LBA 07 - Efficacy of Hypofractionated Stereotactic Radiotherapy with Different Dose Fractionation Regimens Combined with Concurrent Bevacizumab in Recurrent High-Grade Gliomas: A Randomized Controlled Trial

02:20pm - 02:30pm PT

San Francisco Ballroom

Presenter(s)

Feng Liu, MD - Hunan Cancer Hospital, Changsha, Hunan

F. Liu¹, H. Wang^1,2, Y. Li¹, X. Chen¹, W. Zhu¹, Y. Li¹, Y. Qiu¹, C. Jiang¹, C. Fan¹, X. Ye¹, S. Xiao¹, S. Hu¹, K. Chen¹, X. Wu¹, W. Wu¹, and L. He¹; ¹Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, ²Key Laboratory of Translational Radiation Oncology, Hunan Province, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China

Purpose/Objective(s):

Hypofractionated stereotactic radiotherapy (HSRT) combined with concurrent bevacizumab represents a promising treatment strategy for recurrent high-grade gliomas (HGG). However, the optimal dose fractionation pattern of HSRT remains undefined. This randomized phase 2 trial aimed to compare the efficacy and toxicity profiles of HSRT delivered in different dose fractionation schedules (27 Gy/3 fractions, 30 Gy/5 fractions, and 35 Gy/10 fractions) in combination with concurrent bevacizumab for treating recurrent HGG.

Materials/Methods:

Eligible patients were those with recurrent HGG (WHO grade 3-4) and an interval of =6 months from completion of prior chemoradiation to recurrence. A total of 102 patients were enrolled and received HSRT combined with concurrent bevacizumab. These patients were randomly assigned in a 1:1:1 ratio to three HSRT groups: group A (27 Gy in 3 fractions, 9 Gy/fraction), group B (30 Gy in 5 fractions, 6 Gy/fraction), and group C (35 Gy in 10 fractions, 3.5 Gy/fraction), with 34 patients per group. All patients initiated bevacizumab administration on day 1, concurrent with HSRT, and continued treatment every 14 days until disease progression. The primary end point was objective response rate (ORR), with secondary end points including the 6-month progression-free survival (PFS), overall survival (OS) and treatment-related toxicities.

Results:

Both group A and group B demonstrated significantly higher ORRs than group C (79.4%, 73.5%, and 50.0%, respectively; p = 0.023). The six-month PFS rates were also notably higher in group A and group B when compared to group C (67.6%, 61.8%, and 47.1%, respectively; p = 0.023). No significant intergroup differences were observed in OS (85.3%, 79.4%, and 76.5%, respectively; p = 0.81). Multivariate analysis identified HSRT dose fractionation (27 Gy/3F or 30 Gy/5F vs 35 Gy/10F), tumor grade (grade 3 vs 4), IDH status (mutation vs wild-type), 1p/19q status (codeletion vs non-codeletion) as significant predictors of PFS. There were no significant intergroup differences in severe (= grade 3) treatment-related toxicities. However, group A and group B showed higher incidences of grade 1–2 headache, nausea/vomiting, insomnia, alopecia, loss of appetite, and fatigue compared to group C, with no significant differences observed between group A and group B.

Conclusion:

In the treatment of recurrent high-grade gliomas with fractionated stereotactic radiotherapy combined with concurrent bevacizumab, HSRT regimens with higher single-fraction doses (27 Gy/3 fractions and 30 Gy/5 fractions) demonstrated improved ORR and PFS compared to the lower single-fraction dose regimen (35 Gy/10 fractions). Although severe adverse events were comparable, these higher single-fraction dose regimens were associated with increased grade 1–2 toxicities.