bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) ± gemcitabine (Gem) in solid tumors: Interim results from the pancreatic cancer (PC) cohorts.
Authors: Wainberg Zev A. , Hochster Howard S. , George Ben , Gutierrez Martin , Johns Mark Emery , Chiorean E. Gabriela , Kwak Eunice Lee , Kalyan Aparna , Manax Victoria , Ye Moncy , Chen Tianlei , Trunova Nataliya , O'Dwyer Peter J. 
Published: March 2017

412 Background: Immune checkpoint inhibitors, such as nivo, an anti−PD-1 antibody, have demonstrated antitumor activity in various cancers. Chemotherapy has demonstrated immune system activation via multiple mechanisms, providing a rationale for combination approaches. nab-P + Gem is a standard of care in PC which does not require immunosuppressive corticosteroids. Here we report interim results from 2 PC cohorts (Arms A and B) of a phase I study in patients (pts) receiving nivo + nab-P ± Gem for locally advanced or metastatic PC. Methods: This 2-part study was designed to identify dose-limiting toxicities (DLTs) of nivo + nab-P ± Gem in Part 1 and assess tolerability and efficacy in Part 2 dose expansion (+ Gem). Pts were DLT evaluable if they received ≥ 2 cycles of treatment and remained on study for 14 days after last dose or discontinued due to a DLT prior to completing 2 cycles. After Arm A, Part 1 was deemed safe, Arm B, Part 1 was initiated. In Arm A, pts with 1 prior chemotherapy regimen received nab-P 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle (qw 3/4) + nivo 3 mg/kg on days 1 and 15 of a 28-day cycle starting with cycle 1. In Arm B, treatment-naive pts received the same regimen in Arm A + Gem 1000 mg/m2qw 3/4. Results: As of June 28, 2016, 11 and 6 pts were treated in Arms A and B in Part 1, respectively. No DLTs were reported in Arm A, and 1 in Arm B (nonimmune hepatitis, suspected to be due to Gem; resolved and pt continued nivo + nab-P without Gem). The most common grade 3/4 teatment-emergent AEs were pulmonary embolism, neutropenia, and anemia in 2/11 pts (18%) in Arm A and anemia in 2/6 pts (33%) in Arm B. Nine patients discontinued due to progressive disease (8 in Arm A, 1 in Arm B). Best overall response is shown in the Table. Median treatment duration was 12.6 and 15.5 weeks for Arms A and B, respectively. Clinical trial information: NCT02309177. Conclusions: These results indicate that adding nivo to nab-P ± Gem is feasible for pts with advanced PC, and antitumor activity of this regimen appears to be encouraging. Based on promising results from Part 1, Arm B, Part 2, is enrolling pts.[Table: see text]
Frailty: A major consideration for short- and long-term outcomes in resected pancreatic cancer.
Authors: Konstantinidis Ioannis , Lewis Aaron G , Tozzi Federrico , Ituarte Philip HG , Warner Susanne , Woo Yanghee , Singh Gapandeep , Fong Yuman , Melstrom Laleh Golkar 
Published: March 2017

418 Background: Frailty has been associated with adverse postoperative outcomes. However, little is known about its correlation with survival in resected pancreatic cancer. This study examined the correlation of frailty with postoperative outcomes and survival after pancreatectomy for cancer. Methods: Data from National Surgical Quality Improvement Program (NSQIP) patients (n = 7400) who underwent pancreatectomy between 2011 to 2013. A modified frailty index (mFI) validated for use in NSQIP was used to examine correlations between frailty and postoperative outcomes. California Cancer Registry (CCR) data for patients (n = 4959) who underwent pancreatectomy for cancer between 2000 to 2012 was used to assess the association between the Charlson Comorbidity Index (CCI), as a surrogate for frailty, and overall survival. Results: The distribution of NSQIP patients according to the mFI was 0, 1, 2, 3, 4 in 2797 (37.8%), 3422 (46.2), 1074 (14.5), 104 (1.4) and 3 (0.04) respectively. The patients were divided to non frail (mFI = 0), mildly frail (mFI = 1-2), or severely frail (mFI3 ≥ 3). Overall, 8.7% of patients experienced a grade 4 Clavien complication and 3.1% experienced postoperative mortality. Worsening frailty correlated with an increase in grade 4 Clavien complications (non-frail: 6.3% vs. mildly frail: 9.7% vs. severely frail: 26.2%; p < 0.001) and mortality (1.9% vs. 3.8% vs. 4.7% respectively; p < 0.001). The majority of CCR patients had similarly few comorbidities: CCI: 0, 1, ≥ 2 in 3869 (77.8%), 861 (17.31%) and 243 (4.89%) respectively. Median survival decreased as CCI increased (for CCI 0, 1 and ≥ 2 was 23 vs. 19 vs. 15 months respectively; p < 0.001). Conclusions: Frailty is a powerful correlate of postoperative outcome and survival for resected pancreatic cancer patients and is an important consideration in planning for surgical intervention.
The relationship between antitumor effects and relative dose intensity of gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer.
Authors: Ishigaki Kazunaga , Ozaka Masato , Kataoka Seita , Kanata Ryo , Yamada Ikuhiro , Sasaki Takashi , Matsuyama Masato , Takano Kouichi , Sasahira Naoki 
Published: March 2017

419 Background: Gemcitabine plus nab-paclitaxel (GEM+nab-PTX) is the standard first-line chemotherapy for unresectable pancreatic cancer, but the relationship between antitumor effects and relative dose intensity (RDI) remains unclear. Methods: A retrospective analysis of pancreatic cancer patients treated with GEM+nab-PTX as first-line chemotherapy between January 2015 and July 2016 at Cancer Institute Hospital of JFCR was performed. The RDI of GEM+nab-PTX was calculated as the delivered dose intensity divided by standard dose intensity. The patients were divided into two groups by median RDI. Kaplan Meier curves were constructed in order to analyze progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS), and differences between the two groups were compared with a log-rank test. Results: A total of 102 patients (52 male, a median age of 66 years) were enrolled. Eighty-two (80%) had metastatic disease. The best overall response was partial response in 30 (29%) and stable disease in 53 (52%). The median PFS, TTF and OS of the total cohort was 188 days (95% confidence interval: CI, 162 to 224), 161 days (95% CI, 146 to 183) and 369 days (95% CI, 309 to 440) respectively. The median RDI were 77% (range 30-100). In the RDI < 77% (n = 50) and the RDI ≥ 77% (n = 52) groups, the median PFS was 196 and 183 days (p = 0.33), the median TTF was 162 and 160 days (p = 0.186) and the median OS were 410 and 312 days (p = 0.10), respectively. Twenty-nine (28%) were eventually administered GEM+nab-PTX biweekly. The median RDI of biweekly regimen was 63% (range 29-86). The TTF of biweekly regimen and original weekly regimen was 196 and 160 days (p = 0.004) respectively. Conclusions: RDI is not a significant predictor of antitumor effects, and an appropriate dose reduction and extension of dosing interval may be permitted in pancreatic cancer patients treated with GEM+nab-PTX.
A new complementary approach to endoscopy for esophageal cancer diagnosis.
Authors: Jiang Gengxi , Tao Hongmei , Tang Xing , Lou Da , Lin Yue , Li Yutao , Wu Junjie , Wang Baoxia , Ding Ning , Xu Pengkun , He Xing , Hu Hao , Yu Chris Chang , Chen Hezhong , Du Xuedong 
Published: March 2017

42 Background: For esophageal cancer, no viable non-invasive detection technologies are available today. In earlier investigations, Cancer Differentiation Analysis (CDA) Technology which measures information relating to both protein fragments and cellular signals in blood samples in a single test has showed a significant advantage in esophageal cancer diagnosis. Methods: Blood samples from 105 individuals in EDTA tubes were collected from Shanghai Changhai Hospital, China, between July and December 2014, CDA and endoscopy tests were carried out on all samples before clinically diagnosed. A performance predication model of CDA and endoscopy test results was built using pROC package in R Language for the data of Area Under the Curve (AUC) and CDA threshold values. Further analysis was carried out based on the CDA threshold values. Results: Out of the 105 individuals, samples from 6 individuals diagnosed as esophageal benign diseases were selected as control group. 99 samples from individuals diagnosed as esophageal cancer, of which 3 and 82 cases were adenocarcinoma and squamous carcinoma, 2, 26, 33, 31 and 7 cases were classified as stage 0,I,II, III, IV, respectively. Details of AUC results of endoscopy, and CDA plus endoscopy for each group were given in Table 1 below. Conclusions: Even though the sensitivity of the endoscopy is usually high due to its pathological examination, this investigation showed that CDA technology could further enhance the diagnosis sensitivity of endoscope, especially for early stage of esophageal cancer, and it (CDA) can be an effective complementary tool to clinical diagnosis and operation determination while obtaining the pathological information via endoscopy. In conclusion, CDA technology is of great value in esophageal diagnosis and therapeutic decision-making. [Table: see text]
Primary care vs. oncology-driven surveillance following adjuvant chemotherapy in resected pancreas cancer.
Authors: Samawi Haider H , Cheung Winson Y. 
Published: March 2017

421 Background: Major oncology societies outline different recommendations following curative intent treatment for pancreas cancer and this has resulted in wide variations in practice among institutions. We aim to describe patterns of surveillance and evaluate their impact on outcomes. Methods: A total of 147 adult patients who received at least one cycle of adjuvant chemotherapy with gemcitabine or 5-fluorouracil monotherapy at any of the British Columbia Cancer Agency centers between 2004 and 2015 were included in this analysis. Surveillance strategies were divided into two groups: discharged to primary care physicians (PCP) or follow up with oncologists that included regular clinical assessments, laboratory testing and/or diagnostic imaging. Results: Median age at diagnosis was 64 (range 38-85) years and 48% were men. More patients were followed by oncologists than PCP (66% vs. 44%). Among the measured prognostic factors, only patients with advanced tumor stage (T3/4) were more likely to be followed by cancer specialists (78% vs. 62%, P = 0.03), while age, gender, performance status, node status, pathologic grade and surgical margins were balanced between the two groups. In the entire cohort, 100 (68%) patients had a documented recurrence. Patient followed by oncologists were more likely to receive chemotherapy on recurrence than those followed by PCP (58% vs. 34%, respectively, P = 0.03). The median overall survival (OS) was 2.82 (95% CI 2.17-3.32) years in the oncology group and 3.35 (95% CI 2.85-5.06) years in the PCP group while the median relapse free survival (RFS) was 2.4 (95% CI 2.07-4.59) and 1.4 (95%CI 1.37-1.77) years, respectively. On multivariate analysis, there was no significant difference in OS between oncology and PCP-driven surveillance (HR 1.23; 95% CI 0.74-2.04, P = 0.4); however, RFS favored the PCP group (HR 1.62; 95% CI 1.01-2.56, P = 0.04, for oncology). Conclusions: In this population-based analysis, surveillance tests and imaging performed by oncologists detected recurrences earlier when compared to follow up by PCPs, but this did not result in OS differences. PCPs may have a larger role in the follow up care of selected patients with resected pancreas cancer.
Prognostic factors in patients (pts) with advanced biliary tract cancer (BTC) treated with first-line gemcitabine plus cisplatin (GEMCIS): Retrospective analysis of 740 pts.
Authors: Cho Hyungwoo , Kim Bumjun , Yoo Changhoon , Kim Kyu-Pyo , Hyung Jaewon , Lee Sang Soo , Park Do Hyun , Song Tae Jun , Seo Dong Wan , Lee Sung Koo , Kim Myung-Hwan , Park Jin-hong , Chang Heung-Moon , Ryoo Baek-Yeol 
Published: March 2017

424 Background: BTC is a heterogeneous group of disease consisted of intrahepatic, extrahepatic cholangiocarcinoma and gallbladder cancer. Although GEMCIS has been established as a standard first-line chemotherapy based on the ABC-02 trial, more data is needed to define the clinical course of BTC and its prognostic factors. Methods: Between April 2010 and May 2015, 740 pts with histologically documented BTC were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea. All pts received GEMCIS as described in the ABC-02 trial. Response was graded according to the RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Maier curves. Multivariate analyses were performed to define prognostic factors. Results: Median age was 60 years (range, 27-82) and 425 (57%) pts were male. Initially metastatic disease was the most common disease status at GEMCIS (n = 377, 51%) followed by recurrence after surgery (279, 38%) and locally advanced unresectable disease (84, 11%). Liver (37%) and peritoneum (25%) were the common metastatic sites. Pts received a median 5 cycles of GEMCIS (range, 1-42). Objective response rates were 13% and there was no significant difference according to the primary tumor sites (p = 0.45). With a median follow-up duration of 27.3 months (mo) (95% CI, 24.2-30.5), median PFS and OS were 5.2 mo (95% CI, 4.7-5.6) and 10.4 mo (95% CI, 9.6-11.2), respectively. In the multivariate analyses, male gender (female vs male; HR = 0.83), pretreatment CA 19-9 level (elevated vs normal; HR = 1.31), initially metastatic disease (vs locally advanced disease, HR = 1.92), poor performance status (ECOG 2 vs 0-1; HR = 1.45), and measurable disease by the RECIST criteria (vs non-measurable; HR = 1.40) were significantly associated with poorer OS (p < 0.05 for all). Conclusions: Our retrospective analysis based on large number of pts demonstrated that first-line GEMCIS in the real world setting has comparable efficacy with the results of the ABC-02 trial. Prognostic factors demonstrated in this study may help to predict clinical outcomes and design future clinical trials for advanced BTC.
Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary cancer after failure of gemcitabine plus cisplatin: Retrospective analysis of 321 patients.
Authors: Kang Jihoon , Kim Bumjun , Yoo Changhoon , Hyung Jaewon , Kim Kyu-Pyo , Ryoo Baek-Yeol , Chang Heung-Moon 
Published: March 2017

425 Background: In advanced biliary tract cancer (BTC), the role of 2nd line chemotherapy after failure of 1st line gemcitabine plus cisplatin (GEMCIS) has not been established. Fluoropyrimidine(FP)-based regimens are widely used as 2nd line treatment in clinical practice. We retrospectively analyzed the efficacy of 2nd line FP-based chemotherapy in patients(pts) with advanced BTC after failure of GEMCIS. Methods: Histologically confirmed advanced BTC pts who received 1st line GEMCIS at Asan Medical Center between December 2010 and June 2016 were identified. Among 748 pts treated with GEMCIS, 331 patients (44%) subsequently received 2nd line chemotherapy and FP-based regimens were used in 321 pts (97%). Results: The median age was 60 years (range, 27-82) and 57% of pts were male. Intrahepatic cholangiocarcinoma(IH-CCC) (44%) was the most common type, and followed by extrahepatic cholangiocarcinoma (32%). Most pts (n = 289, 89%) had metastatic/recurrent disease at the time of 1st line treatment. FP alone and FP plus platinum combination were used in 255 pts (79%) and 66 pts (21%), respectively. In pts with measurable disease, response rate (RR) was 3% (8/301) and disease control rate was 47% (142/301). After a median follow-up of 27.6 months (0.9-70.4 months), the median progression free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0). RR was significantly higher in pts with combination of FP and platinum compared to FP alone (8% vs 1%, p = 0.009). However, there were no statistically significant differences in terms of PFS (p = 0.43) or OS (p = 0.88) between two groups. In the multivariate analysis for OS, IH-CCC, initially metastatic disease and elevated CA 19-9 level at the time of 1st line treatment, and time-to-progression at 1st line GEMCIS > 4 months were independent poor prognostic factors. Conclusions: In this analysis, FP-based regimen showed modest efficacy as 2nd line chemotherapy for advanced BTC patients after failure of 1st line GEMCIS. Combination of FP and platinum was not associated with improved survival outcomes compared to FP monotherapy, despite of higher RR.
Risk factors associated with recurrent cholangitis in pancreatic and hepatobiliary cancers.
Authors: Jain Apurva , Song Juhee , Javle Milind M. , George Marina C. 
Published: March 2017

428 Background: Acute cholangitis due to malignant biliary obstruction is frequent in patients with pancreatic and hepatobiliary cancers. Recurrent cholangitis (RC) results in repeated hospitalization and delayed cancer care. The risk factors associated with RC are not yet defined. Methods: A pilot review was done on 146 patients admitted with a diagnosis of cholangitis from 2005 to 2014. We included demographics, cancer stage, details of first admission (FA) and interventions. Univariate and multivariate Fine-Gray models were used for statistical analysis. Results: The mean age at FA was 62 yrs, 84 (58%) were males and 99 (68%) were white. Most common cancer was pancreatic 100(69%) and 27(19%) pts had primary cholangitis at FA. During FA, interventions were performed in 114(78%), of whom 51 (45%) had percutaneous drainage (PTBD) and 63 (55%) had endoscopic drainage (ED). Readmission with cholangitis was noted in 35 (24%) cases. Univariate analysis did not show a difference between PTBD and ED. However, subgroup analysis showed external only PTBD and covered metallic stent ED had lower risk of RC. These variables remained significant on multivariate analysis (Subdistribution HR= 0.00, p<.0001 for both). Multiple previous PTBD (≥2) before FA was significantly associated with increased risk of RC (Subdistribution HR= 2.64, p= 0.01) on univariate analysis. Conclusions: Having multiple previous PTBD is associated with recurrent cholangitis. Though no significant difference was noted between PTBD and ED, the subgroups indicated a trend towards less recurrent cholangitis with covered metallic stent. [Table: see text]
A phase II study of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low- to intermediate-grade, unresectable, recurrent, or metastatic pancreatic, or GI neuroendocrine tumors/carcinoid (GI-NETs/PNETs) with elevated biomarkers.
Authors: Libutti Steven K. , Anthony Lowell Brian , Chaplin David J. , Sosa Julie Ann 
Published: March 2017

432 Background: GI-NETs/PNETs are highly vascular tumors. CA4P, a vascular disrupting agent (VDA), occludes tumor vasculature resulting in ischemic necrosis. Pre-clinical studies of CA4P have shown activity in GI-NETs/PNETs. Methods: OX4218s is a phase II, single-arm, open-label study (NCT02132468) of CA4P in patients (pts) with GI-NETs/PNETs with elevated biomarkers who relapsed during or after standard-of-care treatment. Pts received CA4P 60 mg/m2 IV on days 1, 8, and 15 of a 21-day cycle for 3 cycles. Primary endpoint was change in biomarkers from baseline. Secondary endpoints were safety, tolerability, symptoms, and QOL. Exploratory endpoints were ORR (RECIST 1.1). Pts achieving biomarker or symptom response were eligible for a rollover study. Results: 18 pts were enrolled; 7 subsequently entered the rollover study. Pts were on average aged 58 years, white (89%), male (50%) with ECOG status of 0-1. The majority (94%) had well-differentiated disease (GI-NETS 78%) and received prior Tx (94%). There were no meaningful changes in biomarkers. Eleven (61%) pts had stable disease (SD) and 1 (6%) had a partial response (PR). In the rollover study, 5 (71%) had SD, and 1 had SD for 14 cycles prior to progression (PD). 77% of pts had treatment-related AEs. Key grade 3-5 AEs (> 10%): anemia, abdominal pain, fatigue, hypertension, ALT and AST increases, with 1 grade 5 carcinoid syndrome. Conclusions: The primary endpoint was not met. However, the number of pts entering the rollover study and ORR suggest that CA4P conferred some activity and was generally safe and well tolerated. These findings suggest that due to their inherent variability, tumor biomarkers may not be an ideal endpoint for this population. Clinical trial information: NCT02132468. [Table: see text]
Biweekly cisplatin (C) and gemcitabine (G) in patients (pts) with advanced biliary tract cancer (ABTC): A retrospective analysis.
Authors: Ahn Daniel H. , Reardon Josh , Ahn Chul , Bupathi Manojkumar , Ciombor Kristen Keon , Wu Christina Sing-Ying , Bekaii-Saab Tanios S. 
Published: March 2017

434 Background: Based on the ABC 02 trial, standard therapy for ABTC is CG for up to 8 cycles. However, a recent abstract (Doherty et al, ASCO 2016) confirmed that a cohort of pts does benefit from continued therapy. The weekly administration of G and C can add significant toxicities that may prohibit prolonged treatment (trmt). Previous studies have shown that a biweekly schedule (Ko AH et al JCO 2012) of fixed dose rate (FDR) G helps optimize the prescribed regimen with an improved toxicity profile and added convenience to pts while maintaining efficacy. Methods: Pts with ABTC treated with FDR G (1000mg/m2 at 10mg/m2/min) with C 20mg/m2(GC) on days 1 and 15 of every 28-day cycle were included for analysis. Pts received trmt until time of progression. Data was collected including demographics, clinico-pathologic features, toxicities and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). Results: The study included 109 evaluable pts with ABTC who received CG. Pts had disease that was locally advanced (16.5%) or metastatic (83.5%). Median age was 60 years (28-86). Sites of tumor included gallbladder (21.1%), ampullary (3.6%) and bile duct (75.2%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade 3 or 4 adverse events included neutropenia (11%), fatigue (10%), thrombocytopenia (TCP) (6.4%), anemia (2.8%), and abnormal liver function tests (2.8%). Fifty-two percent of pts received second line therapy. Conclusions: Biweekly CG in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many. Further prospective exploration should consider evaluating the role of biweekly gemcitabine and cisplatin regimen in ABTC especially as a potentially more favorable platform to combine with novel agents. [Table: see text]