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Observational Study
. 2023 Jul;149(8):4455-4463.
doi: 10.1007/s00432-022-04359-6. Epub 2022 Sep 19.

Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors

Jizhuang Luo  1 , Bowen Ding  2 , Alessio Campisi  1   3 , Tangbing Chen  1 , Haohua Teng #  4 , Chunyu Ji #  5
Affiliations
Observational Study

Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors

Jizhuang Luo et al. J Cancer Res Clin Oncol. 2023 Jul.

Abstract

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.

Keywords: Immunotherapy; SMARCA4; SMARCA4-dNSCLC; SMARCA4-dUT; Surgery.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
The selection process of eligible patients
Fig. 2
Fig. 2
Molecular characteristics of SMARCA4-deficient tumors. Grid depicts the category of SMARCA4-deficient tumors (a) and mutation type of selected genes (b)
Fig. 3
Fig. 3
Survival cures for TTP (a, c) and OS (b, d) for SMARCA4-deficient tumors. Comparison of SMARCA4-dNSCLC versus SMARCA4-dUT for TTP (a) and OS (b). Comparison of stage I versus stage II/III for SMARCA4-dNSCLC patients for RFS (c) and OS (d). p values from log-rank test
See this image and copyright information in PMC

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