=0.83 (0.68–1.01), p=0.034). Methods: The survival information of all surviving 103 pts at the primary analysis was updated in Apr 2008 when 660 pts (94%) were dead. An updated analysis and multivariate analyses with Cox proportional hazard model were conducted. The multivariate analysis model included arms, sex, age, tumor status (unresectable/recurrent), PS, the number of metastatic sites, target lesion (TL), macroscopic type, histological type and peritoneal dissemination. Results: The updated results are shown in Table . OS curves and HRs remained almost identical to the previous report. Multivariate analyses showed that number of metastatic sites (≥2), PS (≥1), presence of TL were associated with worse survival, and that the adjusted HRs of CP and S-1 were 0.79 (0.65–0.95, p=0.014) and 0.80 (0.66–0.96, p=0.017), respectively. There was no significant interaction among baseline factors and treatment arms. Conclusions: The updated results reconfirmed the primary conclusion that S-1 monotherapy can be a new standard regimen for advanced gastric cancer, and suggest that CP is still worthy for further clinical investigation. [Table: see text] [Table: see text]
Chemoradiation of resected gastric cancer: A 10-year follow-up of the phase III trial INT0116 (SWOG 9008)
Authors: Macdonald J. S. , Benedetti J. , Smalley S. , Haller D. , Hundahl S. , Jessup J. , Ajani J. , Gunderson L. , Goldman B. , Martenson J. 
Published: August 2020

4515 Background: INT0116 (SWOG 9008) was a prospectively randomized phase III trial of postoperative adjuvant therapy utilizing 5-FU/leucovorin plus external beam radiation in 582 eligible cases of resected stage IB-IV(M0) stomach and gastroesophageal junction cancers. Initial results (NEJM 345: 725, 2001) showed both overall and disease free survivals improved by chemoradiation. Methods:We now report INT0116 results with >10years median follow-up. Exploratory subset outcomes are also reported. Results: INT0116 continues to show benefit for chemoradiation with hazard ratios (HR) for survival (HR=1.32, p=.004) and disease free survival (HR=1.51, p<.001) favoring chemoradiation. Subset analyses were performed for sex, race, T and N stage, D-level of surgical resection, tumor location (proximal or other), histology (intestinal or diffuse) and Maruyama index. Chemoradiation benefited all subsets with the exceptions of women and diffuse histology. In women the HR for therapy was 1.0(0.68–1.45). The HR for therapy in diffuse histology cases was 0.97(0.62–1.40). Interaction between these factors is suggested as women were significantly more likely to have diffuse histology than men (56% versus 33%). A multivariate analysis of sex and histology did not detect an effect of sex once histology was included. These data suggest that sex may not be an independent variable for lack of response to chemoradiation but that diffuse histology may be. Long term toxicities were examined. Thirty-five second tumors occurred in 31 cases. Twenty-two occurred in chemoradiation cases and 9 in surgery only cases. Second tumors represented a spectrum of types of neoplasms commonly occurring in this age group (median age 60 years). Excessive numbers of tumors known to be caused by radiation and/or chemotherapy were not noted. More tumors may have occurred in the treated patients since their death rates were less than surgery only cases. Conclusions: With >10 years median follow-up, survival remains improved in stage IB-IV (M0) gastric cancer cases treated with post-operative chemoradiaiton. All subsets benefit from this treatment with the exception of cases with diffuse histology. Women may be more likely to have diffuse histology gastric cancers. No increases in late toxic effects were noted. No significant financial relationships to disclose.
Use of bone marrow micrometastasis to predict disease-free and overall survival in esophageal cancer: Evaluation of 304 cases
Authors: Vashist Y. K. , Effenberger K. E. , Bachmann K. , Pantel K. , Izbicki J. R. , Yekebas E. F. 
Published: August 2020

4519 Background: The presence of bone marrow micrometastases (BMM) yields prognostic information for patients at higher risk for recurrence and death. Aim of the study was to evaluate the role of BMM in esophageal cancer (EC). Methods: 304 consecutive patients operated for EC and with BMM status were included into the prospective study. BMM were assessed by a pan-anti- cytokeratin monoclonal antibody, A45-B/B3. Associations between BMM status and clinicopathological parameters as well as disease-free (DFS) and overall survival (OS) were calculated with chi-square-, log-rank test and Cox multivariate analysis. Results: Out of 304 patients 109 (35.9%) were BMM positive (BMM+) and 195 (64.1%) negative (BMM-). Significant correlation was found between BMM and tumor size, nodal stage and recurrence (P=0.02, 0.002 and <0.0001). DFS and OS were significantly better in BMM- compared to BMM+ patients (median 44.2 and 31.6 vs. 10.4 and 12.4 months, P<0.0001). Sub-analyses revealed that nodal negative (N-) patients with BMM- had a significant better DFS and OS compared to N- and BMM+ patients (50.8 and 41.5 vs. 18.0 and 16.3 months, P<0.0001). Nodal positive patients (N+) with BMM- had a better DFS and OS compared to N+ and BMM+ patients (22.1 and 24.8 vs. 9.0 and 11.3 months, P<0.0001). In the Cox multivariate analysis BMM was the strongest predictor of DFS and OS with a hazard ratio of 3.1 and 2.9 (P<0.0001). Also tumor size and nodal stage were found to be significant predictors, whereas age and sex were not. All analyses were repeated after stratification of the study group to underlying tumor type (adenocarcinoma (AC) and squamous cell carcinoma (SCC)). Significant differences were found at all levels as reported for the entire study group above within the AC and SCC group as well. Conclusions: To our knowledge this is the largest study evaluating the role of BMM in EC. Survival sub-analyses stratified to nodal and bone marrow status revealed a significant role of BMM in EC. Presence of BMM proved to be the strongest predictor of DFS and OS in AC and SCC of the esophageus. No significant financial relationships to disclose.
Outcome prediction based on single nucleotide polymorphisms (SNPs) in DNA repair paths in patients (pts) with esophageal adenocarcinoma (EAC) treated with preoperative (preop) cisplatin (C)-based chemoradiation (CRT): Results from the Eastern Cooperative Oncology Group (ECOG)
Authors: Yoon H. H. , Powell M. , Murphy K. , Montgomery E. A. , Hafez M. J. , Liu G. , Forastiere A. A. , Benson A. B. , Kleinberg L. R. , Gibson M. K. ,   for the ECOG E1201-T1 Study Group
Published: August 2020

4530 Background: EAC has eluded cure even with platin-based CRT. Stratifying pts by likelihood of success is one approach to improving outcomes. We assessed whether SNPs in DNA repair paths are associated with complete pathologic response (pCR) in EAC pts who received C-based CRT followed by surgery. Methods: Patients and specimens: Pretreatment biopsy or post-CRT resection samples were obtained from pts (EAC, stage II-IVa) treated on a randomized phase II trial, E1201 (n=86), of preop CRT (RT to 45 Gy). Arm A: Preop C 30 mg/m2 + irinotecan (I) 50 mg/m2 days (d) 1, 8, 22, 29 with RT. Post-op C 30 mg/m2 + I 65 mg/m2 d 1, 8 q21 days x 3. Arm B: Preop C 30 mg/m2 + paclitaxel (P) 50 mg/m2 d 1, 8, 15, 22, 29 with RT. Post-op C 75 mg/m2 + P 175 mg/m2 d 1 q21 days x 3. Clinical outcome - pCR: (A) 14% [95% CI 5.5%, 28.5%]; (B) 16% [95% CI 6.7%, 30.1%]. Median overall survival (OS): (A) 34.9 m (months) [90% CI 23.5, not reached]; (B) 20.9 m [90% CI 17.4, 46.7]. Experimental procedure: Normal tissue was microdissected from unstained sections of paraffin-embedded tissue. DNA was extracted (Qiagen). Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight (Sequenom) for all SNPs. Each SNP was dichotomized a priori into: (1) major homozygote vs (2) minor (heterozygote plus minor homozygote) allele groups. Data analysis was performed centrally, with lab investigators blinded to clinical data. Exact logistic regression was used to derive ORs for non-pCR, using the major homozygote as the reference (2-sided p values). Results: Germline DNA was available in 68 pts; 60 were eligible and began therapy ( Table ). Conclusions: In this homogenous, well-defined cohort, the XRCC1 Arg399Gln minor allele group was associated with lower pCR (p=0.06). Lab data on a panel of additional SNPs have been collected and are under analysis for presentation at the meeting. [Table: see text] [Table: see text]
A multicenter phase II study of induction CT with FOLFOX-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC)
Authors: De Vita F. , Orditura M. , Innocente R. , Vecchione L. , Pinto C. , Chiarion Sileni V. , Martinelli E. , Ruol A. , Catalano G. , Ciardiello F. 
Published: August 2020

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate. Results: Up to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35–70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patient's refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after > 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease. Conclusions: The current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.
Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) mRNA expression in patients with metastatic gastric cancer receiving first-line chemotherapy
Authors: Pauligk C. , Wirtz R. , Steinmetz K. , Hartmann J. T. , Homann N. , Hofheinz R. D. , Petry C. , Altmannsberger H. M. , Jäger E. , Al-Batran S. 
Published: August 2020

4547 Background: In preclinical tumor models, VEGF and MMP-9 induced each other, resulting in the enhancement of tumor angiogenesis and the formation of metastases. This study evaluated MMP-9 and VEGF in patients (pts) with metastatic gastric cancer. Methods: Patient tumor samples from a phase III trial of the AIO were prospectively collected. VEGF and MMP-9 mRNA were isolated from paraffin embedded tissues using a new patented method based on nanotechnology. The expression was then assessed by qRT-PCR and by immunohistochemistry (IHC). Results: A total of 137 (training cohort 96; validation cohort 41) out of 220 pts enrolled were analyzed. In the training cohort, increased MMP-9 levels were strongly associated with increased VEGF expression, resistance to chemotherapy and shorter progression-free and overall survival. At the cut-off with the highest predictive value, the rate of disease progression as best response associated with elevated MMP9 expression was 50% (vs. 22.4%; Fisher's test p=.027) and median overall survival (OS) was 3.1 months (vs. 8.7 months, log rank p=.0000165). This prognostic value for survival was maintained when data were analyzed in the multivariate setting (relative hazard ratio for death 3.67, p=.00045) or were categorized according to the quartile (p=.004) or median (p=.024) distributions for MMP-9. VEGF showed a prognostic effect in pts with low MMP-9 expression, only. In the validation cohort, the prognostic value of increased MMP-9 expression could be confirmed at the best cut off derived from the training cohort, with the hazard ratio for death being 3.45 (p=.02). Interestingly, in the IHC, stromal but not tumoral MMP-9 protein expression predicted survival (log rank p=.033). Conclusions: Tumoral MMP-9 mRNA expression levels are the first validated molecular prognostic factor in metastatic gastric cancer. These results have implications for novel anti-protease/ anti-VEGF treatment strategies. [Table: see text]
A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results
Authors: Sym S. , Park S. , Park J. , Kwon K. , Jung I. , Cho E. , Lee W. , Chung M. , Shin D. , Lee J. 
Published: August 2020

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.
Registry of gastric cancer treatment evaluation (REGATE): Baseline characteristics of 10,299 patients from 22 countries
Authors: Ter-Ovanesov M. D. , Bang Y. , Yalcin S. , Roth A. , Zalcberg J. R. , Soloviev V. , Mallath M. K. , Ecstein- Fraisse E. B. , Wu C. 
Published: August 2020

4575 Background: Gastric cancer (GC) is the second most common cause of cancer death in the world. Recent advances in diagnosis and treatment provide new options in the management of this poor-prognosis disease. REGATE is an international disease registry designed to assess real-world practice patterns for patients (pts) with GC. Methods: Pts with newly diagnosed GC were enrolled. The target sample size was calculated according to the GC prevalence in participating countries. Data were collected at 2 visits occurring within a 10-month timeframe: baseline (pts and tumor characteristics, treatment plan) and after completion of initial treatment (actual therapy received). Characteristics of the patients at the time of enrollment are described. Results: From August 2004 to July 2008, 10,299 pts were enrolled by 223 investigators in 22 countries (Asia-Pacific 43%, Europe 31%, Latin-America 20%, and North Africa 6%). Characteristics are as follows. Median age 60 years (range: 18–104) with 23% of pts <50 years. Male 65%, female 35%; 91% of pts were symptomatic; 8% had family history of GC; and 32% had H. pylori infection. GC was diagnosed by endoscopy in 95% of pts. Primary tumor location: antrum 39%, body 39%, proximal 17%. Histopathological type was assessed using WHO, Lauren, and/or Ming classifications in 75%, 60% and 31% of pts, respectively. The most common histopathological sub-types were diffuse (51%) and intestinal (44%) according to Lauren; signet ring cell (41%) and tubular (22%) according to WHO. Most patients (55%) had a poorly/undifferentiated tumor. AJCC stage at diagnosis: I-21%, II-20%, III-21%, IV-38%. Initial choice of planned therapy was mainly based on stage (69% of pts) and determined by either a multidisciplinary team (41%) or a surgeon alone (37%). Conclusions: REGATE is the largest prospective international disease registry that provides new insight into the characteristics of patients with newly diagnosed GC. Results including worldwide treatment patterns over time are expected after all patients have completed their initial treatment. [Table: see text]
Adequate lymph node assessment for extrahepatic bile duct cancer: Do the data support the current AJCC recommendations?
Authors: Ito K. , Ito H. , Gonen M. , Allen P. J. , D’Angelica M. I. , Fong Y. , DeMatteo R. P. , Blumgart L. H. , Jarnagin W. R. 
Published: August 2020

4576 Background: AJCC staging manual 6th edition states that histologic examination of at least 3 lymph nodes (LN) is required for adequate N stage determination for extrahepatic bile duct cancer (EHBDCA). We hypothesize that this recommendation is insufficient and will lead to underestimation of N stage of EHBDCA. Methods: 257 patients (144 hilar [HCCA] and 113 distal [DCA] cholangiocarcinoma) who underwent curative intent resection for EHBDCA at our institution (1993 -2007) were analyzed. Final disease staging, including lymph node status and total number of nodes examined, was obtained from the pathology report. Differences in disease specific survival (DSS), according to nodal status, were compared using log rank test. R1 resections (n=51) were excluded from this analysis. Results: There were 89 patients (34.6%) with LN metastasis. On multivariate analysis, LN metastasis was an independent prognostic factor of poor survival (median DSS N0 vs N1: 53.3 months vs 19.3 months, p<0.0001, HR= 2.2 [95%CI: 1.5 - 3.2]). Median total LN count (TLNC) was 6 (range: 0 - 42). There was a significant difference in TLNC between HCCA and DCA (median = 3 [range: 0 - 16] vs 12 [range: 1 - 42], p<0.001, respectively). Among patients who underwent R0 resection for EHBDCA, “N0” based on TLNC < 11 was associated with worse DSS than “N0” based on TLNC > 11. When analyzed separately, “N0” based on TLNC < 7 for HCCA and < 11 for DCA revealed poorer DSS than “N0” based on greater TLNC ( Table ). Conclusions: The recommendation for LN assessment of EHBDCA by AJCC 6th Edition (“at least 3”) could lead the underestimation of N stage. HCCA and DCA should have separate recommendations for adequate LN assessment. [Table: see text] No significant financial relationships to disclose.
A randomized phase II trial of intra-arterial chemotherapy using a novel lipophilic platinum derivative (SM-11355) in comparison with zinostatin stimalamer in patients with hepatocellular carcinoma
Authors: Okusaka T. , Kasugai H. , Ishii H. ,   SM-11355 Japan Study Group
Published: August 2020

4583 Background: SM-11355 (Miriplatin Hydrate) is a platinum complex developed to treat HCC via administration into the hepatic artery as a sustained-release formulation suspended in lipiodol. We conducted a phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355 using zinostatin stimalamer as a control. Methods: Patients with unresectable HCC were randomized 2:1 to receive an injection of SM-11355 or zinostatin stimalamer suspended in lipiodol into the hepatic artery at doses of up to 6 mL (SM-11355: 120 mg; zinostatin stimalamer: 6 mg) according to the tumor size. A second injection was given 4–12 weeks after the first injection. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I. The primary endpoint was achievement of TE V, which was defined as disappearance or 100% necrosis of all treated tumors. Lipiodol accumulation in tumors was regarded as indicating necrosis. Results: The study included 126 patients, of whom 122 were evaluable for efficacy and toxicity (SM-11355, n=83; zinostatin stimalamer, n=39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and zinostatin stimalamer groups, respectively. The most frequent drug-related adverse events (AEs) of ≥ grade 3 (shown as SM-11355 vs. zinostatin stimalamer) were elevated AST (26.5 vs. 33.3%), elevated ALT (22.9 vs. 20.5%), thrombocytopenia (12.0 vs. 7.7%), and hyperbilirubinemia (9.6 vs. 5.1%). Serious AEs occurred in 9 (10.8%) and 3 (7.7%) patients in the SM-11355 and zinostatin stimalamer groups, respectively. The AEs with the largest difference in frequency between the two groups (SM-11355 vs. zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year survival rates were 75.9 and 70.3% in the SM-11355 and zinostatin stimalamer groups, respectively, and the 3-year survival rates were 58.4 vs. 48.7%, respectively. Conclusions: Our results suggest that SM-11355 in lipiodol has similar efficacy to that of zinostatin stimalamer, and that repeated dosing is possible without hepatic vascular injury in cases of relapse. No significant financial relationships to disclose.