Hálfdánarson, Þorvarður R.

Objectives A platinum/etoposide doublet is standard first-line therapy for poorly differentiated neuroendocrine carcinoma (PD NEC); however, evidence to guide treatment beyond first-line regimens is lacking. This study aimed to evaluate the efficacy of second-line regimens in PD NEC. Methods We performed a retrospective analysis of patients treated with second-line chemotherapy for PD NEC. Inclusion criteria were previous first-line therapy with platinum/etoposide, extrapulmonary PD NEC, and follow-up data. The primary end points were overall survival (OS) and progression-free survival (PFS) after second-line therapy. Secondary end points included OS and PFS from first-line therapy. Results Sixty-four patients were included. The median OS from initiation of second-line therapy was 6.2 months (95% confidence interval [CI], 4.9–8.9). The median PFS was 2.3 months (95% CI, 2.0–3.2). No second-line regimen showed a statistically significant difference in OS or PFS. There was a significant increase in OS for cisplatin first-line regimens compared with carboplatin (17.0 months [95% CI, 12.5–22.6] vs 11.7 months [95% CI, 8.0–14.0]). Conclusions The efficacy of current second-line therapy in PD NEC is poor. No second-line regimen showed statistically significant superiority. Cisplatin was associated with longer OS regardless of second-line regimen or age. However, unmeasured confounders such as performance status or comorbidities may explain this effect.

e20029 Background: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pulmonary disorder with neuroendocrine cell proliferation with potential progression to lung neuroendocrine tumor (Lu-NET). Optimal diagnostic and treatment strategies have yet to be well defined. Herein, we aim to describe the Mayo Clinic experience with DIPNECH. Methods: A retrospective analysis was performed of patients diagnosed with DIPNECH within Mayo Clinic between January 2000-Febuary 2019. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, disease characteristics, time of diagnosis, surgery, and last follow up date were extracted. Extent of symptom burden, treatment approaches, disease progression, and disease-free survival (DFS) were evaluated by chart review. Results: A total of 59 patients were identified with a median age of 63(43-81) years. The cohort was predominantly female (93.2%) and non-smoking (76.3%). Most patients (86.4%) had symptomatic disease with chronic cough being the most common (71.2%) followed by exertional dyspnea (44.1%). Imaging typically showed bilateral lung nodules (93.2%) with mosaic attenuation noted 69.5% of the time. Surgical resection was frequently completed to confirm diagnosis (94.9%). Most patients received inhaled glucocorticoids combined with a beta agonist (79.7%). Oral steroid use was seen in 49.2% of patients whereas a somatostatin analog was used in 15.3% following the diagnosis of DIPNECH. These medical interventions led to symptom relief in 23.7% of the patients. The median follow up for all patients was 19.5 months. Progression of tumorlets was seen in 48.7% of patients with only 7(17.9%) patients progressing to a diagnosis of Lu-NET. The 3-year DFS was 90.5%. Conclusions: This is amongst the largest studies completed evaluating DIPNECH patients. DIPNECH remains a rare disease more commonly diagnosed in women in their early 60’s. DIPNECH appears to have an indolent course with obstructive symptoms being the most common finding. A minority of patients experienced symptom relief with therapy. Overall, DIPNECH appears to have a low risk of progressing to Lu-NET based on the observation of this study.

6542 Background: Adjuvant chemotherapy (ACT) and postoperative radiotherapy (PORT) are used in the treatment of resected NSCLC to reduce risk of relapse, but guideline-based recommendations for these treatment modalities have varied over time. ACT is now recommended for stage II-IIIA NSCLC following resection based on phase III trial results which, starting in 2003, showed improved survival. Conversely PORT recommendations have been rescinded due largely to a 1998 Lancet meta-analysis. In this study we explore the rates of these two adjuvant treatment modalities across areas over time. Methods: Using SEER-Medicare data we identified 18,410 patients diagnosed 1992-2007 with resected NSCLC. Adjuvant treatment was defined as the first treatment received within 4 months of surgery. The study period was divided into 3 eras: 1992-1998, 1999-2003, and 2004-2007. Area treatment rates were calculated using the 50 patients closest to each zip code, adjusting for patient and area characteristics. Areas were then ranked and divided into quintiles. Percent differences were calculated to measure the variation between the highest and lowest quintiles. Results: Between 1992-1998 when the results of the phase III ACT trials were still unknown and utilization of ACT was low, areas with the highest treatment rates were 35 times more likely than areas with the lowest rates to administer ACT. After 2003 ACT use increased swiftly and geographic variation fell. In contrast, PORT utilization rates have declined and become more geographically dispersed since 1998. Receiving no adjuvant treatment was highest between 1999-2003, after the Lancet PORT meta-analysis and before the major ACT trials. Conclusions: NSCLC adjuvant treatment has been shifting from PORT to ACT. The positive results of the ACT trials and publication of treatment guidelines have increased usage and reduced geographic variation in ACT use. Geographic variation in PORT use however has increased over time, although overall usage has decreased. [Table: see text]

e19065 Background: Treatment decisions for patients with advanced stage (stages IIIB and IV) non-small cell lung cancer (AS NSCLC) are influenced by comorbidity at time of diagnosis. We studied the effects of comorbidity on survival and whether effects differ for short-term (120 days) vs. for long-term (>120 days) survival. Methods: Data were from surveys and medical records of 1498 patients withnewly diagnosed AS NSCLC in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS). Respiratory disease severity and comorbidities at diagnosis were measured from the Adult Comorbidity Evaluation (ACE-27) index and model fitting used the Akaike Information Criteria. The log-rank test was used for univariable survival models, and Cox proportional hazards regression for multivariable survival models. Results: Five comorbidities were significantly associated with survival and 437 (29.2%) patients had one or more of these. Survival to 120 days was significantly poorer for patients with a baseline diagnosis of stroke [hazard ratio (HR) 1.92; 95% confidence interval (CI) 1.26–2.93], diabetes (HR 1.33, 95% CI 1.08–1.65), or congestive heart failure (HR 1.45, 95% CI 1.07–1.96), controlling for age, gender, smoking status, stage, severe respiratory disease, and brain metastases. Given survival to 120 days (885 pts, 59%), survival beyond that was significantly poorer only for patients with baseline arrhythmia (HR 1.47, 95% CI 1.15–1.87) or end stage renal disease (HR 1.82, 95% CI 1.09–3.04), controlling for the covariates above. Adjustment for chemotherapy use had no effect on these associations. Conclusions: Several comorbidities present at diagnosis affected survival for AS NSCLC, with some comorbidities having a more immediate relationship to survival than others. Our finding provides information that could be used to tailor treatment decisions to patients’ comorbidities at diagnosis.

e14594 Background: PNETs are uncommon malignancies and little is known about risk their factors and association with other cancers. Our aim was to evaluate smoking, alcohol use, personal history of diabetes and a family history of PNET and other cancers as potential risk factors. Methods: PNET cases seen at Mayo Clinic Rochester from 2000 to 2011 were evaluated. Insulinoma and high-grade PNETs were excluded. Primary care patients served as controls and were matched (2:1 ratio) to cases on age, sex and region of residence. Cases and controls completed questionnaires at the time of evaluation. Categorical variables were compared with the chi-square test; continuous variables were compared using a two-sample t test. Results: 355 cases were evaluated, mean age was 56.6 years, 52% were males and 96% were White. Personal smoking history was not associated with PNETs (cases 51%, controls 47%, p=0.24). Ever-alcohol use was less common among cases (54% vs. 67%, p=0.001). 19% of cases reported a history of diabetes compared with 11% of controls (p<0.001). Cases were more likely than controls to report a family member with sarcoma (p=0.02), PNET (p=0.024), gall bladder cancer (p=0.024), ovarian cancer (p=0.04) and stomach cancer (p=0.01). Conclusions: Cases with PNETs were more likely than controls to report a history of diabetes and less likely to report alcohol use. There was no association with smoking. Several types of cancer were more commonly reported in family members of cases than controls.

4127 Background: Small bowel adenocarcinoma (SBA) is a rare tumor accounting for less than 2% of all GI tumors. The prognosis of advanced disease is poor. Benefits of adjuvant therapy following complete resection are uncertain. Methods: We retrospectively reviewed the records of 491 pts with primary SBA diagnosed at the Mayo Clinic from 1970–2005. Patients with ampullary and periampullary tumors were excluded. Results: 303 pts (62%) were male and the median age was 62 years. 280 (57%) of the tumors were located in the duodenum, 143 (29%) in the jejunum, 48 (10%) in the ileum and in 20 (9%) the location was not specified. Abdominal pain was the most common principal symptom occurring in 203 pts (43%), followed by anemia/GI bleeding in 104 pts (22%) and nausea/vomiting in 76 pts (16%). The most common histologic grading was 3, occurring in 224 pts (45%). 79 pts (16%) grade 4, 170 pts (35%) grade 2, with 7 (1.4%) grade 1. The TNM staging was as follows: 0: 3 (0.6%), I: 36 (7.3%), II: 133 (27.1%), III: 137 (27.9) and IV: 163 (33.2). In 18 pts (3.7%), data were insufficient for staging. The median survival for the entire cohort was 20.7 months, with 5 and 10 year survival 26% and 19% respectively. Increasing age (p < 0.0001), male sex (p = 0.026), advanced stage (p < 0.0001), grade 4 tumors (p = 0.005) and residual disease after surgery (p < 0.0001) were independently associated with shortened survival in a multivariate analysis. Neither adjuvant chemoradiation (n = 40) nor 5-FU based chemotherapy (n = 33) improved overall survival after complete resection, even after adjusting for age, sex, location, lymph node status and grade (RR 1.17, p = 0.45). This remained true for the subset of patients with resected duodenal tumors as well (RR 1.06, p = 0.83). The use of chemotherapy was associated with prolonged survival in patients with metastatic disease. The median survival and 1-year survival was 15.3 mos vs. 3.1 mos and 59% vs. 5.9% respectively (p < 0.0001), in this highly selected group. Conclusion: SBA is a rare tumor with a relatively poor prognosis. Complete resection of all disease offers the only chance of cure. The benefits of adjuvant therapy remain unknown, but chemotherapy in the metastatic setting may provide survival benefit. No significant financial relationships to disclose.

4584 Background: PETs (islet cell tumors) are uncommon and often indolent tumors, but little is known about the incidence of PETs in the US and trends in survival. Methods: The SEER registry was used to identify cases of functional PETs (fPETs) and non-functional PETs (nfPETs) diagnosed from 1973–2000. Benign insulinomas were excluded. Incidence rates were age adjusted to the standard US population for 2000. Results: Of 971 patients with PETs, 824 (85%) were nfPETs, 37 (4%) were malignant insulinomas, 88 (9%) were fPETs other than insulinoma, and data were missing for 22 (2%). The crude annual incidence of PETs (per 100,000) for all ages was 0.1 in females and 0.2 in males. The incidence was highest in the age group >70 years (0.4, Table ). Tumors were localized in 109 (11%), regionally advanced in 228 (23%), and distant metastases were present in 545 (56%). Patients with fPETs were younger than patients with nfPETs (mean age 54.2 vs. 57.6, p=0.038) and had a longer median survival (MS) (47 vs. 30 months (mos), p=0.001) but were as likely to have advanced disease (p=0.50). The 5 and 10 year overall survival was 45.3% vs. 32.7% and 31.7% vs. 18.1% for fPETs vs. nfPETs, respectively. MS was 95 mos for localized PETs, 66 mos in regionally advanced PETs and 19 mos for distant metastases (p<0.001). Race did not influence incidence and survival. On multivariate analysis, only age (p<0.0001) and stage (<0.0001) were independently associated with prognosis but the functional status of the tumor approached significance (p=0.053). Survival has improved over time with longer MS in patients diagnosed in later quartiles of the observation period (p<0.001, Table). This difference is not explained by stage migration, as patients in all four quartiles had a similar stage distribution (p=0.79). Conclusions: PETs are uncommon tumors and the prognosis is highly dependent on the stage and the age of the patients. Patients with fPETs may have a better prognosis than nfPETs. Survival has improved over time. [Table: see text] No significant financial relationships to disclose.

630 Background: Neuroendocrine tumors (NET) are heterogeneous in terms of prognosis based on location, grade, and stage. In this study we report causes of deaths (COD) in patients with NET. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to query data of NET patients diagnosed between 2000 and 2016 and report COD following NET diagnosis. Results: We reviewed 94,399 NET cases of which 38,692 died during the follow-up period. The highest number of deaths (5,721) occurred within less than a year following grade 3 (G3) NET diagnosis while most deaths in grade 1/2 (G1/G2) cases occurred within 1-5 years of diagnosis (1,889 and 987, respectively). During the first year of diagnosis, most deaths were from NETs (73%), followed by other cancers (11.2%) and cardiac diseases (CD) (4.6%). As time passed, NET deaths decreased to be responsible for 24.3% of deaths after > 10 years of diagnosis, while other cancers (14%) and CD (19.7%) became more common. When dividing NET cases by grade, NETs were responsible for 42.8%, 63.4%, and 81.2% of deaths in G1, G2, and G3, respectively, while other cancers were responsible for 16.2%, 11.8%, and 7.2% of deaths, respectively and CDs were responsible for 12.3%, 7.2%, and 3.2% of deaths, respectively. For G1 localized NET: non-NET cancers (22.2%) was the most common COD followed by NET (19.7 %) and CD (16.8%). For G2 localized NET, NET was COD in 31.1% of cases followed by non-NET cancers (22.4%) and CD (13.8%). In metastatic disease, NET was the most common COD regardless of grade. Conclusions: In G1 and G2 localized NET, deaths were mostly secondary to non-NET causes. Therefore, counseling patients regarding survivorship with cancer-screening and focusing on prevention from non-cancer deaths is important. On the other hand, NET is responsible for most deaths in metastatic NET regardless of grade. Further advances in systemic therapies are needed to improve the outcomes of advanced disease.

629 Background: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms with outcome varying by stage, grade, and clinical presentation. We present an analysis of the epidemiology and prognosis of patients (pts) with PNETs over the last two decades using a large population-based database. Methods: Using 2000-2016 data from the SEER 18 registry, we identified pts with PNETs using a combination of ICD-O-3 and histology codes. Age-adjusted incidence rates were calculated using SEER*Stat 8.3.5. Using SAS 9.4, overall survival (OS) was analyzed using the Kaplan–Meier method, and prognostic factors were investigated using a multivariate Cox proportional hazards model. Results: We identified 8,944 pts with PNETs. Annual incidence rates increased over the study period from 0.27 to 1.00 per 100,000. This was largely explained by a significant increase in number of pts diagnosed with localized disease in recent years (2012-2016). Median OS (mOS) for the entire cohort was 68 months (95% CI 64-73) and 5-year OS rates in localized, regional, and metastatic disease were 83%, 67%, and 28%, respectively. There was a significant improvement in OS for pts diagnosed between 2009-2016 (mOS 85 months) compared to those diagnosed between 2000-2008 (mOS 46 months) (HR 0.66; p < .001). In addition, pts with grade I/II metastatic disease who underwent surgery experienced significantly longer OS (mOS 84 months) compared to those who did not undergo surgery (mOS 18 months) (HR 0.31; p < .001). In the multivariate analysis, more recent diagnosis, younger age, female sex, surgery, early stage, and lower grade favorably predicted OS. On the other hand, functional status and race did not predict OS. Conclusions: There has been a steady increase in the incidence of PNETs with notable stage migration as most patients are diagnosed in early stages of disease in recent years. Additionally, this increase in incidence is accompanied by a significant improvement in survival across different disease stages.