[Clinical Characteristics and Prognosis Analysis of Thoracic SMARCA4-deficient
Undifferentiated Tumor versus...

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a newly defined type of epithelial tumor in the 2021 World Health Organization (WHO) fifth edition classification of thoracic tumors, with a low incidence. Currently, its treatment and prognosis remain unclear. Pathologically, it can be distinguished from SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) based on histological morphology and immunohistochemistry, yet whether there are differences in their clinical features, sensitivity to radiotherapy, and prognosis remains unknown. This study aimed to analyze the clinical characteristics of patients with SMARCA4-UT and SMARCA4-dNSCLC and to identify prognostic factors.

A retrospective analysis was performed on pathologically confirmed SMARCA4-UT and SMARCA4-dNSCLC patients with complete follow-up data who were admitted to Shandong First Medical University Affiliated Tumor Hospital from June 2022 to February 2025. The differences in clinicopathological characteristics and imaging findings between the two groups were statistically analyzed, and the impacts of surgery, radiotherapy, immunotherapy, and clinicopathological factors on the prognosis of patients in both groups were assessed.

A total of 27 SMARCA4-UT patients and 40 SMARCA4-dNSCLC patients were enrolled. Both groups showed similar biological characteristics in terms of gender, age, smoking history, tumor size, symptoms, stage, presence of pleural metastasis, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). However, there were differences in the predilection sites: SMARCA4-UT occurred more frequently in the mediastinal pleura (22.22%) and right lower lobe (25.93%), while SMARCA4-dNSCLC occurred more frequently in the right upper lobe (25.00%) and left upper lobe (22.50%) (P<0.05). Furthermore, SMARCA4-UT more often presented with local invasion into adjacent structures and more extensive lymph node metastasis (proportion with metastasis in ≥5 lymph node stations: 55.56% vs 27.50%). Both types showed high sensitivity to radiotherapy, with a 6-month local control rate (LCR) of 84.62% vs 83.33% after radiotherapy; the objective response rate (ORR) of immunotherapy was 91.67% vs 68.18% (P>0.05). Regarding survival, the two groups did not show significant differences in progression-free survival (PFS) or overall survival (OS). Cox multivariate regression analysis indicated that surgery could improve the prognosis of both types, while a high NLR (≥3.57) was a predictor of poor prognosis.

SMARCA4-UT and SMARCA4-dNSCLC share similar clinical characteristics and survival outcomes, with minor differences in local invasion, mediastinal lymph node metastasis, and primary tumor location. Surgery improved survival in both groups. Although both tumor types exhibited high sensitivity to radiotherapy, this did not translate into a significant survival benefit for the patients. Pretreatment NLR is a potential prognostic indicator.