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  • [Cancer.] Targeted sequencing and intracranial outcomes of patients with lung adenocarcinoma brain metastases treated with radiotherapy.

    Emory University School of Medicine / Robert H. Press*

  • 출처
    Cancer.
  • 등재일
    2018 Sep 1
  • 저널이슈번호
    124(17):3528-3535. doi: 10.1002/cncr.31568. Epub 2018 Jul 5.
  • 내용

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    Abstract
    BACKGROUND:
    Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy.

    METHODS:
    The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed.

    RESULTS:
    The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P < .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P < .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P < .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P < .05).

    CONCLUSIONS:
    The results of the current study quantified the frequency of genetic aberrations in patients with AC-BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.

     


    Author information

    Press RH1, Zhang C2, Cassidy RJ1, Ferris MJ1, Zhong J1, Steuer CE3, Pillai RN3, Owonikoko TK3, Kahn S1, Ramalingam SS3, Patel PR1, Curran WJ1, Shu HG1, Sica GL4, Higgins KA1.
    1
    Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
    2
    Bioinformatics and Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia.
    3
    Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
    4
    Department of Pathology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

     

  • 키워드
    DNA sequence analysis; adenocarcinoma; brain metastases; distant brain failure; intracranial failure; neoplasm metastases; next-generation sequencing; non-small cell lung cancer; stereotactic radiosur
  • 편집위원

    NSCLC의 adenocarcinoma는 mutation 여부 및 종류에 따라 CTx 및 target agents가 사용되고, 특히 brain metastases에서 방사선치료의 역할에 대한 논란이 많은 영역인데, NGS 기반으로 SRS or WBRT 치료결과를 분석함으로써, 방사선치료 역시 personalized approach가 가능함을 제시하는 좋은 연구로 생각됩니다.

    2018-11-14 15:50:08

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