Radiation Therapy

The inadequacy of surgery alone or surgery plus local irradiation was first conclusively demonstrated in Harvey Cushing's seminal report from 1930 in which only 1 of 61 patients survived 3 years after surgery alone (n = 30) or surgery plus limited field irradiation (n = 31).12 In 1936, Cutler reported on 20 chil dren with medulloblastoma who were treated with surgical resection followed by radiation therapy to the brain and spine. Cutler concluded, "Roentgen therapy to the ventricular system and the entire spine, as well as to the cerebellum, is essential."13 In 1969, Bloom5 reported a 5- and 10-year survival rate of 40% and 30%, respectively, in 71 patients treated with craniospinal irradiation (CSI).5 Since that time, numerous studies have reinforced the importance of neuraxis radiation therapy for the successful treatment of medulloblastoma in both adults and children.

When radiation therapy is used in newly diagnosed patients, the standard dose delivered to the craniospinal axis is

35 to 36 Gy if patients have no evidence of neuraxis dissemination (M0). The PF is then boosted for an additional 18 to 20 Gy so that the total dose to the PF is approximately 54 to 56 Gy. If CSF cytology is positive (Mj), the recommended dose to the CSA according to the pediatric experience is still only

36 Gy. If nodular disease in the subarachnoid space (M2 or M3) is present, a boost is delivered immediately following CSI to the site of the original metastatic disease (M2 to M3) up to a total dose of 45 Gy. The fractionation scheme used most often in the United States is 1.8 Gy daily, 5 days per week.

Because of the endocrinologic and neurocognitive toxicity of CSI in children, a CCG and POG randomized trial compared treatment with a CSI dose of 23.4 Gy to the standard CSI dose of 36 Gy; both groups received a boost to the PF to 54 Gy. The study was closed prematurely because an early analysis showed an increased incidence of failures in the low-dose group.14 Of the 126 patients enrolled, 81 were evaluable for the final analysis. This longer-term follow-up showed marginally significant differences at 5 years (5-year event-free survival [EFS] 52% [reduced dose] vs. 67% [standard dose], P = .08). However, with follow-up reported at 8 years, there is no statistically significant difference in EFS (8-year EFS 52% vs. 67%, P = .141).62 It thus appears from this study that a lower CSI dose results in earlier failures, but with time there is no statistically significant difference between the two dose regimens. Comparable data are lacking for the adult population of medulloblastoma patients.

There are clear data regarding the dose necessary for control of the primary PF tumor, with a dose relationship clearly seen for doses greater than 50 Gy. The current standard therapy is to boost the entire PF to a total dose of 54 to 55.8 Gy at a fractionation of 1.8 Gy per day using high-energy photons (x-rays). There are no convincing data that administering higher doses to the PF by conventional fractionation or hyperfrac-tionated treatment schedules improves outcomes,55 although boosting residual disease with a stereotactic radiosurgical boost has shown promise in a limited number of patients.52,64

The duration of radiation therapy may also influence outcomes. Taylor et al61 showed a statistically significant reduction in overall survival and EFS if the time from the first radiation treatment to the last radiation treatment was more than 50 days. In this study, there was no difference in the mean or median duration of radiation therapy between those patients treated with radiation therapy alone and those treated with chemotherapy followed by irradiation. It is advisable to complete radiation therapy without breaks.

Complications associated with radiation therapy can be divided into two time frames: acute effects occurring during or shortly after treatment, and late effects occurring months to years after completion of treatment. Acute side effects in adults are usually more pronounced than in children and consist of nausea, vomiting, fatigue, alopecia, skin erythema, significant bone marrow suppression, soreness in the back of the throat with resultant dysphagia, transient loss of taste, transient xerostomia, and occasionally wound dehiscence (usually when there is not an adequate 10- to 14-day interval between surgery and initiation of radiation therapy). Late effects are generally less prominent in adults than in children and include potential pituitary dysfunction, possible infertility, effects on cognition, and possible induction of second malignancies. Although the neu-rocognitive effects in treated adults have not been studied as extensively as in children, there are data to suggest that cranial doses of 30 to 36 Gy may have an impact on cognitive function in survivors, especially on memory, reasoning, visual-spatial ability, and arithmetic calculation skills.40

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