Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.
Lung Cancer
; 192: 107818, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38763102
ABSTRACT
INTRODUCTIONS The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS:
From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy.RESULTS:
SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028).CONCLUSIONS:
SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Torácicas
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Fatores de Transcrição
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Proteínas Nucleares
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DNA Helicases
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Neoplasias Pulmonares
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Irlanda