Re-irradiation for recurrent glioma- the NCI experience in tumor control, OAR toxicity and proposal of a novel prognostic scoring system

Abstract

Purpose/objectivesDespite mounting evidence for the use of re-irradiation (re-RT) in recurrent high grade glioma, optimal patient selection criteria for re-RT remain unknown. We present a novel scoring system based on radiobiology principles including target independent factors, the likelihood of target control, and the anticipated organ at risk (OAR) toxicity to allow for proper patient selection in the setting of recurrent glioma.Materials/methodsThirty one patients with recurrent glioma who received re-RT (2008–2016) at NCI – NIH were included in the analysis. A novel scoring system for overall survival (OS) and progression free survival (PFS) was designed to include:1) target independent factors (age, KPS (Karnofsky Performance Status), histology, presence of symptoms), 2) target control, and 3) OAR toxicity risk. Normal tissue complication probability (NTCP) calculations were performed using the Lyman model. Kaplan-Meier analysis was performed for overall survival (OS) and progression free survival (PFS) for comparison amongst variables.ResultsNo patient, including those who received dose to OAR above the published tolerance dose, experienced any treatment related grade 3–5 toxicity with a median PFS and OS from re-RT of 4 months (0.5–103) and 6 months (0.7–103) respectively. Based on cumulative maximum doses the average NTCP was 25% (0–99%) for the chiasm, 21% (0–99%) for the right optic nerve, 6% (0–92%) for the left optic nerve, and 59% (0–100%) for the brainstem. The independent factor and target control scores were each statistically significant for OS and the combination of independent factors plus target control was also significant for both OS (p = 0.02) and PFS (p = 0.006). The anticipated toxicity risk score was not statistically significant.ConclusionOur scoring system may represent a novel approach to patient selection for re-RT in recurrent high grade glioma. Further validation in larger patient cohorts including compilation of doses to tumor and OAR may help refine this further for inclusion into clinical trials and general practice.Electronic supplementary materialThe online version of this article (10.1186/s13014-017-0930-9) contains supplementary material, which is available to authorized users.

Re-irradiation of recurrent glioblastoma using helical TomoTherapy with simultaneous integrated boost: preliminary considerations of treatment efficacy

“…In the re-irradiation setting 42,43 , a smaller irradiated volume is preferable in terms of toxicity, while limiting treatment to contrast-enhancing lesions may lead to lower local control given the invasiveness of gliomas 14 . Accurately determining tumor spread is especially difficult in diffuse tumors, thus increasing the risk of local failure.…”

<p>Carbon Ion Beam Reirradiation in Recurrent High-Grade Glioma</p>

“…14 median 30 Gy. 4 Furthermore, Scholtyssek et al reported on reirradiation applying median total doses of 36 Gy in single doses of 2-5 Gy. 15 In their cohort the median OS from the start of reirradiation was 7.7 months and the OS rates at 6and 12-months were 60% and 24%, respectively.…”

“…15 In addition, Krauze et al did not observe any grade 3-5 AE during follow-up and reported mainly fatigue and alopecia as AE. 4 Fogh et al reported that none of their patients required hospitalization or surgery due to toxicity, while 1 patient developed grade 3 headaches. 14 However, even though treatment was generally well tolerated in our cohort and none of the patients was diagnosed with CTC grade 5 or 4 AE, 8 patients (27%) developed CTC grade 3 AE, requiring medical intervention.…”

“…2 Median overall survival (OS) after reirradiation for recurrent glioma lies between 6 and 10.7 months. [3][4][5][6] Carbon ions have different radiobiological effects that might have the potential to overcome radioresistence. 7,8 For example, carbon ions were able to eradicate hypoxic and stem celllike tumor cells and create an antiangiogenic and less immunosuppressive state.…”

“…Recent developments in prognostic scoring systems for patient selection for reirradiation might help to further optimize the management in recurrent glioma. 3,4 It was our aim to retrospectively assess the outcome and toxicity of patients with recurrent high-grade glioma consecutively treated with carbon ion beam reirradiation at the Marburg Ion-Beam Therapy Center.…”