bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparities associated with the receipt of palliative care in patients with metastatic gastric cancer.
Authors: Paul Subhadeep , Hester Caitlin , Wang Sam C. , Polanco Patricio , Yopp Adam Charles , Augustine Mathew M , Mansour John C. , Zeh Herbert , Porembka Matthew R. 
Published: January 2019

28 Background: Metastatic gastric adenocarcinoma (mGA) is frequently associated with debilitating symptoms that negatively impact quality of life. We aim to determine the rate of palliative care (PC) use in mGA and the factors which are associated with receipt of PC. Methods: Using the National Cancer Database, mGA patients were selected. Receipt of PC as defined by the NCDB participant use file was correlated to demographic and clinicopathologic factors. As defined according to NCDB, PC treatment included surgery, radiation, systemic therapy, and pain management to alleviate symptoms. Logistic regression was performed to assess the impact of factors on the likelihood of receiving PC. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Results: Between 2004 and 2013, 45519 patients with mGA and reported PC status were identified. Median age was 66 years (IQR: 55-76 years) and 64% were male. 7365 (16.2%) patients received PC. PC utilization increased over time (2004-6 13.4%, 2007-10 15.8%, 2011-13 19.1%; p < 0.001). Factors associated with PC on univariate analysis included insurance status, education level, income, sex, race, Charlson/Deyo comorbidity score, and year of diagnosis (all p < 0.001). On multivariate analysis, female sex (0.87, 95%CI: 0.83-0.92) and minority race were associated with less receipt of PC (Hispanic 0.73, 95%CI: 0.66-0.80, Black 0.87, 95%CI: 0.80-0.95, Asian 0.89, 95%CI: 0.77-0.98 compared to non-Hispanic White patients). Higher education level was associated with greater receipt of PC (1.46, 95%CI: 1.31-1.62). Receipt of PC was associated with decreased overall survival (PC 4.8 months vs no PC 6.0 months; p < 0.001). Conclusions: Although use of PC has increased over time, PC is underutilized in mGA. Disparities exist in receipt of PC in regard to race, gender, and education. Additional research is necessary to better optimize PC use in mGA and mitigate potential disparities.
Outcomes of patients with borderline-resectable pancreatic cancer treated with FOLFIRINOX versus gemcitabine plus nab-paclitaxel.
Authors: Templeton Shaina D'Lee , Moser Michael , Chalchal Haji I. , Shaw John , Luo Yigang , Zaidi Adnan , Ahmed Shahid 
Published: January 2019

299 Background: Pancreatic cancer is a major cause of cancer-related death. Less than 20% of patients have resectable disease at diagnosis. Patients with borderline-resectable pancreatic cancer (BRPC) are at high risk of incomplete resection with upfront surgery. Currently there is no standard induction chemotherapy regimen exists for BRPC. Both FOLFIRINOX (5-FU, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) have shown better efficacy than gemcitabine in advanced pancreatic cancer. The current study aims to assess outcomes of real-world patients with BRCP who received induction FOLFIRINOX or GnP. Methods: In this population-based multicenter retrospective cohort study patients with biopsy proven BRPC as defined by the pancreatic surgical team diagnosed from 2011-2017, in the province of Saskatchewan, Canada, who received FOLFIRINOX or GnP were assessed. Kaplan Meier methods and log rank tests were performed for survival analyses. Results: Of 161 patients with pancreatic cancer who received FOLFIRINOX or GnP during the study period, 20 eligible patients with BRPC, with median age of 65 yrs (54-79) and M:F 14:6, were identified. 85% had pancreatic head tumours with a median CA19-9 of 470 u/mL. Of eligible patients, 10 each received FOLFIRINOX or GnP. No significant differences were found between the two groups, except more patients in FOLFIRINOX group had a WHO performance status of 0 (50% vs. 10%, p = 0.057) and had a higher body mass index (27.0 vs. 23.0, p = 0.027). Eleven patients showed partial response (5–FOLFIRINOX and 6–GnP), three progressed during treatment. Five patients (4–FOLFIRINOX, 1–GnP, p = NS) underwent curative surgery. Five patients (1–FOLFIRINOX, 4–Gnp) had radiation and four underwent Nanoknife procedure (3–FOLFIRINOX, 1–GnP). The median progression free survival was 17 months in FOLFIRINOX (95% CI: 5.3-28.6) versus nine months (3.0-15) in GnP group (p = 0.26). The median overall survival was 32 months in FOLFIRINOX (not reach) versus 16 months (9.3-22.7) in GnP group (p = 0.15). Conclusions: The current study suggests that patients with BRPC who received FOLFIRINOX tends to have better outcomes. Future study are warranted to establish a preferred systemic therapy for BRPC.
Integrated population pharmacokinetic (PopPK) modeling of cabozantinib (C) in patients (pts) with various cancer types including hepatocellular carcinoma (HCC).
Authors: Nguyen Linh Thuy , Chapel Sunny , Meyer Tim , Cheng Ann-Lii , El-Khoueiry Anthony B. , Kelley Robin Kate , Abou-Alfa Ghassan K. , Lacy Steven 
Published: January 2019

305 Background: C significantly improved overall survival vs placebo in pts with previously treated advanced HCC in the phase 3 CELESTIAL trial (NCT01908426). In a previous single dose PK study, increased C exposure was observed in healthy volunteers (HV) with mild or moderate hepatic impairment (Nguyen, J Clin Pharmacol, 2016). An integrated PopPK model was recently developed to characterize C concentration data from HV and pts with various cancers, including renal cell carcinoma, castration-resistant prostate cancer, and medullary thyroid cancer (MTC) (Lacy, Cancer Chemother Pharmacol, 2018). Here, we update the model to include data for pts with advanced HCC from CELESTIAL and a prior phase 2 trial. Methods: The updated PopPK model was developed using nonlinear mixed effects modeling methodology (NONMEM v7.3) and incorporated data from 10 clinical studies with 9510 measurable C concentrations from 2023 subjects, including 489 pts with advanced HCC. Eligible pts with HCC were Child-Pugh class A. Evaluated covariates included age, gender, race, body weight, cancer type, and liver dysfunction as defined by the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG). Results: Overall, 70% of pts had normal hepatic function by NCI-ODWG criteria; 28% had mild, 1% had moderate, and <1% had severe hepatic dysfunction. A 2-compartment model with first-order elimination and dual first- and zero-order absorption processes adequately described the data. As in the previous model, the MTC population was the only cancer type to have a notable difference in C PK, with ~90% increase in apparent clearance (CL/F) versus HV and pts with other cancers including HCC. For a White male, CL/F was estimated as 2.48 L/hr and apparent volume of the central compartment (Vc/F) as 212 L. Inter-individual variability was ~46% for CL/F and ~67% for Vc/F. Other demographic covariates were predicted to have a small to moderate impact on C CL/F. Liver dysfunction, per NCI-ODWG criteria, had no discernable effect on C CL/F. Conclusions: C exposure at an equivalent daily dose is predicted to be similar in pts with several cancer types including advanced HCC with mild liver dysfunction.
Single-shot celiac plexus radiosurgery in pancreatic cancer: Palliative and functional outcomes—Final results of a prospective clinical trial.
Authors: Lawrence Yaacov Richard , Shmueli Einat Shacham , Hammer Liat , Morag Ofir , Ben-Ayun Maoz , Margalit Ofer , Halpern Naama , Yarom Nirit , Boursi Ben , Jacobson Galia , Symon Zvi , Shefer Kinneret , Yanovsky Inessa , Golan Talia , Hausner David 
Published: January 2019

309 Background: Pancreatic cancer is characterized by severe epigastric/lower back pain caused by infiltration of the celiac plexus. The celiac plexus is a network of nociceptive nerves, located along the abdominal aorta. Contemporary approaches (opioids, celiac plexus chemical neurolysis, systemic chemotherapy) are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate pain. Here we report results for pancreatic cancer patients treated with a single fraction of radiation. Methods: We conducted a single-institution single-arm prospective clinical trial. Eligible cancer patients had celiac-pain > 4/10 on Numerical Rating Scale (NRS) and completed treatment per protocol with at least one post-treatment visit. The celiac plexus was irradiated from D12 to L2. Radiation was given as a single-fraction 25 Gy. The primary endpoint was NRS pain 3 weeks post-treatment. Secondary endpoints were toxicity, pain at 6w, analgesic use, and pain interference with daily activities as evaluated by the ‘The Brief Pain Inventory’. Analgesia was not restricted. Total daily dose of opioids was measured in morphine milligram equivalents (MME). Results: Seventeen patients were evaluable, 65% female, median age 68 yr (range 51-79), three had undergone pancreatic resection, nine had liver metastases, median ECOG = 1. Sixteen patients reported 3-week outcomes, and 10 reported 6-week outcomes. At time of treatment subjects were a median of 8.2 months from diagnosis, and had received a median of one systemic treatment (range 0-3). Toxicity was limited to grade 1. Median baseline pain was 6/10 (IQR 5-7), was reduced to 2.3/10 (IQR 0.9-3.6) (p < 0.0005) at 3 w, and to 2.5/10 (IQR 0-3.1) at 6 w post-treatment, for both p < 0.001. Median opioid consumption numerically decreased (baseline 52.9 MME, 3 w 43.9 MME, 6 w 37.5 MME, NS). ‘BPI pain interference’ improved significantly: median baseline score 7.1 dropped to 1.1 at 3 weeks and 0 at 6 weeks (p < 0.01 for both time points). Conclusions: Celiac plexus radiosurgery alleviates pain, and improves quality of life among patients with pancreatic cancer. A follow-up international trial is accruing. Clinical trial information: NCT02356406.
Ramucirumab (RAM) as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline α-fetoprotein (AFP): An analysis of AFP kinetics in the phase III REACH-2 study.
Authors: Finn Richard S. , Kudo Masatoshi , Kang Yoon-Koo , Yen Chia-Jui , Galle Peter R. , Llovet Josep , Assenat Eric , Brandi Giovanni , Lim Ho Yeong , Pracht Marc , Rau Kun Ming , Merle Philippe , Motomura Kenta , Ohno Izumi , Daniele Bruno , Shin Dongbok , Gerken Guido , Abada Paolo , Hsu Yanzhi , Zhu Andrew X. 
Published: January 2019

326 Background: REACH-2 (NCT02435433) demonstrated a significant survival benefit with RAM vs placebo in the second-line treatment of patients with advanced HCC and AFP ≥ 400 ng/mL. This analysis investigated changes in AFP during treatment, as well as potential relationships with survival or progression. Methods: Patients were randomized (2:1) to RAM 8 mg/kg IV or placebo Q2W plus best supportive care until disease progression or unacceptable toxicity. Serum AFP levels were measured at baseline and every 3 cycles. Percent change in AFP from baseline was analyzed at each time point up to Cycle 12 with descriptive statistics and Wilcoxon rank sum test between treatment arms. AFP response was defined as ≥ 20% decrease from baseline. The association between AFP progression and radiographic progression in each time interval was assessed by odds ratio [OR] and Fisher’s exact test. Time to AFP progression and time to radiographic progression (TTP) were evaluated by the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test. AFP progression was defined as ≥ 20% increase from baseline. Hazard ratio (HR) was generated using a stratified Cox regression model. Results: AFP response was significantly higher with RAM compared with placebo (42.1% vs 10.5%, p < 0.0001). Overall survival (OS) was longer in patients with AFP response (13.5 months) than in patients without (6.7 months), irrespective of treatment (HR 0.470, p < 0.0001). The median percent increase in AFP level from baseline was smaller in the patient population treated with RAM (0.4%, 6.1%, 15.4%, 10.8%) than with placebo (45.7%, 98.5%, 122.2%, 91.3%) at Cycles 3, 6, 9 and 12, respectively. Time to AFP progression (HR 0.422, p < 0.0001) and TTP (HR 0.427, p < 0.0001) favored a RAM benefit; subsequent analyses demonstrated a strong association between AFP progression and radiographic progression at 6 weeks (OR 2.44, p < 0.0084) and at 12 weeks (OR 1.89, p = 0.0430). Conclusions: Changes in AFP levels were associated with TTP and OS. RAM prolonged time to AFP progression and radiographic TTP, and slowed the rate of AFP increase during treatment. Clinical trial information: NCT02435433.
Checkmate-040: Nivolumab (NIVO) in patients (pts) with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B (CPB) status.
Authors: Kudo Masatoshi , Matilla Ana , Santoro Armando , Melero Ignacio , Gracian Antonio Cubillo , Acosta-Rivera Mirelis , Choo Su Pin , El-Khoueiry Anthony B. , Kuromatsu Ryoko , El-Rayes Bassel F. , Numata Kazushi , Itoh Yoshito , Di Costanzo Francesco , Crysler Oxana V. , Reig Maria , Shen Yun , Neely Jaclyn , Dela Cruz Christine Marie , Baccan Carlos , Sangro Bruno 
Published: January 2019

327 Background: Pts with aHCC and CPB liver status are often excluded from clinical trials of novel therapies due to their poor prognosis (Greten British J Cancer 2005). Historical overall survival (OS) for these pts when treated with sorafenib (SOR) has ranged ≈3–5 mo in retrospective or descriptive studies (Abou-Alfa Gastrointest Cancer Res 2011; Da Fonseca Mol Clin Oncol 2015; Pressiani Ann Oncol 2013; Chiu Cancer 2012); thus, novel treatment options are needed for these pts. The PD-1 inhibitor NIVO is approved in the US, Canada, and elsewhere, most recently Australia, for SOR-treated pts with aHCC based on results from CheckMate-040 (NCT01658878) (El-Khoueiry Lancet 2017). Here we report data from the CPB cohort of CheckMate-040, the first prospective study of immunotherapy in this pt group. Methods: Pts with CPB (B7–B8) aHCC who were SOR-naïve (n = 25) or -experienced (n = 24) received NIVO 240 mg IV for 30 min Q2W until unacceptable toxicity or disease progression. Primary endpoints were objective response rate (ORR) (investigator assessed [INV], RECIST v1.1) and duration of response (DOR). Safety was assessed in all treated pts using NCI CTCAE v4.0. Results: Of 49 analyzed pts, 28 (57.1%) had vascular invasion or extrahepatic spread. During a follow-up range of 6–18 mo, INV ORR was 10.2% with 5 pts responding; disease control rate (DCR) was 55.1%. Median (m) time to response was 2.7 mo and mDOR was 9.9 mo; 2 pts had ongoing responses at data cutoff. The mOS was 7.6 mo (mOS follow-up was 7.4 mo); mOS in SOR-naïve and -treated pts was 9.8 and 7.3 mo, respectively. Treatment-related adverse events (TRAEs) were reported in 25 (51%) pts; 4 (8.2%) pts had select hepatic TRAEs. TRAEs led to discontinuation in 2 pts (4.1%). NIVO safety profile in these pts appeared comparable to cohorts of pts with CPA aHCC. Comparison data for pts with CPA aHCC and extended follow-up for pts with CPB aHCC will be presented. Conclusions: Encouraging DCR and durable responses were observed in pts with CPB aHCC treated with NIVO. AEs were manageable and did not lead to higher discontinuation compared with pts with CPA aHCC. NIVO showed promising efficacy and tolerability compared with historical data, supporting further investigation. Clinical trial information: NCT01658878.
Safety and efficacy of high-intensity focused ultrasound in pancreatic cancer.
Authors: Kim Jin Il , Cheung DaeYoung 
Published: January 2019

339 Background: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer. Methods: Patients with pancreatic cancer TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the non-perfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. Results: High-intensity focused ultrasound treatment was performed without severe adverse event in 52 patients, 53 times (male/female = 28/24; mean age, 62.7 ± 12.1; TNM stage 3/stage 4 = 21/31). Average size of the pancreatic cancer lesion was 4.5 ± 1.6 cm (1.4 - 9.5 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 41 lesions, 90% to 50% in 11, and within 50% in 3. Overall median survival (S1) from initial pancreatic cancer diagnosis was 13.1 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 53.1%, 31.6%, and 23.5%, respectively, with a median survival of 7.4 months. Conclusions: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced pancreatic cancer.
Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced (nonresectable) and metastatic biliary tumors: A randomized double-blinded placebo-controlled phase II trial.
Authors: Demols Anne , Borbath Ivan , Van Den Eynde Marc , Houbiers Ghislain , Peeters Marc , Maréchal Raphael , Delaunoit Thierry , Goeminne Jean Charles. , Laurent Stéphanie , Holbrechts Stephane , Paesmans Marianne , Van Laethem Jean L. 
Published: January 2019

345 Background: A high clinical unmet need remains in treating advanced or metastatic biliary tract cancers (BTC) after failure of gemcitabine and platinum-based chemotherapy, with no standard of care. Regorafenib is potent oral multi-kinase inhibitor of kinases involved in tumor angiogenesis, oncogenesis and tumor microenvironment. It has demonstrated efficacy and acceptable safety in some GI tumors that have progressed on standard therapies. Methods: REACHIN (NCT02162914) is a multicenter double-blinded placebo-controlled randomized phase II study to evaluate the safety and efficacy of regorafenib (REG) in patients with locally advanced (non resectable) and metastatic histologically proven BTC, progressing after gemcitabine-platinum. 66 patients were randomized (1:1) to receive BSC plus REG160 mg od, 3 weeks on/ one week off (cycle = 4 weeks) or BSC + placebo (P) until progression or unacceptable toxicity. Sample size calculation was based on the logrank test, assuming a one-sided significance of 10%, 80% power, and an improvement in median PFS of 50% (6 to 12 weeks in the REG group). Primary endpoint is PFS. Secondary endpoints are response rate and OS. Results: Between May 2014 and February 2018, 68 (33 REG, 35 P) patients have been included (2 patients died before starting treatment and were replaced). Of 66 patients treated (26 F/ 40 M), tumors were intra-hepatic and hilar (n = 48), extra-hepatic (n = 10) and gallbladder (n = 8). One patient remains on REG treatment. Median PFS for REG is 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI : 1.2-2.0) for P with a HR of 0.48 (95% CI : 0.29-0.80), p = 0.004. Rates of PR+SD are 23/33 (70%) for REG and 11/33 (33%) for P (p = 0,002). Median treatment duration is 10,9 weeks for REG vs 6,3 weeks for P (p = 0,004). Dose reductions were applied in 14/33 patients in REG and in 5/33 patients in P. There is no unexpected/new safety signal. Median OS is 5.3 months for REG and 5.1 months for P (p = 0.21). Conclusions: Regorafenib significantly increases median PFS and tumor control in patients with previously treated metastatic/ unresectable biliary tract cancer. Clinical trial information: NCT02162914.
Randomized phase II trial of sorafenib, capecitabine and oxaliplatin (SECOX) versus single agent sorafenib in patients with advanced hepatocellular carcinoma.
Authors: Yau Thomas Cheung , Tang Vikki , Leung Roland Ching-Yu , Kwok Gin Wai , Lee Ann-Shing , Law Ada , Chiu Joanne , Li Bryan , Cheung Tan To 
Published: January 2019

365 Background: We aimed to compare the efficacy and tolerability of SECOX regimen with sorafenib alone as first-line treatment of advanced hepatocellular cancer (HCC) in a multicenter, open-label and randomized setting. Methods: Patients not suitable for surgery or various loco-regional therapies and no prior systemic therapy for advanced HCC were recruited in 3 centres. Eligible patients were randomly assigned to receive either SECOX (sorafenib 400 mg BD continuously, oxaliplatin 85 mg/m2 on D1, and capecitabine 1700 mg/m2 on D1-7 q2w) or sorafenib alone continuously in 1:1 ratio. Primary endpoint was time-to-progression (TTP). Secondary endpoints were tolerability, overall tumor response rate, overall survival (OS) and progression-free survival (PFS). Results: Forty-six patients were randomized and treated, of whom 22 were in the SECOX arm. Median age was 64 years and majority of the patients were male (72%). 40 patients (87%) were hepatitis B carrier, and 42 patients (91%) had Child-Pugh A liver function. Thirty patients (65%) had received prior non-systemic treatment for HCC. Median duration of follow-up was 7.8 months (mos) (range 0.3-25.8). At the time of analysis,one patient in the SECOX arm is still receiving treatment. Median TTP was 3.2 mos (95% CI 1.7-5.8) for SECOX vs 2.8 mos (95% CI 1.8-4.0) for sorafenib. The hazard ratio (HR) for TTP was 0.91 (95% CI 0.5-1.7; p=0.77; predetermined futility boundary HR ≥ 0.86). Median OS was 7.1 mos (95% CI 3.0-15.3) for SECOX vs 12.5 mos (95% CI 7.2-15.4) for sorafenib (p=0.29). Median PFS was 3.1 mos (95% CI 1.6-5.8) for SECOX vs 2.7 mos (95% CI 1.8-4.0) for sorafenib. 2 patients (9%) and no patients achieved partial response in the SECOX and sorafenib arms, respectively. The clinical benefit rate (CR+PR+SD) was 36% for the SECOX arm and 21% for the sorafenib arm (p=0.50). Incidence of treatment-related adverse events (trAEs) was common in both SECOX and sorafenib arms (64% and 71% respectively, p=0.75). The most common grade 3-4 trAE was ALP increase (14%) for SECOX and hand-foot skin reaction (25%) for sorafenib. Conclusions: The addition of capecitabine and oxaliplatin to sorafenib did not result in significant improvement in TTP. Clinical trial information: NCT02716766.