Metabolic Tumor Volume as a Predictor of Benefit From Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer

BACKGROUND: Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases (BMs) in patients with limited-stage small cell lung cancer (LS-SCLC). However, predictive biomarkers that identify patients most likely to benefit from PCI have not been established. This study investigates the potential of 18F-fluoro-2-deoxyglucose (18F-FDG) PET as a predictor of PCI benefit in patients with LS-SCLC. PATIENTS AND METHODS: This multicenter study analyzed patients with LS-SCLC who underwent brain MRI and 18F-FDG PET/CT at baseline, followed by treatment with concurrent chemoradiotherapy. To evaluate whether the benefit of PCI varies according to BM risk, we compared outcomes between PCI-treated and untreated patients stratified by risk group. RESULTS: Of 261 patients overall, 171 received PCI and 90 did not. In patients not receiving PCI, high metabolic tumor volume (MTV; >45.201 cm3) was associated with inferior intracranial time to progression (iTTP; hazard ratio [HR], 5.62; 95% CI, 1.69-18.77; P=.005), progression-free survival (PFS; HR, 2.35; 95% CI, 1.38-4.02; P=.002), and overall survival (OS; HR, 2.23; 95% CI, 1.27-3.91; P=.005). Conversely, MTV demonstrated no significant association with survival outcomes among PCI recipients. Subgroup analysis revealed that PCI conferred no survival advantage in the low-MTV group, whereas in the high-MTV group, PCI was associated with improved iTTP (HR, 0.27; 95% CI, 0.15-0.51; P<.001), PFS (HR, 0.49; 95% CI, 0.35-0.69; P<.001), and OS (HR, 0.56; 95% CI, 0.40-0.80; P=.001). Interaction analysis confirmed a significant effect modification between MTV status and PCI benefit for iTTP, PFS, and OS, supporting MTV as an independent predictive biomarker for PCI benefit. CONCLUSIONS: Baseline PET-derived MTV serves as a clinically relevant predictor of PCI benefit in LS-SCLC, supporting a risk-adapted PCI strategy guided by metabolic imaging biomarkers. This approach may reduce unnecessary neurotoxicity and optimize treatment outcomes and should be prospectively validated.