bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1b/2 study of INCB039110 + nab-paclitaxel (N) and gemcitabine (G) in patients (pts) with advanced solid tumors and pancreatic cancer (PC).
Authors: Beatty Gregory Lawrence , Shahda Safi , Beck J. Thaddeus , Uppal Nikhil Premparkash , Cohen Steven J. , Donehower Ross C. , Gabayan A. Eli , Assad Albert , Switzky Julie C. , Zhen Huiling , Von Hoff Daniel D. 
Published: March 2017

362 Background: JAK-STAT activity has been associated with malignant cell proliferation and production of proinflammatory cytokines involved in cancer progression. INCB039110 is a potent and selective inhibitor of JAK1. Methods: This was a 2-part phase 1b/2 open-label study evaluating INCB039110 (300 or 400 mg QD) in combination with N and G in pts with advanced or metastatic solid tumors (Part 1 [P1], dose optimization phase) and pts with advanced or metastatic PC who had not received prior chemotherapy (Part 2 [P2] and 2A [P2A]). Pts in P2 received the MTD established in P1: INCB039110 (300 mg QD) + N (125 mg/m2 day [d] 1, 8, 15) + G (1000 mg/m2 d 1, 8, 15), 28-d cycle. For exploratory purposes, pts in P2A underwent a 7-d induction phase with INCB039110 (200 mg QD) before receiving INCB039110 (200 mg QD) + N (125 mg/m2 d 1, 8, 15) + G (1000 mg/m2d 1, 8, 15). The primary objective was to evaluate safety/tolerability. Results: 55 pts were enrolled (27 P1, 20 P2, and 8 P2A). Most patients had advanced PC (n = 46). Median age was 65 (P1), 67 (P2), and 66 years (P2A). Prior therapy: 67% in P1, 30% in P2, and 0% in P2A. The most common reasons for treatment discontinuation were adverse events (AEs; 41% P1, 20% P2, 38% P2A), disease progression (37% P1, 45% P2, 0% P2A), and study termination by the sponsor (0% P1, 0% P2, 38% P2A). Median treatment durations were 84 d (P1), 121 d (P2), and 47 d (P2A). The most common non-hematologic AEs (all grades) were fatigue (59% P1, 75% P2, 88% P2A), nausea (41% P1, 50% P2, 38% P2A), pyrexia (37% P1, 40% P2, 13% P2A), and peripheral edema (30% P1, 50% P2, 25% P2A), with few grade 3 or 4 non-hematologic AEs. The most common grade 3 or 4 hematologic AEs (laboratory values) were neutropenia (33% P1, 60% P2, 13% P2A), lymphopenia (30% P1, 30% P2, 13% P2A), and leukopenia (30% P1, 45% P2, 0% P2A). The most common serious AEs occurring in ≥ 3 pts were pneumonia (n = 4 P1, n = 2 P2, n = 0 P2A) and anemia (n = 3 P1, n = 2 P2, n = 2 P2A). Among evaluable patients, ORR (all PRs) and DCR were 27% (13/48) and 75% (36/48), respectively. Responses were seen across INCB039110 doses. Conclusions: INCB039110 + N/G showed an acceptable safety profile in pts with advanced PC, with the combination demonstrating clinical activity. Clinical trial information: NCT01858883.
Clinical implication of inflammation-based prognostic score and perioperative nutrition control in pancreatic cancer.
Authors: Takano Nao , Yamada Suguru , Fujii Tsutomu , Tashiro Mitsuru , Tanaka Nobutake , Morimoto Daishi , Ninomiya Go , Niwa Yukiko , Takami Hideki , Iwata Naoki , Hayashi Masamichi , Kanda Mitsuro , Tanaka Chie , Kobayashi Daisuke , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: March 2017

390 Background: Systemic inflammation and nutrition status are considered to influence survival in cancer patients. A variety of systemic inflammation-based prognostic scores have been explored; however, there has been no study to clarify which score could best reflect survival in resected pancreatic cancer patients. Methods: Between 2002 and 2016, 422 consecutive patients who underwent curative resection of pancreatic cancer were enrolled. The Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI) scores for each patients were calculated. Survival of each score was evaluated, and correlations between the score selected on the basis of the prognostic significance and various clinicopathological factors were analyzed. On the other hand, the nutrition markers (pre-albumin, transferrin, and retinol-binding protein) of 30 patients who received the enteral nutrition during the perioperative period were also evaluated. Results: In the analysis of the GPS, the median survival time (MST) was 29.4 months for score 0, 25.5 for score 1, and 17.7 for score 2 ( p< 0.001), and mGPS was also found to be significant ( p= 0.003). On the contrary, there were no significance in MST between other scores (NLR, PLR, PI, or PNI). Multivariate analysis revealed that lymph node metastasis, positive peritoneal washing cytology, and a GPS score of 2 were significant prognostic factors. There was also statistically significant correlation between the GPS score and tumor location (head), tumor size ( > 2.0cm), bile duct invasion, and duodenal invasion. In terms of nutrition status, the postoperative nutrition markers of 30 patients managed by enteral nutrition tended to recover earlier than 79 patients managed by intravenous nutrition. Conclusions: Our results demonstrated that the GPS could be an independent predictive marker and was superior to other inflammation-based prognostic scores in patients with resected pancreatic cancer. The results also suggested that perioperative nutrition support and infection control would improve survival of pancreatic cancer patients.
Interim analysis of perioperative modified FOLFIRINOX (mFOLFIRINOX) in resectable pancreatic cancer (PC).
Authors: Cecchini Michael , Salem Ronald R , Zaheer Kidwai Wajih , Kortmansky Jeremy S. , Fischbach Neal A. , Patel Abhijit , Hochster Howard S. , Lacy Jill 
Published: March 2017

393 Background: The mortality of patients (pts) with resectable PC is > 70% with surgery and adjuvant therapy. Based on the favorable results of our prospective phase II study of mFOLFIRINOX in locally advanced PC (Stein SM et al. Br J Cancer. 2016), we are conducting a single arm open-label phase II trial to evaluate the efficacy of peri-operative mFOLFIRINOX in resectable PC. Here we report our interim results. Methods: Pts with untreated resectable PC were treated with 6 cycles of mFOLFIRINOX every 2 weeks before and after surgical resection. Pre-op FDG-PET and CT scans were obtained at baseline and after 3 and 6 cycles, respectively. After study treatment pts were followed with serial CT scans and CA 19-9 levels. We performed our validated test for circulating tumor DNA (ctDNA) at baseline and multiple time points thereafter. Results: At our interim analysis, 19 pts are enrolled; 1 pt withdrew consent after 1 cycle and is not included. Baseline characteristics: median age 64; male 12; median CA-19 94 (range 0.8-1926); head of pancreas tumor 14; biliary stent 9; ECOG 0 17. Two pts received < 6 cycles pre-op for reasons other than progression or treatment-related adverse events (AEs). Response by RECIST for the 17 pts who received ≥ 3 pre-op cycles was: CR/PR 1 (6%), SD 15 (88%) (8 with minor response defined as 10-30% decrease in target lesion), and PD 1 (6%). Six of 14 pts (43%) who received FDG-PET scans had > 50% decrease in SUV. At present, 2 pts have yet to complete 6 pre-op cycles. Fifteen pts have undergone surgical exploration, and 2 were not deemed resectable during exploration due to peritoneal implants and adhesions from chronic pancreatitis. Thirteen of 16 (82%) underwent resection; 12 (92%) were R0; 2 (15%), 5 (39%), and 6 (46%) pts had pathologic stage I, IIA, and IIB disease, respectively. 4 pts developed disease recurrence and died. AEs were not different than we previously reported and were manageable with protocol-mandated dose adjustments. Conclusions: Our interim analysis suggests that perioperative mFOLFIRINOX for resectable PC is feasible and associated with a 92% rate of R0 resection. Accrual will continue to 46 pts, and analysis of efficacy endpoints and correlative studies including ctDNA are ongoing. Clinical trial information: NCT02047474.
Safety and efficacy of accelerated hypofractionation and stereotactic body radiotherapy for hepatocellular carcinoma in the setting of advanced liver dysfunction.
Authors: Nabavizadeh Nima , Waller Joseph , Fain Robert , Chen Yiyi , Degnin Catherine , Elliott David , Mullins Brandon T , Patel Ishan , Dyer Brandon Alan , Naugler Willscott E , Farsad Khashayar , Tanyi James , Fuss Martin , Thomas Charles R. , Hung Arthur 
Published: March 2017

403 Background: To report toxicities and outcomes for stereotactic body radiotherapy (SBRT) and accelerated hypofractionated radiotherapy (AHRT) in patients with Child-Pugh (CP) A/B/C and Albumin-Bilirubin (ALBI) score 1/2/3 hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 151 patients with HCC treated with SBRT (50 Gy in 5 fractions) or AHRT (45 Gy in 18 fractions) between 2007 and 2015. Primary endpoint was incidence of grade 3 or higher toxicities within 6 months of radiotherapy (RT). Patients were censored for toxicity upon local progression, further liver-directed therapy, or if they exhibited grade 3 or higher toxicities prior to RT, unless RT elevated the grading or a new toxicity class was observed. Secondary endpoints of overall survival and local control were calculated. Results: Median follow-up was 11 months (1 – 90 months). Most received SBRT (72%), while 28% received AHRT due to size criteria ( > 5 cm) or proximity to a critical organ-at-risk. Grade 3 or higher hyperbilirubinemia and hypoalbuminemia was greater in the CP-B8/B9/C patients (42% and 22%) or ALBI-3 patients (45% and 31%) compared to patients with CP-A/B7 (11% and 4%, p < 0.001) or ALBI-1/2 (14% and 4%, p < 0.001). For all other toxicity classes, no difference between liver functionality groups was seen. Eleven grade 4 and no grade 5 toxicities were observed. For all pts, 1- and 2-year treated-lesion local control (LC) rates were greater for SBRT as compared to AHRT (2-year LC 95% vs. 66%, p < 0.0001). When excluding patients with planning treatment volumes > 115 cc (equivalent to a 6 cm sphere), SBRT still yielded superior outcomes. Conclusions: Other than higher rates of grade 3+ hypoalbuminemia and hyperbilirubinemia, highly conformal RT appears to be a potentially safe and effective treatment option for HCC patients with advanced liver dysfunction. Compared to AHRT, SBRT is associated with superior local control.
A phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer.
Authors: Chiang Nai-Jung , Chen Jen-Shi , Chen Ming-Huang , Yang Shih-Hung , Hsu Chiun , Yen Chia-Jui , Tsou Hsiao-Hui , Yanshen Shan , Chen Li-Tzong 
Published: March 2017

417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m2 gemcitabine with 10 mg/m2/min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p0= 0.4, p1= 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD≥ 12weeks]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p0) would be rejected if 24 or more patients with CR/PR/SD≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD>12weeks. The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD≥ 12weeks, the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.
Clinical outcome of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first line chemotherapy in metastatic pancreatic cancer.
Authors: Watanabe Kazuo , Hashimoto Yusuke , Umemoto Kumiko , Takahashi Hideaki , Sasaki Mitsuhito , Imaoka Hiroshi , Ohno Izumi , Mitsunaga Shuichi , Ikeda Masafumi 
Published: March 2017

438 Background: FOLFIRINOX and Gemcitabine plus nab-paclitaxel (GN) have been established as first line chemotherapy in metastatic pancreatic cancer (mPC). But few data support preferable first line choice of these two regimens in “real-world” clinical setting. Methods: We retrospectively enrolled 135 chemotherapy-naive mPC patients treated with modified FOLFIRINOX (mFFX) or GN at National Cancer Center Hospital East between December 2013 and September 2015. mFFX is a modified regimen of reduced dose of irinotecan 150mg/m2 and eliminated bolus 5-FU from original FFX. GN consists of gemcitabine 1000mg/m2 plus nab-paclitaxel 125mg/m2 day1,8,15 every 4 weeks. We compared characteristics, efficacy and adverse events between mFFX and GN. Results: Seventy patients were treated with mFFX and 65 patients with GN as first line therapy. Demographic and baseline characteristics (mFFX/GN) were similar as follows: ECOG performance status (0-1): 100% / 99%, Gender (male): 66% / 69%, liver metastasis: 56%/49%, peritoneal metastasis: 34% / 31%, prior biliary drainage: 21%/17%, median observation period: 330 / 265 days, respectively. The population of elderly patients ( > 75y) was smaller in mFFX than GN (4.3% vs. 12%, p = 0.05). Objective response rate (27% vs. 39%, p = 0.02) and disease control rate (79% vs. 92%, p = 0.02) were significantly lower in mFFX than in GN. Median OS was 11.5 months (95% CI: 9.7-16.8) in mFFX and 14.0 months (95% CI: 12.2 - not reached) in GN. Median PFS was 5.7 months (95% CI: 3.4-7.1) in mFFX and 6.5 months (95% CI: 6.1-7.9) in GN. One-year survival rate was significantly higher in GN than in mFFX (44% vs. 67%, p = 0.0006). Incidences of grade 3 or 4 neutropenia (47% vs. 45%), diarrhea (1.4% vs. 2.0%), and peripheral neuropathy (4.2% vs. 4.6%) were similar in each group. On the other hand, incidences of febrile neutropenia (8.5% vs. 2.0%, p = 0.06) and G-CSF use rate (21% vs. 0%, p < 0.0001), anorexia (13% vs. 3%, p = 0.03) were significantly higher in mFFX than those of GN. Conclusions: Patients treated with GN showed more favorable efficacy and survival. Incidences of most adverse events did not differ between mFFX and GN,whereas febrile neutropenia occurred more frequently in mFFX.
Surgical intervention in early-stage pancreatic adenocarcinoma.
Authors: Jabbari Javaneh , Ahmed Aabra , Walters Ryan W , Silberstein Peter T. 
Published: March 2017

443 Background: Bilimoria et al (2007) reviewed 9,559 patients from the 1995-2004 National Cancer Database (NCDB) showing that 38.2% of patients with early-stage pancreatic cancer without any identifiable contraindications failed to undergo pancreactomy. We used the 2004-2013 NCDB to look at the role of surgery in initial care plans of patients with stage I pancreatic adenocarcinoma. We also assessed differences in practice in this regard at different types of cancer centers. Methods: We analyzed 12,927 patients diagnosed with stage I pancreatic adenocarcinoma between 2004-2013 from the NCDB. Survival differences between patients who received surgery at the primary site versus patients not offered surgery were estimated by the Kaplan-Meier method. Differences in surgery were compared using chi-squared analysis. Results: Of the stage I patients, 27.3% had surgery, 52.8% were not offered surgery, 9.3% were not offered surgery due to risk factors, 4.4% refused surgery. Patients who received surgery had an increased median survival time compared to patients who were not offered surgery (30.2 months versus 7.1 months, p < 0.05). Patients at academic/research programs were most likely to have surgery compared to those at community cancer programs who were least likely to have surgery (39.8% versus 22.9%, p < 0.05). Conclusions: Patients who had surgery of the primary site had a significantly longer median survival time than those that were not offered surgery. Patients were most likely to be offered surgery if they were at an academic/research facility. Future studies should examine other factors that could possibly influence whether a patient is offered surgery or not for early-stage pancreatic adenocarcinoma. [Table: see text]
Cell free circulating tumor DNA (ctDNA) landscape in patients with advanced gastroesophageal adenocarcinoma (GEC).
Authors: Catenacci Daniel V.T. , Nagy Rebecca J , Braiteh Fadi S. , Kim Seung , Kwak Eunice Lee , Maron Steven Brad , Banks Kimberly C. , Lanman Richard B. , Talasaz Amirali , Lee Jeeyun 
Published: March 2017

47 Background: Esophageal (EC), gastroesophageal junction (GEJ) and gastric cancer (GC), together GEC, have a poor prognosis with few targeted therapeutic options. As genomic profiling is becoming increasingly useful, we queried whether comprehensive genomic profiling of ctDNA would reveal relevant genomic alterations leading to targeted therapies. Methods: Patients (pts) with advanced GEC undergoing next-generation sequencing (NGS) of ctDNA in a CLIA certified lab were identified. ctDNA was analyzed using Guardant360, a digital NGS assay to identify single nucleotide variants, indels, amplifications and fusions in 54-70 genes. Results: 546 pts with GEC had ctDNA testing and 54 pts (10%) had more than one ctDNA test (range 2-6). Pts were similar across the 3 groups, with the exception of an increased male:female ratio (5:1) in the GEJ and EC cohorts. Mean age was 61.5 yrs (range 24-91). ctDNA alterations were detectable in 455 pts (83.3%). Recurrent alterations and therapeutic options for each cohort are shown in Table 1. Serial monitoring of ctDNA correlated with tumor markers, imaging and clinical response. Multiple antitumor responses to targeted therapy will be presented. Conclusions: ctDNA was detected in 83.3% of pts with advanced GEC with a frequency similar to TCGA. The diverse genomic landscape of GEC, obtained noninvasively, along with matched therapies have potential to improve outcomes for this aggressive disease. [Table: see text]
Premorbid body mass and mortality in patients with hepatocellular cancer: A systematic review and meta-analysis.
Authors: Gupta Arjun , Das Avash , Arora Nivedita , Majumder Kaustav , Singh Preet Paul , Beg Muhammad S. , Singh Siddharth 
Published: March 2017

477 Background: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid body mass index (BMI) and HCC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to March 2016, we identified observational studies reporting the association between premorbid BMI, and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing obese (BMI > 30 kg/m2) and overweight (BMI 25-29.9 kg/m2) categories with reference category using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: 9 studies were included in which 6,052 HCC deaths occurred in 1,599,453 cancer-free individuals at cohort inception. 5 studies reported data as obese vs. overweight vs. normal BMI, and 4 reported data as obese + overweight combined (BMI > 25 kg/m2). On meta-analysis, pre-morbid obesity was associated with higher HCC-related mortality, as compared to individuals with normal BMI (obese: aHR, 1.96; 95% CI, 1.46-2.46, I2= 37%; overweight: aHR, 1.08; 95% CI, 0.97-1.21, I2= 0%), in dose-dependent manner. This effect was stronger in males [3 studies, aHR, 2.50; 95% CI, 2.02-3.09] vs. females [2 studies, aHR, 1.45; 95% CI, 1.08-1.97]. This effect was seen primarily in Western populations [4 studies, aHR, 2.10; 95% CI, 1.77-2.48], but not in Asian population [1 study, aHR, 1.10; 95% CI, 0.63-1.92]. Conclusions: In this meta-analysis, there was a dose-dependent increase in HCC-related mortality with pre-morbid obesity, particularly in men, and in Western populations. Strategies targeting obesity-induced metabolic abnormalities may provide novel pathways for HCC therapy.
Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: Update from CheckMate 142.
Authors: Overman Michael J. , Lonardi Sara , Leone Francesco , McDermott Raymond S. , Morse Michael A. , Wong Ka Yeung Mark , Neyns Bart , Leach Joseph L. , Garcia Alfonso Pilar , Lee James J. , Hill Andrew , Lenz Heinz-Josef , Desai Jayesh , Moss Rebecca A. , Cao Z. Alexander , Ledeine Jean-Marie , Tang Hao , Kopetz Scott , Andre Thierry 
Published: March 2017

519 Background: Approximately 4% of metastatic colorectal cancers (mCRCs) are associated with high microsatellite instability (MSI-H), indicating a deficient DNA mismatch repair (dMMR) system. dMMR/MSI-H CRC exhibits an increased tumor neoantigen load and immune cell infiltration and is hypothesized to be targetable by immune checkpoint inhibitors. CheckMate 142 (NCT02060188) evaluates the efficacy and safety of nivolumab (nivo) in patients (pts) with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC who progressed on/were intolerant to ≥1 prior line of therapy received nivo 3 mg/kg (nivo 3) every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) per investigator (INV). The secondary endpoint was ORR per independent radiology review committee (IRRC); exploratory endpoints included safety, PFS, OS, and efficacy in biomarker-defined populations. Results: Among pts treated with nivo 3 Q2W (N = 74), 84% had received ≥2 prior lines of therapy. ORRs were 31% (INV) and 27% (IRRC); disease control rates were 69% (INV) and 62% (IRRC). The median time to response was ≈2.7 mo (INV/IRRC). PFS rates at 12 mo were 48.4% (INV) and 45.6% (IRRC). The duration of response and OS medians were not yet reached; OS rates were 83.4% (6 mo) and 73.8% (12 mo). Responses were observed in pts regardless of tumor programmed death-1 ligand 1 (PD-L1) expression level or BRAF or KRAS mutation status and were observed in pts with or without a history of Lynch syndrome (Table). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 20% of pts. TRAEs leading to discontinuation included acute kidney injury, increased ALT, colitis, and stomatitis (1 each). No treatment-related deaths occurred in this arm. Conclusions: Nivo showed durable responses and disease control in heavily pretreated pts with dMMR/MSI-H mCRC. Treatment was well tolerated, with no new safety signals. Clinical trial information: NCT02060188. [Table: see text]