Association between Radiation Dose and Local Failure in Recurrent High-Risk Neuroblastoma

Abstract

Historically, standard-of-care (SoC) for high-risk neuroblastoma recurrences is irradiation to 2160 cGy for gross or microscopic disease. Boosting gross disease to 3000-3600 cGy remains controversial. Prior reports have demonstrated worse local control with gross disease irradiated to <3000 cGy. We sought to evaluate whether higher radiation doses delivered to sites of recurrence affected local control. We identified seventy-five high-risk neuroblastoma patients aged 6 months to 26 years that completed definitive treatment between 2007 and 2021 at two large academic centers. Only patients with distant recurrences treated with radiotherapy were included for analysis. Treatments were stratified into 1800-2160 cGy or 3000-3600 cGy dose levels. Local failure after irradiation was defined as progression within the radiation field after salvage RT. The Fine-Gray competing risk model was used to identify cumulative incidence of local failure (CILF) after irradiation with competing risk of death. Thirteen patients experienced recurrence after completion of definitive treatment, representing 30 metastatic lesions. Thirteen lesions received 1800-2160 cGy and seventeen received 3000-3600 cGy. With a median follow-up of 42.0 months (IQR 30.8-60.8), local failure after irradiation occurred in 10% (3/30) of metastatic lesions. Median time to failure was 7 months. All three failures had been treated to 2160 cGy; two in the calvarium and one in the femur. There were no local failures among patients treated to 3000-3600 cGy. The 1-year and 2-year CILF for the low- versus high-dose levels were 15% versus 0% (p<0.01) and 25% versus 0% (p<0.01), respectively. Four of the 13 patients (31%) died at a median time of 12.5 months after first recurrence; all four had distant recurrences. Dose-escalated irradiation ≥3000 cGy was associated with improved local control in recurrent high-risk neuroblastoma; prospective study and validation is warranted.