bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathologic outcomes of systemic therapy followed by stereotactic body radiation therapy (SBRT) for pancreatic cancer (PC) in a novel lateral decubitus treatment position.
Authors: Song Ethan , Frakes Jessica , Latifi Kujtim , Malafa Mokenge Peter , Hodul Pamela Joy , Pimiento Jose Mario , Kim Dae Won , Kim Richard D. , Hoffe Sarah E. 
Published: January 2019

415 Background: Outcomes of multi-fraction stereotactic body radiotherapy (SBRT) for PC report low rates of toxicity and high local control, improving feasibility for combination with more aggressive systemic therapy regimens. However, SBRT in the ablative range poses risk to adjacent normal structures, excluding this option for tumors within 1 cm of a mucosal organ. In this study, we report our initial experience with treatment in the lateral decubitus position. Methods: An IRB retrospective query identified patients with pancreatic body adenocarcinoma treated with systemic chemotherapy followed by SBRT in the lateral decubitis position. SBRT was delivered to the entire gross disease with 30 Gy in 5 fractions with focal dose escalation up to 40 Gy to the tumor/vessel interface (TVI) as long as constraints were met. Patients were explored for resection if no metastasis or progression on restaging scans. The primary endpoints were pathologic response and margin status. Descriptive analysis was performed with SPSS 24. Results: The median age of the cohort was 68.6 (range, 50-83 yrs), with a white (94%) and male (59%) predominance. Initial staging of the 17 patients who met criteria included 10 (59%) patients diagnosed with borderline resectable disease (BRPC) and 7 (41%) with locally advanced disease (LAPC). 7 (41%) patients were treated with FOLFIRINOX, 5 (29%) with gemcitabine/nab-paclitaxel, 4 (24%) with gemcitabine/capecitabine/docetaxel, and 1 (6%) with gemcitabine/paclitaxel preceding SBRT. A median dose of 40 Gy (range, 33-40 Gy) was delivered to the TVI for all patients. 5 BRCP (29%) and 2 LAPC (12%) patients went to surgery, with 6 of these patients undergoing an R0 resection (86%) and 1 BRPC patient with an R1 resection. Pathologic tumor regression grades by the College of American Pathologists guidelines were 14% Grade 1, 71% Grade 2, and 14% Grade 3. Conclusions: Lateral decubitus treatment expands inclusion of pancreatic body patients for SBRT with focal TVI dose escalation leading to margin negative resection and significant partial tumor response, warranting future studies exploring ablative dosing in this position.
Prognostic factors associated with long term survival in chemotherapy-treated advanced pancreatic cancer: A Canadian multicenter analysis.
Authors: Kim Christina , Ahmed Shahid , Armstrong Dawn Elizabeth , Baig Tayyba , Cardoso Miguel , Ko Yoo-Joung , Kong Shiying , Mackinnon Madison , Meyers Brandon Matthew , Pratt Michelle , Ward Julie , Xu Yuan , Cheung Winson Y. 
Published: January 2019

416 Background: The outcomes of patients (pts) with advanced pancreatic cancer (APC) are poor. With the use of currently available multi-agent regimens, median overall survival (mOS) remains < 12 months. Select pts, however, experience a protracted survival. Little is known about the clinical, pathologic and treatment characteristics associated with long term survival (LTS) in APC. Methods: Pooled individual level data from six Canadian cancer centers of pts diagnosed with APC from 2012 to 2016 who received at least one cycle of chemotherapy (CT) were analyzed. Clinical, pathologic and treatment characteristics, as well as survival, were compared between pts who lived < and ≥ 18 months. Multivariable logistic regression was used to identify independent predictors of survival. Results: Of 455 pts, 96% had metastatic disease and 88 (19%) survived ≥ 18 months. Compared to pts who survived < 18 months, those with LTS had lower WBC (p = 0.0025), CA 19-9 (p < 0.001), ALP (p < 0.001) and LDH (p = 0.007) at baseline. Pts with LTS also had higher albumin (p < 0.001) and BMI (p = 0.0268). In addition, they had better ECOG (p < 0.001) and were more likely to have tumors in the head of the pancreas (p = 0.0204). LTS pts were more likely to have a complete response (CR) or partial response (PR) to 1L CT (p < 0.001). The mOS seen with LTS was 29.2 months, compared to 4.3 months (p < 0.001). On multivariable logistic regression, independent predictors of LTS included: primary tumor in the head of the pancreas (OR 3.42 95% CI 1.2-9.76); experiencing a CR or PR to 1L CT (OR 9.19 95% CI 3.78-22.32); and receipt of 2L doublet CT (OR 2.72 95% CI 1.05 to 7.08). Conversely, factors associated with lower likelihood of LTS included: ECOG ≥ 2 (OR 0.32 95% CI 0.11-0.95); and elevated CA 19-9 (OR 0.43 95% CI 0.21-0.9). Conclusions: A select proportion of pts with APC experience LTS and have clinical features which differentiate them from those without LTS. The use of performance status, primary tumor location, pre-treatment CA 19-9, 2L CT type and radiologic response may help identify LTS and inform discussions regarding treatment and prognosis.
Impact of hospital volume and type on survival in hepatocellular carcinoma: Results from the National Cancer Database.
Authors: Uhlig Johannes , Sellers Cortlandt , Khan Sajid A. , Cha Charles , Kevin Kim Hyun S. 
Published: January 2019

417 Background: To assess the impact of hospital volume and type on survival in patients with hepatocellular carcinoma (HCC). Methods: Patients with histopathological or imaging-based diagnosis of HCC were identified from the 2003-2015 National Cancer Database (NCDB). First-line treatment was stratified as liver transplant, surgical resection, interventional oncology (IO) and chemotherapy. Hospital volume was stratified as high (ranking among top 10% in case numbers) and low volume, separately for each treatment modality. Hospital type was categorized as academic and non-academic. Overall survival was assessed using multivariable Cox proportional hazards models. Results: A total of 63,877 patients were included (transplant n = 10,596, surgical resection n = 11,132, IO n = 12,286, chemotherapy n = 29,863). Of 1,261 hospitals systems which treated HCC, 226 (17.9%) were academic centers and 1,035 (82.1 %) were non-academic centers. Mean number of cases treated annually was higher in academic centers (55.2; 34.6; 40.7; 79.9) versus non-academic centers (10.7; 6.25; 6.6; 11.9 for transplant; surgical resection; IO and chemotherapy; p < 0.001, respectively). Young African American patients and those with private insurance, high income and education were more likely to receive treatment at academic centers. Geographical difference were evident among US regions, with highest proportion of HCC treated at academic centers in New England states (83.6%) and lowest in South Atlantic states (48.6%). Overall survival was superior for academic versus non-academic centers (HR = 0.89, 95% CI: 0.87-0.91, p < 0.001) and high versus low volume centers (HR = 0.79, 95% CI: 0.77-0.81, p < 0.001), after multivariable adjustment for potential confounders. These effects were evident among all HCC treatment modalities. Conclusions: HCC treatment in academic centers shows distinct patterns according to patient demographics and US geography. Among all treatment modalities, both academic setting and hospital volume independently affected HCC outcomes, with highest patient survival observed in high-volume academic centers.
The impact of histology (adenocarcinoma vs. SCC) on outcomes in nonmetastatic pancreatic cancer.
Authors: Gruhl Joshua , Francis Samual Roberts , Tao Randa , Solomon Benjamin Lev , Nevala-Plagemann Christopher Duane , Garrido-Laguna Ignacio , Lloyd Shane 
Published: January 2019

419 Background: Outcomes in squamous cell carcinoma (SCC) of the pancreas are generally thought to be poor compared with adenocarcinoma; however, this has not been sufficiently demonstrated in prior studies. This is the first NCDB analysis of the prognostic role of SCC histology in non-metastatic pancreatic cancer. Methods: We analyzed patients with non-metastatic pancreatic cancer using the National Cancer Database (NCDB) diagnosed from 2006-2014. Patients were analyzed according to histology—only adenocarcinoma, adenosquamous carcinoma, or SCC were selected for. The primary endpoint was overall survival (OS) from the time of diagnosis. Kaplan-Meier and Cox proportional hazard modeling were used to analyze OS. Results: A total of 94,928 patients were included; 94,016 in the adenocarcinoma group, 757 in the adenosquamous group, and 155 in the SCC group. There was a statistically significant decrease in median OS for patients with SCC (MS = 8.67 months, 95% CI: 7.23–9.92 months), compared to patients with adenosquamous carcinoma (MS = 12.7 months, 95% CI: 11.9–13.7 months) and adenocarcinoma (MS = 14.0 months, 95% CI: 13.86–14.06 months, p < .001). On multivariate Cox regression, both adenocarcinoma and adenosquamous carcinoma were associated with a longer OS compared with SCC (for adenocarcinoma, HR 0.45, 95% CI: 0.31–0.66, p < .001; for adenosquamous carcinoma, HR 0.60, 95% CI: 0.39–0.92, p = 0.02). On subgroup analysis, this OS improvement for adenocarcinoma histology was seen for patients with resectable/borderline resectable disease (HR 0.50, 95% CI: 0.32–0.79, p =.003) and for those with unresectable disease (HR 0.39, 95% CI: 0.19–0.77, p = 0.01). Conclusions: In patients with non-metastatic pancreatic cancer, there was a statistically significant detriment in OS for those with SCC histology compared with adenosquamous carcinoma or adenocarcinoma histology. On subgroup analysis, this difference persisted for those with resectable/borderline resectable disease and for those with unresectable disease. [Table: see text]
Evaluation of disease-specific and functional symptom items on carcinoid tumor patients treated with telotristat ethyl.
Authors: Hudgens Stacie , Lapuerta Pablo , Floden Lysbeth 
Published: January 2019

427 Background: Within the pivotal, phase III TELESTAR trial, telotristat ethyl significantly reduced bowel movement (BM) frequency compared to placebo ( P < 0.001) (NCT01677910). Assessing patient-related outcomes can help understand the impact of changes in BM frequency on patient lives. An analysis was done to determine whether individual items on patient-reported outcome measures show relevant patterns over the course of treatment for patients with carcinoid syndrome (CS). Methods: The TELESTAR study was a phase III, double-blind, parallel-group, randomized, placebo-controlled study comparing placebo (PBO) to telotristat ethyl (TE) in 135 patients with Carcinoid Syndrome (CS). Clinical quality of life (QoL) measurements included the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer (EORTC) GI.NET21 scales. Analyses on identified individual gastrointestinal (GI) symptom and role function items were conducted using longitudinal generalized estimation equations (GEE; reference=PBO) to characterize the likelihood of a 1-grade categorical improvement (e.g., improvement by one category on the verbal response scale). Forest plots of odds ratios (OR) and associated confidence intervals (CI) on individual items are presented. Results: At week 12, the likelihood of patients experiencing a 1-grade improvement on most GI symptoms were equivalent (OR approx. 1.0). The highest odds ratios observed with TE were for improvement in diarrhea (OR=1.86, CI=0.848-4.090) and a reduction in weight bother (OR=2.95, CI=0.713-12.199), in parallel to TELESTAR results for bowel movement frequency reduction and weight gain. Interference with daily activities (IADL) and limitations in doing work demonstrated similar outcomes (IADL OR=1.63, CI=0.617,4.288; Work OR=1.97, CI=0.722,5.376). Conclusions: The overall pattern of item level change on telotristat suggested clinical relevance for bowel movement frequency reduction and weight gain, and it was consistent with symptomatic and functional benefit in CS. Clinical trial information: NCT01677910.
Stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion.
Authors: Munoz-Schuffenegger Pablo , Barry Aisling S , Atenafu Eshetu G. , Kim John , Brierley James D. , Ringash Jolie , Brade Anthony M. , Dinniwell Robert Edward , Wong Rebecca , Cho Charles , Sapisochin Gonzalo , Dawson Laura A. 
Published: January 2019

428 Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. This study describes long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were eligible for analysis. Patients who had extrahepatic disease or who had prior liver transplant were excluded. Demographical, clinical, and treatment variables were collected, under IRB approval. The degree of vascular invasion was quantified into two categories: main portal vein branch/IVC and distal portal/hepatic vein. Results: 128 eligible pts with HCC and MVI were treated with SBRT ( > 4.5 Gy/fraction). The median age was 61 yrs (range: 39 to 90 yrs). Underlying liver disease was hepatitis B in 23%, hepatitis C in 45%, other in 20%; no known liver disease in 12%. Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%, B7 or higher in 13%. 35% received previous liver-directed therapies. Median HCC volume was 153.7 mL (range: 3.9 to 1,813.5 mL). Median AFP was 205 ug/L (range: 1 to 171,154 ug/L). Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 6 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). SBRT dose or HCC volume were not significant on univariate analysis. Median overall survival was 18.3 months (95% CI 11.2 to 21.4 months). ECOG PS > 1 (HR:1.73, p = 0.03), CP score (HR: 1.67, p = 0.04), and treatment between 2004 and 2010 (HR: 2.28, p = 0.0009) were significant on multivariable analysis, while SBRT dose, HCC volume, and degree of vascular invasion were not. In 35 patients who received sorafenib following SBRT, median survival was 38.5 months (95% CI 17.23 to 43.16 months). 4/128 pts. developed GI bleeding and 35/112 patients with liver function evaluable at baseline and 3 months had a deterioration in CP class. Conclusions: SBRT was associated with excellent outcomes for patients with HCC and MVI. Randomized phase III trials of SBRT are warranted and ongoing.
DNA methylation signature predictive of benefit from neoadjuvant chemotherapy in esophageal adenocarcinoma: Results from the MRC OEO2 phase III trial.
Authors: Sundar Raghav , Ng Alvin , Zouridis Hermioni , Sheng Taotao , Zhang Shenli , Lee Ming Hui , Padmanabhan Nisha , Ooi Wen Fong , Qamra Aditi , Nankivell Matthew Guy , Langley Ruth E. , Allum William H. , Cunningham David , Grabsch Heike I , Tan Patrick 
Published: January 2019

43 Background: Platinum and 5-Fluorouracil (5FU) neoadjuvant chemotherapy followed by surgery is one of the standard approaches for patients with resectable EAC. To date, there are no predictive biomarkers of chemotherapy benefit. We hypothesize that DNA methylation of genes in key biologic and oncogenic pathways predict for chemotherapy benefit in EAC. Methods: In the OE02 trial, 802 patients with resectable esophageal carcinoma were randomised to surgery alone (S) versus two cycles of cisplatin and 5FU chemotherapy followed by surgery (CS). DNA was extracted from 213 EAC resection specimens (110 from the (CS) arm, 103 from the (S) arm). DNA methylation was analyzed at 1505 CpG sites within 807 genes using the Illumina GoldenGate platform. Cox proportional hazard analysis was performed to identify predictive markers of survival in (CS) arm; non-negative matrix factorization (NMF) was used to delineate methylation signatures. Results: Methylation status of 1505 CpG sites had no statistical difference between the (CS) and (S) arms. In the (CS) arm, 87 (5.7%) CpG sites were initially identified as promising candidates in univariate analysis (p < 0.05 cutoff). NMF generated a 4 CpG site signature which divided patients into poor risk and good risk. Genes involved in the signature include RUNX1T1, CCND2, MST1R and MMP14. Survival was significantly different between poor risk and good risk in (CS) arm (HR 0.32, 95% CI: 0.21 to 0.52, p < 0.0001). No difference in survival was detected in the surgery arm (HR 1.12, 95% CI: 0.76 to 1.80, p = 0.48), suggesting the signature served as a predictive and not prognostic biomarker. Methylation signature remained an independent predictor of survival in multivariate analysis with clinicopathologic factors (along with age and vascular invasion). Conclusions: Chemotherapy does not appear to change methylation status of EAC. Hypermethylation of RUNX1T1, CCND2 and hypomethylation of MST1R and MMP14 leads to significantly decreased benefit from chemotherapy in EA. We describe an epigenetic signature which may serve as a predictive biomarker for chemotherapy benefit using data form the largest bank of DNA methylation in EA reported to date.
A retrospective study of hepatic arterial infusion (HAI) FUDR/Dex and mitomycin C (MMC) for chemotherapy refractory unresectable intrahepatic cholangiocarcinomas (ICC).
Authors: Fernandes Gustavo Dos Santos , Kemeny Nancy E. , Hauser Haley , Harding James J. , Boerner Thomas , Varghese Anna M. , Kingham Peter , D'Angelica Michael Ian , DeMatteo Ronald P. , Drebin Jeffrey A. , Balachandran Vinod P. , Jarnagin William R. , Cercek Andrea 
Published: January 2019

432 Background: ICC are aggressive tumors with approximately 6,000 cases a year in US. The 5-year survival rate is less than 30% even for localized disease. There is only one approved line of systemic (SYS) treatment and further treatment options are necessary. HAI chemotherapy is an option to treat liver predominant cancers. Methods: After obtaining IRB approval, we retrospectively reviewed patients (pts) with ICC chemo refractory unresectable liver limited (LL) or liver dominant (LD) disease who received intrahepatic chemotherapy with HAI MMC. Baseline characteristics, previous lines of therapy, toxicity profile, combinations and radiographic responses were reviewed. Tumor genomic analyses were performed on samples using an on-site next generation sequencing (NGS) assay. Results: Between January 2011 and October 2018, 19 patients ICC with LL or LD disease were treated with HAI FUDR/Dex/MMC at Memorial Sloan Kettering Cancer Center. Disease was confined to the liver in 58% of the pts. All pts had previous chemotherapy (1-4 lines) and 14 (74%) previously had HAI FUDR/Dex. Of the 19 pts, 56% had HAI with FUDR/Dex and MMC, 43% had FUDR/Dex, MCC and SYS and 5% had HAI MMC and SYS. Seventeen patients were evaluable for response, two are being treated and will have response assessment for the meeting. Response was noted in 4 (23.5%), stable disease in 6 (35.5%) and progressive disease in 7 (41%) pts. Median overall survival from treatment was 6.1months (0.36-26). Median progression free survival was 3.65 months (0.36-9.53). Four patients had dose reductions. Common toxicity attributed to MMC was grade (G) one fatigue (32%), thrombocytopenia G1(16%) and G2 (5%). Of the 12 tumors analyzed to date the most 92% of tumors harbored at least one (0-10) genomic alteration. Common genomic alterations were ARID1 (25%), RASA1 (25%), IDH1(16.6%), NTRK (16.6%), TERT (16.6%), NRAS (16.6%), CDKN2 (16. 6%). FGFR2-FOXP1 and GTL2MEt fusions were found in one patient each. Conclusions: HAI FUDR/Dex/MMC containing regimens are active in pts with heavily pretreated refractory unresectable ICC. This strategy should be further investigated. Translational data will be presented.
Clinical outcomes of hepatocellular carcinoma variants compared to hepatocellular carcinoma.
Authors: Zakka Katerina Mary , Jiang Renjian , Alese Olatunji B. , Shaib Walid Labib , Wu Christina , Wedd Joel , Sellers Marty T. , Behera Madhusmita , El-Rayes Bassel F. , Akce Mehmet 
Published: January 2019

435 Background: There is no consensus regarding treatment for HCC variants. Clinical outcomes of HCC variants differ from pure HCC. The aim of this study is to compare clinicopathological characteristics, treatment, and outcomes of HCC variants with pure HCC. Methods: Patients with HCC and variants with 8170/3-8175/3 and 8180/3 ICD-O-3 codes were identified from National Cancer Database between 2004 and 2013. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS). Results: 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. The mean age was similar in all except FLHCC (37.9 vs. 60.9-64.1 years, p < 0.001). Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p < 0.001). Pure HCC (10.57%) underwent surgical resection less often than variants; FLHCC (54.8%), clear cell (34.5%), mixed HCC (29.8%), spindle cell (33.3%), pleomorphic (34.8%), and scirrhous (9.9%) (p < 0.001). Ablation was performed in 9.8% of pure HCC, and in up to 8.7% of HCC variants. More than a third of all patients received chemotherapy; pure HCC (42.3%), mixed HCC (38.5%), scirrhous (31.1%), spindle cell (36.1%), clear cell (35.5%), pleomorphic (34.8%), and FLHCC (41.3%). FLHCC had the best 5-year OS (38.7%), spindle cell and pleomorphic had the worst (9.6% and 13.0%). In univariate and multivariate analyses, fibrolamellar histology, female sex, diagnosis between 2009 and 2013, treatment at academic center, well/moderately differentiated histology, early stage, and chemotherapy was associated with better OS compared to pure HCC, male sex, diagnosis between 2004 and 2008, treatment at community cancer program, poorly differentiated, late stage, and no chemotherapy (p < 0.001). Conclusions: HCC variants underwent surgical resection more often than HCC. FLHCC had the best 5-year OS. Liver transplant is commonly performed in HCC variants.