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.
Highlights
Survival following concurrent radiation (RT) and temozolomide (TMZ) as per the EORTC 26981/22981-NCIC CE3 trial remains poor with median survival ranging from 39 months in RPA (Recursive Partitioning Analysis) class I patients to 5.2 months in RPA class VI patients [1]
Our scoring system may represent a novel approach to patient selection for re-RT in recurrent high grade glioma
The median age was 47y/o (18-73y), 58% were male, and 81% had a pre re-RT Karnofsky Performance Status (KPS) ≥70 (Table 2). 58% of patients were initially diagnosed with a GBM with the majority located in the fronto-parietal lobes
Summary
Survival following concurrent radiation (RT) and temozolomide (TMZ) as per the EORTC 26981/22981-NCIC CE3 trial remains poor with median survival ranging from 39 months in RPA (Recursive Partitioning Analysis) class I patients to 5.2 months in RPA class VI patients [1]. Brain tumor recurrences can be identified by the development of new neurological symptoms, radiographic changes or both [3]. The treatment recommendations can vary widely and are partially based on the patient’s performance status, tumor location, and time interval since last treatment. Krauze et al Radiation Oncology (2017) 12:191 on these factors, options may include re-resection, chemotherapy, re-irradiation (re-RT) or enrollment on a clinical trial [4]. Tumor re-resection is possible in less than 50% of patients [5] and the response to systemic treatment, if it occurs, is short lived with overall survival (OS) from 7.1 to 9.6 months [4]. For a significant proportion of patients with recurrent glioma in whom re-resection is not possible and for whom systemic options have been exhausted, re-RT has emerged as a possible treatment option
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