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Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients.
Chen, Xi; Fang, Liangjie; Zhu, Yanping; Bao, Zhang; Wang, Qing; Liu, Rong; Sun, Wenjia; Du, Haiwei; Lin, Jing; Yu, Bing; Chen, Songan; Zhou, Jianya; Zhou, Jianying.
Afiliación
  • Chen X; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Fang L; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Zhu Y; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Bao Z; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Wang Q; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Liu R; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Sun W; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
  • Du H; Burning Rock Biotech, Guangzhou, China.
  • Lin J; Burning Rock Biotech, Guangzhou, China.
  • Yu B; Burning Rock Biotech, Guangzhou, China.
  • Chen S; Burning Rock Biotech, Guangzhou, China.
  • Zhou J; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China. zhoujy@zju.edu.cn.
  • Zhou J; Department of Respiratory Diseases, Thoracic Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
Cancer Immunol Immunother ; 70(12): 3513-3524, 2021 Dec.
Article en En | MEDLINE | ID: mdl-33899131
BACKGROUND: Tissue tumor mutation burden (tTMB) assessed by whole-exome sequencing (WES), which has been regarded as the gold standard method of tTMB measurement, can predict the clinical benefits of immune checkpoint inhibitors (ICIs). Multiple studies have investigated the feasibility of utilizing large panels to evaluate TMB but have obtained conflicting results. Furthermore, whether blood TMB (bTMB) can also be a predictive biomarker in NSCLC has not been determined. METHODS: Fifty-six advanced NSCLC patients treated with ICIs were enrolled, including an exploratory cohort (n = 42) and a small independent validation cohort (n = 14). Next-generation sequencing was performed on tumor and plasma samples collected prior to ICI treatment using a panel consisting of 520 cancer-related genes (OncoScreen) to evaluate tTMB/bTMB. WES was also performed on tumor samples to serve as references. RESULTS: A positive correlation between tTMB derived from WES and OncoScreen was observed. OncoScreen-derived tTMB showed a positive correlation with OncoScreen-derived bTMB. Patients with OncoScreen-derived tTMB [Formula: see text] 7 mutations/Mb (p = 0.003) or bTMB [Formula: see text] 11 mutations/Mb (p = 0.0029) had superior progression-free survival (PFS). In the small validation cohort, patients with OncoScreen-derived bTMB [Formula: see text] 11 mutations/Mb exhibited longer PFS (p = 0.192) with a nonsignificant difference. In all 42 patients who had available bTMB and PFS, patients with bTMB [Formula: see text] 11 mutations/Mb had significantly longer PFS (p = 0.011) than those with bTMB [Formula: see text] 11 mutations/Mb. CONCLUSION: Our study confirmed the feasibility of using large panels to estimate TMB. We also demonstrated that bTMB can serve as a potential biomarker for predicting the efficacy of ICIs in NSCLC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Inhibidores de Puntos de Control Inmunológico / Neoplasias Pulmonares / Mutación Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Inhibidores de Puntos de Control Inmunológico / Neoplasias Pulmonares / Mutación Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania