Treatment of Recurrent Orbital Rhabdomyosarcoma with Exenteration and HDR Brachytherapy in a Custom Mold

Abstract

Rhabdomyosarcoma (RMS) is the most frequent cancer affecting the orbit in children. The orbit is classified as a favorable site for RMS as treatment with chemotherapy and radiation is effective. Local failure for patients with RMS of the orbit has ranged from 2-16% on IRS and COG protocols. In the event of local recurrence, survival is poor, and management is difficult. We report four patients with local recurrence of orbital RMS managed with orbital exenteration followed by high dose rate (HDR) brachytherapy. Four patients were treated from 2016-2022. HDR brachytherapy with Ir-192 was delivered in a custom mold of the orbit made after the orbital exenteration procedure. Brachytherapy was given in 6-7 twice daily (BID) fractions starting 1 week after the orbital exenteration. At the time of brachytherapy, patient ages were 3, 1, 7, and 7 years. Three patients had embryonal histology and underwent initial systemic therapy with ARST0331 regimen A. The fourth patient had alveolar, FOXO1 fusion positive RMS and was initially treated as per COG D9803 regimen A. All patients had received proton radiotherapy as part of initial treatment. Three received 50.40 Gy and one received 45 Gy. Patients developed biopsy-proven, recurrent disease an average of 56 weeks (range 38-77) after initial diagnosis. All patients received salvage chemotherapy before undergoing orbital exenteration at an average of 12 weeks after recurrence (range 5-16). Three patients received 30 Gy in 6 BID fractions, and one patient received 28 Gy in 7 fractions with HDR brachytherapy using an Ir-192 source. All four patients are alive without evidence of disease at an average of 27 months (range 6-70) from recurrence and 39 months (range 21-78) from initial diagnosis. All patients have acceptable orbit healing. Two patients have asymptomatic evidence of frontal lobe edema (and in one case possible necrosis) extending 1-2 cm above the orbit. This appears to be beyond the range of the brachytherapy dosimetry, but the combination of proton beam and brachytherapy are implicated. No other toxicities have occurred. Orbital RMS has a favorable prognosis, but local failure after initial combined modality therapy can be fatal. Options for successful local salvage are limited. Orbital exenteration with HDR brachytherapy in a custom mold is an effective and safe procedure for local control in these difficult cases.