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

Luo, Jizhuang; Ding, Bowen; Campisi, Alessio; Chen, Tangbing; Teng, Haohua; Ji, Chunyu

doi:10.1007/s00432-022-04359-6

Cited by 11 publications

(16 citation statements)

References 27 publications

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“…Additionally, cisplatin and vinorelbine can be used as effective regimens for resectable SMARCA4‐dNSCLC in stage IB–II 16 . SMARCA4‐dNSCLC other than stage I has a high risk of relapse following surgery, and immunotherapy is effective 26 . In a study by Shinno et al on ICIs in SMARCA4‐deficient thoracic tumors, the response rate to ICIs was 42%, and the progression‐free survival time with ICIs was significantly longer with the first‐line regimen than with the second‐line or later treatment; additionally, TMB could be used to predict patients who would benefit from ICIs 5 .…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognostic analysis of SMARCA4‐deficient non‐small cell lung cancer

Liang,

Gao,

Wang

et al. 2023

Cancer Medicine

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To improve the understanding of special types of tumors, we summarized and analyzed the clinicopathological features and prognostic factors of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC). Methods:We selected 105 patients with SMARCA4-dNSCLC and 221 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) by performing immunohistochemical analysis of 1520 NSCLC samples, and we assessed the patients' clinicopathological features and survival state. Results:(1) SMARCA4-dNSCLC was significantly associated with older age, male sex, smoking history, larger invasive tumor size, higher tumor proliferation index (Ki-67), more adrenal metastases, more lymph node metastases, and few EGFR mutations (p < 0.05). The tumors were mostly negative for thyroid transcription factor-1 (TTF-1), CD34, and p40 and positive for cytokeratin 7 (CK7) in immunohistochemistry (IHC). Nineteen SMARCA4-dNSCLC patients mostly had TP53, SMARCA4, and LRP1B mutations, and 48% of them had SMARCA4 frameshift mutations. SMARCA4-dNSCLC patients have a worse prognosis than SMARCA4-iNSCLC patients (HR: 0.27; 95% CI: 0.17-0.45). The overall survival (OS) of patients with stage III SMARCA4-dNSCLC was worse than that of patients with SMARCA4-iNSCLC, and the OS of stage IV SMARCA4-dNSCLC patients was also worse than that of SMARCA4-iNSCLC patients (p < 0.01). ( 2) Multivariate regression analysis showed that sex (HR: 4.12; 95% CI: 1.03-16.39) and smoking history (HR: 2.29; 95% CI: 1.04-5.02) had significant effects on the survival time of SMARCA4-dNSCLC patients. In SMARCA4-dNSCLC patients without distant metastases (stage I-III), patients with stage N2 or N3 lymph node metastases (HR: 6.35; 95% CI: 1.07-37.47) had a poor prognosis. Among patients with SMARCA4-dNSCLC who were treated and had distant metastases (stage IV), male patients and patients treated with immunotherapy combined with chemotherapy showed a longer median overall survival (mOS). Conclusion:SMARCA4-dNSCLC has unique clinicopathological features and a shorter survival prognosis than SMARCA4-iNSCLC. The efficacy of

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognostic analysis of SMARCA4‐deficient non‐small cell lung cancer

Liang,

Gao,

Wang

et al. 2023

Cancer Medicine

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“…30,31 Our NGS analysis of 27 SMARCA4-deficient thoracic tumors identified frequent mutations in TP53, CDKN2A, KRAS, STK11, NF1, and PTEN, with rare actionable oncogenic driver mutations. 6,17 Two cases harbored EGFR L858R mutation, and both were lost to follow-up after diagnosis. One patient harboring EML4-ALK rearrangement received first-line alectinib and experienced PD after 4 months.…”

Section: Discussionmentioning

confidence: 99%

“…In 2021, the World Health Organization (WHO) recognized SMARCA4‐deficient undifferentiated thoracic tumor (SMARCA4‐UT), formerly known as SMARCA4‐deficient thoracic sarcoma (SMARCA4‐DTS), as a distinct entity that was different from SMARCA4‐deficient NSCLC, due to its unique histological, immunohistochemical, clinical, and prognostic features 14 . SMARCA4‐UT predominantly affects younger males with history of heavy smoking and presents as large masses often involving lungs and other thoracic structures 15–19 . Histologically, these tumors are undifferentiated round cell or exhibit rhabdoid morphology 20 .…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological characteristics and treatment outcomes of advanced SMARCA4‐deficient thoracic tumors

Wang,

Jin,

Cao

et al. 2023

Cancer Medicine

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PurposeSMARCA4‐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.MethodsMedical 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.ResultsThe 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).ConclusionSMARCA4‐deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD‐1 inhibitors show promise in treating advanced SMARCA4‐deficient thoracic tumors.

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“…It occurs mainly in middle-aged male patients with a history of smoking 1 . Patients may benefit from immunotherapy 4,5 . On CT, the tumors appear as generally large compressive and infiltrative masses with ill-defined margins and heterogeneous enhancement in mediastinum, pleura, lung, or in 2 or more of these locations 2,3,6 .…”

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confidence: 99%

“…The common sites of metastases at diagnosis are the lymph node, adrenal gland, lung, bone (lytic), and brain, in descending order 6 . On FDG PET/CT, both the primary tumor and its metastases can show intense FDG uptake, 4–11 suggesting that FDG PET/CT may be useful for detecting and staging of this rare malignancy. This case indicates that thoracic SMARCA4-deficient undifferentiated tumor should be included in the differential diagnosis of FDG-avid pleural lesions including malignant mesothelioma, solitary fibrous tumor, and metastasis 12 …”

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confidence: 99%

FDG PET/CT in a Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor

Guo,

Liao,

Chen

et al. 2023

Clin Nucl Med

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Thoracic SMARCA4-deficient undifferentiated tumor is a rare, newly recognized poorly differentiated tumor with poor prognosis. FDG PET/CT findings of thoracic SMARCA4-deficient undifferentiated tumor are rarely reported. We describe FDG PET/CT findings in a case of thoracic SMARCA4-deficient undifferentiated tumor. The tumor presented as a pleural mass, destroyed the adjacent ribs, and showed intense FDG uptake with SUVmax of 12.7. This case indicates that thoracic SMARCA4-deficient undifferentiated tumor should be included in the differential diagnosis of FDG-avid pleural lesions.

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

Cited by 11 publications

References 27 publications

Clinical characteristics and prognostic analysis of SMARCA4‐deficient non‐small cell lung cancer

Clinical characteristics and prognostic analysis of SMARCA4‐deficient non‐small cell lung cancer

Clinicopathological characteristics and treatment outcomes of advanced SMARCA4‐deficient thoracic tumors

FDG PET/CT in a Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor

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