Impact of carbon-ion radiotherapy on tumor hypoxia detected by F-FMISO PET/CT in locally advanced non-small cell lung cancer.

[PURPOSE] The study aimed to assess the impact of carbon-ion radiotherapy (CIRT) on intratumoral hypoxia in patients with locally advanced non-small cell lung cancer (LA-NSCLC) and the predictive value of F-fluoromisonidazole (FMISO) and F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).

[METHODS] We retrospectively analyzed patients with stage IIB-IIIC NSCLC treated with CIRT who underwent baseline F-FMISO and F-FDG PET/CT and post-CIRT F-FMISO PET/CT. Regions of interest (ROIs) with a diameter ≥ 3 cm were analyzed. An ROI was defined as hypoxia with a tumor-to-muscle ratio (TMR) ≥ 1.4 on F-FMISO PET/CT. Survival outcomes were evaluated using Kaplan-Meier curves, and group comparisons were performed using Log-rank test.

[RESULTS] Thirty-seven eligible patients with 42 ROIs were included. Significant reductions in all F-FMISO parameters were observed after CIRT. ROIs with or without pre-CIRT hypoxia achieved similar local control (LC, with vs. without hypoxia: 75.5% vs. 85.5%, p = 0.799). The overlap ratios of hypoxic volumes between pre-/post-CIRT were 58.13%-81.34%. The combination of F-FDG uptake and post-CIRT hypoxia status demonstrated the strongest predictive value for LC (high vs. low uptake: 46.8% vs. 95.8%, p = 0.0004) with the highest area under the receiver operating characteristic curve (0.783, p = 0.01) among all evaluated combinations.

[CONCLUSION] Tumor hypoxia detected by F-FMISO PET/CT was significantly decreased after CIRT in patients with LA-NSCLC. Similar LC was achieved in patients with or without pre-CIRT hypoxia, while post-CIRT hypoxia clearance resulted in a non-significant trend toward improved LC. Combining F-FMISO and F-FDG PET/CT might provide enhanced prognostic value. Further investigation is warranted to explore individualized CIRT dose painting strategies guided by multi-tracer PET/CT imaging.