bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative imatinib for locally advanced gastrointestinal stromal tumors (GIST): CONVERT trial.
Authors: Vilhena Pereira Bruno Dos Santos 
Published: February 2017

130 Background: Primary GISTs are frequently diagnosed as large masses requiring wide resections. Our primary objective is to evaluate response rate of imatinib through RECIST and Choi criteria in these patients. Secondary endpoints were downstaging, resectability, safety and tolerability. Methods: This phase II Brazilian study was conducted in 7 centers between 2008 and 2012. To standardize elegibility, inclusion criteria took into account the primary site, size and multi-visceral resection need per surgeon evaluation. Thirty-nine non-metastatic GIST patients with measurable disease and no previous systemic or local treatment were assigned to daily imatinib 400mg for 16 weeks followed by surgery or until medical decision, progressive disease or toxicity. Imatinib could be continued whether adjuvant or palliative according to risk stratification and residual disease. Clinicaltrials.gov NCT01483014. Results: The objective response rate was 32,1% (IC95% 17,9% - 50,7%) on RECIST and 78,6% (IC95% 60,5% - 89.8%) on Choi. One patient (3,8%) had progressive disease, six patients (20%) had serious adverse events with two (6,7%) deaths, not related to the study drug. Treatment discontinuation due to intolerance was observed in 10% of patients caused by extremities pain, nausea, neutropenia, constipation and thrombocytopenia. Surgery was performed on 23 patients (82.1%), with 83,3% being R0. Median tumor size was 9,4cm (1,2 to 22,0cm) and 72,7% had <5 mitosis/50HPF. Conclusions: Imatinib is active and safe in the preoperative setting. Although Choi criteria evaluates responses earlier, a longer course of imatinib, from 6 to 12 months, should be studied to evaluate if longer courses can increase tumor shrinkage and improve this strategy’s usefulness. Clinical trial information: NCT01483014.
Comparison of adjuvant chemoradiation to perioperative chemotherapy for the treatment of resected gastric and gastroesophageal junction adenocarincoma.
Authors: Lim Howard John , Kim Hae Rin , Schellenberg Devin , Kollmannsberger Christian K. , Cheung Winson Y. 
Published: February 2017

139 Background: There are several accepted peri-operative treatment modalities for resected gastric (GC) and gastroesophageal junction (GEJ) adenocarcinoma. In 2008, peri-operative chemotherapy (CT) using the MAGIC protocol was adopted as the preferred approach over adjuvant chemoradiation with the MacDonald protocol (cXRT) in British Columbia. An era to era comparison was performed to determine if there were differences in outcomes. Methods: Data from pharmacy records of patients (pts) referred to 1 of 5 cancer treatment centres in BC were analyzed from Jan 2001-July 2010. Pts that underwent curative resection for GC or GEJ were included. The cXRT cohort was defined as those treated from Jan 2001-Dec 2007, prior to the introduction of CT. The CT cohort included those treated from Jan 2008-July 2010. Descriptive statistics were used to compare the groups. Survival analysis was performed using Kaplan Meier methods. Results: Table 1 summarizes the patient characteristics. In the CT arm, there were more males, fewer pts with a LN ratio >0.2, and shorter median follow-up. 92.1% completed pre-operative chemotherapy and 44.7% completed post-operative chemotherapy whereas 73.3% of pts completed cXRT (p<0.05). Median survival was 37.5 and 36.9 months in the CT and cXRT arms, respectively. Conclusions: Delivery of CT was consistent with the MAGIC trial whereas more patients completed cXRT than in the MacDonald trial (73.3% vs. 64%). Outcomes of CT compared to cXRT appear to be similar in this comparative analysis with similar relapse and survival rates. Pre-operative CT results in fewer pts with a LN ratio > 0.2. Either modality can be considered in the peri-operative management of GC or GEJ adenocarcinoma. [Table: see text]
Salvage endoscopic submucosal dissection for the treatment of esophageal squamous cell carcinoma after local treatment failure with chemotherapy, radiotherapy, or chemoradiotherapy.
Authors: Iizuka Toshiro , Kikuchi Daisuke , Hoteya Shu , Yamada Akihiro , Kaise Mitsuru 
Published: February 2017

148 Background: Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are efficacious treatment options for esophageal squamous cell carcinoma (ESCC). However, local treatment failure remains a major problem. In this study, we applied endoscopic submucosal dissection (ESD) for the treatment of ESCC after local treatment failure with CT, RT, or CRT. The efficacy, safety, and feasibility of salvage ESD were assessed. Methods: Between 2008 and 2014, 611 patients underwent ESD for superficial ESCC in our hospital. Of them, 14 required salvage ESD: 7 for local treatment failure after CT, 4 after CRT, and 3 after RT. Each patient was treated with CT using 5-fluorouracil + cisplatin or RT, which consisted of >50 Gy of irradiation with or without concurrent CT. The following clinical findings were confirmed in all patients: no evidence of lymph node or distant metastasis after treatment, and an endoscopically resectable lesion. Results: The male to female ratio was 11:3 and the mean age was 64.9 (44-81) years. Clinical stages before treatment were T1b/T2/T3/T4 in 10/1/2/1, N0/1 in 7/7, and M0/1 in 13/1, respectively. The mean tumor size was 18.6 mm, and the mean procedure time was 45.7 min. En bloc resection was achieved in 100% of cases, and the R0 resection rate was 78.6%. Histopathological assessment of specimens taken at salvage ESD revealed that 6 lesions (42.9%) had invaded the submucosal layer and had been resected noncuratively because of a positive vertical margin (n = 2) or positive lymphovascular invasion (n = 5). No immediate or delayed complications, including major bleeding or perforation, and no ESD-related deaths occurred. At a mean follow-up period of 26.5 (range, 5–55) months, local recurrence had developed at the treatment site in 2 patient. Overall, 10 patients were still alive. The remaining 4 had developed lymph node metastasis, 2 of whom had died from it. Conclusions: Salvage ESD is an option for ESCC patients with local treatment failure after CT, RT, or CRT.
The feasibility and safety conversion surgery in stage IV gastric cancer.
Authors: Sato Tsutomu , Nishimura Ken , Nakayama Norisuke , Motohashi Osamu , Segami Kenki , Hayashi Shigeya , Kawabe Taiichi , Aoyama Toru , Hayashi Tsutomu , Yamada Takanobu , Oshima Takashi , Rino Yasushi , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki 
Published: February 2017

164 Background: Conversion surgery could be an option for stage IV gastric cancer when distant metastasis (M1) is disappeared by palliative chemotherapy, however, feasibility, safety and efficacy of surgery after long-term chemotherapy remains unclear. Methods: This retrospective study examined 21 gastric cancer patients who underwent curative conversion surgery between 2001 and 2013. Postoperative complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) was estimated by Kaplan-Meier method. Results: Median follow-up period (range) was 43.9 months (7.2-72.1 months). The number of M1 factors was one in 17 patients and two in 4, including metastases to non-regional lymph node in 11, peritoneum in 11, and liver in 3. The regimen of chemotherapy was S-1/CDDP in 11 patients, S-1/docetaxel/CDDP in 5, S-1/docetaxel in 2, 5FU/leucovorin/paclitaxel in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to disappearance of M1 factor was 3.5 months and the median duration from initiation of chemotherapy to the operation was 7.5 months. A total of 19 patients (90.4%) underwent over D2 lymphadenectomy including modified D2 in 2 patients, D2 in 16, and D2 plus para-aortic nodal dissection in 3. M1 tumor was not resected except para-aortic nodal dissection in 3 patients. The median operation time and bleeding were 205 minutes and 228 ml, respectively. Grade 2/3/4 morbidities were observed in 5 patients (23.8%); 2 pancreatic fistula (grade 2), 2 abdominal abscess (grade 2 and 3), and 1 anastomotic leakage (grade 3). No mortality was observed. Pathological response of the primary tumor, defined as disappearance of more than two third of the tumor cells, was 66.7% including 19.0% of complete response. The overall survival (OS) after initiation of chemotherapy was 90.5% at 1-year, 85.7% at 2-year, and 75.9% at 3-year with median survival time (MST) of 52.9 months, while OS after surgery was 90.5% at 1 year, 76.2% at 2-year, and 64.5% at 3-year with MST of 40.9 months. Conclusions: Curative conversion gastrectomy for stage IV gastric cancer was feasible and safe. Considering excellent survival, conversion surgery has a value to be evaluated in prospective studies.
Phase I study of ABT-700, an anti-c-Met antibody, in patients (pts) with advanced gastric or esophageal cancer (GEC).
Authors: Kang Yoon-Koo , LoRusso Patricia , Salgia Ravi , Yen Chia-Jui , Lin Chia-Chi , Ramanathan Ramesh K. , Kaminker Patrick , Sokolova Irina , Bhathena Anahita , Wang Lan , Naumovski Louie , Strickler John H. 
Published: February 2017

167 Background: MET is a receptor tyrosine kinase associated with treatment resistance. MET amplification (MA) results in c-Met overexpression and activation through autodimerization, and may be an important oncogenic driver in patients (pts) with advanced GEC. MA is relatively rare in primary tumors (<5%), but may increase under the selective pressure of systemic therapy. ABT-700 is an anti-c-Met antibody with significant preclinical single-agent activity against MA human xenograft tumors. Efficacy and safety data for ABT-700 in patients with MA advanced GEC are presented. Methods: MA was assessed in tumor biopsy tissue by fluorescence in situ hybridization (FISH; Abbott Molecular Diagnostics) or DNA sequencing. MA, identified by FISH, was defined as a MET/CEP7 ratio>2 in ≥20% of cells. The dose of ABT-700 is 15 mg/kg IV, once every 3 weeks, established during the dose escalation phase of the study. Responses were assessed using RECIST version 1.1. Results: As of May 31, 2014, 6 pts with chemotherapy refractory GEC have been treated with ABT-700. All pts had disease progression on 3 or more prior lines of chemotherapy. 4/6 pts had MA. 1 pt had MA identified retrospectively, and 3 pts had MA identified through a prospective screening effort. Among the 4 pts with MA GEC, 3 pts had a partial response (PR) and 1 pt had progressive disease (PD) as best response (ORR= 75%). Of the 3 pts who responded, the best response in target lesions was –56%,-52%, and –58%, and the PFS was 27, 18, and 24 weeks, respectively. Each of these three responders had a longer PFS with ABT-700 than with their preceding chemotherapy. In each of the 4 cases of MA identified in this study, MA was only detected in metastatic recurrent tumors and not the primary tumor tissue. The 2 pts without MA had PD as best response. ABT-700 was well tolerated, with no treatment related Grade 3-5 adverse events. Conclusions: In 4 pts with MA GEC, ABT-700 was well tolerated and appeared to have substantial single-agent activity. In this small cohort of gastric patients MA appears to be more common in treatment-refractory tumors than in primary untreated tumors, suggesting that screening efforts should focus on this treatment-refractory patient population. Clinical trial information: NCT01472016.
Quality of life (QOL) in patients with esophageal cancer treated with radiation (RT) in the radical setting.
Authors: Choudhary Anita , Liu Geoffrey , Chacko Pravin Philip , Fadhel Ehab , Cho Charles , Woo Rachel , Cheung Agnes , Vanderwater Catherine , Xin Cindy , Xu Wei , Wong Jason , Lee Alex , Kassam Zahra 
Published: February 2017

186 Background: QOL is poorly documented in patients with esophageal carcinoma treated with curative intent, especially trimodality therapy. QOL and survival outcomes were evaluated in a single centre prospective cohort study of esophageal carcinoma patients treated with RT in the radical setting. Methods: Patients completed the EORTC-QLQC30 at baseline, the end of RT, 6 months and 1 year after RT. A 10-point difference in scores was considered clinically significant. Results: Thirty-three of 45 consequently treated patients between February 2012 and June 2014 participated, all male, median age 63 years (range 40-76), with T1-4N1-3M0 disease (AJCC 7thedn), median follow up 0.9 years (range 0.1-2.3). Four patients were treated definitively with chemoradiation 45-50Gy in 25 fractions; 14 neoadjuvantly 45-50Gy in 25 fractions; 15 neoadjuvantly 41.4Gy in 23 fractions, with concurrent chemotherapy. Compliance for questionnaire completion was 80-100%. 2 year overall survival (OS) and disease free survival (DFS) were 77% and 63%. Median scores on role, social, fatigue and appetite showed clinically significant worsening at the end of RT; in addition statistical significance was found for global QOL, physical, nausea/vomiting, and shortness of breath [median difference (MD): global -8.3 p=0.004, physical -6.6 p=0.003, role -16.6 p=0.001, social -16.6 p=0.78, nausea/vomiting 8.3 p=0.02, fatigue 22.2 p=0.001, shortness of breath 0 p=0.037, appetite 33.3 p=0.009]. At 6 months post RT global QOL (MD -16.6 p=0.23), physical (MD -13.3 p=0.007), role (MD -16.7 p=0.11) and fatigue (MD 11.1 p=0.18) were clinically significantly depressed. At one year all scores had returned to baseline, except pain, which was clinically significantly worse (MD 16.7 p=0.41); 64% of the cohort reported worse pain compared to baseline. Although global QOL on average returned to normal, 46% reported this to be clinically worse at one year compared to baseline. No association was found between baseline global QOL and OS (p=0.15) or DFS (p=0.57). Conclusions: QOL was worsened in several domains during and up to 6 months post RT. At one year all scores had returned to baseline except for pain which was significantly worsened in 64% of patients.
Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer (EC) trials with preoperative therapy (PreTx): Literature-based meta-analysis.
Authors: Kataoka Kozo , Nakamura Kenichi , Mizusawa Junki , Eba Junko , Katayama Hiroshi , Kato Ken , Shibata Taro , Fukuda Haruhiko 
Published: February 2017

199 Background: Disease-free survival after adjuvant chemotherapy in colon and gastric cancer has already been validated as a surrogate endpoint for OS. However, there have been no reports evaluating PFS as a surrogate endpoint in resectable EC. Standard treatment for resectable EC is preoperative chemotherapy (preCx) or chemoradiotherapy (preCRT) followed by surgery. This study was conducted to evaluate the trial level correlations between PFS and OS in resectable EC with PreTx and to explore potential merit of PFS as a surrogate endpoint for OS. Methods: A systematic literature search of randomized trials with preCx or preCRT for EC reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R2) within PFS and OS. 95% confidence interval of R2 was estimated by bootstrap method. The primary analysis included trials in which the HR of PFS and OS were reported. A sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Results: Of 615 articles, 9 trials (2,725 patients) were selected for the primary analysis and 12 (3,020) for the sensitivity analysis. Median numbers of enrolled patients were 256 (range 101-802) in primary analysis, and 209 (75-802) in sensitivity analysis. The numbers of trials including only preCx, only preCRT and both, were 5, 4 and 0 in the primary analysis, and 5, 6 and 1 in the sensitivity analysis. The primary analysis did not show the correlation between treatment effects on PFS and OS (R2 0.217, 95%CI [0.003-0.910]). The sensitivity analysis did not show the association of PFS and OS (R2 0.153, 95%CI [0.000-0.682]). Conclusions: Although the number of randomized controlled trials evaluating PreTx for EC is limited at the moment, PFS was not suitable as a surrogate endpoint for OS. OS should be used as the primary endpoint in trials of PreTx for resectable EC.
Impact of sarcopenia (Sp) on outcomes in patients (pts) undergoing trimodality therapy for esophageal cancer.
Authors: Weston Brian , Shaikh Talha , Handorf Elizabeth , Scott Walter Joseph , Cohen Steven J. , Meyer Joshua E. 
Published: February 2017

221 Background: Sp, or severe muscle wasting, has been implicated as an important prognostic factor in cancer pts. We assessed the association between body composition changes and outcomes in pts with esophageal cancer undergoing tri-modality therapy. Methods: Following IRB approval, we reviewed all pts who underwent chemoradiation followed by esophagectomy at an NCI-designated cancer center from 2000-2013. Pts who underwent CT assessment pre- and post-neoadjuvant chemoradiation were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of 55.4 cm2/m2 for males and 38.9 cm2/m2for females. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (SFMR), and visceral to subcutaneous adipose tissue ratio (VSATR) were also derived using CT-based measures. Changes in the above parameters and Sp were correlated to post-operative (post-op) complications (cx), treatment (tx) response, disease free survival (DFS), and overall survival (OS). Analysis was performed using non-parametric Wilcoxon and Kruskal-Wallis tests, and Kaplan-Meier curves with log-rank tests. Results: A total of 48 pts met the inclusion criteria; the median age was 62 (range 42-80) with a median follow up of 28 months (range 4-103). Most pts had T3 (85%), N1 (70%), or M0/M1a disease (92%). Ten pts (21%) had Sp at the initiation of tx, with 9 of these remaining Sp post-tx, and 1 patient developing Sp. Post-tx Sp was associated with an increased rate of post-op mortality (p=0.03). Three of the 10 patients with Sp died post-op versus 1/36 in the non-Sp group. Post-tx Sp was associated with a decreased rate of post-op strictures (p = 0.04). Thirteen of the 36 pts in the non-Sp group developed strictures versus none in the Sp group. There was a significant change in all other measures pre vs. post-tx; FM (-4.3 kg/m2, p<0.01), FFM (-5.0 kg/m2, p<0.01), SFMR (-0.1, p=0.04), and VSATR (-0.02, p<0.01). None of these were correlated with post-op cx, tx response, DFS, or OS. Conclusions: Post-tx Sp was associated with an increased incidence of post-op mortality but a lower rate of strictures. Our study was limited by sample size, and further studies should examine the relationship between Sp and peri-operative outcomes.
Patterns and severity of chemotherapy-induced nausea (CIN) in patients with gastrointestinal cancers associated with highly to moderately emetogenic chemotherapy (HEC and MEC).
Authors: Aiba Keisuke , Tamura Kazuo , Saeki Toshiaki , Baba Hideo , Kitagawa Yuko , Yoshida Kazuhiro , Furuse Junji , Kakeji Yoshihiro , Wakabayashi Go 
Published: February 2017

24 Background: Chemotherapy-induced nausea and vomiting (CINV) is well controlled recently thanks to novel antiemetic therapy, but the incidence of nausea remained high in patients receiving either HEC or MEC. The aim of the study is to investigate patterns and severity of CIN in cancer patients who are to receive chemotherapy for the first time. Methods: A nationwide survey on CINV was conducted by the CINV study group of Japan. A 7-day diary for CINV was provided to the patient prior to chemotherapy to record daily occurrence and severity of CINV. CIN was measured using visual analog scales(VAS) of 10cm length scales. Acute and delayed CINV were defined as nausea and vomiting which developed within or after 24 hours after the start of chemotherapy, respectively. Results: A total of 2,068 patients were registered and 1,910 patients were analyzed. A mean age was 62 (range:19-87) and there were 873 males and 1,037 females. MEC was given to 715 as was HEC to 1,195 patients. Underlying diseases were esophageal (192 patients), gastric (152), colorectal (90), hepato-biliary-pancreatic (100), lung (426) and breast cancer (429), and gynecological (214) and hematological malignancy (197). Comparing patients with various cancers treated with similar emetogenic agents or regimens, we easily could find that there are several patterns of CIN severity. Firstly, temporal profiles of CIN severity of esophageal, gastric and lung cancers were similar, having daily increased delayed nausea up to Day 7. The reason of this phenomenon seems due to a single high dose of CDDP. Colorectal and hepato-biliary-pancreatic cancer had a similar mild CIN pattern over 7days, probably due to mild emetogenic nature of oxaliplatin and moderate dose of CDDP. Conclusions: Temporal profile and severity of CIN patterns seem to be divided into several groups and delayed CIN remained to be high and needs further investigation.
Combined use of methylated reprimo cell-free DNA and pepsinogens for noninvasive detection of early gastric cancer.
Authors: Alarcon Alejandra , Olivares Wilda , Maturana Maria Jose , Rodriguez Andres , Padilla Oslando , Wichmann Ignacio Alberto , Calvo Alfonso , Corvalan Alejandro 
Published: February 2017

27 Background: Gastric cancer (GC) has been described as a multistep cascade of precursor lesions such as non-atrophic chronic gastritis (NACG), multiphocal atrophic gastritis (MAG), intestinal metaplasia (IM), low grade dysplasia (LGD) and high grade dysplasia (HGD) leading to early stages of GC (EGC). Currently, no non-invasive biomarkers for this progression are clinically available. We have previously identified a potential biomarker based on methylated Reprimo (RPRM) cell-free DNA (cfDNA) (Clin Cancer Res 2008;14:6264-9). In a cross-sectional study of 1,076 patients, we showed a sensitivity of 70.8% (95% CI: 60.3 to 81.3) and specificity of 74.3% (95% CI: 71.5 to 77) for methylated RPRM cfDNA, to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC (Digestive Disease Week 2014 #108). However, the crude detection rate of EGC was only 46.6%. Here, we aim to explore the role of the combined use of methylated RPRM cfDNA and well stablished atrophy biomarkers such as pepsinogens, for non-invasive detection of EGC. Methods: A case-control study was performed including 237 patients (NACG:40; MAG:94; IM:55; LGD:11; HGD:5: EGC:15; AGC:17) scheduled for upper gastrointestinal endoscopy (UGIE). A heparinized venous blood sample was collected and methylated RPRM cfDNA and Immunoassays for Pepsinogen I and II were performed. Positive value was considered if methylated RPRM cfDNA > 0 copies/mL and PG I/II ratio <3.0 were found. Results: Overall sensitivity and specificity for the combined use of methylated RPRM cfDNA and PGI/II to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC was 67.5% (95% CI: 50.2% to 81.9%) and 63% (95% CI: 55.9% to 69.7%), respectively. Positive and negative predictive values were 25.2% (95% CI: 17% to 34.9%) and 91.3% (95% CI: 85.3% to 95.4%), respectively. Importantly, crude detection rate for EGC increased from 46.6% to 86.7%. Conclusions: The combined use of methylated RPRM cfDNA and PGI/II reached similar sensitivity and specificity compared to methylated RPRM cfDNA alone to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC. However, combined use of methylated RPRM cfDNA and PGI/II significantly improved the detection rate of EGC, a lesion with a curability rate over 95%.