bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2 study of BGJ398 in patients (pts) with advanced or metastatic FGFR-altered cholangiocarcinoma (CCA) who failed or are intolerant to platinum-based chemotherapy.
Authors: Javle Milind M. , Shroff Rachna T. , Zhu Andrew , Sadeghi Saeed , Choo SuPin , Borad Mitesh J. , Lowery Maeve Aine , El-Khoueiry Anthony , Macarulla Teresa , Philip Philip Agop , Oh Do-Youn , Van Cutsem Eric , Yeh Kun-Huei , Isaacs Randi , McGarry Carolyn , Sen Suman , Bekaii-Saab Tanios S. 
Published: February 2017

335 Background: CCA is a hepatobiliary malignancy with poor prognosis and few treatment options following cytotoxic therapy in the first-line metastatic setting. The fibroblast growth factor receptor (FGFR) axis may promote CCA tumorigenesis. FGFR2 fusions (in up to 17% of intrahepatic CCAs) may predict FGFR inhibitor sensitivity. A prior phase 1 trial of the selective pan-FGFR inhibitor BGJ398 showed antitumor activity in a pt with CCA harboring an FGFR2 fusion. Methods: This ongoing phase 2, open-label study is evaluating oral BGJ398 125 mg once daily on a 3-week-on/1-week-off schedule (28-day cycle) in pts with advanced or metastatic CCA with FGFR2 fusions (n ≈ 40) or other FGFR genetic alterations (n ≤ 15) who progressed after cisplatin/gemcitabine or are cisplatin intolerant (NCT02150967). The primary endpoint is investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints include progression-free survival, best overall response (BOR), disease control rate (DCR), overall survival, safety, and pharmacokinetics. Results: As of 10 July 2015, 26 pts with CCA harboring FGFR2 fusions (n = 22) or other FGFR alterations (n = 4), pretreated with 1 to ≥ 4 prior regimens, were enrolled. Common adverse events (AEs; ≥ 20% of pts), were hyperphosphatemia (50%), fatigue (42%), constipation (38%), cough (23%), and nausea (23%). Grade 3/4 AEs occurring in ≥ 2 pts were hyper/hypophosphatemia, lipase increase, and hyponatremia. AEs were manageable, reversible, and rarely led to treatment discontinuation. Among 22 pts evaluable for BOR, 3 achieved partial response and 15 had stable disease, including 10 with tumor reductions (-41%, n = 1; -2% to -29%, n = 9). Overall DCR was 82%. As of the cutoff date, 18 pts remained on therapy, of which 13 were on for > 120 days. Kaplan-Meier estimated lower limit (95% CI) of median time on study was 143 days. Conclusions: BGJ398 shows impressive anti-tumor activity and a manageable safety profile in pts with advanced FGFR-altered CCA, an indication of high unmet medical need. Updated data including additional responses post data cutoff will be presented. Clinical trial information: NCT02150967.
Risk factors of chemotherapy-induced nausea and vomiting in patients with advanced pancreatic cancer receiving modified FOLFIRINOX.
Authors: Shinohara Akira , Ikeda Masafumi , Irisawa Ai , Kobayashi Misaki , Udagawa Ryoko , Funazaki Hideki , Asanagi Yuko , Mitsunaga Shuichi , Ohno Izumi , Takahashi Hideaki , Hashimoto Yusuke , Umemoto Kumiko , Watanabe Kazuo , Saito Shinichiro 
Published: February 2017

344 Background: Modified FOLFIRINOX (mFFX) has been reported to be a high incidence of chemotherapy-induced nausea and vomiting (CINV). However, CINV is difficult to adequately control in patients receiving treatment with mFFX. The aim of this study is to evaluate the incidence of delayed CINV and to identify as risk factors for CINV in patients receiving treatment with mFFX. Methods: The study subjects were patients with advanced pancreatic cancer treated with mFFX from December 2013 to June 2015 at National Cancer Center Hospital East. The mFFX regimen consisted of oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, l-leucovorin 200 mg/m2 and a 46-h continuous infusion of fluorouracil 2400 mg/m2. The antiemetic prophylaxis consisted of aprepitant (125 mg on day1 and 80 mg on day 2-3), palonosetron (0.75 mg on day1) and dexamethasone (12 mg on day1 and 8 mg on day 2-3). All adverse events, including nausea and vomiting were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE version 4.0). Results: A total of 115 patients were enrolled in this study. The incidence rates of nausea and vomiting of any grade during the first treatment cycle were 45.2% and 5.2%, respectively. Grade 2-3 of nausea and vomiting were observed in 13.9% and 0.9% of the patients, respectively. Any grade of CINV occurred frequently during days 4 to 7 for the first treatment cycle. Univariate and multivariate analyses identified female and younger age ( < 50 years) as significant independent factors associated with the incidence of any grade of CINV on days 4 to 7 for the first treatment cycle (Odds ratio [OR], 7.44; 95%CI, 2.21 to 25.1; p = 0.001; OR, 4.57; 95% CI, 1.04 to 20.1; p = 0.044). Conclusions: The risk factors of delayed CINV for the first treatment cycle were identified as female and younger age in patients treated with mFFX. Therefore, in patients with these risk factors, additional dexamethasone should be considered as an antiemetic treatment on day 4-5.
Incorporating trans-arterial radioembolization (TARE) in the treatment of metastatic pancreatic adenocarcioma: A single center experience.
Authors: Kim Alexander Y. , Unger Keith Robert , Pishvaian Michael J. 
Published: February 2017

346 Background: There is a lack of data on the potential efficacy of the incorporation of trans-arterial radioembolization (TARE) for metastatic pancreatic adenocarcinoma. We retrospectively evaluated the efficacy of TARE in the management of patients with liver dominant metastatic pancreatic adenocarcinoma Methods: Sixteen patients were treated with concurrent systemic therapy and TARE for liver-dominant pancreatic adenocarcinoma from February, 2014 to August, 2015. Electronic chart review was performed for this group of patients to assess response Results: Eleven male and 5 female patients were treated for liver dominant metastatic pancreatic adenocarcinoma with Yttrium-90 resin microspheres. The average age was 64 (50 - 77). All patients were treated with at least one line of systemic therapy. Five had prior or concurrent SBRT treatment for the primary lesion. Eleven patients had extra-hepatic disease with evidence of nodal, pulmonary and/or omental disease on pretreatment imaging. All patients had adequate hepatic reserve and functional status at treatment. Eight of the 16 patients were alive at the time of analysis. The median overall survival from diagnosis of liver metastases to time of analysis is 22 months (11 – 50, 95% CI). The median time of survival from TARE is 12.5 months (4 – not reached, 95% CI). The estimated survival rate at 6 months, 1 year, 2 year and 3 years from diagnosis is 100%, 84%, 39% and 26%. Follow up imaging was available on 13 patients. Local PR, SD and PD based on RECIST criteria were seen in 4 (31%), 7 (54%) and 2 (15%) patients. The average local and systemic PFS was 4.9 and 3.4 months, respectively Conclusions: We found promising results for the incorporation of TARE in the treatment of patients with metastatic pancreatic adenocarcinoma. In our cohort, the median overall survival from the time of metastatic diagnosis was 22 months, a significant improvement from the expected median survival. Although our data is promising, there are inherent weaknesses of our study due to the small number of patients and its retrospective nature. Further studies are needed to validate our findings. For this purpose, a prospective trial is currently being in development.
Comparison of a new prognostic system and other three current staging systems in predicting the survival rate of patients with HBV-associated advanced hepatocellular carcinoma.
Authors: Hong Ying-Fen , Chen Zhan-Hong , Lin Qu , Dong Min , Li Xing , Wen Jin-Yun , Ma Xiao-kun , Wei Li , Ruan Dan-yun , Lin Ze-xiao , Chen Jie , Wang Tian-tian , Wu Xiang-yuan 
Published: February 2017

347 Background: HBV infection is one of the main reasons for hepatocellular carcinoma(HCC). Patients with advanced HBV-associated HCC have poor prognosis. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. Prediction of 3-month OS and OS survival rate of advanced HCC patients is very important. A new prognostic system called PS-JIS system (proposed Performance Status combined Japan Integrated Staging system, variables and risk classification criteria are listed below) was established in 2015 and now we want to compare this new prognostic system and other three current staging systems in predicting the survival rate of patients with advanced HBV-associated HCC. Methods: From September 2008 to June 2010, 220 patients with advanced HCC who didn’t receive anti-cancer therapy recommended by NCCN guidelines were analyzed. Data were collected to classify patients according to CLIP (Cancer of the Liver Italian Program), PS-JIS, GETCH(Groupe d’étude et de Traitement du Carcinome Hepatocellulaire) and TNM staging system at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of CLIP, PS-JIS, GETCH and TNM is 0.806, 0.761, 0.654 and 0.643. AUC of CLIP and PS-JIS is similar (P=0.1174), both significantly higher than the other two staging system (P<0.01). When predicting overall survival, likelihood ratio test show χ2 of CLIP, PS-JIS, GETCH and TNM is 74.00, 39.71, 23.09, 21.40. AIC of CLIP, PS-JIS, GETCH and TNM is 1601.46, 1635.80, 1655.06, 1654.77. The CLIP system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: The PS-JIS and CLIP systems were both the best score system in prediction of 3-month OS among the 4 systems and CLIP was still the best to predict OS analyzed for Chinese advanced HBV-associated HCC patients. [Table: see text]
Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (KOBTC02).
Authors: Itano Osamu , Minagawa Takuya , Shinoda Masahiro , Kitago Minoru , Abe Yuta , Hibi Taizo , Yagi Hiroshi , Kitagawa Yuko 
Published: February 2017

353 Background: Although surgery plays a key role in the curative treatment for biliary tract cancer (BTC), the prognosis is not satisfactory because of frequent postoperative recurrence. Multimodal treatment has been warranted in order to improve this situation. The aim of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of cisplatin as neoadjuvant chemoradiotherapy with S-1 and external beam radiation for BTC. Methods: Patients with resectable BTC at initial diagnosis were eligible for inclusion. The planned dosages of cisplatin (mg/m2)/S-1 (mg/m2/day) were as follows: 40/80 (level 0); 50/80 (level 2); 60/80 (level 3). S-1 was orally administered twice daily from day 1 to 14 and day 29 to 42. Cisplatin was administered intravenously over 2 hours in each dosage of level at day 1 and 29. Radiation was delivered as a total dose of 50.4 Gy (28 fractions to 1.8 Gy). Dose-limiting toxicity (DLT) was a delay factor of the schedule due to incomplete recovery. (Response rate (RR) was evaluated according to the RECIST version 1.0.). Results: Twelve patients were enrolled, and level 1 was chosen as the starting dose. One of six patients developed DLTs at level 1, and the dose was escalated to level 2. DLTs occurred in two of six patients at level 2. As the MTD were determined as over 60 mg/m2, the RD were confirmed as level 2 for a subsequent phase II study. Conclusions: We determined the MTD and RD of cisplatin with concurrent S-1 and external beam radiation as neoadjuvant chemoradiotherapy for resectable BTC. Although further clinical trials are warranted to evaluate efficacy, this new regimen is potentially expected to become a standard neoadjuvant treatment for resectable BTC. Clinical trial information: 000009028.
Impact of hepatic function and tumor extent on survival in patients with unresectable hepatocellular carcinoma treated with liver-directed therapies.
Authors: Hill Marisa E. , Basu Sanjib , Arslan Bulent 
Published: February 2017

358 Background: Transarterial chemoembolization (TACE) has demonstrated survival advantage over best supportive care in patients with unresectable hepatocellular carcinoma (HCC), and non-randomized data suggests that survival in HCC treated with yttrium-90 radioembolization (90Y) is similar to that achieved with TACE. Eighty to 90% of patients with HCC have underlying cirrhosis, so survival analyses of liver-directed treatments (LDT) should take into account both tumor extent and liver function. Methods: We conducted a retrospective study to evaluate the effect of tumor extent and liver function on the survival of patients treated with TACE and/or 90Y for HCC. Patients with unresectable HCC treated at Rush University Medical Center between 2002 and 2014 were analyzed. Liver function parameters prior to first treatment were recorded for each patient, and survival measured from time of first treatment to death or last follow up was calculated. Statistical inference for overall survival was performed using Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Results: The difference in overall survival between patients with unilobar disease and with bilobar disease (n=35 and 23, median survival of 19.4 and 12.8 months, respectively) was not found to be significant (p=0.838). However, the difference in overall survival among patients with Child Pugh A (n=22, median not reached), B (n=30, median= 11.4 months) and C (n=6, median=3.8 months) cirrhosis was strongly significant (p < 0.001). In a multivariate Cox proportional hazards analysis, the association of Child class (coded on an integer scale) with overall survival, adjusted by the extent of the disease, continued to be strongly significant (HR=1.93, p < 0.001). Conclusions: Liver function may be just as important a determinant of survival in patients undergoing liver directed treatments for HCC as is extent of disease. Larger, prospective studies are needed to confirm this hypothesis.
Importance of subset classification based on tumor size for patients with single hepatocellular carcinoma.
Authors: Zhong Jian-Hong , Xiang Bang-De , Ma Liang , Wang Yan-Yan , Peng Ning-Fu , Gong Wen-Feng , Lu Shi-Dong , Li Le-Qun 
Published: February 2017

373 Background: Single hepatocellular carcinoma (HCC) regardless of size that without vascular invasion is classified as stage A disease in the Barcelona Clinic Liver Cancer staging system. However, patients with different tumor size may have different overall survival after hepatectomy. This study compared the prognosis of patients with single HCC after hepatectomy among groups with different tumor size. Methods: Patients with newly diagnosed single HCC from January 1, 2004 to October 31, 2013 were classified according to tumor size: group 1, ≤ 5 cm; group 2, > 5 cm and ≤ 8 cm; group 3, > 8 cm and < 10 cm; and group 4, ≥ 10 cm. Overall survival analysis was performed according to tumor size. Results: A total of 857 patients were enrolled. Among them, 814 (95.0%) were with Child-Pugh A class liver function. Blood loss was 367 ± 424 mL. Groups 1, 2, 3, and 4 consisted of 426 (49.7%), 229 (26.7%), 52 (6.1%), and 150 (17.5%) patients, respectively. The 5 years overall survival ranged from 35 to 63% in all four groups. The median survival time differed significantly according to tumor size (76, 49, 43, and 38 months in groups 1, 2, 3, and 4, respectively; P  <  0.001). Group 3 had overall similar survival to group 4. Multivariate analysis showed that group 3 and 4 had significantly worse overall survival compared to group 1 and 2. Conclusions: Patients in group 3 and 4 had significant worse prognosis than those in group 1 or group 2. Our results suggest that subset classification based on tumor size is warranted to patients’ prognosis.
Impact of concurrent medications use on outcome of pancreatic cancer: SEER Medicare analysis.
Authors: Beg Muhammad Shaalan , Stewart Tyler , Gao Ang , Ahn Chul , Berry Jarett , Mortensen Eric 
Published: February 2017

378 Background: Preclinical studies have suggested concurrent non-antineoplastic medication use may impact pancreatic cancer. We performed an analysis to examine these associations on survival in pancreatic cancer. Methods: Data from the Surveillance, Epidemiology and End Results (SEER)-Medicare with available part D data between 2006 and 2009 were analyzed. Cases with non-adenocarcinoma histology, autopsy only and death certificate only data were excluded. Drug use was defined as having two prescriptions filled within 12 months of pancreatic cancer diagnosis. The following medications were analyzed: beta-blocker, statin, insulin, metformin, thiazolidinedione, warfarin and heparin. The primary end point was overall survival. Stepwise Cox proportional hazard models were employed including each medication group as well as age, gender, stage, site, grade, diabetes, race and Charlson comorbidity score. Results: There were 13,702 cases which met inclusion criteria and had available Part D data. Median age was 76 years, There were 42.5% males, 77.1% were white and 34.0%had diabetes. Head of the pancreas tumors accounted for 49.9% cases and 49.6% had stage 4 disease and at diagnosis. The results of the stepwise Cox proportional hazard models are summarized in table 1. Beta blockers, heparin, insulin, warfarin were associated were significantly with improved survival (p<0.05). Conclusions: Concurrent medication use, particularly heparin, insulin warfarin and beta-blockers are associated with improved survival in patients with pancreatic cancer. Diabetes medications (metformin, TZD) did not have an impact in the multivariable model. Additional studies are needed to examine whether these medications may improve outcomes for patients with pancreatic cancer. [Table: see text]
Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer.
Authors: Stein Stacey , James Edward Samuel , Cong Xiangyu , Deng Yanhong , Salem Ronald R , Cha Charles , Chang Bryan William , Hochster Howard S. , Doddamane Indukala , Boustani Annmarie , Patel Vatsal , Kortmansky Jeremy S. , Li Jia , Staugaard Carol , Lacy Jill 
Published: February 2017

395 Background: Toxicities associated with FOLFIRINOX have prompted use of modifications, despite absence of prospective data validating comparable efficacy and improved tolerability. To determine the impact of attenuated doses of irinotecan and bolus 5FU on efficacy and tolerability, we conducted a prospective phase II study of modified FOLFIRINOX in advanced PC. The efficacy of a FOLFIRINOX regimen has not been previously examined in locally advanced PC (LAPC). Previous studies in LAPC have compared chemo vs chemoRT with median OS in the 9-12 mo range (Loehrer et al, Chauffert et al, Hammel et al). Methods: Previously untreated pts with MPC or LAPC received modified FOLFIRINOX with pegylated filgrastim. Irinotecan and bolus FU were reduced by 25%. AEs were compared to historical control (Conroy et al NEJM 2011). Objective RR in MPC was compared to historical control. PFS and OS were calculated for both cohorts. Results: 31 and 44 pts with LAPC and MPC enrolled. Treatment-related grade 3 and 4 AEs were diarrhea (16.2%), neutropenia (12.2%), fatigue (12.2%), thrombocytopenia (9.5%), anemia (5.4%). Neutropenia (p < 0.0001), vomiting (p = 0.001), and fatigue (p = 0.01) were significantly decreased compared to historical control patients. In MPC, the RR (35.1%) was similar to the historical control group (36.3%; p 0.82); median PFS and OS were 6.1 months (95% CI, 5.19 to 8.31) and10.2 months (95% CI, 7.65 to 14.32) respectively. In LAPC, the RR was 17.2% and median PFS and OS were 17.8 mo (95% CI, 11.0 to 23.9) and 26.6 mo (95% CI, 16.7, NA) respectively. 13 pts went on to surgical resection with 10 now alive and 6 without recurrence. We found no significant association between early metabolic response by FDG-PET imaging and PFS and OS. Conclusions: In this first prospective study of modified FOLFIRINOX, the regimen was well tolerated and associated with decreased incidence of AEs compared to historical control of standard FOLFIRINOX. In MPC pts, the efficacy of the modified regimen appear uncompromised. In this first prospective study of a FOLFIRINOX regimen in LAPC, the PFS and OS surpasses that of previously studied regimens in LAPC. Clinical trial information: NCT01523457.
The outcome of surgical treatment for oldest-old patients with gastric cancer.
Authors: Hikage Makoto , Makuuchi Rie , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Kinugasa Yusuke , Sugiura Teiichi , Uesaka Katsuhiko , Terashima Masanori 
Published: February 2017

40 Background: The number of the oldest-old patients with gastric cancer has been increasing in Japan. Selecting optimal operation for these patients is difficult because coping with both radicality and tolerability of surgery is mandatory. The aim of this study is to clarify the feasibility and effectiveness of gastrectomy for these patients. Methods: A total of 721 old patients (aged 75 years old and older) with gastric cancer who underwent curative gastrectomy at Shizuoka Cancer Center between from Oct. 2002 to Aug. 2015 were included in this study. The patients were classified into oldest-old group (OOP; aged 85 years and older) and old group (OP; aged 75 to 84 years old). Characteristics of the patients and short and long-term outcomes were compared between the groups. Results: OOP group included 57 patients, and OP group 664 patients. Though median serum albumin level in OOP group (3.8 g/dl) was significantly lower than in OP group (4.1 g/dl) (p = 0.002), the other clinicopathological characteristics including gender, BMI, co-morbidity, ASA-PS, ECOG-PS and preoperative stage were not significantly different between the groups. In terms of operative results, gastrectomy with reduced extent of lymph node dissection was frequently performed in OOP group (33.3%) than in OP group (6.0%) with significant difference (p < 0.001). Median operation time was significantly shorter in OOP group (195 minutes) than in OP group (222 minutes) (p = 0.001), and median blood loss was significantly less in OOP group (154 ml) than in OP group (227 ml) (p = 0.041). There was no significant difference of the incidence of postoperative complications between the groups. There was no significant difference of overall survival (p = 0.973) and disease-specific-survival (p = 0.549) between the groups. In multivariate analysis, preoperative BMI < 20, serum albumin < 3.8 g/dl and 15 days or more postoperative hospital stay were revealed as significant independent prognostic factors. Conclusions: Gastrectomy is safe with acceptable oncologic outcomes for OOP with optimally reducing the extent of surgery in each patient. In order to improve the outcome in OOP, preoperative nutritional management and support for home health care system should be considered.