Optimal intervention timing for craniocerebral radiotherapy in EGFR mutant lung adenocarcinoma patients with brain metastases.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      ErbB Receptors*/genetics ; ErbB Receptors*/antagonists & inhibitors ; Brain Neoplasms*/secondary ; Brain Neoplasms*/radiotherapy ; Brain Neoplasms*/genetics ; Lung Neoplasms*/genetics ; Lung Neoplasms*/pathology ; Lung Neoplasms*/radiotherapy ; Lung Neoplasms*/drug therapy ; Adenocarcinoma of Lung*/genetics ; Adenocarcinoma of Lung*/pathology ; Adenocarcinoma of Lung*/radiotherapy ; Adenocarcinoma of Lung*/drug therapy ; Mutation* ; Cranial Irradiation*/methods ; Protein Kinase Inhibitors*/therapeutic use ; Protein Kinase Inhibitors*/administration & dosage; Humans ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; Prognosis ; Aged, 80 and over ; Time Factors ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/radiotherapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy
    • Abstract:
      Background: Intracranial radiation in combination with EGFR targeted therapy demonstrated signals of superiority to EGFR targeted therapy alone based on several observational studies. The timing based on specific criteria is not clear, and we evaluated the efficacy of intervention timing of craniocerebral radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on prognosis of patients with EGFR mutant lung adenocarcinoma complicated with brain metastasis.
      Methods: In total, 603 patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations were enrolled in this retrospective study between March 2008-September 2023. Propensity score matching (PSM) was conducted to adjust for demographic and clinical covariates and to compare survival differences between the EGFR-TKI plus craniocerebral RT group and the EGFR-TKI only group. Patients were divided into upfront group and delayed group according to timing of craniocerebral RT interventions and analyses. Graded prognostic assessment for lung cancer using molecular markers (Lung molGPA), overall survival (OS), and intracranial progression-free survival (iPFS) were calculated. Kaplan-Meier was used to compare iPFS and OS in different groups.
      Results: In our study, the median overall survival (OS) was 48.8 months, and the median intracranial progression-free survival (iPFS) was 14.2 months before PSM. After PSM, the median OS of EGFR-TKIs + craniocerebral RT group and EGFR-TKI only group was 52.0 months and 43.2 months, respectively (p = 0.0363). In total of 417 patients who underwent craniocerebral RT, were enrolled subsequently and divided into groups A (Lung-molGPA 1-2) and B (Lung-molGPA 2.5-4) according to the lung-molGPA score. For group A, the median OS of upfront-group and delay-group was 27 and 42.1 months, respectively (p = 0.0019). For patients in group B, there was no significant difference in OS between the two groups (p = 0.9642).
      Conclusion: For patients with craniocerebral metastases of EGFR-mutant lung adenocarcinoma, combination of EGFR-TKIs and craniocerebral RT confers enhanced survival benefits. In patients with lower Lung-molGPA scores, delayed administration of craniocerebral RT is recommended to improve both iPFS and OS.
      Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of Shandong Cancer Hospital and Institute and was conducted in accordance with the Declaration of Helsinki. All the patients were diagnosed and treated in Shandong Cancer Hospital and Institute, so we obtained the permissions to access the data from the Ethics Committee of Shandong Cancer Hospital and Institute (No.: SDTHEC2021012002).Considering the retrospective nature of the study and policy of the Ethics Committee of Shandong Cancer Hospital and Institute, the informed consent was waived. The data used in this study was anonymised before its use. Competing interests: The authors declare no competing interests.
      (© 2024. The Author(s).)
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    • Grant Information:
      Grant No.81902355 National Natural Science Foundation of China
    • Contributed Indexing:
      Keywords: Brain metastasis; Craniocerebral radiotherapy; EGFR-mutant; Lung adenocarcinoma; Lung-molGPA
    • Accession Number:
      EC 2.7.10.1 (ErbB Receptors)
      EC 2.7.10.1 (EGFR protein, human)
      0 (Protein Kinase Inhibitors)
    • Publication Date:
      Date Created: 20241223 Date Completed: 20241224 Latest Revision: 20250104
    • Publication Date:
      20250104
    • Accession Number:
      PMC11664826
    • Accession Number:
      10.1186/s12885-024-13363-7
    • Accession Number:
      39716108