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SWItch/Sucrose Nonfermentable complex-deficient pulmonary neoplasms: clinicopathologic characteristics and outcomes
Yu Gu1,2,3,4, Songtao Lai1,2,3,4, Juan Yang5
1Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.
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% vs. 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 vs. 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.
Insights
SWI/SNF-deficient pulmonary neoplasms show aggressive traits but respond well to treatments. Immunotherapy and radiotherapy significantly improve survival, with potential synergistic effects when combined, offering new hope for patients.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- SWI/SNF complex deficiency is linked to aggressive tumors.
- Accurate SWI/SNF expression status is vital for targeted therapies.
- Limited data exists on immunotherapy and radiotherapy for SWI/SNF-deficient (SWI/SNF-d) pulmonary neoplasms beyond NSCLC.
Purpose of the Study:
- To analyze clinicopathological characteristics of SWI/SNF-d pulmonary neoplasms.
- To identify prognostic factors for SWI/SNF-d pulmonary neoplasms.
- To evaluate the effectiveness of radiotherapy and immunotherapy in SWI/SNF-d pulmonary neoplasms.
Main Methods:
- Retrospective analysis of 101 SWI/SNF-d pulmonary neoplasms.
- Immunohistochemistry used to assess ARID1A, SMARCA2, SMARCA4, and SMARCB1 expression.
- Analysis of survival data and treatment outcomes for radiotherapy and immunotherapy.
Main Results:
- SWI/SNF-d pulmonary neoplasms exhibit high malignancy, with TP53 as the most common co-mutated gene.
- Immunotherapy improved 3-year overall survival (OS) from 20.8% to 68.4%.
- Radiotherapy increased 3-year OS to 61.7% from 30.7%; combination therapy showed promising results.
Conclusions:
- SWI/SNF-d pulmonary neoplasms share similar characteristics regardless of subunit loss.
- Radiotherapy and immunotherapy are effective treatments for SWI/SNF-d pulmonary neoplasms.
- Combining radiotherapy with immunotherapy may yield synergistic benefits for patients.
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