bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II study of Chinese patients (pts) treated with nab-paclitaxel (nab-P) plus gemcitabine (Gem) for metastatic pancreatic cancer (MPC).
Authors: Shen Lin , Yu Xianjun , Hao Jihui , Wang Liwei , Pan Hongming , Han Guohong , Xu Jian-Ming , Zhang Yanqiao , Yang Shujun , Chen Jia , Ying Jieer , Dai Guanghai , Li Mingyu , Begic Damir , Lu Brian D. , Xu Ruihua
Published: February 2017

327

Background: nab-P + Gem demonstrated significantly better overall survival (OS; median: 8.7 vs 6.6 mo; HR 0.72; P < 0.001) than Gem alone as first-line treatment for pts with MPC in the MPACT study. This phase II bridging study evaluated efficacy and safety of nab-P + Gem in Chinese pts with MPC. Methods: Efficacy and safety of nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 4 weeks was evaluated in a 3-part sequential study. In part 1, safety was examined. In part 2, efficacy was evaluated by the Simon optimal 2-stage design. If there were > 2 responses in 28 pts in stage 1 of part 2, an additional 54 pts would be treated in stage 2. The study would be completed if > 9 responses were observed. If there was an insufficient number of responses in either stage of part 2, part 3 would be triggered to compare nab-P + Gem vs Gem alone. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), OS, and safety. Correlation of OS and baseline neutrophil-to-lymphocyte ratio (NLR) was also analyzed. Results: Eighty-three pts were treated. Median age was 57.0 y; 19% were aged > 65 y; baseline Karnofsky performance status was 90 - 100 in 70% of pts and 70 - 80 in 30%. Combining results for stages 1 and 2, ORR was 35% by independent assessment, median DOR was 8.9 mo (95% CI, 6.01 - 8.94), median OS and PFS were 9.2 mo (95% CI, 7.60 - 11.10) and 5.5 mo (95% CI, 5.29 - 7.16), respectively (Table). Baseline NLR ≤ 5 was associated with a nonsignificant trend toward longer OS vs NLR > 5 (median, 10.0 vs 8.3 mo; HR 0.62; P= 0.148). The most common grade ≥ 3 adverse events included neutropenia (37%), leukopenia (31%), and fatigue (14%). Grade ≥ 3 peripheral neuropathy occurred in 7% of pts. Part 3 was not triggered per study design. Conclusions: nab-P + Gem demonstrated efficacy in Chinese pts with MPC. The OS and ORR were numerically better than those of the phase III MPACT trial (Table). A trend toward longer OS in pts with baseline NLR ≤ 5 vs > 5 confirmed previous findings from the MPACT study. No new safety signals were identified. Clinical trial information: NCT02135822. [Table: see text]
Gallbladder cancer presenting with jaundice: Uniformly fatal or still potentially curable?
Authors: Tran Thuy , Ethun Cecilia Grace , Pawlik Timothy M. , Buettner Stefan , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Krasnick Bradley , Weber Sharon M. , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles R. , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar , Poultsides George A.
Published: February 2017

336

Background: The prognosis of patients with gallbladder cancer (GBC) who present with jaundice has historically been considered dismal, however recent Eastern literature has demonstrated that surgical resection can be associated with long-term survival. The objective of this study was to utilize a contemporary, Western, multi-institutional dataset to examine the prognostic significance of preoperative jaundice on short- and long-term outcomes after GBC resection. Methods: Patients with GBC managed surgically from 2000 to 2015 in 10 academic institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium were stratified based on the presence of preoperative jaundice (bilirubin > 3 mg/ml or requiring preoperative biliary drainage). Postoperative morbidity, mortality, and overall survival were compared. Results: Of 449 patients with GBC evaluated for resection, 301 (67%) eventually underwent curative-intent resection. Resectability for cure was much lower in patients with preoperative jaundice (48% vs. 79%, p < 0.001). Of 273 patients who underwent curative-intent resection and had available preoperative bilirubin levels, 53 (19%) had preoperative jaundice and were noted to have tumors of T3/4 stage (63% vs 42%, P = 0.008), with lymph node metastasis (63% vs. 41%; p = 0.014), lymphovascular invasion (68% vs 39%; p = 0.003), and R1 margins (37 vs. 9%; p < 0.001). Patients with jaundice more commonly required CBD (55% vs 32%, P = 0.004), major liver (25% vs. 7%; p < 0.001) and portal vein resection (8% vs. 0.5%; p = 0.006), as well as intraoperative blood transfusion (29 % vs. 11%; p = 0.002). Overall morbidity (57% vs. 38%; p = 0.031) and in-hospital mortality (7.5% vs. 1.4%; p = 0.029) rates were higher in patients with jaundice. Overall survival after curative-intent resection was worse in patients with jaundice (median 12 vs 33 months; p < 0.001). Conclusions: Half of GBC patients presenting with jaundice are not resectable for cure and when they are, their 5-year survival is 12%. These patients should not be excluded from multidisciplinary treatment strategies that include surgery, however expectations should be clearly set and selection should be cautious.
Survival of pancreaticoduodenectomies with venous reconstruction using a population-based database.
Authors: Goldner Bryan S. , Tozzi Federrico , Melstrom Laleh , Warner Susanne , Singh Gagandeep
Published: February 2017

340

Background: Locally advanced disease requiring pancreaticoduodenectomy (PD) with venous reconstruction is a controversial topic that is often determined by careful patient selection. There are numerous published single institution, but sparse multicenter studies, demonstrating the safety and efficacy of PD with venous reconstruction. The goal of this study is to evaluate survival outcomes in patients who underwent a PD with our without venous reconstruction utilizing a large statewide database. Methods: The California Cancer Registry (CCR) was used to obtain data on all PD performed from 2000-2011. This data was merged with Office of Statewide Planning and Development data to obtain inpatient hospitalization data. ICD-09 codes were used to identify all PD with or without venous reconstruction. Data was obtained on demographics, disease process, surgery, hospitalization statistics, and survival. Venous reconstruction was divided into venous segmental resection with reconstruction (VSR) and primary repair of the vein with a patch (PR). Survival was analyzed using Kaplan-Meier Survival analysis (KM). Results: Data were obtained on 5,228 patients who underwent PD, 3.7% (161) underwent venous reconstruction (148; 2.8% VSR and 43; 0.8% PR). A significant overall survival difference between PD and all vascular reconstruction was observed (23 months vs 17 months respectively, p < 0.001). Further analysis revealed no significant difference in survival between standard PD and PD with PR (median 21 months; p = 0.2). However, there was a significant survival advantage of PD compared to PD with VSR (21 vs 16 months respectively, p < 0.001). Evaluation of length of stay and complications revealed no statistical difference (p = 0.07 and p = 0.8). Conclusions: Venous reconstruction in PD is associated with worse survival compared to PD alone. Interestingly, patients who had a PR had a better survival than VSR alone. Overall survival for all comers of vascular reconstruction remains inferior which reinforces the biology of disease as an important predictor of outcomes as well as shorter segment portal vein involvement conferring improved survival.
Comprehensive analysis of radiographic, clinical, and inflammatory markers demonstrating changes in lean muscle correlate with outcome in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) who undergo taxane-based chemotherapy (CT).
Authors: Ahn Daniel H. , Ahn Chul , Nagar Veena , Noonan Anne M. , Farren Matthew , Lesinski Gregory B. , Knopp Michael V. , Bekaii-Saab Tanios S.
Published: February 2017

349

Background: MPDAC is associated with a poor prognosis. The mechanisms of carcinogenesis are complex; involve multiple signaling pathways and inflammatory cytokines that may promote cachexia, a major cause of morbidity and mortality in mPDAC. The purpose of this study is to understand factors related to skeletal muscle changes, and its effect on outcomes in pts with mPDAC. Methods: Pt and clinical data were obtained from a recent prospective clinical trial in mPDAC where all pts received first-line taxane-based CT. We examined changes in modified Glasgow prognostic score, neutrophil lymphocyte ratio, a 32-cytokine panel, weight, and skeletal muscle area (SMA), determined by validated methodology with computed tomography, at baseline and cycle 3. We defined > 6cm2 in SMA, correlating to 1kg of skeletal muscle gain (SMG), as significant. Univariate and multivariate Cox regression models were used to determine the association between laboratory, radiographic and clinical findings with progression free survival (PFS) and overall survival (OS). Results: 66 evaluable pts were included. Independent of clinical response, an OS advantage was seen in pts who experienced significant SMG (p = 0.023) and in patients with nominal SMG (p = 0.012). A numerical benefit in PFS was observed with SMG. Decreases in IFN-a (p = 0.024), IFN-g (p = 0.001) and IL-6 (p = 0.042) were inversely associated with SMG. A comprehensive analysis incorporating all relevant laboratory, radiographic and clinical assessments demonstrated a 4.62-month OS advantage in pts with favorable characteristics vs. those with poor prognostic factors (11.47 versus 6.84 mos., p = 0.0029). Conclusions: SMG, or the reversal of cachexia confers an OS advantage in pts with mPDAC treated with taxane-based CT regardless of clinical response. A comprehensive assessment of muscle change is a precise measurement that can identify pts at greatest risk for muscle loss, which could predict for trmt response and pt outcomes. This merits further investigation as a tool and in trials directed at reversing the process of cachexia.
A phase II study of biweekly gemcitabine at fixed dose rate infusion plus S1 as first-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer.
Authors: Xiang Xj , Zhang L , Li Jh , Zhan Zy , Feng M , Chen J , Xiong JP
Published: February 2017

357

Background: The combination regimen of gemcitabine plus S1 (GS) as first-line chemotherapy has shown good efficacy in advanced pancreatic cancer. However, it is inconvenient to deliver gemcitabine on days 1 and 8 within one treatment cycle. In addition, previous studies have demonstrated that the gemcitabine administration by fixed dose rate infusion of 10 mg/m2/min should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. The aim of this study was to evaluate the efficacy and safety of biweekly gemcitabine at fixed dose rate infusion combined with S1 (FGS) in chemonaive patients with locally advanced or metastatic pancreatic cancer. Methods: Forty-three eligible patients with locally advanced or metastatic pancreatic cancer received gemcitabine at a fixed dose of 10 mg/m2/min intravenously over a 2-h period on day 1, together with oral S1 40mg/m2twice daily on days 1 to 10, every 2 weeks. Tumor assessment was performed for every 3 cycles of chemotherapy. Results: All patients were evaluable for toxicity and 42 patients for efficacy. The overall response rate was 35.7% with 1 complete response, 14 partial responses, 17 stable diseases, and 10 progressions. Median time to progression was 5.9 months and median overall survival was 9.6 months. The main grade 3/4 toxicities included neutropenia (30.2%), thrombocytopenia (6.9%), anemia (2.3%), nausea (4.6%), diarrhea (2.3%). Conclusions: The biweekly FGS regimen is active, well tolerated and conveniently delivered as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.
Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors.
Authors: Kirichenko Alexander V. , Parda David S. , Sanguino Angela , Gayou Olivier , Raj Moses S. , Monga Dulabh K. , Thai Ngoc
Published: February 2017

360

Background: We report on the outcome and toxicity of liver SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors. Methods: Patients with up to four isolated hepatic metastases (sum of tumor diameters ≤ 8cm) and individual tumor diameter ≤ 9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. In patients with hepatic cirrhosis, liver dose constraints were imposed exclusively on residual functional liver volume defined on SPECT during SBRT treatment planning. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. Results: Between 2007-2014, 120 lesions in 91 patients with either unresectable primary (n = 43) or metastatic liver cancer (n = 48) completed liver SBRT to 36-60 Gy delivered in 4 to 6 treatment fractions, with a mean BED of 197 Gy3 (range 108 – 300 Gy3). Median followup was 20.3 months (range 1.9 - 64.1). Fourteen patients underwent liver transplant with SBRT as a bridging therapy or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤ 4cm. Ten of 14 transplanted patients developed complete pathological response with median time to transplant of 5.7 months (range 1.7 – 23.3). No incidence of grade > 2 treatment toxicity was observed. There was no accelerated Child-Pugh class migration from A to B or from B to C. There were no operative or perioperative complications in patients who received SBRT prior to liver transplant or in combination with planned hepatectomy. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). Conclusions: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates with minimal toxicity.
Defining radiation induced liver toxicity in the treatment of hepatocellular carcinoma: Which metric is most predictive for survival?
Authors: Chapman Tobias Robert , Bowen Stephen R. , Nyflot Matthew J. , Apisarnthanarax Smith
Published: February 2017

361

Background: Radiation induced liver disease (RILD) is of critical concern in the treatment of hepatocellular carcinoma (HCC) with radiation therapy (RT). Variability exists in metrics used to define RILD with no consensus on which best predict for overall survival (OS) and RILD-specific survival (RILDSS). We examined the correlation between toxicity metrics and clinical outcomes in a heavily pre-treated population that received RT. Methods: The charts of 37 HCC patients treated from 2013 - 2015 were reviewed retrospectively. At baseline, 62% were Child-Pugh (CP)-A, 32% CP-B and 5% CP-C. The majority (59%) had prior liver-directed therapy (LDT), 43% received stereotactic body RT and 49% proton RT. Pre-treatment, toxicity ( ≤ 6 months from treatment) and outcomes data were collected. Deaths from RILD were scored. Pre-treatment factors and toxicity outcomes were assessed by univariate Cox models for association with OS and RILDSS. Statistically significant predictors formed the basis for stepwise multivariate Cox regression to retain independent predictors of survival. Results: At a median follow-up of 8 months, 14 patients had an increase in CP score ( ≥ 2, n = 7) and 3 had ≥ G3 RTOG transaminitis. There were 11 deaths, 5 from RILD. On univariate analysis (UA), tumor size, pre-treatment liver function, prior LDT and 5 toxicity metrics (CP score increases and transaminitis) were significantly associated with OS. An increase of ≥ 1 CP score (HR 22.7, p = 0.005), pre-treatment ALBI grade (HR 6.0, p = 0.02) and tumor size (HR 1.2, p = 0.01) were independent predictors of OS on multivariate analysis (MVA). Similar factors were associated with RILDSS on UA, including ≥ 2 CP score increase and ≥ G3 ALT elevation; however, only pre-treatment CP score (HR 4.0, p = 0.01) and tumor size (HR 1.5, p = 0.03) were independently predictive on MVA. Conclusions: Pre-treatment liver functional status and tumor size were highly predictive of OS and RILDSS, suggesting that baseline functional hepatic reserve is the primary determinant in developing fatal RILD rather than post-RT changes in liver function. Further work is needed to define dosimetric parameters and pre-treatment factors that predict RILD toxicity.
Using the ALBI grade as a prognostic marker for radioembolization of hepatocellular carcinoma.
Authors: Mohammadi Homan , Abuodeh Yazan , Jin Will , Frakes Jessica M. , Friedman Mark , Biebel Benjamin , Choi Junsung , El-Haddad Ghassan , Kis Bela , Sweeney Jennifer , Kim Richard D. , Pimiento Jose Mario , Malafa Mokenge Peter , Anaya Daniel A. , Hoffe Sarah E.
Published: February 2017

366

Background: The Childs-Pugh class (C-P) is a commonly used scoring system to measure liver function in patients with hepatocellular carcinoma (HCC). While originally developed for patients undergoing esophageal resection for varices in the setting of cirrhosis and portal hypertension, it is now a widely accepted measure of liver function. The Albumin-Bilirubin (ALBI) grading system is a model developed in 2015 to assess liver function that has eliminated the subjective measures present in C-P. We correlate the ALBI grading system and C-P classes to overall survival in our HCC patients receiving radioembolization. Methods: With IRB approval, we retrospectively evaluated patients who received radioembolization for HCC between 2009-2014. We evaluated the albumin and bilirubin levels in our patients prior to receiving their first radioembolization (n = 121). The ALBI grades were calculated from these data with the formula (log10 bilirubin x 0.66) + (albumin x -0.085) and separated into grades based on the thresholds set in the original manuscript. These grades were then correlated to outcomes using Mantel-Cox Log analysis. The statistical comparisons were duplicated with C-P classes. Results: Median survival for C-P class A and B were 13.1 and 8.4 months (p < 0.0005), respectively while median survival for ALBI grades 1 and 2 were 20.9 and 11.0 months (p < 0.0005), respectively. Our C-P class A patient group was re-stratified using the ALBI formula and found to have two cohorts of patients with statistically significant differences in survival. The median survival between ALBI grades 1 and 2 within this patient group was 20.9 and 11.0 months (p = 0.002), respectively. Too few C-P class C or ALBI grade 3 patients were within our dataset for statistically significant results. Conclusions: We demonstrated that the ALBI grading system is a more sensitive marker of liver function than the C-P classes in the setting of mild to moderate dysfunction. Using the ALBI grade, we identified a subset of patients that have significantly better outcomes from radioembolization for HCC within C-P class A.
Phase I trial of biweekly S-1, leucovorin, oxaliplatin, and gemcitabine (the SLOG regimen) in metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Chiang Nai-Jung , Tsai Kelvin K. , Chen Jen-Shi , Yang Shih-Hung , Hsu Chiun , Shan Yan-Shen , Chen Li-Tzong
Published: February 2017

369

Background: Gemcitabine and S-1 had been approved as the frontline treatment for mPDAC in Taiwan and Japan. Our previous study showed biweekly gemcitabine plus modified FOLFOX4 (the GOFL regimen) was a moderate active and well-tolerated regimen in mPDAC. To explore whether oral S-1/LV can be a substitute for infusion 5-FU/LV in combination with gemcitabine and oxaliplatin as “the SLOG regimen” to improve treatment efficacy and convenience. To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary anti-tumor efficacy of SLOG in patients with chemo-naïve mPDAC. Methods: Enrolled patients would receive intravenous infusion of 800 mg/m2 gemcitabine (fixed-dose rate infusion, 10 mg/m2/min) followed by 85mg/m2 oxaliplatin (2 hours) on D1 and escalating dose of oral S-1 and 20 mg/m2 leucovorin, twice daily D1-D7, every 14 days. DLTs were evaluated during the first 2 cycles of treatment. The treatment was continued until disease progression, unacceptable toxicity or withdrawal of informed consent. Results: 19 patients were enrolled into four dose levels of S-1, 20 mg/m2 (three), 30 mg/m2 (seven), 35 mg/m2 (six) and 40 mg/m2 (three). At 30 mg/m2 dose level, one patient who withdrew consent after one cycle treatment was replaced with another one. DLTs were observed in three patients, one at 30 mg/m2 (grade 3 diarrhea) and two at 40 mg/m2 (grade 3 hypersensitivity reaction and diarrhea in one each). MTD of S-1 was determined as 35 mg/m2. The median treatment duration was 8 cycles (ranged, 1-26). Of the 16 evaluable patients, the objective response rate and disease control rate were 37.5% (6 partial response, PR) and 81.3% (6 PR + 7 stable disease, SD), respectively. The median progression-free survival (PFS) was 4.6 months. At MTD dose level, there were 4 PR and 2 SD, with 6.7 months of PFS. The most common grade 3-4 adverse events included neutropenia (26.4%), diarrhea (15.8%), ALT increased (10.5%) and anemia (10.5%). Conclusions: The MTD of S-1 was 35 mg/m2 in the SLOG regimen. Extension phase II study in mPDAC is ongoing. Clinical trial information: NCT 01415713.
A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).
Authors: Hong Theodore S. , Wo Jennifer Yon-Li , Ben-Josef Edgar , McDonnell Erin , Drapek Lorraine C. , Blaszkowsky Lawrence Scott , Kwak Eunice Lee , Clark Jeffrey W. , Goyal Lipika , Ryan David P. , Javle Milind M. , Arellano Ronald , Wolfgang John A. , Mullen John Thomas , Ferrone Cristina , Tanabe Kenneth , DeLaney Thomas F. , Crane Christopher H. , Zhu Andrew X.
Published: February 2017

376

Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate > 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( > 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.
Multidisciplinary management of pancreatic adenocarcinoma with isolated pulmonary metastases.
Authors: Jain Supriya K. , Meguid Cheryl , Leong Stephen , Edil Barish H. , McCarter Martin , Schefter Tracey E. , Schulick Richard D. , Lieu Christopher Hanyoung
Published: February 2017

384

Background: Metastatic pancreatic adenocarcinoma (PAC) with isolated pulmonary metastases has recently been associated with prolonged overall survival. The purpose of this study was to review multi-disciplinary management and outcomes of these patients. Methods: Patients with PAC with pulmonary-only metastases were queried between 2012 to 2015 from a prospective single-institutional database. Results: Ten patients (median age: 71 yrs) were identified. Median number of lung metastases at diagnosis was 3 (range: 1 to innumerable). Seven patients had biopsy-proven lung metastases. Five presented with synchronous metastatic disease and five developed metachronous lung metastases as their first site of progression. Median time to progression between diagnosis of primary cancer to diagnosis of pulmonary metastases was 15 months (range: 4 to 31). Seven patients are alive as of this analysis. Median overall survival (OS) of this series (including two patients diagnosed 3 and 6 months ago) is 17 months, with longest overall survival = 40+ months (patient is still alive). All patients received gemcitabine-based chemotherapy; however, systemic regimens differed and included investigational agents. 3 of 5 patients with metachronous metastases underwent pancreaticoduodenectomy and are long-term survivors (34-40+ months). 2 of these 3 patients had diagnostic VATS of lung metastases and are alive with overall survival of 36+ months (resection of 2/3 nodules) and 34+ months (resection of all visible disease). Two patients with metachronous disease underwent neoadjuvant chemotherapy and pancreatic SBRT with progression to lung prior to planned surgery (OS: 30 months (deceased) and 6+ months (recently diagnosed)). 0 of 5 patients with synchronous metastatic disease had surgical resection; 3 of 5 received pancreatic SBRT. 3 of 10 patients are deceased due to visceral disease (14 months), pulmonary failure (18 months), and unknown causes (30 months). Conclusions: We report a recent single-institutional series of PAC with isolated lung metastases. Our data support that metastatic PAC patients with isolated pulmonary metastases have prolonged overall survival and suggest that local intervention may be beneficial.
Impact of chemotherapy and external beam radiation therapy on outcomes among patients with resected gallbladder cancer: A multi-institutional analysis.
Authors: Kim Yuhree , Amini Neda , Wilson Ana , Ethun Cecilia Grace , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Weber Sharon M. , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar , Pawlik Timothy M.
Published: February 2017

387

Background: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) in the treatment of resectable gallbladder cancer remains varied. We sought to define the utilization and effect of adjuvant therapy on patients having undergone curative-intent resection for gallbladder cancer. Methods: Using a multi-institutional national database, 291 patients with gallbladder cancer who underwent curative-intent resection between 2000 and 2015. Patients with metastasis or an R2 margin were excluded. The impact of adjuvant therapy on survival was analyzed among patients who received surgery alone versus CTx versus cXRT. Results: Median patient age was 66 years. Most patients had a T2 (41.9%) or T3 (35.1%) lesion and 37.8% of patients had lymph node (LN) metastasis. A total of 186 (63.9%) patients underwent surgery alone, 61 (21.0%) received CTx, whereas the remaining 44 (15.1%) patients received cXRT. At a median follow-up of 16.3 months, median and 5-year overall survival (OS) was 28.3 months and 33.0%, respectively. On multivariable analysis, factors associated with worse OS included AJCC T3/T4 (hazard ratio [HR] 2.97), LN metastasis (HR 1.75) and lymphovascular invasion (HR 1.98; all P<0.05). In contrast, receipt of CTx or cXRT was associated with improved long-term OS (CTx, HR 0.33; cXRT, HR 0.27; P<0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS)(CTx, HR 0.53; cXRT, HR 0.45; P<0.01). Of note, the OS benefit for CTx or cXRT was observed among patients with high risk features such as AJCC T3/T4 disease (HR 0.61; HR 0.31), LN-metastasis (HR 0.45; HR 0.46), and R1 disease (HR 0.33; HR 0.11) (all P<0.05). In contrast, the OS benefit of CTx and cXRT was not noted among patients with T1/T2 or N0 disease, or among those with an R0 margin (all P>0.05). Conclusions: Adjuvant CTx and cXRT were utilized in 36% of patients undergoing curative-intent resection for gallbladder cancer. After adjusted analysis, CTx and cXRT were independent factors associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.
Treatment strategy for intrahepatic cholangiocarcinoma: From optimal surgical management to adjuvant therapy.
Authors: Morine Yuji , Shimada Mitsuo , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Yamada Shinichiro , Yoshikawa Masato , Teraoku Hiroki
Published: February 2017

392

Background: Surgical strategy for intrahepatic cholangiocarcinoma (IHCC) including systemic lymph nodes (LN) dissection is still controversial. Also, as adjuvant chemotherapy, we adopted this GFP regimen (GEM, 5-FU, and Cisplatin). We demonstrate the adequate surgical strategy, the effect of adjuvant therapy and the tumor malignancy evaluation. Methods: Study 1: Surgical strategy) In period 1 (1994.4-2004.3, n = 20), extended surgery was basically performed. In period 2 (2004.4~, n = 34), extent of hepatectomy is conducted according to tumor conditions. Swelling LN exterpation for macroscopic curability and bile duct resection for positive surgical margin are performed. Study2: Adjuvant GFP therapy) Induction of 2 cycles of GFP for advanced IHCC with prognostic factors (LN metastasis, intrahepatic metastasis and R2 resection). Study 3: Malignancy evaluation) Significance of serum CA19-9 levels, the relationships its levels and expressions ( immunostaining ) of hypoxic inducible factor 1 (HIF-1) /Histone deacetylase 1 (HDAC1) were evaluated. Results: Study 1) In period 2, LN dissection and extrahepatic bile duct resection were significantly infrequent. Surgical outcome is rather good regardless of limited surgery in recent periods (Period 1 vs. Period 2: 5yrs survival 24.9% vs. 34.9%, p = 0.119). There was no significant difference in recurrent pattern. Study 2) There were 32 cases had some kind of prognostic factors, and of these 11 patients received adjuvant GFP. Patient’s prognosis received adjuvant GFP was significantly prolonged (GFP vs. non GFP: 1yrs survival 71.6% vs. 45.0%, p < 0.02). Study 3) CA19-9 ( > 300U/ml) high group revealed the independent prognostic factor with stepwise model, as well as LN metastasis and vessels invasion. CA19-9 levels significantly correlated to HDAC1 and HIF-1 expressions. Conclusions: Extended surgery including LN dissection might not control malignant behavior of IHCC, and adjuvant GFP should be introduced in patients with poor prognostic factors.
Intention to treat analysis of neoadjuvant chemoradiation and liver transplantation for perihilar cholangiocarcinoma.
Authors: Loveday Benjamin , Knox Jennifer J. , Dawson Laura A. , May Gary , Metser Ur , Brade Anthony M. , Horgan Anne M. , Cummings Bernard , Grant David , Gallinger Steven , Greig Paul David , Moulton Carol-anne
Published: February 2017

394

Background: Neoadjuvant chemoradiation and liver transplantation is an option for selected unresectable patients with early stage perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate, morbidity and survival of patients who entered a modified tri-modality protocol at Princess Margaret Cancer Centre. Methods: All patients enrolled into the protocol (Jan 2009 – Aug 2015) were included in the analysis. Enrollment criteria: ≤ 65 years old with brush biopsy-proven, unresectable pCCA proximal to the cystic duct, < 3.5 cm in diameter. Neoadjuvant protocol consisted of conformal radiation therapy (54-75 Gy, 1.5 Gy BID) concurrent with Capecitabine 800 mg/m2 BID until radiation completion. Following surgical staging patients received maintenance chemotherapy (Cisplatin 25 mg/m2 and Gemcitabine 1000 mg/m2, day 1 and 8 of 21 day cycle), until transplant or progression. Intention to treat analyses were performed on prospectively collected data to determine time to progression (TTP), dropout rate, overall survival (OS), and number of biliary procedures. Results: Seventeen patients were enrolled, with a median age of 53.9 (26.7-62.8) years, and tumour diameter of 2.7 (2.0-3.4) cm. Five patients had primary sclerosing cholangitis. Median follow up was 14 (6-41) months. The cohort required a median of 3 (0-8) biliary stents, and percutaneous transhepatic biliary drainage in 11/17. Median TTP was 6 (2-16) months. Protocol dropout occurred in 10/17 due to metastatic disease identified during chemoradiation (2), surgical staging (6), or maintenance chemotherapy (2). No dropouts were due to neoadjuvant toxicity. Four patients underwent transplantation (two living donor, two deceased donor), and three are on the transplant waiting list. Median survival from first consultation and start of chemoradiation was 18.2 and 17 months, respectively. Conclusions: Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although dropout during the protocol is high. Less than half of patients who began the treatment protocol remained eligible for transplantation due to cancer progression or upstaging after surgical staging.
Splenic embolization as an alternative to surgical splenectomy for the restoration of blood counts suitable for effective chemotherapy in gastrointestinal malignancies (GIM).
Authors: Marsh Robert de Wilton , Alonzo Marc , Ferral Hector
Published: February 2017

396

Background: Chemotherapy regimens used for GIM are often notably myelosuppressive and may also engender hypersplenism. This can result in platelet (plt) and/or absolute neutrophil counts (ANC) too low for the maintenance of required dose intensity or frequency. One successful approach to this problem is surgical splenectomy but this is both morbid and invasive. An alternative strategy uses super-selective embolization of the splenic arterial tree, which is performed as an outpatient, and is far better tolerated. The true efficacy of this technique is uncertain and the optimal patients (pts) for this procedure are not well defined. Methods: Between 11/2012 and 6/2015, pts with ECOG PS 0/1 currently on active therapy for GIM in our clinics, whose plts and/or ANC were consistently below threshold values for appropriate frequency or intensity of therapy, were referred to Interventional Radiology for splenic embolization. Selective catheterization of the splenic artery was achieved via a femoral approach. This was followed by super-selective catheterization of branches of the splenic artery, as distally as possible, with subsequent embolization using Embosphere particles (300-500 micron spheres). All pts received prophylactic IV antibiotics. Results: 10 pts were identified and referred and all were deemed suitable for embolization. The mean plt count prior to the procedure was 73,000 (39,000-167,000) and the mean ANC was 3.5 (1.3 – 5.3). Following one procedure in 9 pts and 2 procedures in 1 pt, the mean plt count rose to 175,000 (55,000-432,000) and the ANC to 7.2 (2.9 – 13.2) immediately, and to a maximum of 253,000 (76,000-511,000) and 9.3 (5.0 – 14.5) within one to two months.Splenic enlargement was noted in 6 pts (mean size 18.3 cm) prior to the procedure and was not present in 4 pts. Following embolization all patients were able to resume chemotherapy with previously effective doses and/or frequency. Conclusions: In our cohort of pts with GIM, splenic embolization was successful at restoring acceptable plt and/or ANC levels for the resumption of effective chemotherapy. Splenomegaly does not appear to be a prerequisite for success.
Outcomes in metastatic pancreatic adenocarcinoma (MPAC) patients treated with FOLFIRINOX (FFX)/FOLFOX(FX) and gemcitabine + nab-paclitaxel (NabG).
Authors: Schmidt Shannon Leah , Durkal Vipal , Pattali Jayavalsan Shinoj , Thomas James P. , Ritch Paul S. , Erickson Beth , Christians Kathleen K. , Tsai Susan , Evans Douglas B. , George Ben
Published: February 2017

397

Background: Standard front line (FL) chemotherapy regimens for MPAC include FOLFIRINOX (FFX)/FOLFOX(FX) and Nab-paclitaxel plus Gemcitabine (NabG). Outcome data in patients treated with both FFX/FX and NabG has not been well characterized. We retrospectively reviewed our single institution experience in MPAC patients treated with FFX/FX and NabG in either sequence. Methods: All MPAC patients treated with FFX/FX or NabG, in either sequence, from 1/1/11 to 12/31/14 at the Froedtert and Medical College of Wisconsin (MCW) Clinical Cancer Center were identified and their charts reviewed. This study was approved by the Froedtert & MCW Institutional Review Board. Results: Among the 64 patients reviewed, median age at diagnosis was 62 years, 64.1% were male and 95.3% were Caucasian. Median Ca19-9 and CEA at diagnosis were 855 and 10.4 respectively. Liver, lung and peritoneal metastases were appreciated in 87.5%, 20.3% and 35.9% of patients. 37/64 (57.8%) patients received second line (SL) therapy. Response Rate (RR) with FFX/FX and NabG in both FL and SL therapy are summarized in the Table. The median Progression Free Survival (PFS) with FL therapy was 3.7 months and 3.5 months with SL therapy. Median overall survival (OS) of the entire cohort was 8.7 months. In patients who received 2 lines of therapy the median OS was 12.1 months. Median OS in patients who received only one line of therapy was 4.1 months. Conclusions: In patients with MPAC, sequential therapy with FFX/FX and NabG is both feasible and effective in either sequence. RR and DCR with these regimens, while modest, are acceptable in the SL setting. Patients who received two lines of therapy have a substantially better OS than patients who receive one line of therapy, suggesting a more favorable tumor biology in the former population. [Table: see text]
Outcomes of neoadjuvant chemotherapy versus chemoradiation among patients with resected pancreatic head adenocarcinoma.
Authors: Franko Jan , Hsu Harold W , Thirunavukarasu Pragatheeshwar , Frankova Daniela , Goldman Charles David
Published: February 2017

398

Background: Increasing use of neoadjuvant therapy in pancreatic cancer has been reported. We compared patterns of practice and outcomes of neoadjuvant chemotherapy (nCHT) versus chemoradiation (nCRT) among pancreatic cancer pts receiving pancreaticoduodenectomy. Methods: National Cancer Data Base pancreatic head adenocarcinoma patients (pts) diagnosed between 2003 and 2011 treated by nCHT or nCRT followed by pancreaticoduodenectomy. Backward elimination logistic and Cox regression models were used. Primary outcome measures were 30-day and 90-day postsurgical mortality and overall survival; adjusted odds (aOR) & hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results: In all 1,432 pts received neoadjuvant treatment with nCHT (n = 523) or nCRT (n = 909). Odds of 30-day mortality were influenced by age (aOR 1.03, CI 0.99-1.06,p = 0.077), average annual resection volume of facility (aOR 0.98, CI 0.97-1.00, p = 0.135), and household income quartile (aOR 1.94, CI 0.97-3.90, p = 0.060), but not by delivery of RT, comorbidities, gender, insurance status or facility type. Odds of 90-day mortality were influenced by age (aOR 1.03, 1.01-1.05,p = 0.004), household income quartile (aOR 1.37, CI 0.87-2.16, p = 0.171), and delivery of nCRT (aOR 1.69, CI 1.04-2.74, p = 0.032), but not by average annual resection volume of facility, comorbidity, gender, insurance status or facility type. Survival odds were influenced by age (aHR 1.01, CI 1.00-1.02, p = 0.001), margin status (aOR 1.50, CI 1.27-1.77, p < 0.001), ypN status (aHR 1.45, CI 1.26-1.68), p < 0.001), adjuvant CHT (aHR 0.81, CI 0.69-0.94, p = 0.006), and nCRT (aHR 1.21, CI 1.04-1.40, p = 0.012). On average pts with nCHT as compared to nCRT lived longer (median OS 26.4 vs. 24.2 months, p = 0.001; actuarial 3 yr 58% vs 49%, and 5 year survival 30% vs 14%). Conclusions: There is no detectable difference in early outcome (30-day postsurgical mortality) among pancreaticoduodenectomy pts treated with nCHT or nCRT. Trend toward a more favorable long-term outcome (30-day postsurgical mortality and overall survival) among those with nCHT without radiation is noted. Further studies with more detailed data sources are needed.
Radiological markers of treatment responsiveness in patients (pts) with metastatic pancreatic ductal adenocarcinomas (mPDAC) receiving systemic chemotherapy.
Authors: Park Peter Yong Soo , McAferty Kenyon Verner , Ahmadi Michael , Chen Kewei , Chang John , Dragovich Tomislav , Kundranda Madappa N.
Published: February 2017

403

Background: mPDAC is a deadly disease with dismal survival. Newer systemic therapies including gemcitabine/nab-paclitaxel (GA) and FOLFIRINOX (FF) have resulted in modest increases in median overall survival(mOS). Currently, no good predictors exist to prioritize the use of one regimen over the other. We investigated imaging patterns in patients receiving these two regimens. Methods: A single institution retrospective analysis of pts with mPDAC receiving either GA or FF as the front-line therapy between Jan 2012 - Dec 2014 was conducted. Data included demographics and systemic therapy.Baseline CT evaluated six imaging features; lung metastases, liver metastases, peripancreatic adenopathy, retroperitoneal adenopathy, mesentery/omentum infiltration and ascites. Statistical analysis included Kaplan Meier survival analysis with Chi-square test to compare imaging features that predict mOS or median response duration (mRD). Results: N = 27 pts; median age:GA-66 years( range: 52-76), FF-55 years (range: 40-67); 13 pts (48 %) were women and 24 pts had an ECOG performance status of ≤ 1. 18 pts received GA and 9 received FF. mOS with GA = 6.1 months(m) ( range: 1.9-15.7) and FF = 9.9 m (range: 2.5-24.1). 5/18 (28%) of the GA group and 7/9(78%) of the FF group received subsequent therapies. The presence of peripancreatic adenopathy in GA pts correlated with prolonged mRD (2.2 vs. 0.6 m; p < 0.001) without statistical difference in mOS (8.5 vs. 2.9 m; p = 0.4). In pts receiving FF the absence of hepatic metastasis resulted in a significant mRD (2.3 vs. 0.9 m; p = 0.01) and mOS (7.9 vs. 1.9 m; p = 0.04). The remainder of the radiological features did not show any statistically significant difference. Conclusions: In patients with mPDAC receiving GA or FF in front-line therapy; we observed that metastasis to the liver predicts worse outcome with FF than GA. Interestingly, peripancreatic lymphadenopathy was predictive of longer mRD for GA pts, without difference in mOS. Our pilot data demonstrates the potential of using CT imaging features to predict likelihood of response to different chemotherapy regimens. A larger study is needed to confirm these findings.
FOLFIRINOX for patients with borderline and never-resectable locally advanced pancreatic cancer, with the addition of chemoradiotherapy for potentially resectable patients: A phase II study.
Authors: Bjerregaard Jon Kroll , Ladekarl Morten , Fromm Anna-Lene , Pfeiffer Per
Published: February 2017

408

Background: Locally advanced pancreatic cancer (LAPC) is often a mix of borderline and never-resectable tumors. Multimodality treatment might downstage these tumors to allow a potential radical resection, especially the borderline group. In this ongoing phase II study we examined the feasibility of FOLFIRINOX with or without CRT followed by surgery for both borderline and never-resectable tumors (NCT-01397019). Methods: Patients in performance status 0-1, with initially non-resectable stage II/III pancreatic cancer were offered FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2+ 2400 mg/m2) every 14 days. Every 4th series the patients were evaluated and offered CRT (50.4 Gy/27F & capecitabine) if deemed potentially resectable. Resections were performed if deemed possible by the MDT. Results: Between August 2012 and present, 58 patients have been recruited with a median observation time of 14.5 months. Median age was 65(range 38-75) years, with 47%/53% stage II/III distribution. Median CA19-9 was 299(range 2-13,432). Two-hundred-seventy-four courses of FOLFIRINOX have been given, with a median of 6.5 per patient, with a median of 2 without dose modifications. Presently twenty-one patients have been treated with CRT. Twelve patients have been resected, of which 7 received prior CRT. Median survival for all patients was 15.6 months (11-NR) with a 1-year survival of 70% (49-84). For patients not resected the median survival was 12.8 months (9-16) for resected the median survival has not yet been reached. The FOLFIRINOX was associated with adverse events similar to what is expected in metastatic patients. Conclusions: FOLFIRINOX with or without CRT in patients with LAPC shows promising efficacy in patients with both borderline and never-resectable tumors. Unmodified FOLFIRINOX had acceptable toxicity, however dose reductions are often needed. CRT following initial FOLFIRINOX was feasible and without unexpected toxicity. Clinical trial information: NCT-01397019.