Randomized Prospective Trial of Stereotactic Radiosurgery versus Chemotherapy for Recurrent Malignant Glioma after Second-line Chemotherapy
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Resident PGY 5
Henry Ford Hospital
Purpose: Outcomes for patients with recurrent malignant glioma are dismal. Fractionated radiosurgery (FSRS) has been shown to be feasible and safe when delivered in this setting, but prospective evidence is lacking. We conducted a single-institutional randomized trial on the use of FSRS versus chemotherapy for recurrent malignant glioma after second-line chemotherapy.
Methods: High-grade glioma patients with tumor progression after two previous treatment regimens were enrolled. They were randomized to FSRS with bevacizumab or bevacizumab with irinotecan, temozolomide, or carboplatin (discretion of the treating provider). FSRS was delivered using a frameless linear-accelerator based intensity modulated technique with 32 Gy (8 Gy x 4 treatments within 2 weeks) prescribed to the gross target volume (gadolinium enhancing lesion and DWI abnormality), and 24 Gy (6 Gy x 4) to the clinical target volume (FLAIR abnormality). The primary endpoints were local tumor control (LC) at 2 months and progression-free survival (PFS) in an intention to treat fashion. Toxicity was scored using the Common Terminology Criteria for Adverse Events v.4.0. Response to treatment was evaluated in a multi-disciplinary setting according to the Response Assessment in Neuro-Oncology criteria. The study planned to accrue 78 patients total, but was closed early due to slow accrual.
Results: 35 patients were enrolled from February 2012 to December 2016. 28 patients had glioblastoma (WHO IV) and 7 had anaplastic glioma (WHO III). The median number of prior recurrences was 3. Patients on the FSRS arm had an improved PFS (5.1 vs 1.8 months, p<0.001) and improved LC at 2 months (3/17 patients progressing with FSRS compared to 11/15 on chemotherapy alone) (p=0.002). The overall median survival was 6.6 months (7.2 months in the FSRS arm, 4.8 months in the chemotherapy alone arm, p=0.11). Five patients on the chemotherapy alone arm received FSRS at time of subsequent progression. Four patients died within 2 months of study enrollment. The overall rate of grade 3 toxicity attributable to treatment and not disease progression was 29% and includes hematologic (n = 2), intratumoral hemorrhage (n = 2), new neurological deficit (n =2), headache (n = 1), vomiting (n = 1), cerebral edema (n = 1), seizure (n = 1). No treatment related grade 4 or higher toxicity was observed.
Conclusions: Findings of our study suggest that FSRS in heavily pretreated patients with recurrent malignant glioma is feasible and improves LC and PFS when compared to treatment with next line chemotherapy alone.
Modh, Ankit; Bergman, David; Schultz, Lonni; Hanna, Renee; Snyder, James; Mikkelsen, Tom; Ryu, Samuel; Walbert, Tobias; and Siddiqui, M Salim, "Randomized Prospective Trial of Stereotactic Radiosurgery versus Chemotherapy for Recurrent Malignant Glioma after Second-line Chemotherapy" (2019). Clinical Research. 34.