bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial signals of efficacy in cholangiocarcinoma from a phase Ib trial of varlitinib in combination with doublet chemotherapy (cisplatin + 5-fluororacil or capecitabine).
Authors: Hsieh Chih-Yi , Wu Ming-Shiang , McHale Mark , Lindmark Bertil , Chow Lilian , Chao Yee 
Published: September 2018

e15671 Background: Varlitinib (ASLAN001) is a potent, reversible, small molecule pan-HER inhibitor that selectively binds to HER1 (IC50 7nM), HER2 (IC50 2nM) and HER4 (IC504nM). Clinical data in cholangiocarcinoma, gastric cancer, colorectal cancer and breast cancer indicate that varlitinib is a safe and well tolerated inhibitor of tumor growth and survival. Here we conducted a phase Ib trial to determine the safety and early efficacy signals of varlitinib in combination with cisplatin (CIS) and 5-fluorouracil (5-FU) or CIS and capecitabine (CAP). Methods: Eligible patients had metastatic solid tumors. Doses of varlitinib were escalated in a standard 3+3 design with corresponding chemotherapy for 6 cycles after which patients remained on varlitinib montherapy. Responses were defined using RECIST 1.1 criteria. Results: To date, 27 patients have been enrolled. Most common treatment related adverse events ( > 10%) were nausea (56%; ≥G3 4%), vomiting (48%; ≥G3 4%), decreased appetite (44%; ≥G3 7%), diarrhea (37%; ≥G3 11%), anemia (26%; ≥G3 11%), fatigue (22%; ≥G3 0%), creatinine increase (19%; ≥G3 4%), stomatitis (15%; ≥G3 4%), acute kidney injury (11%; ≥G3 11%), bilirubin increase (11%; ≥G3 7%), leukopenia (11%; ≥G3 7%), abdominal pain (11%; ≥G3 0%), and neutropenia (11%; ≥G3 0%). All patients with diarrhea, including those with G3 diarrhea were well controlled with standard doses of loperamide. Of 15 patients evaluable for response, three had partial response (20%), ten had stable disease (67%), and two had progressive disease (13%). Of note were strong and durable responses in cholangiocarcinoma. One cholangiocarcinoma patient demonstrated an 87% reduction in liver tumor size by cycle 2 and a complete resolution in one liver lesion by cycle 4. Another cholangiocarcinoma patient without measurable lesions in the liver or biliary tract achieved long-term disease control for a total of 15.2 months with good tolerability on varlitinib as monotherapy. Conclusions: The combination of varlitinib and CIS + 5-FU or CAP doublet chemotherapy is safe, well tolerated and has demonstrated strong efficacy signals in cholangiocarcinoma. Clinical trial information: NCT02648425.
The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.
Authors: Kim Seung Tae , Lee Su Jin , Lee Jeeyun , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki 
Published: September 2018

e15686 Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.
The role of modified FOLFIRINOX regimen in unresectable advanced pancreatic cancer: A retrospective clinical study.
Authors: Qian Yuan , Zheng Song , Jia Changku 
Published: September 2018

e15709 Background:Pancreatic cancer was the fourth leading cause of death from cancer in the United States in 2015, with a 5-year survival rate only 6%.More than 85% of patients has an unresectable disease at diagnosis for most patients remain asymptomatic. This population including locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). Gemcitabine has been the standard treatment option for these patients for more than a decade, with a median overall survival nearly 6 months. In 2011, the phase 3 randomised controlled trial(PRODIGE 4/ACCORD 11) reported that FOLFIRINOX regimen had a significantly improved OS,PFS and a predominant ORR in patients with metastatic disease.FOLFIRINOX, as an encouraging regimen, its actual higher adverse events rate in clinical practice should not be underestimated, especially the grade 3/4 neutropenia and sensory neuropathy. The aim of our study is to explore whether a modified FOLFIRINOX regimen with the decrements of oxaliplatin and irinotecan had maintained efficacy and decreased grade 3/4 adverse events rate for the advanced pancreatic cancer. Methods:Retrospectively collected data of all patients carrying a diagnosis of advanced pancreatic cancer at the department of medical oncology, Hangzhou First People’s Hospital and Hangzhou cancer hospital between January 2014 and September 2016.The endpoint were overall survival, objective response rate and grade 3/ 4 adverse events. Results:Among 21 patients who received median 5(1-12) cycles modified FOLFIRINOX regimen,15 of total patients received this regimen for more than 4 cycles (71.4%). The median overall survival of MPC patients in this study is 12.6 months (95% CI, 6.2 months to 19 months). The objective response rate was 42.9%, with partial remission in 9 cases, stable disease in 8 cases and progression disease in 4 cases. Totally 8 patients had grade 3/4 adverse events, the most frequent were neutropenia (14.3%), neuropathy (14.3%) and diarrhea (9.5%). No chemotherapy-related death occurred. Conclusions:mFOLFIRINOX regimen in this study has maintained efficacy for its high objective response rate and an improved safety profile in patients with advanced pancreatic cancer.
Outcomes of resectable and borderline resectable pancreatic cancer patients in rural practice.
Authors: Rashad Sadaf , Bulbul Ajaz , Jean Brian , Gholam Sami , Araujo-Mino Emilio Paul , Braik Tareq , Khorsand-Sahbaie Masoud ,   Kymera Physicians
Published: September 2018

e15712 Background: Accurate selection of patients based on radiological and biological variables is crucial to avoid over treatment and unnecessary R1 resection in pancreatic cancer (PC). Methods: We retrospectively investigated 73 patients diagnosed with PC treated between January 1998 to October 2015. We applied NCCN definitions for Resectable (RD), borderline resectable (BRD) and unresectable disease(URD). Logistic regression was used to identify significant indicators of R0 resection. Odds ratios were used to compare differences of overall survivability by R0 and No surgery. Fisher’s Exact Test was used for significance on all tabulated data. Wilcoxon Rank-Sum was used for the comparison of two medians and Kruskal-Wallis to compare more than two medians, and log-rank test was used to compare Kaplan-Meyer Curves. Results: Radiologically RD comprised 21% (15/73) of total cases, 80% (12/15) of these underwent R0 resection. URD comprised 79% (58/73). Patients presenting with abdominal pain were 2.5 times (Odds Ratio; p = 0.0275) more likely to be URD. The mean tumor size for R0 resectability was 2.28 cm (n = 12). The median CA 19-9 for URD was 1473 vs 162 for RD (p = 0.0124). Stage at presentation and resectability were statistically associated. (p = 0.0002): 100% of Stage 1 (n = 4) and, 27% of Stage 2, (11/41) were resectable. Twenty-three cases were identified as BRD, 21/23 received neoadjuvant chemotherapy, 47.83% had radiological PR, 28.26% had SD and 23.91% PD. There was no association between type of Neoadjuvant treatment (Chemo XRT vs Chemotherapy) and radiological response (p = 0.8798). None of the 21 BRD patients underwent surgery. Median Overall Survival for R0 resection was 22.3 months (95% CI 15.23, 36.50) vs. 5.1 who did not have surgery (95% CI 3.55, 7.57) (p = 0.0010). Conclusions: Nearly 80% patients identified as resectable on imaging underwent R0 resection. Although there were partial responses seen in BRD patients that underwent neoadjuvant treatment eventually none underwent R0 resection. Patients presenting with abdominal pain and high CA19-9 ( > 1400 U/ml) are likely to URD. Early stage and R0 resection were associated with positive outcomes.
A phase II study of oral S-1 with concurrent hypofractionated simultaneous integrated boost radiotherapy for metastatic pancreatic cancer with helical tomotherapy.
Authors: Ren Gang , Zhu Feng , Wang Yingjie , Xia Tingyi 
Published: September 2018

e15720 Background: This study was conducted to evaluate the efficacy as well as toxicity of oral S-1 with concurrent hypofractionated simultaneous integrated boost radiotherapy for metastatic pancreatic cancer using helical Tomotherapy. Methods: Patients with metastatic pancreatic cancer, adequate organ and marrow function and no prior anticancer therapy were enrolled in our study. S-1 was administered orally at a day of 40mg/m2 twice daily from day for 2 weeks, repeated every 3 weeks. Dose to the primary lesion was delivered as PTV for 50Gy, CTV for 60Gy and GTV for 70Gy in 15 to 20 fractions. Radiation induced toxicities were evaluated with the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.02. The overall survival (OS), progressive-free survival (PFS) and freedom from local progression (FFLP) were estimated using the Kaplan-Meier survival curve. Results: 45 patients were enrolled in this prospective clinical study. Pain relief rate was 91.7% (33/36). 1 year FFLP rate of the pancreatic lesion was 92.5%. 1 year OS rate was 17.6%. 1 year PFS was 4.2%. Median OS was 6 months. Grade 3 gastrointestinal reaction and blood reaction both appeared in 3 cases (13.3%). Conclusions: S-1 with concurrent hypofractionated simultaneous integrated boost radiotherapy using helical Tomotherapy resulted in high pain relief rate for patient with metastatic pancreatic cancer, with a tolerable side effect.
The prognostic significance of exosomal marker (CD63) expression using immunohistochemistry (IHC) in patients with pancreatic ductal adenocarcinoma (PDAC).
Authors: Khushman Moh'd M. , Bhardwaj Arun , Patel Girijesh K. , Laurini Javier , Roveda Kelly , Donnell Robert , Sherling Kelley , Case Brittany , Tan Marcus Chuan Beng , Thompson Lee W. , Nelson Cindy , Wyatt Mary , Singh Seema , Taylor William R. , Singh Ajay 
Published: September 2018

e15730 Background: Exosomes are important mediators of intercellular communication, and play pivotal roles in cancer progression, metastasis and chemoresistance. Exosomal membranes are enriched in endosomes-specific tetraspanins (CD63 and CD9). In patients with PDAC, positive correlation between CD9 expression and overall survival (OS) was reported. However, CD63 expression was conserved in all patients without reported prognostic significance. Here, we explored the prognostic significance of CD63 expression using IHC in patients with PDAC of mixed gender and racial background. Methods: Between 2012 and 2016, 49 patients with PDAC treated at Mitchell Cancer Institute had available tissue (pancreatic resected tissue/biopsy [N = 29] or metastatic site biopsy liver, omentum or bone (N = 20)) for CD63 staining using IHC. Two pathologists independently scored the expression of CD63. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean Quick-score (Intensity X Percentage of staining) was calculated. Unpaired t test was used for statistical analysis. Results: Median age was 64 years (range 42-85). 53% are males. 67% white, 27% African Americans (AA) and 6% are other ethnicities. 41% had stage IV disease while 49% had stage I, II and III. Tumor involved the head (51%), body (20%) and tail (29%). The mean CD63 Q score is slightly higher in AA compared to white (157 vs 149, P = 0.76). The mean CD63 Q score is higher in the pancreatic tissues compared to metastatic sites tissues (185 Vs 102, P = 0.0002). In our cohort, patients with mean CD63 Q score > = 140 had longer median OS compared to patients with mean Q score of < 140 (19 months Vs 3 months, P = 0.0003) and progression free survival (PFS) (12 months vs 1 month, P = 0.0043). Conclusions: In our cohort of patients with PDAC, there was no racial difference in CD63 expression between white and AA. The expression of CD63 is higher in the pancreas compared to metastatic sites (liver, omentum and bone). There is positive correlation between CD63 expression and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC.
The impact of second-line chemotherapy on advanced pancreatic cancer: A retrospective study in Reggio Emilia Clinical Cancer Centre.
Authors: Baldi Licia , Panebianco Michele , Giorgi Rossi Paolo , Mancuso Pamela , Cassetti Tiziana , Sassatelli Romano , Pinto Carmine 
Published: September 2018

e15732 Background: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma. The aim of this study is to evaluate the impact of a second-line therapy prior to the introduction of nab-paclitaxel. Methods: From 01/2009 to 12/2014, 204 patients were treated for pancreatic cancer. 166 (81.3%) received first(I)-line chemotherapy. Patients treated in second(II)-line were evaluated in two different periods, before and after FOLFIRINOX introduction. Results: 99 patients (59.6% treated in I line) received II line therapy. The main regimens used in I line were gemcitabine during the period 2009-2011 and FOLFIRINOX from 2012 to 2014 (some patients were treated with nab-paclitaxel/gemcitabine approved before AIFA registration). We observed that the increased use of gemcitabine in the second period was related to a reduction in I line use (52.1% patients after 2012 vs 21.4% before 2012). Considering the different therapeutic regimens employed in I and II line, no statistically significant differences in overall survival were observed over the two periods (Table). The probability of receiving II line chemotherapy did not change in the two groups (HR 0.6; p=0.2). Conclusions: Within the limits of a retrospective analysis, all II line regimens used showed the same effectiveness, regardless of I line treatment employed. It is likely that the large number of patients treated with effective therapies in II line have concealed the impact of front-line schemes. In an ongoing study we are evaluating the impact of introducing nab-paclitaxel in clinical practice. [Table: see text]
FOLFIRINOX versus gemcitabine nab-paclitaxel for advanced pancreatic cancer: KU Cancer Center experience.
Authors: Kasi Anup , Middinti Akshay , Cao An , Vekaria Pratikkumar , Patel Devangi , Subramaniam Dipti , Chen Guoqing J. , Saeed Anwaar Mohammed , Paluri Ravi Kumar 
Published: September 2018

e15744 Background: FOLFIRINOX (FFN) and Gemcitabine plus nab-paclitaxel (GN) have been established as first line chemotherapy in advanced pancreatic cancer (PC). But there is no head-to-head randomized trial data available to support preferable first line choice between these two regimens. Methods: We retrospectively evaluated 154 chemotherapy-naïve locally advanced and metastatic PC patients treated with FFN or GN at KU Cancer Center between January 2011 and November 2016. FFN consisted of Oxaliplatin 85mg/m2, Irinotecan 180mg/m2, 5-FU 400mg/m2 as a bolus and 2,400 mg/m2over 46 hour on days 1 and 15 every 4 weeks. GN consisted of Gemcitabine 1000mg/m2 plus nab-paclitaxel 125mg/m2 day1,8,15 every 4 weeks. We compared characteristics, efficacy and adverse events between FFN and GN. Results: 107 patients were treated with FFN and 47 patients with GN as first line therapy. Demographic and baseline characteristics (FFN/GN) were as follows: Median age 61/63 years, ECOG performance status (0-1): 90% / 83%, Gender (male): 57% / 54%, distant metastases: 52%/70%, biliary stenting: 41%/20%, locally advanced tumor: 48%/30%, pancreatic head tumors: 63%/55%, median number of cycles: 4/4 respectively. Objective response rate (13% vs. 10%), Stable disease rate (76% vs 82%) and disease control rate (89% vs. 92%, p = 0.5) were similar in FFN and in GN. Median PFS was 11.7 months (95% CI: 7.2-16.1) in FFN and 5.7 months (95% CI: 2.7-8.8) in GN [p = 0.07]. Median OS was 15.9 months (95% CI: 13.7-18.1) in FFN and 10.8 months (95% CI: 7.1 – 14.5) in GN [p = 0.17]. Incidences of grade 3 or higher adverse effects were neutropenia (33% vs. 17%), anemia (14% vs 31%), thrombocytopenia (28% vs 6%), elevated creatinine (2.8% vs 4%), elevated transminases (3.7% vs 6%), diarrhea (5% vs. 0%), and peripheral neuropathy (6% vs. 6%) respectively. Conclusions: Patients treated with FFN showed statistically better PFS compared to GN. However this difference in PFS did not translate into statistically significant difference in OS. Response rates were similar. Incidences of adverse events were relatively more with FFN compared to GN as expected.
Predictive value of hENT1 immunohistochemistry for gemcitabine-treated pancreatic cancer is antibody dependent.
Authors: Yusuf Dimas , Lui Arthur , Abdelaziz Zainab , Spratlin Jennifer L. , Mackey John Robert 
Published: September 2018

e15746 Background: Pancreatic cancer (PC) continues to have poor outcomes, and biomarkers to guide individualized therapy are needed. Gemcitabine (GEM), a pyrimidine nucleoside, requires plasma membrane transporter proteins to enter cells, and deficiency of the human equilibrative nucleoside transporter 1 (hENT1) protein confers high-level GEM resistance in pre-clinical models. Furthermore, abundance of hENT in PC cells, as determined by immunohistochemistry (IHC), has been variably reported to be associated with improved survival in people with PC treated with GEM. The antibodies (Abs) used for IHC differ in targeted epitope, method of generation, and species of origin. The purpose of this review is to evaluate the contribution of anti-hENT1 Ab choice in finding a link between hENT1 expression and outcomes. Methods: We reviewed the published literature investigating relationships between hENT1 IHC tumor expression and survival in people with PC treated with GEM. Results: Eighteen studies were identified, using five distinct Abs (Table 1). We identified apparent differences in predictive value among Abs (Chi square test p = 0.065). All seven studies using the 10D7G2 Ab reported that high hENT1 expression is associated with significantly better outcomes in GEM-treated patients. Studies that used other anti-hENT1 Abs, in particular SP120 and 11337-1-AP, had lower rates of success. Pooled HRs and additional metrics will be presented. Conclusions: There is significant heterogeneity among studies evaluating the link between hENT1 expression and outcomes. hENT1 IHC with the 10D7G2 Ab is a strong and reproducible predictive marker for improved survival in people with PC treated with GEM. [Table: see text]
Prognostic role of neutrophil-to-lymphocyte ratio (NLR) dynamics during first-line FOLFOXIRI in advanced pancreatic cancer (aPC).
Authors: Pecora Irene , Musettini Gianna , Catanese Silvia , Vivaldi Caterina , Pasquini Giulia , Caparello Chiara , Lencioni Monica , Falcone Alfredo , Fornaro Lorenzo , Vasile Enrico 
Published: September 2018

e15754 Background: Elevated pre-treatment NLR is a well-known poor prognostic factor in several tumours, including aPC. However, the role of NLR changes during first-line chemotherapy is less investigated. Methods: We retrospectively evaluated aPC patients (pts) treated with FOLFOXIRI (infusional 5-fluorouracil, oxaliplatin, irinotecan). NLR was calculated before the first (NLR-0) and the fourth (NLR-3) cycle, high NLR being defined as > 4. We evaluated the correlation between NLR change and overall survival (OS), progression-free survival (PFS), response rate (RR) and disease-control-rate (DCR). Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Multivariate analysis was performed by Cox proportional hazards model. Results: Ninety-four pts were evaluable. Median age was 62 years; at diagnosis, 38 (40.4%) pts had unresectable stage III and 56 (59.6%) had stage IV disease. In the overall population, median PFS (mPFS) and OS (mOS) were 8.0 and 12.9 months, respectively. NLR-0 was significantly associated with poor prognosis: among the 12 pts with NLR-0 > 4 mOS was 5.1 months compared with 13.5 months for the 82 pts with NLR-0 ≤4 (p < 0.001). As regards NLR dynamics, NLR-3 remained high or was increased (H/I) in 5 pts (5.3%) while was stably low or decreased (L/D) in 89 pts (94.7%). mOS was 5.1 months (95%CI 0.4-9.8) in H/I and 13.5 months (95%CI 10.9-16.1) in L/D (p < 0.001) pts. The same association was found for PFS, with 4.7 (95%CI 2.1-7.3) vs 8.3 months (95%CI 6.2-10.4, p = 0.004), respectively, but not for RR and DCR. At multivariate analysis, NLR change was confirmed as independent predictor of OS (HR 6.854, 95%CI 2.109-22.269, p = 0.001) and, when added to performance status, liver metastases and NLR-0, allowed a better risk stratification in good (no negative factors), intermediate (1-2 factors) and poor (3-4 factors) risk groups, with mOS of 18.0, 10.0 and 5.1 months, respectively (p = 0.012). Conclusions: Not only NLR-0, but also changes after 3 cycles of first-line FOLFOXIRI could predict OS in aPC pts. Early variations in NLR might be a cheap, reproducible and useful factor to predict prognosis and to better refine treatment strategy.