[Choice of fractionation regimen for Grade IV gliomas depending on rapid early progression]

To investigate the effect of two fractionation regimens on survival in patients with Grade IV gliomas depending on rapid early progression (REP).

Fractionation with prescribed doses of 2 and 3 Gy was alternately used in 140 patients with morphologically confirmed Grade IV glioma using a pairwise modeling strategy.

REP was diagnosed in 60 (42.9%) out of 140 patients with Grade IV gliomas and 55 (45.5%) out of 121 patients with glioblastomas. Fatal outcome was observed in 111 (79.3%) patients, 99 (70.7%) ones died from progression of glioma. In case of no REP, the median overall survival as of December 2023 was 32.20 (95% CI 25.7-38.7) months, with REP - only 16.03 (95% CI 13.5-18.6) months (p<0.0001). Median survival was slightly lower in patients with glioblastoma - 28.2 and 16.5 months, respectively (p<0.0001).

In patients with Grade IV gliomas and no REP, 3 Gy (n=40) fractionation regimen was followed by median overall survival 44.98 (95% Cl 15.3-74.6) months, 2 Gy (n=40) - 20.99 (95% CI 9.2-32.7) months (p=0.027). In case of glioblastoma, differences between fractionation regimes lose significance - medians 33.7 and 19.7 months, respectively (p=0.081). According to multivariate analysis, 3 Gy fractionation regimen is more effective than standard radiotherapy (p=0.009) in patients without REP, while significance of isoeffective doses <59.5Gy≥ is slightly lower (p=0.020). Radiotherapy on the background of temozolomide is equally important (p=0.007).

In patients with grade 4 gliomas and REP, 3 Gy (n=30) fractionation regimen was followed by median overall survival 17.18 (95% CI 14.2-20.2) months, 2 Gy (n=30) - 12.88 (95% CI 5.4-20.3) months (p=0.849). In case of glioblastoma, Cox model classification matrix looks as follows: fractionation variant (p=0.423), isoeffective dose <59.5Gy≥ (p<0.0001), temozolomide during radiotherapy (p=0.701), functional status (p=0.485).

In patients with Grade IV gliomas and no REP, 3 Gy fractionation regimen has significant advantages over standard radiotherapy regarding overall survival. In case of more aggressive course of tumor (REP), higher single dose does not improve treatment outcomes. Isoeffective dose ≥59.5Gy is of great importance.