bluuebunny/crossref_metadata_2025 huggingface dataset:
Overall survival with preoperative biliary drainage in patients with resectable pancreatic cancer.
Authors: Strom Tobin Joel Crill , Hoffe Sarah E. , Vignesh Shivakumar , Klapman Jason , Harris Cynthia L. , Choi Jungsun , Springett Gregory M. , Meredith Kenneth L. , Hodul Pamela Joy , Malafa Mokenge Peter , Shridhar Ravi
Published: February 2017

314

Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 >90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.
Outcomes and toxicity of SBRT for patients with unresectable pancreatic adenocarcinoma.
Authors: Pollom Erqi L. , Alagappan Muthuraman , Chan Cato , Shultz David , Kunz Pamela L. , Koong Albert , Chang Daniel Tandel
Published: February 2017

317

Background: To report updated outcomes and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma treated over the past 11 years from a single institution. Methods: One hundred and ninety-nine patients with primary, unresectable pancreatic adenocarcinoma were treated with SBRT at our institution from 2002 to 2013. One hundred and sixty-four had locally advanced disease, 12 had borderline resectable disease, 21 were medically inoperable, and 2 had resectable disease but refused surgery. Fifteen patients had metastases at the time of SBRT. Forty-six patients were treated with prior RT, 16 of whom were enrolled on a combined IMRT/SBRT trial. Most common treatment regimens were 25 Gy x 1 (51.3%), 6.6 Gy x 5 (25.6%), 6 Gy x 5 (15.0%). Fifty-seven patients had no prior/current chemo while 142 patients had prior/current chemo (134 had gemcitabine-based chemo). BED10 and BED3 were defined using the linear quadratic equation assuming an α/β of 10 and 3, respectively. Results: Median follow-up was 7.1 months (0.13-63.58). The 6- and 12-month cumulative incidence of local recurrence (CIR) were 7.93% (4.07-11.80%, 95% CI) and 12.48% (7.68-17.28%, 95% CI), respectively. Three patients converted to resection after SBRT. BED10 (median 87.5, range 19.5-97.5), prior RT, prior/current chemo, and tumor location did not predict for CIR. OS rates at 6 months and 12 months were 71.23% (65.02-78.0%, 95% CI) and 36.23% (29.54-44.4%, 95% CI), respectively. Median OS from date of diagnosis was 14.27 months (13.25-16.90 95% CI). Patients who received prior/current chemo had better OS (p=0.0035). There were 26 (13%) recorded GI ulcers/strictures/bleed (5 acute, 21 late) after treatment. BED3 (median 233.3, 30-233.3) predicted for these toxicities (OR 1.01, 1.00-1.01 95% CI, p=0.022), while age, prior RT, prior/current chemo, tumor location did not. Conclusions: SBRT for pancreatic adenocarcinoma is effective for local control with associated risk of toxicity. The risk of GI toxicity is correlated with BED3. Survival is associated with the use of chemotherapy. SBRT may be advantageous due to its good local control with shortened treatment duration that minimizes interruption in chemotherapy.
Second-line FOLFOX chemotherapy in patients with metastatic gallbladder cancer and cholangiocarcinoma.
Authors: Leal Jose Luis , Roa Juan Carlos , Jarufe Nicolas , Madrid Jorge , Ibanez Carolina , Herrera Maria Elisa , Garrido Marcelo , Nervi Bruno
Published: February 2017

322

Background: After first-line treatment with gemcitabine-based regimen, there is not standard second-line chemotherapy for patients with metastatic gallbladder cancer (GB) and cholangiocarcinoma (CC). The aim of this study was to evaluate the activity, progression free survival (PFS), and overall survival (OS) of the FOLFOX4 regimen as second-line chemotherapy. Methods: We performed a retrospective analysis of all metastatic GB and CC that were treated with gemcitabine (Gem) based first-line chemotherapy, and second-line FOLFOX4 chemotherapy (oxaliplatin 85 mg/m2, day 1; leucovorin 200 mg/m intravenously, days 1 and 2; 5-fluorouracil 400 mg/m intravenous bolus, days 1 and 2; and 600 mg/m in 22 h intravenously, continuous infusion days 1 and 2; every 14 days) in our Institution since 2003. The response rate was evaluated every 2 to 4 months according to the RECIST criteria, and PFS/OS were calculated according to the Kaplan-Meier method. Results: Eighty patients (n=40 GB; n=40 CC) received Gem based first-line treatment (42 Gem alone; 38 Gem + platinum). There was no survival difference between Gem or Gem+platinum treatment (161 versus 254 days; p=0.09). Response rate (complete and partial response) was 16% and stable disease was 31%. Ca19-9 at presentation was predictive for OS: <100U/ml =403 days versus >100 U/ml =223 days (p=0.025). Eighteen patients (22%; n=10 GB and n=8 CC) were treated with second-line FOLFOX4. In the second-line group, stable disease was achieved in 4 patients (22%), and 11 patients progressed (66%). The median DFS and OS were 96 and 138 days respectively. The median OS for patients that received one versus both lines of chemotherapy were 161 versus 400 days (p=0.009). Conclusions: FOLFOX4 has activity in second line chemotherapy for patients with metastatic GB and CC. A prospective study is warranted to confirm this observation.
Economic burden of advanced hepatocellular carcinoma (HCC) in Spain among patients discontinuing first-line sorafenib.
Authors: Liepa Astra M. , Candrilli Sean D. , D'yachkova Yulia , Taipale Kaisa , Kaye James A.
Published: February 2017

324

Background: No treatments (Txs) are currently recommended after discontinuation (DC) of sorafenib (SOR) for advanced HCC and there are limited reports of Tx patterns. This study assessed Tx patterns, resource use, and associated costs for a select cohort of patients (pts) from Spain. Methods: Via an internet-based chart review, 50 physicians provided clinical and resource use data for 5 de-identified pts each. Medical records were eligible if the pt was ≥18 years old, was diagnosed with advanced HCC, initiated first-line SOR after 2008, subsequently discontinued SOR, survived ≥2 months post-SOR DC, and had ≥6 months of follow-up data (or had died). Unit costs for healthcare resources were obtained from publicly-available sources and applied to the number of each resource type to obtain cost estimates. All analyses were descriptive in nature. Results: From September to October 2012, physicians provided data for 250 pts. Mean pt age was 61 years and 73% were male. At SOR initiation, 35% were Barcelona Cancer Liver Clinic stage B and 63% C. From SOR initiation to DC, 43% declined in Child-Pugh status. Following SOR DC, inpatient hospitalization was reported for 45% and emergency room visits for 49%. For those reported as having received supportive care (n=209), 73% received pain interventions, 42% nutritional support, 33% antiemetics, and 17% transfusions. 28% received anti-cancer Tx (chemotherapy, procedures). For all pts, hospitalization represented about half of total costs. For pts who received further anti-cancer Tx, chemotherapy and procedures represented about one-third of costs and hospitalization less than one-third. Total costs per pt are summarized (Table). Conclusions: Following sorafenib DC, most advanced HCC pts who we studied did not receive further anti-cancer Tx. Those who received further anti-cancer Tx had greater total healthcare costs, but these costs accrued over a longer period of time. [Table: see text]
First report of a prospective trial of proton therapy and concomittant capecitabine for patients with nonmetastatic unresectable pancreatic adenocarcinoma.
Authors: Nichols Romaine Charles , Morris Christopher G. , George Thomas J. , Zaiden Robert Anthony , Johnson Elizabeth , Ahmed Bestoun H. , Ho Meng Wei , Huh Soon N. , Mendenhall Nancy P. , Hoppe Bradford S.
Published: February 2017

326

Background: Review initial outcomes for patients enrolled on the University of Florida Proton Therapy Institute PC01 protocol for patients with unresectable pancreatic cancer. Methods: The protocol received Institutional Review Board (IRB) approval in 7/2007. The first patient was enrolled in 4/2010. The accrual target was 66 patients to test if the Serious Adverse Event (SAE) ratecould be reduced from 15% (expected) to less than 5%. Protocol therapy consisted of proton therapy to a planning target volume (PTV) dose of 59.4 Cobalt Gray Equivalent (CGE) at 1.8CGE per fraction with concomitant oral Capecitabine (1000mg PO BID 5 days/week on radiation treatment days). Only gross disease was targeted. Results: 12 patients were enrolled. 1 patient died of a gunshot wound 5 days after starting treatment so only 11 patients are reported. Median follow up from start of treatment: 13 months (range 2 to 21 months). Median age: 68 (range 51 to 86) years. Gender: Males 5, Females 6. Race/Ethnicity: 9 White, 2 Hispanic. Overall survival: 90% at 6 months and 60% at 12 months. Freedom from progression: 80% at 6 months and 53% at one year. Local control: 100% at 6 months and 86% at 12 months. Freedom from metastasis: 80% at 6 months and 67% at 12 months.No patient experienced any grade 3 or greater toxicity during treatment or the follow up period. Grade 2 toxicity was limited to a single patient experiencing grade 2 fatigue. Median weight loss over the course of treatment was 1.7 (range: loss of 5.7 to gain of 4.9) Kg. 4 patients were deemed to have had an adequate radiographic response to radiotherapy so as to justify surgical exploration. Conclusions: Proton therapy to 59.4 CGE with concomitant Capecitabine was well tolerated with no grade 2 or greater gastrointestinal toxicities. 4 of 11 patients achieved a radiographic response allowing for attempted surgical resection. The study was closed to accrual on 9/1/2013 due to recognition that slow accrual made achievement of the primary study endpoint unlikely. At the same time, the lack of any meaningful gastrointestinal toxicity suggests significant opportunities for treatment intensification when proton therapy is used in this setting. Clinical trial information: NCT00685763.
Influence of obstructive jaundice on chemotherapy in patients with unresectable biliary tract cancer.
Authors: Shimizu Satoshi , Mitsunaga Shuichi , Ohno Izumi , Takahashi Hideaki , Okuyama Hiroyuki , Kuwahara Akiko , Okusaka Takuji , Ikeda Masafumi
Published: February 2017

336

Background: The aim of this study was to investigate the influences of obstructive jaundice (OJ) in unresectable biliary tract cancer (BTC) patients. Methods: Data of a total of 200 patients who were newly diagnosed as having unresectable BTC and received chemotherapy between July 2006 and December 2012 were retrospectively reviewed. Patients were divided into two groups according to whether or not they presented with OJ as the incipient chief complaint (Group 1, patients with OJ; Group 2, patients without OJ). Results: There were 81 patients in Group 1 and 119 patients in Group 2. In regard to the primary site (Group 1/Group 2), 29 had perihilar (27/2), 7 had distal (7/0), 68 had intrahepatic (15/53), 92 had gallbladder (31/61) and 4 had ampulla of vater (1/3) (p<0.01). The rate of distant metastasis was 60% in Group 1 and 76% in Group 2 (p=0.02). The performance status was good (0 or 1) in 96% of cases of both the groups. There were no significant differences in the median survival time between Group 1 and Group 2 (9.0 months vs. 9.0 months, p=0.42) or in the progression free survival of 1st line chemotherapy between the two groups (4.1 months vs. 3.7 months, p=0.08). The rate of development of biliary obstruction in Group 1 was significantly high during the first line chemotherapy (56% vs. 10%, p<0.01). Discontinuation of 1st line chemotherapy was necessitated due to biliary obstruction in 9 patients (10%) of Group 1 and none of the patients (0%) of Group 2. Multivariate analysis showed that absence of metastasis and use of a doublet chemotherapy regimen were significantly correlated with the overall survival, but not the presence of OJ as the incipient chief complaint (HR, 0.772; 95% CI, 0.532-1.119). Conclusions: Patients with OJ as the incipient chief complaint showed high rate of recurrent biliary obstruction and discontinuation chemotherapy due to biliary obstruction. However, OJ may not disadvantage for overall survival in BTC.
Effect of neoadjuvant therapy in patients with resected pancreatic adenocarcinoma.
Authors: LoConte Noelle K. , Mohammed Tabraiz Aijaz , Winslow Emily , Neuman Heather B. , Smith Maureen , Allen Glenn , Schmacher Jessica
Published: February 2017

338

Background: Retrospective data suggest that neoadjuvant therapy in patients with resectable pancreatic cancer may improve the R0 resection rate and potentially survival. We examined the impact of neoadjuvant therapy on survival rates at a population level for patients with resected pancreatic adenocarcinoma. Methods: Treatment and outcome data were obtained from the Surveillance, Epidemiology and End Results (SEER) Medicare database for patients with pancreatic adenocarcinoma, who underwent a curative intent pancreatectomy from 2001-2007. Patients were stratified by treatment (neoadjuvant vs no neoadjuvant therapy). Kaplan Meier curves were constructed to analyze survival. Cox proportional hazards regression models with and without propensity score weighting were performed to determine the effect of neoadjuvant therapy and race on mortality while adjusting for age, gender, race, marital status, SEER site, urban/rural location, income, education, year of diagnosis, and Charlson Comorbidity Score. Results: 2608 patients were included. 58.4% (n=1523) were between age 66-75 and 41.6% (n=1085) were age 76 or older. 94% (n=2459) did not receive neoadjuvant therapy and 6% (n=162) received neoadjuvant therapy. Patients undergoing neoadjuvant therapy were 28% less likely to experience death at one year (HR 0.72; 95% CI, 0.53-0.97; p=0.03). There was also a trend towards a lower risk of death in this group at 2 years (HR 0.82; 95% CI, 0.66-1.01; p=0.07). Conclusions: Patients with pancreatic adenocarcinoma who underwent neoadjuvant therapy followed by resection had an improved one-year survival relative to patients who did not receive neoadjuvant therapy in this cohort. This effect may partially reflect the role of neoadjuvant chemotherapy in allowing for better selection of patients likely to benefit from surgery. To our knowledge this is the first population-based study that suggests an improved survival in patients with pancreas cancer undergoing neoadjuvant therapy prior to resection. [Table: see text]
A qualitative study of patient and clinician attitudes regarding surveillance following resection of pancreatic and periampullary cancer.
Authors: Deobald Raymond Gilbert , Cheng Eva , Ko Yoo-Joung , Wright Frances Catriona , Karanicolas Paul Jack
Published: February 2017

339

Background: Pancreatic carcinoma is the fourth leading cause of cancer death in North America. Following surgical resection, most patients will develop recurrence within two years. Intense follow-up is often recommended; however, the impact on survival is unknown. We sought to qualitatively assess patient and clinician attitudes towards follow-up and the perceived benefits and challenges. Methods: The research team developed a semi-structured interview guide. Purposive sampling identified patients who had undergone curative attempt resection and were in active surveillance or had developed recurrence. Clinicians involved in patient care were also interviewed.Themes were derived using standard qualitative methods. Results: Fifteen patients and seven clinicians were interviewed. Patient themes included (1) Limited understanding of disease prognosis; (2) Desire for reassurance through follow-up; (3) Desire to know if and when recurrence occurred; (4) Challenging treatments; (5) Minimal difficulties with the follow-up protocol; and (6) Limited role of family doctors in pancreatic cancer follow-up. Clinician themes included (1) Expectation that patients are aware of recurrence risk; (2) Desire to provide reassurance to patients; (3) Support for intense follow-up protocol despite lack of supporting evidence; (4) Secondary goals for surveillance; (5) Perceived patient challenges in follow-up; (6) Openness to family doctors doing follow-up. Overall, the dominant theme was one of disconnect between patients and clinicians in the understanding of the disease and its prognosis. Conclusions: Patients with pancreatic or periampullary cancer have an intense need for reassurance and obtain this through the follow-up process. Consequently they express few difficulties with follow-up despite the intensity of testing. Oncologists recognize this desire for reassurance and provide it through follow-up despite the lack of evidence to show benefit. There appears to be a disconnect between patients and clinicians in the understanding of the disease and its prognosis suggesting further work is needed to improve patient-physician communication.
CD44-overexpressed gastric cancer imaging by near IR using HA-based supramolecular hydrogels.
Authors: Park Jungmin
Published: February 2017

34

Background: To establish NIR optical probe based on the HA-based supramolecular hydrogels (HASHs) conjugated with Cy5.5 for CD44-overexpressed gastric cancer imaging. Methods: To establish HASHs, Cy5.5 NHS ester was conjugated with polyethyleneimine (PEI, 25k Da) and mixed with hyaluronic acid (HA, 1M Da) by an electric interaction. The optimazed ideal molar ratio of PEI to HA was confirmed by DLS and gel electrophoresis. The CD44-expression level for various gastric cancer cell lInes (MKN1, MKN28, MKN45, MKN72, AGS, and N87 cells) was evaluated by FACS analysis. For establishment of the gastric cancer xenograft model, CD44-overexpressed gastric cancer cells were implanted into the BALB/c nude mouse's proximal thigh region. For in vitro targeting study, the cellular affinity of HASHs for CD44-low expressed gastric cancer cell line and CD44-overexpressed gastric cancer cell line was verified by confocal microscopy and IHC staing. For in vivo NIR imaging, HASHs were injected into established xenograft mouse via tail vein and NIR optical imaging was conducted time-dependently. Results: The colloidal size of HASHs was 1.4 micrometer and their morphology was confirmed by electron microscopy. CD44-expression level of MKN45 cells was 92.53% that was higher than MKN28 cells (2.66%). After the treatment of HASHs, the endocytosis into the cytosol was examined for MKN45 cells, but not observed in MKN28 cells due to the deficiency of CD44. 30 days after the transplantion of MKN45 cells, for in vivo imaging study, the prepared HASHs were intraveneously injected into tumor-bearing mouse model. By NIR optical imaging, the optical intensity at tumor site was enhanced upto 3 hours and the maximum intensity was 350 times larger than normal tissue. Conclusions: HASHs was established using supramolecular HA and Cy5.5-conjugated PEI for the targeted imaging of CD44-overexpressed gastric cancer cells. In vitro and in vivo studies demonstrated that SHAHs can visualize the individualized CD44-overexpressed gastric cancer cells by non-invasive optical imaging.
Second-line gemcitabine plus nab-paclitaxel (G+A) for advanced pancreatic cancer (APC) after first-line FOLFIRINOX: Single institution retrospective review of efficacy and toxicity.
Authors: Zhang Yue , Hochster Howard S. , Stein Stacey , Lacy Jill
Published: February 2017

344

Background: Gemcitabine (G) plus paclitaxel protein-bound particles for injectable suspension (Abraxane, A) is an active first line regimen for APC based on improved efficacy compared to G (Van Hoff, DD et al. J Clin Oncol 31, 2013 [suppl;abstr 4005]). However, there is a paucity of data regarding efficacy of G+A in pts who received prior FOLFIRINOX. To assess efficacy and tolerability of 2nd line G+A, we reviewed our single institution experience with G+A in APC pts who received 1st line FOLFIRINOX. Methods: We conducted a retrospective review of dose, toxicity, efficacy of second line G+A in FOLFIRINOX-treated APC pts treated at Yale Cancer Center between 12/2011 and 08/2013. Pts were treated until progression, unacceptable toxicity, or pt preference. Doses were at treating physician’sdiscretion. Dose densities were compared to full doses (A 125 mg/m2 + G 1000 mg/m2 days 1, 8,15 q 4 wks). Response rate, med time to treatment failure (TTF), med overall survival (OS) were calculated. Results: 23 pts were treated with G+A after 1st line FOLFIRINOX. Pts characteristics: metastatic, 18; locally advanced, 5; med age, 61 (range 50-74);male, 9; ECOG PS ≤1, 22; med # FOLFIRINOX cycles, 12 (range 5-46). Med interval from FOLFIRINOX to G+A was 5 wks (range 1.7-40.3). Responses by RECIST were: PR, 2 (8.7%); SD for ≥7 wks, 8 (34.8%); PD, 10 (43.4%); ineval, 3 (13.1%). 9 (39%) and 8 (34%) pts had >30% decrease in CA 19-9 and CEA, respectively. 13 pts died, 6 pts stopped G+A, 4 pts are still receiving G+A. Med TTF was 11 wks (range 1-35). Med OS was >17.9 wks (range 2.1-69.6). All pts had initial dose reductions of G or A; 7 and 12 pts required further dose reductions with A and G, respectively. Dose densities were 56.9% and 63.5% for A and G, respectively. Grade ≥3 hematologic toxicities included neutropenia 17%, anemia 26%, thrombopenia 26%. Conclusions: In this single institution pt population, G+A has limited activity after FOLFIRINOX. Most of our pts received FOLFIRINOX for >6 months and were still able to receive a 2nd line doublet. Most required dose reductions for cytopenias, but this sequence was tolerable. In this setting, an additional 11 wks med TTF is about half of the TTF in 1st line G+A and may be clinically valuable.
A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.
Authors: Suzuki Eiichiro , Kaneko Shuichi , Okusaka Takuji , Ikeda Masafumi , Yamaguchi Kensei , Moriguchi Michihisa , Sato Tosiya , Furuse Junji
Published: February 2017

354

Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.
Utility of [18F] flourodeoxyglucose positron emission tomography (FDG-PET) to predict resectability after neoadjuvant therapy in patients with unresectable pancreatic cancer on CT scans.
Authors: Khawandanah Mohamad Osama , Kurkjian Carla , Penaroza Shyla , Arnold Charles , Herman Terence S. , Talbert Michael , Postier Russell , Pant Shubham
Published: February 2017

357

Background: The standard imaging approach in patients with pancreatic cancer is contrast enhanced computed tomography (CT), however, Response Evaluation Criteria in Solid Tumors (RECIST) may not be adequate in evaluating response to neoadjuvant therapy. A growing body of evidence exists to suggest that there is additional useful information to be gained from the use of FDG-PET scans in this setting. Methods: We conducted an IRB approved retrospective chart review of patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy at the University of Oklahoma and who had PET/CT imaging before and/or after neoadjuvant therapy between September 2006 and September 2013. Complete remission (CR) was defined as decrease in SUV to ≤ 3.0 or background, and partial response (PR) was defined as decrease in SUV from baseline, but > 3.0. Results: A total of 13 patients underwent Whipple surgery after neoadjuvant therapy at our institution. Four patients (31%) had persistent unresectable disease on CT scans post-neoadjuvant therapy, but demonstrated CR (three patients) or PR (one patient; Pre-treatment SUV: 10.1, Post Treatment: 4.6) on the PET scan. These patients underwent Whipple surgery based on PET response. All four (100%) patients underwent R0 resection. Two patients (50%) received neoadjuvant chemo-radiation in addition to chemotherapy. Conclusions: Response on FDG-PET/CT can be a predictor of R0 resection in cases with evidence of unresectable disease on conventional CT scan. A protocol to study larger number of patients prospectively is being designed.
Long-term outcome of patients with hepatocellular carcinoma treated with hypofractionated stereotactic radiation therapy as a bridge to liver transplantation.
Authors: Katz Alan W. , Rosenzweig Douglas P
Published: February 2017

368

Background: Stereotactic hypofractionated radiation therapy (SHORT) is a safe, non-invasive, treatment modality for patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the long-term outcome of patients with HCC receiving SHORT as a bridge therapy to LT. Methods: We reviewed 9 consecutive patients who underwent LT between 2008 and 2010 after receiving SHORT as bridge therapy. Radiation therapy was delivered using a 6 MV linear accelerator and an infrared based patient posititiong system. Total dose was 50 Gy in 10 fractions. Doses were prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor plus a minimum margin of 7 mm. Survival was measured from the date of LT. Results: Median time from completion of SHORT to LT was 5.9 months (range; 0.9-15.7 months). After a median follow up of 48.6 months (range; 17.8-65.3 months) all patients were still alive. No significant surgical complications were seen in any of the patients. 8 patients demonstrated necrosis in the treated tumors, ranging from 8-100%. Only 1 patient did not show any treatment effect on pathological examination. One patient developed recurrent disease in a lymph node and in the transplanted liver, both treated by SHORT with complete response. Conclusions: SHORT is a safe and effective bridging therapy with patients experiencing excellent disease-free and overall survival following LT.
The time trends of gallbladder cancer and cholangiocarcinoma in 1,047 patients.
Authors: Mitsunaga Shuichi , Ikeda Masafumi , Shimizu Satoshi , Ohno Izumi , Takahashi Hideaki , Okuyama Hiroyuki , Kuwahara Akiko , Ochiai Atsushi
Published: February 2017

376

Background: Gallbladder cancer (Gb ca) and cholangiocarcinoma (CC ca) are major primary sites in biliary tract cancer. Progresses of diagnosis and anti-cancer therapy for Gb and CC ca lead to the changes of patients’ characteristics and overall survival time, but is not fully understood. This study aimed to identify the time trends in patients with Gb and CC ca. Methods: The inclusive criteria in this study was the patients receiving initial treatment including surgery (Op), chemotherapy (Chemo), radiotherapy (RT), or best supportive care (BSC) for Gb or CC ca in our institution, and 1047 patients were reviewed. Patient who received initial treatment at 1992-2005 were in 54.1 % of the study subjects and was defined as Group 1. Patients with initial treatment at 2006-2012 were categorized to Group 2 and were in 45.9% of all patients. The differences between two groups were evaluated, and the features of Group 2 were identified. Results: Age more than 60 years (Odd ratio [OR]: 2.37), the absence of distant metastasis (OR: 2.13), and ECOG performance status score (PS) = 0 (OR: 1.70) were identified as the independent features of Group 2. The rates of Op, Chemo, RT, and BSC were 38.5, 24.7, 14.9, and 21.7% in Group 1, and 40.8, 49.9, 1.5, and 6.0% in Group 2. The rate of Chemo in Group 2 was higher than that in Group 1 (P < 0.01). The median times of overall survival (OS) in Op, Chemo, RT, and BSC were 21.1, 5.2, 6.9, and 2.4 months in Group 1 and 60.6, 9.2, 10.5, 2.8 months in Group 2. The OS in Op or Chemo of Group 2 was longer than that in Group 1 (P < 0.01, P < 0.01). The independent poor prognostic factors were distant metastasis (HR: 3.91), Group 1 (1.81), and PS > 0 (1.72) in all patients, distant metastasis (HR: 3.56), Group 1 (2.12), biliary drainage (1.75) in Op, and PS>0 (HR: 1.97), Group 1 (1.74), and distant metastasis (1.64) in Chemo. Conclusions: The recent trends in patients with Gb and CC ca were aging, low rates of distant metastasis, good PS, increased cases with chemotherapy, and the prolonged survival times in surgery and chemotherapy. The presence of distant metastasis, the worsened PS, and the previous treatment group were the independent poor prognostic factors.
Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010.
Authors: Bailey Christina Edwards , Hu Chung-Yuan , You Y. Nancy , Chang George J.
Published: February 2017

392

Background: The overall incidence of colorectal cancer (CRC) has been decreasing since 1998, but there has been an apparent rise in the incidence of CRC in young adults. The primary aim of this study was to evaluate age-related disparities in secular trends in CRC incidence in the United States. Methods: A retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER) registry. All patients diagnosed with colon or rectal cancer from 1975 to 2010 was queried. SEER*Stat (version 8.04, National Cancer Institute) was used to obtain the annual cancer incidence rates, annual percent change (APC), and corresponding p values for the secular trends. Results: Overall age-adjusted CRC incidence decreased by 0.92% between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed in patients 20 to 34 years of age. The APC for patients with localized, regional, and distant colon cancer at diagnosis in the 20 to 34 year age group was 1.10 (95% CI 0.28 to 1.93; p=0.01), 0.91 (95% CI 0.23 to 1.61; p=0.01) and 1.81 (95% CI 0.88 to 2.75; p<0.001). The APC for patients with localized, regional ,and distant rectal cancer in the 20 to 34 year age group was 4.03 (95% CI 3.02 to 5.05; p<0.001), 3.05 (95% CI 1.95 to 4.17; p<0.001) and 2.66 (95% CI 1.33 to 3.99; p<0.001). Based on current trends, in 2030 the incidence rate for colon and rectal cancer will increase by 90% and 124.2% respectively for patients 20 to 34 years of age while decreasing by 37.8% and 34.3% for patients 50 to 75 years of age. Conclusions: There has been a significant increase in the incidence of CRC diagnosed in patients age 20 to 34, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies. [Table: see text]
Efficacy of a population-based colorectal cancer screening program and analysis of outcomes in screen-detected and non-screen-detected tumors.
Authors: Mansouri David , Mcmillan Donald C. , Morrison David S. , Crighton Emilia M. , Horgan Paul G.
Published: February 2017

394

Background: Population based faecal occult blood test (FOBt) screening for colorectal cancer reduces cancer specific mortality through the detection of early stage disease. However, programmes are limited by uptake and the characteristics of the test itself. The aim of the present study was to compare features of screen detected (SD) and non-screen detected tumours (NSD) and assess the effect on cancer specific mortality. Methods: Prospectively maintained databases of both the prevalence round of a biennial population based FOBt screening programme and a regional cancer audit database were analysed. Mortality data was obtained from the national registry. Results: Of the 395,097 males and females aged 50 to 74yrs invited to screening, 203,886 (52%) responded, 6,085 (3%) tested positive and 4,632 (76%) attended for colonoscopy. A total of 951 patients were diagnosed with cancer within two years of screening invite: 378 (40%) SD and 573 (60%) NSD. Of the NSD patients, 376 (66%) were non-responders, 134 (23%) were FOBt negative and 63 (11%) did not attend or did not have cancer diagnosed at colonoscopy. Therefore, estimated FOBt sensitivity was 77%, and specificity was 99%. Comparing SD and NSD patients, SD patients were more likely to be male, less socioeconomically deprived, have a tumour with a lower Dukes stage, and more likely to have a left-sided tumour (all p<0.05). In addition, SD patients were more likely to undergo an operation with a curative intent, less likely to undergo an emergency procedure, and less likely to die within 30 days of their procedure (all p<0.001). With a median follow-up of 2 years, SD patients had improved cancer specific survival versus NSD patients (p<0.001). This remained significant on multivariate survival analysis (Cox proportional hazards) including age, sex, deprivation, emergency presentation, tumour site and stage, and curative surgery (p<0.001). Conclusions: Independent of established prognostic factors, SD patients have more favourable outcomes than those with NSD tumours. Therefore, further studies to improve the response rate to a screening invitation and the sensitivity of the current screening test are warranted.
Nomogram for predicting overall and colostomy-free survival for patients with anal cancer.
Authors: Tsikitis Vassiliki Liana , Lu Kim , Kim Jong Sung , Billingsley Kevin G. , Thomas Charles R. , Herzig Daniel
Published: February 2017

400

Background: The incidence of anal cancer, currently about 5,000 persons a year, is increasing in the United States. Its treatment has evolved from a radical surgical treatment including abdominoperineal resection to a combined chemoradiotherapy (CRT) (Nigro protocol) approach which allows for sphincter preservation. The specific aim of this study was to develop an accurate model and nomogram to predict overall (OS) and colostomy free survival (CFS) for patients (pts) presenting with anal cancer. Methods: Pts with de novo anal cancer were selected from the National Cancer Database (NCDB) from years 1998-2010. The database included 53,523 pts. After excluding anal margin cancer pts and pts with missing data points; 1,823 pts were included and their data analyzed. Variables included time to death, censoring indicator, age, race, sex, tumor size, surgery status, nodal status, radiation (RT) and chemotherapy (CT) separately and as a CRT. A stratified Cox proportional hazards model for OS and a logistic regression model for CFS were developed, respectively. For each primary end point, our final model was validated to ascertain whether predicted values from the model are likely to accurately predict responses on future subjects or subjects not used to develop our model. Results: Statistically significant variables in the CFS model were age, nodal status, TNM stage, RT (p ≤ 0.0001), and tumor size (p = 0.010). Similarly, for OS model statistically significant variables (all with p ≤ 0.005) fitted across the strata of TNM clinical stage included age, sex, tumor size, nodal status, and CRT. Nomograms that predict events are based on our final models with the estimated mean absolute bootstrap calibration error being only 0.011 for OS model and 0.02 for CFS model, respectively. Conclusions: A nomogram can predict OS and CFS over lifetime. Such outcome prediction tools may potentially be used as prognostic and decision support tools to guide therapy and predict pts that may need surgery in their lifetime.
The role of metformin for primary prevention in non-elderly diabetic colorectal cancer patients.
Authors: Sehdev Amikar , Shih Ya-Chen T. , Vekhter Benjamin , Lyttle Christopher , Polite Blase N.
Published: February 2017

406

Background: There is growing evidence for the beneficial effect of metformin in reducing the incidence of colorectal cancer (CRC) in diabetic patients. However, no such studies are done in the US population. We conducted a case control study (N=8,046) in non-elderly diabetic adult US population (age 18-64 years) to investigate the role of metformin for the primary prevention of CRC. Methods: MarketScan claims database was used to identify diabetic patients with CRC using ICD-9 codes. Only incident cases of CRC in diabetic patients were included in the study. Two matched controls (matched for age, sex, and geographical region) were selected per case. The exposure to metformin was assessed from prescriptions in the 12 months prior to the earliest date of CRC diagnosis. The primary objective was to assess the odds of having CRC in metformin users as compared nonusers. Adjusted odds ratios (AOR) were calculated by adjusting for multiple potential confounders using conditional logistic regression. Results: The mean age of CRC patients was 56 years, 60% were males. Metformin was prescribed to 38.13% patients. A total of 37% (995/2,682) patients developed CRC in metformin exposed group compared to 62.9% (1,687/2,682) patients in non-metformin exposed group. In a multivariate model, any metformin use was associated with a statistically significant 12% reduced risk of developing CRC (AOR 0.88, 95% CI, 0.79-0.98, p<0.026). Prescribed NSAIDs were also associated with decreased incidence of CRC (AOR 0.84, 95% CI, 0.73-0.97, p=0.019). Variables associated with increased incidence of CRC in the multivariate model were IBD (AOR 1.94, 95% CI, 1.13-3.33, p<0.015); use of insulin (AOR 1.45, 95% CI, 1.27-1.65, p<0.001); coronary artery disease (AOR 1.66, 95% CI, 1.43-1.93, p<0.001). There was no significant relationship between CRC incidence and obesity (AOR 1.19, 95% CI, 0.93-1.53, p=0.158); polycystic ovary disease (AOR 0.32, 95% CI, 0.03-2.76, p=0.3); sulfonylureas (AOR 1.09, 95% CI, 0.96-1.24, p=0.15); thiazolidinediones (AOR 0.94, 95% CI, 0.82-1.08, p=0.41); statins (AOR 0.914, 95% CI, 0.82-1.01, p=0.108). Conclusions: The use of metformin appears to reduce the incidence of CRC in non-elderly diabetic adult US population.
Characterization of family history profiles in a large series of Lynch syndrome carriers.
Authors: Saraiya Devki , Wiyrick Sara J. , Tong Barry S. , Moyes Kelsey , Garner Elizabeth
Published: February 2017

414

Background: The identification of Lynch syndrome carriers is an unmet medical need. Large studies characterizing family history profiles of unaffected individuals diagnosed with Lynch syndrome in the absence of a known family mutation have not been reported. Methods: We queried our laboratory database for unaffected patients who underwent Lynch syndrome genetic testing between September 2010 and May 2013 and had a positive test result. All individuals underwent full sequence and large rearrangement analysis of MLH1 and MSH2, and full sequence analysis of MSH6. Some patients also underwent full sequence and large rearrangement analysis of PMS2 and large rearrangement analysis of MSH6 and EPCAM. Those being tested for a known mutation in the family and patients undergoing single gene testing were excluded. We assessed family history profiles in 200 unaffected patients with genetically confirmed Lynch syndrome. Results: Of the 200 patients, 162 female and 38 male Lynch syndrome carriers were identified. Mutations in MLH1 and MSH2 were the most common (30.0% and 32.5%) while mutations in MSH6, PMS2, and EPCAM accounted for 21.0%, 13.5%, and 3.0% of all deleterious mutations, respectively. Eighteen patients did not have a first or second degree relative with colorectal cancer. Only 37.8% (73/193) of individuals had a first- or second-degree relative meeting the Amsterdam II criteria and 76.8 % (149/194) of individuals had a first or second degree relative meeting the Revised Bethesda criteria. The average PREMM1,2,6 score was 10.0% with 43.5% (87/200) falling below 5%. In this large cohort, 15.5% (31/200) had neither a first or second degree relative who met the Amsterdam II or Revised Bethesda criteria nor a PREMM1,2,6 score of 5% or greater. Conclusions: In order to improve detection of Lynch syndrome in the population, it is important to consider genetic testing in unaffected individuals even in the absence of a known family mutation. Development of guidelines that include having a single affected relative and extra-colonic cancers is needed to support healthcare providers in identifying appropriate patients for testing.
Universal screening for Lynch syndrome (LS) in colorectal cancer (CRC) and survival.
Authors: Haraldsdottir Sigurdis , Wu Christina Sing-Ying , Hampel Heather , Frankel Wendy , Pan Xueliang Jeff , Bekaii-Saab Tanios S. , Goldberg Richard M.
Published: February 2017

415

Background: It has been argued that universal screening for LS should be performed on all patients (pts) diagnosed with CRC because screening LS pts and their relatives can detect early cancers and improve outcomes. This approach is being adopted by many comprehensive cancer centers around the country. The Ohio State University (OSU) began screening for deficient mismatch repair (dMMR) proteins by immunohistochemistry (IHC) on all CRC cases in 2006. This retrospective study aims to assess whether universal screening with IHC followed by conclusive testing (BRAF mutation in setting of MLH1 deficiency, and/or gene sequencing) affects pts survival. Methods: All CRC pts diagnosed at OSU from 3/2006-6/2012 with dMMR testing per IHC were included, and their charts were reviewed. Chi-square test was used to for categorical parameters, t-test was used for continuous variables, and the log-rank test for overall survival (OS) to compare the difference between pts with full conclusive testing vs those without full testing. Patients who expired within 4 weeks of diagnosis were excluded (n=10) from the OS analysis. Results: One hundred and twenty-two tumors (15.7% of 777 tumors tested) had dMMR by IHC during the study period. Fifty-one pts went on to have conclusive testing done; thirteen patients (25.5%) were diagnosed with LS, 29 patients (56.9%) had MLH1-hypermethylated tumors, and 9 patients (17.6%) were not found to have MMR mutations on gene sequencing. In an OS analysis, patients undergoing conclusive testing had significantly longer survival as compared to those with abnormal IHC without further testing (median OS not reached vs. 38 months, p=0.04). The difference was similar and remained marginally significant (p= 0.04-0.09) after correcting for age, stage and testing date using different models. Conclusions: Patients who had conclusive testing after initial abnormal universal screening with IHC had significantly longer OS compared to pts who had abnormal IHC without follow-up testing. It is possible that ascertainment bias and pts compliance influenced survival so larger prospective studies that document stage and treatment are needed to determine if increased surveillance in the setting of a LS diagnosis leads to better OS.
Pretreatment rectal tumors quantitative dynamic contrast-enhanced MRI characterization and predictability of outcome: Pilot study.
Authors: Shabana Wael , Saif Sameh , Cron Greg , Thornhill Rebecca , Koudrina Natalia , Koudrina Anna , Jonker Derek J.
Published: February 2017

416

Background: Treatment of rectal cancer is currently a one-size-fits-all approach. Unfortunately, some rectal tumors do not respond well to treatment and/or give rise to latent metastases. Therefore, a need exists for biomarkers which can better characterize tumor aggressiveness and help guide treatment decisions. We investigated the feasibility and performance of dynamic contrast-enhanced (DCE) MRI (performed pre-treatment) as a potential biomarker to predict rectal cancer response to treatment. Methods: 47 patients with rectal masses underwent DCE-MRI at 3T pre-treatment. DCE-MRI was performed with 3D FLASH (TR/TE/flip 6ms/1.6 ms/25 deg). Gadolinium concentration-versus-time in tissue was estimated with the aid of a variable-flip-angle T1 mapping procedure performed pre-DCE. The arterial input function was estimated by measuring phase-versus-time in major arteries. Tracer kinetic modeling was used to obtain maps of the quantitative perfusion parameters Ktrans and Kep. Treatment outcome was categorized as successful (regression) or unsuccessful (progression, stable, or recurrence). We also dichotomized latent metastases as absent or present. The pathology outcome of the lesions was categorized as cancerous or non-cancerous. A support vector machine classifier was constructed from the perfusion parameters, and the accuracy of each classifier was determined by 10-fold cross validation. Results: Clinical characteristics were 31 successful outcomes, 8 unsuccessful; 25 with latent metastases absent, 5 with latent metastases present; 40 cancerous, 7 non-cancerous. The accuracies of quantitative DCE-MRI parameters for predicting treatment outcome, latent metastases, and pathology outcome were 78%, 83%, and 84%, respectively. Conclusions: Pre-treatment DCE-MRI appears to be a useful predictor of rectal tumor malignancy, treatment outcome, and latent metastases. Perfusion parameters have very promising potential to predict rectal cancer outcome and may serve as an added tool for rectal cancer treatment planning.