bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of chemoradiotherapy with docetaxel for elderly patients with stage II/III esophageal carcinoma: An updated report.
Authors: Ohba Akihiro , Hashimoto Jun , Kato Ken , Ito Yoshinori , Hokamura Nobukazu , Katada Chikatoshi , Ishiyama Hiromichi , Yamamoto Sachiko , Ura Takashi , Kodaira Takeshi , Kudo Shigehiro , Nakamura Takayuki 
Published: February 2017

208 Background: Definitive chemoradiotherapy (CRT) is one of the curative options for resectable esophageal carcinoma (EC). However, there are limited data on CRT in elderly patients, and it is difficult for elderly patients to receive chemotherapy containing cisplatin. The aim of this prospective study was to clarify the efficacy and safety of definitive CRT with docetaxel (DTX) in elderly patients. Methods: The eligibility criteria for this study were as follows: clinical stage II-III (UICC 6th, non-T4) EC; performance status (PS) 0-1; age > 70; and no desire for surgical treatment. Chemotherapy consisted of 6 cycles of a 1-h infusion of DTX (10 mg/m2) repeated weekly. Radiation was concurrently applied at a dose of 60 Gy in 30 fractions. We calculated that with a sample size of 37 patients, assuming that the expected and threshold 2-year survival was 50% and 30% with one-sided alpha of 5% with 80% power. Results: Between July 2008 and January 2011, 16 patients were enrolled. The study was closed prematurely due to poor accrual. The median age was 77 years (range, 73-81); male/female: 14/2; PS 0/1: 4/12; clinical Stage IIA/IIB/III: 3/4/9. Of the 16 patients, 14 (88%) completed the CRT, 1 patient (6%) could not complete the treatment because of grade 3 esophagitis, and 1 (6%) refused to continue the treatment. The median follow-up time was 57.9 months. Six patients achieved complete response (CR), resulting in a 37.5% CR rate (95% confidence interval (CI): 15.2-64.6). The 2-year overall survival rate was 62.5% (95% CI: 39.0-86.0). The median survival time was 27.8months (95% CI: 23.7-31.9). Acute toxicities included grade 3/4 esophagitis (31%), anorexia (13%), leukopenia (6%), neutropenia (6%), thrombocytopenia (6%), mucositis (6%), and infection (6%). No treatment-related deaths were observed. Grade 3 or 4 esophagitis, pleural effusion, pericardial effusion, and pneumonitis developed as late adverse events in 13%, 13%, 6%, and 6% of patients, respectively. Conclusions: Although it is difficult to conclude about efficacy of CRT with DTX for elderly stage II-III EC patients, considering that this study was terminated prematurely, CRT with DTX seemed to have substantial clinical activity. Clinical trial information: 000001846.
Usefulness of modified PERCIST for defining response of neoadjuvant chemotherapy in esophageal cancer.
Authors: Izumi Daisuke , Yoshida Naoya , Watanabe Masayuki , Ishimoto Takatsugu , Kosumi Keisuke , Tokunaga Ryuma , Harada Kazuto , Ida Satoshi , Hiyoshi Yukiharu , Iwagami Shiro , Baba Yoshifumi , Sakamoto Yasuo , Miyamoto Yuji , Baba Hideo 
Published: February 2017

209 Background: It is sometimes difficult to exactly measure maximum diameters of tumor after chemotherapy in esophageal cancer. Richard et al. proposed PET Response Criteria in Solid Tumor (PERCIST) for assessing response of tumor after chemotherapy by PET in 2009. The first purpose is to investigate the utility of PERCIST after neoadjvant chemotherapy in esophageal cancer. The second purpose is to clarify the utility of modified PERCIST of which we use the SUV of normal (non-cancerous) esophagus as a reference of comparison for diagnosing complete response (CR) instead of the right lobe liver SUV. Methods: The clinicopathological data of the 71 esophageal cancer patients who received neoadjuvant chemotherapy (DCF) and underwent curative resection from November 2008 to May 2012 were collected. Among them, we compared pathological grade with PERCIST of the 26 esophageal cancer patients who were examined by PET before and after chemotherapy. Furthermore we investigated which reference of comparison is appropriate for diagnosing complete response between the right lobe of liver (L group) and normal esophagus (E group). Results: We could measure the tumor size of all cases after chemotherapy by PERCIST although 6 cases could not be assessed by RECIST. All of the 6 cases which were diagnosed as stable disease or progressive disease by PERCIST were pathological grade1a. The cases of complete response are 7 cases in L group and 3 cases in esophageal cases. Among the complete response cases in L group, 1 case were pathological grade1 a and 2 cases were grade 2 although all the complete response cases in E group were pathological grade 3. One case of L group relapsed after curative resection although there was no recurrent case in E group. Conclusions: The esophageal cancer patients often have history of massive alcohol intake or liver damage caused by viral hepatitis or fatty liver. Although PERCIST is useful for evaluating the effect of neoadjuvant chemotherapy of esophageal cancer, it is better to use normal esophagus as a comparison standard for diagnosing complete response.
The prognostic factors and the cause of death in patients with advanced or recurrent gastric cancer.
Authors: Lee Sang Woo , Choi In Keun , Lee Chang Min , Kim Seung Young , Hyun Jong Jin , Jung Sung Woo , Jung Young Kul , Koo Ja Seol , Kim Jong-Han , Park Seong-Heum , Kim Seung-Joo , Kim Jun Suk 
Published: February 2017

215 Background: The purpose of this study is to evaluate significant prognostic factor and compare the cause of death in patients with advanced or recurrent gastric cancer. Methods: We reviewed the medical records of 170 patients who had been diagnosed as advanced or recurrent gastric cancer between January 2006 and September 2013. The patients were divided into two groups. One group (advanced gastric cancer: AC) included 104 patients had undergone chemotherapy for advanced gastric cancer, and the other group (recurrent gastric cancer: RC) 66 for recurrence after surgical treatment. The causes of death and overall survival were compared between two groups, and the significant prognostic factors were investigated by multivariate analysis. Also, subgroup analysis was performed for 18 patients with gastrectomy for curative intent, and they were proved to have unresectable gastric cancer after surgery (non-palliative surgery for advanced gastric cancer: NS). Results: In the comparison for the causes of death, two groups showed no statistical difference, but AC group had more tendency to die because of bleeding ( p = 0.054) and infection ( p = 0.075). Overall survival of AC group did not differ from that of RC ( p = 0.901). In multivariate analysis, bone metastasis ( p = 0.013, HR = 1.923), peritoneal seeding ( p = 0.001, HR = 2.182) and the frequency of chemotherapy ( p < 0.001, HR = 0.887) were significantly associated with the overall survival. In a subgroup analysis, the overall survival of NS was significantly higher than AC ( p = 0.032). Conclusions: In the patients with advanced or recurrent gastric cancer, AC might have more possibility to die because of bleeding and infection than RC. Additionally, the prognosis of patients with advanced or recurrent gastric cancer was affected by the presence of bone metastasis, peritoneal seeding and frequency of chemotherapy. Non-palliative surgery for gastric cancer might show the better prognosis than AC in the specific conditions.
Impact of first-line fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with advanced gastroesophageal adenocarcinoma: A retrospective analysis.
Authors: Lino Aline Da Rocha , Moreira Raphael Brandao , Gomes Jessica Ribeiro , Sousa Tarcia Tarciane Soares de , Abrahao Carina Mina , Martins Junior Rodnei Merlrina , Alessandretti Matheus Bongers , Amarante Marcus Paulo Fernandes , Schutz Fabio Augusto Barros , Kawamura Carolina , Schmerling Rafael , Cruz Marcelo Rocha , Maluf Fernando C. , Buzaid Antonio C. , Peixoto Renata D'Alpino 
Published: February 2017

216 Background: Despite a large number of randomized trials, there is no consensus as to the best regimen for advanced gastroesophageal cancer. Combination therapy with docetaxel, cisplatin, and 5-FU has shown increased response rates, progression-free survival (PFS) and overall survival (OS), but at the cost of significant toxicity. Based on a small phase II study, FLOT has been adopted by some groups given its better toxicity profile. We aim at reporting our experience with this regimen Methods: Patients with unresectable advanced gastroesophageal adenocarcinoma who received FLOT (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2 as a 24h infusion in combination with docetaxel 50 mg/m2 on day 1 every 2 weeks) as first-line therapy at our institution were retrospectively evaluated. PFS and OS were estimated by the Kaplan-Meier method. Results: A total of 23 patients were reviewed, most of them with metastatic disease (60%). Median age was 56 years (range 26–76) and 74% were male. Median PFS and OS were 5,2 (95% CI 4,0-6,3) and 8,5 months (95% CI 4,4-12,6), respectively. Only 13%of the patients experienced prolonged PFS (>12 months). There were no deaths due to the treatment. Conclusions: Before FLOT could be adopted as a first-line regimen for metastatic gastroesophageal cancer, phase III trials are urgently needed comparing FLOT with more traditional regimens.
The comparison of the usefulness of nab-paclitaxel and paclitaxel for advanced or recurrent gastric cancer.
Authors: Kimura Yasue , Kusumoto Tetsuya , Kusumoto Eiji , Sugiyama Masahiko , Ohta Mitsuhiko , Tsutsumi Norifumi , Sakaguchi Yoshihisa , Ikejiri Koji 
Published: February 2017

217 Background: For patients who do not respond to S-1-based treatment in Japan, weekly paclitaxel (PTX) therapy is more frequently used as second-line chemotherapy. On the other hand, the agent could not be used for alcohol hypersensitivity in some cases. Nab-Paclitaxel (N-PTX), which is the protein-bound paclitaxel, has recently been introduced in Japan. The purpose of this study was to retrospectively determine the more preferable agent, N-PTX or PTX, following the S-1-containing chemotherapy in patients with advanced or recurrent gastric cancer (ARGC). Methods: We conducted a retrospective review of the data for 40 patients with ARGC, who received either N-PTX monotherapy for 5 patients or PTX monotherapy for 35 patients. N-PTX was used as the second-line for all patients in this group. On the other hand, in the PTX group, 4, 28 and 3 patients received PTX monotherapy as the 1st-, 2nd- and 3rd-line, respectively. N-PTX was administered intravenously at a dose of 260 mg/m2 repeated triweekly. PTX was administered intravenously at a dose of 80 mg/m2repeated weekly (on days 1, 8 and 15) every four weeks. The objective response rate (ORR), adverse events, progression-free survival (PFS) were compared between the two groups. Results: For tumor response, in the N-PTX group, CR/PR/SD/PD were 0/3/1/1, respectively for an ORR of 60% and a DCR of 80%; in the PTX group, CR/PR/SD/PD were 0/3/15/13, respectively for an ORR of 10% and a DCR of 58%. The ORR of the N-PTX group was higher, which might result from the higher dose intensity in the group, compared with the PTX group. For the adverse toxicity, in the both group, events of grade ≥ 3 were not observed. Serious neurotoxicity (≥grade 3), as commonly described for treatment with paclitaxel, was not observed in this study. The survival data showed that the PFS was 253 days in the N-PTX group, compared with 176 days in the PTX group, which were not significantly different. Conclusions: We suggest the application of N-PTX in place of PTX after S-1 containing chemotherapy for ARGC, only from the perspective of the tumor response. Further data accumulation is required for overall survival.
Efficacy and feasibility of neoadjuvant chemotherapy for elderly patients with stage II/III esophageal cancer: Retrospective study.
Authors: Miyamoto Takahiro , Terazawa Tetsuji , Goto Masahiro , Asaishi Ken , Shimamoto Fukutaro , Kuwakado Shin , Nishitani Hitoshi , Kii Takayuki , Kawai Masaru , Higuchi Kazuhide 
Published: February 2017

220 Background: From the result of JCOG 9907 study, which showed the supremacy of neoadjuvant chemotherapy (NAC) of 5-fluorouracil plus cisplatin infusion (FP) over adjuvant chemotherapy, NAC FP is standard therapy for stage II or III esophageal cancer in Japan. However, the efficacy and feasibility of NAC FP for elderly patients (pts) still remains unclear. Methods: We examined stage II or III esophageal cancer patients aged 70 or over, who received NAC FP at our institution between April 2008 and August 2014, retrospectively. Results: 12 pts received NAC FP at least 1 course. The pts characteristics were as follows: median age (range), 73 (70-78); male/ female, 11/1; PS 0/1, 3/9. Location of primary tumor and clinical stage based on UICC 2009 were as follows: upper/middle/lower, 3/6/3; stage IIA/IIB/IIIA/IIIB, 3/3/3/3. 2 pts (16.7%) occurred grade3/4 neutropenia (16.7%). grade3/4 non-hematotoxicities were nausea; 2 pts (16.7%), vomiting; 1 pt (8.3%), appetite loss; 4 pts (33.3%), stomatitis; 1 pt (8.3%) and acute kidney injury; 1 pt (8.3%). 3 pts were underwent surgery after 1 course of NAC FP due to renal dysfunction. 3 pts were not performed surgery because of decreased respiratory function, decreased PS and progression disease. 9 pts were performed surgery after NAC FP. The histological efficacy was 1a/1b/2/3; 4/3/1/1 and curativity was R0 (degree A)/R0 (degree B); 8/1. 4 pts (44%) had down staging. Median follow-up time was 16.5 months (range; 4-63), the 5-year relapse free survival rate was 19.0% (95% CI: 2.7-66.4%) and the 5-year overall survival rate was 67% (95% CI: 32-89%). Conclusions: NAC FP for stage II/III esophageal cancer might be effective even in pts ≥70 years of age. However, gastrointestinal toxicity and renal toxicity were developed frequently, therefore the indication of NAC FP for elderly pts must be decided carefully.
The possibilities of treatment of gastrointestinal stromal tumors.
Authors: Gluszek Stanislaw , Koziel Dorota , Matykiewicz Jarosław , Rylski Rafal 
Published: February 2017

222 Background: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal tumour of digestive tract, presesting less than 1% of all digestive tumours. This study is analyse a group of patients treated surgically due to GIST. Methods: The group of 71 patients consisted of 34 males and 37 females between the age of 32 and 89 (M 44-83, average 64.6; F 43-89, average 66.5) treated surgically due to GIST. Analysis included clinical symptoms, diagnosis, surgical treatment, location of tumour, outcome of histopathological and immunohistochemical examinations, recurrence of disease, metastases and mortality rate. Results: Among 71 GIST patients 35 were with low aggressivity level, 14 with average and 22 with high. Most of patients were subjected to surgical treatment (laparoscopic or open) on a planned basis and in 3 cases on an emergency basis due to the intensified symptoms of intestinal occlusion, 50 patients were found to have gastric tumours, 3 duodenal tumours, 13 small intestine tumours, 3 colonic tumours, 2 rectal tumours. Histopathological examination outcome showed radical tumour resection in all cases Tumours of size exceeding 5 cm in diameter were found in 30 cases. Most patients had definited type of mutation. Predominated mutations localized in exon 11. There was no perioperative mortality rate. During follow up (from 1 month to 130 months), 16 patients died, including 4 due to GIST dissemination, 4 were diagnosed with recurrence of GIST and two of them were qualified for imatinib treatment others died of cardio-vasculary diseases. Most of patient underwent resection of tumor with safety margin of gastric wall (21), 5 patients were treated by laparoscopic surgery. All patients, who subsequently had postoperative recurrence or died due to GIST metastases, were diagnosed with highly aggressive tumor. Conclusions: GIST - still unknown treatment possibilities [surgery, imatinib, other specific tyrosine kinase inhibitors, what next?]. Analysis of cases from our study confirms that large size of tumor (diameter > 5cm) and high mitotic index (MI >5/50 HPF) are factors associated with bad prognosis (metastases, recurrence).
Intraoperatively assessed macroscopic serosal changes in patients with curatively resected advanced gastric cancer (GC): Clinical implications for prognosis and peritoneal recurrence.
Authors: Yoo Changhoon , Ryu Min-Hee , Chang Heung-Moon , Yook Jeong Hwan , Park Young Soo , Ryoo Baek-Yeol , Park Sook Ryun , Oh Sung Tae , Kim Byung Sik , Kang Yoon-Koo 
Published: February 2017

23 Background: To validate the prognostic relevance of macroscopic serosal changes in patients with resected GC, we analyzed prospectively collected databases of two multicenter randomized phase III trials on adjuvant chemotherapy. Methods: In total, 655 patients in the control groups of AMC 0101 (NCT00296322) and 0201 (NCT00296335) trials were selected. Macroscopic serosal changes were determined according to disruptions in serosal continuity, such as changes in color or nodular texture by the operating surgeon. Correlations with recurrence-free survival (RFS), overall survival (OS), and time-to-peritoneal recurrence were analyzed. Results: About two-thirds of the patients were male (69%), and the median age was 55 years (range = 29–70 years). According to Lauren’s classification, 215 patients (33%) showed intestinal type. After a median follow-up period of 61.6 months (range = 2.6–113.9 months), the 5-year RFS and OS rates were 55.0% (95% CI = 51.2–58.9%) and 59.9% (95% CI = 56.2–63.6%), respectively. Intraoperatively assessed macroscopic serosal changes were identified in 432 patients (66%). This was significantly associated with multifocal or diffuse gastric cancer (p = 0.001), Borrmann type IV (p = 0.005), advanced pathological T stage (p < 0.001), advanced pathological N stage (p < 0.001), advanced pathological stage (p < 0.001), and total gastrectomy (p < 0.001). In multivariate analyses, which included prognostic factors of localized gastric cancer, macroscopically serosal changes were significantly associated with poor RFS (hazard ratio [HR] = 2.0, 95% CI 1.4–2.7; p < 0.001) and OS (HR = 2.1, 95% CI 1.5–3.0; p < 0.001). It was also significantly related with shorter time-to-peritoneal recurrence (HR = 2.9; 95% CI = 1.7–5.0; p< 0.001). Conclusions: Intraoperatively assessed macroscopic serosal changes confer a poor prognosis and increased peritoneal recurrence in patients with curatively resected GC. Macroscopic assessment of serosal changes may be a useful indicator that allows better risk stratification of patients with resected GC in terms of prognosis and peritoneal recurrence.
eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib.
Authors: Casadei Gardini Andrea , Marisi Giorgia , Scarpi Emanuela , Scartozzi Mario , Faloppi Luca , Tenti Elena , Tamberi Stefano , Foschi francesco Giuseppe , Tamburini Emiliano , Frassineti Giovanni Luca , Cascinu Stefano , Ulivi Paola 
Published: February 2017

230 Background: Cancer cells adapt to hypoxic microenvironment through the activation of many molecules, including endothelial nitric oxide synthase (eNOS). Sorafenib, by blocking the vascular endothelial growth factor receptors (VEGFRs), induces an inhibition of eNOS activity with a consequent decrease of the production of nitric oxide (NO). NO is associated with an increase of tumor angiogenesis, tumor invasion and metastasis formation. In our study we analysed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma treated with sorafenib. Methods: From a database of 257 patients diagnosed with hepatocellular carcinoma from 2004 to 2014, we selected 54 patients who received sorafenib. Peripheral blood samples or FFPE tumor tissues were available for DNA extraction and genotyping analysis. Three eNOS polymorphisms (eNOS +894 G/T, eNOS VNTR 27bp 4a/b, eNOS -786 C/T) were analyzed by direct sequencing or Real Time PCR method. We analyzed 21 patients for the VNTR 4a/b polymorphism and 32 patients for -786 C/T polymorphism. All the candidate genotypes were evaluated to identify a potential correlation with overall survival (OS) (log-rank test). Results: With regard to eNOS VNTR it was observed that patients carrying the b allele (5 repetitions of 27bp) both in homozygosity (4bb) and in heterozygosity (4ab) were associated with a better OS. The variants 4aa (4 repeats of 27bp in homozygosity), 4ab and 4bb, were associated with a median OS of 5.7, 13.9 and 23.6 months, respectively (p = 0.016). For eNOS-786 the presence of the T allele both in homozygosity (TT) and in heterozygosity(TC) was associated with a statistically significant longer OS with respect to patients with CC genotype (15.6 versus 13.9 months, respectively, p = 0.031). No correlations were observed in relation to PFS (p = 0.494). Conclusions: eNOS VNTR and eNOS -786 could represent prognostic markers in patients with advanced hepatocellular carcinoma treated with sorafenib.
Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study.
Authors: Zhu Andrew X. , Ryoo Baek-Yeol , Yen Chia-Jui , Kudo Masatoshi , Poon Ronnie Tung-Ping , Pastorelli Davide , Blanc Jean-Frédéric , Chung Hyun Cheol , Baron Ari David , Pfiffer Tulio Eduardo Flesch , Okusaka Takuji , Kubackova Katerina , Trojan Jorg , Sastre Javier , Chau Ian , Chang Shao-Chun , Abada Paolo , Yang Ling , Hsu Yanzhi , Park Joon Oh 
Published: February 2017

232 Background: REACH was a global, multicenter, randomized, double-blind, phase 3 study evaluating the efficacy and safety of RAM as a single agent for the treatment of pts with advanced HCC after prior sorafenib therapy. The primary outcome for REACH was presented at ESMO 2014. The overall survival (OS) HR for the ITT population (RAM 283; placebo [PBO] 282) was 0.866 (95% CI 0.717, 1.046; p=0.1391); median OS was 9.2m for RAM vs 7.6m for PBO. The pre-specified subgroup analysis of baseline AFP (cutoff 400 ng/mL) suggested AFP is a predictive marker for RAM survival benefit. Methods: Pre-specified subgroup analysis was performed based on baseline AFP with a cutoff of 400 ng/mL. Additional analyses were conducted using stratified/unstratified cox regression models and corresponding log rank test to evaluate the relationship between baseline AFP and RAM treatment effect. Results: In 250 pts with baseline AFP ≥400 ng/mL (RAM 119; PBO 131), OS HR was 0.67 (95% CI 0.51–0.90; p=0.0059). Median OS was 7.8m for RAM vs 4.2m for PBO. In 417 pts with a baseline AFP ≥1.5 × upper limit of normal (ULN; RAM 205; PBO 212), mOS was 8.6m for RAM vs 5.7m for PBO and the HR was 0.749 (95% CI: 0.603, 0.930) (p=0.0088). The interaction testing of baseline AFP and RAM treatment effect on OS using both cutoffs (400 ng/mL and 1.5 xULN) are significant (p-value = 0.0272 and 0.0372, respectively). The safety profile in these pt populations was similar to that observed in the overall safety population. Additional REACH analyses demonstrating the predictive value of baseline AFP for RAM treatment effect on OS will be presented. Conclusions: A clinically meaningful improvement in OS was observed in populations with a baseline AFP ≥400 ng/mL or ≥1.5 × ULN. Additional analyses demonstrated a consistent RAM OS benefit for the pt population with baseline AFP over a wide range of values above the normal range. Baseline AFP is a likely predictive marker for RAM OS benefit. Clinical trial information: NCT01140347.