ML-guided PPRT (dose-escalated RT boost) doubles PFS in newly diagnosed IDH-wt glioblastoma—at a necrosis cost

Personalized precision radiation therapy (PPRT) is an ML-guided radiotherapy dose-escalation approach that uses MRI-derived “tumor infiltration” maps to boost dose beyond conventional fields; it was prospectively piloted with concurrent/adjuvant temozolomide in newly diagnosed IDH-wildtype glioblastoma after gross total resection (n=20; NCT03477513). Efficacy compared against a propensity score–matched historical standard chemoradiation cohort (n=68) showed median PFS 24.4 vs 11.6 months (HR 0.28, 95% CI 0.13–0.61; p=0.001) and median OS 35.4 vs 17.7 months (HR 0.34, 95% CI 0.17–0.69; p=0.003)—well above the classic Stupp chemoradiation benchmark mOS ~14.6 months. Acute toxicity was mild (no grade ≥3 acute AEs; 47% grade 1 and 53% grade 2), but radiation necrosis was substantially higher with PPRT (47% vs 12% with SOC; p<0.001), a tradeoff that matters given necrosis can mimic progression and drive steroid use/interventions.