Retrospective Insights into the Clinicopathological Features and Treatment Outcomes of Thoracic SMARCA4-Deficient Tumors.

Abstract

IntroductionThoracic SMARCA4-deficient tumors, which are rare and aggressive malignancies found in the lung or thoracic cavity, present a challenge in treatment standardization. This challenge arises from their resistance to chemotherapy and the absence of targeted therapy options.MethodsThoracic SMARCA4-deficient tumors were identified retrospectively using pathology databases. The clinicopathological characteristics of these tumors are outlined, and the clinical outcomes of advanced patients treated with immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy alone are reviewed.ResultsThirty-nine patients had thoracic SMARCA4-deficient tumors, with a median age of 62 years. The cohort consisted of 92.3% males, and 89.7% had a history of smoking. Within this group, 94.9% had stage III/IV disease at diagnosis. SMARCA4-deficient non-small cell lung cancer (SMARCA4-DNSCLC) and SMARCA4-deficient undifferentiated tumors (SMARCA4-DUT) display distinct histological and immunohistochemical features. Thirty-five patients underwent systemic therapy, achieving an ORR of 51.4%, a DCR of 82.9%, and a median OS of 20.9 months. Patients were categorized into chemotherapy (28.6%) and ICIs plus chemotherapy (71.4%) groups. The ICIs plus chemotherapy group exhibited an ORR of 64.0% and a DCR of 96.0%, while the chemotherapy group had an ORR of 20.0% and 50.0%, respectively (P < .0001 for ORR and DCR). The median OS for ICIs plus chemotherapy and chemotherapy groups were 20.9 months and 6.5 months, and median PFS were 9.6 months and 3.5 months, respectively, all statistically significant (P < .05). Multivariate COX regression analysis indicated that treatment was an independent prognostic factor for OS.ConclusionThoracic SMARCA4-deficient tumors exhibit a lack of SMARCA4 expression, displaying high malignancy and aggressiveness while exhibiting poor response to standard chemotherapy. The combination of ICIs with chemotherapy could potentially serve as an effective treatment approach for thoracic SMARCA4-deficient tumors.