Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia.

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Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.

Background Successful therapy for ependymoma includes aggressive surgical intervention and radiation therapy administered using methods which minimize the risk of side effects. We extended this treatment approach to include children under the age of 3 years. Methods Between July 1997 and 2007, 153 pediatric patients (median age 2·9 years, range 0·9–22·9 years) with localized ependymoma received conformal radiation therapy after definitive surgery. Doses of 59·4 (n=131) or 54·0 Gy (n=22) were prescribed to a 10mm clinical target volume margin surrounding the post-operative residual tumor and/or tumor bed. The patients had the following characteristics: anaplastic ependymoma (n=85), infratentorial location (n=122), prior chemotherapy (n=35) and extent of resection (gross-total=125, near-total=17, subtotal=11). Disease control, patterns of failure and complications were recorded for patients followed through 10 years. Findings With a median follow-up of 5·3 years (range 0·4 to 10·4 years), death was recorded in 23 patients and tumor progression in 36, including local (n=14), distant (n=15) and combined failure (n=7). Tumor grade predicted overall (OS) and event-free (EFS) survival and distant failure. Extent of resection predicted OS, EFS and local failure. Race predicted OS. The 7 year local control, event-free and overall survival were 83·7% (95% CI: 73·9–93·5%), 69·1% (95% CI: 56·9–81·3%) and 81·0% (95% CI: 71·0–91·0%), respectively. The cumulative incidence of local and distance failure were 16·3% (95% CI: 9·6–23·0%) and 11·48% (95% CI: 5·9–17·1%), respectively. Considering only those patients treated with immediate post-operative CRT (without delay or chemotherapy) the 7 year OS, EFS and CI of local and distant failure were 85·0% (95% CI: 74·2–95·8%), 76·9% (95% CI: 63·4–90·4%), 12·59% (95% CI: 5·1–20·1%)and 8·56% (95% CI: 2·8–14·3%), respectively. The incidence of secondary malignant brain tumor at 7 years was 2·3% (95% CI: 0–5·6%) and brainstem necrosis 1·6% (95% CI: 0–4·0%). Interpretation This study provides new disease control benchmarks and a unifying approach for the treatment of ependymoma that should include surgery with the aim of gross-total resection and conformal, high-dose, post-operative irradiation even for the youngest children. Future trials might consider treatment stratification based on gender and age as female patients are more likely to be long-term survivors and younger patients have higher rates of failure.