A comprehensive predictive model for radiation-induced brain injury in risk stratification and personalized radiotherapy of nasopharyngeal carcinoma

Radiother Oncol. 2024 Jan:190:109974. doi: 10.1016/j.radonc.2023.109974. Epub 2023 Oct 31.


Background and purpose: Radiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification.

Materials and methods: By performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction.

Results: The 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 × 10-34). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27-103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 × 10-2).

Conclusions: The PRS, together with clinical factors, could improve RBI risk stratification and implies personalized radiotherapy.

Keywords: Personalized radiotherapy; Polygenic risk score; Radiation-induced brain injury; Risk stratification.

MeSH terms

  • Brain Injuries* / etiology
  • Genome-Wide Association Study
  • Humans
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms* / drug therapy
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / radiotherapy
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Retrospective Studies
  • Risk Assessment