bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of pathological response and tumor regression following neoadjuvant therapy in advanced gastric cancer patients.
Authors: Ribeiro Ulysses , Ramos Marcus Fernando Kodama Pertille , Pereira Marina Alessandra , Dias André Roncon , Yagi Osmar Kenji , Faraj Sheila , de Mello Evandro Sobroza , Charruf Amir Zeide , Pereira Guilherme Luiz Stelko , Zilberstein Bruno , Hoff Paulo Marcelo , Cecconello Ivan
Published: March 2017

206

Background: Neoadjuvant chemotherapy (NACT) has became the standard approach for patients with advanced gastric cancer. Clinicopathological characteristics can be utilized to evaluate the effect of NACT, and may be a useful tool to identify responsive patients. Methods: We retrospectively reviewed all patients with GC treated with NACT and R0 resection between 2009 and 2015 from a prospective collected database. Histopathological response to the treatment was graded from 0% to 100% and the clinicopathological characteristics assessed to identify predictors of tumor response. A threshold of 50% histopathological response was used for the analysis. Results: NACT was performed in 45 patients. Cisplatin-irinotecan therapy was used in 64.4% of patients and 11 (24.4%) tumors were located in the proximal stomach. Ten (22.2%) patients demonstrated a tumor regression of at least 50% and one patient had complete response. The mean number of lymph node retrieved was 38.1 and 66.7% patients had lymph node metastasis (LNM). Factors associated with > 50% of response by univariate analyses included lower neutrophil-lymphocyte ratio (NLR) ( p = 0.035), diffuse/mixed Lauren type ( p = 0.007), lower depth of tumor invasion ( p = 0.043) and non cisplatin-irinotecan therapy (p = 0.01). A slight tendency of poorly differentiated tumors respond better to NACT than differentiated type was observed ( p = 0.05). There was no significant difference regarding the presence of mucin, calcification and/or necrosis and the tumor response. Multivariate analysis identified NLR and diffuse/mixed tumors as independent predictors of pathologic response. Median follow-up for all patients was 26.5 months and recurrence-free survival (RFS) rate was 74.3% and 60% for patients with > 50% and < 50% of response, respectively ( p= 0.08). RFS was significantly different in patients without LNM compared to patients who have LNM (100% vs. 55.2%, p = 0.01), and in patients with fibroinflammatory/inflammatory stroma infiltration compared to patients with only fibrotic stroma (80% vs. 53.3%, p = 0.015). Conclusions: Diffuse/mixed histopathological type and lower NLR are independently predictors of tumor response after NACT.
Clinical significance of p53 protein, beta-catenin, and HER2 in patients with Epstein-Barr virus-associated gastric cancer.
Authors: Baek Dong Won , Lee In Hee , Lee Soo Jung , Kang Byung Woog , Chae Yee Soo , Kim Jong Gwang
Published: March 2017

22

Background: Epstein-Barr virus (EBV) infection can cause cancer tumorigenesis and malignant transformation of host cells through the activation of oncogenic pathways. Therefore, we assessed the expression of p53 protein, beta-catenin, and HER2 and their prognostic implication in patients with EBV-associated gastric cancer (EBVaGC). Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The results of immunohistochemistry were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result; strong positive cytoplasmic-nuclear expression patterns for β-catenin ( ≥ 10%) were considered altered expression; moderate or strong complete or basolateral membrane staining in 10% of tumor cells for HER2 was reported as a positive results. Results: The median age of the patients was 62 years (32-80) and 93 (79.5%) were male. The pathologic stages were as follows : stage I (n = 74), stage II (n = 25), and stage III (n = 18). Among the 117 patients, immunohistochemical staining for p53 was performed in 105 patients and 25 patients (23.8%) were positive. Beta-catenin was positive in 10 patients (17.5%) and HER2 was positive in 8 patients (6.8%), respectively. The positive expression of p53 was significantly associated with a high T stage (p = 0.006). Conversely, more patients without lymph node metastasis were p53 positive (p = 0.013). In the univariate analysis, the patients with p53 positive tumors showed a significantly improved disease-free survival (DFS) compared to the patient with negative tumors (p = 0.022), although the p53 status was marginally associated with overall survival (OS)(p = 0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Meanwhile, beta-catenin and HER2 was not found to be associated with DFS and OS in the survival analysis. Conclusions: The current study found a significant correlation between p53 expression and tumor progression in patients with EBVaGC.
A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).
Authors: Nugent Francis W. , Qamar Amir , Stuart Keith E. , Galuski Kari , Flacke Sebastian , Molgaard Chris , Gordon Frederick , Iqbal Shams , Hunter Klaudia Urbaniak , Hartnett Erin , Gunturu Krishna
Published: March 2017

223

Background: For HCC pts undergoing LT, local regional treatment as a "bridge" is standard to decrease tumor progression. The most common treatment is TACE, but the best bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts planned for accrual. From 9/2014-9/2016, 29 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE pts received 2 treatments one month apart utilizing DEBDOX beads (n = 15). TACE pts were hospitalized after each TACE. Pts receiving SBRT (n = 12) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was time to retreatment of treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. Results: A. Demographics/Toxicity. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears equally effective to TACE as a bridge to liver transplantation, may engender less toxicity, and eliminates hospitalizations. Clinical trial information: NCT02182687. [Table: see text][Table: see text]
Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.
Authors: Edeline Julien , Bonnetain Franck , Phelip Jean Marc , Watelet Jérôme , Hammel Pascal , Joly Jean-Paul , Ben Abdelghani Meher , Rosmorduc Olivier , Bouhier-Leporrier Karine , Jouve Jean-Louis , Faroux Roger , Guerin Meyer Véronique , Assenat Eric , Seitz Jean Francois , Malka David , Louvet Christophe , Bertaut Aurelie , Juzyna Beata , Stanbury Trevor , Boucher Eveline
Published: March 2017

225

Background: No standard post-surgery adjuvant treatment is currently recommended in localized biliary tract cancer (BTC). Gemcitabine combined with platinum is the standard chemotherapy for advanced BTC. The aim of this phase III randomized trial was to assess whether GEMOX would increase relapse-free survival (RFS) while maintaining health-related quality of life (HrQoL). Methods: We performed a multicenter randomized phase III trial. Patients were randomized, within 3 months of R0 or R1 resection of a localized BTC (intra-hepatic, perihilar, extra-hepatic cholangiocarcinoma or gallbladder cancer), to receive either GEMOX 85 for 12 cycles (Experimental Arm A) or surveillance (Standard Arm B). Co-primary objectives were RFS and HrQoL. 190 patients and 126 RFS events were required to show an increase of median RFS from 18 to 30 months. Results: Between July 2009 and February 2014, 196 patients were included in 33 French centers. Baseline characteristics were balanced, with similar primary sites, R0 resection rates were 86.2% (Arm A) vs 87.9% (Arm B), lymph node invasion present in 37.2% vs 36.4%. In Arm A, a median of 12 cycles was delivered (mean: 9.3, range: 0-12). Maximal grade of adverse events were grade 3 in 57.5% vs 22.2%, and grade 4 in 17.0% vs 9.1%. During treatment one patient died in each arm. The main grade ≥ 3 adverse events in the year following inclusion were peripheral neuropathy (50.0% vs 1.1%), and neutropenia (22.3% vs 0%). Median follow-up was 44.3 months, with 54 and 64 RFS events in arms A vs B. There was no significant difference in RFS between the arms (log-rank p = 0.31), with a hazard ratio of 0.83 [95% CI: 0.58-1.19], p = 0.31 (futility boundaries were crossed). Median RFS was 30.4 [95% CI: 15.4-45.8] vs 22.0 months [95%CI: 13.6-38.3] in arms A & B respectively, and 4-years RFS was 39.3% [95%CI: 28.4%-50.0%] vs 33.2% [95%CI: 23.1-43.7%]. Global Health HrQoL scores were not different at 12 months (70.8 vs 83.3, p = 0.18) and at 24 months (75.0 vs 83.3, p = 0.50). Conclusions: Adjuvant chemotherapy in BTC with GEMOX was feasible and associated with expected toxicities and no deterioration of HrQoL. There was no significant difference in RFS between GEMOX and surveillance. Clinical trial information: NCT01313377.
Nivolumab dose escalation and expansion in patients with advanced hepatocellular carcinoma (HCC): The CheckMate 040 study.
Authors: Melero Ignacio , Sangro Bruno , Yau Thomas Cheung , Hsu Chiun , Kudo Masatoshi , Crocenzi Todd S. , Kim Tae-You , Choo SuPin , Trojan Jorg , Meyer Tim , Welling Theodore Hobart , Yeo Winnie , Chopra Akhil , Anderson Jeffrey , Dela Cruz Christine Marie , Lang Lixin , Neely Jaclyn , Tang Hao , El-Khoueiry Anthony
Published: March 2017

226

Background: HCC diagnosed at advanced stages has a poor prognosis. Patients who progress on sorafenib have few options. Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), has demonstrated clinical and survival benefit in a number of tumor types. Here we report updated interim analyses of safety, efficacy, and exploratory biomarkers in patients with advanced HCC treated with nivolumab in the CheckMate 040 study (NCT01658878). Methods: Patients enrolled had advanced HCC with or without hepatitis C or B virus (HCV or HBV) infection. Prior sorafenib was allowed. Phase 1 dose-escalation evaluated nivolumab (0.1–10 mg/kg) Q2W. Phase 2 dose-expansion was initiated in 4 cohorts: sorafenib naïve/intolerant, sorafenib progressors, HCV infected, and HBV infected. All cohorts received nivolumab 3 mg/kg Q2W. The primary endpoint in the dose-escalation phase was safety/tolerability, and the primary endpoint in the dose-expansion phase was objective response rate (ORR) by RECIST v1.1 (central review). Secondary endpoints included duration of response (DOR), disease control rate (DCR), and overall survival (OS). Biomarkers within pre-treatment tumors were assessed. Results: Across dose escalation and expansion phases, 262 patients have been treated. Grade 3/4 treatment-related adverse events occurred in 20%. No maximum tolerated dose was reached during dose escalation (n = 48). The ORR (investigator-assessed) was 20% (95% CI 15–26) in 214 patients treated in the dose expansion phase with a median DoR of 9.9 months; DCR was 64% (95% CI 58–71). Responses were observed across etiologies and regardless of tumor PD-L1 expression. ORRs of 23% (95% CI 13–36) and 21% (95% CI 11–34) were observed in the uninfected sorafenib-naive and -treated patients, respectively. The 9-month overall survival rate in the expansion phase was 74% (95% CI 67–79). Association between immune-cell biomarkers and clinical outcomes will be presented. Conclusions: In this heavily pretreated population, responses to nivolumab were durable with encouraging overall survival. Safety was manageable and consistent with that observed in other solid tumors with no new safety signals. Clinical trial information: NCT01658878.
Survival by pattern of tumor progression during prior sorafenib (SOR) treatment in patients with hepatocellular carcinoma (HCC) in the phase III RESORCE trial comparing second-line treatment with regorafenib (REG) or placebo.
Authors: Bruix Jordi , Merle Philippe , Granito Alessandro , Huang Yi-Hsiang , Bodoky Gyorgy , Pracht Marc , Yokosuka Osamu , Gerolami René , Masi Gianluca , Ross Paul J. , Qin Shukui , Song Tianqiang , Bronowicki Jean-Pierre , Ollivier-Hourmand Isabelle , Kudo Masatoshi , Le Berre Marie-Aude , Meinhardt Gerold , Han Guohong ,   On Behalf of RESORCE Investigators
Published: March 2017

229

Background: HCC progression may be due to tumor growth or new intrahepatic or extrahepatic lesions. RECIST does not discriminate between progression patterns even though the prognosis may differ (Reig, Hepatology 2013). REG improves overall survival (OS) in patients with HCC who progress during SOR treatment (HR 0.63; 95% CI 0.50, 0.79; P < 0.001). This exploratory analysis aimed to validate the pattern of progression concept in a global cohort treated with prior SOR and to assess the impact of REG on survival by prior progression. Methods: Adults with HCC who tolerated SOR and had radiologic progression during SOR, Child–Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to REG 160 mg/day or placebo during weeks 1–3 of each 4-week cycle. Progression during SOR was due to tumor growth or new lesions. Post-progression survival (PPS) was the time from progression on SOR until death. Results: Baseline characteristics of the 573 randomized patients (REG = 379; placebo = 194) were balanced; median age was 63 years, 88% were male, 87% were BCLC stage C, 29% had macrovascular invasion, and 72% had extrahepatic disease. Hazard ratios favored REG irrespective of pattern of progression during prior SOR, but differed according to progression pattern (Table). Conclusions: The development of new extrahepatic lesions is associated with worse survival irrespective of treatment. REG provided an OS benefit, regardless of progression pattern. Progression pattern may be a key prognostic parameter and should be considered in future trial design and analysis. Clinical trial information: NCT01774344. [Table: see text]
Multi-agent and single-agent chemotherapy in stage IV pancreatic cancer: An NCDB analysis.
Authors: Ahmed Aabra , Walters Ryan W , Malouff Timothy Dean , Chintalacheruvu Lakshmi Manogna , Silberstein Peter T.
Published: March 2017

231

Background: Cartright et al (2014) examined 2,422 patients in the iKnowMed database and found that patients with advanced pancreatic cancer lived longer with multi-agent chemotherapy compared to single-agent chemotherapy (11.2 months vs 7.2 months). Our goal was to compare survival of patients with stage IV pancreatic cancer receiving multi-agent, single-agent, or no chemotherapy using a significantly larger sample of patients identified in the National Cancer Database (NCDB). Methods: We identified 86,048 patients with stage IV pancreatic cancer. Between-chemotherapy survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p < .05 indicated statistical significance. Results: Patients receivingmulti-agent chemotherapy were more likely to have private insurance than single-agent and no chemotherapy patients (49.9% vs. 33.0% vs. 22.9%, respectively), live in an area with a median income of $63,000+ (36.9% vs. 30.2% vs. 28.4%, respectively), receive treatment at an academic center (43.3% vs. 34.5% vs. 32.8%, respectively), and have no comorbidities (72.9% vs. 66.9% vs. 61.1%, respectively). Statistically significant survival differences were indicated between all chemotherapy groups (all adjusted p < 0.05), such that patients receiving multi-agent chemotherapy had the longest survival followed by patients receiving single-agent chemotherapy and patients receiving no chemotherapy (median survival = 7.4, 4.9, and 1.4 months, respectively). A larger proportion of patients receiving multi-agent chemotherapy were alive at 6, 12, and 24 months relative to patients receiving single-agent or no chemotherapy. Conclusions: Our study is the largest to show the benefit of multi-agent chemotherapy over single-agent chemotherapy for stage IV pancreatic cancer, as well as analyze the demographics of patients receiving differing chemotherapy treatments. [Table: see text]
Short and long-term survival in metastatic pancreatic adenocarcinoma, 1993-2013.
Authors: Golan Talia , Sela Tal , Margalit Ofer , Amit Uri , Halpern Naama , Aderka Dan , Shmueli Einat Shacham , Urban Damian , Lawrence Yaacov Richard
Published: March 2017

232

Background: Over the previous two decades several new agents have been approved for the treatment of metastatic pancreatic cancer (mPDAC). Their efficacy was demonstrated amongst highly selected patients that participate in randomized phase III trials, hence it is not clear to what extent these advances are reflected within the broader mPDAC population. We performed a population-based survival analysis of newly diagnosed patients who presented with mPDAC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mPDAC between 1993-2013. Demographic variables collected included age, gender, race, and marital status. Tumor characteristics collected included location and grade. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, unknown histology and pancreatic neuroendocrine tumors. Results: The study population consisted of 57,263 patients diagnosed with mPDAC from 1993-2013, 52% male, median age 69 years (range 15-104). Prognosis correlated with age, gender, race, marital status, tumor location, grade and year of diagnosis. Median overall survival (OS) stayed stable at 2 months between 1993 and 2013. Improvements in OS were seen for all patients, but especially for younger patients ( < 50 years of age) and more recent year of diagnosis group (2009-2013). The percentage of patients who died within two months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%, p < 0.0001). The subgroup of patients achieving longer-term survival has increased, with 12-month survival improving from 4.9 % to 12.7% (p < 0.0001) between 1993 and 2013. Conclusions: There has been a continuous but modest improvement in OS of patients diagnosed with mPDAC between 1993 and 2013. The percentage of patients living beyond one year has significantly increased over time; however the percentage of patients dying within 2 months has only slightly decreased.
Larger size extracellular vesicle as early biomarker in patients with metastatic pancreatic cancer.
Authors: Kim Dong Uk , San Lucas Francis A , Cagley Matthew , Stephens Bret , Mulu Feven C , Castillo Jonathan , Bernard Vincent , Varadhachary Gauri R. , Katz Matthew H. G. , Alvarez Hector A , Maitra Anirban
Published: March 2017

234

Background: Current research suggests that tumor-derived extracellular vesicles (EVs) play an important role in tumor progression especially with regard to metastasis. Atypically large EVs have been reported to have the ability to transport bioactive molecules through the blood stream. Therefore, EV physical properties such as diameters and concentrations may have a biological impact on tumor progression. However, it has not been described which characteristics are clinically relevant in the longitudinal assessment of tumor progression and chemo-response. Methods: Plasma from 19 metastatic PDAC patients was collected at treatment-naïve baseline and in more than 2 consecutive assessments during chemotherapy between May 2015 and July 2016. EVs from plasma were isolated using a sequential centrifugation protocol, confirmed as described previously and analyzed using the Particle Metrix (Zetaview, Diessen, Germany) and proprietary software. The clinical variables along with concentration and size distribution of EVs were analyzed to identify prognostic factors associated with chemo-response. Results: Mean EV size and concentration were 122.85 nm and 4.13x109/mL plasma at treatment naïve baseline, 123.62 nm and 4.39x109/mL plasma at first response assessment during chemotherapy. Median overall and progression-free survivals were 256 and 165 days, respectively. The change of CA 19-9 (hazard ratio 17.477, p = 0.001, 95% CI 0.995-1.045) and proportion of EVs larger than 150nm (hazard ratio 11.022, p = 0.017, 95% CI 3.183-95.964) was a significant independent predictor of progression-free survival at first response assessment during chemotherapy. In addition, we observed a dramatic increase in the proportion of larger EVs earlier than the increases in CA 19-9. Conclusions: Our data suggests that increases in the amounts of larger EVs are independent predictors of tumor progression and chemo-response in metastatic pancreatic cancer patients. Furthermore, the increases in the amounts of larger EVs may potentially be more clinically useful than CA19-9 in the earlier stages of progression. Concentrations of larger-sized EVs could be a valuable component of more sophisticated diagnostics in liquid biopsies.
Effect of perioperative transfusion on recurrence and survival after resection of distal cholangiocarcinoma: A 10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium.
Authors: Lopez-Aguiar Alexandra G , Ethun Cecilia , Pawlik Timothy M. , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C , Krasnick Bradley , Weber Sharon M. , Salem Ahmed , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar
Published: March 2017

236

Background: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in several malignancies. Its effect on recurrence and survival in distal cholangiocarcinoma (DCC) is unknown. Methods: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000-2015 were included. 30-day mortalities were excluded. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Results: Of 314 pts with DCC, 206 (66%) underwent curative-intent pancreaticoduodenectomy. Median age was 67yrs, and 53 pts (28%) received perioperative blood transfusions, with a median of 2 units.There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups.Compared to no-transfusion, patients who received a transfusion were more likely to have (+)margins (28vs14%; p < 0.03) and major complications (46vs16%; p < 0.001). Receipt of neoadjuvant or adjuvant therapy was similar between groups. Transfusion was associated with lower median RFS (19vs32mos; p = 0.006) and OS (15vs29mos; p = 0.003), which persisted on multivariable (MV) analysis for both RFS (HR 1.8; 95%CI 1.1-3.1; p = 0.03)and OS (HR 1.9; 95%CI 1.1-3.2; p = 0.03), after controlling for portal vein resection, EBL, margin status, grade, LVI, LN status, and major complications. Similarly, transfusion of ≥ 2 pRBC units was associated with lower RFS (17vs32mos; p < 0.001) and OS (14vs29mos; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95%CI 1.4-4.6; p = 0.002) and OS (HR 3.9; 95%CI 2.1-7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was similar to those not transfused. Conclusions: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit is not associated with the same adverse effects as ≥ 2units. This supports the judicious use of perioperative transfusion; protocols should be developed and followed.
Comparison of the pathological features among HBV, HCV, and nonviral etiology-related hepatocellular carcinoma using explanted whole liver examinations.
Authors: Akashi Hayato , Hidaka Masaaki
Published: March 2017

245

Background: The aim of this study is to compare the pathological features among HBV, HCV and non-viral etiology related hepatocellular carcinoma (HCC) in the explanted cirrhotic liver using whole liver examinations. Methods: Ninety patients (HBV 23, HCV 53, HBV+HCV 3, nonBnonC 16) out of 246 recipients of liver transplantation were analyzed. All specimens were sectioned serially at 5-7 mm intervals and then were examined by an experienced pathologist. The pathological characteristics of HCC among each group were retrospectively analyzed using whole liver thin sliced histological examinations. Results: The median number and maximum size of HCC were one nodule (range 0-3 nodules), 22 mm (range 7-50 mm) by pre-operative imaging, and two nodules (range 0-37 nodules), 20 mm (range 4-50 mm) based on histological examinations. Twenty-six patients (27.4%) had more than 3 nodules measuring less than 1 cm diameter based on histological examinations. Fifteen patients (15.8%) had HCC with micro vascular invasion. Twenty-seven patients (28.4%) demonstrated findings beyond the Milan Criteria based on pathological examinations. NonBnonC related HCC tended to be within the Milan Criteria based on pathological examinations in contrast to viral related HCC (nonBnonC 12.5%, HBV 34.8% and HCV 39.6%). There were significantly more undetectable HCCs in HCV related HCC than in detectable HCCs by imaging. Conclusions: The undetectable HCCs in HCV tended to be found in the explanted liver. HCCs exceeding the rate of the Milan Criteria were less frequently found in non-viral related HCC than in viral related HCC.
Heterogeneous growth rates of pancreatic adenocarcinoma by retrospective analysis of CT imaging data.
Authors: Mortenson Tanner , Bigeh Allison , Chen Yighua , Malek-Ahmadi Michael , Chen Kewei , Kundranda Maddapa , Chang John
Published: March 2017

248

Background: Pancreatic ductal adenocarcinoma (PDAC) remains the fourth leading cause of cancer death in the United States. Despite its high mortality, there is no effective screening method or frequency. The purpose of this study is to retrospectively evaluate prediagnostic CT images in order to identify growth rate and determine a potential surveillance frequency for at risk patients. Methods: 188 PDAC patients were seen at Banner MD Anderson Cancer Center (BMDACC) from 1/1/2012 to 12/31/2015. 24 patients met the final inclusion and exclusion criteria. Tumor area on CT imaging was then evaluated for rate of change prior to diagnosis. Both absolute and relative areas were plotted against time prior to diagnosis at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months. Results: With two exceptions, no evidence of malignancy was identifiable at two or more years prior to diagnosis. Growth rates per year varied significantly. Absolute area change ranged from 1.7 cm2/yr to 139.22 cm2/yr; relative area change ranged from 1.17 to 7.15. Assuming a spherical mass, these relative changes correspond to relative volume change (ratio) per year of 1.27 and 19.13; the equivalent linear tumor doubling times are 3.7 years and 20 days respectively. Student’s T-test yielded no significant difference for relative growth, absolute growth, PFS, or OS between male and female patients. Conclusions: The heterogeneity in growth rate has significant implications for potential screening of PDAC. Screening interval greater than 1 year is feasible with other slow growing tumors. However, annual screening is not feasible for rapidly growing PDAC. Based on our findings, screening may need to be as frequent as 3-month intervals which would incur significant economic cost. Further correlation of prediagnostic growth rate with molecular changes may be necessary to discover the driver of this heterogeneous growth pattern.
Can we expect long-term survival in patients with extrahepatic metastasis of hepatocellular carcinoma?
Authors: Kim Kangpyo , Seong Jinsil
Published: March 2017

251

Background: Hepatocellular carcinoma presenting metastases has been considered detrimental situation. However, it is not infrequent observing long term survivors following active therapeutic intervention in selected patients. In this study, we investigated whether long term survival could be real as well as its common clinical features. Methods: From november 2005 to december 2014, among 1020 HCC patients with extrahepatic metastasis, 75 patients survived over 2 years. The patient and tumor characteristics were examined involving the site, number of metastatic lesions, liver function, and other factors. Treatment methods for liver and metastatic lesions were also reviewed with subgroup survival analysis according to the treatment strategies. Results: We observed survival over 2 years in 7.3 % with median survival of 41 months. The most common sites of extrahepatic metastasis were lung, bone, adrenal gland and lymph nodes in order of frequency. Of 75 survivors, 72 (96%) had single organ metastasis, and 46 (64%) had four or less countable metastatic lesions. Child-Pugh score was within 5 to 7 points for 71 patients when extrahepatic metastasis first occurred. More than two-thirds of patients (52 patients, 69.3%) received local treatments such as surgery or radiotherapy showing significantly higher survival than systemic treatment only (23 patients, 30.7 %) group; 3 year survival 65.7 % versus 21.7 % for the group with and without local treatment respectively (p = 0.001). For patients with a viable tumor in the liver, the application of local treatments such as transarterial treatment or radiotherapy showed a significant survival benefit (3-year survival 46.6 % versus 31.3%, p = 0.045). Conclusions: The long-term survivors presented limited number of extrahepatic metastasis (oligometastasis) and received local treatment for their metastatic lesions. Local treatments to metastatic lesions will increase the survival of advanced HCC patients who have proper liver function and a small number of metastases in a single organ. This study suggests the application of individually tailored therapeutic strategies for advanced HCC patients with extrahepatic metastasis.
A population-based analysis of urban-rural disparities in advanced pancreatic cancer (APC) management and outcomes.
Authors: Canale Thomas , Cheung Winson Y.
Published: March 2017

254

Background: Given the significant morbidity burden associated with APC, its management is complex and frequently requires multidisciplinary care. Because of potential geographical barriers to healthcare access, we aimed to determine the effect of rurality on management and outcomes of APC patients. Methods: Patients diagnosed with APC (locally advanced or metastatic disease) from 2008 to 2015 and received gemcitabine (gem), gem plus nab-paclitaxel (gem/nab), or FOLFIRINOX at any 1 of 6 British Columbia cancer centers across the province were reviewed. Using postal codes, the Google Maps Distance Matrix determined the distance from each patient’s residence to the closest cancer center. Rural and urban status were defined as patients living >= 100 km and < 100 km from the closest treatment site, respectively. Univariate and Cox regression analyses were applied to examine whether rurality resulted in variations in management and outcomes. Results: In total, we identified 667 patients: median age 68 years, 54.3% men, and 45.7% metastatic disease. Among them, 19.5% lived rurally and 80.5% resided in urban areas. For treatment, 67.8%, 9.4%, and 22.8% received gem, gem/nab, and FOLFIRINOX, respectively. However, there were no differences in baseline clinical characteristics between rural and urban patients (all p > 0.05). Also, there were no significant variations in treatment patterns. For example, time from diagnosis to oncology appointment and time from appointment to treatment were 31.6 and 29.5 days for rural patients and 28.7 and 39.9 days for urban patients, respectively (all p > 0.05). Use of gem/nab (9.8 vs 9.4%) and FOLFIRINOX (20.5 vs 23.3%) were similar regardless of rurality. In multivariate Cox regression, risk of death was similar between rural and urban groups (HR 1.34, 95% CI 0.95-1.87, p = 0.09). Conclusions: Our findings suggest that there is no correlation between rurality and outcomes in APC. The strategic and geographic allocation of cancer care delivery across the province of British Columbia may serve as a model for other jurisdictions that experience disparities in the outcomes of cancers that often require complex multidisciplinary care.
Clinical impact of sarcopenia on prognosis in pancreatic ductal adenocarcinoma.
Authors: Ninomiya Go , Fujii Tsutomu , Yamada Suguru , Asano Tomonari , Takano Nao , Takami Hideki , Iwata Naoki , Kanda Mitsuro , Niwa Yukiko , Hayashi Masamichi , Kobayashi Daisuke , Tanaka Chie , Nakayama Goro , Sugimoto Hiroyuki , Fujiwara Michitaka , Koike Masahiko , Kodera Yasuhiro
Published: March 2017

259

Background: In the past, various prognostic factors in pancreatic ductal carcinoma (PDAC) have been identified, and there found to be not only tumor-specific clinicopathological factors but also individual patient characteristics. In particular, weight loss, muscle wasting and cachexia are hallmarks of PDAC that may be associated with depletion of both skeletal muscle and adipose tissue. Most notably, sarcopenia is defined to be degenerative loss of skeletal muscle mass that is quantifiable using cross sectional imaging computed tomography (CT) by measurement of psoas area and the muscle’s density. Furthermore, visceral adipose tissue loss also has been reported to associate with a poor survival among patients with PDAC. Methods: A total of 265 patients who underwent curative surgery for PDAC were examined in this study. The total skeletal muscle and fat tissue areas were evaluated in a single image obtained at the third lumber vertebra during a preoperative computed tomography (CT) scan. The patients were assigned to either the sarcopenia or non-sarcopenia group based on their skeletal muscle index (SMI) and classified into high visceral fat area (H-VFA) or low VFA (L-VFA) groups. The association of clinicopathological features and prognosis with the body composition were statistically analyzed. Results: There were 170 patients (64.2%) with sarcopenia. The median survival time (MST) was 23.7 months for sarcopenia patients and 25.8 months for patients without sarcopenia. The MST was 24.4 months for H-VFA patients and 25.8 months for L-VFA patients. However, sarcopenia patients with BMI ≥ 22 exhibited significantly poorer survival than patients without sarcopenia (MST: 19.2 vs. 35.4 months, P = 0.025). There was a significant difference between patients with and without sarcopenia who did not receive chemotherapy (5-year survival rate: 0% vs. 68.3%, P = 0.003). The multivariate analysis revealed that tumor size, positive dissected peripancreatic tissue margin, and sarcopenia were independent prognostic factors. Conclusions: Sarcopenia is an independent prognostic factor in PDAC patients with a BMI ≥ 22. Therefore, evaluating skeletal muscle mass may be a simple and useful approach for predicting patient prognosis.
Clinical impact of visceral thrombosis (VT) in pancreatic ductal adenocarcinoma (PDAC).
Authors: Mier Hicks Angel , Raj Micheal , Do Richard Kinh Gian , Yu Kenneth H. , Lowery Maeve Aine , Varghese Anna M. , O'Reilly Eileen Mary
Published: March 2017

260

Background: VT or splanchnic thrombosis is defined as thrombi within the hepato-portal venous system including; portal (PV), mesenteric (MV) and splenic vein (SV), as well as thrombi in renal or gonadal veins. Limited evidence has explored the prognostic significance, incidence and current clinical management of VT in patients with PDAC. Methods: We conducted an analysis of N = 95 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between 1/1/13 and 12/31/15 with PDAC who developed a VT either at presentation or which developed during the disease course. Results: N = 134 VT events (VTe) occurred. Median age of PDAC diagnosis was 62.5 yrs. Overall survival (OS) was 10.5 months (m); seven patients were still alive in 7/ 16. Time to develop first VTe was 4.3m (SD6.71, 0-31) and time to death from VTe development was 6.1m (SD 5.7,0-24). Subsequently, N = 42 pts developed a second VTe and N = 13 pts a third VTe. At time of VT diagnosis, N = 37 (38%) pts were asymptomatic, and N = 58 (61%) pts had an incidental finding. N = 39 (39%) pts were treated with short-term anticoagulation (STAC) ( < 1m) (N = 35 pts, treated with Low Molecular Weight Heparin (LMWH)). N = 45(46%) pts were treated with long-term anticoagulation (LTAC) ( > 1m) (LMWH N = 32, N = 11 pts were transitioned to an oral anticoagulant (NOAC)). Only N = 12(12%) pts were treated with a NOAC. N = 8 (8%) pts developed a bleeding complication from LTAC. OS for pts receiving LTAC was 4m vs 3m with STAC. Conclusions: In patients with PDAC, VT can frequently present as an incidental finding on routine abdominal imaging. The most common location is PV followed by MV and SV. We observed that AC is under-utilized in this setting despite a low bleeding complication rate. LMWH appeared to be the preferred treatment with LTAC, followed by use of a NOAC. PV was associated with reduced OS. Use of therapeutic anticoagulation for treatment of VT is limited by lack of data. Future large prospective studies should explore the role of AC and value in this setting.[Table: see text]
Prospective evaluation of the clinical implications of the tumor metabolism and chemotherapy-related changes in advanced biliary tract cancer.
Authors: Jo Jaemin , Oh Do-Youn , Park Seongyeol , Kwon Hyun Woo , Cheon Gi Jeong , Bang Yung-Jue
Published: March 2017

261

Background: Tumor metabolism measured by [18F] fluorodeoxy-D-glucose (18F-FDG) positron emission tomography (PET) has a diagnostic and prognostic role in several cancers. The clinical implication of tumor metabolism in biliary tract cancer (BTC) has not been studied well. Therefore, we prospectively evaluated the prognostic value of tumor metabolism and chemotherapy-related changes in advanced BTC patients. Methods: We prospectively enrolled advanced BTC patients before the initiation of palliative chemotherapy. Using 18F-FDG PET, we assessed the baseline maximum standardized uptake value (SUVmax) and monitored the changes of SUVmax during chemotherapy. We analyzed the associations between SUVmax, and clinicopathologic factors and clinical outcomes. Results: A total of 75 patients were enrolled. All patients received gemcitabine/cisplatin as first-line chemotherapy. Primary tumor site, histologic differentiation, molecular characteristics, laboratory findings, and disease extent were associated with the metabolic characteristics. The high metabolism group showed worse survival outcome [Hazard ratio (HR)=4.09, p=0.001 for progression-free survival (PFS); HR=2.61, p=0.019 for overall survival (OS)] than the low metabolism group. The lesser reduction of SUVmax during chemotherapy was also associated with worse outcome (HR=3.35, p=0.002 for PFS; HR=1.96, p=0.082 for OS). Considering both baseline tumor metabolic activity and chemotherapy-related changes in the tumor metabolism, patients with a low metabolism and a more reduction in metabolism obtained the best OS (20.7 months, p=0.013). Conclusions: Tumor metabolic activity and the chemotherapy-related changes in the metabolism were associated with prognosis in advanced BTC patients.
A study on thromboembolism of patients with pancreatic cancer.
Authors: LAM Kwan Yu , Lee Kirsty , Chong Charing , Chan Anthony WH , Mok Tony , Chan Stephen Lam
Published: March 2017

262

Background: There have been studies on the association between thromboembolism (TE) and pancreatic cancer in Caucasian patients. This study aims to study the TE in Chinese patients with pancreatic cancer. Methods: This study retrospectively reviewed consecutive patients with confirmed diagnoses of pancreatic cancers from 2010-2015 in the Prince of Wales Hospital in Hong Kong. Patients with radiologically confirmed TE were identified. Corresponding information related to the type and site of TE were recorded. Predictive factors for the TE were studied by multivariate analysis. Results: Total 372 patients with pancreatic cancer were identified. In the cohort, the diagnoses of cancers were made by histology in 225 (60.5%) of them while others were made by radiology. The stage was as follows: 15 (4.1%) stage I; 113 (30.4%) stage II; 47 (12.7%) stage III and 196 (52.7%) stage IV. Total 55 (14.7%) patients had TE after diagnosis of pancreatic cancer. Of these 55 patients, 33 (60%) and 18 (32.7%) had venous and arterial events, respectively. For patients with TE, 27 (49.1%) were treated with anti-coagulants, and 13 (23.6%) had surgery within 2 years. The median time from surgery to the development of TE was 1.06 years. Patients with ECOG ≥2 and metastatic disease (HR 2.92, 95% CI 1.58-5.37; HR 6.90, 95% CI 3.63-13.14 respectively) had a higher risk of developing TE. Patients with venous, arterial, or both types of TE did not have significantly different overall survival. Poor prognostic factors for overall survival include ECOG ≥2 (HR 2.80, 95% CI 2.18-3.60) and tumour stage (stage II disease HR 1.36, 95% CI 0.70-2.62; stage III disease HR 1.85, 95% CI 0.92-3.70; stage IV disease HR 4.92, 95% CI 2.58-9.36). The presence of TE equated to a worse overall survival (median overall survival 148 vs. 228 days, HR 1.03, 95% CI 0.75-1.40, P=0.87), which was statistically insignificant. Conclusions: TE was similarly high in Chinese patients with pancreatic cancer. Patients with poorer performance status and metastatic disease had a greater risk of developing TE. Patients with TE had a worse overall survival (which was statistically insignificant) compared to patients without TE.
Evaluation of tumor marker cancer antigen 72-4 (CA 72-4) in the monitoring of metastatic or recurrent tumors of the gastrointestinal tract, lung, breast, and ovaries.
Authors: Mariampillai Anusiyanthan Isaac , Dela Cruz Josephine Pineda , Suh Jason , Sivapiragasam Abirami , Nevins Kyle , Hindenburg Alexander A.
Published: March 2017

263

Background: In management of metastatic and recurrent cancers, measuring response is a constant challenge. CA72-4 is a tumor marker (TM) that has been found elevated in a variety of human adenocarcinomas, with reported sensitivities of up 50% and overall specificity of over 95%. Using the DRG TM-CA72-4 assay, we quantified the abnormality rate of TM CA72-4 compared with current FDA-approved TM in various cancers. Methods: We conducted a prospective, single center study by enrolling 96 patients between March 2013 and August 2016 with various de novo or previously diagnosed locally advanced, unresectable and/or metastatic cancers known to express CA72-4. Quantification of CA72-4 was performed according to manufacturer’s instructions using the DRG TM-CA72-4 ELISA kit, which was developed by DRG International (Germany) utilizing the CC-49 monoclonal mouse antibody directed against an epitope on the CA72-4 antigen. Positivity was calculated as greater than A) 0.8 U/mL or B) 4.0 U/mL based on systematic review of prior studies. Results: The positivity rates based on different cut-off points (0.8 U/mL vs 4 U/mL) and their corresponding FDA approved tumor markers are shown in the Table. Conclusions: Positivity rates of CA72-4 varied based on different assay cut-off levels with the highest positivity noted in the pancreatic, ovarian and colorectal carcinomas indicating a potential role for disease monitoring. [Table: see text]
Field deployable platform for prognostic hepatic cancer screening.
Authors: Shea Jill E. , Granger Jennifer H , Porter Mark D , Scaife Courtney L.
Published: March 2017

267

Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.