Aggressive pituitary tumours and carcinomas, characteristics and management of 171 patients

Abstract

Objective: To describe clinical and pathological characteristics and treatment outcome in a large cohort of aggressive pituitary tumours (APT)/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 an aggressive behavior after 5.5 years (IQR 2.8-12). 63% of patients were men. ACTH-secreting tumours constituted 30% of the APT/PC, the gonadotroph subtypes were underrepresented.5/13 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, Ki67 index was ≥3% in 74/93 (80%), ≥10% in 38/93 (41%) tumours. An absolute increase of Ki67 ≥10% after median 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 behavior. Temozolomide is the first line chemotherapy, other oncological therapies are emerging. Treatment response continues to be difficult to predict with currently studied biomarkers.

Individualized medical treatment options in Cushing disease

“…The outcomes of ICIs treatment in the presented group were not satisfactory-in all cases disease progression were reported (25). Nevertheless, in general, clinically significant responses (at least SD of longer duration) of ICIs treatment in aggressive PitNETs were observed in 7 out of 15 cases published in the literature (25).…”

“…Immune checkpoint inhibitors were used as second-line treatment in six patients, five of whom were ACTH-secreting PitNETs [two patients were presented previously by Cassese et al (82) and Duhamel et al (83)]. The outcomes of ICIs treatment in the presented group were not satisfactory-in all cases disease progression were reported (25). Nevertheless, in general, clinically significant responses (at least SD of longer duration) of ICIs treatment in aggressive PitNETs were observed in 7 out of 15 cases published in the literature (25).…”

“…The treatment with temozolomide resulted in complete response in 9.5% of cases. Partial response was observed in 30.1% cases, stable disease in 28.1%, and progressive disease in 32.2% of patients (25). However, still there are no randomized prospective trials or case-control studies.…”

“…Temozolomide causes cell injury, and as a result, leads to apoptosis and tumor shrinkage. Based on European cohorts (25,(58)(59)(60), temozolomide has been used as rescue therapy in aggressive or malignant PitNETs with promising results and good tolerance. The first case reports were described in 2006 (61), and to date, more than 150 patients with aggressive pituitary tumors have been treated (62, 63).…”

“…A clinical and pathological characteristics and treatment outcomes in a large cohort including 171 patients with aggressive pituitary tumors and pituitary carcinomas were recently published (25). Adrenocorticotrophic hormone (ACTH)-secreting tumors constituted 30% of all presented cases.…”