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Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.
Fu, Ying; Liu, Qing; Wang, Xiaohan; Sun, Liangchao; Han, Xiao; Meng, Xue.
Afiliação
  • Fu Y; School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
  • Liu Q; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • Wang X; Department of Oncology, Changqing District People's Hospital, Jinan, Shandong, China.
  • Sun L; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • Han X; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • Meng X; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. hxzbb1983@163.com.
Clin Transl Oncol ; 26(10): 2513-2521, 2024 Oct.
Article em En | MEDLINE | ID: mdl-38637357
ABSTRACT

PURPOSE:

Despite the generally favourable prognoses observed in patients with ALK-positive non-small cell lung cancer (NSCLC), there remains significant variability in clinical outcomes. The objective of this study is to enhance patient stratification by examining both the specific sites of gene fusion and the presence of co-occurring mutations.

METHODS:

We collected retrospective clinical and pathological data on ALK-positive patients with locally advanced or metastatic disease. ALK fusion variants and concomitant mutations were identified through next-generation sequencing technology. We then assessed treatment efficacy via tumor response and survival metrics.

RESULTS:

This study included a total of 59 patients, with 49 harboring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions and 10 presenting with rare fusions. The median follow-up period was 33 months. Clinical outcomes between non-EML4-ALK and EML4-ALK patients were comparable. Among the EML4-ALK cohort, patients with longer variants (v1, v2, v8) demonstrated superior progression-free survival (PFS) (median PFS 34 months vs. 11 months; hazard ratio [HR] 2.28; P = 0.05) compared to those with shorter variants (v3, v5). Furthermore, patients treated with second-generation ALK inhibitors (ALKi) displayed a progression-free survival advantage (median PFS not reached [NR] vs. 9 months; HR 5.37; P = 0.013). Baseline TP53 co-mutation were linked with a substantially shorter OS (median OS,37 months vs. NR; HR 2.74; P = 0.047).

CONCLUSIONS:

In ALK+ NSCLC, longer EML4-ALK variants correlate with improved prognosis and enhanced response to second-generation ALKi, while TP53 co-mutations indicate a negative prognosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Fusão Oncogênica / Carcinoma Pulmonar de Células não Pequenas / Quinase do Linfoma Anaplásico / Neoplasias Pulmonares / Mutação Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Itália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Fusão Oncogênica / Carcinoma Pulmonar de Células não Pequenas / Quinase do Linfoma Anaplásico / Neoplasias Pulmonares / Mutação Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Itália