Citations

e16702 Background: There are only a few reports examining the treatment patterns for poorly differentiated rectal/anal NEC. In this study, we sought to report treatment and survival outcomes for patients with NEC of the anus and rectum seen at Mayo Clinic. Methods: We identified patients with a primary NEC of the anus or rectum using Mayo Clinic databases (Minnesota, Arizona, Florida) from the year 2000 to present. NEC identified within polyps on colonoscopy was excluded from this study. Patients’ demographics were compiled. Kaplan Meier analyses were performed to evaluate overall survival (OS) for all patients, as well as subgroups with locoregional disease (LRD) and metastatic disease at diagnosis. Progression free survival (PFS) was also evaluated for patients with LRD treated with chemoradiation therapy (CRT). Results: 38 patients with NEC of the anus/rectum were identified with a median age of 55.5 years. 23 patients (61%) had metastatic disease at diagnosis and 15 (39%) had LRD. The most common site of metastasis was the liver (n = 20). Patients with metastatic disease at presentation had significantly shorter OS compared to patients with LRD (median OS 10.4 vs. 18.9 months, p = 0.039; HR 2.46, 95% CI [1.001-6.050]). 34 total patients received chemotherapy (ORR 11.8%), with platinum + etoposide (EP) being the most common first-line chemotherapy (n = 26). 10 of 15 patients with LRD received CRT (9 with EP and 1 with 5-FU) with median PFS of 6.3 months (95% CI 2.3-16.5 months), a 1-year PFS rate of 20%, and median OS of 18.6 months (95% CI 13.5-23.7 months). 2/10 received induction chemotherapy prior to CRT with 6/10 undergoing primary tumor resection (1 prior to CRT and 5 after CRT). Only 3 CRT patients were living at time of analysis (all underwent surgical resection), 2 without any active disease, 1 who achieved complete response with CRT then suffered recurrence and is still undergoing treatment. Conclusions: NEC of the anus and rectum is an aggressive malignancy with most patients experiencing metastatic disease at presentation and poor response to chemotherapy at all stages. Even those with LRD experience a very poor prognosis with OS of 18.9 months from diagnosis. For LRD, most patients underwent CRT with only a short-lived response (median PFS 6.3 months). Those achieving sustained response also underwent surgical resection. Overall, prognosis is poor for all stages and further study on a large scale is warranted to better characterize this rare, aggressive malignancy.

e16691 Background: Recent WHO classification of NET has defined high-grade well-differentiated NET (NET G3) as a distinct entity that is clinically different from neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aims to evaluate NET G3 response to different treatment regimens. Methods: This is a retrospective study of NET G3 patients within the Mayo Clinic database (Arizona, Florida, and Minnesota). Patient demographics along with treatment responses and survival were assessed. Primary end points were progression-free survival (PFS) and objective response rate (ORR) by RECIST 1.1 criteria. Results: 71 patients with NET G3 were identified. Systemic treatment data was available in 30 patients who had a median age of 59.5 years at time of diagnosis. The primary tumor was most commonly pancreatic (73.3%). Ki 67 index was ≥55% in 26.7% of cases. 56.7% of cases had > 1 metastatic site. Treatment regimens included: capecitabine+temozolomide (CAPTEM) (n = 20), somatostatin analog (SSA) (n = 14), carboplatin/cisplatin+etoposide (EP) (n = 7), everolimus (n = 2), FOLFOX (n = 7), and lutetium Lu 177 DOTATATE (PRRT) (n = 10). CAPTEM was the most commonly used regimen (10 first-line, and 10 second-line) with ORR of 35%, disease control rate (DCR) of 65%, and median PFS of 9.4 months. The table summarizes the treatment data and responses rates for the various therapies used. Conclusions: Among NET G3 patients treated at Mayo Clinic, CAPTEM was found to be the most commonly used treatment with reasonable efficacy and disease control. Other treatment options include SSA, PRRT, FOLFOX, and EP. Prospective studies evaluating different treatments effects in NET G3 patients are needed to determine an optimal treatment strategy. [Table: see text]

4541 Background: Anti-VEGFR2 therapy (ramucirumab/paclitaxel [RAM/TAX]) and ICI are approved as 2nd- and 3rd-line therapy (Tx), respectively, for pts with mGEA. We unexpectedly saw durable responses in 2 pts on RAM/TAX after progression on an ICI trial (KN-059; PMID 29674442). We performed a pilot to examine the clinical activity of ICI followed by RAM/TAX. Then we retrospectively compared the outcomes of pts who received this serial Tx to pts who received RAM/TAX without prior ICI. Methods: All pts with mGEA at Mayo Clinic who received RAM/TAX (2014-19) were included (N = 87). Outcomes were best objective response rate (ORR: complete [CR] or partial response) per RECIST1.1, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Chi square and multivariate (MV) logistic and Cox regression were used. Results: 15 consecutive pts with measurable mGEA received ICI immediately followed by RAM/TAX after irRECIST progression. Most pts (95%) did not respond to ICI. Yet on RAM/TAX, 100% (15/15) had tumor reduction (range -8% to -100%) with an ORR of 73% (11/15), including 3 CRs. In these pts (who received ICI followed by RAMTAX), PFS on RAMTAX was longer than on last chemotherapy before ICI (12.3 vs 3.0 m, P < .001). Outcomes on RAM/TAX in these pts were significantly better than in pts who received RAM/TAX alone (see Table). Associations were strengthened after adjusting for total lines of Tx, line of Tx of RAM/TAX, age, and ECOG PS. Exploratory analysis of paired tumor biopsies collected pre-ICI and on RAM/TAX in a small subset revealed that the frequency of intratumoral immunosuppressive FOXP3+ Tregs decreased on RAM/TAX, whereas the frequency of antitumor CD8+ T cells was preserved. Conclusions: RAM/TAX immediately preceded by ICI was associated with significantly higher OS, ORR, and DOR than RAM/TAX alone, suggesting ICI may enhance efficacy of subsequent anti-VEGFR/taxane therapy. This novel sequence of therapy will be tested prospectively in a new randomized phase 2 trial (NCT04069273). [Table: see text]

AbstractOver the last 5 years, there have been more than 140 new drug approvals in the field of Oncology alone, all based on newly published clinical trials. These approvals have led to an ongoing change in clinical practice, offering new therapeutic options for patients. Therefore, it is important for healthcare providers to be able to appraise a clinical trial and determine its validity, understand its results, and be able to apply such results to their patients. In this guide, we provide a simplified approach tailored to practicing clinicians and trainees. The same concepts and principles apply to other medical specialties.

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.

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.