[Role of radiotherapy in recurrent gliomas]

Abstract

Intracranial gliomas account for less than 2% of primary solid tumors in adults, but are among the most frequent causes of death from cancer in children. Their increasing incidence and the weak impact of treatments on the prognosis justify all the efforts expended to improve results. Surgery, radiation therapy (RT) and chemotherapy are proposed as first-line therapy, according to indications and modalities that remain controversial. In this palliative setting, the only consensus is to search for an optimal efficacy/toxicity ratio. Finally, after a very variable duration of local control depending on the histologic type, recurrence is virtually inevitable, with mainly local progression. The prognosis is then generally dismal, with a median survival of less than 6 months. Although re-operation is efficient for the rapid relief of symptoms, it is often rejected. After or in the absence of surgery, different chemotherapy schedules are proposed according to the histologic type and the patient's general status and objective response rates are very limited, except in the case of oligodendrogliomas. Re-irradiation has a rather bad reputation: even as first-line therapy, total doses never exceed 60 Gy in 30 fractions of 2 Gy over six weeks (conventional fractionation). The main reasons are concerns about increasing unacceptable late neurologic complications and the absence of a demonstrated dose-effect beyond this threshold. However, some arguments have led clinicians to consider lifting the ban on re-irradiation. Among adult patients receiving focal RT for low-grade gliomas, late neurologic toxicity was recently evaluated prospectively using a battery of neurocognitive tests. Compared with the initial status, no significant deleterious effects were observed with a follow-up of at least 3 years. In addition, studies on primates demonstrated that the spinal cord was capable of repairing, at least partially, RT-induced injury. There appears to be room for further irradiation: the results of re-irradiation in more than 300 patients have been documented. The techniques used, patient selection and re-irradiation modalities reported were varied: interstitial brachytherapy or intraoperative-RT within the surgical bed, conformal 3D RT, stereotactic-RT delivered in one or several fractions. Treatment efficacy and toxicity endpoints were very heterogeneous. Nevertheless, with a clearly defined prospective assessment, re-irradiation seems possible without any unacceptable clinical neurotoxicity under the following conditions: a good general status (WHO 0-1); at least a one-year disease-free interval; an initial WHO grade 2 or 3 histology with a maximal tumor diameter not exceeding 3 cm. In this very selective setting, re-irradiation is possible at a dose of 30 to 40 Gy, if possible in stereotactic mode, with a hypofractionated schedule (less than 4 Gy/fraction). Median survival exceeding one year is expected, the main endpoint being the control of symptoms and quality of life.