Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

• Published in: Journal of neuro-oncology Vol. 148; no. 2; pp. 353 - 361
• Main Authors: Bergman, David, Modh, Ankit, Schultz, Lonni, Snyder, James, Mikkelsen, Tom, Shah, Mira, Ryu, Samuel, Siddiqui, M. Salim, Walbert, Tobias
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2020; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - therapeutic use; Bevacizumab; Bevacizumab - therapeutic use; Brain Neoplasms - therapy; Carboplatin; Chemoradiotherapy - methods; Chemotherapy; Clinical Study; Dose Fractionation, Radiation; Drug Resistance, Neoplasm; Etoposide; Female; Glioblastoma; Glioma; Glioma - therapy; Humans; Immunotherapy; Irinotecan; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neurology; Oncology; Patients; Prospective Studies; Radiosurgery; Survival; Targeted cancer therapy; Temozolomide; Treatment Outcome; Fractionated radiosurgery; Re-irradiation; High-grade glioma; Glioblastoma; Bevacizumab
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-020-03526-4

Purpose
Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. This single-institution randomized trial compared FSRS plus BEV-based chemotherapy versus BEV-based chemotherapy alone for BEV-resistant recurrent malignant glioma.
Materials and methods
HGG patients on BEV with tumor progression after 2 previous treatments were randomized to 1) FSRS plus BEV-based chemotherapy or 2) BEV-based chemotherapy with irinotecan, etoposide, temozolomide, or carboplatin. FSRS was delivered as 32 Gy (8 Gy × 4 fractions within 2 weeks) to the gross target volume and 24 Gy (6 Gy × 4 fractions) to the clinical target volume (fluid-attenuated inversion recovery abnormality). The primary endpoints were local control (LC) at 2 months and progression-free survival (PFS).
Results
Of the 35 patients enrolled, 29 had glioblastoma (WHO IV) and 6 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients treated with FSRS had significantly improved PFS (5.1 vs 1.8 months,
P
 < .001) and improved LC at 2 months (82% [14/17] vs 27% [4/15],
P
 = .002). The overall median survival was 6.6 months (7.2 months with FSRS vs 4.8 months with chemotherapy alone,
P
 = .11).
Conclusions
FSRS combined with BEV-based chemotherapy in recurrent HGG patients progressing on BEV is feasible and improves LC and PFS when compared to treatment with BEV-based chemotherapy alone.