Treatment Options for Gonadotroph Tumors: Current State and Perspectives

• Published in: The journal of clinical endocrinology and metabolism 2020-10, Vol.105 (10), p.e3507-e3518
• Main Authors: Ilie, Mirela Diana, Raverot, Gérald
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Antitumor activity; Brain tumors; Cabergoline - therapeutic use; Cancer; Care and treatment; Clinical Trials as Topic; Diagnosis; Dopamine Agonists - therapeutic use; Excision (Surgery); Gonadotrophs - pathology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Medical treatment; Methods; Oncology, Experimental; Patient outcomes; Phenotyping; Pituitary (anterior); Pituitary gland tumors; Pituitary Neoplasms - pathology; Pituitary Neoplasms - therapy; Protein-tyrosine kinase; Radiation therapy; Radiopharmaceuticals - administration & dosage; Rapamycin; Somatostatin; Somatostatin - administration & dosage; Somatostatin - analogs & derivatives; Surgery; Temozolomide; Temozolomide - therapeutic use; TOR protein; Treatment Outcome; Tumor cells; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptors
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa497

Abstract Context Gonadotroph tumors represent approximatively one-third of anterior pituitary tumors, but despite their frequency, no medical treatment is currently recommended for them. This would be greatly needed because following surgery, which is the first-line treatment, a significant percentage of gonadotroph tumors regrow. Evidence Acquisition We performed PubMed searches in March 2020 using the term “gonadotroph” in combination with 36 different keywords related to dopamine type 2 receptor agonists, somatostatin receptor (SST) ligands, temozolomide, peptide receptor radionuclide therapy (PRRT), immunotherapy, vascular endothelial growth factor receptor (VEGFR)-targeted therapy, mammalian target of rapamycin (mTOR) inhibitors, and tyrosine kinase inhibitors. Articles resulting from these searches, as well as relevant references cited by these articles were reviewed. Evidence Synthesis SST2 analogs have demonstrated only very limited antitumor effect, while high-dose cabergoline has been more effective in preventing tumor regrowth, but still in only a minority of cases. In the setting of an aggressive gonadotroph tumor, temozolomide is the recommended medical treatment, but has demonstrated also only limited efficacy. Still, its efficacy has been so far better than that of PRRT. No case of a gonadotroph tumor treated with pasireotide, VEGFR-targeted therapy, mTOR inhibitors, tyrosine kinase inhibitors, or immune checkpoint inhibitors is reported in literature. Conclusions Gonadotroph tumors need better phenotyping in terms of both tumor cells and associated tumor microenvironment to improve their treatment. Until formal recommendations will be available, we provide the readers with our suggested approach for the management of gonadotroph tumors, management that should be discussed within multidisciplinary teams.