bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreaticoduodenectomy versus radiosurgery for octogenarians with pancreatic head adenocarcinoma.
Authors: Hogg Melissa Ellen , Kim Carolyn H , Boone Brian A. , Lee Kenneth K , Moser Arthur J. , Bartlett David L , Heron Dwight Earl , Burton Steven A. , Zeh Herbert J. , Zureikat Amer H.
Published: February 2017

220

Background: Recent reports have justified pancreaticoduodenectomy (PD) in octogenarians. Given the morbidity of PD and the increasing availability of stereotactic body radiosurgery (SBRT) we compared survival and morbidity of PD vs SBRT in octogenarians. Methods: A retrospective chart review was performed on all octogenarians with pancreatic head adenocarcinoma (PDA) who underwent open PD or SBRT from 2002-2011. Results: Twenty-six patients underwent PD, 17 (65%) resectable and 9 (35%) borderline, and 14 patients underwent SBRT, 10 (71%) resectable and 4 (29%) borderline (p=NS). All PD pts underwent R0/R1 resection. The groups differed in mean age (PD=83 vs SBRT=86 years, p=.01) and sex [males: PD=16 (62%) vs. SBRT=4 (29%)], but had the same BMI, Charlson Comorbidity Index, Karnofsky Performance Status, tumor size, and nodal status (p=NS). Of the SBRT group, 8 (57%) refused surgery; females were more likely to refuse surgery than males (8 (80%) vs 0, p=.0063). Compared to PD, SBRT patients took longer to intervention (26 vs 68 days, p=.0001). Twelve (46%) PD and 5 (36%) SBRT patients received chemotherapy (p=NS).Compared to the PD group, SBRT patients had no treatment related 90 day mortalities (0 vs 2 (8%), p=0.29), no complications (0 vs 14 (54%), p=.0007), and reduced length of hospital stay (0 vs 18.5 days, p=.0001). PD complications included pancreatic fistula and delayed gastric emptying in 3 (12%) and 4 (15%) patients respectively, and disposition was home=8 (31%), rehab=12 (46%), Skilled Nursing Facility =5 (19%), and Long Term Acute Care 1=(4%). Median time to metastasis was similar (PD=8.7 vs SBRT=7.3 months, p=NS). Median overall survival (PD=10.4 vs SBRT=10.2, p=NS) was the same in both groups. Four (15%) PD patients, stage II, are still alive (42-58 months); however, no SBRT patients are alive or have survived greater than 17 months. Conclusions: Octogenarians tolerated SBRT without morbidity, mortality, admission, or loss of independence compared to PD. Within this small series, disease specific survival and disease progression were not different between SBRT and PD raising a provocative question when counseling octogenarians about treatment strategy for head PDA.
Phase II study of induction therapy with gemcitabine and nab-paclitaxel followed by consolidation with mFOLFIRINOX in patients with metastatic pancreatic cancer.
Authors: Ramanathan Ramesh K. , Lee Peter , Leach Joseph W. , Anthony Stephen Patrick , Weiss Glen J. , Rosen Peter J. , Picozzi Vincent J. , Sachdev Jasgit C. , Larson Tim , Korn Ronald , Hu Chengcheng , Jameson Gayle S. , Stoll Amy C. , Von Hoff Daniel D. , Seng John E.
Published: February 2017

233

Background: We designed a phase II study to evaluate the efficacy, toxicity and feasibility of administering nab-paclitaxel/gemcitabine (NabP-Gem) followed by mFOLFIRINOX in MPC. Methods: Eligible patients had evidence of untreated MPC with performance status of ECOG 0-1 and adequate organ function. Induction therapy was with Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 every 4 weeks for a maximum of 6 months (6 cycles). mFOLFIRINOX every 2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given upto 6 months (12 cycles). The FOLFIRINOX regimen (NEJM,364:1817-25: 2011) was modified to omit the bolus 5FU and requires addition of granulocyte growth factor prophylaxis. A primary endpoint is to increase 1 year survival (n=30) to >70%, (95% confidence intervals for one year survival rate is +/- 20%). Results: As of 9/1/2012, 26 of 30 subjects have been accrued. M/F ratio is 58%/42%, median is 65 years. In 20 patients treated on the induction phase, 75% have a > 90% decrease in CA 19-9 levels. The partial response rate (PR) in the first 19 patients who have completed 4 cycles is 50%. Early image analysis on 9 subjects with concurrent CT and PET showed 44% PR (RECIST 1.1) but 89% by CHOI and PET criteria. A novel approach to interrogate tumor texture composition demonstrated substantial change in lesion texture following induction therapy. To date selected Grade > 3 adverse events are neutropenia (n=8), fatigue (n=5), thromboembolic events (n=4), peripheral neuropathy (n=3), dehydration (n=2), anemia (n=3), thrombocytopenia (n=2), febrile neutropenia (n=2) and myalgias (n=2). Among 26 patients who have received at least one cycle of NabP-Gem, ten dose reductions and four dose delays were seen. To date, 11 patients have begun the Consolidation regimen with mFOLFIRINOX. Conclusions: The induction NabP-Gem regimen shows preliminary evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). Study will now evaluate the safety, efficacy and feasibilty of the Consolidation regimen with mFOLFIRINOX. Supported by the Seena Magowitz Foundation. Clinical trial information: NCT01488552.
Patterns of recurrence and outcomes in pancreatic cancer.
Authors: Chen Kathryn Tzung-Kai , Singla Smit , Papavasiliou Pavlos , Arrangoiz Rodrigo , Gaughan John P. , Hoffman John Parker
Published: February 2017

234

Background: There is limited evidence supporting improved overall survival in patients with pancreatic cancer with isolated lung metastases compared to other metastatic sites. We reviewed our experience with patterns of metastases and outcomes in pancreatic cancer. Methods: A retrospective review of 378 patients who underwent potentially curative pancreatic resection for pancreatic adenocarcinoma at a tertiary care cancer center between 1997-2010. All patients were restaged in accordance with AJCC 7th edition guidelines. Kaplan-Meier analysis with log-rank test and Cox regression was used to compare median overall and disease-free survival (OS and DFS). Results: Patients were divided into 8 groups based upon site of first recurrence. 40% of patients were without evidence of recurrence at time of last follow up (n=165). Sites of first recurrence are as follow: liver (n=93, 24.6%), lung (n=37, 9.8%), locoregional (n=49, 13%), peritoneum (n=17, 4.5%), bone (n=6, 1.6%), and distant (n=2, 0.5%). 23 patients (6.1%) presented with multiple sites as first recurrence. Patients with isolated lung metastases had longest median OS while those with liver metastases had the shortest median OS (32 months vs. 17 months, p<0.001). Time to recurrence for lung vs. liver metastases was 14.9 vs. 7.4 months (p<0.005). Patients with liver metastases uniformly had significantly worse median OS as compared to other sites of recurrence. Finally, with respect to isolated lung recurrences, only CA19-9 was a significant prognostic factor. Those patients with a CA19-9 at diagnosis >185 had a 5-fold greater risk of death in our length of follow-up. Conclusions: Pancreatic cancer patients with isolated lung metastases as the site of first recurrence have improved OS compared to other sites, while patients with liver metastases have worse OS. CA19-9 >185 at time of diagnosis among patients with isolated lung recurrences was predictive for worse outcomes.
A phase I study of GC33 in Japanese patients with advanced hepatocellular carcinoma (HCC).
Authors: Okusaka Takuji , Ikeda Masafumi , Ohkawa Shinichi , Yamamoto Shunsuke , Suzuki Ikue , Furuse Junji
Published: February 2017

235

Background: Glypican-3 (GPC3) belongs to a family of cell-surface heparan sulfate proteoglycans and is specifically expressed in HCC. In this phase I study, we examined the safety, tolerability, and pharmacokinetics of GC33, a recombinant, humanized monoclonal antibody against GPC3, in Japanese patients (pts) with advanced HCC. Methods: This study was a 3+3 design for dose escalation to determine the maximum tolerated dose (MTD) of GC33 given intravenously at 5, 10, and 20 mg/kg weekly. Key eligibility criteria included histological or cytological confirmation of HCC, ECOG PS ≤ 1, Child-Pugh A or B, adequate organ function, and tumor tissues available for GPC3 immunohistochemistry. Results: Thirteen pts were enrolled at 3 dose levels: median age=65 years (range 48-78), M/F=12/1, ECOG PS 0/1=9/4, HBV/HCV=4/8, liver cirrhosis +/-=8/5, Child-Pugh A (5-6)/B (7) =10/3. All pts received prior systemic therapy including sorafenib. Treatment was well tolerated at all dose levels without DLT, and MTD was not reached. The most common AEs were lymphocyte count decrease (77%), Natural Killer cell count decrease (77%), C-reactive protein increase (69%) and pyrexia (62%). Grade 3 AEs (≥ 2 pts) were lymphocyte count decrease (23%), blood pressure increase (23%) and platelet count decrease (15%). Infusion reactions were seen in 62% of pts and medically manageable. Anti-GC33 antibody was not detected in any of the patients. PK analysis of GC33 showed a half-life of 4 to 7 days and dose proportional for AUC after the first dose. Trough concentrations reached a steady state after 4 to 6 doses. Twelve out of 13 biopsied tumor specimens showed immunoreactivity with mouse GC33 antibody. There was no CR or PR, but 7 SD and 3 of them had SD for more than 5 months before progression (all with GPC3 expression). Conclusions: GC33 was well-tolerated up to 20 mg/kg weekly in Japanese HCC pts with Child-Pugh A or B liver cirrhosis and potentially beneficial to GPC3+ HCC. A randomized phase II study of GC33 monotherapy as 2nd line therapy in advanced HCC pts is currently ongoing. Clinical trial information: JapicCTI-101255.
Activity observed in a phase I dose escalation trial of the hypoxia-activated, NO prodrug, RRx001.
Authors: Reid Tony R. , Infante Jeffrey R. , Burris Howard A. , Scribner Curtis , Knox Susan Jane , Oronsky Bryan , Stephens Janet L. , Scicinski Jan
Published: February 2017

241

Background: RRx-001, the first member of a new class of anticancer compounds sourced from the defense industry, is a hypoxia-selective, nitrite reductase-activated prodrug of nitric oxide (NO). The active metabolites selectively enhance oxidative and nitrosative stress in cancer cells through glutathione depletion, ROS formation, and the generation of high local concentrations of NO. The objectives of this Phase 1 dose-escalation trial were to investigate safety, dose-limiting toxicities (DLTs), pharmacodynamics and pharmacokinetics (PK) of RRx-001. Methods: Eligible patients had advanced solid tumor malignancies; ECOG PS 0-2; adequate bone marrow function. In a 3+3 escalation design, RRx-001 was administered intravenously (IV) over 2-3 hours once weekly for 8 weeks to patients with advanced cancer in successive dose-escalating cohorts. PK was collected on days 1 and 50, and tumor blood flow, assessed by CEUS or DCE/DWI-MRI, was performed on days 1 and 8. Tumor response was determined every 8 weeks. Results: To date 12 patients have been dosed across 3 successive cohorts (10, 16.7, and 24.6 mg/m2). Tumor types included pancreas (3), colorectal (5), head and neck (2), melanoma (1), and cholangiocarcinoma (1). No DLTs or treatment-associated SAEs were observed. Transient infusion site pain was reported in 10/12 patients, grade 1 (9/10) or grade 2 (1/10), generally managed by lengthening the infusion duration and using peripheral venous access. No relevant treatment-related changes in laboratory values were observed. Seven patients were evaluable for response, with 1 partial response (parotid tumor). Three patients had stable disease ≥ 2 months (2 pancreas, 1 colorectal with treatment duration 10+ months, exceeding the response to his previous chemo regimen). One pancreas patient with an increase in tumor size due to treatment-related central necrosis was diagnosed with pseudoprogression and remained on study for 4 months. Conclusions: RRx-001, an anticancer agent with a novel structure and mechanism of action, is well tolerated with mild infusion-site pain. PK and PD data will be presented. Escalation is ongoing, but preliminary evidence of anti-tumor activity is promising. Clinical trial information: NCT01359982.
A retrospective review of chemotherapy for patients with small bowel adenocarcinoma in British Columbia.
Authors: Duerr Donat , Ellard Susan , Cormier Eric , Taylor Marianne , Rao Sanjay C.
Published: February 2017

242

Background: Small bowel adenocarcinoma (SBA) can be associated with a poor prognosis. Randomized phase III trials of chemotherapy are not available due to the rarity of the disease. The Provincial Cancer Registry of the British Columbia Cancer Agency (BCCA) contains data on patients with SBA. Therefore we analyzed the outcome of patients with SBA diagnosed between 1990 and 2008. Methods: Individual charts of 150 patients with a histological diagnosis of SBA were retrospectively analyzed. Epidemiological data as well as information on chemotherapy administered were collected. DFS, PFS and OS were estimated by the Kaplan-Meyer method. Cox proportional hazards regression was performed to model the dependence on different parameters and model selection was done to determine their significance. Results: The baseline characteristics of patients, such as median age at diagnosis (65 years), tumor stage (I-II 33%, III-IV 58%, unknown 9%), and tumor location (duodenum 48%, jejunum 31%, ileum 21%) were consistent with data published in the literature. 55% of our patients had a positive family history of cancer; 29% developed a second tumor. CEA was elevated in 84% of stage IV patients, while it was normal in 85% of stage I-III patients. The DFS of 28 patients treated with adjuvant chemotherapy was identical to that of 47 patients without. However prognostic factors such as nodal status were not well balanced in the two groups. In the palliative setting patients treated with polychemotherapy (20 patients) had a statistically better OS than patients treated with monochemotherapy (12 patients) (p= 9.31e-06). Conclusions: Our study suggests a survival benefit for advanced-stage SBA patients treated with poly- versus monochemotherapy. However it should be taken in account that this is a retrospective analysis with several potential confounders. Nevertheless our study adds support to the body of evidence that chemotherapy may be beneficial for patients suffering from SBA, at least in the palliative setting.
Should all patients (pts) with advanced biliary cancers receive first-line treatment with cisplatin and gemcitabine (GC)?
Authors: Miranda Vanessa Costa , Dib-Faria Luiza , Braghiroli Maria Ignez Freitas Melro , Sabbaga Jorge , Saragiotto Daniel Fernandes , Castro Gilberto , Hoff Paulo M. , Riechelmann Rachel
Published: February 2017

244

Background: GC is considered the standard of care for pts with advanced biliary tract cancer (BTC), providing median survival of nearly one year. (Valle J et al. NEJM 2010) Nevertheless, many pts experience poor outcomes, leading to a growing interest to identify pts who might benefit from such treatment. Here we aimed to investigate clinical and laboratory factors associated with poor survival among BTC pts treated with GC. Methods: We retrospectively evaluated all consecutive pts with advanced/metastatic BTC who received first line GC at the Instituto do Cancer do Estado de Sao Paulo, Brazil, in a 2 year-period. Clinical and laboratory variables that could influence pts’ outcomes were gathered from medical charts. Cox regression proportional hazard model was used to investigate the following prognostic factors for death: pre-treatment biliary deobstruction, baseline Ca 19.9, any GC interruptions or dose reductions, baseline ECOG status, Charlson Comorbidity Index (CCI) and age. P values < 0.05 in multivariable analysis were considered significant. Results: From January/2009 to July/2011, 72 pts were identified. The median age was 60 years (range 30-80 years), 45 pts (62.5%) were female and 50 (69.4%) presented baseline ECOG 0-1. The median number of cycles of CG was 4 (range 1-9). Grade 3 /4 neutropenia and thrombocytopenia occurred in 16.6% and 12.5% of pts, respectively. Median survival of the whole cohort was 9.53 months (95% CI: 6.2 - 11.4). Median survival in pts with ECOG 0/1 was 13.5 months (95% CI: 9,5 – NR) and among pts with ECOG 2/3 3,5 months (95% CI: 1-7). In the Cox multivariable model, ECOG 2 /3 versus 0/1 (HR: 8.4, 95% CI: 3.4 to 20.7; p<0.001) and CCI score ≥ 2 (HR: 9.5 95% CI: 1.6 to 55.3; p= 0.012) significantly predicted for poor survival. There was a trend for improved survival among pts who had biliary drainage before starting GC (HR: 2.3 95% CI: 1.0 - 5.3; p= 0.051). Conclusions: In this retrospective cohort of unselected pts with advanced BTC treated with first line GC, poor performance status and multiple comorbid illnesses were associated with dismal prognosis. Treatment with GC should be carefully discussed before being offered to these pts.
Phase II consortium (P2C) study of gemcitabine and tanespimycin (17AAG) for metastatic pancreatic cancer.
Authors: McWilliams Robert R. , Foster Nathan R. , Wang-Gillam Andrea , Erlichman Charles , Kim George P.
Published: February 2017

245

Background: Gemcitabine (GEM) monotherapy for PDA has modest activity. 17-N-Allylamino-17-demthoxygeldanamycin (Tanespimycin/17AAG), is an HSP90 inhibitor, which results in degradation of a number of client proteins such as RAF and Akt. Arlander et al (J Biol Chem. 2003 278:52572-7) have demonstrated that 17AAG targeting of HSP90 leads to Chk1 degradation. Chk1 is upregulated with GEM treatment which affects cell survival (Karnitz et al. Mol Pharmacol. 2005 68:1636-44). In vitro, the combination demonstrated in vitro synergy. Thus the potential clinical activity in pancreatic cancer of the combination was explored. Methods: A phase II multicenter prospective study was performed using GEM 750 mg/m2 d1,8 and 17AAG 154 mg/m2 d2,9 on a 21 day cycle, as defined in a previous phase I trial. Patients with stage IV PDA, with adequate liver, kidney function and counts, ECOG 0-2 and no prior therapy for metastatic disease were eligible. The primary endpoint of 60% overall survival at 6 months was considered of clinical interest. Sixty-six patients were planned for accrual, and an interim analysis was planned after 25 evaluable patients. Informed, written consent was obtained from all pts. Results: Due to lack of drug availability and failure to achieve the planned endpoint, accrual was halted at 21 pts, enrolled from 5/08 to 9/10, of which 20 were evaluable (1 cancelled prior to treatment). Median age was 61.5 yrs., 55% were male, PS 0 (50%), 1 (45%), 2 (5%); 95% were non-Hispanic white, 1 was African American. Two had received adjuvant therapy for PDA. Tolerability was moderate, with 13 pts (65%) having > grade 3 adverse event (AE), with 15% gr 4 AEs and 0% gr 5. Nausea (20%), vomiting (20%), constipation (15%), dehydration (15%), and anorexia (10%), were the most common non-heme AEs. Lymphopenia (15%), leukopenia (10%) and neutropenia (10%) were common grade 3 hematologic AEs. No complete or partial responses were seen. 40% of patients were alive at 6 months, with a median OS of 5.4 months. Conclusions: HSP 90 inhibitor 17AAG in combination with GEM does not show activity for treatment of PDA. Further trials should not be pursued with this combination. Supported by N01-CM-62205. Clinical trial information: NCT00577889.
In vitro and in vivo evaluation of sunitinib eluting beads.
Authors: Bize Pierre E. , Jordan Olivier , Fuchs Katrin , Dormond Olivier , Duran Rafael , Doelker Eric , De Baere Thierry , Denys Alban
Published: February 2017

246

Background: Chemoembolization is used to treat liver malignancies. However recurrence occurs frequently, possibly because of neoangiogenesis triggered by ischemia caused by the embolic agent. In this context, the combination of an embolic agent with an anti-angiogenic drug seems appealing. This study characterizes the in vitro loading and release profile of sunitinib eluting beads of different sizes and their pharmacokinetic profile in a rabbit model. Methods: 70-150 μm and 100-300 μm drug eluting beads (DC Bead, Biocompatibles UK) were loaded by incubation in a sunitinib hydrochloride solution. Drug was quantified by spectrophotometry at 430 nm. Drug release was measured over one-week periods and normalized using an internal standard in 30% ethanol in NaCl 0.9%. New-Zealand white rabbits were used. Eight animals received 0.2 ml of 100-300 μm DC Bead loaded with 6 mg of sunitinib in the hepatic artery (group 1) and 4 animals received 6 mg of sunitinib p.o. (group 2). Half of the animals were sacrificed after 6 hours and half after24 hours. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was determined by tandem mass spectroscopy (LC MS/MS) at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS. Results: High drug loading was obtained for both microsphere bead sizes. Particle shrinking was observed with adsorption of sunitinib. Almost complete release of sunitinib was detected under physiological conditions, with very similar release for 70-150 μm and 100-300 μm (t50%=1.2 h) DC Bead. Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration can be obtained at the site of embolization with minimal systemic passage.
Efficacy and safety of FOLFIRINOX in patients with pancreatic metastatic cancer.
Authors: Metges Jean-Philippe , Ramée Jean François , Faroux Roger , Douillard Jean Yves , Porneuf Marc , Cumin Isabelle , Etienne Pierre-Luc , Gourlaouen Alain , Geslin Guillaume , Achour Nacredine , Delalande Anne Helene , Soulie Patrick , Le Bihan Gerard , Le Roux Catherine , Miglianico Laurent , Deguiral Philippe , Campion Loic , Riche Christian , Grude Francoise
Published: February 2017

248

Background: Efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) is one of the gold standard in metastatic pancreatic cancer as first-line therapy for patients with PS 0-1, good haematological and renal function and a subnormal bilirubin level. Pending approval, this treatment has been allowed in Brittany (B) and Pays de la Loire (PL) respecting these criteria. Methods: Observatory of Cancer B/PL is a network of 50 private/public cancer centers focused on good practice for cancer drugs use. Our aim is to evaluate the use of FOLFIRINOX between July 2010 and June 2013 in B/PL. Sex, age, successive chemotherapeutic regimens, toxicities, response rate, progression free survival (PFS) and overall survival (OS) have been studied. Results: Data of 79 patients, treated in 2010 (37%), in 2011 (54%) or early 2012 (9%) have been studied (44 men, median age 62 years [37-74]). 64 patients were metastatic when cancer was diagnosed. Principal site of metastases was liver (73%). 17 primary tumors were resected and 15 patients received an adjuvant chemotherapy (gemcitabine (n=14)).The median number of treatment cycles was 9 [1-24]. Objective response was observed in 29 patients (37%), disease stabilization in 18 patients (23%) and progression in 18 patients (23%). During treatment, 75% of patients had a dose adjustment and 30 % had one or more dose delays. 22 patients presented grade III/IV toxicity (almost neurotoxicity or haematologic). 42 patients had a second line of treatment (mainly gemcitabine) and 7 patients a third line. The median PFS and OS were respectively 174 days IC95% [125-216] and 309 days IC 95% [229-376]. Conclusions: Our preliminary results are relatively convenient with those of Conroy et al in 2011. A higher rate of response (37% vs 32%) has been found. Concerning PFS and OS, our results are clearly worst with 174 vs 195 days and 309 vs 338 days. Our results confirm the aggressiveness of this schedule with 75% of the patients requiring a dose adjustement. Analysis of all pancreatic metastatic patients treated by FOLFIRINOX in B/PL by the Observatory of Cancer allows to assess its good use in the real life.
Effect of body mass index in patients undergoing resection for gastric cancer: A single-center U.S. experience.
Authors: Wong Joyce , Rahman Shams , Saeed Nadia , Lin Hui-Yi , Almhanna Khaldoun , Shridhar Ravi , Hoffe Sarah , Meredith Kenneth
Published: February 2017

25

Background: With the rise of obesity in the U.S., the impact of body mass index (BMI) on surgical outcomes and survival in gastric cancer remains undetermined. Methods: An IRB-approved, prospectively-maintained institutional database of patients referred for surgical evaluation of gastric cancer was reviewed. Patients were stratified according to BMI: <18.5 (underweight), 18.5-25 (normal weight), 25.1-30 (overweight), and >30 (obese). Clinicopathologic factors and overall survival (OS) were analyzed using polytomous regression, Pearsons correlation and Kaplan Meier when appropriate. Results: From 1997-2012, 222 patients underwent exploration for gastric adenocarcinoma. Of these, 186 (84%) patients had BMI recorded: 9 (5%) with BMI<18.5, 72 (39%) 18.5-25, 62 (33%) 25.1-30, and 43 (23%) >30. 135 (73%) ultimately underwent resection. Operative factors including American Society of Anesthesiology (ASA) score and blood loss were not significantly associated with BMI. Increased BMI was associated with longer operative time, P=0.02. Pathologic factors including proximal tumor location, perineural invasion (PNI), lymphovascular invasion (LVI), positive surgical margins, and positive lymph nodes (LN+) were all associated with a worse OS. Although increased BMI was associated with a lower total lymph node count, P=0.004, the number of LN+ was not associated with BMI. Tumor location, PNI, LVI, margin status, and final pathologic stage were not significantly associated with BMI. Additionally, the use of neoadjuvant or adjuvant chemotherapy was not associated with BMI. Median OS for the group was 22 months. When stratified by BMI, median OS was improved with increased BMI: 21 months for <18.5, 13 months for 18.5-25, 28 months for 25-30, and 34 months for >30, P=0.02. Similarly, disease free survival (DFS) improved with increasing BMI: 2 months for <18.5, 7 months for 18.5-25, 15 months for 25.1-30, and 15 months for >30, P=0.02. Conclusions: Although BMI may impact the technical difficulty of resection for gastric cancer, increasing BMI is not associated with more aggressive disease. In this experience, increased BMI does not adversely impact OS or DFS.
Clinical efficacy of adjuvant surgery following systemic treatments in patients with initially unresectable pancreatic cancer: Results of a project study for pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Authors: Hirano Satoshi , Satoi Sohei , Yamaue Hiroki , Kato Kentaro , Takahashi Shinichiro , Hirono Seiko , Takeda Shin , Eguchi Hidetoshi , Sho Masayuki , Wada Keita , Shinchi Hiroyuki , Kwon A-Hon , Kinoshita Taira , Nakao Akimasa , Nagano Hiroaki , Nakajima Yoshiyuki , Sano Keiji , Miyazaki Masaru , Takada Tadahiro
Published: February 2017

255

Background: Medical oncologists or pancreatic surgeons have identified candidates for surgical resection in patients with initially unresectable pancreatic cancer who favorably responded to multimodal treatment. Additional surgical resection during multimodal treatment, is called “adjuvant surgery”. A multicenter survey was conducted to explore the clinical efficacy of adjuvant surgery for initially unresectable pancreatic cancer with a long-term favorable response to systemic treatments. Methods: Clinical data, including the primary endpoint of overall survival were retrospectively compared between 58 initially unresectable pancreatic cancer patients that underwent adjuvant surgery with a favorable response to non-surgical cancer treatments over 6 months after the initial treatment (adjuvant surgery group) and 101 patients who did not undergo adjuvant surgery (control group). Results: The median observation periods were 51 months (20-122) in the control group, and 54 months (26-125) in the adjuvant surgery group, respectively. The actuarial survival rate at 1, 3, and 5 years after initial treatment in adjuvant surgery group (95, 53, and 34%) was significantly better than that in control group (88, 18, and 10%, p<0.0001). The propensity score analysis to provide adjustment of significant differences in the clinical backgrounds between the two groups revealed that adjuvant surgery was a significant independent prognostic variable with an adjusted hazard ratio (95% confidential interval) of 0.569 (0.36-0.89). Subgroup analysis according to the time from initial treatment to surgical resection showed a significant favorable difference in the overall survival in patients who underwent adjuvant surgery over 240 days after the initial treatment. Conclusions: The adjuvant surgery can occupy an important position in the multimodal therapy for patients with initially unresectable pancreatic cancer. The overall survival rate from the initial treatment is extremely high, especially in patients who received systemic treatments for more than 240 days.
A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer.
Authors: Sasaki Takashi , Isayama Hiroyuki , Nakai Yousuke , Takahara Naminatsu , Akiyama Dai , Yagioka Hiroshi , Kogure Hirofumi , Matsubara Saburo , Ito Yukiko , Yamamoto Natsuyo , Sasahira Naoki , Hirano Kenji , Toda Nobuo , Tada Minoru , Koike Kazuhiko
Published: February 2017

258

Background: The data of second-line treatment for advanced biliary tract cancer is still limited. We have previously reported feasibility study of gemcitabine and cisplatin combination therapy for refractory biliary tract cancer (Sasaki T et al, Invest New Drugs 2011). In this feasibility study, only 20 pts were enrolled, and both second-line and third-line treatments were involved. Therefore, we conducted a retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment to clarify the treatment outcome of this combination therapy. Methods: Pts with advanced biliary tract cancer who were refractory to gemcitabine containing regimen were enrolled in this study. Gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2were administered intravenously on days 1 and 8 repeated every 3 weeks. Results: Fifty-nine pts were enrolled in this study. Patient characteristics were: median age 68 (range 25-84); male/female 32/27; performance status 0/1/2 (15/38/6). The primary tumor site was; 24 pts in gallbladders, 18 pts in intrahepatic bile ducts, 15 pts in extrahepatic bile ducts, and 2 pts in ampulla of Vater. The numbers of the pts with locally advanced, metastatic, and recurrent cases were 8, 44, and 7, respectively. Four pts received gemcitabine monotherapy and 55 pts received gemcitabine and S-1 combination therapy as first-line treatment. Response rate and disease control rate were 1.7% and 56.0%, respectively. The median time-to-progression and median overall survival were 3.9 months (95%CI, 2.6 – 5.0 months) and 6.4 months (95%CI, 4.9 – 8.0 months), respectively. Conclusions: Gemcitabine and cisplatin combination therapy showed a moderate efficacy for the treatment of advanced biliary tract cancer as second-line treatment.
Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Results from the french cohort of the HER-EAGLE study.
Authors: Monges Genevieve , Terris Benoit , Chenard Marie-Pierre , Penault-Llorca Frederique , Beauclair Sophie , Bibeau Frederic , Emile Jean-François , Volant Alain , Doucet Laurent
Published: February 2017

26

Background: HER2 is an important prognostic and also a predictive biomarker for trastuzumab response in gastric cancer. Therefore, HER2 status should be tested in all gastro-esophageal junction (GEJ) and gastric cancer (GC) patients. ToGA phase III study showed a benefit in overall survival of trastuzumab added to standard chemotherapy in patients with HER2-positive advanced GEJ/GC. The objective of the HER-EAGLE study was to assess the incidence of HER2 positivity in GEJ/GC cancer. Methods: HER-EAGLE was an international epidemiological, non-interventional study assessing HER2 status by IHC/ISH in tumor samples from any stage in patients with GEJ/GC. Samples were obtained by excision or core biopsy and routinely analyzed via validated Ventana or Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+ or IHC 2+ if FISH/SISH negative ratio < 2.0. Overall and subgroup estimates calculated with 95% CI. Data from the French cohort are presented. Results: The HER-EAGLE French cohort included 267 patients (68.6% males) from 7 centers (May 2007 to March 2012), with 150 biopsies (56.2%) and 117 excisions (43.8%). Tumor locations were 65.9% stomach and 34.1% GEJ, and adenocarcinoma types were according to Lauren classification: 170 intestinal (63.7%), 72 diffused (27%), 22 mixed (8.2%) and 3 not available (1.1%). HER2 status was: 36 cases IHC 3+ (13.5%), 51 IHC 2+ (19.1%) whereof 18 ISH positive (35.3%), 35 IHC 1+ (13.1%) and 145 IHC 0 (54.3%). Overall HER2 positivity (IHC 3+ or IHC 2+/ISH+) was 20.2%. Heterogeneity for HER2 staining was observed in 81 samples (30.3%). No statistical difference was found according to cancer stage. HER2 positivity was higher in GEJ (31.9%) than in GC (14.2%), p<0,001, and higher in intestinal (28.2%) compared to diffused adenocarcinomas (5.6%), p<0,001. Conclusions: HER-EAGLE French cohort results confirmed the feasibility of HER2 testing in GEJ/GC in routine practice. The incidence of HER2 overexpression was similar to the literature review, and it was higher in GEJ and intestinal adenocarcinomas type.
Outcome and patterns of care in advanced biliary tract carcinoma (ABC): Experience from two tertiary institutions in the United Kingdom.
Authors: Huggett Matthew T. , Passant Helen , Hurt Chris , Pereira Stephen P. , Bridgewater John A. , Mukherjee Somnath
Published: February 2017

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Background: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC), however outcome in an unselected patient population in the UK has not been described. We report the outcome of a series of patients with ABC from two large UK cancer networks. Methods: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a 9-year period. Patients with a diagnosis recorded under anatomical site (liver, gallbladder or biliary tree) or histological diagnosis (cholangiocarcinoma or adenocarcinoma, liver), were included. Any patients who had surgery with curative intent were excluded. Overall survival (OS) and factors influencing OS were assessed. For the analysis, chemotherapy regimens were considered as: (i) gemcitabine (G)-based vs. non-G-based, (ii) platinum (P)-based vs. non-P-based and (iii) fluoropyrimidine (F)-based vs. non-F-based. Results: 402 patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥ 70 years (p=0.047), advanced disease stage (p<0.001), gall bladder primary (p=0.033), poor performance status (p<0.001) and lack of chemotherapy (p<0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 versus 4.3 months; p<0.001). In patients receiving chemotherapy, on multivariate analysis males had higher mortality than females (HR=1.71; p=0.006) and stage 4 disease had a higher mortality (HR=2.62; p=0.002) than stage 1-2 disease. Patients who did not receive F-based regimens (HR=5.12; p=0.022) or G-based regimens (HR=5.01; p=0.021) had a higher mortality, whereas the effect of P-containing regimens was of borderline significance (HR=2.23; p=0.086). Sites, age, and multi-agent regimens were not significant. Conclusions: This is the first retrospective series from the UK and one of the largest population-based studies in ABC and confirms the benefit of palliative chemotherapy in an unselected group of patients. F-based regimens appear to be as effective as G-based treatments.
Efficacy and clinical outcomes of radiotherapy with or without chemotherapy in inoperable or post-operative high-risk cholangiocarcinoma.
Authors: Kalyani Nikhil Dhirendra , Engineer Reena , Chaudhari Suresh , Dharia Tejas , Shetty Nitin , Chopra Supriya , Shrivastava Shyam K
Published: February 2017

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Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after radiotherapy (endobilliary and/or external RT) with or without chemotherapy in patients with unresectable or post operative high risk extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours). Methods: From Aug 2005 to July 2012, 67 patients with non-metastatic EHBDC and hilar cholangiocarcinoma were treated with radiotherapy (endobilliary and / or EBRT) with or without chemotherapy at our institution. Sixty one patients had unresectable disease while remaining six patients were post operative patients. Twenty two patients received only endobilliary RT, 20 patients received only EBRT, while 25 patients received both. Concurrent Gemcitabine during EBRT was given in 10 patients. Histopathological diagnosis was available in 50 patients (75%). Median dose for EBRT and endobilliary RT was 45 Gy (range: 25 Gy to 57 Gy) and 14 Gy (range: 12 Gy to 20 Gy) respectively. Results: Median age was 54 years (range 23-76 years) and there were 37 men and 30 women. Median follow up for whole group was 6 months (range 1-28 months). Seven patients had complete response, 22 patients had partial response, 4 patients had stable disease, while 6 patients had progressive disease after EBRT. Twenty five patients were alive at last follow up. The median overall survival was 7 months and one year survival was 30% for whole group. Patients receiving EBRT (with or without endobilliary) had better survival as compared to patients receiving only endobilliary RT (median survival 13 months Vs 5 months, p=0.001). The main sites of distant disease progression were liver and peritoneum. Eighteen patients had developed cholangitis while 3 patients developed hematemesis due to duodenitis. Conclusions: Radiation in unresectable cholangiocarcinoma is feasible with acceptable clinical outcome and toxicity. Patients receiving EBRT has better outcome as compared to those receiving only endobilliary RT.
Molecular profiles of gastric cancer: The UCSD experience.
Authors: McGee Devon Marcus , Shen John P. , Fanta Paul Timothy , Lowy Andrew M.
Published: February 2017

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Background: Gastric cancer is the 2nd leading cause of cancer mortality globally. A small number of studies reported that low TS and ERCC1 mRNA levels are associated with improved survival, and may be important as prognostic factors. Methods: Intratumoral gene expression levels were assessed using laser-captured micro-dissection and quantitative Real-Time PCR on formalin fixed paraffin embedded tumor samples from 22 gastric adenocarcinomas. A retrospective chart review was performed to measure clinical parameters. Primary objectives were to determine the range of expression of TS, ERCC1, and HER2, and to investigate if these biomarkers are predictive of survival. Results: TS, ERCC1, and HER2 median expression levels using RT-PCR were 3.56, 1.54, and 0.085, respectively. Median OS was 62 months. Subjects with low TS trended towards improved survival (92 months vs. 34 months, p: 0.17), as did subjects with low ERCC1 (92 months vs. 55 months, p: 0.44). There was no association between HER2 expression and OS. All subjects had HER2 levels below 0.55. With regard to treatment, 90.9% of patients received platinum-based chemotherapy and 4.5% received HER2-guided therapy. Conclusions: Our results are consistent with prior reports that associate low TS and low ERCC1 with improved OS, and may imply prognostic significance. Although these trends did not reach statistical significance, they are consistent with prior studies. Further molecular studies are needed to better assess the utility of these markers as prognostic indicators. There was no clear trend between HER2 levels and OS, most likely because all subjects had low HER2 levels. However, as accurate determination of HER2 expression is becoming increasingly important in the management of gastric cancer patients, further research into the degree of concordance between RT-PCR assessment and FISH assessment of HER2 gene amplication is warranted. Overall, more molecular studies are needed to better stratify this disease into subtypes, and identify new drug targets for chemo-resistant subtypes.
Small bowel carcinoid: Location isn’t everything.
Authors: Hari Danielle M. , Reich Heidi M Hari , Leung Anna Mary , Lee Ji Hey Hey , Sim Myung-Shin , Wolin Edward M. , Amersi Farin F.
Published: February 2017

292

Background: Contemporary data has revealed that small bowel carcinoid (SBC) accounts for the majority of gastrointestinal carcinoids. However, data remains limited regarding prognostic factors that impact survival for SBC patients. Using a population-based analysis, we investigate the significance of the primary site of disease for SBC. Methods: The Surveillance, Epidemiology, and End Results database was queried for histologically confirmed SBC between the years 1988 and 2009. Patients were excluded if adequate demographic and staging information was unknown. Overall and disease survival curves (OS and DSS respectively) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analysis was used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, TNM stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. Results: Of the 3,834 patients analyzed, the mean age was 62.13 years and 51.2% were male. Median follow up was 50 months. The 10-year OS (63%) and DSS (91%) for duodenal primaries was statistically significant when compared to jejunal (53%, 74%), ileal (50%, 68%) and overlapping primaries (50%, 78%), (p = 0.0290 and < 0.0001, respectively). However, more the 90% of duodenal primaries had stage I and II disease only. On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (p = 0.948 for OS and = 0.625 DSS) while TNM stage, age, tumor size and number of LNs examined portend improved OS and DSS. Conclusions: This population-based study of SBC over the past 30 years refutes the concept that the location of the SBC influences survival. A key element to consider is that more than 90% of duodenal primaries present at early stages. Further screening and diagnostic methods to detect other SBC primary sites could significantly impact survival.
Understanding variations in referral patterns and treatment choices for patients with hepatocellular carcinoma.
Authors: Hyder Omar , Cosgrove David , Nathan Hari , Hirose Kenzo , Wolfgang Christopher Lee , Bridge John , Geschwind Jean-Francois , Bhagat Nikhil , Gurakar Ahmet , Herman Joseph M. , Kamel Ihab R. , Pawlik Timothy M.
Published: February 2017

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Background: Patterns of care of physician specialists may differ for patients with hepatocellular carcinoma(HCC). The extent and reasons underlying possible variations are poorly understood. One source of variation may be disparate referral rates to specialists leading to differences in cancer-directed treatments. Methods: We queried the Surveillance, Epidemiology, and End Results(SEER) linked Medicare database for patients with HCC diagnosed between 1998-2007 who consulted one or more physicians following diagnosis. Visit and procedure records were abstracted from Medicare billing records and factors associated with visiting a specialist and subsequent treatment were examined. Results: 6752 patients with HCC were identified;median age was 73 yrs and the majority was male(66%), White(60%) and from a West geographical region(56%). 1379(20%) patients had early-stage disease. In the six months after diagnosis, referral to a specialist varied considerably (hepatology/gastroenterology-60%; medical oncology-62%; surgery-56%; interventional radiology-33%; radiation oncology-9%). 22% patients saw one specialist, while 39% saw ≥3 specialists. Time between diagnosis and visitation with a specialist varied by sub-specialty (surgery-37 days vs. interventional radiology-55 days;P=0.04). Factors associated with referral to a specialist included younger age(OR=2.13), geographic location(Northeast OR=2.09), and presence of early-stage disease(OR=2.21)(all P<0.05). Among patients with early-stage disease, 77% saw a surgeon, while 50% had a medical oncology consultation. Receipt of therapy among patients with early-stage disease varied (no therapy-30%; surgery-39%; interventional radiology-9%; other-22%). Factors associated with receipt of therapy included younger age(OR=2.82), as well as time to consultation with cancer specialist(OR=1.05)(both P<0.05). Conclusions: Following HCC diagnosis, referral to a specialist varied considerably. Both clinical and non-clinical factors were associated with consultation. Variations in referral to a specialist and subsequent therapy need to be better understood to ensure all HCC patients receive appropriate care.
Predictive factors for outcome after biliary stenting in malignant obstructive jaundice.
Authors: Punia Pankaj , Anthoney David Alan , Khanom Koudeza , Swinson Daniel
Published: February 2017

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Background: Stenting of the biliary treeis a common palliative procedure to relieve obstructive jaundice in advanced malignancy. Although effective in relief of biliary obstruction and subsequent palliation of symptoms, little information is available on predictive factors for survival post-procedure to better guide selection of patients. This retrospective study sought to assess factors influencing post-procedure survival in cancer patients after biliary stenting. Methods: Case notes of all patients from a regional academic cancer centre, who underwent biliary stenting for obstructive jaundice related to malignancy during 2008 and 2009, were reviewed. We collected epidemiological, biochemical, treatment (post-stenting) and survival data on all patients. Kaplan-Meyer analysis was used to assess median survival of patients from the day of first biliary stenting (adjusted for cancer types) and Cox proportional hazard model was used for univariate and multivariate analysis. Results: 194 patients were included in the final analysis. Most cases were related to pancreatic cancer or cholangiocarcinoma (89 and 46 cases each). Median survival (MS) for all the patients was 143 days. Median survival was similar, whether obstruction was secondary to the primary tumor (141cases) or metastatic disease (53 cases). In multivariate analysis serum albumin < 3.4 g/dL ( HR 1.770; 95% confidence interval 1.312 – 2.389, P < 0.001) and age > 75 years (HR 1.490; 95% confidence interval 1.086 – 2.043, p = 0.013) at the time of procedure were two independent prognostic factors predicting for a worse survival post-stenting. The 30 day mortality post-procedure in the 194 patients was 12%. Conclusions: This study suggests that stenting of the biliary tree in cases of malignant obstruction allows durable palliation of symptoms even in cases where further active chemotherapy treatment is not possible. However, the worse outcome observed in those > 75 yrs old or with low albumin at the time of procedure, identify groups with less certain benefit from this invasive procedure and requires confirming in future studies.