bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness and safety of the implementation of universal public funding of FOLFIRINOX (FFX) and gemcitabine (G) + nab-paclitaxel (GnP) in advanced pancreatic cancer (APC): A population-based study.
Authors: Guo Helen , Beca Jaclyn Marie , Redmond-Misner Ruby , Isaranuwatchai Wanrudee , Qiao Lucy , Earle Craig , Berry Scott R. , Biagi James Joseph , Welch Stephen , Meyers Brandon Matthew , Mittmann Nicole , Coburn Natalie G. , Pardhan Aliya , Arias Jessica , Schwartz Deborah , Gavura Scott , Forbes Leta Marie , McLeod Robin , Kennedy Erin Diane , Chan Kelvin K. 
Published: January 2019

375 Background: FFX has been universally publicly funded in Ontario, Canada, for metastatic pancreatic cancer (mPC) and unresectable locally advanced pancreatic cancer (uLAPC) since 11/2011 and 04/2015, respectively. GnP has been publicly funded for uLAPC and mPC (APC) since 04/2015. We examined the real world comparative effectiveness and safety of implementing funding of FFX and GnP for patients with APC. Methods: Patients with APC who received first-line FFX, GnP, or G from 01/2008-03/2016 were identified in CCO’s New Drug Funding Program database and divided into 3 periods: 01/2008-10/2011 (P1), 11/2011-03/2015 (P2), and 04/2015-03/2016 (P3). Data were linked with the Ontario Cancer Registry and others to ascertain demographics, comorbidities, and outcomes. Matching weights of propensity score to simultaneously compare three periods were generated using multinomial logistic regression. Crude and adjusted survival analyses were conducted to assess overall survival (OS) using Kaplan-Meier and weighted Cox regression methods.Weighted negative binomial models were used to estimate rate ratios (RR) for all-cause hospitalization (H) and ED visits. Results: We identified 3696 patients (1250 in P1, 1891 in P2, 555 in P3) (overall mean age 65, female 46%). In P2, 49% received FFX. In P3, 53% received FFX and 35% received GnP. Median OS was 5.7, 7.0, and 7.5 months for P1, P2, and P3, respectively. Median OS for FFX and GnP in mPC were 8.8 and 5.5 months, respectively. OS was improved in P2 vs. P1 (HR = 0.84, 0.78-0.90) and in P3 vs. P2 (HR = 0.82, 0.73-0.92). ED visits were similar compared P2 vs. P1 (RR=1.02, p = 0.75) and P3 vs. P2 (RR=1.04, p = 0.48), and H was reduced in P2 vs. P1 (RR = 0.86, p = 0.01), but similar in P3 vs. P2 (RR = 0.98, p = 0.78). H for febrile neutropenia (FN) was increased in P2 vs. P1 (RR = 2.18, p = 0.04) but not in P3 vs. P2 (RR = 1.32, p = 0.45). Conclusions: Implementation of universal public funding of FFX for mPC improved OS and reduced the rates H overall, but increased FN-related H. Funding of FFX for uLAPC and GnP for APC improved OS without increased in ER and H.
The influence of biliary drainage in patients with advanced pancreatic cancer receiving FOLFIRINOX.
Authors: Ueno Makoto , Yamanaka Takeharu , Ogura Takashi , Yamaguchi Atushi , Mizuno Nobumasa , Ozaka Masato , Ueno Hideki , Uesugi Kazuhiro , Kobayashi Noritoshi , Hayashi Hideyuki , Sudo Kentaro , Okano Naohiro , Horita Yosuke , Kamei Keiko , Hosokawa Takafumi , Henmi Toshiyuki , Kobayashi Marina , Todaka Akiko , Fukutomi Akira 
Published: January 2019

378 Background: FOLFIRINOX (FFX) is a standard of care for patients (pts) with advanced pancreatic cancer (APC). In the original FFX report by Conroy (NEJM, 2011), pts with a biliary drainage were limited and the occurrence of cholangitis was not reported. In practice, however, we experience that a certain fraction of APC pts needs a biliary drainage and some of them have an elevated risk of cholangitis or febrile neutropenia (FN) during the course of FFX. We evaluated the influence of biliary drainage on the efficacy and safety of FFX. Methods: We used individual data from nationwide survey of FFX (JASPAC06). The JASPAC06 was a prospective registry of pts with FFX treated in clinical practice and enrolled 399 pts between December 2013 and November 2014 from 27 centers in Japan. We evaluated the associations of OS and PFS, as well as the frequencies of cholangitis and FN, with the use of biliary drainage. We excluded resected cases because an operative method with choledochojejunostomy was unknown. Results: Of 399 pts in the JASPAC06, 319 were eligible for this analysis and 80 resected cases were excluded. The use of biliary drainage was seen in 28% of pts (mainly bile duct stent inserted); primary dose reduction (modified FFX), 67%; previously untreated tumor, 77%; distant metastases, 76%; pancreas head, 47%. The main results are shown in the table. In summary, cholangitis was more frequent in pts with biliary drainage. Grade 3 or higher FN as well as CRP elevation was observed more frequently in pts with biliary drainage. There was no difference in PFS (median PFS, 7.3 vs. 6.5 mo; logrank, p=0.24) and OS (median OS, 12.3 vs. 12.2 mo; p=0.86) between the two groups. Conclusions: Our observation that the frequency of FN and CRP elevation was significantly higher in pts with biliary drainage indicates a higher risk of infection during the FFX treatment by using biliary drainage.[Table: see text]
Neoadjuvant FOLFIRINOX and IMRT concurrent with FDR-gemcitabine in patients with borderline resectable pancreatic cancer (BRPC).
Authors: Tran Nguyen H. , Sahai Vaibhav , Griffith Kent A. , Nathan Hari , Kaza Ravi , Cuneo Kyle Clifford , Sonnenday Christopher J , Cho Clifford , Lawrence Theodore Steven , Zalupski Mark 
Published: January 2019

381 Background: Preoperative therapy in BRPC is intended to increase the likelihood of R0 resection although an optimal regimen is yet to be defined. Methods: Patients (pts) with BRPC (NCCNv.2.2010 guidelines) and ECOG PS 0-1 were enrolled in a single-institution, phase II trial (NCT01661088). Pts received FOLFIRINOX x 6, followed by IMRT (50 Gy in 25 fractions) concurrent with FDR-gemcitabine 1 g/m2 on days 1, 8, 22, 29. Two additional FDR-gemcitabine infusions completed pre-operative treatment. Pancreatic protocol CT scans (dual phase, 0.65 mm slices) were performed after 4 infusions of FOLFIRINOX, 3 weeks after IMRT, and at treatment completion. Pts without distant disease were offered surgical exploration. The primary objective was to determine R0 resection rate. Secondary objectives included progression free survival (PFS), overall survival (OS), response rate and safety. Results: A total of 25 pts (64% men) median age 60 years (range 47-77) were enrolled from 11/2011 through 01/2017. Twenty-one (84%) pts completed FOLFIRINOX and 19 (76%) all protocol therapy. Treatment-related grade 3-4 adverse events ( > 10%) included neutropenia (40%), nausea/vomiting (28%), diarrhea (16%) and fatigue (12%). One early death and 1 discontinuation due to toxicity occurred during FOLFIRINOX. Response to pre-op therapy included 11 PR, 9 SD, 3 PD and 2 NE. Of 25 treated pts, 18 (72%) had laparotomy and 13 (52%) underwent resection (all R0). The median PFS and OS were 18.1 (95% CI, 10.6 to 25.1) and 24.2 (95% CI, 12.6 to 40.0) months, respectively. The median OS for R0 resected pts was 37.1 (95% CI, 15.4 – not reached) months. Conclusions: Neoadjuvant therapy with FOLFIRINOX, followed by IMRT with concurrent FDR-gemcitabine in BRPC is feasible and tolerated. While R0 resection rate was not obviously improved, OS of the entire cohort and especially in R0 resected pts was favorable. Clinical trial information: NCT01661088.
Phase 1 studies of 3- and 6-peptide vaccine cocktail derived from GPC3, WDRPUH, and NEIL3 in patients with advanced hepatocellular carcinoma (HCC).
Authors: Ikeda Masafumi , Okusaka Takuji , Ohno Izumi , Mitsunaga Shuichi , Takahashi Hideaki , Kondo Shunsuke , Morizane Chigusa , Furuse Junji 
Published: January 2019

387 Background: Glypican 3 (GPC3), WD-Repeat-containing Protein Up-regulated in HCC (WDRPUH), and Nei Endonuclease VIII-Like 3 (NEIL3) are tumor antigens in HCC. We conducted two phase 1 multicenter open-label studies for advanced HCC: one to evaluate the HLA-A*24-restricted 3-epitope peptide vaccine cocktail named ONO-7268MX1 (MX1); the other to evaluate the HLA-A*24 and -A*02-restricted 6-epitope peptide vaccine cocktail named ONO-7268MX2 (MX2). Both vaccines contain epitope peptides derived from GPC3, WDRPUH, and NEIL3. MX1 and MX2 cover most of Japanese HCC patients (pts). Safety is the primary, and efficacy and immunological response are the exploratory objectives. Methods: Pts received SC MX1 or MX2 once weekly. In MX1 study, pts received each of 3 peptides at 0.3 mg (cohort 1), 1 mg (cohort 2), and 3 mg of GPC3, 1.1 mg of WDRPUH and 3 mg of NEIL3 (cohort 3). In MX2 study, pts received each of 6 peptides at 1 mg. Results: In MX1 study, 3, 8, and 7 pts with HLA-A*24 were enrolled to cohort 1, 2, and 3, respectively. In MX2 study, 14 pts (7 with HLA-A*24, 6 with HLA-A*02, and 1 with HLA-A*24/A*02) were enrolled. No dose limiting toxicities were observed in both studies. The most commonly related AEs were Grade 1/2 injection site reaction (erythema, induration, pain, and pruritus), 44.4% (8/18) in MX1 and 78.6% (11/14) in MX2. Grade 3-related AEs occurred only in MX2 study; neutrophil count decreased, white blood cell count decreased, and decreased appetite (each 1 patient). No grade 4-related AEs occurred in both studies. No response (CR or PR) were seen in both studies. In MX1 study, median and mean of PFS [range], median duration of SD were 2.8, 3.4 [0.5-16.8], 3.7 months respectively, in MX2 study those were 1.9 and 2.8 [0.4-8.3], 5.7 respectively. In both studies, some pts showed long disease control (≥6 months). For those pts, each peptide-specific Cytotoxic T Lymphocyte (CTL) responses were shown by the ELISPOT assay. Conclusions: MX1 and MX2 showed good tolerability. Both vaccines induced CTL responses which may be related to antitumor effect. In addition, some pts showed long disease control. These results implied the potential usefulness of these vaccines for the treatment of HCC. Clinical trial information: JapicCTI-121933 and JapicCTI-142477.
Dose modifications of liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) in NAPOLI-1: Impact on efficacy.
Authors: Wang-Gillam Andrea , Hubner Richard , Mirakhur Beloo , de Jong Floris A , Belanger Bruce , Chen Li-Tzong 
Published: January 2019

388 Background: In NAPOLI-1 (NCT01494506), a randomized phase 3 study in patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV improved overall survival (OS; primary endpoint) vs 5-FU/LV (6.1 mos vs 4.2 mos; HR = 0·67, 95% CI 0.490.92; P = 0.012). This exploratory analysis examined the impact of dose modifications or delays used to manage adverse events (AEs) on OS. The study protocol allowed ≤2 dose reductions for nal-IRI and 5-FU and for up to 3 weeks. Methods: Patient who had a dose delay or reduction within the planned first 6 weeks of the study were included. Delays were defined as any delay in dosing > 3 days from target dosing date and dose reductions were defined as any reduction in dose from initial administered dose. OS was compared within the nal-IRI+5-FU/LV arm and with the 5-FU/LV arm. Comparisons were made using the cohort of 5-FU/LV and nal-IRI+5-FU/LV patients enrolled under protocol version 2. Median OS was based on Kaplan-Meier estimates and Cox regression analysis was used to calculate HRs. Results: More patients in the nal-IRI+5-FU/LV treatment group experienced AEs that required dose delay and/or reduction than in the 5-FU/LV treatment group (62% vs 33%). Within the nal-IRI+5-FU/LV arm, median OS was numerically but not significantly different between patients who did (n = 34) vs did not (n = 83) have a dose reduction (9.3 vs 5.4 mos; HR = 0.66 [95% CI 0.43, 1.01]) and for those who did (n = 49) vs did not (n = 68) have a dose delay (8.4 vs 5.6 mos; 0.82 [95% CI 0.56, 1.23]). Between treatment arms, OS was greater in the nal-IRI+5-FU/LV arm regardless of dose delay or reduction (Table). Conclusions: Dose modifications in the nal-IRI+5-FU/LV arm did not significantly impact OS compared with those who did not need a dose modification, and OS remained greater than in 5-FU/LV-treated patients. This suggests that appropriate dose modification of nal-IRI+5-FU/LV for AEs may not adversely affect outcomes. Clinical trial information: NCT01494506. [Table: see text]
Retrospective analysis of patients using olaparib (O) in pancreatic cancer (PC).
Authors: Borazanci Erkut Hasan , Guarnieri Carol , Haag Susan , Korn Ronald Lee , Snyder Courtney Edwards , Hendrickson Kristin , Caldwell Lana , Von Hoff Daniel D. 
Published: January 2019

389 Background: Molecular analysis has revealed four subtypes of PC giving clinicians further insight into treating this deadly disease. One subtype that was elucidated termed “unstable” is significant for the presence of DNA damage repair deficiency and can be targeted therapeutically. One such therapy, O, from the drug class poly ADP ribose polymerase (PARP) inhibitors, has already been FDA approved for individuals with BRCA mutated ovarian cancers. We performed a retrospective analysis on patients with PC treated at a single institution who have DNA damage repair deficiency mutations and have been treated with O. Methods: A chart review identified pancreatic cancer patients with DNA repair pathway mutations who were treated with O. The primary objective examined ORR in patients with PC with DNA repair mutations receiving O. Secondary objectives included tolerability, overall survival (OS), CA 19-9 change, and changes in quantitative textural analysis (QTA) on CT. Results: 11 individuals were identified, 5 carriers of a pathogenic germline (g) BRCA2 mutation, 1 carrier of a pathogenic g ATM mutation, 1 carrier of a pathogenic g BRCA1 mutation. Variants of uncertain significance (VUS) included 1 g ATM mutation, 1 g PALB2 mutation, 1 somatic (s) C11orf30 mutation, and 1 s BRCA2 mutation. Median age at diagnosis was 59, with 4 M and 7 F. No patients met criteria for familial PC and 7 had a family history consistent for breast and ovarian cancer syndrome. All individuals had metastatic PC and had progressed on at least 1 line of systemic therapy. ORR was 18%. Median time of therapy on O was 5 months (mo) (Range 1.4 to 29.567 mo) with 5 of the individuals still undergoing treatment at the time of analysis. Mean OS was 12.35 mo, 9 of the 11 individuals still alive. QTA of baseline CTs from subjects with liver (8/11) and pancreatic tumors (7/11) revealed a strong association between lesion texture and OS (Pearson correlation coefficient (PCC): hepatic mets = 0.952, p = 0.0003) and time on O (PCC: panc lesions = 0.889, p = 0.006). Conclusions: In individuals with metastatic PC with mutations involved in DNA repair, O may provide clinical benefit. QTA of individual tumors may allow for additional information that predicts outcomes to PARP inhibitors in this population.
Clinical impact of obesity-related factors in perioperative management of esophageal cancer.
Authors: TAKEUCHI HIROYA , Kikuchi Yuji , Kawakubo Hirofumi , Suda Koichi , Kitagawa Yuko 
Published: January 2019

39 Background: Obese patients with esophageal cancer have been increasing worldwide. However, the impact of obesity on esophagectomy still remains controversial. In this study, we clarified the relations between obesity and postoperative outcomes after esophagectomy in patients with esophageal cancer. Methods: A total of 215 patients who underwent esophagectomy for esophageal cancer between 2008 and 2014 were retrospectively assessed. We qualified the body mass index (BMI), visceral fat area (VFA) and subcutaneous fat area (SFA) using CYNAPSE VINCENT™. Clincopathological factors, postoperative morbidity, and survival after esophagectomy were assessed with these obesity-related factors. Results: The mean BMI, VFA, and SFA were 22.0 kg/m², 83.0cm², and 87.3cm². BMI, VFA and SFA were significantly correlated each other (P < 0.001). The prevalence of diabetes mellitus and hypertension were significantly more in high SFA than normal SFA (20% vs 10%, 30% vs 14%). When the patients were divided to two groups according to BMI (< 25 or ≥25kg/m²), VFA ( < 100 or ≥100cm²) and SFA ( < 100 or ≥100cm²), operative time was significantly longer in high SFA (P = 0.03) than normal SFA, and tended to be longer in high BMI, but blood loss were similar in each groups. Maximum level of postoperative CRP was significantly higher in high BMI (P < 0.001), in high VFA (P < 0.001), and in high SFA (P < 0.001). Length of systemic inflammatory response syndrome was significantly longer in high BMI than normal BMI (1.9 days vs 1.4 days P = 0.04), and length of ventilator support was significantly longer in high SFA than normal SFA (3.0 days vs 2.2 days P = 0.006). The incidence of anastomotic leakage and surgical site infection were significantly higher in high SFA than normal SFA (27% vs 10%, 37% vs 19%). There were no significant difference in overall survival, however, patients in high VFA tended to be longer survival than those in normal VFA (P = 0.078). Conclusions: Anastomotic leakage and surgical site infection occurred more frequently in high SFA. It might be useful to examine SFA preoperatively in obese patients with esophageal cancer for prevention of postoperative complications. Patients in high VFA tended to be longer survival than those in normal VFA.
Effect of multiagent chemotherapy and chemoradiotherapy on rates of resection and survival in patients with locally advanced pancreatic cancer: a National Cancer Database Analysis.
Authors: David John , Kim Sungjin , Anderson Eric , Torossian Arman , Lo Simon , Nissen Nicholas N. , Hendifar Andrew Eugene , Tuli Richard 
Published: January 2019

391 Background: The role of multiagent chemotherapy (MAC) has not been prospectively investigated in LAPC and data are extrapolated from randomized trials in patients with metastatic disease. Data regarding the use of chemoradiation (CRT) for LAPC is mixed and similarly there is no prospective data investigating its use after MAC. Herein, we investigate clinical outcomes associated with the use of MAC and CRT. Methods: The National Cancer Database (NCDB) was utilized to identify LAPC patients treated with single agent chemotherapy (SAC), MAC, surgery, and/or CRT. Univariate (UVA) and multivariate (MVA) Cox regression were performed to identify the impact of MAC and CRT on surgical resection and median overall survival (mOS) rates. Results: From 2004-2014, a total of 10139 patients were identified. The median age was 66 years (range 22-90) with median follow up of 49 months (46-52 months); 49.9% were male and 50.1% female. All patients had clinical stage 3/T4 disease irrespective of nodal metastases. All patients who received post-op RT were excluded. Surgical resection was performed in 506 (5%) patients. Median OS rates for patients who received SAC vs. MAC was 9.8 months vs 13.7 months (p < 0.001), respectively. Median OS rates for patients who received SAC/MAC vs. SAC/MAC+CRT was 9.9 months vs. 12.9 months (p < 0.001), respectively. Odds ratio for undergoing surgical resection in patients receiving MAC vs. MAC+RT was not significant. Of the 5% of patients who underwent resection after neoadjuvant therapy, mOS for those who received MAC vs. MAC+RT were 19.4 months and 25.6 months (p = 0.001), respectively. Conclusions: Median OS was improved in patients receiving MAC versus SAC. The use of CRT after chemotherapy led to increased mOS compared to chemotherapy alone. In all patients undergoing surgical resection, the addition of neoadjuvant CRT after MAC led to improved mOS rates. Treatment with MAC followed by CRT should be utilized for all patients with LAPC.
Treatment at high-volume facilities and academic centers in relation to overall survival in patients with locally advanced pancreatic cancer: A National Cancer Database analysis
Authors: David John , Kim Sungjin , Anderson Erik , Torossian Arman , Lo Simon , Nissen Nicholas N. , Hendifar Andrew Eugene , Tuli Richard 
Published: January 2019

392 Background: Numerous studies have shown that treatment at a high volume facility (HVF) for patients (pts) with pancreatic cancer is associated with improved outcomes, particularly with pancreatectomy. In fact, a recent study showed that pts undergoing a pancreatectomy at an academic center (AC) is independently associated with improved outcomes. However, the role of chemotherapy (CT) and radiation (RT) in the treatment of locally advanced pancreatic cancer (LAPC) at HVF and AC, to our knowledge, has not been studied. Herein, we investigate the benefit of treatment at HVF and AC compared to low volume facilities (LVF) and non-academic centers (NAC) with CT or chemoradiation (CRT) in pts with LAPC. Methods: The National Cancer Database (NCDB) was utilized to identify LAPC patients treated at all facility types. All patients were treated with CT or CRT. Univariate (UVA) and multivariate (MVA) Cox regression were performed to identify the impact of HVF and AC on overall survival (OS) when compared to LVF and NAC, respectively. HVF was defined as the top 5% of facilities by number of pts treated. Results: From 2004 – 2014, a total of 10139 pts were identified. The median age was 66 years (range 22-90) with median follow up of 48.8 months (46-52.1 months); 49.9% were male and 50.1% female. All pts had clinical stage 3/T4 disease irrespective of nodal metastases. Of these, 4779 pts were treated at an AC and 5260 were treated at a NAC and 588 were treated at HVF and 9551 were treated at LVF. On UVA, age, high median income, high education level, comorbidities, and recent year of diagnosis were associated with improved OS. ACs were associated with improved OS when compared to non-AC (HR 0.92 95% CI 0.88 – 0.96, p = 0.004), as were HVF when compared to LVH (HR 0.84 95% CI 0.76 – 0.92, p < 0.001). Odds ratio for undergoing surgical resection at HVF and AC was 1.68 and 1.37 (p < 0.001), respectively, when compared to LVF and NAC. Conclusions: The treatment of LAPC patients with CT or CRT at an AC led to significantly improved rate of surgical resection and OS. In the absence of prospective data, these results support the referral of pts with LAPC to HVF and/or AC for evaluation and treatment.
Safety and outcomes of an oncologic robotic whipple program.
Authors: Powers Benjamin D , Pimiento Jose Mario , Saeed Sabrina D , Deperalta Danielle , Hodul Pamela Joy , Fleming Jason B. , Malafa Mokenge Peter 
Published: January 2019

393 Background: Robotic-assisted surgery is a new technology being used more commonly in surgical oncology. We evaluated the outcomes of robotic pancreaticoduodenectomy over time from a single U.S. cancer center. Methods: The Moffitt Cancer Center Tumor Registry was queried for robotic pancreaticoduodenectomy cases performed by two surgeons from 2012-2017 after IRB approval. Descriptive statistics and analyses with t-test and chi-square test were performed. Results: 61 case were analyzed; the first cohort comprised 31 cases and the second cohort comprised the next 30 cases. The most common pre-operative diagnosis was adenocarcinoma. For the entire cohort, the estimated blood loss was 498mL, ASA class was 2.5, and OR duration 546 minutes. The first cohort had 14 conversions to open Whipple and the second cohort had 11. There were no anesthesia or surgical complications. There was one 30-day mortality and one R1 resection. There was no significant difference in EBL, OR transfusions, or post-op transfusions. There was a significant decrease in the operative time between the two cohorts. Additionally, there was a significant increase in total number of nodes examined in the second cohort, though no difference in the number of positive nodes. Conclusions: In selected patients, robotic pancreaticoduodenectomy is a safe alternative to open pancreaticoduodenectomy. Published data suggest a learning curve of approximately 60-80 cases. In our cohort we observed a significant decrease in OR time and an increase in lymph node retrieval after 31 cases, suggesting an earlier inflection point. Further studies are needed to examine additional follow-up and outcome variables. [Table: see text]