Progression of potentially aggressive PitNETs after radiotherapy: risk factors, management, and outcomes

Radiotherapy plays a relevant role in uncontrolled pituitary neuroendocrine tumors (PitNETs). Radiotherapy controls tumor progression in most cases, but not always. Prognostic factors for tumor progression after radiotherapy remain poorly defined. The aim was to evaluate tumor progression after radiotherapy, to identify risk factors, and to report management and outcomes in a cohort of PitNETs with uncontrolled progression. This was a retrospective, single-center, observational study. In total, 123 consecutive patients who underwent radiotherapy for PitNETs and were followed at Cochin Hospital between 2000 and 2022 were included. Indication for radiotherapy was uncontrolled tumor progression (80%), adjuvant (9%), or uncontrolled secretion (11%). The median follow-up after radiotherapy was 10.0 years. Tumor progression after radiotherapy was observed in 28/123 (23%) patients. Higher risk of progression was associated with lactotroph and corticotroph tumor types (HR [95% CI] 12.0 [1.2-117.1] and 9.3 [1.3-69.6], respectively), male sex (3.7 [1.6-8.4]), and necrotic-hemorrhagic changes before radiotherapy on magnetic resonance imaging (3.1 [1.1-8.4]). Surgery, temozolomide, and re-irradiation were the most frequent treatments for the management of patients with tumor progression after radiotherapy, used in 18/28(64%), 16/28(57%), and 8/28(29%) cases, respectively. The most common complication of radiotherapy was the new onset of pituitary deficits, observed in 41% of cases; other complications, including radiation-induced neuroinflammation, cerebrovascular events, and second brain tumors, were rare. Three patients developed metastases, and 6 patients died because of tumor progression. Lactotroph and corticotroph PitNETs, in male patients, and/or with necrotic-hemorrhagic changes are at higher risk of progression after radiotherapy. Patients with progression after radiotherapy require additional heavy treatments with variable outcome.