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I. J. Radiation Oncology d Biology d Physics

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Volume 71, Number 1, 2008

the recurrence was local. The nature and timing of the local failure may provide helpful clues about the risk of neuraxis dissemination and move caregivers to recommend focal or craniospinal treatment. The specter of metastatic disease may be decreased in a patient who experiences disease pro- gression where residual tumor was known to remain after ini- tial surgery or in a patient who develops obvious local failure relatively late, longer than 3 years after RT. Clinical condi- tion and age of a patient also require consideration; very young or debilitated patients may not fare well with CSI. We do not propose a lower age cutoff for CSI, but consider it to be an option in children older than 3 years because pa- tients of a similar age with medulloblastoma continue to un- dergo high-dose CSI as a front-line treatment option. The role of radiosurgery is difficult to define from our series because of the small number of patients and prepon- derance of treatment sites that involve the brainstem. Al- though it might be considered a better option for patients with supratentorial local or metastatic disease, these patients tend to have operable disease that may be removed and sim- plify follow-up, which, after radiosurgery, is often com- plicated by changes in the treated volume and normal tissues. Even with radiosurgery, some normal brain is irra- diated. High-dose single-fraction treatment can be harmful, especially when such a critical structure as the brainstem is involved. Reirradiation for recurrent primary brain tumors has been a long-standing treatment option, with investigators cogni- zant of the attendant risks of necrosis or neurologic compli- cation (9) . One published series reported a 9% risk of necrosis and overall complication rate of 29% in 34 patients with primary brain tumors, including children, undergoing fractionated reirradiation to a median combined dose of 79.7 Gy (range, 43.2–111 Gy) (1) . This series showed only a modest palliative and survival benefit in a diverse group of patients. A more specific evaluation of combined reirradia- tion and lomustine therapy was conducted in a small cohort of patients with high-grade glioma, showing a median overall survival of 13.7 months. The reirradiation dose was limited to 34.5 Gy in 23 fractions, with a median interval between first and second courses of irradiation of 14 months (10) . With the advent of conformal RT, investigators attempted to minimize the dose to normal tissues when reirradiation was attempted. 1. BaumanGS, Sneed PK,WaraWM, et al . Reirradiation of primary CNS tumors. Int J Radiat Oncol Biol Phys 1996;36:433–441. 2. Milker-Zabel S, Zabel A, Thilmann C, et al . Results of three- dimensional stereotactically-guided radiotherapy in recurrent medulloblastoma. J Neurooncol 2002;60:227–233. 3. Weprin BE, Hall WA, Cho KH, et al . Stereotactic radiosurgery in pediatric patients. Pediatr Neurol 1996;15:193–199. 4. Lo SS, Chang EL, Sloan AE. Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in the management of intracranial ependymoma. Expert Rev Neurother 2006;6: 501–507. 5. Merchant TE, Mulhern RK, Krasin MJ, et al . Preliminary results from a phase II trial of conformal radiation therapy and evalua-

One series included 20 patients with primary brain tumors unsuitable for brachytherapy or radiosurgery, predominantly high-grade glioma. With a median reirradiation dose of 36 Gy (range, 30.6–59.4 Gy) and combined dose range of 80.6–119.4 Gy, neurologic improvement and stabilization of disease was observed in more than 67% of patients (11) . Different dose and fractionated schemes were attempted for similar patients. For example, low-dose (36 Gy) fractionated reirradiation was applied successfully to predominantly adult patients with low- and high-grade astrocytoma. The lack of observed toxicity might be attributable to the long interval between courses (median, 50 months) for patients with low grade and relatively short time to progression for patients with high grade (12, 13) . Similar low hypofractionated doses were applied in patients with high-grade glioma (14) and EP (15) with modest results. The FFRT and radiosurgery for medulloblastoma appears to be safe, provided doses are rela- tively low, and locally effective. However, overall results are poor in a tumor system prone to metastatic failure, not unlike EP (2) . The patients in this report continue to be followed up for treatment-related side effects involving neurologic, endo- crine, and cognitive function. None was lost to follow-up. Of the 23 patients for whom salvage therapy did not fail, 4 have notable disabilities, including the 2 patients alive and without disease progression after necrosis (1 radiosurgery pa- tient and 1 patient treated with CSI), 1 patient who was func- tionally disabled by surgery before reirradiation, and the patient who is the longest survivor in our series (>20 years) who lives with parents and is simply employed. The rest of the children continue to be followed up, and the magnitude of side effects has been greatest in children treated with CSI. Given the very small volume targeted for FFRT, barring structure damage to the brainstem, the risks of endocrinop- athy, ototoxicity, and cognitive decline for these patients do not appear to be significantly greater than those observed after their initial treatment course. In summary, reirradiation with curative intent should be considered for patients with recurrent EP after previous adju- vant focal irradiation. Aggressive attempts to resect local and metastatic disease are favored in this approach. Patients treated in this manner require careful surveillance for side effects of this combined salvage treatment approach. tion of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 2004;22:3156–3162. 6. Nieder C, Milas L, Ang KK. Tissue tolerance to reirradiation. Semin Radiat Oncol 2000;10:200–209. 7. Sminia P, van der Kleij AJ, Carl UM, et al . Prophylactic hyper- baric oxygen treatment and rat spinal cord re-irradiation. Cancer Lett 2003;191:59–65. 8. Nieder C, GrosuAL, Andratschke NH, et al . Update of human spi- nal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys 2006;66:1446–1449. 9. Dritschilo A, Bruckman JE, Cassady JR, et al . Tolerance of brain to multiple courses of radiation therapy. I. Clinical expe- riences. Br J Radiol 1981;54:782–786.

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