Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas

Context: Radiation therapy is a potentially curative treatment for corticotroph adenomas refractory to surgery. Protons have an advantage over photons(x-rays) by depositing energy at the target with no exit dose, providing a lower dose to adjacent normal tissues. Until recently, proton stereotactic radiotherapy (PSR) was available at only two U.S. centers; use will increase as proton facilities are under development. Objective: Our objective was to evaluate the efficacy and safety of PSR for persistent Cushing's disease (CD) and Nelson's syndrome (NS). Design: This was a retrospective review of 38 patients (33 with CD and five with NS) treated between 1992 and 2005. Participants: All patients had transsphenoidal surgery without biochemical cure. Four had previous irradiation with photons. The patients with INS underwent bilateral adrenalectomy 29-228 months (median 40) before PSR. Intervention: Single-fraction PSR was delivered at a median dose of 20 Cobalt Gray Equivalents (range 15-20) on 1 treatment day. Main Outcome Measures: Complete response (CR) was defined as sustained ( >= 3 months) normalization of urinary free cortisol off medical therapy. CR in NS was based on normalization of plasma corticotropin. Results: At a median follow-up of 62 months (range 20-136), CR was achieved in five patients (100%) with NS and 17 (52%) patients with CD. Among all patients with CR, median time to CR was 18 months (range 5-49). No secondary tumors were noted on follow-up magnetic resonance imaging scans, and there was no clinical evidence of optic nerve damage, seizure, or brain injury. There were 17 patients (52%) who developed new pituitary deficits. Conclusions: PSR is effective for patients with persistent corticotroph adenomas with low morbidity after a median follow-up of 62 months; longer follow-up is warranted for late radiation related sequelae.