4-Hydroxyacetophenone modulates the actomyosin cytoskeleton to reduce metastasis.

Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Facilities that service economically advantaged neighborhoods perform surgical metastasectomy more often for patients with colorectal liver metastases.

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.

For Gastroesophageal Junction Cancers, Does an "Esophageal" or "Gastric" Surgical Approach Offer Better Perioperative and Oncologic Outcomes?

BACKGROUND: The optimal surgical approach to the resection of gastoesophageal junction cancer is unknown. A comprehensive literature search was conducted to further compare the esophageal and gastric approaches to gastroesophageal junction cancer. METHODS: A systematic review of the literature from January 1990 to May 2018 was performed to determine whether an esophageal or gastric surgical approach offers better perioperative and oncologic outcomes. RESULTS: A total of 179 abstracts were identified and after excluding publications for non-English language, primary focus on neoadjuvant and/or adjuvant treatment, lack of comparison of surgical approaches or not addressing morbidity, mortality, or survival-related outcomes, a total of 14 nonrandomized, comparative studies were reviewed in detail. CONCLUSIONS: The proximal and distant extent of the tumor based on Siewert type classification greatly influences choice of operation. Overall survival rates and surgical outcomes are comparable, and surgical approach should be dictated by patient factors.

Virtual Surgical Fellowship Recruitment During COVID-19 and Its Implications for Resident/Fellow Recruitment in the Future.

BACKGROUND: The COVID-19 pandemic has overlapped with the scheduled interview periods of over 20 surgical subspecialty fellowships, including the Complex General Surgical Oncology (CGSO) fellowships in the National Resident Matching Program and the Society of Surgical Oncology's Breast Surgical Oncology fellowships. We outline the successful implementation of and processes behind a virtual interview day for CGSO fellowship recruitment after the start of the pandemic. METHODS: The virtual CGSO fellowship interview process at the University of Chicago Medicine and NorthShore University Health System was outlined and implemented. Separate voluntary, anonymous online secure feedback surveys were email distributed to interview applicants and faculty interviewers after the interview day concluded. RESULTS: Sixteen of 20 interview applicants (80.0%) and 12 of 13 faculty interviewers (92.3%) completed their respective feedback surveys. Seventy-five percent (12/16) of applicants and all faculty respondents (12/12) stated the interview process was 'very seamless' or 'seamless'. Applicants and faculty highlighted decreased cost, time savings, and increased efficiency as some of the benefits to virtual interviewing. CONCLUSIONS: Current circumstances related to the COVID-19 pandemic require fellowship programs to adapt and conduct virtual interviews. Our report describes the successful implementation of a virtual interview process. This report describes the technical steps and pitfalls of organizing such an interview and provides insights into the experience of the interviewer and interviewee.

Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer: Follow-up Results of the ACOSOG Z6051 Randomized Controlled Trial.

OBJECTIVE: To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection. BACKGROUND: This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051. METHODS: The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months. RESULTS: The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4-84.9) and OPEN 83.2% (95% CI 78.3-88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21-2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85-3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40-3.79); positive distal margin (HR 2.53, 95% CI 1.30-3.77). CONCLUSION: Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

Comparative Age-Based Prospective Multi-Institutional Observations of 12,367 Patients Enrolled to the American College of Surgeons Oncology Group (ACOSOG) Z901101 Trials (Alliance).

BACKGROUND: The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients. METHODS: This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts. RESULTS: The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3-1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7-1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30-0.70; p < 0.0001). CONCLUSION: Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.

Perioperative Gemcitabine + Erlotinib Plus Pancreaticoduodenectomy for Resectable Pancreatic Adenocarcinoma: ACOSOG Z5041 (Alliance) Phase II Trial.

BACKGROUND: There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC. METHODS: A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed. RESULTS: Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31-50), with a median OS of 21.3 months (95% CI 17.2-25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41-63), with a median OS of 25.4 months (95% CI 21.8-29.6). CONCLUSIONS: For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.

Steps to Getting Your Manuscript Published in a High-Quality Medical Journal.

Publication of your research represents the culmination of your scientific activities. The key to getting manuscripts accepted is to make them understandable and informative so that your colleagues will read and benefit from them. We describe key criteria for acceptance of manuscripts and outline a multi-step process for writing the manuscript. The likelihood that a manuscript will be accepted by a major journal is significantly increased if the manuscript is written in polished and fluent scientific English. Although scientific quality is the most important consideration, clear and concise writing often makes the difference between acceptance and rejection. As with any skill, efficient writing of high-quality manuscripts comes with experience and repetition. It is very uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful and respectful responses to the journal reviewers' comments are critical. Success in scientific writing, as in surgery, is dependent on effort, repetition, and commitment. The transfer of knowledge through a well-written publication in a high-quality medical journal will have an impact not only in your own institution and country, but also throughout the world.

In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.

Interdisciplinary Oncology Education: a National Survey of Trainees and Program Directors in the United States.

Oncologists must have a strong understanding of collaborating specialties in order to deliver optimal cancer care. The objective of this study was to quantify current interdisciplinary oncology education among oncology training programs across the USA, identify effective teaching modalities, and assess communication skills training. Web-based surveys were sent to oncology trainees and program directors (PDs) across the USA on April 1, 2013 and October 8, 2013, respectively. Question responses were Yes/No, five-point Likert scales (1 = not at all, 2 = somewhat, 3 = moderately, 4 = quite, 5 = extremely), or free response. Respondents included the following (trainees/PDs): 254/55 medical oncology, 160/42 surgical oncology, 102/24 radiation oncology, and 41/20 hospice and palliative medicine (HPM). Trainees consistently reported lower rates of interdisciplinary education for each specialty compared with PDs as follows: medical oncology 57 vs. 77% (p < 0.01), surgical oncology 30 vs. 44% (p < 0.01), radiation oncology 70 vs. 89% (p < 0.01), geriatric oncology 19 vs. 30% (p < 0.01), and HPM 55 vs. 74% (p < 0.01). The predominant teaching method used (lectures vs. rotations vs. tumor board attendance vs. workshop vs. other) varied according to which discipline was being taught. The usefulness of each teaching method was rated statistically different by trainees for learning about select disciplines. Furthermore, statistically significant differences were found between PDs and trainees for the perceived usefulness of several teaching modalities. This study highlights a deficiency of interdisciplinary education among oncology training programs in the USA. Efforts to increase interdisciplinary education opportunities during training may ultimately translate into improved collaboration and quality of cancer care.

Doubling of 30-Day Mortality by 90 Days After Esophagectomy: A Critical Measure of Outcomes for Quality Improvement.

OBJECTIVES: Our objectives were to (1) compare 30- and 90-day mortality rates after esophagectomy, (2) compare drivers of 30- and 90-day mortality, and (3) examine whether 90-day mortality affects hospital rankings. BACKGROUND: Operative mortality has traditionally been assessed at 30 days. Ninety-day mortality has been suggested as a more appropriate indicator of quality, particularly after complex cancer surgery. METHODS: Esophagectomies for nonmetastatic esophageal cancer patients diagnosed between 2007 and 2011 were identified in the National Cancer Data Base. Mortality rates were examined by patient demographics, tumor characteristics, and hospital procedural volume. Risk-adjusted hierarchical logistic regression models examined hospital performance for mortality. RESULTS: A total of 15,796 esophagectomy patients at 977 hospitals were available for analysis. Ninety-day overall mortality was more than double the 30-day mortality (8.9% vs 4.2%; P < 0.0001). In multivariate analysis, while both 30- and 90-day mortality were associated with patient factors such as age, comorbidity, and hospital volume, only 90-day mortality was influenced by tumor- and management-related variables such as stage, tumor location, and receipt of neoadjuvant therapy. Hospital performance was examined as top 10%, middle 10% to 90%, and lowest 10% as ranked using risk-adjusted odds of mortality. There was moderate correlation between ranking based on 30- and 90-day mortality [weighted κ = 0.45 (95% confidence interval, 0.39-0.52)]. Compared with 30-day mortality rankings, nearly 20% of hospitals changed their ranking category when 90-day mortality rankings were used. CONCLUSIONS: Examination of 90-day mortality after esophagectomy reflects cancer patient management decisions and may provide actionable targets for quality improvement.

Consensus Conference on North American Training in Hepatopancreaticobiliary Surgery: A Review of the Conference and Presentation of Consensus Statements.

The findings and recommendations of the North American Consensus Conference on Training in HPB Surgery held October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), Americas Hepatopancreaticobiliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways-HPB, Surgical Oncology, and Solid Organ Transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and non-operative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems, and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force comprised of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.Copyright © 2016 The American Society of Transplantation, the American Society of Transplant Surgeons, and the Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by The American Society of Transplantation, the American Society of Transplant Surgeons, or the Society of Surgical Oncology.

Adjuvant Therapy Improves Survival for T2N0 Gastric Cancer Patients with Sub-optimal Lymphadenectomy.

BACKGROUND: The benefit of adjuvant therapy following resection of early stage, node-negative gastric adenocarcinoma following a margin negative (R0) resection is unclear. METHODS: The National Cancer Data Base was used to identify patients with a T2N0 gastric adenocarcinoma (tumor invasion into the muscularis propria) who underwent R0 resection. Patients treated with neoadjuvant therapy and those for whom lymph node count was unavailable were excluded from the analysis. Kaplan-Meier and Cox regression were used to evaluate differences in and predictors of overall survival. RESULTS: A total of 1687 patients underwent R0 resection for T2N0 gastric adenocarcinoma between 2003-2011. Adjuvant chemotherapy treatment was administered to 7.1 and 14.1 % received adjuvant chemoradiation; 65.4 % had <15 lymph nodes examined. Multivariate Cox regression identified higher Charlson score, <15 lymph nodes examined, higher tumor grade, and tumor location in the cardia as factors associated with significantly decreased overall survival. With a median follow-up of 36 months, the 5-year overall survival was 71 % for patients with ≥15 lymph nodes examined and 53 % for those with <15 lymph nodes (p < 0.001). In patients who had <15 lymph nodes examined, there was an overall survival benefit for adjuvant chemoradiation (hazard ratio 0.71, p = 0.043). In patients with ≥15 lymph nodes examined, no survival benefit for adjuvant therapy was identified (p > 0.74). CONCLUSIONS: Adequate lymph node dissection and pathologic staging is critical in directing optimal treatment of patients with early gastric cancer. Understaging as a result of suboptimal lymphadenectomy may explain the perceived benefit of adjuvant chemoradiation after an R0 resection for T2N0 gastric cancer.

Defining the Benefit of Adjuvant Therapy Following Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is rare but is increasing in incidence. While hepatectomy can be curative, the benefit of adjuvant therapy (AT) remains unclear. We utilized the National Cancer Data Base (NCDB) to isolate predictors of overall survival, describe the national pattern of AT administration, and identify characteristics of patients who experience a survival benefit from AT following resection for ICC. METHODS: Patients who were diagnosed with ICC between 1998 and 2006 and underwent surgical resection were identified through the NCDB. Kaplan-Meier and Cox regression analyses evaluated differences in overall survival between patients who received AT and those who did not. RESULTS: Overall, 638 patients who underwent surgery for ICC were identified. Multivariate Cox regression analysis identified positive lymph nodes, unexamined lymph nodes, positive margins, and lack of AT as predictors of decreased overall survival; 28.1 % of patients had positive margins while 20.1 % had positive nodes. These patients, as well as those who were younger and had fewer co-morbid conditions, were most likely to receive AT. After adjusting for other prognostic variables, patients were found to significantly benefit from AT if they had positive lymph nodes [chemotherapy: hazard ratio (HR) 0.54, p = 0.0365; chemoradiation: HR 0.50, p = 0.005] or positive margins (chemotherapy: HR 0.44, p = 0.0016; chemoradiation: HR 0.57, p = 0.0039). CONCLUSIONS: Positive lymph nodes and positive margins were associated with poor survival after resection for ICC. After controlling for other prognostic factors, AT was associated with significant survival benefits among patients with positive nodes or positive margins.

Research gaps in pancreatic cancer research and comparative effectiveness research methodologies.

Despite advances in cancer care, pancreatic adenocarcinoma remains one of the most lethal tumors. Most patients with pancreatic cancer are diagnosed with late stage disease, and approximately 6 % of patients are alive 5 years after diagnosis. Of the 10-20 % of patients who are candidates for resection and multi-modality therapy, most will succumb to the disease with 5-year survival rates only reaching approximately 25 % (Lim et al. in Annals of surgery 237(1):74-85, 2003 [1]; Trede et al. in Annals of surgery 211(4):447-458, 1990 [2]; Crist et al. in Annals of surgery 206(3):358-365, 1987 [3]). Clearly, there is a need to improve the management of this disease. To identify gaps in research and formulate strategies to address these issues, we designed a framework to encompass the scope of research for pancreatic cancer. In this chapter, we will examine each topic heading within this framework for gaps in knowledge and present research strategies focusing on diverse comparative effectiveness research (CER) methodologies to address the identified gaps.