SWItch/Sucrose Nonfermentable complex-deficient pulmonary neoplasms: clinicopathologic characteristics and outcomes to radiotherapy and immunotherapy.

Background: The SWItch/Sucrose Nonfermentable (SWI/SNF) complex, a multi-subunit chromatin remodeler, is linked to aggressive tumors when deficient. Accurate identification of SWI/SNF expression status is crucial for tailoring targeted therapies. Previous studies on the efficacy of immunotherapy for SWI/SNF-deficient (SWI/SNF-d) pulmonary tumors primarily focus on non-small cell lung cancer (NSCLC), with limited data on other modalities like radiotherapy. This study aims to analyze the clinicopathological characteristics and prognostic factors of SWI/SNF-d pulmonary neoplasms, including NSCLC and undifferentiated tumors, and to evaluate the effectiveness of radiotherapy and immunotherapy, providing a foundation for improved treatment strategies and prognostic assessments.

Methods: Patient data on SWI/SNF-d pulmonary neoplasms were collected from Fudan University Shanghai Cancer Center, assessing ARID1A, SMARCA2, SMARCA4, and SMARCB1 subunit expression via immunohistochemistry, with retrospective analysis of survival and treatment results.

Results: The study analyzed 101 SWI/SNF-d pulmonary neoplasms from 675 SWI/SNF-d cancer patients (January 2017 to August 2023), mostly male smokers, showing high malignancy. Clinicopathologic features were consistent across patients with various SWI/SNF subunit deficiencies. TP53 was the most common co-mutated gene (71%), followed by STK11, CDKN2A, KRAS, APC, and EGFR. Key prognostic factors for overall survival (OS) were distant metastasis, radiotherapy, and immunotherapy. Immunotherapy improved 3-year OS rates from 20.8% to 68.4% (P<0.001). KRAS-mutated patients on immunotherapy showed a lower 1-year survival rate (60.0% . 83.1%, P=0.08). Radiotherapy increased 3-year OS rates to 61.7% from 30.7% (P=0.012). Of 38 patients treated with immunotherapy, 16 benefited from radiotherapy [median OS: 31.4 months . not estimable (NE), P=0.045], with an average 17.2 days between radiotherapy and immunotherapy.

Conclusions: 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.