39MO - Genomic framework of lung carcinoid: Analysis of the AACR GENIE database

Background

Carcinoid tumors, rare neuroendocrine tumors, occur in the lungs in approximately 25% of cases. The 5-year survival rate for lung carcinoid in the US is 98% for localized disease and 86% for regional disease, with a drop to 55% for metastatic cases. Patients with metastasis are often treated with temozolomide-based chemotherapy, mTOR inhibitors (everolimus), platinum-based chemotherapy, or peptide receptor radionuclide therapy. We aim to investigate potential unexplored genetic targets. We intend to explore if there is a role for immunotherapy for treatment for lung carcinoid as it is generally better tolerated and less toxic compared to chemotherapy.

Methods

Using the cBioPortal platform, we accessed the AACR GENIE version 15.0 database. Demographic data were gathered from patients with lung carcinoid. We outlined the frequency of mutated genes, copy number alterations, and structural variations in the population.

Results

We analyzed 242 patients and 253 samples. 73.1% of the patients were females and 26.9% were males. 74.7% of samples were collected from a lung primary, while 16.2% of samples were from metastatic sites. The median age at sequencing was 62 years. The highest frequency of mutations was seen in LRP1B gene (18.4%), followed by the MN1 gene (15.8%) and the ARID1A gene (11.8%). The most structural variants were found in the MEN1 gene at 0.9% (n =2, total number of profiled samples = 226). The most common copy number alteration was PDCD1 (n=5, number of profiled samples=134) at 3.7% and CCND1 on 11q13.3 (n=4, number of profiled samples=201) at 2%.

Conclusions

Prior studies have shown that one of the most frequently mutated pathways in pulmonary carcinoids involves MEN1 gene. We found that genomic alterations in LRP1B, ARID1A, PDCD1 and CCND1 are also frequently observed. It is well known that anti-PD1 therapy is efficient in PD1 expressing cancers. LRP1B mutation in lung cancers has been shown to affect the immune microenvironment and enhance the efficacy of immune checkpoint inhibitors. While ARID1A mutations correlate with longer median overall survival when treated with immunotherapy. The limited number of ongoing clinical trials on targeted therapies underscores the clear need to explore the genomic targets for precision therapies in lung carcinoids.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.