Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

2 Background: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy with high rates of local control. There is some thought that perhaps chemotherapy can be omitted for the earliest stages without worse outcomes. We used the National Cancer Database (NCDB) to identify predictors of chemotherapy receipt or omission to assess the impact on outcomes. Methods: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation with and without chemotherapy and at least 2 months of follow-up. Logistic regression was used to generate predictors of chemotherapy use. Cox regression identified predictors of survival. Propensity matching was done to help account for indication bias. Results: We identified 2,959 patients meeting eligibility, of which 8% (n = 237) were treated without chemotherapy. The vast majority (n = 2722, 92%) were recorded as having multi-agent chemotherapy. Median radiation dose was 50.4 Gy (IQR 45-54) in 28 fractions (IQR 49.4-59.4) with chemotherapy and 54.0 Gy (IQR 49.4-59.4) in 30 fractions (IQR 25-33) in those who had chemotherapy omitted. Predictors of omission of chemotherapy were older age (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and more remote year of treatment (OR 1 1 for years 2004-2006). Predictors of survival were younger age (HR 1.73 for age > 58 years, 95% CI [1.41-2.11], P < 0.001), multi-agent chemotherapy use (HR 0.48, 95% CI [0.38-0.62], P < 0.0001), higher income (HR 0.57, 95% CI [0.40-0.81], P = 0.0016), female gender (HR 0.68, 95% CI [0.57-0.82], P = 0.0016), and private insurance (HR 0.54, 95% CI [0.34-0.87], P = 0.0104). After propensity matching, overall survival at 120 months for patients treated with and without chemotherapy was 86% and 65%, respectively (p < 0.0001). Conclusions: Chemotherapy is utilized the majority of the time in early stage SCCA. Being mindful of the limitations of a retrospective database analysis, our results suggest an association with worse survival outcomes when chemotherapy is omitted.

35 Background: Local excision (LE) alone is a standard treatment option for appropriately selected early stage rectal adenocarcinoma patients. Guidelines for this therapeutic approach are based upon retrospective single institution data, some of which dates back 30 years. We thus sought to use the National Cancer Database (NCDB) to examine outcomes in a large cohort of patients with early stage rectal adenocarcinoma treated with LE and to identify/confirm predictors of outcome. Methods: We queried the NCDB for patients with pT1N0M0 rectal adenocarcinoma treated with local excision alone. Baseline characteristics were tabulated and included lymphovascular invasion (LVI), perineural invasion (PNI), grade, and size all of which have been recorded in the NCDB since 2010. Multivariable Cox regression was used to identify predictors of overall survival. Kaplan Meier curves were generated to compare survival based upon significant factors found on multivariable analysis. Results: Using the above criteria, we identified 887 patients eligible for analysis across 2010-2014. The median age was 67 and 57% of patients were male. The median tumor size was 1.5 cm (IQ range: 0.9-2.5 cm). A minority of patients had grade 3 tumors (5%), LVI (8%), or PNI ( < 1%). Median follow up was 36 months (1-83). On multivariable Cox regression, predictors of worse survival included: size > 4 cm, age > 67, higher comorbidity score, and presence of LVI. On Kaplan Meier analysis, 5 year OS was 75% vs. 74% for patients without and with LVI, respectively (p = 0.0115). In terms of size, the 5 year OS was 74% vs. 51%for size < 4cm and size > 4cm (p = 0.0138). Conclusions: Our large contemporary series demonstrates excellent survival outcomes in patients with early stage rectal adenocarcinoma treated with LE alone. LVI remains a predictor of outcome, while grade and perineural invasion were not significant in this analysis. This finding is likely due to a small number of patients with those characteristics.

Standard of care for locally advanced rectal cancer (LARC) (stage II/III) includes preoperative chemoradiation (CRT) followed by resection and adjuvant chemotherapy. Total neoadjuvant therapy (TNT) is a new treatment paradigm that delivers systemic therapy prior to CRT aimed at improving outcomes for high-risk patients. Here we analyzed the national cancer database (NCDB) comparing short-term post-operative outcomes between patients receiving TNT and CRT. The NCDB was queried to identify patients with LARC between the 2004 and 2014 treated with TNT or CRT. Primary outcomes included post-operative 30-day mortality and readmissions between TNT and CRT which were analyzed via logistic regression. Secondary outcomes included post-operative length of stay (LOS) and OS which were compared with two-tailed t-test and Kaplan-Meier with log rank testing, respectively. A total of 9066 patients met inclusion criteria with a median age at diagnosis that was 57 years (IQR, 19–65); 62.3% were male and 87.8% white. Neoadjuvant therapy consisted of either standard CRT (97.2%) or TNT (2.8%). Patients treated at academic programs and those with N1 [p < 0.001, OR 2.34, 95%CI 1.71–3.19] or N2 [p < 0.001, OR 3.29, 95%CI 2.19–4.94] disease were associated with increased utilization of TNT. TNT was not significantly associated with either 30-day mortality (p = 1.0) or readmissions (p = 0.82). Further, there was no significant difference identified between CRT and TNT for hospital LOS or OS (p = 0.18). This large-scale analysis of patients with LARC demonstrates increased utilization of TNT in patients harboring node-positive disease. Further, TNT does not appear to increase 30-day post-operative mortality, readmissions, or hospital LOS.

616 Background: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. We therefore utilized the national cancer database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. Methods: We analyzed 5,086 patients between 2010-2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4,450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional hazard ratios were used for survival. Results: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher grade tumors (P < 0.05). The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (OR = 0.65, 95% CI 0.43 – 0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared to 73% without it (< 0.001). Conclusions: Microsatellite instability was independently associated with a reduction in pathologic complete response for locally advanced rectal cancer following neoadjuvant chemoradiation in this NCDB-based analysis.[Table: see text]

The neoadjuvant rectal cancer (NAR) score is a prognostic tool for locally advanced rectal cancer treated with total neoadjuvant therapy (Valentini V, et. al. J Clin Oncol 2011). It has been previously validated as an endpoint that predicts survival more accurately than pathologic complete response (pCR) (Raissouni S, et. al. J Clin Oncol 2014) and is the primary endpoint of the ongoing NRG-GI002 Phase II trial. The score uses the variables of clinical tumor stage, pathologic tumor stage, and pathologic nodal stage which are commonly available, furthering its utility in the clinical setting. Using the National Cancer Database (NCDB) we aimed to validate the NAR score’s ability to predict survival in a large hospital based dataset. We queried the NCDB from 2004-2014 to identify all stage II and III rectal cancer patients that received total neoadjuvant therapy (TNT) followed by surgical resection. Selection for patients receiving TNT included receipt of preoperative multi-agent chemotherapy and radiation. Patients were excluded if they had non-adenocarcinoma histology, unknown clinical or pathologic staging, less than 6 months of follow up, and positive margins. Overall survival (OS) was calculated using Kaplan-Meier curves evaluating NAR score and pCR separately. A multivariable Cox proportional hazards model was used to identify factors associated with survival. Multivariate regression was used to evaluate characteristics associated with a favorable ( < 15) NAR score. Our final patient cohort yielded 209 patients for analysis with a median age of 62. The median follow up time was 43.8 months (Range: 7.1 – 135.3 months). Factors associated with worse survival included age > 62 years old (P=0.046), lower income (P=0.03), and unfavorable (≥15) NAR score (P=0.04). Comorbid score, CEA level, race, lymphovascular invasion, perineural invasion, and insurance status did not predict for survival. On multivariate regression, tumors with perineural invasion and a higher comorbidity score (>1) were less likely to have a favorable NAR response (P=0.0093 and P=0.0117). Of note, pCR was not associated with improved survival (P=0.0949). This NCDB analysis further validates the utility of the NAR score as a prognostic tool in patients receiving TNT for locally advanced rectal cancer. Tumors with perineural invasion and patients with a higher comorbidity score had worse NAR scores.

593 Background: Immunotherapy (IO) in combination with chemoradiotherapy (CRT) in the neoadjuvant treatment for locally advanced rectal adenocarcinoma (RAC) is an area of active clinical research. There are no well-defined biomarkers in RAC predicting response to neoadjuvant therapy. Increase in tumor PD-L1 expression and tumor infiltrating lymphocytes (TIL) has been observed after neoadjuvant CRT which potentially enhances response to IO. We report herein expression of PD-L1 and CD8+ TIL and other biomarkers of immune activation including CXCL9, TIM3 (HAVCR2), IDO1, IFNG, IL17RE, LAG3 and OX40 (TNFRSF4) pre and post neoadjuvant CRT in RAC. Methods: We retrospectively evaluated 38 RAC patients from 2007-2016 treated with neoadjuvant CRT using 5FU based therapy. Pre and post CRT tissue samples were stained with VENTANA PD-L1 (SP263) rabbit monoclonal antibody to quantify PD-L1 expression. CD8+ TIL were recorded over one high power field (hpf) (40x objective) in the area of densest infiltrate. Additional biomarkers CXCL9, TIM3 (HAVCR2), IDO1, IFNG, IL17RE, LAG3 and OX40 (TNFRSF4) were assayed with RT-PCR. Independent sample and paired sample t-tests were used for statistical analysis of difference in biomarker expression. Relevant clinical endpoints including local relapse, distant metastases and survival were collected. Results: Median age was 60 years (range 32–87). Median follow up was 16.7 months (range 2.6-120.1). Median duration from completion of CRT to resection was 73 days (range 44–315). PD-L1 expression increased from 10% to 23% in pre-CRT versus post-CRT patients. CD8+ TIL increased in 30/39 (83%) patients with an average increase from 66.48 to 129.20 CD8+ TIL/hpf in the pre-CRT versus post-CRT setting. Using RT-PCR, a statistically significant increase in the expression of CXCL9, IFNG and OX40 (TNFRSF4) was found pre-CRT versus post-CRT using paired samples t-test. Conclusions: Neoadjuvant CRT for RAC increased PD-L1 expression and CD8+ TIL along with an increased expression of CXCL9, IFNG and OX40 (TNFRSF4). These data suggest a novel role for IO in neoadjuvant treatment of rectal cancer. Clinical outcome data on these patients will be presented.

621 Background: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemo and XRT, reserving surgery for salvage. Many different radiation dose schemes have been used, varying from 30 Gy to doses exceeding 60 Gy. RTOG 0529 established IMRT as a standard of care for anal canal SCC, using doses of 50.4-54 Gy. We used the National Cancer Database(NCDB) to examine trends in dose selection and radiation technique over time, as well as any potential effect on outcome. Methods: We queried the NCDB from 2004-2015 for cases of anal canal SCC stage 1-3, treated with definitive doses of XRT to the pelvis with chemo. Dose escalation was defined as > 54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of increased dose and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: We identified 7,792 patients meeting the eligibility criteria, with 4,269 treated to conventional doses and 3,163 treated to > 54 Gy. Patients that were older, had government or private insurance, were treated with IMRT, or at an academic center in a more recent year were less likely to get dose escalation. Increasing T and N stage were predictive of escalated dose. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. In contrast, IMRT use increased over that time from 2% to 63%. On multivariable analysis increasing age, higher comorbidity score, treatment at an academic center, and increasing stage corresponded to worse OS. Increased income, private insurance, IMRT use, increased distance to facility, and female gender all predicted improved OS. Multivariable analysis with propensity score included confirmed increased age, higher comorbidity score, income, distance, and gender as predictive of OS. In addition, escalated dose was found to have inferior outcome (OR: 1.10 95%CI: 1.01-1.20, p = 0.03). Conclusions: The results of this NCDB analysis show a steady increase in the use of IMRT over time, with a corresponding decrease in dose escalation. In this study, dose escalation was shown to have inferior outcomes, although that result is likely influenced by the increasing age, stage, and comorbidity scores in that group of patients.

714 Background: With recent advances in systemic therapies and increased survival of patients with metastatic rectal cancer, the role of primary tumor resection may be of increased importance and is often debated. However, the role of combining radiotherapy to surgical resection in the metastatic setting is unknown. Accordingly, we utilized the NCDB to quantify survival in metastatic rectal adenocarcinoma patients with primary tumor resection with and without pelvic radiotherapy. Methods: Of the 15,643 Stage IV rectal adenocarcinoma patients receiving chemotherapy from 2004 to 2014, 4051 patients had primary tumor resection with sufficient follow up for analysis. Patients were stratified by receipt of pelvic radiotherapy (n = 1882) or no pelvic radiotherapy (n = 2169). Univariable/multivariable analyses and propensity-adjusted Cox proportional hazard ratios for survival were performed. Results: Median age was 63 years (18-90) with median follow up of 32.3 months (3.02-151.29). There were more patients with T3/T4 disease (69.6% vs 46.5%) or N1 disease (41.5% vs 27.3%) in the surgery plus radiotherapy arm. Metastatic burden was confined to one organ in 40.5% of patients and was equally distributed between radiotherapy and non-radiotherapy groups (OR 0.92; 95%CI 0.81-1.04). Median survival was 46.3 months vs. 35.3 months in favor of adding radiotherapy (p < 0.001). The 2, 5 and 10-year overall survival were 68.4%, 24.8%, and 9.5% for surgical resection alone compared to 77.2%, 39.6%, and 22.3% for surgery + radiotherapy. On multivariable analysis radiotherapy was associated with a statistically significant reduction in the risk of death (HR 0.718; 95% CI 0.661-0.780). This benefit was upheld on propensity matched analysis (HR 0.722; 95% CI 0.0665-0.784). Conclusions: Our study indicates that adding radiotherapy to surgical management of the primary tumor in patients receiving systemic chemotherapy for metastatic rectal adenocarcinoma improves survival. Prospective investigation of the management of the rectal primary tumor with chemotherapy, pelvic radiotherapy, and surgical resection is warranted.

The present study examines outcomes in patients with stage IV rectal cancer receiving some form of local therapy. That local therapy was either surgery alone or chemoradiation followed by surgery. The authors' analysis showed a benefit to the addition of chemoradiation to surgery, even in the metastatic setting highlighting the need for multidisciplinary management in this patient population. Background: With advances in systemic therapies, the role of primary tumor resection may be of increased importance in patients with metastatic rectal cancer. The role of combining pelvic radiotherapy with surgical resection in the metastatic setting is unknown. We utilized the National Cancer Database to examine outcomes in patients with metastatic rectal adenocarcinoma with primary tumor resection with and without pelvic radiotherapy. Materials and Methods: We queried the National Cancer Database from 2004 to 2014 for patients with stage IV rectal adenocarcinoma receiving chemotherapy. We identified 4051 patients in that group that had primary tumor resection. Patients were then stratified by receipt of pelvic radiotherapy (yes = 1882; no = 2169) Univariable and multivariable analyses identified characteristics predictive of overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: The median patient age was 63 years (range, 18-90 years) with a median follow-up of 32.3 months (range, 3.02-151.29 months). There were proportionately more patients with T3/T4 disease or N1 disease in the surgery plus radiotherapy arm. The median survival was 46.3 months versus 35.3 months in favor of addition of radiotherapy (P < .001). The 2- and 5-year overall survival was 68.4% and 24.8% for surgical resection alone compared with 77.2% and 39.6% for surgery radiotherapy. On propensity-adjusted multivariable analysis, radiotherapy was associated with a statistically significant reduction in risk of death (hazard ratio, 0.722; 95% confidence interval, 0.0665-0.784). Conclusion: This analysis indicates that in patients with metastatic rectal adenocarcinoma receiving chemotherapy, pelvic radiotherapy in addition to primary tumor resection may be of significant benefit. (C) 2019 Elsevier Inc. All rights reserved.

Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome. We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan–Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival. We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36 months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan–Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47 months, p = 0.02). Receipt of adjuvant radiation was associated with improved OS [hazard ratio (HR): 0.86 (0.80–0.93) p = 0.0002] on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival. Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.

Background: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemoradiation, reserving surgery for salvage. The dosage of radiation has varied from 30 Gy to in excess of 60 Gy. RTOG 0529 established intensity modulated radiation therapy (IMRT) as standard of care for anal canal SCC with doses of 50.4 to 54 Gy. We sought to use the National Cancer Database to examine trends in dose selection and radiation technique over time. Methods: We queried the National Cancer Database from 2004 to 2015 for cases of anal cancer stage groups 1 to 3, treated with definitive doses of radiation with chemotherapy. Dose escalation was defined as >54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of dose, IMRT, and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: We identified 7792 patients meeting the eligibility criteria, with 4269 treated to doses of 45 to 54 Gy and 3163 treated to doses >54 Gy. Patients who were older, had government or private insurance, IMRT treatment, treatment at an academic center, or more recent years were less likely to get dose escalation. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. IMRT use increased over time from 2% to 63%. On multivariable analysis with propensity score included it was found that increased age, higher comorbidity score, lower income, shorter distance to facility, and male sex were predictive of decreased overall survival. In addition, escalated dose was associated with a lower survival (hazard ratio: 1.10, 95% confidence interval: 1.01-1.20, P =0.03). Conclusions: The results of this analysis show a steady increase in the use of IMRT, with corresponding decrease in dose escalation. These findings correlate with the results of RTOG 0529 establishing IMRT as standard of care for anal SCC, using doses of 50.4 to 54 Gy.

Abstract Importance Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage. Objective We conducted this National Cancer Database (NCDB)‐driven retrospective study to analyze treatment trends and outcomes in the current time from 2004 to 2015 with respect to chemoradiation and surgery. Design Retrospective NCDB tumor registry data review—using propensity score‐adjusted multivariable analyses for survival. Setting Database review. Participants We selected for patients listed in the NCDB with AJCC stage 1‐3 anal adenocarcinoma diagnosed between 2004 and 2015 and selected out patients with undocumented/stage 4 disease, those with radiation outside the pelvis, not treated with systemic therapy and patients lost to follow‐up. Exposure(s) None. Main outcomes and measures Overall survival and use of surgery in the up‐front management of anal adenocarcinoma. Results Of the 1729 patients eligible in this study, 1028 were treated with surgery as up‐front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5‐year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (P < 0.0001) with 5‐year survival rates of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively. Propensity score‐adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome. Conclusions and Relevance The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior to the year 2000 for surgery to be included in the definitive management of anal adenocarcinoma.

Aim: Stereotactic body radiotherapy (SBRT) has been used as an alternative to surgical intervention to treat primary malignanices of the lung as well as lesions from other primaries. In this study, we evaluate the safety and efficacy of SBRT in treating lung metastases from colorectal cancer (CRC). Materials & methods: We reviewed 22 patients that underwent lung SBRT for metastases from CRC. Almost all patients received chemotherapy before and after undergoing SBRT. Outcomes that were analyzed included overall survival, distant failure and progression-free survival, as well as the effects of biologically effective dose (BED) and KRAS status on local control. Results: Seven females and 15 males underwent SBRT to lung metastases from CRC. The median Eastern Cooperative Oncology Group status was one (0-2). The median dose was 48 Gy (40-54 Gy) in 5 fx (4-8 fx) and the median number of nodules treated with SBRT was one (1-3). Median follow-up was 28.5 months from SBRT and 79 months (9-145) from primary diagnosis. Local control at 1 and 3 years was 75 and 58%, respectively. There was a trend toward improved local control with increasing biologically effective dose (BED10 > 100; p = 0.07). Cancers that were positive for the KRAS mutation had increased local control at 12 months, 100 versus 75% (p = 0.0199). Median OS from the primary diagnosis of CRC and from SBRT was 79 and 31 months, respectively. There were no predictors for OS. There were no episodes of acute or late grade 3 or higher toxicity. Conclusion: The results of this study add to the growing body of literature to support SBRT for lung metastases, specifically those patients with limited lung metastases from CRC. The choice of radiation dose remains important, even in metastatic disease, as highlighted by the trend toward improved local control with increasing BED10.

e24146 Background: Immunotherapy (IO) is a new treatment option for advanced microsatellite unstable colorectal cancer. Radiotherapy is an integral part of neoadjuvant treatment for locally advanced rectal adenocarcinoma and has been shown to increase tumor PD-L1 expression and tumor infiltrating lymphocytes (TIL). These changes in the tumor microenvironment enhance the response to IO. We report herein on expression of PD-L1 and CD-8 + TIL pre and post neoadjuvant chemoradiotherapy (CRT) in rectal adenocarcinoma. Expression of TIM-3, LAG-3, IDO1, OX40, IFN-ɤ, IL-17 and CXCL9 will also be reported. Methods: We retrospectively evaluated 39 patients with rectal adenocarcinoma from 2007-2016 treated with neoadjuvant CRT using 5FU based therapy. Pre and post CRT tissue samples were stained with VENTANA PD-L1 (SP263) rabbit monoclonal antibody to quantify PD-L1 expression. CD8 + TIL were recorded over one high power field (40x objective) in the area of densest infiltrate. Additional biomarkers are being assayed with RT-PCR. Relevant clinical endpoints of local relapse, distant metastasis, and survival were also collected. Results: Median age was 60 years (range 32-87). Median follow up was 16.7 months (range 2.6 -120.1). Median duration from completion of CRT to resection was 73 days (range 44 - 315). Among the pre-CRT cases 7.7% expressed PD-L1 versus 20.5% post-CRT (OR 3.1, p = 0.11). Median number of CD8+ TIL in the pre-CRT biopsies was 49. In post-CRT specimens, 82.1% cases had TIL > 50 (p = 0.002). PD-L1 expression did not correlate with pathological complete response, local or distant failure. Radiation dose/fractionation, time from CRT completion to resection, and CD8+ TIL did not correlate with increase in PD-L1 expression. Conclusions: Neoadjuvant CRT for rectal adenocarcinoma increased PD-L1 expression and CD8+ TIL which are known biomarkers for IO response. These data suggest a novel role for IO in neoadjuvant treatment of rectal cancer.

e15115 Background: Chemoradiotherapy (CRT) followed by surgery is standard treatment for most rectal cancers. This creates an inflammatory reaction which recruits and enhances T-cell mediated killing. Tumors can evade destruction by expressing immune modulating proteins such as PD-L1. Inhibitors of PD-L1 can circumvent immune evasion potentially enhancing neoadjuvant treatment. We assessed CD8+ infiltrates and PD-L1 expression before and after neoadjuvant CRT. We correlated these changes with clinical and pathological endpoints. Methods: We obtained tissue from 22 patients treated with neoadjuvant CRT followed by primary surgery for rectal adenocarcinoma from 2005-2015. Patients received 5FU based chemotherapy with concurrent radiation (mean 51.2 Gy in 27 fractions). Pre- and post-CRT samples were stained with VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody to quantitate PD-L1 expression. CD8 + lymphocytes were assessed over one high power field (40x objective) in the area of densest expression. Analysis of 8 patients was completed at the time of this submission. Results: 37.5% of cases had upregulated PD-L1 expression post-CRT. 62.5% maintained similar PD-L1 expression in the biopsy and resection specimen. All patients had a CD8+ infiltrate after CRT with 87.5% demonstrating an increase in CD8+ lymphocytes. Patients without increased PD-L1 expression had a trend toward improved pathologic response. Conclusions: A majority of patients had an increased inflammatory infiltrate post-CRT indicating immune activation within the tumor microenvironment. A subset of tumors had increased PD-L1 expression. This population might benefit from neoadjuvant PD-L1 inhibition, which could translate to better pathological response and clinical outcomes. We will present the results from 22 patients currently under study. [Table: see text]

Mirizzi syndrome (MS) is characterized by extrinsic compression of the common bile duct (CBD) by an impacted stone in the cystic duct or Hartmann's pouch. An 80 year old female with history of questionable ulcerative colitis (UC) presented to the hospital after sustaining a fall with complaints of abdominal pain and diarrhea. Physical exam was negative for organomegaly or tenderness. Labs showed a WBC of 14,000/μL with normal LFTs. Computed tomography (CT) of the abdomen showed transverse and descending colon thickening consistent with colitis, intra and extra-hepatic dilation and choledocholithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and stone removal was done. No extravasation of dye or air was noted. Colonoscopy was performed which showed diffuse mucosal erythema of the entire colon, multiple pseudo-polyps and a 10 mm polyp at approximately 70 cms proximal to the anus with 1 mm mucosal defect (? fistula vs microperforation) in the region of the flat polyp. Biopsies were not performed for concerns of perforation. Pathology with random biopsies of the colon revealed features suggestive of UC without dysplasia. She was taken up for laparoscopic total abdominal colectomy for refractory colitis and concern for DALM. The diagnosis of MS was made intra operatively. A thick, hard mass of gallbladder (GB) containing a stone with chronic inflammatory changes involving the duodenum and colon was found along with a cholecysto-colonic fistula (CCCF), correlating with the indentation noted endoscopically. CCCF take down and stone removal was done. A cholangiogram showed a normal anatomy to the intrahepatic ducts and duodenum. A partial cholecystectomy with a T tube placement in the CBD for MS type II was done. Pathology of the resected specimen was negative for malignancy of the GB and colon. MS is seen in 1% of gall stone disease. It is associated with GB cancer in 2% of the cases. Incidence of CCCF has decreased over the past two decades due to increased frequency of cholecystectomy at a younger age, reducing cholecystectomy in the elderly, when a long lasting GS disease is more likely to cause it. Etiology of CCCF is likely due to chronic inflammatory process of the GB. Preoperative diagnostic tools often fail to demonstrate it, with low sensitivity (50%). Diagnosis is often achieved intraoperatively. In those circumstances intraoperative hepatobiliary exams should be performed to look for other possible anomalies.