Abstract 1656P
Background
Although the pace of genetic research has dramatically accelerated, little is known about the pathogenic germline variants in DNA damage repair (DDR) genes in small cell lung cancer (SCLC).
Methods
Peripheral blood samples were collected from patients with untreated histologically confirmed SCLC who were included in the clinical trial of ChiCTR1900023956. DNA was isolated from leukocytes and sequenced using a 1021-gene panel that included 40 DDR genes according to KEGG database. Germline variants were interpreted following ACMG guideline, and pathogenic and likely pathogenic variants were included in the final analysis cohort. Clinical and demographic information were collected through the medical records and patient interviews.
Results
A total of 38 patients with SCLC were enrolled with 2 patients' withdrawal of informed consent, and 36 patients were included in the final analysis set (FAS). All patients were treated with first-line standard platinum-based chemotherapy. There were 29,723 germline variants found in FAS, and 1.7% (510/29723) were in the DDR associated pathways. A total of four patients (4/36, 11.1%) hold the pathogenic or likely pathogenic germline variants in genes involved in DDR pathways (Table). The patient with BRCA1 germline mutation was diagnosed with SCLC at the young age of 44. The 1-year progression-free survival rate of all patients with germline variants was 100% (4/4), and 75% (3/4) patients had a more than 23 months' duration of remission time. Table: 1656P
Characteristics of patients with germline mutations
| Age at diagnosis | Sex | Smoker | Germline mutation | Cancers in first-degree relatives | Tumor mutation burden | Follow up time (months) | Progression-free survival (months) | Efficacy of platinum-based chemotherapy |
| 54 | Female | No | MUTYH c.799C>T | None | 7.68 | 17.4 | 12.6 | Partial response |
| 59 | Male | Yes | BLM c.2556-1G>A | None | 19.2 | 23.3 | Not reach | Partial response |
| 56 | Male | Yes | MUTYH c.820C>T | Lung cancer, lung cancer, brain cancer | 0.96 | 23.3 | Not reach | Partial response |
| 44 | Female | No | BRCA1 c.3897_3904delGTGCAGTG | Cardiac cancer | 13.44 | 23.3 | Not reach | Partial response |
Conclusions
A small number of SCLC patients may have an inherited predisposition associated with the germline variants of MUTYH, BLM and BRCA1. All of them had a durable response to platinum-based chemotherapy.
Clinical trial identification
ChiCTR1900023956.
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.