External beam radiotherapy of recurrent glioma: radiation tolerance of the human brain

Abstract

Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative). Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials.

Figure 1

Total dose in 2 Gy fractions (EQD2_cumulative) as a function of the time interval between initial treatment and conventional re-irradiation (squares), fractionated stereotactic radiotherapy (triangles) and stereotactic radiosurgery (circles). Open symbols: none of the patients in the study showed brain necrosis; solid symbols: patient(s) with radionecrosis in the study. Symbol size represents the number of patients in the study. Small-sized symbol <25 patients; median-sized symbol 26–50 patients; large-sized symbol >50 patients. Symbols in the figure match the symbols used in Table 1, Table 2, Table 3. (Spearman nonparametric correlation: p = 0.016).

Figure 2

Correlation of the initial dose (EQD2_initial) and re-irradiation dose (EQD2_{reirradiation}) for patients re-irradiated with conventional radiotherapy, fractionated stereotactic radiotherapy and stereotactic radiosurgery (see legend to Figure 1 for an explanation of the symbols).

Figure 3

Treatment volume versus cumulative dose in 2 Gy fractions (EQD2_cumulative). The symbols match the studies presented in Table 2 and Table 3 (see legend to Figure 1 for an explanation of the symbols).