Abstract PURPOSE/OBJECTIVE(S): Identify prognostic factors for progression-free survival (PFS) and overall survival (OS) after reirradiation (re-RT) for recurrent high grade glioma (HGG). MATERIALS/

METHODS

Patients with HGG received re-RT from 2010 to present. PFS and OS prognostic variables were examined using Cox models. Receiver operative curve (ROC) analysis identified predictive thresholds for continuous variables.

RESULTS

58 patients received surgery and adjuvant radiation for HGG (51 grade IV, 7 grade III). The median time to first progression after initial radiation was 11 months. 36% received single fraction stereotactic re-RT (SRS) (median 18 Gy) and 64% received fractionated re-RT (median 35 Gy in 10 fractions). The median planning target volume (PTV) was 16.8 mL. The median biologically effective dose (BED10) of re-RT was 47 Gy (range 15–72). 50% received chemotherapy and 36% received bevacizumab concurrent to re-RT. Toxicity ≥ grade 3 was 7%. The median PFS after re-RT was 4.7 months and the median OS was 11 months. Lower PFS was significantly associated with shorter time to first progression, lower KPS, and lower re-RT dose. Lower OS was associated with shorter time to first progression, lower KPS, and larger PTV. Other factors were not significantly associated with PFS or OS. ROC analysis of time to first progression and re-RT dose showed best predictive thresholds at time > 12 months and BED10 > 42 Gy. CONCLUSIONS: Reirradiation was tolerated with infrequent high grade toxicity. PFS and OS after re-RT were both predicted by time to progression after initial radiation. Published prognostic scores have used total time from first to second radiation courses; however in our series the period from initial progression to re-RT did not add prognostic information. There was evidence for a dose threshold irrespective of radiotherapy technique. Use of chemotherapy and bevacizumab with re-RT were not associated with improved outcomes.

Background

Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores.

Methods

A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients.

Results

Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively.

Conclusions

Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.