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.
Highlights
Gliomas are the most common primary brain tumours, with glioblastoma multiforme (GBM) being the most frequent, aggressive and invasive tumour type
This paper presents an overview of current clinical data on re-irradiation of recurrent glioma with respect to the tolerance dose of normal, healthy brain tissue
Re-irradiation studies are summarized according to conventional radiotherapy (Table 1), fractionated stereotactic radiotherapy (FSRT) (Table 2) and LINAC-based stereotactic radiosurgery (SRS) (Table 3)
Summary
Gliomas are the most common primary brain tumours, with glioblastoma multiforme (GBM) being the most frequent, aggressive and invasive tumour type. Postoperative radiotherapy with concomitant temozolomide (TMZ) has become the standard of care for patients with newly diagnosed GBM, based on the results of a large European-Canadian phase III trial [1]. This latter randomised trial demonstrated a significant increase in median survival from 12.1 months after radiotherapy alone to. Benefits of TMZ with radiotherapy lasted throughout 5 years of follow-up, with a survival rate of 9.8% versus 1.9% after radiotherapy alone [2] Despite this important success, most patients die from recurrent disease. The high recurrence rate of about 100% is due to the infiltrative growth characteristics of this tumour type, with its spread throughout normal brain tissue, and high resistance to both radiotherapy and chemotherapy
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