2798 - SWItch/Sucrose NonFermentable Complex-Deficient Pulmonary Neoplasms: Clinicopathologic Characteristics and Outcomes to Radiotherapy and Immunotherapy

Y. Gu¹, S. Lai¹, J. Yang², J. Zhang¹, X. Fan¹, and Q. Zheng¹; ¹Fudan University Shanghai Cancer Center, Shanghai, China, ²Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, xiaogan, China

Purpose/Objective(s): The SWItch/Sucrose Nonfermentable (SWI/SNF) complex, a multi-subunit chromatin remodeler, is linked to aggressive tumors when deficient. Research on different SWI/SNF complex subunit deficiencies (SWI/SNF-d) across pathologies is limited, and effective treatment strategies are unclear. Materials/

Methods: Patient data on SWI/SNF-d pulmonary neoplasms were collected from our center, assessing ARID1A, SMARCA2, SMARCA4, and SMARCB1 subunit expression via immunohistochemistry, with retrospective analysis of survival and treatment results.
Results: The study included 101 cases of SWI/SNF-d pulmonary neoplasms out of 675 SWI/SNF-d cancer patients from January 2017 to August 2023, predominantly male smokers, exhibiting high malignancy levels. Clinicopathologic features were similar across patients with single and multiple SWI/SNF complex subunit deficiencies. The most frequent co-mutated gene was TP53 (71.0%), followed by STK11, CDKN2A, KRAS, APC, and EGFR. Independent prognostic factors for overall survival (OS) included distant metastasis, radiotherapy, and immunotherapy. Immunotherapy significantly improved 3-year OS rates (20.8% vs 68.4%, p<0.001). KRAS-mutated patients receiving immunotherapy showed a trend towards reduced OS (1-year survival rate: 60.0% vs 83.1%, p=0.083). Radiotherapy enhanced the 3-year OS rates, achieving 61.7% compared to 30.7% observed in the absence of radiotherapy (p=0.012). Among 38 patients undergoing immunotherapy, 16 demonstrated a survival benefit from radiotherapy (median OS 31.4mons vs NE, p=0.045), with an average interval of 17.2 days between radiotherapy and immunotherapy.
Conclusion: SWI/SNF-d pulmonary neoplasms, whether with multiple or single subunit losses, exhibit similar clinicopathological characteristics. Radiotherapy and immunotherapy are effective treatments for these patients, and the combination of radiotherapy with immunotherapy may offer synergistic effects.