Aggressive pituitary tumours and carcinomas, characteristics and management of 171 patients
Pia Burman, Jacqueline Trouillas, Marco Losa, Ann McCormack, Stephan Petersenn, Vera Popović, Marily Theodoropoulou, Gérald Raverot, Olaf M. Dekkers, Agathe Guénégo, Alexander Micko, Alicia Hubalewska-Dydejezky, Amineh Troendle, Ann McCormack, Åse Krogh Rasmussen, Ben Whitelaw, Bénédicte Decoudier, Bertil Ekman, Britt Edén Engström, Charlotte Höybye, Christel Jublanc, Christine Cortet Rudelli, Claire Higham, C. Garcia, Damien Bresson, David Henley, Delphine Larrieu‐Ciron, Dominique Maiter, Edward R. Laws, Emanuel Christ, Emmanuelle Kuhn, Filippo Ceccato, F. Schillo, Frédéric Castinetti, Gérald Raverot, Giovanna Mantovani, Greisa Vila, Hélène Lasolle, Ismene Bilbao Garay, Ivana Kralievic, Jens Otto Lunde Jørgensen, Katarina Berinder, Katrin Ritzel, Leon A. Bach, León Darío Ortiz, Lise Crinière, Luis V. Syro, Magalie Haissaguerre, Marco Losa, Maria Chiara Zatelli, Marie Batisse‐Lignier, Marie‐Lise Jaffrain‐Rea, Márta Korbonits, Marta Ragonese, Martín Reincke, Miklós Tóth, Nathalie Bourcigaux, Nicolas Chevalier, Óskar Ragnarsson, Philippe Chanson, Pia Burman, Sandra Pekić, Stephan Petersenn, Susana Mallea-Gil, Takeshi Usui, Timo Deutschbein, Tânia Longo Mazzuco, Tina Dušek, Ulla Feldt‐Rasmussen, Vera Popović, Yona Greenman
Abstract
Objective: To describe clinical and pathological characteristics and treatment outcomes in a large cohort of aggressive pituitary tumours (APT)/pituitary carcinomas (PC). Design: Electronic survey August 2020-May 2021. Results: 96% of 171 (121 APT, 50 PC), initially presented as macro/giant tumours, 6 were microadenomas (5 corticotroph). Ninety-seven tumours, initially considered clinically benign, demonstrated aggressive behaviour after 5.5 years (IQR: 2.8-12). Of the patients, 63% were men. Adrenocorticotrophic hormone (ACTH)-secreting tumours constituted 30% of the APT/PC, and the gonadotroph subtypes were under-represented. Five out of 13 silent corticotroph tumours and 2/6 silent somatotroph tumours became secreting. Metastases were observed after median 6.3 years (IQR 3.7-12.1) from diagnosis. At the first surgery, the Ki67 index was ≥3% in 74/93 (80%) and ≥10% in 38/93 (41%) tumours. An absolute increase of Ki67 ≥ 10% after median of 6 years from the first surgery occurred in 18/49 examined tumours. Tumours with an aggressive course from outset had higher Ki67, mitotic counts, and p53. Temozolomide treatment in 156/171 patients resulted in complete response in 9.6%, partial response in 30.1%, stable disease in 28.1%, and progressive disease in 32.2% of the patients. Treatment with bevacizumab, immune checkpoint inhibitors, and peptide receptor radionuclide therapy resulted in partial regression in 1/10, 1/6, and 3/11, respectively. Median survival in APT and PC was 17.2 and 11.3 years, respectively. Tumours with Ki67 ≥ 10% and ACTH-secretion were associated with worse prognosis. Conclusion: APT/PCs exhibit a wide and challenging spectrum of behaviour. Temozolomide is the first-line chemotherapy, and other oncological therapies are emerging. Treatment response continues to be difficult to predict with currently studied biomarkers.