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Published on: July 28, 2020
Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors
Jizhuang Luo1, Bowen Ding2, Alessio Campisi1,3
1Department of Thoracic Surgery, School of Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Rd, Xuhui District, Shanghai, 200030, China.
Purpose:
SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown.
Methods:
In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients.
Results:
Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months.
Conclusion:
Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.
Insights
Surgery for SMARCA4-deficient thoracic tumors shows high recurrence rates, especially for undifferentiated types. Immunotherapy offers a promising treatment option for recurrent SMARCA4-deficient non-small cell lung cancer (NSCLC) and other thoracic malignancies.
Area of Science:
- Thoracic Oncology
- Molecular Diagnostics
- Surgical Oncology
Background:
- SMARCA4-deficient thoracic tumors are aggressive and often diagnosed at advanced stages.
- The efficacy of surgical resection for these tumors is not well-established.
Purpose of the Study:
- To evaluate the outcomes of pulmonary resection for resectable SMARCA4-deficient thoracic tumors.
- To compare clinicopathological features and survival between SMARCA4-deficient non-small cell lung cancer (dNSCLC) and SMARCA4-deficient undifferentiated tumors (dUT).
Main Methods:
- Observational study of 45 patients who underwent surgery for stage I-III SMARCA4-deficient tumors.
- Comparison of molecular profiles, clinicopathological characteristics, and survival outcomes.
- Analysis of treatment responses to immunotherapy and targeted therapy.
Main Results:
- Eleven SMARCA4-dUT patients had significantly worse Time to Progression (TTP) and Overall Survival (OS) compared to 34 SMARCA4-dNSCLC patients.
- SMARCA4-dUT histology, advanced stage, incomplete resection, and lymphovascular invasion were poor prognostic factors.
- Immunotherapy showed a 50% objective response rate in 8 patients; one patient with ALK rearrangement achieved stable disease with crizotinib.
Conclusions:
- SMARCA4-deficient tumors, excluding stage I, have a high likelihood of recurrence post-surgery.
- Immunotherapy represents a potentially valuable treatment strategy for recurrent SMARCA4-deficient thoracic tumors.
