bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of definitive chemoradiotherapy with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R) for advanced esophageal cancer.
Authors: Sato Yasushi , Ohnuma Hiroyuki , Hirakawa Masahiro , Okagawa Yutaka , Osuga Takahiro , Murase Kazuyuki , Takada Kohichi , Kawano Yutaka , Iyama Satoshi , Hayashi Tsuyoshi , Sato Tsutomu , Miyanishi Koji , Takimoto Rishu , Kobune Masayoshi , Sagawa Tamotsu , Hori Masakazu , Someya Masanori , Sakata Koh-ichi , Takayama Tetsuji , Kato Junji 
Published: February 2017

123 Background: Deﬁnitive chemoradiotherapy is one of the options for advanced esophageal cancer (AEC). However, AEC patient survival remains unsatisfactory. To investigate a regimen of definitive chemoradiotherapy that exerts good local control of AEC, we performed a phase I/II study to assess the safety and efficacy of triple-drug chemoradiotherapy with docetaxel, 5-fluorouracil, and nedaplatin (DNF-R) that has less adverse events than cisplatin. Methods: Eligible patients had stage II-IVA AEC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m2 for dose levels 1, 2, or 3) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5-fluorouracil (400 mg/m2/day) on days 1-5 and 8-12, with concurrent radiotherapy (on days 1-5, 8-12, and 15-19, total 60 Gy) every 5 weeks. After DNF-R, patients received at least 2 more cycles of DNF. The recommended dose (RD) was determined with a 3 + 3 design. Results: Thirty-one patients were enrolled from July 2010 to April 2013. In the phase I study, the dose-limiting toxicity (DLT) was grade 4 neutropenia, which was observed in all 3 patients at dose level 2.Thus, the RD schedule was level 1. In the phase II study, the 25 eligibles had a median age of 64 (range 56-78; male/female: 21/4), with PS0/1/2 of 13/10/2 and cStage II/III/IVA of 6/10/9. Grade 3/4 acute toxicity included neutropenia (46%), leukopenia (43%), febrile neutropenia (11%), thrombocytopenia (18%), esophagitis (18%), and nausea (11%) during CRT. Grade3/4 late radiotoxicity included 2 cases of esophagostenosis (7%), but they improved by dilatation. Of the 28 patients treated at the RD level 1, including 3 patients of the RD phase I portion, all of them showed response including 23 (82%) CR and 5 PR. The protocol completion rate was 96.4% (27/28). No treatment-related death was observed. The median PFS (1-year PFS: 67.6% and 3-year PFS: 44.8%) and OS were 21 months and 33.2 months, respectively. The 3-year survival rate was 62.5%. Conclusions: DNF-R showed good tolerability and achieved a high CR rate, suggesting that it is a potentially effective therapeutic regimen for AEC. Clinical trial information: UMIN000005446.
Comparison between neoadjuvant chemotherapy followed by surgery (NAC-S) and definitive chemoradiotherapy (CRT) in overall survival for patients with clinical stage II-III esophageal squamous cell carcinoma (ESCC) (JCOG1406-A).
Authors: Nomura Motoo , Kato Ken , Mizusawa Junki , Kataoka Kozo , Ando Nobutoshi , Muro Kei , Ohtsu Atsushi , Igaki Hiroyasu , Shinoda Masayuki , Takeuchi Hiroya , Shimizu Hideaki , Hayashi Kazuhiko , Daiko Hiroyuki , Goto Masahiro , Komatsu Yoshito , Konishi Kazuo , Miyata Yoshinori , Kitagawa Yuko 
Published: February 2017

127 Background: NAC-S is a standard treatment for patients (pts) with stage II/III (UICC-TNM 5th ed.) ESCC in Japan. CRT is also optionally performed for pts who refused or who are not tolerable to surgery. However, no randomized clinical trial has been conducted comparing NAC-S with CRT. The aim of this study is to explore subgroups in which survival outcome of pts undergoing CRT was potentially equivalent to NAC-S. Methods: The data of two trials for cStage II/III ESCC, JCOG9907 (accrual period: 2000-2006) and JCOG9906 (2000-2002) were used. J9907 demonstrated that NAC-S (2 course of cisplatin and 5-fluorouracil [CF] followed by surgery) showed superior OS compared with surgery followed by postoperative chemotherapy. J9906 was a single arm trial which explored the efficacy and safety of CRT (CF plus 60 Gy). Both two trials were conducted under similar eligible criteria. Subgroup analyses between two trials (serum Albmin (Alb), cT, cN, c-stage, and tumor location) using Cox proportional hazard model were performed for pts assigned to receive NAC-S in J9907 and pts in J9906. Results: All eligible pts for NAC-S group (n=164) in J9907 and all eligible pts in J9906 (CRT group: n=73) were analyzed. Pts backgrounds were similar between two groups. OS for NAC-S group was better than that for CRT group (adjusted HR 1.73; 95% CI 1.19-2.51). Subgroup analysis using Cox proportional hazard model demonstrated that all subgroups in NAC-S group showed shorter OS compared with those in CRT group (see Table). Conclusions: OS of NAC-S was favored over that of CRT. The subgroup in which OS of CRT was equivalent to that of NAC-S was not detected. For further improvement of CRT for this population, single arm trial (JCOG0909) is ongoing to evaluate the efficacy and safety of CRT modifying chemotherapy regimen and total radiation dose. [Table: see text]
Value of peritoneal drain placement after total gastrectomy for gastric adenocarcinoma: A multi-institutional analysis from the U.S. Gastric Cancer Collaborative.
Authors: Dann Gregory C. , Squires Malcolm Hart , Postlewait Lauren McLendon , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Saunders Neil , Cho Clifford Suhyun , Winslow Emily , Russell Maria C. , Staley Charles A. , Maithel Shishir Kumar , Cardona Kenneth 
Published: February 2017

131 Background: A recent randomized trial of peritoneal drain (PD) placement after pancreaticoduodenectomy concluded that placement of PDs decreased the frequency and severity of complications. The role of PD placement after total gastrectomy for gastric adenocarcinoma (GAC) is not well-established. Methods: Patients who underwent total gastrectomy for GAC at 7 institutions from the U.S. Gastric Cancer Collaborative from 2000-2012 were identified. Univariate and multivariate analyses were performed to evaluate the association of PD placement with postoperative outcomes. Results: 344 patients were identified and anastomotic leak rate was 9%.253 (74%) patients received a PD. Those with PD placed had similar ASA class, tumor size, TNM stage, and need for additional organ resection when compared to their counterparts with no PD. No difference was observed in the rate of any complication (54% vs. 48%;p=0.45), major complication (25% vs. 24%;p=0.90), or 30-day mortality (7% vs. 4%;p=0.51) between the two groups. In addition, no difference in anastomotic leak (9% vs. 10%;p=0.90), need for secondary drainage (10% vs. 9%;p=0.92), or reoperation (13% vs. 8%;p=0.28) was identified. On multivariate analysis, PD placement was not associated with a decrease in frequency or severity of postoperative complications. Subset analysis of patients stratified by whether they underwent concomitant pancreatectomy similarly demonstrated no association of PD placement with reduced complications or mortality. In patients who experienced an anastomotic leak (n=31), placement of PD was similarly not associated with a decrease in complications, need for secondary drainage, or mortality. Conclusions: Peritoneal drain placement after total gastrectomy for adenocarcinoma, regardless of concomitant pancreatectomy, is not associated with a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, or decrease in the need for secondary drainage procedures or reoperation. Routine use of peritoneal drains is not warranted.
A phase I/II study of divided-dose docetaxel, cisplatin, and fluorouracil (DCF) for patients with recurrent or metastatic squamous cell carcinoma of the esophagus.
Authors: Ojima Toshiyasu , Nakamori Mikihito , Nakamura Masaki , Iwahashi Makoto , Katsuda Masahiro , Hayata Keiji , Matsumura Shuichi , Yamaue Hiroki 
Published: February 2017

132 Background: The aim of this phase I/II study was to evaluate the efficacy and safety of the combined use of docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (DCF) in patients with recurrent/metastatic squamous cell carcinoma of the esophagus (SCCE). This study adopted divided doses of docetaxel and CDDP in order to reduce the toxicities of the treatment. Methods: The dose of docetaxel was escalated using the following protocol in the phase I stage: level 1, 30; level 2, 35 and level 3, 40 mg/m2, which was intravenously infused for two hours on days 1 and 8. CDDP was administered at a dose of 12 mg/m2 infused for four hours on days 1-5. The 5-FU was administered at a dose of 600 mg/m2continuously infused from day 1 to 5. This regimen was repeated every four weeks. Results: The study subjects were nine patients (phase I) and 48 patients (phase II). The recommended dose was determined as level 3 in phase I. In the phase II stage, the overall response rate was 62.5%, with a complete response rate of 12.5%. The median progression-free survival was six months, and the median overall survival was 13 months. Grade 3/4 toxicities of leukopenia, neutropenia and febrile neutropenia occurred in 64.6, 68.8 and 14.6% of the patients, while grade 3/4 non-hematological toxicities were relatively rare. No treatment-related death was recorded. Conclusions: This modified DCF regimen can be a tolerable definitive chemotherapy for unresectable SCCE because of its high efficacy, although adequate care for severe neutropenia is needed. Clinical trial information: NCT00915850.
Survival trends in advanced gastrointestinal stromal tumor patients: A population-based study.
Authors: Shah Binay Kumar , Budhathoki Nibash 
Published: February 2017

136 Background: In February 2002, imatinib was approved by US FDA for treatment of patients with advanced gastrointestinal stromal tumor (GIST). This study was performed to evaluate survival trends in patients with advanced GIST in pre- (1992-2001) and post- (2002-2008) imatinib era in the United States. Methods: We selected adult patients (≥18 years) with advanced GIST (regional and distant metastasis based on SEER’s LRD staging) from the Surveillance, Epidemiology, and End Results 18 database diagnosed during 1992-2008. We excluded patients diagnosed at autopsy or from death certificate only, or those without survival date. We analyzed 1- and 3- year relative survival (RS) rates of the patients by age (all ages,18-64yrs,64+yrs), race [White, Black and Others (American Indian/AK Native, Asian/Pacific Islander)], and gender in pre-imatinib (1992-2001) and post-imatinib (2002-2008) eras. We used Z-test in SEER*Stat to compare RS rates. Results: There were total of 1,734 cases of advanced GIST (regional and distant metastasis) during the study duration. Of the total population, 744 were females and 990 were males. The 1- and 3- year RS rates were significantly higher for patients diagnosed in post-imatinib era compared to those in pre-imatinib era (83.8±1.1% vs 72.5±2.3%; Z 4.47 at one year and 68.8±1.4% vs 51.0± 2.6%; Z 6.25). The survival rates in younger patients (18-64 years) improved significantly in post-imatinib era compared to pre-imatinib era (88.60±1.2% vs 74.20±2.9%; Z 5.19 at 1 year and 75±1.6% vs 56.1±3.4%; Z 5.81 at 3 years). Among older patients, there was improvement in 3- year survival rate (76.90±2% vs 70.40±3.5%; Z 1.22 at 1 year and 59.80±2.5% vs 44.9±4%; Z 2.82 at 3 years). Survival rates improved for both sexes and for Whites and Blacks (1 year RS: 83.80±1.3% vs 73.40±vs2.6%; Z 3.45 for Whites and 85±2.4% vs 68.80±6%; Z 2.53 for Blacks; 3 year RS: 68.60±1.7% vs 51.20±3.1%; Z 5.02 for Whites and 69.10±3.3% vs 42.6±6.6%; Z 3.76 for Blacks). There was no improvement in survival rates for Others. Conclusions: Overall, survival rates of advanced GIST patients have improved significantly in post-imatinib era compared to pre-imatinib era. There was no improvement in survival rates of Others.
Impact of surgical care on survival in esophageal cancer.
Authors: Campbell Chase , Hill Joshua S. , Boselli Danielle , Salo Jonathan C. 
Published: February 2017

142 Background: Survival after multimodality treatment of localized esophageal cancer depends upon complex interactions between the patient, tumor biology, and treatment factors. The National Cancer Database (NCDB) was used to analyze prognostic factors to identify areas for treament optimization. Methods: 8,072 patients with localized esophageal cancer treated with neoadjuvant therapy undergoing surgical resection between 2004 and 2006 were identified from the NCDB. Covariates were analyzed for association with survival using univariate and multivariate Cox models. Results: A multiviariate Cox proportional hazards model was constructed, with the following significant factors predictive of survival. (See Table.) Survival varied markedly based upon the annual surgical volume of esophageal resection performed at the hospital. For hospitals performing 5 or fewer esophageal resections per year (15% of cases), 5-year survival was 40.0%, compared with 48.6% for hospitals performing 20 or greater (26% of cases). Hospital length of stay after surgery also profoundly affected survival. For patients with a post-operative length of stay of less than 14 days, 5-year survival was 40% and median survival 39.1 months. Median survival was 28 months, 19 months, and 15 months in patients with a hospital length of stay of 14-21 days, 21-28 days, and greater than 28 days, respectively. Conclusions: Data from the NCDB confirms the association between perioperative events and long-term survival after resection for esophageal cancer. Given the wide variance in outcomes based upon perioperative treatment factors, future improvements in outcomes are unlikely to be dramatically influenced by optimization of chemotherapy and radiation therapy. Improvement in outcomes of the treatment of esophageal cancer will likely require understanding how the perioperative period influences long-term survival, which should drive priorities for research and treatment improvement. [Table: see text]
First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5- fluorouracil (DCF) plus panitumumab (P) in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction (GEJ): A phase II multicenter trial.
Authors: Tomasello Gianluca , Liguigli Wanda , Toppo Laura , Mattioli Rodolfo , Negri Federica , Curti Alessandra , Ratti Margherita , Poli Rossana , Lazzarelli Silvia , Gerevini Fabiana , Colombi Chiara , Martinotti Mario , Rovatti Massimo , Olivetti Lucio , Passalacqua Rodolfo 
Published: February 2017

146 Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.
Prognostic value of the circumferential resection margin after neoadjuvant treatment in esophageal cancer patients.
Authors: Hulshoff Jan-Binne , Faiz Zohra , Smit Justin Kendrick , Kats-Ugurlu Gursah , Burgerhof Johannes , Plukker John Theodorus 
Published: February 2017

147 Background: Involvement of the circumferential margin (CRM) is an important factor in esophageal cancer (EC) patients. CRM definitions are commonly based on the College of American Pathologists (CAP) at 0 mm and the Royal College of Pathologists (RCP) at >1 mm. We evaluated which CRM definition is useful in current practice with neoadjuvant chemoradiotherapy (CRT) and whether the CRM cut-off value differs after CRT. Methods: We prospectively included 209 patients (104 with CRT) with locally advanced EC (stage II-III), who underwent radical transthoracic esophagectomy. Patients were followed for at least 2 years after surgery or until death. Patients with <1 mm longitudinal resection margins were excluded. Cancer related death was scored as event and death of other causes as end of follow-up (median 27: IQR 14.0 - 42.8 months). CRMs were measured in tenths of millimetres by experienced pathologists. Pathologic proven tumor regrowth, unequivocal radiologic suspicion or obvious clinical manifestations were marked as recurrence. Prognostic factors with a P<0.1 in univariate analyses were incorporated in multivariate Cox-regression analyses in which both CRM definitions were assessed separately. In an explorative analyses the CRM cut-off values in the surgery-only and CRT group for 2-year disease free survival (DFS) was assessed using CRM between 0-1.5 mm in the Cox-regression model. Results: Independent prognostic factors for 2-year DFS (P<0.05) in the study group were: tumor length (>5cm), >0.2 L/N+ ratio, angioinvasion and CAP R0. In the surgery group; tumor length, >4 N+, angioinvasion and CAP R0 were independent prognostic factors (P <0.05). In the CRT group only pN stage (P<0.01) was independent prognostic for 2-year DFS. The CRM cut-off value was significant at 0.2-0.3 mm for the surgery and CRT group, respectively. Conclusions: The CAP value was only independent prognostic for 2-year DFS in the surgery group. The CRM cut-off value was significant at 0.2 and 0.3 mm in the surgery and CRT group, respectively.
Identification of novel upregulated microRNAs in the pathogenesis of gastric cancer by the use of open access databases and bioinformatics tools.
Authors: Wichmann Ignacio Alberto , Artigas Rocio , Alarcon Alejandra , Olivares Wilda , Roldan Nicole , Fry Jacqueline , Cerda Paulina , Corvalan Alejandro 
Published: February 2017

15 Background: Gastric cancer (GC) is the third leading cause of cancer death worldwide. Chronic infection by H.pylori and EBV is related to the multistep cascade of GC. This cascade hypothesizes that a specific sequence of lesions leads to GC. Epigenetic processes, such as DNA methylation or miRNAs, are new players in the pathogenesis of GC. We aim to identify novel upregulated microRNAs associated with the multistep cascade through the use of open access databases and bioinformatics tools. Methods: We selected 3 GEO DataSets with human miRNA expression levels in paired tumor and non-tumor samples from gastric cancer patients. The largest library, GSE 23739 (40 matched T/N samples) was used as a "discovery dataset”. Only miRNAs upregulated >1.2 fold T over N were considered. Upregulated miRNAs were further validated in two independent datasets: i) GSE28700 (22 fresh-frozen paired T and N samples) and ii) GSE54397 (16 formalin-fixed T and N samples) and confirmed with TCGA Stomach Adenocarcinoma (STAD) data (doi:10.1038/nature13480). Finally, upregulated miRNAs were analyzed by Diana Tools miRPath, for associated oncogenic pathways and target genes. Results: From the discovery dataset GSE 23739 we identified 231 upregulated miRNAs between 40 matched T/N samples. Only 12 of these candidates were found in both validation datasets GSE28700 and GSE54397. Only three of these miRNAs were undescribed in GC: miRNAs-505, -552 and -592. TCGA STAD data confirmed our results. Analysis in miRPath revealed association with three oncogenic pathways PI3K-AKT, TGFβ and Erbβ; as well as genes relevant in oncogenesis: MAP2K1, RPS6KB1, TGFA, SMAD3, IGF1, LAMC1, IFNAR1, ITGB6, PIK3CA, PPP2R2D, EIF4E, BRCA1, FOXO3 and CREB3L3. Conclusions: The use of open access databases and bioinformatics tools enabled us to identify three novel upregulated microRNAs with oncogenic potential in GC. The analysis of these miRNAs revealed associated oncogenic pathways and target genes. These findings need to be further inquired in an experimental manner in order to assess the potential role of these miRNAs in the multistep cascade of GC.
A phase II trial of pralatrexate (P) plus oxaliplatin (O) in advanced esophagogastric cancer (aEGC).
Authors: Malhotra Usha , Miller Austin , Bushunow Peter Walter , Loud Peter , Adjei Araba , Yendamuri Saikrishna S. , Robins Melissa , Iyer Renuka V. , Khushalani Nikhil I. 
Published: February 2017

152 Background: Advanced EGC is an aggressive cancer with limited treatment (Rx) options. In preclinical studies P has demonstrated increased cellular uptake and polyglutamylation relative to other anti-folates plus is synergistic with platinum. We evaluated combination P plus O in aEGC and examined pharmacogenomics and tumor microRNA profiling to identify predictive signatures for response and toxicity. Here we report on clinical outcome data for the entire cohort. Methods: Objective response (OR) following P+O was assessed in an exact 2-stage design, including early stopping for futility and a safety lead-in cohort of 6 patients (pts) with provisions for dose de-escalation for dose limiting toxicity (DLT). Eligibility included metastatic/unresectable, therapy-naïve EGC pts with adequate organ and functional status and < G2 neuropathy. Rx consisted of biweekly O (85mg/m2) plus P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). O was stopped after 12 cycles. Secondary endpoints were toxicity, survival and molecular correlates. Results: The study met its interim efficacy threshold and proceeded to full accrual. 35 pts, median age 67 yrs (39-83), 32 males, mostly adenocarcinoma (29) were accrued. 2/4 pts at D1 developed DLTs (1 G3 diarrhea, 1 G3 mucositis). All remaining pts were treated at D-1, which had no DLTs in the safety cohort. G4 toxicity included neutropenia (2) and myocardial infarction (1). The most common G3 events were mucositis (5), dehydration and neutropenia (4 each), anorexia, neuropathy, fatigue and nausea/vomiting (all 3 each). Including G1 and 2 events, myelosuppression, mucositis and neuropathy were the most common toxicities. Median # of P cycles administered at D-1 was 8 (1, 17). In an intent to treat analysis, confirmed OR was 23% (8/35) and 16 pts (46%) had stable disease. 3 pts were non-evaluable for response. Conclusions: Combination O and P administered biweekly at 85mg/m2 and 100 mg/m2 respectively is safe, well-tolerated and has modest efficacy in aEGC. Survival analysis results will be available for the meeting. This study was approved and funded by the NCCN from general research support provided by Allos Therapeutics, a subsidiary of Spectrum Pharmaceuticals, Inc. Clinical trial information: NCT01178944.