bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II study to evaluate the safety and efficacy of RAD001 plus erlotinib in patients with well-differentiated neuroendocrine tumors (NET).
Authors: Bergsland Emily K. , Watt Lindsey , Ko Andrew H. , Tempero Margaret A. , Korn Wolfgang Michael , Kelley Robin Katie , Weber Thomas , Siah Iche , Hwang Jimmy , Nakakura Eric K. , Venook Alan Paul
Published: February 2017

285

Background: Building on strong preclinical data, we hypothesized that concomitantly targeting mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR) signaling pathways will inhibit neuroendocrine tumors (NET) more effectively than targeting either pathway alone (thus improving likelihood of shrinkage). We initiated a prospective, phase II study to assess the safety and efficacy of RAD001 plus erlotinib in patients (pts) with advanced NET.

Methods: Pts with well-differentiated NET were enrolled using a Simon 2-stage design with 2 groups: pancreatic NET (PNET) and other low-grade NET/ carcinoid (CARC). Eligibility criteria included histological diagnosis of a well- to moderately-differentiated NET and no prior mTOR- or EGFR-inhibitor. Pts treated with RAD001 5 mg PO QD and erlotinib 100 mg PO QD without scheduled breaks (1 cycle = 28 d). Pts followed for toxicity and radiographic response, with first planned analysis after 8 evaluable pt/group.

Results: Since 6/09, 17 pt enrolled: M/F 9/8; PNET/CARC 8/9. Pts on octreotide remained on drug. All pt had PD at enrollment. Median # cycles: 12 in CARC (range 2-20); 5.5 (to date) in PNET (range 0.5-18). Excessive toxicity in first 7 pts prompted reduction in starting erlotinib dose from 150 to 100 mg/d, resulting in improved tolerability: Gr 3 stomatitis in 3/7 initial pts (43%) vs 1/10 (10%) after new starting dose. Overall, the most common side effects include diarrhea, stomatitis, rash, anorexia, and fatigue. Enrollment to CARC cohort stopped after first stage due to insufficient efficacy (7/9 SD, 2/9 PD; 0 PR).

Conclusions: RAD001 plus erlotinib appears to be associated with radiographic stability, but not shrinkage, in CARC. Combining the two agents has proven challenging; toxicity precludes administration of either agent at full dose. Interim efficacy analysis for PNET stratum pending. Correlation with expression of mTOR pathway components in archived tissue planned.
Retrospective review of doxorubicin plus sorafenib as second-line therapy in hepatocellular carcinoma (HCC).
Authors: Abou-Alfa Ghassan K. , Ma Jennifer , O'Reilly Eileen Mary , Gansukh Bolorsukh , Chou Joanne F. , Capanu Marinela , Saltz Leonard
Published: February 2017

298

Background: Doxorubicin plus sorafenib has yielded an improved overall survival, progression-free-survival, and time-to-progression when compared to doxorubicin plus placebo, in the first line setting in patients with advanced HCC (Abou-Alfa, GK, et al. JAMA 2011). We explored the activity of doxorubicin and sorafenib following sorafenib failure.

Methods: An IRB exemption was obtained to identify patients with HCC who were treated with doxorubicin and sorafenib after sorafenib failure. Demographic data, including age, gender, race, stage of disease, and risk factors were collected. Data were collected on treatment doses, duration, response, and adverse events including left ventricular ejection fractions (LVEF). Median progression-free survival (PFS) and overall survival (OS) were calculated from the start of combined therapy.

Results: N=14 patients: Median age 60 years (range 43-70), median KPS 80%, 12 males (86%), 4 stage III (29%)/10 stage IV (71%), 8 HBV (57%) /3 HCV (21%). The median number of doxorubicin doses was 3 (range 1-11). Eight patients had grade 3-4 toxicities, including neutropenia, febrile neutropenia, thrombocytopenia, hepatitis B flare, dehydration, nausea, vomiting, mucositis, pain, and seizure. No >20% relative drops in LVEF from baseline were noted. There were no toxicity-related deaths. There were no objective responses. Of 14 evaluable patients, 5 (36%) had SD for ≥ 4 months, and 9 (64%) had POD. Median PFS was 3.4 months (95% CI 2.30-8.36), and OS 10.1 months (95% CI 4.34-11.45).

Conclusions: In this small retrospective review of a select group of patients, doxorubicin plus sorafenib was tolerable, albeit with substantial toxicity. Doxorubicin and sorafenib may have activity after sorafenib failure however whether this is due to a synergy between the drugs, or to doxorubicin alone, cannot be determined from this review. A formal evaluation of doxorubicin plus sorafenib versus doxorubicin alone, versus best supportive care in the second line setting is warranted.
Predictive value of KIT immunohistochemical staining for KIT mutations in patients with gastrointestinal stromal tumors (GIST): A systematic review.
Authors: Tun Nay Min , Villani Gina M.
Published: February 2017

30

Background: Immunohistochemical staining for KIT (CD117) is used as part of diagnostic tool for GIST. Approximately 95% of GIST are known to be positive for CD117. Studies have shown that not all CD117-positive GIST carry KIT mutations nor does CD117 negativity rule out KIT or PDGFRA mutations. We performed a systematic review to investigate the positive and negative predictive values of KIT immunostaining for KIT mutations in GIST.

Methods: A Medline search of the MeSH terms “KIT mutation” and “GIST” and “prevalence” yielded 54 articles from year 1999 to 2011. English language studies on GIST with data available for KIT immunostaining as well as KIT gene mutations were included. Studies lacking data on either CD117 positivity or KIT mutations were excluded. Immunostaining was done using Dako polyclonal rabbit antibody or PKCh monoclonal mouse antibody in eligible studies. Denaturing high-pressure liquid chromatography (DHPLC) was used to screen mutations in majority of eligible studies, and ABI Prism Genetic Analyzer to sequence DNA.

Results: 6 studies including 708 CD117-positive GIST patients were eligible for analysis of positive predictive value of KIT immunostaining for KIT mutations and 5 studies including 47 CD117-negative GIST patients for negative predictive value. Many studies were excluded due to insufficient data on CD117 positivity or KIT mutational analysis. 72.8% of CD117-positive GIST tumors carried KIT mutations (exon 11 62.2%, exon 9 10.2%, exon 13 1.8% and exon 17 1%), and 4.1% harbored PDGFRA mutations. In contrast, 74.5% of CD117-negative GIST tumors did not have KIT mutations. 25.5% of CD117-negative GIST harbored KIT exon 11 mutations (no mutations in exon 9, 13 or 17 were observed). In addition, 30% of CD117-negative GIST were found to have PDGFRA mutations.

Conclusions: PDGFRA mutations were found to be 7 times more common in CD117-negative than in CD117-positive GIST (30% vs. 4.1%). Over half (55.5%) of CD117-negative GIST carried KIT exon 11 or PDGFRA mutations. We recommend mutational analysis in all tumors clinically suspected of GIST and that are CD117-negative for two reasons: 1. in order to make a diagnosis, and 2. to help tailor therapy.
Margin status and neoadjuvant chemoradiation in patients with borderline resectable pancreatic cancer.
Authors: Papavasiliou Pavlos , Piposar Jonathan R , Arrangoiz Rodrigo , Chen Kathryn T , Zhu Fang , Chun Yun Shin , Hoffman John Parker
Published: February 2017

304

Background: The objective of this study was to examine the effect of margin status and neoadjuvant therapy in determining outcomes for borderline resectable (BLR) pancreatic cancer and how neoadjuvant chemoradiation impacts margin of resection.

Methods: A retrospective chart review was conducted to identify patients who underwent resection for BLR pancreatic cancer based on the AHPBA/SSO/SSAT consensus definition. Outcomes including overall survival (OS) and disease free survival (DFS) were determined based on margin status, location of positive margin (artery, vein, or pancreas), and receipt of neoadjuvant chemoradiation.

Results: One hundred and three patients who met the definition of BLR pancreatic cancer and underwent resection between April 1993 and July 2010 were reviewed. Mean age at diagnosis was 65 with a median follow up time of 19.7 months. Neoadjuvant chemoradiation was administered in 49.5% of patients. Twenty-five percent of patients underwent portal and/or superior mesenteric vein resection, and 7% hepatic artery resection. Microscopic positive margin rate was 54%. Median OS was 17.2 months for patients with positive margins versus 24.9 months for patients with negative margins (p=0.003). Median DFS was 13.1 months for patients with positive margins versus 18.6 months for patients with negative margins (p=0.001). There was no difference in OS or DFS for patients with positive margins based on location or number of positive margins. Of the patients who received neoadjuvant chemoradiation, 61.7% had a negative margin of resection versus a 38.3% negative margin of resection rate for patients who did not receive neoadjuvant chemoradiation (p=0.02). Among patients with a positive margin, there was no difference in OS or DFS with or without neoadjuvant chemoradiation.

Conclusions: A positive margin of resection, irrespective of location or number, is associated with worse outcome in patients with BLR pancreatic cancer. The use of neoadjuvant chemoradiation is associated with higher rates of margin free resection.
FOLFIRINOX in locally advanced or metastatic pancreatic cancer.
Authors: Faris Jason Edward , Hong Theodore S. , McDermott Shaunagh , Guimaraes Alexander R , Sahani Dushyant , Clark Jeffrey W. , Ryan David P. , Blaszkowsky Lawrence Scott
Published: February 2017

313

Background: The recently published Phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability with FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX.

Methods: 29 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX between July 2010 and April 2011 were used for this analysis. Clinical characteristics, and gradeable toxicities were tabulated, and formal radiographic review performed to determine best overall response rates (ORR).

Results: 17 patients received FOLFIRINOX for metastatic disease and 12 patients for locally advanced disease. The median age of patients was 60 (range 39-76). 22/29 patients were men. 18/29 patients had received no prior chemotherapy. There was one patient with PS 2; all others had PS 0 or 1. 8/29 patients had biliary stents. Overall, 11 partial responses (PR) were observed (ORR 38%); 10/11 partial responses were in chemo-naïve patients, who had an ORR of 56%. In the metastatic setting, there were 6 PR, for an ORR of 35%, and 7 patients with stable disease (SD). In the locally advanced setting, there were 5 PR (ORR 42%), and 7 patients with SD. Following treatment with FOLFIRINOX, one patient with locally advanced disease has subsequently undergone R0 resection. The median number of cycles performed was 8 in both the locally advanced and metastatic settings. 12/29 patients required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 10 patients; 7/10 had not received prophylactic growth factor treatment from the start of FOLFIRINOX. 4 patients developed febrile neutropenia, 4 patients developed grade 3/4 thrombocytopenia, and 1 patient developed grade 4 anemia.

Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both the metastatic and locally-advanced settings. FOLFIRINOX appears to be associated with manageable, but significant toxicities, with over 40% of patients requiring hospitalization.
Helical tomotherapy and concurrent gemcitabine-based chemotherapy for locally advanced pancreatic cancer.
Authors: Seong Jinsil , Chang Jisuk , Song Siyoung , Keum Woong
Published: February 2017

318

Background: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed.

Methods: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between May 2006 and May 2009. Radiotherapy was directed to the primary tumor with a 0.5 cm margin without prophylactic nodal coverage. Twenty nine patients (79%) received full-dose (1000 mg/m2) gemcitabine based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%).

Results: The median follow-up was 15.5 months (range 3.4-43.9) for the entire cohort, and 22.5 months (range 12.0-43.9) for surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (20%) were converted to resectable status, including one with a pathologic complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than grade 3. Severe late GI toxicity (≥ Grade 3) occurred in 10 patients (26%); one treatment related death due to GI bleeding was observed.

Conclusions: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.
Multiple utilities of portal vein embolization for patients with hepatocellular carcinoma.
Authors: Beppu Toru , Okabe Hirohisa , Okabe Kazutoshi , Masuda Toshiro , Mima Kosuke , Imai Katsunori , Hayashi Hiromitsu , Doi, Koichi , Chikamoto Akira , Ishiko Takatoshi , Takamori Hiroshi , Baba Hideo
Published: February 2017

319

Background: Portal vein embolization (PVE) is a multi-potential treatment for hepatocellular carcinoma (HCC). The aim of this study is to identify the efficacies of PVE for resectable and unresectable HCC patients.

Methods: Until 2011, 668 HCC patients underwent hepatic resection and 102 HCC patients treated with PVE. PVE was performed with percutaneous and ipsilateral approach using ethanolamine oleate iopamidol. Preoperative future remnant liver volume (%LV) and functional liver volume (%FLV ) were assessed with our developed combined 99mTc- galactosyl human serum albumin (GSA) scintigraphy (SPECT)/CT system. In unresectable cases chemoembolization (TACE) was repeated after PVE.

Results: 1. Comparison of %LV and %FLV after right-PVE (n=40). %FLV before PVE was significantly lower in PVE group (38%) compared to non-PVE group (58%), but increased remarkably after PVE (from 38% to 55%, P < 0.0001). Right hepatectomy was successfully completed in 10 patients based on %FLV, instead of conventional %LV. 2. Long-term prognosis after right-hepatectomy with /without PVE (n=60). The 3- and 5-year disease-free survival (DFS) rates in the PVE group were significantly greater than those in the non-PVE group (78% and 78% versus 20% and 0%, P = 0.01). The 3- and 5-year overall survival (OS) rates in the PVE group were also higher than those in the non-PVE group (72% and 72% versus 57% and 12%, P <0.05). By multivariate analysis, independent prognostic factors for DFS were application of PVE (HR3.59), Multiple tumor (HR3.57), Fibrosis stage F3–4 (HR2.81), and protein induced by vitamin K absence or antagonists-II (PIVKA-II) ≥678AU/ml (HR2.69). 3. Prevention of intrahepatic metastases in unresectable HCCs in hemi-liver (n=40). The 3-year intrahepatic recurrence rates in the non-portal-embolized area was 58.8% and 81.8%, and the 5-year OS was 38.2% and 8.5%, in the PVE/TACE group and TACE group, respectively. The former rates were sinificantly higher (P<0.05).

Conclusions: PVE can improve resectability, and might improve disease-free and overall survival for patients with both resectable and unresectable HCC.
Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.
Authors: Chakraborty Samhita , Bauer Todd W. , Morris Monica M , Yarde Erin , Parsons J Thomas , Adams Reid B , Sanoff Hanna Kelly
Published: February 2017

329

Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients.

Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts.

Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy.

Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.
A prospective randomized controlled trial comparing 4-weekly versus 3-weekly adjuvant chemotherapy with gemcitabine after curative resection of biliary tract cancer.
Authors: Nakahira Shin , Kobayashi Shogo , Miyamoto Atsushi , Shimizu Junzo , Kashiwazaki Masaki , Ueshima Shigeyuki , Kim Yong-Kook, , Kitagawa Toru , Dono Keizo , Mori Masaki , Doki Yuichiro , Nagano Hiroaki
Published: February 2017

345

Background: Resection of biliary tract cancer, employing pancreatoduodenectomy and major hepatectomy, is highly aggressive. Thus, postoperative gemcitabine cannot be administered employing a routine dosage protocol. We theorized that a 3-weekly protocol (days 1 and 8, every 3 weeks) of gemcitabine as adjuvant chemotherapy would be superior to the usually administered 4-weekly protocol (days 1, 8, and 15 every 4 weeks).

Methods: The outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol were compared in a prospective randomized clinical setting. The primary endpoint was the treatment completion rate, while secondary endpoints were adverse events and recurrence-free survival.

Results: We enrolled a total of 27 patients. Only two patients (14%) on the 4-weekly protocol and three (23%) on the 3-weekly protocol (p=0.8099) completed treatment with no omissions and/or dose modifications. Most of the remaining patients (70%) experienced grade 3/4 neutropenia. Relative dose intensities were 72% and 78%, respectively, with the 4-weekly and 3-weekly protocols. Recurrence-free survival rates did not differ significantly between the two protocols.

Conclusions: Contrary to our hypothesis, the 3-weekly protocol did not produce superior results in terms of completion, adverse events or recurrence-free survival rates as compared to the standard 4-week protocol.
Stereotactic body radiotherapy (SBRT) in combination with surgery for primary and metastatic liver tumors.
Authors: Lappinen Erik , Thai Ngoc , Tom Kusum , Khan Akhtar , Day Ellen , Green William Ross , Christensen James , Kirichenko Alexander V.
Published: February 2017

347

Background: Evaluate the feasibility, safety, and efficacy of SBRT in combination with surgery for primary and metastatic liver tumors.

Methods: 12 patients completed hepatectomy and SBRT for either hepatocellular carcinoma (HCC) (3) or metastases from colorectal (4), neuroendocrine (2), uterine (2), or sarcoma (1) primary. All patients with metastases completed chemotherapy. Most patients (7) had resection of their operable metastases, total of 19, and gold fiducials placed in the unresectable lesions, total of 9, to facilitate definitive adjuvant SBRT. One patient with an unresectable metastasis received preoperative SBRT. Two patients with HCC had SBRT as a bridge to liver transplant. Two patients had salvage SBRT for recurrence after surgery. All patients completed 4D-CT for ITV definition and SPECT/CT to define functional normal liver parenchyma volume (NLV). MV-fluoro was performed to confirm tumor/fiducial respiratory motion within the PTV.

Results: All patients successfully completed a combination of hepatectomy and SBRT. Seventeen hepatic lesions (≤ 2/patient) were treated with SBRT with a mean PTV 186.0 cc (15.1-803.5). The mean dose was 49.3 Gy (39-60) prescribed to the PTV in 5-6 fractions. With median follow-up of 9.2 months (2.8-15.3) there was no RILD > Grade 1 observed. The most common toxicity was Grade ≤ 2 fatigue. Nine patients had reduced SPECT-NLV vs. calculated NLV by a mean of 487.5 cc (p = 0.0004). In 6 of these, the SPECT-NLV vs. the CT-NLV was reduced by a mean of 253.9 cc (44.6 - 1076.2) reflecting the importance of SPECT functional imaging for SBRT planning. Postoperative morbidity was ≤ Grade 1. All surgical margins were negative. Three patients developed intrahepatic failures post SBRT. However, on follow-up imaging no in-field failures have occurred.

Conclusions: The combination of liver SBRT with hepatic resection is safe and effective. It can be used preoperatively to increase resectability or to salvage surgical failures. We also report on the combination of limited hepatectomy for peripheral (including bilobar) hepatic metastases with planned SBRT to unresectable metastatic lesion(s). SBRT planning with SPECT/CT allows identification and preservation of the NLV.
Does 18-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) predict survival in advanced pancreatic cancer? A single-institution experience.
Authors: Ashraf Noman , Razzaque Saqib , Weber Jill M. , Malafa Mokenge Peter , Kim Richard D.
Published: February 2017

351

Background: Pancreatic cancer is associated with a poor prognosis. Histological grade, stage and serum tumor markers are well established prognostic factors for survival. Some studies suggest that 18-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) correlates with survival in pancreatic cancer. In this study, we aimed to determine whether standardized uptake value (SUV), a measure of FDG uptake by fusion PET/CT, had prognostic significance in patients with advanced pancreatic cancer.

Methods: Using a comprehensive pancreatic cancer database at H. Lee Moffitt Cancer Center, we identified patients who underwent PET/CT scan as initial workup for resection but were found to have advanced disease (stages III and IV) when surgery was attempted. Data from January 2006 to December 2010 was retrospectively analyzed and correlated with the maximum SUV determined by PET/CT. Other prognostic factors including stage, age, gender, serum tumor marker CA 19-9 levels and the use of chemotherapy were also evaluated using multivariate analysis.

Results: We identified 41 consecutive patients who were deemed resectable by virtue of staging workup with CT, PET/CT and endoscopic ultrasound (EUS), but found to have locally advanced/metastatic disease intra-operatively. At the time of analysis, there were a total of 30 deaths. Twelve patients had metastatic disease and 29 had stage III pancreatic cancer. SUV uptake ranged from 2.9 to 16.2 with a mean of 6.4. Median overall survival for the 28 patients with SUV less than or equal to the mean (≤ 6.4) was 14 months (95% confidence interval 10 – 25 months) vs. 9.1 months for the 13 patients with SUV > 6.4 (95% confidence interval 4-17 months). This difference was not statistically significant (p=0.178). On multivariate analysis, use of chemotherapy was the only independent predictor of survival.

Conclusions: Glucose uptake by PET/CT, reflected by SUV, was not found to be a predictor of survival in patients with advanced pancreatic cancer. The retrospective nature and limited sample size are limitations of our study, however further research is warranted.
Vitamin D deficiency in patients with pancreatic cancer.
Authors: Wang-Gillam Andrea , Ding Kevin , Cho May , Lockhart Albert C. , Chen Ling , Zubal Beth , Tan Benjamin
Published: February 2017

353

Background: Vitamin D deficiency is common in many cancer patients but little is known about the vitamin D status in patients with pancreatic cancer. Frequently, patients with pancreatic cancer have malabsorption syndrome, and since vitamin D is fat soluble, it is likely to be deficient in this population.

Methods: We conducted a retrospective review on patients with pancreatic cancer who were treated at Siteman Cancer Center (SCC). Patients’ demographic information, clinical staging at the time of vitamin D assessment, vitamin D status and survival data were collected. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D [(25(OH)D] <20 ng/mL; vitamin D insufficiency was defined as 25(OH)D <30 but >20.

Results: Between Dec 2007 and June 2011, 184 out of 625 pancreatic cancer patients had their vitamin D level checked at least once. Median age was 64 (range 34-86); 87 patients were female and 97 were male. The majority (159) were Caucasian. Sixty-four (34.8%) patients were post resection, while 34 (18.5%) and 86 (46.7%) had local disease and metastatic disease, respectively. Out of 184, 43 (23.3%) patients had normal vitamin D levels, while 53 (28.8%) and 88 (47.85%) were found to be vitamin D insufficient and deficient, respectively. All 28 non-Caucasian patients had either vitamin D deficiency or insufficiency, and their median 25(OH)D level was 11 ng/mL, compared to 21 ng/mL for Caucasian patients. The median 25(OH)D level was 17.5 ng/mL in patients with resected cancer, 22 ng/mL in patients with local disease, and 23 ng/mL in patients with metastatic disease. After adjusting age and stage, 25(OH)D <20 ng/mL was found to be an independent prognostic factor (p= 0.071).

Conclusions: Vitamin D insufficiency and deficiency is prevalent amongst our patients with all stages of pancreatic cancer. Vitamin D appears to be prognostic and should routinely be assessed in patients with pancreatic cancer.
Liver resection for multifocal hepatocellular carcinoma.
Authors: Kim Peter Tae Wan , Jang Jihyun , Fischer Sandra , Greig Paul David , Gallinger Steven , Wei Alice Chia-chi , McGilivray Ian M , Cattral Mark S , Cleary Sean P
Published: February 2017

355

Background: Liver resection for multifocal hepatocellular carcinoma (HCC) is controversial. This study was conducted to outline our institution’s experience with liver resection for multifocal HCC.

Methods: A retrospective review of patients who underwent liver resections from 1992 to 2011 for histologically confirmed hepatocellular carcinoma was performed. Multifocal disease was defined as more than 1 histologically proven HCC found in the liver resection specimens.

Results: Of the 386 liver resections performed for HCC, 47 were performed for multifocal disease. Mean age was 60+11 years, and most patients (92%) had chronic liver disease. Hepatitis B was the most common etiology (60%), followed by hepatitis C (26%), and other etiologies (15%). Most patients were Child’s class A (89%). Most patients had intermediate Barcelona Clinic Liver Cancer (BCLC) stage (stage B) tumors (81%) and a minority of patients had early stage tumors (BCLC stage A, 19%). Major hepatectomy (>2 segments) was performed in 87% with an in hospital mortality of 6.4%. Major complications (Clavien-Dindo scale >3) occurred in 4 patients (9%). Median length of stay was 7 days and the rate of liver failure was 4.3%. Mean tumor number was 3+2 and the size of the largest lesion was 5+3 cm. Cirrhosis was present in 51% of patients. Majority of tumors were moderately differentiated (60%) and vascular invasion was present in 42%. The recurrence rate was 57% and the liver was the most common site of recurrence (81%). Treatment of recurrences occurred in 74% of patients: ablation (33%), chemotherapy (11%), transarterial chemoembolization (11%), resection (7.4%), sorafenib/radiation (7.4%) and transplantation (3.7%). Median disease free interval was 8 months and the overall survival was 18 months

Conclusions: Liver resection for multifocal HCC can be performed safely in patients with chronic liver disease. Long term survival can be achieved in these patients and it should be considered as an option.
The influence of surgical oncology fellowship programs in training hepatopancreatobiliary surgeons.
Authors: Wiatrek Rebecca Lynn , Lee Wendy , Wray Curtis Jackson , Singh Gagandeep , Yim John H , Chen Steven L. , Garcia-Aguilar Julio , Kim Joseph
Published: February 2017

358

Background: It is unclear how the physician shortage in the US will affect cancer care for our aging population and specifically how it will affect the care of hepatopancreatobiliary (HPB) malignancies. Our objective was to assess the clinical practices of recent surgical oncology fellowship graduates to determine their contribution in caring for this patient population.

Methods: Practice data was gathered for surgeons who completed Society of Surgical Oncology (SSO)-approved surgical oncology fellowship programs between 2003-2008. Types of practice were defined as: (1) University Hospital or NCI-designated Cancer Center (NCICC); (2) University-affiliated hospital with resident training; (3) Private/community hospital with residency training program; (4) Private practice; (5) Military; and (6) International.

Results: Of 253 surgeons who matched into SSO approved programs during our study period, 10 did not complete training, 11 entered military positions, and 17 are practicing internationally. Of the remaining 215 surgeons, 75% (n=161) obtained teaching positions and 25% (n=54) entered private practice. Of those in teaching positions, the majority were at University Hospitals/NCICC (n=133); followed by University-affiliated hospitals (n=16) and private/community hospitals with resident training (n=12). Overall, the practice focus was most commonly general surgical oncology (60%, n=130) followed by primary HPB (20%, n=43), breast/endocrine or melanoma/sarcoma (17%, n=36), and breast alone (3%, n=6).

Conclusions: Our investigation shows that the majority of trainees from surgical oncology fellowship training programs obtain teaching positions with at least a portion of their practice covering HPB malignancies. Thus, recent surgical oncology fellowship graduates are positively contributing to the workforce treating HPB malignancies.
The urinary metabolomic signature of Barrett's esophagus.
Authors: Davis Vanessa Wylie , Schiller Dan E. , Sawyer Michael B.
Published: February 2017

36

Background: Current screening and surveillance strategies for Barrett’s esophagus are inadequate. More reliable tools are needed. A unique urinary metabolomic signature could fill this niche. We applied metabolomic techniques to identify urinary metabolites capable of facilitating in the diagnosis of Barrett’s esophagus.

Methods: Urine samples from patients with histologically confirmed Barrett’s esophagus (n=32) and normal, healthy volunteers (n=25) were collected and examined using 1H-NMR spectroscopy. Targeted profiling of spectra using Chenomx NMR Suite 7.0 software permitted the detection and quantification of 66 distinct metabolites. Unsupervised (principal component analysis, PCA) and supervised (partial-least squares discriminant analysis, PLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra of patients with Barrett’s esophagus and healthy volunteers using SIMCA-P (version 11, Umetrics, Umeå, Sweden).

Results: Significant differences were found when comparing the concentrations of 59 metabolites in the urine of healthy volunteers and patients with Barrett’s esophagus. Those metabolites contributing the most class discriminating information included 3-hydoxybutyrate, adipate and choline. Clear distinction between patients with Barrett’s esophagus and healthy controls was noted when PLS-DA was applied to the data set. Model parameters for both the goodness of fit R2, and the predictive capability Q2, were high (R2 = 0.96; Q2 = 0.90). Model validity was tested using response permutation and results were suggestive of excellent predictive power.

Conclusions: Urinary metabolomics identified a discrete signature associated with Barrett’s esophagus compared to healthy controls. This profile has the potential to aid in diagnosis and the development of new therapeutic targets.
Definitive radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer: A retrospective analysis.
Authors: Nakamura Akira , Shibuya Keiko , Takaori Kyoichi , Kawaguchi Yoshiya , Yoshimura Michio , Matsuo Yukinori , Itasaka Satoshi , Hiraoka Masahiro
Published: February 2017

366

Background: Only surgical resection can provide a chance of long-term survival for patients with pancreatic cancer, but loco-regional recurrence has been a major challenge which inevitably results in poor prognosis and loss of patients’ quality of life. Curative reoperation is seldom attainable but has been suggested to have benefits on overall survival. We hypothesized that definitive radiotherapy could offer a good control for the unresectable local recurrence and improve survival. The primary objective of this retrospective analysis is to evaluate the efficacy and tolerability of definitive radiotherapy for patients with isolated locally-recurrent pancreatic cancer.

Methods: A total of 26 patients, who developed local recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2011, were retrospectively analyzed. The isolated local recurrence was diagnosed with the radiological images (CT/MRI/PET) and tumor marker relapse. The overall survival (OS) and local control rate (LC) were calculated from the start day of radiotherapy and estimated by Kaplan-Meier method. The responses in tumor size and tumor markers were evaluated. The treatment-related toxicity was assessed according to CTC-AE (ver. 4.0).

Results: The median total dose of radiotherapy was 50.4 Gy (range, 39.6–54 Gy). Concurrent chemotherapy consisted of gemcitabine (62%), S-1 (19%), and 5-fluorouracil (4%). At a median follow-up time of 13 months, the 1-year OS and median survival were 75% and 21.6 months, respectively. The 1-year local control rate was 59%. Objective radiological response was not seen. The tumor marker reduction and ≥ 50% reduction were observed in 65% and 12%. Grade≥3 hematological toxicity was seen in 62%. Grade ≥ 3 of acute gastrointestinal toxicity was not observed. At a late phase, Grade 3 ileus observed in one, and Grade 3 gastric bleeding ulcer was seen in one patient.

Conclusions: Definitive radiotherapy resulted in encouraging local control and overall survival for patients with isolated locally-recurrent pancreatic cancer. This treatment strategy should be further evaluated prospectively.
Usefulness of gemcitabine combined with 5-fluorouracil and cisplatin (GFP) for patients with advanced biliary carcinoma as a postoperative adjuvant chemotherapy.
Authors: Morine Yuji , Shimada Mitsuo , Utsunomiya Toru , Imura Satoru , Ikemoto Tetsuya , Hanaoka Jun , Sugimoto Koji , Saito Yu , Yamada Shinichiro , Asanoma Michihito
Published: February 2017

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Background: Prognosis of patients with advanced biliary carcinoma is still poor, and chemotherapy has been shown to have little impact. The aim of the present study was to clarify the effectiveness of GEM combined with CDDP and 5FU (GFP) therapy for advanced biliary carcinoma. The usefulness as a postoperative adjuvant chemotherapy using GFP (UMIN000006924) was evaluated.

Methods: 1. Identification of independent poor prognostic factors: One hundred one patients with biliary carcinoma before induction of GFP chemotherapy, including intrahepatic cholangiocarcinoma (IHC: n=33), hilar cholangiocarcinoma (HC: n=29), and gallbladder cancer (GBC: n=39) were enrolled. The prognostic factors were investigated by multivariate analysis using Cox’s proportional hazard model. 2. Clinical usefulness of adjuvant GFP chemotherapy: One hundred forty-eight patients with biliary carcinoma (IHC: n=46, HC: n=43, GBC: n=39), who were positive for poor prognostic factors, received postoperative adjuvant GFP chemotherapy. The prognosis of these patients was compared to those not having postoperative adjuvant chemotherapy.

Results: 1. In multivariate analysis, non-curative resection, lymph nodes metastasis and intrahepatic metastasis were identified as the independent prognostic factors. 2. Seventy-nine patients (53.3%) had poor prognostic factors. Of these, 22 patients received postoperative adjuvant GFP chemotherapy. The prognosis of patients with poor prognostic factors, who received postoperative adjuvant GFP chemotherapy, was significantly better than those not having such adjuvant chemotherapy (p<0.01) (3y survival: 59.6% vs. 18.9%). Furthermore, in patients with non-curative resection, postoperative adjuvant GFP chemotherapy also prolonged postoperative prognosis (p<0.01) (3y survival: 62.5% vs. 9.4%)

Conclusions: Postoperative GFP adjuvant chemotherapy for patients with poor prognostic factors may improve the surgical outcomes.
Incidence and prediction of venous thromboembolism (VTE) in ambulatory patients (pts) with pancreas cancer receiving chemotherapy.
Authors: Ruperez Blanco Ana Belen , Muñoz Martin Andrés Jesús , Garcia Alfonso Pilar , Alvarez Suarez Sonsoles , Cavanagh Podesta Mercedes , Custodio Cabello Sara , Mondejar Solís Rebeca , Lopez-Trabada Ataz Daniel , Blanco-Codesido Montserrat , Martin Miguel
Published: February 2017

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Background: VTE is considered a main cause of mortality and morbidity in cancer pts and is commonly underestimated by oncologists. Pancreatic cancer is associated with the highest risk of VTE and the true incidence remains uncertain. Chemotherapy has been identified as an independent risk factor for VTE. The aim of this study is to analyze the incidence of cancer-associated thrombosis in ambulatory pts with pancreatic cancer receiving chemotherapy.

Methods: We performed a retrospective review to determine the incidence of VTE in the gastrointestinal cancer unit of our centre. Between 2008 and 2010, 64 consecutives pts were identified and included in the analysis. Pancreatic neuroendocrine tumors were excluded.

Results: Clinical characteristics ( table 1). Twenty pts (31.2%) experienced VTE including 7 pulmonary emboli (PE), 8 deep-vein thromboses (DVT) and 8 visceral vein thromboses (VVT). PE:25%. DVT:25%. VVT:35%. PE+DVT:10%. DVT+VVT:5%. Arterial thromboembolism (ATE): 2 pts (3.1%). 56% of the events were diagnosed during the first six months after diagnosis. Khorana’s predictive model for chemotherapy-associated thrombosis (risk category): intermediate risk (IR) 17 pts (27.9%) and high risk (HR) 44 pts (72.1%). VTE in HR and IR category: 14/44 pts (31.8%) and 6/17 pts (35.3%).

Conclusions: The high incidence of VTE observed in this study is consistent with prior reports. Primary antithrombotic prophylaxis should be considered in this setting. Specific predictive model for chemotherapy-associated thrombosis in pancreas cancer must be investigated.

[Table: see text]
Gemcitabine (G) and nab-paclitaxel (nab-P) in patients with refractory advanced pancreatic cancer (PC).
Authors: Ernani Vinicius , Akunyili Ikechukwu Immanuel , Hosein Peter Joel , Macintyre Jessica , Rocha Lima Caio Max S.
Published: February 2017

373

Background: There is no standard chemotherapy regimen for PC patients who have progressed on G and fluoropyrimidine-based therapy. Single agent nab-P had limited activity on a second-line phase II trial in PC. Synergistic preclinical studies with G and taxanes have been reported. Nab-P targets stromal cells and leads to improved delivery of chemotherapy to PC cells. The combination of G + nab-P might be an effective approach in pretreated PC.

Methods: A retrospective analysis of advanced refractory PC patients treated from Sep 2010 to Aug 2011 with the combination of G + nab-P was performed at the Sylvester Comprehensive Cancer Center. Patients received G 1000mg/m2 and nab-P 100mg/m2 on D1, 8 and 15 of a 28 day cycle. Treatment response was assessed by review of imaging studies using the RECIST criteria, CA19-9 response and symptomatic improvement. The progression-free survival (PFS) and overall survival (OS) were calculated from time of commencement of G + nab-P until documented progression or death respectively.

Results: 10 patients were treated with G + nab-P; 60%, 30% and 10% of patients had received 3, 2 and 1 prior chemotherapy regimen. 90% and 80% received prior G or fluoropyrimidine-based regimen respectively. Therapy was discontinued in one patient following only one dose of G + nab-P (Cycle 1, day 1) due to grade 2 thrombocytopenia. The remaining 9 patients received a median of 4 cycles. Two (22.2%) patients had confirmed PR, 3(33.3%) patients had confirmed stable disease while 4 (44.4%) patients progressed on therapy. The median PFS was 13.7 weeks. The median PFS was 20 weeks in patients with PR or SD and 9.9 weeks in patients with PD. Recurrent malignant ascitis resolved in a patient with peritoneal carcinomatosis. Treatment was well tolerated; grade 3-4 hematologic toxicity included anemia, thrombocytopenia and neutropenia in 2, 1 and 2 patients respectively. 70% of patients required G-CSF support. Non hematologic Grade 3-4 toxicities included fatigue, peripheral neuropathy; nausea and vomiting in 3, 2 and 1 patient respectively.

Conclusions: G + nab-P resulted in clinical benefit in half of this group of advanced PC patients who had previously progressed on G and fluoropyrimidine-based regimens.
Evaluation of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone for unresectable or recurrent biliary tract cancer.
Authors: Kameda Ryo , Ando Tomoko , Kobayashi Satoshi , Ueno Makoto , Ohkawa Shinichi
Published: February 2017

377

Background: As there was no standard chemotherapy for advanced biliary tract cancer before ABC-02, we had treated our patients with gemcitabine alone. However, recently cisplatin plus gemcitabine became standard as first line chemotherapy. We assessed the benefits of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone before ABC-02 era.

Methods: We retrospectively examined the patients with advanced biliary tract cancer, who were treated with chemotherapy using cisplatin plus gemcitabine after failure of gemcitabine alone. The eligible patients had unresectable or recurrent biliary tract cancer, objective tumor progression after gemcitabine alone chemotherapy, adequate organ function including renal function and ECOG performance status (PS) 0-1. The treatment consisted of cisplatin (25 mg per square meter of body-surface area) plus gemcitabine (1000 mg per square meter) on days 1 and 8, every 3 weeks.

Results: Between December 2010 and July 2011, 10 patients were enrolled. Their median age was 63 years, the male : female ratio was 8:2, intrahepatic bile ducts : gall bladder : extrahepatic bile duct 6:3:1, locally advanced : metastatic disease 1:9, PS0 : PS1 7:3. The objective response rate was 30%, and the tumor control rate was 60%. The median progression-free survival was 4.0 months (95% confidence interval (CI): 1.4-6.9 months) with median overall survival 6.4 months (95% CI: 3.7-7.6 months). Grade 3-4 toxicities were neutropenia (30%) and anemia (30%).

Conclusions: Cisplatin plus gemcitabine can be an optional therapy for unresectable or recurrent biliary tract cancer after failure of gemcitabine alone.
Survival analysis of PETCAM: A multicenter randomized controlled trial of PET/CT versus no PET/CT for patients with resectable liver colorectal adenocarcinoma metastases.
Authors: Moulton Carol-anne , Levine Mark Norman , Law Calvin , Hart Richard , Ruo Leyo , Gu Chu-Shu , Hendler Aaron , Gulenchyn Karen Y. , Haider Masoom A. , Marcaccio Michael , Tandan Ved , Quan Douglas , Jalink Diederick , Fairfull Smith Robin , Luu Shelly , Greig Paul David , Husien Mohamed , Finch Terri , Julian Jim A , Gallinger Steven
Published: February 2017

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Background: An increasing proportion of patients with liver CAM are undergoing hepatic resection with curative intent. Detection of occult metastastic disease is important in this setting, and PET/CT is used to identify patients with either inoperable, or limited resectable extrahepatic disease not identified with conventional imaging. We recently reported the results related to the primary objective of PETCAM, a randomized trial for patients with resectable liver CAM, where 7.6% had a change in management based on PET/CT (ASCO 2011). As a secondary objective, we examined whether patients undergoing PET/CT derived a survival benefit, as they may be considered to be better selected.

Methods: PETCAM was a multicenter trial with 404 subjects randomized 2:1 to receive PET/CT or no PET/CT once they were assessed by a hepatobiliary surgeon to have resectable CAM. Subjects were followed over 4 years for overall survival (OS). As well as the intervention, we considered the SUV, Fong Score and other baseline factors as predictors for OS.

Results: After a median 2.8 years of follow-up, 107 of the 404 (26%) study subjects had died. The 270 PET/CT subjects [and the 245 of these who underwent surgery] showed no statistically significant survival advantage over the 134 No PET/CT subjects [123 who underwent surgery] with a hazard ratio (HR) of 0.85, 95% confidence interval (CI): 0.57 to 1.3; p=0.41 [HR=0.81, 95% CI: 0.52 to 1.3; p=0.34]. Fong score was a strong predictor of OS for all patients (HR=1.4, 95% CI: 1.1 to 1.6), and for those who had surgery (HR=1.4, 95% CI, 1.1 to 1.7). In the PET/CT arm, SUV is strongly predictive of OS [HR per unit SUV increase =1.11, 95% CI: 1.05 to 1.18; p=0.0007.

Conclusions: The addition of PET/CT had no effect on improving overall survival for patients who did or did not have hepatic resection for CAM. SUV is strongly predictive of survival for patients who had PET/CT, and Fong score is predictive of survival for all patients. The overall role of PET/CT in patients with resectable CAM appears limited and should be reevaluated in the current era of comparative effectiveness research and health care cost containment.