Fractionated low-dose radiotherapy after myeloablative stem cell transplantation for local control in patients with high-risk neuroblastoma.

ABSTRACT

BACKGROUND: The optimal administration of radiotherapy for patients with high-risk neuroblastoma (NB) currently is undefined in the context of modern therapy using myeloablative chemotherapy with autologous stem cell rescue (hematopoietic stem cell transplantation [HSCT]). METHODS: The authors conducted a retrospective review of the records of 21 consecutive patients with high-risk NB to assess local control and toxicity of external beam radiotherapy (XRT). Therapy included multiagent induction chemotherapy and delayed surgical resection, consolidation of HSCT and local XRT, and 13-cis-retinoic acid maintenance therapy. XRT was delivered to the primary site, using postchemotherapy volumes, and to initial metastatic sites with 1-2 cm margins to 2100 centigrays (cGy) using 14 fractions administered once daily. RESULTS: Four of 21 patients did not receive XRT due to toxic death (n = 2), disease progression before XRT (n = 1), or parental refusal (n = 1). The median time to XRT post-HSCT was 54 days. Thirteen patients received a second peripheral blood stem cell infusion after completing XRT. Twelve of the 14 patients who received XRT post-HSCT and for whom toxicity data were available had Grade 3-4 acute toxicities, including gastrointestinal toxicity (n = 8), hematologic toxicity (n = 9), and infection (n = 1). Nonrecurrent long-term toxicities included prolonged nutritional deficiency (n = 9) and leg-length discrepancy (n = 1). Tumors recurred in 7 of 21 patients (5 of 17 patients who received radiotherapy), either within a radiation field (n = 1) or at distant nonirradiated sites (n = 6). The estimated local failure rate was 7% (95% confidence interval [95% CI], 0-14%), with a 2-year event-free survival rate of 48% (95% CI, 26-70%). CONCLUSIONS: Post-HSCT, fractionated XRT to 2100 cGy was a tolerable and effective treatment for patients with high-risk NB, and minimal recurrences were observed at designated XRT sites.