1280 - Radiation Dose Optimization in Reirradiation for Recurrent Glioblastoma: Results of the Multicenter KROG 21-02 Study
Presenter(s)
C. W. Wee1, D. Kim2, H. I. Yoon1, S. Park1, J. H. Lee3, D. H. Lim4, N. Kim4, J. H. Song5, C. O. Suh6, and I. A. Kim7; 1Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 2Department of Radiation Oncology, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea, Republic of (South), 3Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea, Republic of (South), 4Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South), 5Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South), 6Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-Do, Korea, Republic of (South), 7Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea, Republic of (South)
Purpose/Objective(s): Re-irradiation (re-RT) is increasingly used for recurrent glioblastoma (GBM), yet the optimal cumulative biologically equivalent dose that balances efficacy and toxicity remains unclear. To define a clinically meaningful cumulative dose “therapeutic window” for fractionated re-RT in recurrent IDH-wildtype GBM by evaluating post-progression survival (PPS) and radiation necrosis (RN).
Materials/Methods: We performed a multicenter retrospective study of adults with recurrent IDH-wildtype GBM treated with fractionated external-beam re-RT (2010–2023). Cumulative dose was calculated using the linear–quadratic model as EQD2 and summed across initial RT and re-RT. Unsupervised k-means clustering (k=3; silhouette score=0.615) of cumulative EQD210 informed dose ranges, which were rounded for clinical interpretability to <100 Gy, 100–110 Gy, and >110 Gy. The primary endpoint was PPS (from first recurrence to death/last follow-up). RN-free survival was analyzed for CTCAE v5.0 grade =2 RN; cumulative EQD23 was dichotomized using an ROC-derived cutoff.
Results:
Among 166 patients, median PPS was 10.2 months. PPS differed significantly by cumulative EQD210 group (log-rank P<0.001), with the 100–110 Gy group demonstrating the most favorable outcomes. In multivariable Cox analysis, the 100–110 Gy group remained independently associated with longer PPS compared with the <100 Gy group (HR 0.623, 95% CI 0.442–0.877; P=0.007). In contrast, PPS in the >110 Gy group did not differ significantly from that in the <100 Gy group (P=0.37), indicating no additional survival benefit with further dose escalation beyond the moderate-dose range. Grade =2 RN occurred in 12 patients (7.2%). Cumulative EQD23 =114 Gy was associated with higher RN incidence (12.7% vs 2.3%) and significantly shorter RN-free survival (HR 5.868; P=0.022).Conclusion: Fractionated re-RT for recurrent IDH-wildtype GBM appears to yield maximal PPS benefit within a cumulative EQD210 window of 100–110 Gy, while cumulative EQD23 =114 Gy markedly increases RN risk.