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Clinicopathological characteristics and treatment outcomes of advanced SMARCA4-deficient thoracic tumors
Anni Wang1, Yueping Jin1, Zhengqi Cao1
1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Purpose:
SMARCA4-deficient thoracic tumors, characterized by distinct clinicopathological, morphological, immunohistochemical, and genetic features, differ significantly from conventional non-small-cell lung carcinomas (NSCLCs). This group encompasses both SMARCA4-deficient NSCLCs (SMARCA4-NSCLCs) and SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs). The efficacy of PD-1 inhibitors in treating SMARCA4-deficient thoracic tumors remains uncertain.
Methods:
Medical records of 36 patients diagnosed with stage IIIB, IIIC, or IV SMARCA4-deficient thoracic tumors were analyzed. We assessed the clinical, pathological, and genetic features of these patients through immunohistochemistry (IHC) and a 68-gene panel next-generation sequencing (NGS). We compared the differences between SMARCA4-NSCLCs and SMARCA4-UTs, and evaluated the impact of chemotherapy and immunotherapy on patient outcomes.
Results:
The majority of patients with SMARCA4-deficient thoracic tumors were heavy-smoking males, averaging 64.6 years in age. IHC predominantly showed weak or negative staining for markers such as TTF-1, CK5/6, p40, synaptophysin, chromogranin A, and CD56, which are often associated with adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors. The most common genetic mutations identified via NGS included TP53, CDKN2A, KRAS, STK11, NF1, and PTEN. No significant overall survival (OS) difference was observed between SMARCA4-NSCLCs and SMARCA4-UTs (p = 0.366). The median OS for patients treated with chemotherapy (n = 9) was 447 days, while the median OS for patients undergoing PD-1-inhibitor-based therapy (n = 16) was not reached (p = 0.105).
Conclusion:
SMARCA4-deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD-1 inhibitors show promise in treating advanced SMARCA4-deficient thoracic tumors.
Insights
SMARCA4-deficient thoracic tumors are distinct from NSCLCs. PD-1 inhibitors show promise for advanced cases, with survival data suggesting potential benefits over chemotherapy in this patient group.
Area of Science:
- Oncology
- Thoracic Malignancies
- Molecular Pathology
Background:
- SMARCA4-deficient thoracic tumors present unique clinicopathological, morphological, immunohistochemical, and genetic profiles, differentiating them from conventional non-small-cell lung carcinomas (NSCLCs).
- This distinct tumor category includes both SMARCA4-deficient NSCLCs and SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs).
- The therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors in these specific thoracic tumors remains an area of active investigation.
Purpose of the Study:
- To characterize the clinicopathological, immunohistochemical, and genetic features of SMARCA4-deficient thoracic tumors.
- To compare SMARCA4-deficient NSCLCs with SMARCA4-UTs.
- To evaluate the impact of chemotherapy and immunotherapy, specifically PD-1 inhibitors, on patient outcomes in advanced SMARCA4-deficient thoracic tumors.
Main Methods:
- Analysis of medical records from 36 patients with stage IIIB, IIIC, or IV SMARCA4-deficient thoracic tumors.
- Immunohistochemistry (IHC) and 68-gene panel next-generation sequencing (NGS) were employed to assess tumor features.
- Comparative analysis between SMARCA4-NSCLCs and SMARCA4-UTs, and evaluation of treatment outcomes for chemotherapy and immunotherapy.
Main Results:
- The patient cohort predominantly consisted of male smokers (average age 64.6 years).
- IHC revealed weak/negative staining for common markers (TTF-1, CK5/6, p40, etc.), indicating divergence from typical adenocarcinoma, squamous cell, and neuroendocrine tumors.
- Key genetic mutations included TP53, CDKN2A, KRAS, STK11, NF1, and PTEN. No significant difference in overall survival (OS) was found between SMARCA4-NSCLCs and SMARCA4-UTs (p=0.366).
- Median OS was 447 days for chemotherapy (n=9) versus not reached for PD-1 inhibitors (n=16, p=0.105).
Conclusions:
- SMARCA4-deficient thoracic tumors possess distinct characteristics compared to conventional NSCLCs.
- PD-1 inhibitors demonstrate promising potential for treating advanced SMARCA4-deficient thoracic tumors.
- Further research is warranted to fully elucidate the role of immunotherapy in this patient population.
