bluuebunny/crossref_metadata_2025 huggingface dataset:
Costs of care with liver directed therapy (LDT) and sorafenib (S) in patients (pts) with hepatocellular carcinoma (HCC).
Authors: Singavi Arun K. , Szabo Aniko , Thomas James P. , Ritch Paul S. , Alqwasmi Abdel , White Sarah , Rilling William S. , George Ben
Published: January 2019

383

Background: 80% of HCC pts present with advanced disease, treatment for such pts is palliative in nature. It is important to ascertain cost associated with such palliative therapy, considering modest survival benefit afforded by these treatments. Methods: Utilizing a non-Medicare national claims database (MarketScan), we analyzed a cohort of pts with HCC diagnosis (Dx). Consistent with literature, pts selected had at least two claims with HCC code (155.0) between 1/1/2010 and 12/31/2013, at least 2 claims with chronic liver condition within 1 year of the HCC Dx, no claims for other malignancies for 1 year before HCC Dx, and excluded hepatectomy or transplant. Follow up was from date of first HCC claim to end of continuous insurance coverage (EOC) with prescription drug claim tracking, or 12/31/2015. Pts were divided into 4 groups based on receipt of S, LDT, combined therapy (LDT+S), or best supportive care (BSC) after HCC Dx. Costs obtained by adding payment (Pmt) amounts for all inpatient, outpatient, and drug claims over follow-up period. Demographics and costs were summarized using means for continuous and frequencies for categorical variables. No adjustment for censoring was done, as no reason available for EOC. Average monthly cost was computed for each pt, and then averaged over pts. Results: Data were available for 6,987 patients over specified period, 67% were males, mean age was 60.2 years. Cost data by therapy received are summarized in the table below. Conclusions: Majority of HCC pts in this database were treated with BSC. Time to EOC tracked was significantly shorter for pts treated with S, compared to other 3 groups. Monthly cost associated with LDT, LDT+S, and S were not substantially different, but higher than cost associated with BSC. Prospectively collected survival, quality of life and cost data are important to ascertain true impact of palliative therapy in pts with advanced HCC. [Table: see text]
Adjuvant therapy for margin positive pancreatic cancer.
Authors: Takahashi Caitlin , Shridhar Ravi , Harris Cynthia L. , Lee Justin , Patel Anjan Jayantilal , Brown Richard H. , Huston Jamie , Kucera Stephen , Meredith Ken Lee
Published: January 2019

390

Background: Pancreatic cancer continues to have a dismal prognosis despite improvements in surgical care. Approximately 26% of patients are deemed resectable, and at the time of operation, 28% will have R1 resections. Adjuvant chemotherapy (AC) or chemoradiation (CRT) is recommended, however the magnitude of benefit is unclear. We sought to examine the impact these therapies on R1 resected pancreatic cancer. Methods: Utilizing the National Cancer Database we identified patients who underwent pancreatic resection for adenocarcinoma. Patients were stratified by resection status and adjuvant therapy. Baseline comparisons of patient characteristics were made using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional models(MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α <0.05 was considered significant. Results: We identified 28,440 patients: 22,005 (77.4%) underwent R0 resections and 6,435 (22.4%) underwent R1 resections with a median age of 67.5 years (18-90) and median tumor size of 3.1 cm (2.4-4.2). Patients with tumor size >2cm were more likely to undergo R1 resections, p<0.001. Within the R1 resection group, AC was administered in 1,802 (19.4%), CRT 2,153 (28.5%), and no adjuvant therapy (NA) 2,480 (21.4%). Adjuvant therapy improved survival in all patients with median and 5-year survival of: AC (21.7 months, 17.45%), CRT (23.3 months, 20.9%) vs NA (19.5 months, 19.1%), p<0.001. In the R1 resection cohort survival was also improved with adjuvant therapy with CRT demonstrating the most significant improvement: AC (15.9 months, 6.5%), CRT (18.7 months. 11.2%) vs NA (12.5 months, 8.7%), p<0.001. Additionally CRT but not AC improved survival in the R1 node negative, p<0.004, and node positive, p<0.001. AC benefited survival in R1 node positive patients, p<0.001. MVA revealed age, tumor grade, tumor size >2cm, T-stage, N-stage, AC, and CRT were predictive of survival. Conclusions: Patients with pancreatic cancer who undergo R1 resection have significant improvement in survival when treated with adjuvant CRT and AC. However, benefits were greater in those receiving adjuvant CRT.
Stereotactic body radiotherapy for hepatocellular carcinoma in patients with poor liver function.
Authors: Chan Jason , Behr Spencer , Pai Jonathan , Feng Mary Uan-Sian , Chang Albert , Haas-Kogan Daphne A. , Anwar Mekhail
Published: January 2019

397

Background: Stereotactic body radiation therapy (SBRT) may benefit patients with hepatocellular carcinoma (HCC) who are not candidates for other liver-directed therapies due to poor liver function (plf). However, optimal patient selection, safety, and efficacy of SBRT in plf-HCC patients are not known. We studied dosimetric, baseline liver function, and radiographic features at the time of treatment that may help identify HCC patients with liver dysfunction who would benefit most from SBRT. Methods: Medical records of plf-HCC patients with cirrhosis treated with SBRT at a single institution between 2013-2016 were reviewed. Prescription doses were tailored to liver function based on INR and total bilirubin (tBili) and uninvolved liver volume. Time to local progression was evaluated using cumulative incidence analysis (Gray’s test) and competing risks regression analysis. Local progression was defined using RECIST criteria. Overall survival was estimated using the Kaplan-Meier method and Cox proportional hazards model. Results: 26 plf-HCC patients with median baseline MELD 11 (range 1-35), tBili 1.6 (0.5-6.5), INR 1.2 (1.0-9.0), tumor size of 4.1 cm (1.7-8.5 cm), and liver volume 1251 cc (596-2322 cc) were treated with SBRT. 54% received SBRT for retreatment of the same tumor. Patients were heavily pretreated with 50%, 19%, and 8% previously receiving TACE, ethanol ablation, and RFA, respectively. With a median prescription of 30 Gy (8-50 Gy) in 5 fractions (2-5), the median liver dose was 8 Gy (3-14 Gy). Median increase in MELD 90 days post-SBRT was 1.1 (0-19), with 35% experiencing no increase and 25% increasing >2.5. Local control (LC) was 55% at 6 months with one patient bridged to liver transplant. LC was not associated with improved survival (p = 0.39) and median overall survival (MS) was 8.6 months (0.9-31.7 mo). However, longer MS was seen for patients without ascites (MS=16.5 vs. 4.1 mo, p = 0.005), tBili < 2 (MS=16.5 vs. 5.2 mo, p = 0.015) and MS was not reached in patients treated to > 30 Gy (p = 0.04) or with MELD < 11 (p = 0.02). Conclusions: In this cohort of HCC patients with poor liver function, the absence of ascites, tbili < 2, and lower MELD scores were associated with improved survival following SBRT.
Final report: A phase I trial of BYL719 in combination with gemcitabine and nab-paclitaxel in locally advanced and metastatic pancreatic cancer.
Authors: Soares Heloisa P. , Al-Toubah Taymeyah E. , Kim Richard D. , Kim Jongphil , Lewis Neron K , Mahipal Amit
Published: January 2019

398

Background: The PI3K/mTOR pathway has emerged as a potential target for anticancer therapy. Considerable evidence suggests that targeting a single isoform of PI3K (p110α) would have sufficient antitumor activity and improved therapeutic window. Further, PI3KCA mutations, gene encoding isoform p110α, are described in pancreatic adenocarcinoma (PAC). BYL719 is an oral class I α-specific PI3K inhibitor that showed preclinical anti-tumor activity. The first in human phase 1 trial of BYL719 defined the maximum tolerated dose (MTD) at 400mg QD. Methods: This was a phase I, single center study (standard 3+3 design). The primary objective was to determine the MTD of BYL719 in combination with gemcitabine (G) and nab-paclitaxel (nabP) as frontline therapy in locally advanced or metastatic PAC. BYL719 was given orally daily (Table). Patients (pts) were restaged q2 cycles. The study was closed prematurely due to slow accrual. Results: Fifteen pts were enrolled (median age was 58 years). Three pts each participated in cohorts 1 and 2. Nine pts were enrolled in cohort 3, but 4 were replaced (3 pts withdrew consent prior to evaluation and 1 missed > 10 days of treatment). One pt in cohort 3 had DLT related to grade 3 nausea and vomiting. A total of 19 grade 3 and 4 adverse events were records as probably or possibly associated with BYL719. The most common ones were hyperglycemia, anemia, and neutrophil count decreased. One pt developed Posterior reversible encephalopathy syndrome (PRES) during cycle 7. Although we could not completely exclude BYL719 as a cause, PRES was attributed to G. One pt had sudden death during cycle 4 that was attributed to progression. Only 8 pts were evaluable for response. Two had stable disease, 5 had partial responses and 1 had progression. The median progression-free survival and overall survival were 5.36 months (1.6 to 10 months) and 8.74 months (3.8 to 21.2 months) respectively. Conclusions: The combination of full doses of G + nabP and BYL719 can be safely administered up to BYL dose of 250 mg/day. Clinical trial information: NCT02155088. [Table: see text]
Intraperitoneal immunotherapy with the bispecific anti-EpCAM x anti-CD3 directed antibody catumaxomab for patients with peritoneal carcinomatosis from gastric cancer: Final results of a randomized phase II AIO trial.
Authors: Lordick Florian , Kunzmann Volker , Trojan Jorg , Daum Severin , Schenk Michael , Kullmann Frank , Schroll Sebastian , Behringer Dirk M. , Stahl Michael , Al-Batran Salah-Eddin , Ibach Stefan , Koerfer Justus , Knoedler Maren Kristina
Published: January 2019

4

Background: The peritoneal surface is a common location for metastases in gastric cancer (GC). Intraperitoneal (i.p.) application of the bispecific (anti-EpCAM/CD3) monoclonal antibody catumaxomab (CATU) in addition to i.v. chemotherapy may improve elimination of peritoneal carcinomatosis (PC). Methods: This randomized open-label phase II study aimed to investigate the efficacy of i.p. CATU following i.v. chemotherapy in patients (pts) with GC and PC (Gilly stages P1-4). Pts were randomly allocated to receive four cycles of FLOT (5FU, LV, Oxaliplatin, Docetaxel) followed by i.p. CATU at escalating doses (10, 20, 50, 150µg) on days 0, 3, 7, 10 or FLOT alone. Secondary gastrectomy and peritonectomy were allowed to achieve complete resection of all malignant lesions. The primary endpoint was to show an increased rate of macroscopic complete remission of PC at second-look surgery. Secondary endpoints included toxicity, progression-free and overall survival (PFS/OS). Results: Of 35 pts screened, 31 were enrolled. Median follow-up time is 52 months. 15 pts were allocated to FLOT-CATU (arm A) and 16 to FLOT alone (arm B). Complete remission rate of PC was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects with i.p. CATU were nausea (15%), fever (23%), abdominal pain (31%), and elevated liver enzymes (gGT 31%, bilirubin 23%). Adverse events tended to be more common during FLOT-CATU compared to FLOT alone. Median PFS was not significantly different in both arms with 6.7 months in arm A compared to 5.4 months in arm B (p = 0.71). Median OS was 13.2 and 13.0 months. Conclusions: Addition of i.p. CATU as part of a multimodal treatment approach revealed feasible and tolerable in pts with GC and PC. Although the primary endpoint was not met, the results are promising for future trials investigating i.p. immunotherapy in this patient population. Clinical trial information: NCT01504256.
Surrogacy of time to prgression for overall survival in advanced hepatocellular carcinoma treated with systemic therapy: A systematic review and meta-analysis of randomized controlled trials.
Authors: Terashima Takeshi , Yamashita Tatsuya , Arai Kuniaki , Toyama Tadashi , Kawaguchi Kazunori , Kitamura Kazuya , Yamashita Taro , Sakai Yoshio , Mizukoshi Eishiro , Honda Masao , Kaneko Shuichi
Published: January 2019

403

Background: Time to progression (TTP) is widely used as the endpoint in early-phase trials for advanced hepatocellular carcinoma (HCC). However, the relevance of using TTP as a surrogate marker for overall survival (OS) in pivotal trials remains uncertain. Methods: The PubMed database and ASCO meeting library were searched for reports of randomized controlled trials that investigated patients with advanced HCC, included data for both OS and TTP, and were launched between 2009 and 2016. Correlation between hazard ratios (HRs) for TTP and OS was determined using weighted linear regression. Correlations between median OS and TTP, and between median OS and post-progression survival (PPS), defined as the period obtained by subtracting median TTP from median OS, were also evaluated. Results: The database search yielded 24 trials with 50 arms. Overall, TTP HR correlated with OS HR (R = 0.73); however, the coefficient in the regression equation was 0.48. When trials were stratified by treatment line, TTP HR was more strongly correlated with OS HR in second-line (R = 0.91) than in first-line (R = 0.77) settings. Correlation between median OS and median TTP was weak (R = 0.50), whereas the correlation between median OS and median PPS was strong (R = 0.78). Conclusions: In advanced HCC, the OS HR can be predicted from the TTP HR, especially in second-line trials, which is useful when considering whether to proceed to a pivotal trial based on the results of early-phase trials. However, TTP may not be appropriate as a primary endpoint in a pivotal trial if the trial aims to evaluate the survival benefit of novel agents because improvement of TTP cannot fully reflect improvement of OS because of the impact of PPS on OS.
A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (MOBILITY-002 Trial, NCT02428270).
Authors: Aung Kyaw Lwin , McWhirter Elaine , Welch Stephen , Wang Lisa , Lovell Sophia , Stayner Lee-Anne , Ali Saara , Malpage Anne , Makepeace Barbara , Ramachandran Makilpriya , Dhani Neesha C. , Hedley David W. , Knox Jennifer J. , Siu Lillian L. , Goodwin Rachel Anne , Bedard Philippe L.
Published: January 2019

409

Background: MEK (mitogen-activated protein kinase kinase) is activated through mutated KRAS in > 90% of PDAC. Focal adhesion kinase (FAK) integrates signals from integrins and growth factor receptors. MEK and FAK are frequently co-activated in PDAC providing a rationale for dual inhibition with GSK2256098, an oral FAK inhibitor, and trametinib, an oral allosteric MEK1/2 inhibitor. Methods: Patients with advanced PDAC patients who progressed after first line chemotherapy were treated with GSK2256098 250mg twice daily and trametinib 0.5mg once daily in 28 day cycles. The primary endpoint was antitumor activity measured by clinical benefit (CB; complete response, partial response, or stable disease ≥24 weeks) by RECIST 1.1. We planned to enrol 24 patients using a 2-stage minimax design (p0 = 0.15, p1 = 0.40; alpha = 0.05, power 0.86). The combination would be considered active if > 7/24 response-evaluable patients achieved CB; and inactive if 2/12 or fewer patients achieved CB at the end of stage 1. Response assessment was performed every 2 cycles. Results: Between June/16 and June/17, 16 patients were enrolled. Five were not evaluable for response. Of 11 evaluable patients, 10 had PD as best tumor response and one had SD for 4 months. One response unevaluable patient who had rapidly progressed on 1st line FOLFIRINOX chemotherapy with a basal-like tumor by RNA-sequencing and KRAS amplification achieved clinical stability for 5 months with a > 50% decline in serum CA19-9 after 3 months of treatment and symptomatic improvement. No treatment related Grade≥3 adverse events (AEs) were observed. The most common treatment related grade 2 AEs were acneiform rash (19%), diarrhea (13%), nausea (6%), fatigue (6%), proteinuria (6%), paronychia (6%), and retinal detachment (6%). The median progression free survival was 1.6 (95% CI 1.5-1.8) months and the median overall survival was 3.6 (95% CI 2.7-not reached) months. Conclusions: GSK2256098 and trametinib was well tolerated but was not active in unselected advanced PDAC. Correlative studies are ongoing to evaluate RNA-expression subtypes and dynamic markers of pathway inhibition from serial tumor biopsies and cell free DNA. Clinical trial information: NCT02428270.
Safety and tolerability of 5-FU, irinotecan (IRI), and nab-paclitaxel (FOLFIRABRAX) with genotype-guided dosing of IRI in previously untreated patients with advanced gastrointestinal (GI) malignancies.
Authors: Joshi Smita Suhas , Karrison Theodore G. , Catenacci Daniel V.T. , Peterson Jaclyn D , Zalupski Mark , Phillips Brooke Elizabeth , Sadiq Ahad Ali , Sehdev Amikar , Wade James Lloyd , Picozzi Vincent J. , Amico Andrea Louise , Kozloff Mark , Polite Blase N. , Kindler Hedy L. , Sharma Manish
Published: January 2019

423

Background: 5-FU, IRI, and nab-paclitaxel (NP) are active in advanced GI cancers; the combination (FOLFIRABRAX) has not been evaluated. UGT1A1 clears SN-38, the active metabolite of IRI. UGT1A1*28 polymorphism reduces enzymatic activity and predisposes to severe IRI toxicity. Dose adjustment in patients with this allele may be warranted. Primary objective: to determine the dose-limiting toxicity (DLT) rate of FOLFIRABRAX with genotype-guided dosing of IRI. Secondary objectives included determining objective response rates (ORR) in GI cancers. Methods: Pts with previously untreated GI cancers and ECOG performance status 0/1 received FOLFIRABRAX with prophylactic pegfilgrastim Q14 days. CT scans were obtained Q8 weeks. UGT1A1 *1/*1, *1/*28, and *28/*28 patients (pts) received initial IRI doses of 180, 135, and 90mg/m2, respectively. 5-FU 2400mg/m2 over 46 hours (no bolus), leucovorin 400mg/m2, and NP 125mg/m2 were given IV Q14 days. DLT during cycle 1 was defined as Grade (Gr) 3/4 febrile neutropenia (FN), Gr 4 neutropenia ≥ 5 days, Gr 3/4 non-hematologic toxicity despite medical management, or treatment delay > 14 days due to toxicity. Doses were tolerable if DLT rate during cycle 1 was ≤ 35%. Enrollment of 17 pts per genotype would allow for an α level of 0.05 with 80% power under a sequential toxicity monitoring procedure, with 6 or fewer DLTs being tolerable. Results: 39 pts are evaluable for toxicity: 23 pancreatic cancer (PC), 6 gastroesophageal cancer (GE), 9 biliary tract cancer (BTC), 1 neuroendocrine. DLTs were observed in 4/20 (20%) *1/*1 pts, 1/15 (7%) *1/*28 pts, and 0/4 *28/*28 pts. DLTs were Gr 3 diarrhea (2 pts), Gr 3 nausea (2), and Gr 3 FN (1). ORR is 6/29 (21%), with responses in PC (3/17 evaluable pts, 18%) and GE (3/5 pts, 60%), but no responses in BTC (0/7 pts). Conclusions: FOLFIRABRAX with genotype-guided dosing of IRI is tolerable in pts with advanced GI cancers and UGT1A1*1*1 or UGT1A1*1*28 genotypes. There is activity in PC and GE but not in BTC. Accrual is ongoing to the 3 genotype cohorts to a goal of 51 pts. Study conducted by the University of Chicago Personalized Cancer Care Consortium Clinical trial information: NCT02333188.
Comparative efficacy and safety of sorafenib in elderly versus non-elderly patients with advanced hepatocellular carcinoma (HCC) with varying liver dysfunction.
Authors: Arora Sukeshi Patel , Ketchum Norma S. , Gelfond Jonathan , Michalek Joel , Mahalingam Devalingam
Published: January 2019

430

Background: Sorafenib is the only FDA-approved systemic therapy for advanced HCC. The incidence of HCC increases with age, peaking above 70 years; however, we have limited efficacy and safety data in the elderly. Given the prevalence of HCC in South Texas, we assessed the efficacy and safety of sorafenib in the elderly. Methods: Retrospective analysis of HCC patients (pts) receiving sorafenib from 2008-2013. PFS and OS were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Differences between age groups (65+, < 65) for dose reduction (yes, no), and AEs were analyzed using Fisher’s Exact Test. Results: A total of 118 pts were included. Median age 57 (range 41-93; 65+ 26%). males 81%. Hispanic 73%, Non-Hispanic White 24%. ECOG PS 0–1 93 %. Causes of cirrhosis: Hepatitis C 66%, Hepatitis B 4%, EtOH 58%. Portal vein thrombosis 36%, Extrahepatic disease 38%. Child-Pugh score: A 56%, B 44%. BCLC class: B 13%, C 87%. Among 113 pts 34% were started at 400 mg daily versus 66% started at 800 mg daily. mOS was 11.2 months (mo) (95% CI: 7.8-14.0), mPFS 5.2 mo (95% Cl: 3.9-7.1). In subgroup analysis, mOS for < 65 was 10.2 mo vs 13.5 mo for 65+ (HR 0.67, 95% CI: 0.39-1.16, p = 0.15). mPFS for < 65 was 4.6 mo vs 6.2 mo for 65+ (HR 0.92, 95% CI: 0.58-1.45, p = 0.71). Among 109 pts, dose reductions in < 65 vs 65+ were 64.6 vs 70% (P = 0.66); survival differences were not statistically significant. Among 75 pts there was a trend to improved survival in 65+ patients with AST/Platelet Ratio (APRI) < / = 1.68, but not statistically significant. Sorafenib was tolerated in the elderly. In regards to nausea, fatigue, diarrhea and hand foot syndrome, difference in toxicity was not statistically significant in < 65 versus 65+. Conclusions: In advanced HCC, elderly pts should be offered sorafenib, as it has efficacy and is tolerated in the elderly. Further prospective studies in the elderly are warranted, with evaluation of APRI as a prognostic marker.
A pilot study of vinorelbine safety and pharmacokinetics (PKs) in patients (pts) with varying degrees of liver dysfunction (LD).
Authors: Gong Jun , Cho May Thet , Gupta Rohan , Synold Timothy W. , Frankel Paul Henry , Ruel Christopher , Fakih Marwan , Chung Vincent M. , Lim Dean , Chao Joseph
Published: January 2019

432

Background: Prospective data to support dosing guidelines for intravenous (IV) vinorelbine in pts with LD are limited. One study recommends standard 30 mg/m2 weekly for total bilirubin ≤2 mg/dL and a 50% dose reduction for bilirubin > 2 mg/dL. Another study recommends no dose modifications for bilirubin up to 3X the upper limit of normal (ULN). This phase I study describes the safety and PKs of vinorelbine in pts with varying degrees of hepatic impairment. Methods: Pts with treatment-refractory solid tumors received weekly IV 30 mg/m2 vinorelbine for normal liver function, 20 mg/m2 for mild LD defined as bilirubin < 1.5 mg/dL but aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 1.5-2.5X ULN or alkaline phosphatase (ALK) 1.5-3X ULN, 15 mg/m2 or 30 mg/m2 for moderate LD defined as bilirubin 1.5-3.0 mg/dL and/or AST/ALT > 2.5 or ALK > 3X ULN, and 7.5 mg/m2 or 20 mg/m2 for severe LD defined as bilirubin > 3.0 mg/dL. Vinorelbine PKs were evaluated to describe its relationship with liver function. Results: 47 patients were enrolled (61.7% gastrointestinal and hepatobiliary cancers) and a total of 248 treatment-related adverse events (AEs) occurred. All-grade myelosuppression was the most common AE overall (41.1%). Out of 71 grade ≥3 AEs, 17 (23.9%) were grade 4 in severity with the majority (15/17) being myelosuppression. Rates of grade 4 hematologic AEs in the normal liver function and the 7.5 mg/m2 severe LD group were low ( < 10%). 4/17 grade 4 hematologic AEs were observed in the mild LD group while the remainder and majority occurred in the moderate-severe LD groups. Vinorelbine PKs were not correlated with the degree of LD, however free drug levels or levels of the active metabolite 4-O-deacetylvinorelbine were not measured. Conclusions: Weekly vinorelbine at 30 mg/m2 and 7.5 mg/m2 appears safe with normal liver function and severe LD, respectively. High rates of grade 4 myelosuppression with 15-30 mg/m2 vinorelbine in moderate-severe LD raise concerns for its safety in this population. Vinorelbine PKs are not affected by LD. However, it is possible that levels of the active metabolite could be higher in pts with LD if its elimination is impacted by LD to a greater extent than the parent drug. Clinical trial information: NCT00540982.
TACE combined with apatinib for the treatment of BCLC stage C of hepatocellular carcinoma: A restrospective controlled study.
Authors: Kan Xuefeng , Xiong Bin , Wang Yong , Liang Bin , Zhou Guofeng , Zheng Chuansheng
Published: January 2019

445

Background: To access the safety and effcacy of transarterial chemoembolization (TACE) combined with apatinib (TACE-apatinib) for the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C of hepatocellular carcinoma (HCC). Methods: The medical records of 290 consecutive patients with BCLC stage C of HCC who underwent TACE-apatinib or TACE-alone from June 2015 to June 2017 were retrospectively reviewed. a-Fetoprotein (AFP) response at 4 weeks after treatment in the two groups were evaluated. Tumor response in the two groups were assessed according to modified Response Evaluation Criteria in Solid Tumors (m-RECIST) criteria. The time to tumor progression (TTP) and overall survival (OS) of patients in the two groups were evaluated respectively. Results: One hundred and ninety patients were included in the analysis; 95 patients underwent TACE-apatinib and 95 underwent TACE-alone. The baseline characteristics of patients between the two groups were comparable. The disease control rate (DCR) of tumor and AFP response in TACE-apatinib group was significantly greater than that of TACE-alone group ( P < 0.001). The median TTP was 14.0 months in the TACE-apatinib group and 3.0 months in the TACE-alone group, and the median OS was 17 months in the TACE-apatinib group and 6.0 months in the TACE-alone group. Apatinib-related adverse events of grade 3 occurred in 14 patients in TACE-apatinib group, and there was no occurrence of grade 4 adverse event. Conclusions: The adverse effects of apatinib were acceptable, and TACE-apatinib improved the outcomes for patients with BCLC stage C of HCC in comparison to TACE-alone.
Disparities in surgical resection for pancreatic cancer stratified by insurance coverage.
Authors: Hegde Sheetal , Kintada Jaswanth , Peña Miren , Rouhani Sammira , Seifi Ali , Kumar Pratap , Shah Dimpy
Published: January 2019

451

Background: Roughly 50,000 Americans are diagnosed with pancreatic cancer yearly (Howlader, N, Noone, A, Krapcho, M. Cancer Stat Facts: Pancreas Cancer. http://seer.cancer.gov/statfacts/html/pancreas ). High mortality rates following pancreatic cancer make surgical resection the primary curative method for treatment. Literature suggests significantly higher mortality rates (12.3%) in patients classified as government payers vs those with private insurance (7.3%) (Glasgow, RE, Mulvihill, SJ (1996)). Hospital volume influences outcome in patients undergoing pancreatic resection for cancer. Western journal of medicine, 165(5),294). This study investigated disparities in use of resection as pancreatic cancer treatment, based on insurance status. Methods: A retrospective study was performed to evaluate use of pancreatic resection (ICD9: 52.51-52.53, 52.59, 52.6, 52.7) vs non-surgical options to treat patients with a principal diagnosis of pancreatic cancer (ICD9: 230.9, 157.1-157.4, 157.8, 157.9) from 2005-2014, using the Healthcare Cost and Utilization Project database. Rates of surgical resection were stratified based on insurance coverage status: private insurance, government insurance, or no insurance. Results: After adjusting for total discharges, we observed that percent pancreatic resections were highest for uninsured populations and lowest for Medicare. By 2014, the rate of surgical resections in uninsured patients decreased as a steady increase was observed for patients with Medicaid. Conclusions: Our preliminary findings suggest that the trends in rates of surgical resection as a treatment for pancreatic cancer vary by insurance status. Further research examining factors such as race, socioeconomic status, and comorbidities that increase the likelihood of uninsured patients receiving pancreatic resections vs other treatments are warranted. [Table: see text]
Thromboembolic events in advanced pancreatic cancer: A systematic review.
Authors: Muhsin Mann , Dabbous Omar , Morrison Blake , Vervaet Piet , Chondros Dimitrios
Published: January 2019

461

Background: Pancreatic ductal adenocarcinoma (PDA) is highly associated with thromboembolic events (TEs). There is no consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings. Published ASCO (2014) and ESMO (2011) guidelines recommend use of primary thromboprophylaxis in pancreatic cancer outpatients at high risk of TEs. This systematic review investigated TE rates and prophylaxis among advanced PDA patients. Methods: A literature review identified clinical trials and observational studies reporting TE rates with and without thromboprophylaxis in PDA patients undergoing chemotherapy. A search was conducted using electronic databases including Medline, Medline In-Process, and Embase; limited to English language and publication between 1990 and April 2017. Retrieved articles were cross-referenced and scrutinized to identify additional publications. Results: Seven studies were identified; 2 randomized clinical trials (RCTs) and 5 observational/retrospective studies met the stated criteria. The TE rate in PDA in the 5 observational studies without prophylaxis ranged from 9.6% to 36.0%. Thromboprophylaxis was used in the 2 RCTs and was associated with lower TE rates. Conclusions: This comprehensive literature review shows that PDA patients face a substantial risk of TE after chemotherapy. The high rates of TEs in PDA, and the effectiveness of thromboprophylaxis in patients with PDA, highlight the importance of having consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings as a critical early preventive measure during the treatment of patients with advanced PDA. [Table: see text]
Deterioration of hepatic function after locoregional therapy (LRT) for hepatocellular carcinoma (HCC) measured by hepatic cholate clearance: A pilot study.
Authors: Hoteit Maarouf , Hsu Christine Cho-Shing , Levine Matthew H , Forde Kimberly A , Reiss Kim Anna , Nadolski Gregory , Soulen Michael C. , Kron Laura , Helmke Steve , Everson Gregory T , Ben-Josef Edgar
Published: January 2019

468

Background: LRT is used in treating HCC, but is associated with a risk of hepatotoxicity, which is not accurately predicted by traditional measures of liver function. In this pilot study, we evaluated the change in liver function after LRT as measured by a test using dual, oral and IV, cholate clearances (HepQuantSHUNT). Our hypothesis is that LRT would impose a significant reduction in the disease severity index (DSI) measured in the HepQuant SHUNT test, as an indicator of reduced liver function. Methods: We conducted a prospective cohort study of 11 subjects undergoing LRT for HCC. HepQuantSHUNT was performed at baseline (T0) and 4-10 weeks after LRT (T1). Clinical assessment was performed at T0 and T1, and at 12-18 weeks after LRT (T2). Decompensation was defined as either a new complication of cirrhosis or an increase in Child-Pugh (CP) score by ≥2 points. Results: Median age was 61 years, 73% were men, 55% had hepatitis C. Median CP score was 7[5-8], including 36%CP A and 64%CP B. Subjects had a BCLC stage A(64%) or BCLC stage B(36%) HCC. LRT modalities were TACE (45%) or SBRT (55%). From T0 to T1, there was a reduction in oral cholate clearance(422[235-768] vs 339[208-362], p = 0.03) and in IV cholate clearance(210[150-300] vs 191[144-203],p = 0.04) as well as a trend towards a worsening disease severity index (DSI) (32.0[19.5-37.8] vs 33.0[29.7-38.0],p = 0.10); however, there was no significant change in MELD(12[9-13]vs 11[10-12],p = 0.72) or CP score(7[5-8] vs 7[6-8],p = 0.15). 89% of the subjects had a reduction in oral and IV cholate clearance, and 78% had a worsening DSI; while 44% subjects had increase in CP score, and 56% had an increase in MELD. Decompensation was observed in 43% of CP B patients and none of CP A patients; and in 60% patients with a DSI > 35, and none of the patients with DSI < 35. Conclusions: The dual cholate clearance assay HepQuant-SHUNT detects a deterioration in liver function after LRT for HCC more frequently than clinical measures of liver function. DSI 35 might be a cutoff for risk of clinical decompensation after LRT for HCC. Additional research is needed to evaluate the role of the HepQuant SHUNT test in improving the selection of Child B patients for LRT.
Implications of prolonged time to pancreaticoduodenectomy after neoadjuvant chemoradiation: Analysis of the National Cancer Database.
Authors: Teng Annabelle , Nguyen Trang , Bilchik Anton , O'Connor Victoria , Lee David Y
Published: January 2019

473

Background: For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. The National Cancer Database (NCDB) was used to evaluate the impact of radiation-surgery (RS) interval on outcomes. Methods: The NCDB from 2006-2014 was queried for patients ≥18 years old diagnosed with PA who received CR prior to surgery. Survival and short-term outcomes were compared between patients who had a Whipple procedure performed ≤12 weeks and > 12 weeks after completion of CR therapy. Results: 1610 patients met selection criteria. Average RS interval was 58.2 ± 39.5 days. 1419 patients had RS interval ≤12 weeks (mean 47.4 days) and 191 had RS interval > 12 weeks (mean 138.8 days). Age, race, gender, income, type of treatment facility, CA 19-9 levels, types of chemotherapy and radiation dosage administered were similar between the two groups. Mean tumor size was 32.2 mm in the ≤12 week group and 34.9 mm in the > 12 week group (p = 0.021). There was a higher proportion of patients with clinical stage III cancers in the > 12 weeks group than in the ≤12 weeks group (33.5% vs 14%). Short-term morbidity and mortality was not significantly different between the two groups in terms of length of stay, readmission within 30 days, 30-day and 90-day mortality. However, a long-term survival benefit was observed in the > 12 week group (median 25.8 months in ≤12 weeks vs 30.2 months in > 12 weeks, p = 0.049) that appears to persist. An interval > 12 weeks was associated with significantly prolonged survival on multivariate analysis (HR 0.80 (0.65-0.99 95% CI, p = 0.042)). Higher clinical stage and positive surgical margins were independently associated with worse survival. Conclusions: Surgical resection beyond 12 weeks after CR for PA did not worsen surgical outcomes. Waiting may contribute to better patient selection, especially those with larger tumors and higher clinical stage. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.
A real world multicenter study of first (1L) and second (2L) line treatment patterns and outcomes in advanced pancreatic cancer (APC).
Authors: Cheung Winson Y. , Zhang Hanbo , Tang Patricia A. , Spratlin Jennifer L. , Lee-Ying Richard M. , Goodwin Rachel Anne , Meyers Brandon Matthew , Armstrong Dawn Elizabeth , Ramjeesingh Ravi , Vickers Michael M. , Kim Christina ,   On Behalf of the CHORD Consortium
Published: January 2019

476

Background: FOLFIRINOX (FFX), gemcitabine plus nab-paclitaxel (GN), and gemcitabine (gem) are 3 publicly funded and available treatment options for locally advanced (LAPC) and metastatic pancreatic cancer (MPC) in Canada since 2014. Without head-to-head trials that directly compare all 3 regimens, treatment selection and outcomes in 1L and 2L remain poorly characterized in routine clinical practice. Methods: Data from 4 tertiary, 8 regional, and 28 community hospitals in Canada were pooled. LAPC and MPC patients diagnosed from 2014 onwards and who received at least 1 line of systemic therapy were included. Analyses were conducted to identify predictors of treatment choice and to determine the relationship between treatment patterns and overall survival (OS) from APC diagnosis to death. Results: We identified 279 eligible patients. Median age was 64 (IQR 56-69) years, 55% were men, and 46% were ECOG ≥2. There were 27% LAPC and 73% MPC. In the 1L setting, FFX and GN were given in 44% and 41% of patients, respectively, and gem in 15%. GN was the preferred multi-agent therapy in worse ECOG patients (66% in ECOG 2+ vs 21% in ECOG 0, p = .001) and in more recently diagnosed cases (63% in 2016 vs 25% in 2014, p = .001). 1L treatment selection was not influenced by other baseline characteristics, such as age, sex, tumor location, or LAPC vs MPC status (all p > 0.05). A total of 91 patients proceeded to subsequent therapies, of whom 55 (60%), 27 (30%), and 9 (10%) had received 1L FFX, GN, and gem, respectively. In the 2L setting, GN after 1L FFX (41/55; 75%) and fluoropyrimidine (FP) after 1L GN (21/27; 78%) were the most common sequential approaches. Patients who underwent 2L therapy had better OS than those who did not (13 vs 7 months, p = .001). After adjusting for confounders, receipt of 1L FFX plus 2L GN or 1L GN plus 2L FP resulted in improved OS when compared to other treatment sequences (HR 0.43, 95%CI 0.28-0.67, p = 0.001 and HR 0.57, 95%CI 0.39-0.83, p = 0.004, respectively). Conclusions: One third of APC patients receive 2L therapy, highlighting the feasibility of 2L trials. Use of 1L multi-agent therapy followed by 2L non-cross-resistant regimens represents a reasonable treatment strategy for APC in the real world.
Palliative care and end-of-life health care utilization of pancreatic cancer patients at an urban safety-net hospital.
Authors: Bhulani Nizar , Paulk M. Elizabeth , Gupta Arjun , Donnell Kiauna , Harvey Valorie , Cox Joan , Cox John Vernon , Karri Sirisha , Verma Udit N. , Sanjeevaiah Aravind , Cheedella Naga Koteswari , Khosama Leticia , Arriaga Yull Edwin , Syed Samira K. , Kazmi Syed Mohammad Ali , Korenke Adam , Beg Muhammad Shaalan
Published: January 2019

489

Background: There has been an increase in Palliative care utilization in cancer patients. We examined trends of palliative care and intensive care utilization in pancreatic cancer patients in an urban setting safety net hospital. Methods: This is a retrospective analysis of pancreatic cancer patients seen at the Parkland Health and Hospital System between January 1999 and September 2016. Cancer cases and receipt of palliative care were identified from prospectively maintained registries. Health care utilization including intensive care unit (ICU) was reviewed. All statistical analysis was done using IBM SPSS version 24. Results: We identified 455 new diagnoses of pancreatic cancer, mean age 61 years, 227 (50%) female and 228 (50%) white. Of these, 277 (61%) received palliative care ever. Patient who received palliative care were more likely to be younger (mean age, 59.3+-12 vs 62.8 +- 12 years) and have stage 4 disease vs stage 1-3 disease (p 0.006, and p 0.003 respectively). There was no statistically significant difference in palliative care utilization between gender and ethnicity groups. 140 patients had a DNR order and 29 required ICU admission at any point. A first contact with palliative care consult was obtained < = 7 days before death for 29 (10%) patients, < = 30 days before death for 86 (31%) patients, 30-60 days before death for 50 (18%) and more than 60 days before death for 141 (51%) patients. Patients receiving palliative care were more likely to have a DNR status (p < 0.001) but had no difference in ICU use within the last 30 days of life (p 0.285). Conclusions: The rate of palliative care in patients with pancreatic cancer in this cohort from a safety net hospital is higher than nationally reported studies. Most patients received palliative care > 30 days before death. While patients received early palliative care, it did not result in reduced ICU care. Factors influencing ICU care utilization near the end of life need further study.
The impact of lung and bone metastases on prognosis in advanced PDAC.
Authors: O'Kane Grainne M. , Fraser Adriana , Moignard Stephanie , Dodd Anna , Creighton Sean , Sim Hao-Wen , Aung Kyaw Lwin , Borgida Ayelet , Gallinger Steven , Knox Jennifer J.
Published: January 2019

494

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly fatal disease inherently resistant to cytotoxic treatment. Despite the prevalence of liver and peritoneal metastases, subsets of patients also develop lung and bone metastases highlighting phenotypic heterogeneity. We reviewed the prognostic implications of metastatic sites on survival. Methods: This retrospective cohort study included all patients with PDAC who received surgical or oncological treatment at the University Health Network from September 2012 until December 2016. Clinical and pathological variables were obtained from patient electronic records. Radiological images and pathology reports were reviewed to ascertain sites of metastatic disease. The Kaplan-Meier method for survival and multivariable cox regression analysis identified prognostic factors. Results: 1153 patients were reviewed and 985 were included. 55% were male and the median age at diagnosis was 67 years. 287 (29%) completed curative surgery and 698 (71%) had locally advanced or metastatic disease; the median survival was 22 months and 9 months respectively. Lung and bone metastases were present in 18% (N = 180) and 6% (N = 58) of patients. In multivariable analysis increasing age and stage at diagnosis correlated with inferior survival (p < 0.0001) and the presence of any lung (HR 0.77; 95% CI 0.63-0.94, p = 0.01) or bone metastases (HR 0.74; 95% CI 0.54-1.0, p = 0.05) resulted in improved outcomes. Liver and peritoneal disease were not prognostic. Sex and family history of PDAC did not associate with survival. There was no association between site of metastases and sex however patients with bone metastases were significantly younger at first diagnosis (median age 63yrs, p < 0.01). Conclusions: Patients with advanced PDAC and metastases to lung or bone may represent distinct biological subtypes of PDAC. Molecular profiling of available tissue is ongoing.
Clinical assessment of pancreatic cancer cases with thromboembolism complications.
Authors: Nagata Yusuke , Sawada Ryoichi , Kano Tomohiro , Ishimoto Utako , Nishimura Takashi , Noguchi Masaaki , Amano Katsushi , Kato Tomohiro , Saruta Masayuki
Published: January 2019

495

Background: Cancer patients, particularly those with pancreatic cancer (PC), have an increased risk of developing thromboembolism, such as venous thromboembolism (VTE) and cerebral infarction (CI). Moreover, thromboembolisms in cancer are associated with poor prognosis. The purpose of this study was to investigate the clinical characteristics, clinical courses, and prognosis of PC patients (pts) with VTE and/or CI. Methods: We retrospectively reviewed the medical records of PC pts who were radiologically diagnosed with VTE and/or CI at our institution. We investigated the patients’ clinical information and evaluated overall survival (OS), which was defined as the date from diagnosis of VTE and/or CI to the date of death by any causes or censored. Results: Between January 2012 and December 2015, 100 pts were diagnosed with PC. A total of 14 pts developed VTE and/or CI at our institution. All 14 pts had unresectable advanced or metastatic PC, 10 pts (71%) were men, and the median age at the time of VTE and/or CI diagnosis was 68.8 (range, 29–84) years. Complications of VTE and CI developed in 6 (43%) and 8 pts (57%), respectively (3 pts with development of both VTE and CI were included as CI). The median OS in pts who developed VTE and CI was 7.59 and 1.48 months (p = 0.007), respectively. After the development of VTE and/or CI, 5 pts (36%) (3 with VTE and 2 with CI) received chemotherapy (CTx), while the remaining 9 pts (64%) received best supportive care (BSC). In pts with VTE, the median OS of those who received CTx and BSC was 7.59 and 3.15 months (p = 0.221), respectively. Meanwhile, in pts with CI, the median OS of those who received CTx and BSC was 3.84 and 1.48 months (p = 0.113), respectively. Conclusions: The prognosis of PC pts who developed CI as complications was significantly poorer than those who developed VTE. However, in both cases, treatment with CTx prolonged the OS of these patients.
Association of therapeutic management with a good prognosis in unresectable hepatocellular carcinoma patients undergoing sorafenib treatment: Dose adjustment and conversion therapy.
Authors: Oikawa Takayoshi , Kuroda Hidekatsu , Endo Kei , Sawara Kei , Takikawa Yasuhiro
Published: January 2019

498

Background: When treating hepatocellular carcinoma (HCC) with sorafenib, it is important for the physician to evaluate the therapeutic effects because of the characteristic therapeutic response, the toxicity, and out of consideration for the liver function. We evaluated the relationship between changes in therapeutic management and the efficacy of sorafenib in the treatment of unresectable HCC. Methods: Out of a total of 118 patients who received sorafenib in our hospital between January 2010 and September 2017, 96 patients could be followed up and were included in the present study. We evaluated the profile of sorafenib treatment (etiology, cStage, initial dose, the percentage of cases in which the dose was changed), the clinical response by mRECIST, adverse events by CTCAE v.4.0, overall survival (OS), and the rate of patients continued sorafenib treatment or underwent conversion therapy after the development of progressive disease (PD) in two distinct periods of treatment: the former period (in which ordinary management was applied); and the latter period (in which management practices were strengthened in relation to the dose ). Results: Significant differences were observed in the rate (y/n) of change in the sorafenib dose and the rate of patients continued sorafenib treatment after the development of PD (the former/the latter, 13/42, 25/16, p = 0.005, 24/31,25/16, p = 0.045, respectively). A significant difference was observed in OS in the two periods (the former/ the latter, median OS 8.1/16.5 months, p = 0.019). In the latter period the percentage of dose escalation (400→800mg /day) was 60%. With regard to the clinical course after the development of PD, 15 patients (36.6%) in the latter received transarterial chemoembolization, and had a disease control rate of 60%. Conclusions: The prognosis of patients receiving sorafenib treatment for unresectable HCC can be extended when efforts are made to appropriately manage their medication based on their overall condition. After a sorafenib-treated patient develops PD, the continuation of sorafenib treatment or the addition of locoregional therapy may achieve a good response.