Surgery is the treatment of choice for non-functioning pituitary macroadenomas (NFPAs). In cases of postoperative remnant growth or tumor recurrence, radiotherapy (RT) can be considered. The role of RT in the postoperative management of NFPAs is still debated. The main arguments against routine use of RT are the lack of randomized controlled trials, the use of clinically irrelevant endpoints in most studies on RT, the benign character of the condition, the potential for side effects of RT, and the option to apply RT at a later stage. However, because of its excellent efficacy in inhibiting tumor growth, reducing tumor volume and improving any existing visual defects, and as its side effects seem to be limited compared to the benefits provided, RT keeps a place in the management of NFPAs when a tumor remnant persists, particularly if it is invasive and displays high proliferation markers, if surveillance shows a relevant increase in tumor volume or if the tumor is close to the optic chiasm. The size of the remnant, its vicinity with the optic pathways, and the potential risk to healthy surrounding tissues need to be considered when deciding on an RT procedure.
Context Prospective studies have demonstrated the efficacy of osilodrostat in Cushing's disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing’s syndrome/ectopic ACTH syndrome (PNCS/EAS). Objective Evaluate in France the real-world efficacy and safety of osilodrostat in PNCS/EAS. Patients 33 patients with PNCS/EAS with intense/severe hypercortisolism. Methods Retrospective multicenter real-world study. Patients received osilodrostat between May 2019 and March 2022. Median initial dose (range) 4 mg/day (1-60); maximum dose, 20 mg/day (4-100), first, under patient- then cohort- temporary authorizations and after marketing authorization. Regimens used: titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). Results In 11 patients receiving osilodrostat as first-line monotherapy, median 24h- urinary free cortisol (24h-UFC) decreased dramatically (from 26xULN [2.9-659] to 0.11xULN [0.08-14.9]; p < 0.001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10/13 were not controlled. In these patients, osilodrostat monotherapy, used in second line, induced a significantly decreased of 24h-UFC (from 2.6xULN [1.1-144] to 0.22xULN [0.12-0.66]; p < 0.01). Nine additional patients received osilodrostat in combination with another anticortisolic drug decreasing 24h-UFC from 11.8xULN (0.3-247) to 0.43xULN (0.33-2.4) (p < 0.01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia and hypokalemia, allowing the discontinuation or dose reduction of their treatments. Adrenal insufficiency (grade 3-4) was reported in 8/33 patients. Conclusions Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; Adrenal insufficiency was the main side effect.
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