bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes after cessation of therapy with alkylating agents (AA) for pancreatic neuroendocrine tumors (panNETs).
Authors: Wu Linda , Reidy Diane Lauren , Bielska Agata , Kelly Virginia , Raj Nitya Prabhakar 
Published: January 2019

394 Background: There are several therapies now available for panNETs, raising concern that treatment-related toxicity, namely myelosuppression, may preclude use of all treatments. AA are an effective therapy in panNETs, but can cause irreversible bone marrow suppression. For this reason, our institutional approach is to treat patients (pts) with AA for a defined time period of up to 12 months prior to a treatment holiday; anecdotally, we observed continued disease shrinkage or stability after drug cessation. We aimed to identify and characterize these exceptional responders (ER). Methods: We retrospectively identified pts with well differentiated panNETs treated at MSKCC with AA from 2007 to present, and identified those that were placed on a treatment holiday after response to therapy. Pts with continued disease response by radiographic report (tumor shrinkage or stable disease) for greater than 9 months while on a treatment holiday were considered exceptional responders (ER). Results: 124 patients were evaluable, with 104 pts (84%) receiving temozolomide and 18 pts (15%) receiving dacarbazine. 40 (32%), 57 (46%), and 22 (18%) pts had low, intermediate and high-grade tumors, respectively. 80 pts (65%) achieved a response to AA and 21 pts (17%) responded to therapy initially with subsequent disease progression. In total, 58 pts (47%) entered a treatment holiday; 39/58 pts (67%) were ER and 16/58 pts (28%) had disease growth in < 9 months. No significant differences in tumor grade ( P = 0.85) were seen between ER and those who had disease growth in < 9 months. Next generation sequencing results were available in 17 tumors of pts classified as ER; 14/17 (82%) with alterations in chromatin remodeling genes ( MEN1/DAXX/ATRX). Upon disease progression, 11 ER were reintroduced to alkylating agents; 9/11 (82%) had progressive disease or death after reintroduction of drug, and 2/11 (18%) responded and went on a second treatment holiday. Conclusions: We observed durable responses to AA after cessation of therapy. Many of the ER tumors harbored alterations in chromatin remodeling genes. Reintroduction of alkylating agents upon disease progression was generally ineffective.
The correlation between the proportion of patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and overall survival between 2004 and 2015.
Authors: Molina George , Chawla Akhil , Clancy Thomas E. , Wang Jiping 
Published: January 2019

395 Background: Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is associated with improved overall survival (OS), and this has led to its rising use. The aim of this study was to evaluate the correlation between use of NAT and OS among patients with PDAC. Methods: This population-level study evaluated the Spearman correlation between the annual proportion of patients receiving NAT and the annual 1-year and 5-year OS, respectively, using the 2004-2015 National Cancer Database. Annual 1-year and 5-year OS was calculated from year of diagnosis using Kaplan-Meier survival analysis. All patients with a confirmed diagnosis of PDAC (histology code 8500), without any metastasis, and who underwent an R0 or R1 resection were included. Results: A total of 18,852 patients (median age 67 (IQR 60–74); 49.4% female) with PDAC underwent an R0/R1 resection from 2004 to 2015. Among these patients, there was a significantly positive correlation between the proportion of patients who received NAT (12.1%; n = 2,133) and 1-year OS (Spearman’s rho = 0.9091; P = 0.0001) and 5-year OS (Spearman’s rho = 0.7833; P = 0.01), respectively. Patients who underwent R0 resection (n = 14,547; median age 67 (IQR 60-74); 49.9% female) had a significantly positive correlation between those who received NAT (13.1%; n = 1,773) and 1-year OS (Spearman’s rho = 0.8818; P = 0.0003) and 5-year OS (Spearman’s rho = 0.7333; P = 0.02), respectively. Among 9,142 patients who had upfront resectable disease with R0 resection margin status (median age 68 (IQR 60–75); 49.8% female), there was a significantly positive correlation between proportion of patients who received NAT (9.1%; n = 781) and 1-year OS (Spearman’s rho = 0.7273; P = 0.01) and 5-year OS (Spearman’s rho = 0.8000; P = 0.0096), respectively. Conclusions: Between 2004 and 2015 there has been an increase in the use of NAT for patients with PDAC. Concurrently, the OS has also increased during this time period. This study demonstrates that there is a statistically significant and positive correlation between the proportion of patients with R0/R1 resected PDAC who received NAT and 1-year OS and 5-year OS, respectively.
Impact of direct-acting antivirals and 12-week sustained viral response on clinical outcomes in patients with hepatitis C and hepatocellular carcinoma.
Authors: Kamp William M , Sellers Cortlandt , Stein Stacey , Lim Joseph K , Kevin Kim Hyun S. 
Published: January 2019

397 Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C viral infections (HCV). Methods: Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Results: Nine hundred ninety-six patients met inclusion criteria (mean age 62.8±10.2 yrs, 79% male). Four hundred seventy-eight (50%) patients received interventional oncology (catheter-based therapies, ablation and combination locoregional therapies), 141 (15%) received supportive care (palliative or no treatment), 125 (13%) received a transplant, 112 (14%) had tumor resection and 94 (12%) received chemotherapy or radiation as their primary treatment. Median overall survival (OS) of the entire cohort was 24.2 months (95% CI: 20.9-27.9). Transplant patients were excluded from further analysis. Four hundred seventy patients had HCV (56%). One hundred twenty-three patients received one or more DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCC occurrence and recurrence were reported in 29 (26%) and 38 (45%) patients, respectively, after DAA therapy. HCV-positive and HCV-negative patients had similar survival (OS 20.7 mo vs 17.4 mo, p=0.22). Patients receiving DAA therapy had a higher OS of 71.8 mo (CI: 39.5-not reached) vs 11.6 mo (CI: 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had a higher OS of 75.6 mo (CI: 49.2-not reached) vs the non-SVR12 group (26.7 mo, CI: 13.7-31.1, p<0.0001). Multivariable analysis (MVA) showed that AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment allocation had independent influence on survival for the cohort (p<0.05). In HCV patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p<0.05). In patients receiving DAA, only MELD score and SVR12 remained significant factors (p<0.05). Conclusions: DAA therapy and achieving SVR12 is associated with increased overall survival in HCC patients with HCV. This analysis supports the importance of treating HCV to SVR12 as part of HCC management.
Incidence of and risk factors (RFs) for development of non-alcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) for pancreatic cancer: A single institutional review.
Authors: McGhee-Jez Amy , Ahuja Amisha , Nahar Ritu , Shah Samik , Loh Rebecca , Houtmann Sarah , Shah Rashesh , Chervoneva Inna , Lavu Harish , Cohen Steven J. , Halegoua-De Marzio Dina , Basu Mallick Atrayee 
Published: January 2019

398 Background: PD may increase the risk of development of NAFLD, a precursor for non-alcoholic steatohepatitis and cirrhosis. Studies have not clearly identified consistent RFs for NAFLD, but patients with post-PD NAFLD do not appear to have the traditional RFs for NAFLD such as metabolic syndrome. The primary objective of this study was to identify the incidence of and RFs for post-PD NAFLD. Methods: Retrospective chart review was done on 425 patients who underwent PD for a cancer diagnosis at our institution from 2007 to 2017 and had at least 6 months of postoperative follow up. Cox proportional hazards model was used to examine multiple potential pre-operative RFs for NAFLD including body mass index (BMI), estimated surgical blood loss, LFTs, hemoglobin, albumin, age, sex, comorbidities, and tobacco use as predictors of time to develop post-PD NAFLD. Patients without post-PD NAFLD were considered censored at the time of last follow-up. The proportional hazard assumptions were validated. Post-PD NAFLD was identified by review of radiology reports. Results: Sixty (14.1%) of the 425 patients had post-PD NAFLD. The male to female ratio was 236:189 and median follow up time was 1 year. Median age was 65 years with median time to NAFLD development of 7 months. Multivariate Cox Proportional Hazard model identified higher BMI and female sex as RFs for the development of post-PD NAFLD. Each 1-point increase in BMI implied an 8.43% increase in the hazard of fatty liver (HR = 1.083, 95% CI: 1.032-1.136; p=0.001). Females had 89.7% higher hazard of fatty liver compared to males (HR = 1.897, 95% CI: 1.084 - 3.319; p=0.025). There was no statistically significant association between post-PD NAFLD and other pre-operative characteristics studied. Conclusions: Female sex and higher BMI may be RFs for the development of NAFLD post-PD. No other pre-operative RFs were identified. In conclusion, patients with higher BMI and female gender may need closer monitoring for earlier detection and management of NAFLD. [Table: see text]
Impact of new chemotherapy regimens on the treatment landscape and survival of advanced pancreatic cancer (PAC) patients (pts).
Authors: Kieler Markus , Unseld Matthias , Bianconi Daniela , Scheithauer Werner , Prager Gerald W. 
Published: January 2019

403 Background: The clinical phase III first-line trials MPACT and PRODIGE4/ACCORD11 in metastatic PAC pts have changed the treatment paradigm. We aimed to analyse the impact of these regimens on the treatment landscape and survival of advanced PAC pts. Methods: In this single institutional retrospective cohort analysis patient characteristics and overall survival (OS) from all pts with advanced PAC treated between 01/2011-12/2017 were analysed. Survival analyses were performed by Kaplan-Meier method. Results: A total of 301 pts started a systemic treatment in the observation period. Concerning the first-line treatment, there was a clear shift from four different main regimens (gemcitabine/nab-paclitaxel (G+nab-P), FOLFIRINOX, gemcitabine/oxaliplatin +/- erlotinib, gemcitabine mono) to only two (G+Nab-P, FOLFIRINOX), that made up more than 80% of the administered first-line treatments in each of the groups (2011-2013 vs. 2014-2017). The rate for first-line FOLFIRINOX treatment was balanced between the two groups (19% and 15%). G+nab-P treated pts had a median age of 66 years, 41.3% had an ECOG 1-2, the FOLFIRINOX treated pts were younger and fitter (57 years and 24.5 % ECOG 1, 0% ECOG 2). 60.7% of pts treated with G+nab-P received a second-line and 30.7% pts received a third-line treatment, while for the FOLFIRINOX pts these rates were 69.8% and 41.5%. Median OS of pts that started first-line treatment between 2011 and 2013 was 8.77 months (95% CI 6.98-10.57) and for those that started first-line treatment between 2014 and 2017 median OS was 11.07 months (95% CI 8.94 13.20) (p = 0.038, Log-Rank-Test). Conclusions: There is a clear impact of new chemotherapy regimens on the treatment landscape. Furthermore, we provide real-world evidence that since the introduction of these new treatment options, the survival of pts with advanced PAC has significantly improved.
Plasma hyaluronan is a predictive marker for pegvorhyaluronidase alfa (PEGPH20; PVHA) response in a phase II study of pancreatic ductal adenocarcinoma (PDAC).
Authors: Taverna Darin , Printz Marie , LaBarre Michael J. , Sekulovich Rose E. 
Published: January 2019

404 Background: Hyaluronan (HA) can be a constituent of the tumor microenvironment (TME). Accumulation of HA in the TME may result in elevated interstitial pressure, vascular compression, hypoxia, and reduced drug delivery and immune cell access. Pegvorhyaluronidase alfa (PEGPH20; PVHA) enzymatically degrades HA, potentially increasing access and antitumor efficacy of cytotoxic and immuno-therapies. Liquid biopsies may provide a non-invasive approach to predict therapeutic efficacy of PVHA. Methods: Total plasma HA was analyzed as a pharmacodynamic biomarker for PVHA activity in HALO 109-202 (NCT01839487), a Phase 2, open-label, two-stage randomized study of PVHA + nab-paclitaxel + gemcitabine (PAG) vs AG only, in previously untreated patients with Stage IV metastatic PDAC. HA was measured with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) disaccharide assay using baseline plasma samples from Stage 1 (n = 132) and Stage 2 (n = 128) of the study. Results: Lower baseline plasma HA values were significantly correlated with survival outcomes, predicting progression-free survival (PFS) benefit in PVHA-treated patients in Stages 1 and 2, and overall survival (OS) benefit in PVHA-treated patients in Stage 2 (Table). Conclusions: These results support further exploration of a liquid biopsy-based companion diagnostic (CDx) for predicting the therapeutic efficacy of PVHA. [Table: see text]
Dynamical changes of treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice.
Authors: Nagai Kazuki , Terashima Takeshi , Yamashita Tatsuya , Kido Hidenori , Hayashi Kotaro , Sunagozaka Hajime , Nakai Ryotaro , Mizuno Hideki , Hayakawa Hikaru , Nomura Yoshimoto , Takata Yoshiko , Orita Noriaki , Takabatake Hisashi , Kanno Masataka , Nishitani Masaki , Omura Hitoshi , Shugo Haruhiko , Ooishi Naoki , Mizukoshi Eishiro , Kaneko Shuichi 
Published: January 2019

407 Background: Several new combination therapies, including GEM plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) has been developed for treating pancreatic ductal adenocarcinoma (PDAC) in these ten years. We investigated trends in characteristics, treatment patterns, and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. Methods: We retrospectively reviewed the medical records of 1917 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in our local area between January 2009 and April 2018. Results: The median age was 74, and 53.1% were men; 27.2% had locally advanced and 67.2% metastatic disease, and 5.6% had recurrences. Oncological therapy was administered to 1295 patients (67.6%): chemotherapy (n = 1161), chemo-radiotherapy (n = 117), or radiotherapy (n = 17); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 56.8% of the 266 patients diagnosed in 2017 or 2018 received GnP, 20.3% GEM, and 15.4% FFX. The objective response rates of patients treated with GnP, FFX and GEM were 16.8%, 17.6%, and 5.1%, respectively. The median time to treatment failures were 3.9, 3.6, and 2.8 months, and the overall survivals were 11.5, 11.7, and 6.5 months after GnP, FFX, and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 53.7%, 64.7%, and 34.6% of the patients treated with GnP, FFX, and GEM, respectively. The treatment discontinuation rates due to adverse events were 17.2%, 14.9% and 22.9% in the patients treated with GnP, FFX and GEM, respectively. Conclusions: Chemotherapeutic protocols changed dramatically between 2009 and 2018 in Japan. Both GnP and FFX are well-tolerable and effective in real-life practice despite high frequent adverse events.
Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).
Authors: Oh Do-Youn , Muhsin Mann , Bullock Andrea J. , Abou-Alfa Ghassan K. , Shroff Rachna T. , Sigal Darren , Chung Vincent , Hecht J. Randolph , Wu Wilson , Borad Mitesh J. 
Published: January 2019

408 Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access, is high (67%) in CCA/GBC tumors. PEGPH20 enzymatically degrades HA. HALO 110-101 (NCT03267940) evaluates safety and activity of PEG-C-G-ATZ or PEG-C-G versus C-G in CCA/GBC pts. Methods: This study comprises two parts. In Run-In (RI) six pts were enrolled in PEG-C-G arm, then six pts in PEG-C-G-ATZ arm. Eight additional pts may be enrolled for tolerability. In Expansion (EX), up to 50 pts will be enrolled for efficacy. Treatment (Tx) cycle is 21 days (d). PEGPH20 dose is 3 μg/kg on d1, eight and 15 and ATZ dose is 1200 mg (one–three hours after PEGPH20) on d1 (PEG-C-G-ATZ only). C-G is dosed at 25 mg/m2 C and 1000 mg/m2 G on d2 and nine. In C-G arm (EX only), C-G is dosed on d1 and 8. Primary endpoints are ORR (RECIST v1.1), AEs (NCI CTCAE v4.03), laboratory/safety (RI only); secondary endpoints are PK; DOR, DCR, PFS; OS, OS by PD-L1 expression; ORR and DOR (imRECIST). Results: Eighteen pts have been enrolled (nine in each arm). The mean (SD) age is 57 (12.2) yrs in PEG-C-G and 69 (8.8) yrs in PEG-C-G-ATZ. 56% were men. All pts experienced ≥ 1 AE. The most common AEs are nausea, fatigue (50% each); decreased appetite (44%); anemia, constipation (39% each); thrombocytopenia, oedema peripheral, AST increased, myalgia (33% each). To date, there has been one dose-limiting toxicity (febrile neutropenia) in the PEG-C-G arm. There have been no deaths due to AEs. Conclusions: The overall safety profile of PEGPH20 + C + G ± ATZ is acceptable and consistent with safety observed for the individual components. There were no DLTs resulting in a dose reduction of PEGPH20, which is being dosed at 3 μg/kg in the EX phase. Clinical trial information: NCT03267940. [Table: see text]
Effect of FOLFIRINOX with PEG-G-CSF for unresectable/recurrent pancreatic cancer.
Authors: Moriyama Ichiro , Sonoyama Hiroki , Kawabata Yasunari , Ikejiri Fumiyoshi , Inoue Masaya , Takahashi Fumimasa , Matsuda Shinichiro , Ugata Norimi , Shimasaki Yasumasa , Fujimoto Ayumi , Okada Yusuke , Ito Shunsuke , Okada Takahiro , Jo Yumi , Takahashi Tsutomu , Miyake Takaaki , Kodama Tatsuo , Suzuki Ritsuro , Tajima Yoshitsugu , Suzumiya Junji 
Published: January 2019

411 Background: FOLFIRINOX (FFX) is a standard therapy for unresectable/recurrent pancreatic cancer, but it is associated with a high frequency of severe adverse events, especially blood toxicity. Human pegylated granulocyte colony-stimulating factor (PEG-G-CSF) can reduce the outpatient frequency during outpatient chemotherapy. However, there are few reports on the effectiveness of PEG-G-CSF in preventing febrile neutropenia during FFX. We retrospectively investigated the usefulness of PEG-G-CSF in reducing the incidence of FN during FFX. Methods: From June 2014 to January 2017, 40 patients with unresectable pancreatic cancer received FFX (including modified FFX) at our hospital. Twenty-three patients were administered PEG-G-CSF as primary/secondary preventive therapy (G group) and 17 were not administered any G-CSF (NG group). Results: The median patient ages in the G and NG groups were 65 (range, 48-78) and 63 (range, 42-81) years, respectively, and the male to female ratios were 13:10 and 11:6, respectively. There were 13 and 10 patients, respectively, in the G group with performance statuses of 0 and 1 and 8 and 9 such patients, respectively, in the NG group. Seventeen and five patients in the G and NG groups, respectively, had metastatic disease and six and two patients, respectively, had locally advanced disease. The respective response rates (RRs) in the G and NG groups were 30% and 6% (p = 0.0608), and the respective disease control rates (DCRs) were 30% and 41% (p = 0.0407). The median progression-free survivals in the G and NG groups were 7.3 (95% confidence interval [CI], 3–9.4) and 4.5 (95% CI, 1.9–8.5) months, respectively (p = 0.173), and the respective overall survivals were 16.9 (95% CI, 10.2–NA) and 14.2 (95% CI, 7.8–20.5) months (p = 0.302). Conclusions: The DCR was significantly greater in the G group than in the NG group, and the RR tended to be greater in the G group than in the NG group. A high tumor shrinking effect of FFX with PEG-G-CSF indicated that it might be useful as a neoadjuvant chemotherapy. A prospective study is needed to examine first-line chemotherapy in unresectable/recurrent pancreatic cancer and neoadjuvant chemotherapy in borderline/locally advanced pancreatic cancer.
Hypofractionated radiation therapy for unresectable/locally recurrent intrahepatic cholangiocarcinoma.
Authors: Smart Alicia , Hong Theodore S. , Petkovska Natasa , Noe Bridget N. , Zhu Andrew X. , Ferrone Cristina , Tanabe Kenneth , Allen Jill N. , Drapek Lorraine C. , Qadan Motaz , Murphy Janet E. , Goyal Lipika , Wo Jennifer Yon-Li 
Published: January 2019

412 Background: Our objective was to evaluate outcomes for patients with unresectable/locally recurrent intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). Methods: We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008-18. 51 patients had intrahepatic disease only, and 15 patients had extrahepatic disease at time of RT but received RT for biliary control. Median age at RT was 76 years (range: 30-92), including 27 patients (41%) ≥ 80 years. Median RT dose was 58.05 Gy (range: 37.5-67.5), delivered in 15 daily fractions. 32 patients received proton RT, and 34 patients received photon RT. Rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the Cox proportional hazards method. For multivariate analyses, variables with p < 0.5 on univariate analysis were evaluated by backwards selection. Results: Median follow-up times from diagnosis and RT start were 21 and 14 months, respectively. In total, 5 patients (7.6%) developed local failure. Only 1 patient developed isolated local failure. The 2-yr outcomes were 93% LC, 37% PFS, and 55% OS. Among the 51 patients treated with definitive intent, the 2-yr LC was 96%, PFS 35%, OS 60%. Receipt of protons was significantly associated with younger age (p = 0.02), but not gender, race, ECOG status, metastatic disease at presentation, mean liver dose, cumulative GTV, or number of lesions. There were no significant predictors of LC or PFS, including RT dose. On UVA for OS, younger age, female gender, prior chemotherapy, prior surgery, and proton RT were associated with improved OS (p < 0.05). On MVA, female gender (HR: 0.33, p = 0.001), prior chemotherapy (HR: 0.38, p = 0.002), and proton vs. photon RT (HR: 0.50, p = 0.05) remained significantly associated with OS. Conclusions: HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent IC. HF-RT should be considered for elderly patients who are considered medically inoperable. Proton RT and chemotherapy may further improve outcomes.