Alsidawi, Samer

Abstract Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy that was grouped with myeloid malignancies in the 2008 WHO classification. The current available literature is limited to small case series and single-institution experiences. This population study using the Surveillance, Epidemiology, and End Results Program (SEER) and the National Cancer Database (NCDB) is the largest to explore epidemiologic and outcome data in BPDCN. SEER collects cancer incidence and survival data from cancer registries covering approximately 26% of the US population. NCDB is a nationwide, facility-based, comprehensive, clinical-surveillance resource for oncology data coming from more than 1500 Commission of Cancer (CoC)-accredited programs. Methods Using data from the SEER and NCDB registries, this study respectively identified 379 (years 2000-2013) and 216 (years 2004-2012) adult patients over the age of 20 diagnosed with BPDCN (ICDO-3 coding 9727). We used the SEER registry to estimate incidence rates, ratios and trends and the NCDB registry to study clinical characteristics, survival and outcomes. The JMP statistical software and the SEER*STAT 8.3.2 were used to conduct statistical analysis. We analyzed survival using the Kaplan-Meier method and used log-rank tests to compare survival distributions. The prognostic effect of pertinent clinical variables was studied using multivariate Cox proportional hazards models. All tests of statistical significance were two-sided and P < 0.05 was considered significant. Results The median age at diagnosis for BPDCN was 52 years (20-93). The incidence of BPDCN was found to be 0.45/1,000,000 age-adjusted to the 2000 US standard population with similar trends over the years. No racial disparities were identified. The male:female ratio was 2 (P<0.00001). The bone marrow was the most common primary site of involvement (42%) followed by the skin (20%) and the heart, mediastinum and pleura (13%). The median overall survival for the entire cohort was found to be 23 months (95% CI; 17-34). Survival rates at 1 year, 2 years and 5 years were found to be 66%, 49% and 38% respectively. 20 patients (10%) underwent a hematopoietic stem cell transplantation (HSCT) as part of their initial therapy and the median overall survival for these patients was not reached compared to a median survival of 19 months for patients who did not undergo upfront HSCT (95% CI; 15-30, P=0.006). A univariate and multivariate analysis was performed including age, race, sex, HSCT, insurance status, income, treatment facility (academic versus non-academic) and disease primary site. Young age and HSCT were predictors of better outcomes. 60 years and older was found to be the age cut-off associated with significantly inferior survival based on receiver operating characteristic (ROC) curve analysis. Conclusion BPDCN is a rare hematologic malignancy associated with a poor median survival of less than two years. Males are twice more likely to be affected than females. The bone marrow is the primary site of involvement in most cases. Younger age (<60 years) and HSCT were predictors of significantly better outcomes. Kaplan-Meier survival curve for the entire cohort Kaplan-Meier survival curves in patients Age <60 versus > 60 Kaplan-Meier survival curves in patients who underwent HSCT versus those who did not Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Al-Kali: Celgene: Research Funding; Onconova Therapeutics, Inc.: Research Funding.

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.

e17529 Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age > 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.

6048 Background: The role of Human Papilloma Virus (HPV) infection in non-oropharyngeal squamous cell carcinoma (non-OPSCC) of the head and neck is unknown. Current available studies have yielded conflicting results due to limited number of patients. We present a large analysis from the National Cancer Database (NCDB) evaluating HPV-positive non-OPSCC. Methods: Using the NCDB registry, we included adults diagnosed with non-OPSCC from 2004-2012 with available HPV status. A cohort of patients with OPSCC was analyzed for HPV prevalence comparison. Survival analysis was performed using Kaplan-Meier method and stratified using HPV-status. The prognostic effect of variables was studied using Cox proportional hazards models. The JMP software was used for statistical analysis. Results: A total of 8726 non-OPSCC patients were identified and primary sites included the oral cavity (50%), larynx (41%) and hypopharynx (9%). 11% of non-OPSCC patients had evidence of infection with high-risk HPV strains compared to 61% of OPSCC patients. HPV-positive non-OPSCC patients presented at slightly younger age, had more advanced stage and higher tumor grade compared to HPV-negative patients (P < 0.01). HPV-positive non-OPSCC patients had better survival than HPV-negative patients (HR 0.82, 95% CI 0.72-0.93, P < 0.01) and this was most pronounced in patients with locally advanced disease (5-year survival 50% versus 40%, HR 0.69, 95% CI 0.6-0.8, P < 0.01). A univariate and multivariate analysis were performed adjusting for age, sex, race, stage, primary site, Charlson/Deyo comorbidity score, financial income, tumor grade, surgery, radiation and chemotherapy administration. Smoking history was unavailable. HPV positivity was an independent predictor of better survival in non-OPSCC in multivariate analysis (HR 0.69, 95% CI 0.59-0.8, P < 0.01). Conclusions: HPV infection is seen in a subset of patients with non-OPSCC head and neck cancer and these present with more advanced tumors. The survival of patients with HPV-positive non-OPSCC is significantly better than HPV-negative tumors. Routine HPV testing and enrollment in treatment de-intensification clinical trials similar to OPSCC might be appropriate for this patient population.

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.

404 Background: Testicular sarcomas represent less than 1% of all testicular tumors in adults. Because of their rarity, little is known about the features and outcomes of these tumors. We present an analysis of the prognosis and survival predictors in patients with testicular sarcomas from the Surveillance, Epidemiology, and End Results Program (SEER). Methods: Using the SEER registry, we identified adults with testicular sarcomas between 1980 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan-Meier method. The prognostic effect of variables was studied using Cox proportional hazards models. Results: We identified 264 patients with testicular sarcomas with a median follow-up time of 9.2 years. The median age at diagnosis was 55 years (range 15-94) and the median tumor size was 6.6 cm (range 0.7-45). 20% of patients with documented staging presented with de novo metastatic disease. Rhabdomyosarcomas were the most common histology (37%). The median OS was 129 months (95%; CI 85-180). OS rates at 1 year and 5 years were 85% and 62% respectively. 53% of deaths were related to cancer. 1-year OS rates for localized, locally advanced and metastatic disease were 91%, 93% and 53% (P<0.0001). Variables that were significant for survival in univariate analysis included age, histology, stage, and surgical resection. Factors that negatively affected survival in multivariate analysis were age >55 years (HR 2; 95% CI, 1.1-3.7), advanced stage (HR 4.8; 95% CI, 2.7-8.4) and surgical unresectability (HR 3.7; 95% CI, 1.1-9.3). Patients with rhabdomyosarcoma had favorable outcomes compared to other histologies (59% vs 17% alive at 10 years, P=0.01). Conclusions: Testicular sarcomas are rare entities with overall good prognosis after surgical resection. Patients presenting with distant metastases, however, have worse outcomes with only about 50% of the patients alive at 1 year. Rhabdomyosarcomas are the most common histology encountered and have relatively better survival. Younger age, earlier stage and surgical resection are factors associated with significantly better outcomes.

420 Background: Advanced biliary cancers respond poorly to chemotherapy and have a dismal survival. Currently gemcitabine-cisplatin (GC) is the standard of care for patients with advanced disease. The efficacy of second line treatment options is not well-defined. We retrospectively evaluated outcomes of patients undergoing second line treatment for advanced biliary cancers at Mayo Clinic. Methods: After obtaining approval from the institutional board review (IRB), we identified 42 patients with advanced and metastatic biliary cancers that progressed after first line (GC) and received second line treatment from 2007-2014. All patients had adequate follow up data. 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 61.5 (range 26-87). The most common regimens used for second line settings were 5-FU-based (69%) followed by gemcitabine-based regimens (19%). The overall response rate (ORR) was 9.1%, while the disease control rate (DCR; stable disease and partial response) was 33%. The median overall survival (mOS) for the entire cohort from first line was 16.8 months (95% CI 12.7-21.7) and the progression-free survival (PFS) was 9.16 months (95% CI 7.3-14.7). From second line start the mOS was 10.4 months (95%; CI 7.3-23.7), and PFS was 2.8 months (95% CI 2.3-4.0). 73% of patients who received second line therapy were alive at 6 months and 50% at 12 months. 25 patients received third line treatment after progression. An univariate and multivariate analysis were performed including age, sex, stage at diagnosis, regimen used, CA19-9 and total body weight loss > 5%, but no significant prognostic factors were identified. Conclusions: Patients with biliary cancers who progress after first line treatment have poor prognosis, but may benefit from second line regimens. 5-FU based regimens were the most commonly used in the second line setting, and 73% of patients who received second line therapy were alive at 6 months.

401 Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms comprising less than 2% of pancreatic tumors. Outcomes of PNETs vary by stage, grade, and clinical presentation. New therapies may have improved outcomes. We present an analysis of the epidemiology and prognosis of patients (pts) with PNETs evaluating a more recent period than previously reported. Methods: Using data from the SEER registry, we identified adults with PNETs between 2000 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied using multivariate Cox proportional hazards models. Results: We identified 5993 pts with PNETs. Over the study duration, there was an increase in the annual incidence from 0.3 to 1.2 per 100.000. This was largely explained by the increase in number of pts with localized disease. The OS for the entire cohort was 54 months (95%; CI 50-58) and 5-year OS rates in localized, locally advanced and metastatic disease were 81.7%, 62% and 26% respectively. New therapies were increasingly implemented after 2008 such as sunitinib, everolimus and capecitabine/temozolomide. OS was better for pts diagnosed after 2008 (HR 0.73; 95% CI, 0.69-0.79; P < 0.0001) and this remained significant after excluding pts with localized disease (HR 0.85; 95% CI, 0.78-0.92; P = 0.0002). Factors found to favorably affect OS included younger age, female sex, early stage, low grade, and surgery. In metastatic disease, pts who had surgery had better OS and this was significant after adjusting for possible confounders (HR 0.36; 95% CI, 0.3-0.45). Conclusions: In this large population-based study, we saw an increase in the annual incidence of PNETs mainly due to an increased number of pts with localized disease. The OS has improved over the study duration likely due to both stage migration and new therapies used in advanced disease. Younger age, female gender, low histologic grade, early stage and surgery were found to be factors that favorably affected survival. Surgery was found to be a predictor of better outcomes in metastatic disease.