Hálfdánarson, Þorvarður R.

355 Background: In this study, we sought to determine the prognostic factors impacting survival of patients with NELM who underwent LT at Mayo Clinic. Methods: We performed a three-site retrospective analysis of patients with unresectable NELM treated with LT from 1990 -2017. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, timing of diagnosis and transplant, extent of liver involvement, and tumor grade, were extracted. Extent of liver involvement was calculated using previously validated standardized volumetry with high defined as > 25% increase in the weight of the extracted liver at the time of the transplant as compared to the standard liver volume. Survival was calculated using the Kaplan–Meier method. Results: We identified 37 patients. Median age at LT was 47 (range 17.0-64.0), male: female (73% vs. 27%, respectively). Primary tumor site was in the pancreas in 51.3% and in the small bowels in 43.2%; 78.4% had NELM at presentation. While primary tumor resection was done at the time of LT in 5 (13.9%) cases, most patients (80.6%) had ˃6-months interval between primary tumor resection and LT surgery. Prior to LT, 25 (74.3%) patients received somatostatin analogues and 18 (61.3%) had liver-directed therapy. Median time from diagnosis to transplant was 33.6 months (0-246). High extent of liver involvement was identified in 12 patients (33.3%). Disease-Free Survival (DFS) at 3, 5, and 10 years was 56.8%, 43.1%, and 22.4% respectively. Overall-survival (OS) at 3, 5, and 10 years was 86.9%, 79.6%, and 52.6% respectively. High extent of liver involvement at the time of transplantation was associated with inferior DFS and OS and patients˃45 years-old at the time of transplantation had worse DFS. Patients whose disease met the OPTN (Organ Procurement and Transplantation Network) criteria for NELM transplantation had significantly better DFS and OS with median 10-year OS of 80.7 % vs. 17%. Conclusions: LT is a reasonable therapeutic option for selected patients with unresectable NELM with 10-year OS of 52.6%. High extent of liver involvement was associated with worse long-term outcomes while meeting OPTN criteria resulted in best outcomes.

Abstract Background Early phase clinical trials evaluate the safety and efficacy of new treatments. The exclusion/inclusion criteria in these trials are usually rigorous and may exclude many patients seen in clinical practice. Our objective was to study the comorbidities limiting the participation of patients with breast, colorectal, or lung cancer in clinical trials. Materials and Methods We queried ClinicalTrials.gov on December 31, 2016. We reviewed the eligibility criteria of 1,103 trials. Logistic regression analyses were completed, and exclusion was studied as a binary variable. Results Out of 1,103 trials, 70 trials (6%) excluded patients >75 years of age, and 45% made no reference to age. Eighty-six percent of trials placed restrictions on patients with history of prior malignancies. Regarding central nervous system (CNS) metastasis, 416 trials (38%) excluded all patients with CNS metastasis, and 373 (34%) only allowed asymptomatic CNS metastasis. Regarding chronic viral infections, 347 trials (31%) excluded all patients with human immunodeficiency virus, and 228 trials (21%) excluded all patients with hepatitis B or C infection. On univariate analysis, chemotherapy trials were more likely to exclude patients with CNS metastasis and history of other malignancies than targeted therapy trials. Multivariate analysis demonstrated that industry-sponsored trials had higher odds of excluding patients with compromised liver function. Conclusion Many clinical trials excluded large segments of the population of patients with cancer. Frequent exclusion criteria included patients with CNS metastasis, history of prior malignancies, and chronic viral infections. The criteria for participation in some clinical trials may be overly restrictive and limit enrollment. Implications for Practice The results of this study revealed that most early phase clinic trials contain strict exclusion criteria, potentially excluding the patients who may be more likely to represent the population treated in clinical settings, leaving patients susceptible to unintended harm from inappropriate generalization of trial results. Careful liberalization of the inclusion/exclusion criteria in clinical trials will allow investigators to understand the benefits and drawbacks of the experimental drug for a broader population, and possibly improve recruitment of patients with cancer into clinical trials.

8549 Background: Bronchial carcinoid tumors are a rare group of neoplasms that usually have an indolent clinical behavior. Surgical resection is the main treatment modality for patients with early stage disease, however it is unclear if lobectomy with mediastinal lymph node dissection (L) is superior compared to partial lobectomy (PL). Methods: Utilizing the National Cancer Database from 2004-2012, 1551 patients diagnosed with T1N0 or T2N0 typical carcinoid tumors (CT), and 167 atypical carcinoid tumors (ACT), who underwent L or PL (segmental or wedge resection) as initial treatment strategy, and did not receive chemotherapy or radiation were identified. All patients had pathologically confirmed diagnosis, negative surgical margins, and complete follow up data. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, sex, race, grade, year of diagnosis, Charlson/Deyo Score, insurance, income, and facility type. T-test was used to compare post-surgical hospital stay. Results: The entire cohort median age was 61 years (range 18-90), and male to female ratio was 0.43. 75% of patients with CT and 78% of ATC underwent L. The 90 day mortality following surgery was < 1 % in both surgical groups. Patients who underwent L had longer post-operative hospitalization stay (mean 5.3 vs. 4.3 days; p < 0.001). The 5 year survival for patients with CT was 95% in the L versus 93% in the PL group (p = 0.62), and for ACT 89% in the L versus 81% PL group (p = 0.28). In a multivariate analysis increasing age was the only prognostic factor, and was associated with inferior survival. The HR for death comparing PL to L was 1.09 (95% CI: 0.65-1.78; p = 0.71) for CT and 1.25 (95% CI: 0.45-3.23; p = 0.65) for ACT. Conclusions: Patients with localized node-negative CT and ACT have excellent 5 year survival. Performing a lobectomy with mediastinal node dissection may not provide additional benefit compared to partial lobectomy, but this may increase the length of hospital stay.

3529 Background: Cancer stem cells are considered to be fundamentally important for resistance, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapy and targeted agents. Methods: A phase Ib/II multi-center study in mCRC pts was done to confirm the RP2D and signs of anti-cancer activity of napabucasin in combination with FOLFIRI +/- Bev. Pts received napabucasin 240 mg PO BID with bi-weekly FOLFIRI IV +/- Bev 5 mg/kg until disease progression or other discontinuation criterion. Results: 82 pretreated mCRC pts were enrolled (ITT); including 32 (39%) previously treated with FOLFIRI +/- bev. Of the 82 pts, 48 received FOLFIRI and 34 FOLFIRI plus bev in combination with napabucasin. There was no dose-limiting or unexpected toxicity or significant PK interactions. Most common adverse events (AEs) included grade 1/2 diarrhea, cramping, nausea, vomiting, fatigue and anorexia with grade 4 diarrhea in 1 pt and 27 pts with grade 3 AEs including: diarrhea (15), fatigue (5), dehydration (1), electrolyte imbalance (4), abdominal pain (1), vomiting (1) and weight loss (1), which resolved with dose reduction and supportive care. Disease control (CR+PR+SD) was observed in 55 of 66 pts who received RECIST evaluation (83%), with 1 CR (1.5%), 13 PR (20%) (33-100% regression) and 27 SD with tumor regression (41%). Conclusions: This phase Ib/II study confirmed that napabucasin can be safely combined with FOLFIRI +/- bev, and shows encouraging signs of efficacy in pretreated mCRC pts, including pts previously treated with FOLFIRI +/- bev. Clinical trial information: NCT02024607. [Table: see text]

8533 Background: BNET are a rare and frequently indolent group of neoplasms. Lobectomy is frequently done for patients with non-metastatic disease, and the role of adjuvant chemotherapy for patients with node positive disease (N+) is debated. Methods: Utilizing the National Cancer Database from 2004-2012 we identified 1682 patients with N+ non-metastatic BNET. All patients underwent primary resection, had pathologically confirmed diagnosis, complete follow up data, and were alive > 30 days following surgery. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used to compare 2 groups of patients that differed based on receiving or not adjuvant chemotherapy. Subgroup analyses were performed based on histologic subtypes. Cox proportional hazards was performed to control for age, sex, race, grade, surgical margins, type of surgery, year of diagnosis, Charlson/Deyo Score, insurance, facility type, and location. Results: 651 patients with typical carcinoid (CT), 239 atypical carcinoid (ACT), 426 large cell neuroendocrine carcinoma (LCNEC), and 366 neuroendocrine carcinoma (NEC) were analyzed. The cohort median age was 61, and the female:male ratio was 1.8 for CT, ACT and NEC, and 1 for LCNEC 90% of patients were White and there were no significant differences amongst histologic subtypes. 6% of patients with CT received ADJ-CT, compared to 40% ACT, 42% NEC, and 70% LCNEC. In a multivariate analysis, only increasing age was associated with worse prognosis across all histologic subtypes, and non-academic facility for CT, and male sex for NEC. ADJ-CT was not associated with OS benefit for patients with ACT (HR 1.1; 95% CI 0.68-1.78; p:0.6), was associated with inferior OS in CT (HR: 3.8 (95% CI 1.9-7.0; p = 0.004) and NEC (HR: 2.15; 95% CI 1.5-3.0; p < 0.001), and may provide benefit for LCNEC (HR: 0.67; 95% CI 0.5-0.9; p = 0.009). Conclusions: Adjuvant chemotherapy was not associated with survival benefit for patients with node positive and non-metastatic BNET except for LCNEC, and may be harmful for patients with CT and NEC.

Objectives Prognostic factors for solid pseudopapillary neoplasms (SPN) of the pancreas have been incompletely defined in the literature. We aimed to use the National Cancer Database to describe survival and characterize prognostic factors in patients with pancreatic pseudopapillary neoplasms. Methods We identified 304 patients with pancreatic SPN diagnosed between 2004 and 2012 using the National Cancer Database. All patients were included in the survival analysis. Kaplan-Meier method, χ 2 , and log-rank tests were used for statistical analysis. Cox proportional hazard regression model was used for multivariate analysis. Results The median age at diagnosis was 36.5 years. Eighty-five percent of patients were female, 69% were white, and 25% were black. Metastases were observed in 5% of patients. Median tumor size was 5.1 cm. Ninety-two percent of patients underwent primary tumor resection. At 60 months, 98% of patients who underwent resection were alive, and 40% who did not undergo resection were alive. On multivariate analysis, female sex, resection of primary tumor, and absence of metastasis were correlated with improved survival. Conclusions Patients with SPN who undergo resection have an excellent survival at 5 years. Surgery should be considered in all patients with this diagnosis.