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Significant advances in systemic chemotherapy and surgical techniques have allowed a subset of patients with stage IV colorectal cancer to be suitable candidates for multimodality therapy with curative intent. Care of these patients requires multidisciplinary coordination, close monitoring of disease response, and individualized treatment plan. This review will discuss considerations for treatment planning and sequencing in patients with symptomatic and asymptomatic primary colon cancer in the setting of potentially resectable liver metastases.

Background Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. Methods An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. Results In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Conclusions Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare autosomal recessive predisposition to colorectal polyposis and other malignancies, often childhood-onset, that is caused by biallelic inheritance of mutations in the same mismatch repair gene. Here, we describe a patient with a clinical diagnosis of CMMRD based on colorectal polyposis and young-onset endometrial cancer who was identified to have two alterations in trans in PMS2: one known pathogenic mutation (c.1831insA; p.Ile611Asnfs*2) and one novel variant of uncertain significance (c.505C>G; p.Arg169Glu), a missense alteration. We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity, PMS2 c.505C>G likely has functional consequences that contributes to our patient's phenotype based on the patient's clinical presentation, tumor studies, and bioinformatics analysis.

Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane.The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015.Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %.Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

Patients with germline DNA mismatch repair deficiency (dMMR) have an increased risk of gastric cancer. From our institutional database, we identified 12 patients with germline dMMR gastric cancer. Ten patients (83%) underwent surgical resection, with a 5-year overall survival rate of 88%. None of the three patients who received preoperative therapy and five patients with recurrent or metastatic disease experienced a significant response to 5-fluorouracil-based chemotherapy.

Patients diagnosed with germline mutations in MMR genes (Lynch Syndrome, LS) have up to 70-80% lifetime risk of colorectal cancer. Therefore, this high-risk population has the potential to benefit from effective chemopreventive strategies. Naproxen is an NSAID widely used for pain treatment with an excellent safety profile that has demonstrated to be more efficacious preventing colorectal cancer compared to aspirin in vivo using an intestinal tissue-specific mouse model of LS (VC-Msh2-LoxP). The ‘Naproxen trial' was designed to evaluate the modulation of PGE2 levels in colorectal mucosa, evaluate safety and tolerability, and discover novel molecular pathways involved in the chemopreventive activity of naproxen in LS patients. Methods: Participants were randomized to naproxen 440 mg (HD), 220 mg (LD) and placebo by mouth daily for 6 months. Modulation of prostaglandin levels, number of adverse events (AEs) observed in each treatment arm and gene expression profiles by next-generation sequencing (mRNAseq) in normal colorectal mucosa of LS patients after 6 months of intervention were examined. Results: Eighty participants diagnosed with LS were randomized, 25 participants to HD, 27 to LD, and 28 to placebo. From these patients, 54 were considered evaluable per-protocol analysis: 16 in the HD group, 15 in the LD and 23 in placebo. The level of prostaglandin E2 in the colorectal mucosa decreased significantly after treatment with both LD and HD naproxen when compared to placebo (-91.2%±14.1, -93.6%±7.9, and 23.8%±108.4, P-value Citation Format: Laura Reyes Uribe, Wenhui Wu, Ozkan Gelincik, Prashant V. Bommi, Alejandro Francisco-Cruz, Luisa M. Solis, Patrick M. Lynch, Ramona Lim, Elena Stoffel, Priyanka Kanth, N. Jewel Samadder, Maureen E. Mork, Melissa W. Taggart, Ginger L. Milne, Lawrence J. Marnett, Lana Vornik, Diane D. Liu, Maria Revuelta, Kyle Chang, Y. Nancy You, Levy Kopelovich, Ignacio I. Wistuba, J. Jack Lee, Shizuko Sei, Robert H. Shoemaker, Eva Szabo, Ellen Richmond, Asad Umar, Marjorie Perloff, Powell H. Brown, Steven M. Lipkin, Eduardo Vilar. Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT111.

Background: Current treatment for locally advanced rectal cancer (LARC) includes multimodality therapy in the neoadjuvant and adjuvant settings. Response to neoadjuvant therapy (NT) is prognostic of long-term outcomes. While long-course chemoradiation (CRT) had been the traditional NT regimen, novel regimens adding systemic therapy and/or eliminating radiation have been introduced. We examined if circulating tumor cells provide prognostic information independent of the specific treatment regimen utilized. Specifically, we aimed to define the significance of CTC-defined minimal residual disease (MRD) in LARC. Methods: A prospective longitudinal protocol enrolled LARC patients (N=100; clinical stage II=4; stage III=96) undergoing NT. Peripheral blood was collected at baseline (t1, treatment-naive), after NT (t2, intraoperatively before tumor manipulation), after resection (t3, 2-8 weeks postoperatively), and after completion of adjuvant therapy (t4, 2-12 weeks after completion). CTC was enumerated by the CellSearch® platform within 72 hours of collection. Patients were followed for disease-free survival (DFS). Results: At t1, CTCs were detected in 28/90 (31.1%) patients with available samples with a median CTC count of 1.5 [IQR: 1.0, 2.75]. NT consisted of long-course pelvic CRT (65%), extended NT with systemic chemotherapy and long- or short-course pelvic CRT (22%), and a radiation-sparing regimen with systemic chemotherapy only (13%). At t2, CTCs were detected in 34/75 (45.3%) patients with a median CTC count of 1 [IQR: 1, 1]. Type of NAT did not correlate with CTC positivity (p=0.637). Ten (9.4%) patients declined surgery, while cPR occurred in 12/93 (12.9%) surgical patients. Postoperatively (t3), CTC was detected in 12/47 (25.5%) patients, with a median count of 1.5 (IQR: 1.0-3.0). After completing adjuvant chemotherapy (t4), only 3/29 (10.3%) patients had detectable CTC. With a median follow-up of 47.50 months from diagnosis for the entire cohort, CTC positivity at t4 significantly stratified DFS (p=0.035). Conclusions: One third of locally advanced RC patients harbored detectable CTCs at baseline. CTC detection after completion of curative-intent multimodality therapy (i.e., MRD) correlated with long-term DFS. Citation Format: Lucas Lee, Carol Hall, Antony Lucci, Brian Bednarski, Miguel Rodriguez-Bigas, George Chang, Y. Nancy You. Circulating tumor cell-defined minimal residual disease in locally advanced rectal cancer treated with multimodality therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A47.

4012 Background: Identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) other than for N1c designation. The aim of this study was to determine the prognostic impact, beyond AJCC N1c designation, of TD among primary CRC patients. Methods: Patients with stage 1 to 3 primary CRC diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Cancer specific survival (CSS) stratified by TDs and nodal status was calculated, and Kaplan-Meier method and multivariable COX proportional hazards regression analyses were performed. Results: A total of 74,494 patients with primary CRC were identified. Mean age was 66.4 (SD+/-13.2) years, 36,988 (49.7%) were female and 40,651 (54.6%) were right-sided. TDs were present in 4,481 patients (6.0%) and 26,603 (35.7%) had lymph node metastases. The presence of TDs were significantly associated with adverse tumor characteristics including advanced pathological stage, nodal and metastasis status, higher grade and perineural invasion. Incorporating TDs into each nodal status was independently associated with worse CSS and supported reclassification of nodal status to incorporate TDs following multivariable regression analysis as outlined in the table. Following multivariable regression analysis, the proposed AJCC nodal reclassification incorporating TDs, in combination with tumor stage was a strong predictor of CSS, and also represents a new summary staging. Conclusions: TDs are an independent predictor of worse outcome in CRC. The presence of TDs have distinctly different CSS and these data support modification of the current N classification. This study proposes a reclassification of the AJCC system for CRC to incorporate TDs and informs an updated node and summary stage. [Table: see text]

64 Background: Patients with sporadic young-onset colorectal cancer (CRC) are postulated to have a more biologically active colorectum prone to malignant transformation earlier in life. It is unknown whether there is elevated risk for metachronous colorectal pathology after the index cancer. We aimed to define this risk, to inform their post-resection endoscopic surveillance. Methods: Consecutive CRC patients (aged 18-50, n = 728) were prospectively followed after surgical resection between 2009 and 2017. Patients presenting with hereditary CRC, recurrent disease, or without endoscopy follow-up were excluded. All endoscopy records were subjected to natural language processing and further reviewed. Metachronous colorectal pathology of interest included: high-risk adenoma (≥1cm in size, > 3 in number, or tubulovillious/high-grade dysplasia histology), second CRC, and endoscopically detectable local recurrence. Results: During a 48-month (median) follow-up, 457 patients underwent 1,192 person-years of colonoscopic follow-up. The median age at CRC diagnosis was 44 years. Disease arose from the proximal colon in 9.4%, distal colon in 23.0% and rectum in 67.6%, and was stages I/II in 191 (41.8%), III in 185 (40.4%), and IV in 81 (17.7%). The majority (95.8%) underwent segmental resection, while the remainder had extended resections for synchronous pathology not amendable to preoperative endoscopic clearance. The overall incidence of metachronous pathology was 32 per 1000 person-years: 31 patients developed high-risk adenomas (6.8%), 1 had a second CRC (0.2%), and 7 had luminal recurrences (1.5%). The median time to metachronous pathology was 13.9 (IQR: 11.8-33.1) months, with 21 (53.8%) detected between 12 and 48 months post-resection. Conclusions: For young-onset CRC survivors, the incidence of metachronous colorectal pathology was 32 per 1000 person-years of follow-up. Given the time pattern of detection, adding an interval colonoscopy between the current recommended post-resection surveillance at 12 and 48 months may be beneficial. [Table: see text]

Robotic surgery is increasingly performed for low rectal cancer.1 A redundant sigmoid colon makes retraction and pelvic dissection challenging. We present a ‘pelvis-first’ approach to robotic proctectomy where pelvic dissection occurs prior to colonic mobilization. A 26-year-old woman was diagnosed with a clinical T3N1 rectal adenocarcinoma at 3 cm from the anal verge. The patient had Lynch syndrome, with a germline mutation in the PMS2 gene. A near-complete clinical response was observed after neoadjuvant chemoradiation (NCRT), and the patient wished to delay surgery and permanent colostomy. Additional FOLFOX was administered and led to a complete clinical response. After 2.5 months of watchful delay of surgery, the tumor regrew, and the patient then underwent robotic abdominoperineal resection (APR). Initial exploration revealed a highly redundant sigmoid colon. A pelvis-first approach was undertaken. The colon was left tethered and outside of the pelvis during the pelvic dissection. The levator ani was divided transabdominally. Vascular dissection and left colon mobilization were completed after pelvic dissection.2 The specimen was removed transanally, obviating the need for abdominal incision. An end colostomy was created laparoscopically, and the perineum was closed primarily after omental flap. The patient recovered without complications. The ‘pelvis-first’ approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5

Lynch syndrome (LS), a hereditary cancer syndrome, accounts for approximately 3% of colorectal cancers (CRC). Positive health behaviors and surveillance are preventive strategies, but research on whether recommended behavioral guidelines are followed by individuals with LS is limited. Additional health education and promotion could be beneficial to the improved survivorship of CRC survivors. Explore health and lifestyle behaviors in CRC survivors with and without LS. We conducted a case-control study of CRC survivors with and without LS using a mailed questionnaire. Recruitment was conducted via patient registries at The University of Texas MD Anderson Cancer Center (cases n = 33; controls n = 75) and through social media (cases n = 42). CRC survivors with and without LS in our study had substantially lower smoking prevalence (5.5% and 2.7%) compared to national prevalence (18.0%). However, they had higher levels of alcohol consumption (36.8% and 10.3% for male and female LS survivors, respectively, and 35.8% and 22.0% for male and female sporadic survivors, respectively) compared to national prevalence of 13.88% for males and 6.02% for females. Both groups of CRC survivors participate in negative health behaviors that impact survivorship. More research is needed to examine the relationship between personal engagement in preventive behaviors and patient–provider relationships to improve health behaviors and explore strategies for intervention. Additionally, better health education and lifestyle change recommendations would promote and reinforce positive health outcomes in the CRC population and especially in LS survivors.

Purpose Adolescents and young adults with colorectal cancer (CRC) have attracted recent attention, with a hereditary syndrome identified in one-third of patients diagnosed ≤ 35. We aimed to study this population to determine if a CRC-specific gene panel increased the yield of testing. Methods Patients with CRC ≤ 35 evaluated from 05/2014–11/2017 were identified from the genetic counseling database. Records were reviewed for personal/family history and genetic counseling outcomes. Results One hundred forty-three patients with CRC ≤ 35 were included. One hundred four (72.7%) underwent CRC panel testing. Thirty-nine (27.2%) had syndrome-directed testing, declined, or were lost to follow-up. Forty-two patients had a genetic syndrome (29.4%). Twenty-four of the 42 hereditary patients (57.1%) were identified via syndrome-directed testing. Mutations identified via panel testing were consistent with patient personal/family history. Thirty-three patients had at least one variant of uncertain significance. Conclusion Hereditary syndromes were identified in 29.4% of patients. Panel testing in patients without a phenotype did not increase diagnostic yield, but identified variants in one-third. Disease-specific panel testing is of low yield in young patients without a suggestive personal/family history. Testing broader panels may increase the yield of mutation pick-up in this population, although at the expense of identifying variants.

Because of the low incidence of nongastrointestinal stromal tumor (non-GIST) spindle cell sarcomas of the colon or rectum, the clinical behavior and ideal surgical treatment of these tumors and patient outcomes are poorly defined. The purpose of this study was to characterize these tumors and to determine the best surgical approach. We identified 1056 patients with non-GIST spindle cell sarcomas of the colon or rectum (1998-2010) in the National Cancer Database and collected data for each patient that included patient and tumor characteristics, tumor site (colon vs rectum), surgery type, and outcomes. The median overall survival was significantly longer in patients with rectal tumors than in those with colon tumors (P0.01). Patients with colon tumors who underwent anatomic surgical resection showed a trend toward longer median survival than those with no surgical treatment [hazard ratio (HR), 1.94; P = 0.09] or who underwent local excision (HR, 1.74; P = 0.09). Patients with rectal tumors did not benefit from anatomic surgical resection, but there was a trend favoring local excision (HR, 0.55; P = 0.06). Local sphincter-sparing procedures should be considered for rectal non-GIST tumors whenever technically feasible.

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs.

Background: Improving the quality of health care is a national priority, and providing patient-centered care is one of the 6 key areas for quality improvement. In the setting of patients with young-onset colorectal cancer (CRC), appropriate genetic workup and testing for potential underlying inherited CRC syndromes is fundamental to patient-centered care. Lynch syndrome (LS) is the most common of these inherited syndromes, and current recommendations from the NCCN and other professional societies advocate universal screening for LS among young patients with CRC. However, practical implementation of these guidelines often falls short. Methods: We conducted a prospective quality improvement intervention trial to optimize universal screening for LS in young (age

Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use.We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age ≥ 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses.Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use.PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care.

BACKGROUND: Ileostomies are a routine part of the care of rectal cancer patients, but are associated with significant risk for dehydration, readmission, and acute kidney injury. Telemedicine has proven beneficial in decreasing readmission in chronic medical illnesses, but its utility in ileostomy patients is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility of televideoconferencing in the assessment of ileostomy output. DESIGN: An institutional review board-approved, prospective clinical trial was conducted at a single institution from November, 2014-December, 2015. SETTINGS: The study was conducted in a single, large academic medical center. PATIENTS: Patients >18 years of age undergoing surgery with plans for ileostomy were eligible. INTERVENTIONS: Televideoconference assessments of ileostomy output and the need for medical intervention were conducted during the postoperative stay and compared to in-person assessment. MAIN OUTCOME MEASURES: The primary endpoint of the trial was feasibility of using teleconferencing to assess the need for medical intervention, defined as 90% agreement between telemedicine and in-person assessments. Secondary endpoints included patient/provider satisfaction and correlative studies examined dehydration events and readmission. RESULTS: Twenty-seven patients underwent 44 teleconferencing assessments of ileostomy output. Compared to in-person treatment decisions, there was a 95% match (95% CI: 85%, 99%). The readmission rate for the study participants was 31% and 18% experienced dehydration events. Both patients and faculty responded favorably to surveys regarding the use of telemedicine in the perioperative period. LIMITATIONS: The study is limited by its in-hospital use of technology and small sample size. CONCLUSIONS: Televideoconference evaluation is a feasible, reliable means of assessing ileostomy output with high patient and physician acceptance. Our pilot study provides rationale for further study in the post-discharge setting for patients with ileostomies. The incorporation of televideoconference assessment within a teledischarge program may enable early intervention to improve patient outcomes.

The goals of rectal cancer treatment include optimal local control, maximal overall survival, as well as the best preservation of pre-therapy function and well-being of the patient. As illustrated in the remainder of this textbook, significant efforts have been devoted to developing surgical and multimodality regimens to achieve these goals. Stage-specific treatments include surgery alone (local excision or radical resection) for early-stage rectal cancer (American Joint Commission on Cancer [AJCC] stage I) and multimodality therapy with radical surgery, chemotherapy, and/or pelvic radiation for locally advanced (AJCC stages II and III) and metastatic (AJCC stage IV) rectal cancer. With this current multimodality strategy, the overall 5-year survival for locally advanced rectal cancer is 65–75%, with local recurrence rates in the range of 5–10% [1, 2, 3, 4, 5, 6].

Despite the availability of effective colorectal cancer (CRC) screening strategies, up to 10% of CRC patients present with obstructive symptoms as the first sign of disease. For patients with acute or subacute malignant obstruction that requires urgent intervention, treatment options include endoscopic stenting as a bridge to surgery, one-stage surgical resection and anastomosis, or diverting ostomy which may or may not be followed by later tumor resection and stoma closure. However, to date, there is no consensus guideline for the optimal approach to manage malignant colorectal obstruction. This article aims to illustrate clinical scenarios in palliative, curative, and potentially curative settings, and delineate the key factors to be considered when making an individualized decision in order to determine the optimal treatment.

The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches. Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999–2003, 2004–2008, and 2009–2014). Overall, 150 (56.0%) patients underwent primary tumor resection first (‘classic’ approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases (‘combined’ approach), and 74 (27.6%) patients underwent liver resection first (‘reversed’ approach). Patients who underwent the reversed approach had more liver metastases (3 [2–5]) at presentation (vs. 1 [1–2.5] in the combined approach or 1 [1–3] in the classic approach; p

This cohort study examines the behavior and outcomes of deficient DNA mismatch repair in patients at elevated risk for malignant neoplasms, including pancreatic ductal adenocarcinoma.

Introduction Definitive treatment of localised colorectal cancer involves surgical resection of the primary tumour. Short-stay colectomies (eg, 23-hours) would have important implications for optimising the efficiency of inpatient care with reduced resource utilisation while improving the overall recovery experience with earlier return to normalcy. It could permit surgical treatment of colorectal cancer in a wider variety of settings, including hospital-based ambulatory surgery environments. While a few studies have shown that discharge within the first 24 hours after minimally invasive colectomy is possible, the safety, feasibility and patient acceptability of a protocol for short-stay colectomy for colorectal cancer have not previously been evaluated in a prospective randomised study. Moreover, given the potential for some patients to experience a delay in recovery of bowel function after colectomy, close outpatient monitoring may be necessary to ensure safe implementation. Methods and analysis In order to address this gap, we propose a prospective randomised trial of accelerated enhanced Recovery following Minimally Invasive colorectal cancer surgery (RecoverMI) that leverages the combination of minimally invasive surgery with enhanced recovery protocols and early coordinated outpatient remote televideo conferencing technology (TeleRecovery) to improve postoperative patien-provider communication, enhance postoperative treatment navigation and optimise postdischarge care. We hypothesise that RecoverMI can be safely incorporated into multidisciplinary practice to improve patient outcomes and reduce the overall 30-day duration of hospitalisation while preserving the quality of the patient experience. Ethics and dissemination RecoverMI has received institutional review board approval and funding from the American Society of Colorectal Surgeons (ASCRS; LPG103). Results from RecoverMI will be published in a peer-reviewed publication and be used to inform a multisite trial. Trial registration number NCT02613728; Pre-results.

Purpose After preoperative chemoradiotherapy followed by total mesorectal excision for locally advanced rectal cancer, patients who experience local or systemic relapse of disease may be eligible for curative salvage surgery, but the benefit of this surgery has not been fully investigated. The purpose of this study was to characterize recurrence patterns and investigate the impact of salvage surgery on survival in patients with rectal cancer after receiving multidisciplinary treatment. Patients and Methods Patients with locally advanced (cT3-4 or cN+) rectal cancer who were treated with preoperative chemoradiotherapy followed by total mesorectal excision at our institution during 1993 to 2008 were identified. We examined patterns of recurrence location, time to recurrence, treatment factors, and survival. Results A total of 735 patients were included. Tumors were mostly midrectal to lower rectal cancer, with a median distance from the anal verge of 5.0 cm. The most common recurrence site was the lung followed by the liver. Median time to recurrence was shorter in liver-only recurrence (11.2 months) than in lung-only recurrence (18.2 months) or locoregional-only recurrence (24.7 months; P = .001). Salvage surgery was performed in 57% of patients with single-site recurrence and was associated with longer survival after recurrence in patients with lung-only and liver-only recurrence ( P < .001) but not in those with locoregional-only recurrence ( P = .353). Conclusion We found a predilection for lung recurrence in patients with rectal cancer after multidisciplinary treatment. Salvage surgery was associated with prolonged survival in patients with lung-only and liver-only recurrence, but not in those with locoregional recurrence, which demonstrates a need for careful consideration of the indications for resection.

Surveillance after colorectal cancer (CRC) treatment is routine, but intensive follow-up may offer little-to-no overall survival benefit. Given the growing population of CRC survivors, we aimed to systematically evaluate the literature for the patient perspective on two questions: (1) How do CRC patients perceive routine surveillance following curative treatment and what do they expect to gain from their surveillance testing or visits? (2) Which providers (specialists, nursing, primary care) are preferred by CRC survivors to guide post-treatment surveillance? Systematic searches of PubMed MEDLINE, Embase, the CENTRAL Register of Controlled Trials, CINAHL, and PsycINFO were conducted. Studies were screened for inclusion by two reviewers, with discrepancies adjudicated by a third reviewer. Data were abstracted and evaluated utilizing validated reporting tools (CONSORT, STROBE, CASP) appropriate to study design. Citations (3691) were screened, 91 full-text articles reviewed, and 23 studies included in the final review: 15 quantitative and 8 qualitative. Overall, 12 studies indicated CRC patients perceive routine surveillance positively, expecting to gain reassurance of continued disease suppression. Negative perceptions described in six studies included anxiety and dissatisfaction related to quality of life or psychosocial issues during follow-up. Although 5 studies supported specialist-led care, 9 studies indicated patient willingness to have follow-up with non-specialist providers (primary care or nursing). Patients’ perceptions of follow-up after CRC are predominantly positive, although unmet needs included psychosocial support and quality of life. Survivors perceived follow-up as reassuring, however, surveillance care should be more informative and focused on survivor-specific needs.

// Cathy Eng 1 , George J. Chang 2 , Y. Nancy You 2 , Prajnan Das 3 , Miguel Rodriguez-Bigas 2 , Yan Xing 2 , Jean-Nicolas Vauthey 2 , Jane E. Rogers 4 , Aki Ohinata 1 , Priyanka Pathak 1 , Salil Sethi 1 , Jonathan K. Phillips 1 , Christopher H. Crane 3 , Robert A. Wolff 1 1 Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 2 Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 3 Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 4 Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 Correspondence to: Cathy Eng, e-mail: ceng@mdanderson.org Received: October 01, 2014 Accepted: October 02, 2014 Published: November 14, 2014 ABSTRACT Metastatic squamous cell carcinoma (SCCA) of the anal canal is a rare malignancy for which no standard treatment algorithm exists. To determine the best approach, all patients diagnosed with metastatic SCCA of the anal canal treated at a single institution were evaluated for choice of chemotherapy and treatment outcome. A retrospective study from January 2000 to May 2012 was conducted. Electronic medical records were reviewed for diagnosis of metastatic SCCA of the anal canal. All patients were treatment naive for metastatic disease and completed all radiographic imaging at our institution. The purpose of this study was to evaluate outcomes among patients who received systemic chemotherapy and if appropriate were referred for multidisciplinary intervention (e.g., surgery, radiofrequency ablation, etc.). Seventy-seven patients fulfilled eligibility criteria. Forty-two patients (55%) received 5-fluorouracil (5-FU) + cisplatin (PF); 24 patients (31%) received carboplatin + paclitaxel (CP); 11 patients (14%) received an alternative regimen. After a median follow-up of 42 months, the median progression-free survival (PFS) for all patients was 7 months; the median overall survival (OS) was 22 months. Thirty-three patients (43%) underwent multidisciplinary management for metastatic disease resulting in a median PFS of 16 months (95% CI: 9·2 -22·8) and median OS of 53 months (95% CI: 28·3 – 77·6). Systemic chemotherapy provides durable survival for patients with surgically unresectable metastatic SCCA of the anal canal. Multidisciplinary management for select patients with metastatic disease effectively improves survival and should be considered whenever possible.

Purpose Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric. Methods This was an observational cohort study of patients with rectal cancer within the National Cancer Data Base (2003 to 2005). Hospital performance was categorized as low outlier (better than expected), high outlier (worse than expected), or non-RAMP outlier using standard observed-to-expected methodology. The association between outlier status and overall risk of death at 5 years was evaluated using Cox shared frailty modeling. Results Among 32,354 patients with cancer (mean age, 63.8 ± 13.2 years; 56.7% male; 87.3% white) treated at 1,349 hospitals (4.9% high outlier, 0.7% low outlier), 5.6% of patients were treated at high outliers and 3.0% were treated at low outliers. Various structural (academic status and volume), process (pathologic nodal evaluation and neoadjuvant radiation therapy use), and outcome (sphincter preservation, readmission, and 30-day postoperative mortality) measures were significantly associated with outlier status. Five-year overall survival was better at low outliers (79.9%) compared with high outliers (64.9%) and nonoutliers (68.9%; log-rank test, P < .001). Risk of death was lower at low outliers compared with high outliers (hazard ratio [HR], 0.61; 95% CI, 0.50 to 0.75) and nonoutliers (HR, 0.69; 95% CI, 0.57 to 0.83). Risk of death was higher at high outliers compared with nonoutliers (HR, 1.12; 95% CI, 1.03 to 1.23). Conclusion Hospital RAMP outlier status is a rectal cancer surgery composite metric that reliably captures hospital quality across all levels of care and could be integrated into existing quality improvement initiatives for hospital performance.

With advances in multimodality therapy, colorectal cancer survivors are living longer. However, little is known about the quality of their long-term survival. We investigated the functional outcomes and symptoms among long-term survivors.A cross-sectional study of 1,215 long-term (5 years) colorectal cancer survivors was conducted using a validated disease-specific questionnaire. Younger onset survivors (18-50 years) were matched 1:2 to later onset survivors (50 years). Standardized mean scores were compared using one-way ANOVA. Key patient and treatment factors that impact function and symptoms were assessed by multivariate linear regression.Eight hundred thirty survivors responded at an interval of 10.8 ± 3 years from diagnosis (68% response rate). Younger onset survivors underwent more surgery (97.9 vs. 93.6%, P 0.001) and received more chemotherapy (86.1 vs. 77.7%, P = 0.004). Anxiety, body image, sexual dysfunction, embarrassment by bowel movements, micturition problems, and impotence were significant concerns. Younger onset survivors reported worse anxiety, body image, and embarrassment with bowel movements, whereas later onset survivors highlighted sexual dysfunction, micturition problems, and impotence. Age at diagnosis was a key independent determinant of long-term function and symptoms.Long-term survivors of CRC face ongoing functional deficits and symptoms, and their survivorship experience differs by age. Age at diagnosis should serve as a basis for tailored, personalized survivorship care plans.

Purpose Health care access and advanced cancer stage are associated with oncologic outcomes for numerous common cancers. However, the impact of patient travel distance to health care on stage at diagnosis has not been well characterized. Methods This study used a historical cohort of patients with colon cancer in the National Cancer Data Base from 2003 through 2010. The primary outcome, stage at diagnosis, was evaluated using hierarchical regression modeling. A secondary outcome was time to receipt of initial therapy that was evaluated using Cox shared frailty modeling. Results Among 296,474 patients with colon cancer (mean age, 68 ± 13.6 years; 47.6% male; 78.5% white), 3.9% traveled ≥ 50 miles to the diagnosing facility. Fewer black patients, patients with higher income, and patients with lower education traveled longer distances (trend test P < .001 for all). Patients traveling ≥ 50 miles were more likely to present with metastatic disease compared with those traveling less than 12.5 miles (odds ratio [OR], 1.18; 95% CI, 1.12 to 1.24) or 12.5 to 49.9 miles (OR, 1.18; 95% CI, 1.12 to 1.24). In sensitivity analyses, the association was robust to alternate methods of modeling travel distance (quintile stratification or continuous). Travel distance ≥ 50 miles was also associated with a higher likelihood of earlier initiation of therapy compared with travel distance of less than 12.5 miles (hazard ratio [HR], 1.10; 95% CI, 1.08 to 1.13) or 12.5 to 49.9 miles (HR, 1.11; 95% CI, 1.08 to 1.13). Conclusion Advanced colon cancer stage at diagnosis is associated with patient travel distance to health care, which may be a barrier to early cancer screening. Health care reform efforts designed to address only insurance coverage may not mitigate disparities based on difficulties accessing cancer care.

Background We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC). Methods We retrospectively evaluated all patients with CRC treated with IORT at our institution from 2001 to 2010. IORT was delivered using high-dose-rate brachytherapy (median 12.5-Gy). We analyzed factors associated with postoperative morbidity, local control (LC), and overall survival (OS). Results One hundred patients were evaluated with 70% received IORT for recurrent tumors. R0 resection rate was 58%. Postoperative Grade ≥3 complications (33%) were independently associated with transfusions ≥3 units packed red blood cells (P = 0.016) and body mass index (BMI) ≥35 (P = 0.0499). Eighty-two patients underwent external beam radiation therapy (EBRT) before IORT. Five-year LC was 94%, for primary and 56%, for recurrent tumors, respectively (P = 0.007). Microscopic positive (R1) margins were not associated with LC (P = 0.316). BMI ≥30 (P = 0.048) and post-discharge complications (P = 0.041) were independent risk factors for worse LC. Median post-IORT OS was 67.7 (95% CI 51.1–84.3) months for all patients. Conclusion For patients with primary or recurrent locally advanced CRC, treatment with radical surgery and IORT achieved excellent LC outcomes irrespective of microscopic margin status. IORT may be indicated for tumors suspected to have close or positive microscopic margins. J. Surg. Oncol 2014; 109:652–658. © 2014 Wiley Periodicals, Inc.

Purpose The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m 2 to 825 mg/m 2 orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

BACKGROUND Neoadjuvant chemoradiotherapy followed by tumor resection and postoperative chemotherapy is the standard of care for patients with clinical stage II or III adenocarcinoma of the rectum. Significant variation exists in the receipt of postoperative chemotherapy after resection in this population. The objective of this study was to determine the demographic and clinicopathologic factors associated with the initiation of postoperative chemotherapy in elderly patients with rectal cancer and to identify potential targets for reducing treatment variation. METHODS A retrospective cohort study was performed of patients with rectal cancer ages 66 to 80 years who received neoadjuvant chemoradiotherapy and underwent radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007). Multivariate logistic regression was used to assess chemotherapy use in relation to patient, tumor, and treatment response characteristics. RESULTS Among 1492 patients who met the study criteria, 61.5% received adjuvant therapy with 5-fluorouracil. Pathologic stage was the strongest determinant of whether patients received postoperative chemotherapy (48.3% of patients with stage I disease, 59.6% of patients with stage II disease, and 77.6% of patients with stage III disease). Increasing age and postoperative readmission also were associated significantly with a decreased rate of adjuvant therapy initiation. CONCLUSIONS Although standard treatment guidelines for locally advanced rectal cancer include postoperative chemotherapy for all patients after neoadjuvant chemoradiotherapy and radical resection, greater than 1 in 3 patients failed to receive adjuvant therapy. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. Cancer 2014;120:1162–1170. © 2014 American Cancer Society.

The role of emergent palliative surgery in the setting of advanced malignancy remains a subject of controversy.The purpose of this study was to identify clinical predictors of outcome in patients with cancer who undergo nonelective abdominal surgery.Individuals who underwent urgent and emergent abdominal operations between 2006 and 2010 at a tertiary cancer center were identified.Analyses were performed to identify predictors of 30-day morbidity and mortality as well as overall survival (OS). A risk score was derived from predictors of OS.Of 143 patients, 93 (65%) had active disease (AD; defined as evidence of malignancy at time of surgery). Thirty-day morbidity and mortality were 36.4% and 9.8%, respectively. Independent predictors of 30-day mortality included ASA score3 (p=0.009) and albumin2.8 (p=0.040). Median OS was 5.4 months in patients with AD and was not reached in patients without AD (p0.001). Independent predictors of decreased OS included AD; ASA3; creatinine1.3; and a tumor-related indication (i.e., bleeding, obstructing, or perforating tumor). A risk or palliative index (PI) score stratified patients into groups with discreet outcomes.Although AD did not predict 30-day morbidity, it was the dominant independent predictor of postoperative OS. In cancer patients undergoing emergency abdominal surgery, outcome is anticipated by disease status and other independent predictors of OS.

Worldwide, at least a quarter of the patients with colorectal cancer (CRC) are diagnosed with metastatic disease at presentation and many of them eventually succumb to their disease. A third of these patients may have their metastatic disease burden confined to the liver. It has been estimated that about 15–25% of CRC patients initially present with synchronous resectable liver metastases (SRLM) (1). These patients represent a group whose oncologic prognosis has significantly improved over the past decades (2).

ObjectiveWe sought to determine patients’ informational needs for post-treatment surveillance and elicit clinicians’ and patient advocates’ (ie, stakeholders) opinions regarding what patients should know about post-treatment surveillance in the USA.DesignA mixed-methods study, using semi-structured interviews followed by a survey study.SettingParticipants for the interviews were from two large academic medical centres and a safety-net hospital. The stakeholders were recruited from attendees at the Alliance for Clinical Trials in Oncology Network Spring 2016 meeting.ParticipantsParticipants for the in-depth interviews were purposively sampled. Eligible patients were 6 months to 5 years post curative resection for colorectal cancer and were fluent in English. Participants for the anonymous survey were stakeholders.Main outcome(s) and measure(s)The main outcome was patients’ with colorectal cancer informational needs for post-treatment surveillance, using an interview guide. The second outcome was the importance of the identified informational needs using an anonymous survey.ResultsOf the 67 patients approached, 31 were interviewed (response rate=46%), the majority were between 1 and 3 years post-treatment (81%) and diagnosed at stage III (74%). Despite a desire to monitor for cancer recurrence, patients had little understanding of the concept of post-treatment surveillance, equating surveillance with screening and a belief that if a recurrence was found early there would be a higher likelihood of cure. The survey suggested that clinicians (n=38) and patient advocates (n=11) had some differing opinions regarding what patients should know about surveillance to be active in decisions. For example, compared with clinicians, patient advocates felt that patients should know recurrence treatment options (100% vs 58%) and likelihood for cure following recurrence treatment (100% vs 38%).ConclusionsThe results of this exploratory mixed-methods study suggest that novel educational interventions targeting both patients and clinicians are needed to address the informational needs for post-treatment surveillance of colorectal cancer.

3505 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel EAs in LARC. EAs are not intended for direct comparison, but rather to test a variety of hypotheses in a consistent high-risk pt population with correlative biomarkers. Primary endpoint (EP) and available secondary EPs from the first EA using veliparib (a PARPi) are reported. NCT02921256. Methods: Stage II/III pts with LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to neoadjuvant FOLFOX (x 4mo) → chemoRT (cape with 50.4Gy +/- veliparib 400mg PO BID) → surgery 8-12 wks later. Primary EP: 4 point reduction in Neoadjuvant Rectal Cancer (NAR) score with a one-sided α = 0.10 and 80% power. NAR compared by linear model controlling for stratification and possibly other factors. Secondary EPs: OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, and SSS. Binary EPs compared by Fisher’s exact test. Reported p-values are two-sided. Results: From 10/2016 - 2/2018, 178 pts were randomized (88 control, 90 veliparib). Baseline characteristics were balanced except for candidate for SSS at entry (39% control, 61% veliparib). 140 pts were evaluable for NAR (72 control, 68 veliparib). Mean NAR was 12.6 control (95% CI: 9.8–15.3) vs 13.7 for veliparib (CI: 10.2–17.2). Controlling for stratification (p = 0.69) or stratification and candidate for SSS (p = 0.78), NAR difference was not significant. pCR = 21.6% vs 33.8% (p = 0.14); cCR = 28.2% vs 33.3% (p = 0.60); and SSS = 52.5% vs 59.3% (p = 0.43). Most common grade 3/4 AEs were diarrhea and cytopenias. The EA had two deaths (cardiac arrest [FOLFOX]; enterocolitis [chemoRT]). Conclusions: Veliparib added to chemoRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. Support: U10CA180868, -180822; UG1-189867; U24-196067; AbbVie. Clinical trial information: NCT02921256.

1515 Background: Self-reported family cancer history (FCH) is one of the key indicators of hereditary cancer risk. Studies have shown that accurate FCH documentation by healthcare providers is suboptimal, but data regarding patient-provided FCH are limited. We evaluated the quality of FCH as entered by the patient into the electronic health record (EHR) to determine its adequacy for Lynch syndrome (LS) risk assessment. Methods: At our tertiary referral cancer center, FCH is self-reported via an online questionnaire sent prior to appointment, which is reviewed/updated by clinic nurse during initial visit and then imported into EHR review of systems. Records of all new patients from September 2016 to August 2017 were retrospectively reviewed and analyzed. FCH quality was estimated by calculating rates of reporting of 3 FCH variables required for PREMM5, a risk-prediction model for LS. Parameters required for the model were sex, age, personal history of cancer, and for FCH, degree of kinship (first/second degree), cancer site/type, and age at diagnosis. Results: Of 47,647 unique patients, 47.5% reported FCH for 1 or more relative (46.1% were first degree, 64.8% second degree, 3.0% other, and 2.4% missing). A cancer type/site was specified for 88.8% reporting FCH. Age at diagnosis was listed for 21.7% of the relatives’ cancers. Overall, only 20.9% provided all 3 FCH data elements required for running PREMM5 (9.9% of the total sample, n=4738). Fewer men (9.5%) than women (28.1%) provided all 3 FCH elements. Furthermore, 46.7% of breast cancer patients, 21.9% of gastrointestinal cancer patients, 47.2% and 23.1% of patients seen for cancer prevention screening and endoscopy respectively, reported 3 FCH elements. Lower rates were observed for other cancers. Conclusions: Patient self-reported FCH is suboptimal for estimation of LS risk and genetic counseling referral. Future steps to optimize online patient-facing FCH collection to enable routine automated risk-assessment in an essentially provider-free setting may include, patient education regarding importance of FCH, EHR prompts for FCH completion, and implementation of algorithms in EHRs using FCH to identify patients at risk for hereditary cancer predisposition syndromes.

1512 Background: Genetic evolution studies have suggested the existence of a window of opportunity to improve clinical outcomes by intercepting pre-malignant lesions. This study reports the outcomes of Pancreatic Cancer (PC) surveillance in a high risk (HR) cohort followed at The University of Texas MD Anderson Cancer Center (MDA) between 2014 and 2018. Methods: The MDA PC High-Risk Clinic (MDA-PCHRC) performs surveillance based on risk stratification. This study reports 54 months of surveillance. The patients were stratified based on PC family history, personal history of other cancers, and germline mutations ( BRCA1/2, PALB2, STK11, CDKN2A, TP53) with high susceptibility to PC. Low risk patients were not offered surveillance while patients in the moderate or high-risk category were enrolled into a program which included annual screening with blood markers (CA 19-9, fasting glucose, HbA1C, amylase, and lipase) and magnetic resonance imaging/ cholangiopancreatography (MRI/MRCP). High risk patients also had a baseline endoscopic ultrasound (EUS). We evaluated the yield of premalignant lesions detection and our main goal was to detect predictive factors of focal pancreatic lesions and to validate our risk stratification strategy. Results: A total of 206 patients have been referred to our clinic during this time period. From this group, 126 (61%) patients completed at least one cycle of baseline surveillance, for the purposes of the analysis we only focus in the high risk (n=71) and moderate risk group (n=38). We have identified de novo pancreatic focal lesions in 22 patients, 20 from the high risk group (28%) and 2 from the moderate group (5%). Those lesions included 7 patients with simple cysts, 9 with side-branch IPMN, 3 with main duct IPMN, 1 with pseudocyst, 1 with mucinous cyst and 1 with a solid nodule (pancreatic neuroendocrine tumor). We compared demographic information (age, gender, and ethnicity) as well as family and personal medical history between patients with focal pancreatic lesions vs negative or diffuse findings. We found that new onset diabetes was significantly correlated with presence of focal pancreatic lesions 5 (22%) of patients with focal lesions versus patients without non focal lesion 2 (2%) ( P=0.003). Conclusions: Screening at the MDA-PCHRC detect pancreatic premalignant lesions in 20% of the patients in our cohort. We validated our risk stratification methodology and found that new-onset diabetes is predictive of pancreatic lesions, thus suggesting that this factor could be an important biomarker of focal lesions in a HR population.

3592 Background: Lynch-like syndrome (LLS) is characterized by a diagnosis of mismatch repair deficient (dMMR) malignancy where somatic bi-allelic mutations in canonical MMR pathway genes ( MLH1, MSH2, MSH6, PMS2) have been identified as the main cause. Yet, a substantial proportion of cases remain unexplained by MMR somatic bi-allelic events or germline mutations. We hypothesize that LLS cases with young-onset cancers carry cryptic germline alterations in other pathways. To explore this contribution, we performed analyses of the germline and tumor mutation landscapes in LLS patients diagnosed with dMMR cancers. Methods: 18 probands with young-onset (age

TPS721 Background: Locally advanced rectal cancer (LARC) improvements have plateaued due to an inability to consistently deliver adjuvant therapy and effective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers is needed to advance treatment outcomes. This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EA) in LARC. The EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk patient (pt) population with correlative biomarkers. Success of any EA will be determined by achievement of pathologic endpoints compared to a control arm. Methods: The NRG-GI002 trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC with any ONE of the following: distal location (cT3-4 ≤ 5 cm from anal verge, any N); bulky (any cT4 or tumor within 3 mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, pts receive neoadjuvant FOLFOX x 4 mo→chemoRT (capecitabine with 50.4 Gy)→surgical resection 8-12 wks later. The first EA will assess activity of veliparib with standard chemoRT. Enrollment to this EA is complete (results anticipated late 2019). The second EA, testing pembrolizumab concurrently with and following chemoRT, is currently active, with several other EAs in development. Primary endpoint is demonstrated improvement in Neoadjuvant Rectal Cancer score for the EA v control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including QOL, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts/arm with additional EAs added through protocol amendments. NCT02921256. Support: U10CA180868, -180822, UG1-189867, U24-196067; AbbVie, Merck. Clinical trial information: NCT02921256.

Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. We sought to evaluate the impact of ileostomy-related complications on the treatment of rectal cancer. We conducted a retrospective study of patients who underwent sphincter-preserving surgery between January 2005 and December 2010 at a tertiary cancer center. The primary outcome was the overall rate of ileostomy-related complications. Secondary outcomes included complications related to ileostomy status, ileostomy closure, anastomotic complications at primary resection, rate of stoma closure, and completion of adjuvant chemotherapy assessed by multivariate logistic regression. Of 294 patients analyzed, 32 % (n = 95) were women. Two hundred seventy-one (92 %) received neoadjuvant chemoradiation. The median tumor distance from the anal verge was 7 cm (interquartile range 5–10 cm). Two hundred eighty-one (96 %) underwent stoma closure at a median of 7 months (interquartile range 5.4–8.3 months). The most common complication related to readmission was dehydration (n = 32–11 %). Readmission within 60 days of primary resection was associated with delay in initiating adjuvant chemotherapy (odds ratio 3.01, 95 % confidence interval 1.42–6.38, p = 0.004). Diverting ileostomies created during surgical treatment of rectal cancers are associated with morbidity; however, this is balanced against the risk of anastomosis-related morbidity at rectal resection. Given the potential benefit of fecal diversion, patient-oriented interventions to improve ostomy management, particularly during adjuvant chemotherapy, can be expected to yield marked benefits.

BACKGROUND The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer. METHODS The authors studied 251 patients with rectal adenocarcinoma who were treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated percentage of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near-complete, ≤ 5% residual cancer cells; major, > 5%, and