Role of Hypofractionated Radiation Therapy in a Multidisiplinary Approach to Treat Persistent Cushing’s Disease

Abstract

To show that hypofractionated radiation therapy (HFRT) to the residual or recurring pituitary adenoma in a multidisciplinary approach together with surgery and medical treatment (MT) may improve tumor control and endocrine remission in persistent Cushing’s Disease (CD). Twenty-one consecutive patients with persistent CD treated with HFRT in addition to MT, following several surgeries without remission were evaluated retrospectively. Three groups of patients consisting of seven (33.3%) patients each have been treated with a total dose of 21 Gy/3 fx, 25 Gy/5 fx and 30 Gy/10 fx to planning target volume (PTV), which was defined as the adenoma or the pituitary gland and the cavernous sinuses with a 0-1 mm margin. The median time to HFRT following diagnosis of CD was 61 (16 – 206) months. After a median follow-up of 41 (1 – 92) months from the end of HFRT to the last control, endocrine remission and tumor control rates of patients with persistent CD were calculated with Kaplan-Meier method with 1 minus survival curves and compared with Log Rank test following the addition of HFRT to MT. Endocrine insufficiency and optic neuropathy related with HFRT have been evaluated. The median age of the study group was 38 (18 to 66) years and female to male ratio was 2 (14/7). Optic neuropathy has been found in 3 (14.3%) of 21 patients at diagnosis of the disease and have improved with the first surgery of the patients. The indication for HFRT was prolonged MT following one to three surgeries without remission in 20 (95.24%) patients and no responsiveness to MT in 1 (4.8%) medically inoperable patient. Endocrine remission was achieved in 12 (57.1%) and tumor control in 19 (90.5%) of 21 patients. Eight (38.1%) patients developed pituitary insufficiency due to HFRT. No patient developed radiation induced optic neuropathy. Median time to endocrine remission in patients with persistent CD following HFRT was significantly shorter with 30Gy/10fx and 25Gy/5fx compared with 21Gy/3fx (17 vs. 36 months; p = .022). Hypofractionated radiation therapy for persistent CD to surgery and MT result in considerably high endocrine remission rates with tolerable toxicity to the hypothalamopituitary axis. Shorter time to endocrine remission with smaller dose per fraction must be further evaluated in HFRT of patients with persistent CD.