bluuebunny/crossref_metadata_2025 huggingface dataset:
Early surgical bypass versus endoscopic stent placement in pancreatic cancer.
Authors: Bliss Lindsay A. , Kent Tara , Watkins Ammara , Eskander Mariam , deGeus Susanna , Ng Sing Chau , Callery Mark , Moser James , Tseng Jennifer F.
Published: February 2017

391

Background: Biliary obstruction frequently occurs in locally advanced or metastatic pancreatic cancer and is often managed by surgical biliary bypass or endoscopic stenting. We compared readmissions/reinterventions among pancreatic cancer patients undergoing bypass vs. stenting. Methods: Retrospective analysis of unresected pancreatic cancer patients in the Healthcare Cost and Utilization Project (HCUP) Florida State Inpatient Database and Florida State Ambulatory Surgery Database 2007-2011 using revisit variables. Patients with early surgical or endoscopic approach analyzed. Subsequent admissions and surgical, endoscopic or percutaneous interventions identified. Propensity score matching by approach. Univariate analysis of patient characteristics and outcomes before and after matching. Multivariate analysis of readmission and reintervention performed by logistic regression. Results: 1,823 and 342 underwent endoscopic treatment vs. early surgical bypass, respectively. After propensity score matching, 684 patients analyzed (table). 64.0% (219) of endoscopic and 70.5% (241) of surgical patients readmitted (p=0.07) and 15.2% (57) and 9.1% (31) underwent reintervention (p=0.01). Endoscopic patients had lower index median length of stay (6 vs 11 days, p<0.01) and admission costs ($11,549 vs $23,215, p<0.01). In multivariate analysis, surgical biliary bypass was predictive of readmission (OR 1.50; 95% CI 1.03-2.18), but initial procedure was not predictive of reintervention (p=0.20). Conclusions: Surgical biliary bypass is less commonly performed than endoscopic stenting. Among propensity score-matched patients, readmission rates are similar, though endoscopic patients require more subsequent interventions. Candidates for both techniques may experience fewer invasive procedures if offered initial surgical biliary bypass. [Table: see text]
Enhanced recovery after surgery protocols as a management strategy following major pancreatic surgery.
Authors: Palani Velu Lavanniya Kumar , Chandrabalan Vishnuvardhan , Carter Ross , McKay Colin , Jamieson Nigel B , Dickson Euan
Published: February 2017

396

Background: Enhanced Recovery After Surgery (ERAS) protocols have been shown to have positive effects on lengths of stay (LOHS) and resource utilisation without a rise in readmission and post-operative morbidity rates in colorectal, hepatic and oesophago-gastric surgery. This study aimed to investigate the effects of an ERAS protocol on postoperative morbidity and readmission rates following pancreatic surgery in a tertiary referral centre. Methods: The perioperative care of patients undergoing pancreatic surgery was guided by a locally developed ERAS protocol incorporating pre-operative counselling and carbohydrate loading. Intra-thecal opiate and Patient Controlled Analgesia devices were utilised for postoperative analgesia. Supplemental intravenous fluid prescription was protocolised. Oral intake was restarted from post-operative day (PoD) 1 and escalated on an on-demand basis. Patients were mobilised from PoD 1 and escalated daily. Drain removal and step down care decisions were guided by serum markers and clinical progress. Results: 212 consecutive patients from 2010 to 2014 were included (conventional, N = 108, ERAS protocol, N = 104). 134 (63.2%) patients underwent pancreaticoduodenectomy, 41 (19.3%) patients underwent distal pancreatectomy, 11 (5.2%) patients underwent total pancreatectomy and the rest underwent palliative bypass or other procedures. There was a statistically significant reduction in the volume of supplemental intravenous fluids received with no significant renal impairment noted. Median LOHS was reduced to 10 days (Inter-quartile range [IQR] 7 – 19) from 16 days (IQR 12 – 26) (P < 0.001). Median critical care stay was reduced from 7 days (IQR 5 – 10) to 6 (IQR 4 -7) (P = 0.020). There was a statistically significant reduction in clinically significant wound complications (P = 0.019). There were no statistically significant increases in readmission rates, pancreas-specific or other generic post-operative morbidity rates. Conclusions: ERAS protocols are a viable peri-operative management strategy after major pancreatic surgery, and data suggests that LOHS can be reduced without an associated increase in readmission or post-operative morbidity rates.
Population pharmacokinetic (PK) analysis of lanreotide autogel/depot in the treatment of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs): Pooled analysis of four clinical trials.
Authors: Buil-Bruna Nuria , Garrido Maria Jesus , Dehez Marion , Manon Amandine , Nguyen Thi Xuan Quyen , Gomez-Panzani Edda L. , Troconiz Inaki F
Published: February 2017

397

Background: Lanreotide Autogel (Depot in US) has been shown in clinical trials to have antitumor effects and control symptoms associated with hormone hypersecretion in GEP NET patients. Objectives: To describe the PK of Lanreotide 60, 90, or 120 mg SC injections every 4 weeks in GEP NET patients, to quantify inter-patient variability (IPV) and to identify PK impacting patient characteristics. Methods: 1,541 serum concentrations were obtained from 290 patients and analysed simultaneously using the population approach with the software NONMEM version 7.2. The covariates evaluated included demographics, renal and hepatic function markers, and disease related information. Results: Serum profiles were described with a one-compartment disposition model and with an absorption process characterized by two parallel absorption pathways following first and zero order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day. No covariate tested showed a statistically significant effect on the PK profile except body weight, which showed a moderate effect on clearance (clearance increased by 25% as weight increased by 30%). However, when comparing a subject with low weight (51 kg) to a subject with high weight (104 kg), their PK profiles were similar with a great degree of overlapping. Therefore, this weight effect on clearance was not considered clinically relevant. The magnitude of IPV was low for clearance (27%) and moderate for absorption constant (61%). However due to the lack of PK timepoints around the Cmax, a higher IPV was observed for volume of distribution (150%). Mean (SD) derived parameters AUC and Cmaxat steady-state were respectively 239 (64.8) ng.day/mL and 13.9 (7.44) ng/mL, showing moderate IPV in the PK profile. Conclusions: The PK of lanreotide Autogel/Depot was well characterized in GEP NET patients using two mechanisms of absorption. The IPVof the PK of lanreotide was moderate. Among all the patients characteristics tested, none were found clinically relevant to a potential dose adjustment in clinical practice.
Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma.
Authors: Kasai Kazuhiro
Published: February 2017

400

Background: The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined hepatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN) α-2b in patients with advanced HCC. Methods: Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG-IFNα-2b (50-100 mg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ³1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival (OS). Results: Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. Prognostic factors affecting patient survival were analyzed by examining 21 potential parameters. Univariate analysis revealed two significant prognostic factors related to survival: PVTT grade (P=0.038); and therapeutic effect (P<0.001). All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. Conclusions: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-FU and PEG-IFNα-2b, this new combination therapy may be useful for patients with advanced HCC.
Defining the optimal timing of adjuvant therapy for resected pancreatic cancer: A statewide cancer registry analysis.
Authors: Saeed Hayder M. , Hnoosh Dima , Huang Bin , Durbin Eric B , McGrath Patrick , Maynard Erin , Kudrimoti Mahesh R. , Anthony Lowell Brian , Hosein Peter Joel , DeSimone Philip A. , Tzeng Ching-Wei David
Published: February 2017

406

Background: Recent long-term results from the ESPAC-3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic adenocarcinoma (PDAC), early initiation of AT before 8 weeks may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the impact of early vs. late AT initiation on OS in a statewide population-based analysis. Methods: Among all patients with stage I-III PDAC in the Surveillance Epidemiology and End Results (SEER) - Kentucky Cancer Registry (KCR) from 2004-2012, those undergoing pancreatectomy were stratified by postoperative chemotherapy/radiotherapy delivery and timing. Patients with preoperative therapy, no AT, or postoperative therapy beyond 16 weeks, were excluded. Remaining patients were stratified into 2 groups defined as “early” (<8 weeks) and “late” AT (8-16 weeks). A Cox regression model was created to analyze the impact of AT timing, adjusting for clinicopathologic variables. Results: Of the 4,882 total patients with PDAC, 1,193 (24%) underwent pancreatectomy. Of these, only 364 (30%) received AT within 16 weeks. With median age 65 years (range 20-101), 86% patients were stage II and 76% were node-positive. Median time to AT initiation was 52 days (range 5-111). Timing of AT did not affect OS (median OS: early AT, 19.5 vs. 19.7 mo, late AT, p=0.63). Median OS for stages I, II, and III were 46.1, 19.3, and 8.6 mo, respectively (p<0.001). Poorly/undifferentiated tumors were associated with worse median OS 17.6 vs. 21.3 mo for well/moderately differentiated tumors (p<0.001). Lymph node positivity was associated with worse median OS 18.1 vs. 25.8 mo for node negativity (p<0.001). On multivariate analysis, factors that affected OS included stage (II, HR 2.54, p=0.022; III, HR 5.16, p<0.001), node positivity (HR 1.57, p=0.008), poorly/undifferentiated grade (HR 1.50; p=0.002), but not AT timing. Conclusions: In this SEER-KCR analysis, there was no difference in OS between early and late AT initiation. Despite its proven value, the ideal window for AT initiation remains unknown as tumor biology continues to trump current treatment regimens.
Survival benefit of TACE plus iodine-125 seed implantation in unresectable hepatitis b-related hepatocellular carcinoma with PVTT.
Authors: Huang Mingsheng , Lin Qu , Wang HaoFan , Wang Long , Bai Mingjun , Zhu Kangshun , Shan Hong
Published: February 2017

408

Background: The aim of this study is to investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine-125 seed implantation on Hepatitis B-related hepatocellular carcinoma (HB-HCC) patients complicated with PVTT and the underlying prognostic factors. Methods: A retrospective matched cohort study was done on unresectable HB-HCC patients with PVTT at our hospitals between January,2011 and June, 2014. The treatment group enrolled 70patients receiving TACE plus Iodine-125 seed implantation. The control group included 140 case-matched HB-HCC patients receiving TACE. The factors that might affect the overall survival (OS) were examined. Results: There was no significant difference in the baseline demographic characteristics between the two groups (p>0.05). Median survival time of the two groups was 11.0months and 7.5 months, respectively (P<0.001). The OS at 6, 12, 24, and 36 months was 85% vs 55%, 50% vs 25%, 14.5% vs 9%, and 14.5% vs 5% in the treatment group and control group, respectively (all P<0.001). The OS rate for type I+II PVTT patients, type III PVTT patients, patients complicated with arterial-portal-shunt (APS) or patients with mass/nodules in the treatment group was significantly higher than that in the control group (P=0.006, P<0.001, P<0.001,and P<0.001, respectively). Multivariate analysis showed that type III PVTT [Hazard ratio (HR)=0.274; 95% confidence interval (CI): 0.187~0.400; P<0.001], ECOG performance status 1~2 (HR=0.647; 95% CI: 0.428~0.979; P=0.039), diffusely infiltrating tumor subtype (HR=0.596; 95% CI: 0.417~0.852; P=0.005), and the presence of APS (HR=2.387; 95%CI: 1.594~3.574; P<0.001) were independent predictors of poor prognosis. Treatment modality of TACE plus Iodine-125 seed implantation (HR=0.291; 95% CI: 0.185~0.456; P<0.001) was independently associated with better survival. Conclusions: TACE plus Iodine-125 seed implantation can improve OS of unresectable HB-HCC patients with PVTT. Treatment modality, ECOG, PVTT type, presence of APS, and subtype of tumor were independent factors for predicting prognosis.
Chemotherapy toxicity predicted by baseline nutrition assessment in gastrointestinal (GI) malignancies: A multicenter analysis.
Authors: Klute Kelsey , Brouwer Julianna , Jhawer Minaxi , Sacks Hayley , Gangadin Anatasia , Ocean Allyson J. , Popa Elizabeta C. , Dai Tong , Wu Guojiao , Christos Paul J. , Shah Manish A.
Published: February 2017

410

Background: Malnutrition is prevalent in GI malignancies and is associated with decreased survival, frequent hospitalizations and increased healthcare costs. Outside the perioperative setting, malnutrition rarely impacts treatment decisions. The subjective global assessment (SGA) is a validated tool that stratifies patients by nutritional status. We hypothesized that malnutrition independently predicts chemotherapy-related toxicity in patients with GI malignancies. Methods: All patients enrolled in the GI Cancer Registry which collects baseline demographic data, comorbid conditions and baseline nutrition status. In patients treated with chemotherapy, we reviewed dosing, schedule and toxicities over the first two months of treatment and compared results between well-nourished (SGA-A) and malnourished (SGA B/C) patients. Two-sample t-test or chi-square tests were used for comparisons as appropriate. Multivariable logistic regression analysis was used to estimate the independent effect of SGA status after controlling for demographic/prognostic factors. Results: We enrolled 184 patients between 5/2012 – 5/2013. The overall rate of malnutrition was 31.0%: 40.4% upper GI, 13.6% lower GI, 50.0% hepatobiliary. Malnourished patients received less chemotherapy (mean 63.9±23.8% vs. 81.4±18.8% of standard dose, p<0.0001) due to toxicity-related dose-reductions, even when stratified by tumor type or treatment type (based on toxicity risk). After controlling for age, gender, ECOG (≥1 vs. 0) and albumin in a multivariable logistic regression model, malnutrition was an independent predictor of receiving less than 80% of the standard dose (adjusted odds ratio = 2.30; 95% confidence interval = 1.07, 4.95, P=0.03). Malnourished patients had a slightly higher rate of hospitalization, not statistically significant (29.8% vs. 22.0%, p=0.26). Conclusions: In patients receiving chemotherapy for GI malignancies, malnutrition (defined by SGA B/C) is an independent predictor of toxicity-related chemotherapy dose-reductions. Prospective studies should evaluate whether nutrition interventions in malnourished patients decrease chemotherapy-related toxicities.
Analysis of prognostic factors in advanced pancreatic cancer (APDAC) patients (pts) undergoing to first-line nab-paclitaxel (Nab-P) and gemcitabine (G) treatment.
Authors: Giordano Guido , Vaccaro Vanja , Lucchini Eleonora , Bertocchi Paola , Bergamo Francesca , Musettini Gianna , Santoni Matteo , Lo Re Giovanni , Giommoni Elisa , Russano Marco , Campidoglio Serena , Santini Daniele , Vasile Enrico , Cascinu Stefano , Zagonel Vittorina , Zaniboni Alberto , Melisi Davide , Milella Michele , Febbraro Antonio
Published: February 2017

412

Background: Nab-P + G combination represents an optimal first line therapeutic option in APDAC. Actually we have no parameters to predict prognosis in pts receiving this regimen. Here we present data of a multicentre retrospective analysis evaluating prognostic impact of clinical or biological factors in a cohort of APDAC pts treated with Nab-P + G first line CT. Methods: Clinical records of 118 APDAC pts receiving first line Nab-P + G were retrospectively reviewed. Overall survival (OS) and progression free survival (PFS) were evaluated with Kaplan Meier method with 95% CI and curves were compared with log-rank test. Cox-regression model was applied to the data with univariate and multivariate approach. Variables included in analysis were age, gender, ECOG PS, primary tumor site, liver metastases, multiple metastatic sites, baseline CA19-9, bilirubin levels, neutrophil/lymphocyte ratio (NLR), CA19-9 decrease > 50%, biliary stent and symptomatic disease. Results: Median age was 66 (37 - 83), M/F:65/53, ECOG PS 0/1/2: 51/46/21 respectively. 4 complete and 27 partial responses were observed with 26% response rate (RR). Median OS and PFS were 11 months (95% CI 9.58 – 12.41) and 7 months ( 95% CI 5.96 – 8.03) respectively. When considered at univariate analysis primary tumor location to the head, ECOG PS of 2, bilirubin levels higher than median and NLR ≥ 5 had a bad prognostic impact both on PFS and OS. Differently, CA19-9 decrease > 50% was considered a positive prognostic factor for PFS and OS. Multivariate analysis confirmed the negative role of NLR ≥ 5 respect of PFS (HR 3.21; 95%CI 1.61 – 5.68, p = 0.002) and OS (HR 3.38; 95%CI 1.88 – 5.79, p = 0.001) and positive impact of CA19-9 decrease > 50% on PFS (HR 0.37; 95% CI 0.11 – 0.68, p=0.006) and OS (HR 0.53; 95% CI 0.15 – 0.97, p=0.005), as independent prognostic factors. Conclusions: This analysis suggest that in APDAC pts receiving first line Nab-P + G, high NLR value (≥5) could be considered an easy detectable, independent parameter to predict poor outcomes in terms of PFS and OS. Furthermore CA19-9 reduction > 50% from baseline may be, in absence of other clinical and molecular parameters, an early marker of good prognosis.
Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer.
Authors: Palacio Sofia , Akunyili Ikechukwu Immanuel , Ernani Vinicius , Macintyre Jessica , Merchan Jaime R. , Pollack Terri , Reis Isildinha , Restrepo Maria H. , Rocha Lima Caio Max S. , Hosein Peter Joel
Published: February 2017

413

Background: The combination of nab-P and Gem improves survival compared to Gem alone in first-line therapy of metastatic pancreatic cancer. Efficacy data with this doublet in previously treated pts are scant. Our group presented preliminary results on 10 pts treated with this two-drug combination in the second and third line setting and herein present updated data on 59 pts. Methods: This IRB approved analysis identified all pts diagnosed with advanced refractory pancreatic cancer, treated with second-line Gem and nab-P at University of Miami and Sylvester Comprehensive Cancer Center between September 2010 and June 2014. Response by RECIST, CA19-9, and symptomatic improvement were assessed. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of Gem + nab-P and were analyzed using the Kaplan-Meier method. Clinical benefit was defined as the percentage of patients with a partial response (PR) or stable disease (SD). Results: Data from59 pts were analyzed. The median age was 60; 55% were male; 54% received Gem + nab-P as second line therapy and 46% received it as third-line or beyond. Five (10%) pts had confirmed PR, 23 (47%) SD and 21 (43%) progressed. Among the 31 (52%) pts who received prior Gem, 18 (58%) had clinical benefit, 3 PR and 15 SD. The median OS was 3.9 months. The median PFS was 3 months. Toxicity appears similar to what has been reported on the MPACT trial with the combination. Conclusions: The clinical benefit seen withGem and nab-P in this group of pretreated pancreatic cancer pts suggests that it can be considered as an option. Additionally, prior Gem treatment appears not to decrease Gem and nab-P benefit in this population. Since nab-P monotherapy has modest activity in pre-treated pancreatic cancer pts, our data suggests a positive interaction between Gem and nab-P that may overcome resistance to Gem. [Table: see text]
FOLFIRINOX for advanced pancreatic cancer: The Princess Margaret experience.
Authors: Chllamma Muralidharan , Cook Natalie , Giby Kazim , Dodd Anna , Wang Lisa , Dhani Neesha C. , Hedley David W. , Moore Malcolm J.
Published: February 2017

417

Background: The FOLFIRINOX regimen has been shown to significantly increase both overall (OS) and progression free (PFS) survival in metastatic pancreas cancer (MPC), albeit with an increase in adverse events (AEs). It is not known whether initial dose reductions compromise FOLFIRINOX efficacy and there are limited data regarding treatment of locally advanced pancreatic cancer (LAPC). Methods: We conducted a retrospective review of patients (pts) treated with FOLFIRINOX for MPC or LAPC at Princess Margaret Cancer Centre, and began treatment between Dec 2011 and April 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications. Results: 102 pts were identified; 66 MPC and 36 LAPC. Median age was 65 years. 72% of pts had pancreatic head tumors. At baseline 95% of pts had an ECOG performance status of 0 or 1; 95% had bilirubin < 1.5 ULN and 45% had a biliary stent. 68% of pts initiated treatment with a dose reduction (93% reduction or omission of bolus 5FU, 88% reduction in Irinotecan, 68% reduction in Oxaliplatin and 66% reduction in infusional 5FU). Median number of cycles was 6 (1-31); 25% of pts received <4 cycles. Median OS in metastatic pts was 12.9 months (mo) and 23 mo in LAPC; Median PFS was 8.7 mo (metastatic) and 11.1 mo in LAPC. There was no significant difference in PFS (10.9 vs. 10.3 mo; p=0.60) or OS (11.1 vs. 14.0 mo; p=0.19) between the full starting dose and reduced starting dose groups respectively. Partial response or stable disease was achieved in 57% of pts; 11% of the LAPC pts had a surgical resection. Grade 3/4 hematologic AEs were observed in 43% of pts (febrile neutropenia in 6%). Only 13% of pts received G-CSF support. Grade 3/4 non-hematologic AEs were observed in 28% of pts, including vomiting (19%), nausea (16%) and diarrhea (16%). 18% of pts had a treatment related hospitalization (5% neutropenic sepsis, 13% GI toxicity/dehydration.) There was one treatment related death. Pt wellbeing (scored on a validated questionnaire) significantly improved from baseline to cycle 4 (p=0.002). Conclusions: Modest dose reductions do not appear to compromise efficacy of FOLFIRINOX. Our median PFS, OS and AEs are comparable to other studies using FOLFIRINOX in both LAPC and metastatic disease.
Preoperative risk assessment of pancreatic surgery for pancreatic cancer by the surgical Apgar score.
Authors: Aoyama Toru , Katayama Yusuke , Murakawa Masaaki , Asari Masahiro , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Ueno Makoto , Morimoto Manabu , Akaike Makoto , Yamamoto Naoto , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro
Published: February 2017

419

Background: Postoperative morbidity is high after pancreatic surgery. Numerous studies have evaluated factors to predict the patients at risk. Recently, a simple and easy-to-use surgical complication prediction system, the surgical Apgar score (SAS) calculated using three intraoperative parameters (estimated blood loss, lowest mean arterial pressure and lowest heart rate) has been proposed for general surgery. In this study, we evaluated the predictability of the SAS for severe complications after pancreatic surgery for pancreatic cancer. Methods: We investigated 189 patients who underwent pancreatic surgery at Kanagawa Cancer Center between 2005 and 2014. Clinicopathological data, including the intraoperative parameters, were collected retrospectively. In this study, the patients with postoperative morbidities classified as Clavien-Dindo grade II or more were classified as having severe complications. Uni- and multivariate logistic regression analyses were performed to identify the risk factors for morbidity. Results: Postoperative complications were identified in 73 patients, and the overall morbidity rate was 38.6%. The results of both univariate and multivariate analyses of various factors for overall operative morbidity showed that a SAS of 0-4 points and a body mass index > 25 kg/m2 were significant independent risk factors for overall morbidity (P=0.024 and P=0.014, respectively). The rate of abdominal abscess formation was significantly higher in the patients with a SAS of 0-4 points, while the occurrence of a pancreatic fistula was significantly higher in the patients with a body mass index > 25 kg/m2. Conclusions: The SAS was a significant risk factor for surgical complications after pancreatic surgery for pancreatic cancer. Careful attention is required for these patients in order to help prevent complications and treat them as soon as they develop.
Gastric cancer prevention and early detection program for an at-risk population: A prospective study of the Korean American community.
Authors: Woo Yanghee , Trapp Garrick , Hyun Jae Geun , Hyun Chul Soo , Katherine Lu Zen , Gonda Tamas , Oberstein Paul Eliezer , Chabot John A. , Wang Timothy C.
Published: February 2017

42

Background: Gastric cancer development is multifactorial with varying incidence rates. People of Korean heritage have the highest rate of gastric cancer in the world and among Americans. While this gastric cancer disparity is well known, an evaluation of the population-specific risk factors and the effectiveness of selective screening in the Korean American communities have not been studied. Methods: Korean Americans living in Northern New Jersey over 40 years of age without a known history of gastric cancer were eligible to participate in this prospective study. Each participant received a 30-minute one-to-one consultation with a gastric cancer surgeon, given a 44-item questionnaire, and underwent an upper endoscopy with biopsies. The consultation included assessment for the presence of relevant history, symptoms, and signs. The questionnaire addressed patient-specific demographic, epidemiologic, and cultural information. Two gastroenterologists blinded to the consultation and questionnaire results performed the upper endoscopies. Results: Between September 2013 and September 2014, one hundred participants enrolled in our study. All participants denied the presence of alarm symptoms, such as acute weight loss, melena or persistent vomiting. Risk factors, including prior H. pylori infection (25%), family history of gastric cancer (15%), cigarette smoking (16%), and daily intake of salty and pickled foods (87%) were present. On upper endoscopy, 18% of the participants were found to have “moderate to severe H. pylori associated chronic active gastritis." Other endoscopic findings were mild gastritis (61%), severe erosive gastritis (4%), polyps (4%), and metaplasia (21%). Only 4 patients had normal mucosal pathology. Gastric dysplasia or cancer has not yet been identified. Conclusions: Korean Americans have high rates of modifiable risk factors for developing gastric cancer. Novel population-specific gastric cancer prevention and early detection strategies should be designed to eliminate gastric cancer from the Korean American Community.
Clinical outcomes of patients with gastrointestinal malignancies participating in phase I clinical trials.
Authors: Mahipal Amit , Burke Nancy , Wapinsky Georgine , Bertels Barbara , Juan TzuHua , Lee Jae K , Lush Richard , Sullivan Daniel , Denson Aaron
Published: February 2017

428

Background: Early phase clinical trials play a pivotal role in drug development. However, limited data is available on the clinical outcomes of patients with gastrointestinal (GI) malignancies enrolled in phase 1 clinical trials. The aim of this study is to evaluate the clinical characteristics and survival of patients with GI cancers participating in phase 1 clinical trials. Methods: All consecutive patients with advanced GI tumors who participated in phase 1 clinical trials from 1/2007 to 12/2013 at Moffitt Cancer Center were included. Data for individual patients were extracted from the OnCore database and clinical charts. Only patients who received at least one dose of the study drug were included. Cox regression model was used to estimate multivariable adjusted hazard ratios and 95% CI. Results: 243 pts with GI malignancies who participated in phase 1 clinical trials were included. Median age was 62 years (26-82 years) with 55% of the patients aged >60 years. Patients had the following disease types: pancreas (42%), colorectal (34%), gastro-esophageal (10%), hepatobiliary (13%) and others (2%). The distribution of patients for baseline variables are: male (55%), DVT/PE (12%), ECOG ≥1 (72%), prior systemic therapies ≥2 (59%), no. of metastatic sites > 2 (31%), lung metastases (40%) and liver metastases (77%). Pts received treatment with chemotherapy only (14%), targeted therapy (41%), chemotherapy + targeted therapy (42%) and others (2%). The response rate was 4% with 38% achieving stable disease; 42% of pts had progressive disease. The median OS was 5.8 months (0.2-52.4). ECOG score of 0, prior systemic therapies < 2 and absence of liver metastases were associated with better OS on multivariate analysis. Conclusions: This is the largest study to assess clinical outcomes in this patient population. Phase 1 clinical trials provide clinical benefit to patients with advanced GI malignancies and should be recommended as a treatment option in appropriate patients. [Table: see text]
Pretreatment lab values to predict overall survival in patients with primary unresectable pancreatic adenocarcinoma treated with SBRT.
Authors: Alagappan Muthuraman , Pollom Erqi L. , von Eyben Rie , Kunz Pamela L. , Fisher George A. , Ford James M. , Poultsides George A. , Visser Brendan C. , Norton Jeffrey A. , Kamaya Aya , Columbo Laurie Ann , Koong Albert , Chang Daniel Tandel
Published: February 2017

433

Background: This study investigates which pre-treatment hematologic and tumor marker values can predict for overall survival (OS) in patients with unresectable pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT) using data from the past 11 years from a single institution. Methods: Clinical data from 196 patients with primary unresectable pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2013 was collected. Of these, 161 (82.1%) had locally advanced disease, 12 (6.1%) had borderline resectable disease, 21 (10.7%) were medically inoperable, and 2 (1.0%) had resectable disease but refused surgery. Prior to the start of treatment, lab values were collected for 191 of these patients including: hemoglobin, platelets, albumin, red blood cell (RBC) count, white blood cell (WBC) count, absolute lymphocyte count, absolute neutrophil count, and neutrophil to lymphocyte ratio (NLR). Additionally, tumor markers CA 19-9 and CEA were collected. Background clinical and demographic data was also available for the entire cohort. Results: The median follow-up for the entire cohort following SBRT was 7.7 months. Median OS from the start of treatment was 7.88 months (IQR 4.96-12.72). Prior radiation therapy (p = 0.0462), lower RBC (p = 0.0307), higher pre-treatment CEA (p = 0.0166), and higher NL ratio (p < 0.0001) correlated with worse OS on univariate analysis. WBC, platelet counts, and CA 19-9 did not predict for OS on univariate analysis. On multivariate analysis, higher NL ratio (p = 0.0455) and higher CEA (p = 0.0148) were both correlated with decreased OS, while RBC and prior radiation therapy had no association. Conclusions: Review of pre-treatment hematologic and tumor marker values serves as a valuable predictor of overall survival in patients with unresectable pancreatic adenocarcinoma treated with SBRT. Higher pre-treatment NL ratio and CEA values are associated with poorer OS, which may help to stratify patients into different risk categories.
A retrospective analysis assessing effects of cytotoxic versus cytostatic agents on body mass, nutritional parameters, and performance status in patients with exocrine pancreas cancer enrolled in phase I and II trials.
Authors: Schwerkoske John Philip , Borazanci Erkut , Schroeder Katy , Zhang Lei , Jameson Gayle S. , Schaffer Joyce Rosemarie , Nieves Jeffery A. , Von Hoff Daniel D.
Published: February 2017

438

Background: The 5-year survival for pancreatic adenocarcinoma is poor, and patients increasingly turn to experimental agents after conventional treatments have failed. Novel chemotherapeutic agents undergo rigorous phase I and II trials to confirm efficacy, safety, tolerability, and optimal dose for entry into late phase trials. Cytostatic therapies are theorized to have an improved tolerability compared to traditional cytotoxic therapies. Methods: This retrospective study compared the tolerability of cytostatic vs cytotoxic therapies in patients with advanced pancreatic cancer who participated in phase I or II trials at a single institution. Nutrition parameters of weight and albumin, performance status, tumor marker CA 19-9 level, and mean tumor dimension defined by RECIST criteria were obtained for patients within four weeks of trial start date and conclusion. Results: 117 patient trials were assessed in final analysis. No statistically significant difference was observed between patients receiving cytostatic and cytotoxic agents with regards to mean weight loss (1.01 vs 1.30 kg; p =.733), decrease in albumin (0.36 vs 0.29 g/dL; p =.397), and percent change in CA 19-9 (-72% vs -76%; p =.882). Results of change in performance status were similar, with mean increase in ECOG (0.63 vs 0.61; p =.948) and decrease in Karnofsky (13 vs 12, p =.709). There was a statistically significant difference in tumor dimension with cytostatic vs cytotoxic agents (18% vs -3%, p =.043). There were no differences in trends between patients enrolled in one trial compared to those enrolled in multiple trials. Conclusions: This study did not show a significant difference between cytostatic and cytotoxic agents in patients with advanced pancreatic adenocarcinoma in early phase trials with regards to nutritional parameters, performance status, or change in CA 19-9. However, there was a statistically significant change in tumor dimension. Thus, cytotoxic agents have similar tolerability to cytostatic agents and may have additional benefit on tumor burden in patients with advanced pancreatic adenocarcinoma.
Phase III study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with metastatic pancreatic adenocarcinoma (mPC): Subgroup analysis of Canadian pts from the MPACT trial.
Authors: Tehfe Mustapha Ali , Dowden Scot D. , Kennecke Hagen F. , El-Maraghi Robert Hassan , Lesperance Bernard , Couture Felix , Letourneau Richard , Penenberg Darryl Neil , Romano Alfredo , Von Hoff Daniel D.
Published: February 2017

439

Background: Weekly nab-P + Gem is a new option for first-line treatment (Tx) of mPC. In the MPACT trial, nab-P/Gem demonstrated superior overall survival (OS; primary endpoint) vs Gem alone as first-line Tx of mPC (Table). Here we report a subgroup analyses evaluating the efficacy and safety outcomes with nab-P + Gem vs Gem alone from the Canadian cohort of the MPACT trial. Methods: Previously untreated pts (N = 861) with mPC were randomized 1:1 (stratified by Karnofsky Performance Status [KPS], region, and the presence of liver metastases) to receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle or Gem 1000 mg/m2 weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of each 28-day cycle (cycle ≥ 2). Results: 63 pts from Canada enrolled in the MPACT trial. Baseline pt characteristics were well balanced. Median age was 61 years and KPS was similar for both groups and comparable to the intent-to-treat (ITT) populations. Primary lesion in the pancreatic head was more common among pts in the nab-P + Gem vs Gem arm (55% vs 30%); use of biliary stent was similar (33% nab-P + Gem; 27% Gem). Median OS and progression-free survival (PFS) were longer with nab-P + Gem vs Gem (Table). Median Tx duration was 4.2 mo with nab-P + Gem vs 3.2 mo with Gem. Use of subsequent therapy was 30% in the nab-P + Gem arm vs 43% in the Gem arm. The median relative dose intensity for Gem was similar in each arm (81% nab-P + Gem vs 85% Gem). The most common grade ≥ 3 AEs for nab-P + Gem vs Gem were neutropenia (22% vs 10%), fatigue (34% vs 33%), and neuropathy (25% vs 0%). Conclusions: Canadian pts participating in MPACT were similar to the ITT population and nab-P + Gem was well tolerated and showed improved median OS, PFS, and ORR vs Gem alone, although not statistically significant (likely due to the small number of pts). Clinical trial information: NCT00844649. [Table: see text]
Interim analysis of fluorodeoxyglucose uptake in patients with metastatic or recurrent gastric cancer treated with fluoropyrimidine based chemotherapy.
Authors: Lee Suk-young , Uh Jaeseon , Oh Sang Cheul
Published: February 2017

44

Background: The role of 18F-FDG PET/CT scanning in advanced gastric cancer (AGC) is still under investigation. We evaluated its prognostic role in patients with recurrent or metastatic AGC who received fluoropyrimidine based chemotherapy. Methods: Forty-six patients with metastatic or recurrent AGC who had the baseline and interim PET/CT scanning during the palliative chemotherapy were analyzed. The lesion with the highest SUVmax value among target lesions was determined to be a main target (SUVmax1), and interim SUVmax of the target lesion was measured after several cycles (4-12 cycles) of chemotherapy (SUVmax2). The formula calculating metabolic change follows: ΔSUVmax2-SUVmax1 (%) = (SUVmax2-SUVmax1)/SUVmax1 * 100 Results: Patients with SUVmax1 value > 6 had a significantly higher response rate than those with the lower SUVmax1 (73.9% vs. 26.1%, p=0.036). SUVmax2 < 5 was significantly associated with better overall survival (OS) (p=0.035) with univariate analysis. ΔSUVmax2- SUVmax1 > -20% or appearance of new lesions with 18F-FDG PET/CT scanning at interim analysis was significantly associated with worse OS (p=0.027). ΔSUVmax2- SUVmax1 > -20% or new lesions (p=0.03) was the only factor significantly independently associated with OS using multivariate analysis (Table). Female (p=0.028), SUVmax2 > 5 (p=0.002), and ΔSUVmax2-SUVmax1 value > -20% (p=0.004) were significantly associated factors with worse progression free survival (PFS) using univariate analysis. Both SUVmax2 (p=0.028) and ΔSUVmax2-SUVmax1 value (p=0.043) were the significant factors associated with PFS using multivariate analysis. Conclusions: Analysis ofmetabolic change by interim PET/CT scanning is useful in predicting prognosis in patients with recurrent or metastatic AGC undergoing fluoropyrimidine based chemotherapy. [Table: see text]
Use of sorafenib in recurrent hepatocellular carcinoma (HCC) after liver transplantation.
Authors: Chiu Joanne Wing-Yan , Yau Thomas Cheung , Cheung Tan To , Chan Albert , Chok Siu-Ho , Dai Wing-Chiu , Leung Roland Ching-Yu , Chan See-Ching , Lo Chung-Mau
Published: February 2017

440

Background: Sorafenib (Sor) is the only approved systemic therapy for advanced HCC yet the safety and efficacy for its use in patients (pts) who developed recurrence after liver transplantation (LT) has not been established. There is an unmet need for treatment option in this group of pts. Methods: This is a retrospective analysis of pts treated with Sor for recurrent HCC post-LT in Queen Mary Hospital, Hong Kong. Results: During year Jan 2008 to Feb 2014, 25 post-LT pts with HCC recurrence were treated with Sor. Tacrolimus and sirolimus were the immunosuppressant of choice during the same treatment period in 76% (19/25) and 40% (10/25) pts respectively. All pts had Child-Pugh A liver function and ECOG performance status 0-1. Majority of pts were chronic hepatitis B carriers (88%) and male (88%). Median time to recurrence was 13.2 months (range 3.4-71.1). Intrahepatic recurrence and extrahepatic recurrence were found in 52% and 80% of pts respectively. Up to 68% of pts received the standard dose of 800 mg/day. The most common adverse events (AEs) were hand-foot syndrome (44%) and diarrhea (28%). G3 transaminase elevation was found in 4 pts (16%), in which 2 had histological evidence of acute graft rejection. Both cases were associated with tailing down of tacrolimus upon tumor progression, and the liver function recovered after adjustment of immunosuppressant. Nine pts (36%) required dose adjustment. The median maintenance dose was 400 mg/day. The median duration of treatment was 4.44 months (95% CI 2.53-6.44). Median time to progression was 6.21 months (95% CI 2.83-9.63). Median overall survival was 13.6 months (95% CI 7.69-19.61). Ten (40%) pts also received other subsequent systemic therapy. Conclusions: Sor given in combination with tacrolimus and sirolimus did not lead to unexpected graft rejection. The drug is in general tolerated in this population and toxicities appeared to be similar to non-transplant pts. Further study is required to evaluate for drug interaction and efficacy.
A retrospective review of the University Health Network (UHN) multimodal treatment experience with extended resection of pancreatic ductal adenocarcinoma (PDAC) in patients with arterial involvement.
Authors: Tremblay St-Germain Amélie , Fox Adrian , Segedi Maja , Serrano Aybar Pablo Emilio , Scholtz Paul , O'Malley Martin , Borgida Ayelet , Bianco Teresa , Dodd Anna , Krzyzanowska Monika K. , Moore Malcolm , Kim Joon-Hyung J. , Wei Alice Chia-chi , Gallinger Steven , Dhani Neesha C. , McGilvray Ian M
Published: February 2017

447

Background: Involvement of a major artery with PDAC is a criteria of unresectability. Although major vein resection/reconstruction is now accepted in PDAC resection, the feasibility of arterial resection requires investigation. The response to neoadjuvant therapy (NAT) may be a useful tool for identifying appropriate candidates for extended resection. Methods: We retrospectively reviewed the UHN experience of multimodality therapy in patients (pts) with histologically confirmed PDAC and single vessel arterial involvement (superior mesenteric, celiac or hepatic artery) on CT from Jan 2009 to Dec 2013. These pts received NAT prior to being re-assessed for surgery; pts whose disease was either stable or improved were considered for surgery. Baseline imaging was reviewed independently. Postoperative complications were assessed and oncologic outcomes were analysed with Kaplan-Meier method. Results: We identified a cohort of 57 pts of whom 56 received NAT. On reassessment, 26 (46%) had no evidence of disease progression and were considered operable, while 31 had local or distant progression and were deemed inoperable. Of 26 pts proceeding to surgery, 21 (81%) underwent resection and 5 had a palliative procedure. In the resection group, 10 pts required arterial resection/reconstruction to achieve R0. The post-operative mortality at 90-days was 0% and morbidity was 86% with 33% major complications (Clavien-Dindo III-IV). With a median follow-up of 12,1 months, the median survival for the resection group was 18.7 months (95% CI: 11.2-NA) vs. 13.6 months (95% CI: 11.9-18.1) for the non-resection group, P=0.0246. Conclusions: Our results suggest that a multimodal approach including NAT +/- segmental arterial resection/reconstruction, can be considered but with high post-operative morbidity. The encouraging survival rates of pts after extended resection must be balanced with the morbidity of this surgery. Given the poor prognosis of pts with locally advanced PDAC, there is a rationale for prospective evaluation of this approach to identify pts who are most likely to benefit from this aggressive strategy.
Survival after Yttrium-90 radioembolization in elderly and nonelderly patients with hepatocellular carcinoma or colorectal cancer liver metastases.
Authors: Redman Rebecca Ann , Coldwell Douglas , Sharma Vivek R.
Published: February 2017

449

Background: Systemic treatment of unresectable hepatocellular carcinoma (HCC) or colorectal cancer liver metastases (CLM) in the elderly can be complicated by increased toxicity. In addition, the increasing incidence of comorbidities with age may preclude surgical resection with curative intent. Hepatic arterial therapy is increasingly utilized in patients with HCC or CLM not amenable to surgical resection. Studies of transarterial chemoembolization in the elderly have generally shown similar safety and efficacy as compared to younger patients, although some studies suggest worse outcomes. The selective nature of radioembolization has the potential for improved tolerability in this patient population. Methods: We report the results of a retrospective review of patients with unresectable HCC or metastatic disease to the liver treated with Yttrium-90 radioembolization at a single institution. Results: Patients were referred for treatment after multidisciplinary evaluation, but were not treated as part of a clinical trial. A total of 94 patients treated were evaluable for follow up. There were approximately twice as many males as females (64% vs 36%). Elderly was defined as 70 years of age or older, representing 20 of the 94 patients. Average age of the elderly cohort was 76 (range 70-90), compared to 56 years of age (range 23-69) for the younger patients. Survival was measured from date of first radioembolization. Median survival was similar for elderly and younger patients when considering all tumor types (337 days vs 288 days). There was no difference in median survival between elderly and non-elderly patients with CLM (377 days vs 365 days) or with HCC (370 days vs 363 days). Conclusions: In our experience, survival after Yttrium-90 radioembolization in elderly and younger patients with primary HCC or CLM is similar. Age alone should not preclude consideration for liver-directed therapy.