Mahipal, Amit

243 Background: The risk factors for gallbladder cancer (GBC) are poorly understood and preventive therapeutic options have not been identified. The use of aspirin (ASA) and/or statin has been associated with reduced risk of several gastrointestinal cancers. In this study, we explore if the use of ASA or statin is associated with a reduced risk of GBC. Methods: We identified patients with GBC diagnosed between the years 2000 and 2016 at Mayo Clinic. We identified matched controls in 2:1 fashion for age, gender and country of residence from patients who underwent cholecystectomy at Mayo Clinic. We collected information on co-morbidities and use of statins or ASA by retrospective chart review. We compared baseline characteristics between cases and controls using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. We used binomial logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to estimate the association of ASA or statin use with GBC. The logistic regression model included history of cholelithiasis, diabetes, hypercholesterolemia (HCL), hypertension (HTN), hyperthyroidism, hypothyroidism, primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD), cirrhosis and statin or ASA use as covariates. Results: 633 cases and 1,266 controls were included in our final analysis. The median age at diagnosis of cases and controls was 67 years. The control group had a significantly (p < 0.05) higher proportion of patients with cholelithiasis, HCL, HTN, hypothyroidism and liver cirrhosis compared to the cases. The case group,contrarily, had a significantly higher proportion of patients with PSC and IBD. In univariate analysis, ASA (OR: 0.41; 95% CI: 0.33-0.52) or statin (OR: 0.48; 95% CI: 0.38-0.60) use was associated with a lower risk of GBC (p < 0.001). However, in multivariate analysis, ASA use was associated with a lower risk of GBC (OR: 0.52; 95% CI: 0.41-0.67, p < 0.001) whereas statin use was not (OR: 0.76; 95% CI: 0.56-1.03, p = 0.08). Conclusions: Our study demonstrates that aspirin use is associated with a reduced risk of GBC, whereas statin use is not. Further studies on GBC are needed to confirm these results and to elucidate mechanisms that explain the risk reduction with aspirin.

131 Background: Trimodality therapy is the standard of care for patients with resectable cancer of the esophagus. However, patients ≥75 years have been underrepresented or excluded from landmark clinical trials to date. We investigated the feasibility and safety of treatment of esophageal cancer with trimodality therapy in patients’ ≥ 75 years. Methods: We performed a retrospective review of all patients ≥75 years who received trimodality therapy for esophageal cancer in 3 high volume tertiary cancer institutions from June 2007 to June 2013. All patients received neoadjuvant radiation with concomitant chemotherapy followed by esophagectomy. Toxicities and clinical outcomes were abstracted from the electronic medical record and partially from a prospectively maintained database. Overall and disease-free survival were estimated using the Kaplan-Meier method. Results: Five hundred seventy patients were treated with trimodality therapy for esophageal cancer from 2007-2013. Of these, 38 patients (7%) were 75 or older at the time of diagnosis. At diagnosis, comorbidities included coronary artery disease (32%), atrial fibrillation (11%) and COPD (13%). The majority of patients (87%) received 50.4Gy/28 fractions. 5-fluorouracil (5-FU)/cisplatin was the most common chemotherapy regimen (37%), followed by 5-FU/docetaxel (24%). A total of 13 patients (34%) developed acute grade ≥3 toxicity associated with neoadjuvant therapy. The most common acute grade 3 toxicities were haematological (10%), nausea (8%), esophagitis (5%) and fatigue (5%). Significant postoperative complications included respiratory (empyema, ARDS, pleural effusion) (39%), arrhythmia (32%), anastomotic leak (5%), and ileus (5%). There were 2 deaths (5%) within 90 days of surgery: one was secondary to empyema, the other developed DIC and sepsis. Median overall survival and disease free survival were 4.4 and 2.3 years respectively. Conclusions: Trimodality treatment is a reasonable approach for management of carefully selected elderly patients with esophageal cancer, with similar rates of cancer outcomes, and treatment related morbidity and mortality as compared to younger patients.

121 Background: We evaluated the role of pre-treatment pulmonary function testing (PFT) in predicting the likelihood of cardiac and/or pulmonary toxicity for esophagus cancer patients receiving trimodality therapy. Methods: From 2007 to 2013, 64 patients with esophageal cancer received trimodality therapy at a single tertiary center with pre-treatment PFTs. The odds ratio of pre-treatment PFT as a predictor of cardiopulmonary toxicity was assess with univariate analysis (UVA). FEV1 (forced expiratory volume in 1 second) and DLCO (diffusion capacity for carbon monoxide) were assessed per 0.5-unit decrease. Percent FEV1 and DLCO predicted were assessed per 10% decrease. Results: The median age was 62 years (range, 41-79) with 88% male patients. A total of 70% of patients had adenocarcinoma with 66% having stage 3 disease. Most patients were former (43%) or current smokers (32%) and 18% had COPD. One or more cardiac comorbidities were observed in 54% of patients. The median RT dose was 50 Gy and the most frequent concurrent chemotherapy was cisplatin/5FU (53%). The median pre-treatment FEV1 and DLCO was 2.8 liters (range, 1-4.9) and 22.5 mL/min/mmHg (range, 17.2-25.5), respectively. This correlated to a median percent predicted value for FEV1 and DLCO of 85% (range, 30-124%) and 81.5% (range, 49-119%), respectively. The overall rate of any cardiac and pulmonary toxicity was 35% and 50%, respectively. Percent predicted value of both FEV1 and DLCO was statistically associated with pulmonary but not cardiac toxicity (Table). Conclusions: Patients with compromised pre-treatment pulmonary function are at higher risk of developing post-treatment pulmonary toxicities. Pulmonary function testing should be routinely performed prior to initiation of trimodality therapy for patient risk stratification. [Table: see text]

864 Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment with local excision alone is unknown and is currently not recommended by NCCN. We retrospectively analyzed outcome of the patients with small (T1 lesion) incidentally found ACSCC who were treated with local excision alone. Methods: On retrospective analysis, a cohort of 12 patients with pathologically confirmed stage I ACSCC treated at Mayo Clinic between 1994 and 2014 was identified who were managed with local excision alone. Baseline as well as followup data were obtained by electronic chart review. Results: Median age of the patients at diagnosis was 68 years (range: 36-81 years) and majority were females (76.9%). Median follow-up duration was 7.5 years. Of the 12 patients, 2 patients did not receive standard CRT due to co-morbid conditions and other 10 patients chose surveillance over CRT. There was only one patient with disease recurrence at 3 years which was salvaged by abdominoperineal resection (APR). This subject remains alive and disease free at the time of data collection (4 years out from APR). There were 4 deaths, all unrelated to ACSCC. Of 12 patients, 10 patients (83%) remained disease free at 5 years and beyond, 1 patient had recurrence and 1 patient was lost to follow up at 5 months from diagnosis. Conclusions: Local excision as a single modality of treatment may be safe and effective for highly selected small stage I ACSCC. Further clinical study is warranted to accurately define the patient population who can be treated with local excision alone, potentially sparing them long term toxicities.

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients > 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p < 0.01), and stage III (HR 1.91 [1.35-2.70], p < 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.

450 Background: The standard treatment for patients with gallbladder cancer is a combination of gemcitabine and cisplatin based on ABC-02 trial. However, there are no guidelines regarding treatment after first-line therapy. We retrospectively analyzed the efficacy and overall survival of different second-line regimens. Methods: We identified 203 patients with advanced gallbladder cancer who received palliative treatment between January 2000 and December 2015 at Mayo Clinic, Rochester. RECIST criteria was used to assess response. Results: 68 patients received second-line chemotherapy. Median age was 63 years (range: 32-86) and majority were males (60.6%). The median time from the diagnosis to the start of the second line chemotherapy was 8 (1-120) months. The most common used second-line chemotherapy were FOLFOX (14), gemcitabine alone (10), single agent fluoropyrimidine (11), gemcitabine with capecitabine (5), and capecitabine with oxaliplatin (4). There were 30 patients that received 5-fluorouracil based regimens, 20 patients received gemcitabine-based regimen, 3 patients received taxane-based regimen, and 15 patients received other types of chemotherapy. Median progression free survival and overall survival was 2.1 (1.8-2.7) and 16.7 (13.2-21.3) months respectively. There were 10 (52%), 11 (37%), 2 (67%), 5 (33%) with partial response and stable disease in 5-fluorouracil-based, gemcitabine-based, taxane-based, and others, respectively. There were no difference in PFS, with median PFS of 2.5, 2.0, 2.8 and 2.3 months, respectively (p=0.43). The overall survival were 15.7 (8.9-40.2), 15.0 (10.7-21.3), 40.3 (22.0-47.0), and 20.4 (9.2-30.7) months, respectively (p=0.83). There were 27 patients that received single agent chemotherapy and 41 patients that received combined regimen. There were 17 (42%) patients and 13 (48%) patients with partial response or stable disease in single and combined regimen. There were no differences in progression free survival and overall survival between single and multi agent chemotherapy. Conclusions: In this largest single institution study, second-line chemotherapy regimens for gallbladder cancer provided benefit in select patients and there is an urgent need to develop more active therapeutic regimens.

398 Background: The PI3K/mTOR pathway has emerged as a potential target for anticancer therapy. Considerable evidence suggests that targeting a single isoform of PI3K (p110α) would have sufficient antitumor activity and improved therapeutic window. Further, PI3KCA mutations, gene encoding isoform p110α, are described in pancreatic adenocarcinoma (PAC). BYL719 is an oral class I α-specific PI3K inhibitor that showed preclinical anti-tumor activity. The first in human phase 1 trial of BYL719 defined the maximum tolerated dose (MTD) at 400mg QD. Methods: This was a phase I, single center study (standard 3+3 design). The primary objective was to determine the MTD of BYL719 in combination with gemcitabine (G) and nab-paclitaxel (nabP) as frontline therapy in locally advanced or metastatic PAC. BYL719 was given orally daily (Table). Patients (pts) were restaged q2 cycles. The study was closed prematurely due to slow accrual. Results: Fifteen pts were enrolled (median age was 58 years). Three pts each participated in cohorts 1 and 2. Nine pts were enrolled in cohort 3, but 4 were replaced (3 pts withdrew consent prior to evaluation and 1 missed > 10 days of treatment). One pt in cohort 3 had DLT related to grade 3 nausea and vomiting. A total of 19 grade 3 and 4 adverse events were records as probably or possibly associated with BYL719. The most common ones were hyperglycemia, anemia, and neutrophil count decreased. One pt developed Posterior reversible encephalopathy syndrome (PRES) during cycle 7. Although we could not completely exclude BYL719 as a cause, PRES was attributed to G. One pt had sudden death during cycle 4 that was attributed to progression. Only 8 pts were evaluable for response. Two had stable disease, 5 had partial responses and 1 had progression. The median progression-free survival and overall survival were 5.36 months (1.6 to 10 months) and 8.74 months (3.8 to 21.2 months) respectively. Conclusions: The combination of full doses of G + nabP and BYL719 can be safely administered up to BYL dose of 250 mg/day. Clinical trial information: NCT02155088. [Table: see text]

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

e15757 Background: SPN is a rare neoplasia of the pancreas, defined by the World Health Organization (WHO) as an epithelial low-grade malignant neoplasm, with a high-grade malignant transformation potential. Literature in this subject is scarce and limited only to small retrospective series. Methods: This is a retrospective study aiming to characterize patients with the diagnosis of SPN at Mayo Clinic between 1992 and 2016. Demographics, clinical and pathological features, recurrence rate and overall survival were recorded. Malignant SPN was defined as per the WHO 2010 classification (Perineural invasion, angioinvasion or deep tissue invasion) and compared to Benign SPN. Results: 44 patients with SPN were identified. 39 patients (88.6%) were female. Median age at diagnosis was 27.5 (Range: 13-64). The most frequent presentation was abdominal pain (52.6%), whereas 36.8% were diagnosed based on incidental imaging findings. Majority (60.4%) of the tumors were located at the pancreatic tail, and 48.5% were solid-cystic lesions. Vascular and lymph node involvement were infrequent. 15 cases (30.23%) were classified as malignant. Tumor size was associated with malignant behavior (Table). Three patients had a metastatic presentation. All but 1 patient were treated with surgery. R1 resection was more frequent in malignant SPN, and 2 patients experienced disease recurrence. Two Stage IV patients were treated with surgery and experienced long term survival, one of them without evidence of disease. There was only 1 death recorded. Conclusions: SNP presents predominantly on young women. The prognosis is excellent even in presence of malignant features, and a complete surgery remains as the main treatment. [Table: see text]

e15703 Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG > = 1), old age ( > = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p < 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score > = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.