Is there a safe therapeutic window for delivery of chemotherapy prior to initiation of surgery and/or radiation-therapy for treatment of the primary tumor in children with rhabdomyosarcoma.

To avoid the delayed consequences of treatment with radiotherapy, an effort was made to determine if patients with rhabdomyosarcoma could be cured with chemotherapy as the sole form of treatment. Alternatively, if radiotherapy and/or surgery were required to reduce the severity and incidence of delayed sequelae, an effort was made to determine if there was an optimum safe period for delaying implementation of these definitive forms of treatment. In patients where primary (immediate) definitive non-mutilating surgical extirpation of tumor was not feasible, exclusive treatment with chemotherapy was implemented. If considered necessary or appropriate, delayed surgery and/or radiation therapy were employed in 3 circumstances: (i) to consolidate a partial response; (ii) failure to respond; (iii) recurrent disease. The outcome of the delays prior to the implementation of definitive therapy was analyzed as a function of local and systemic recurrence and cure. Fifty-two patients were evaluated. Seven underwent primary non-mutilating surgical extirpation of localized tumor followed by adjuvant chemotherapy. The remaining 45 were treated with primary chemotherapy and 44 responded. Actuarial survival curves of the delay in initiating definitive therapy in the 52 patients revealed that the optimum delay to attain the best survival was 5 months. In circumstances where definitive therapy was not electively introduced, recurrent disease during remission appeared between 7 and 14 months in 7 patients on continued treatment, and in one patient at 30 months, 8 months after discontinuation of chemotherapy. Based upon the 5-month delay an analysis of survival was performed: Definitive therapy was introduced in 14 patients within 5 months and 7 were cured. In the remaining 31 patients, definitive therapy was introduced between 5 and 30 months and 15 were cured. The five month delay is supported empirically by tumor doubling times. No patient was cured exclusively with chemotherapy.