The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using ‘common terminology criteria for adverse events’ (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.
F Castinetti, F Albarel, F Archambeaud, J Bertherat, B Bouillet, P Buffier, C Briet, B Cariou, Ph Caron, O Chabre, Ph Chanson, C Cortet, C Do Cao, D Drui, M Haissaguerre, S Hescot, F Illouz, E Kuhn, N Lahlou, E Merlen, V Raverot, S Smati, B Verges and F Borson-Chazot
Iulia Potorac, Patrick Petrossians, Adrian F Daly, Orsalia Alexopoulou, Sophie Borot, Mona Sahnoun-Fathallah, Frederic Castinetti, France Devuyst, Marie-Lise Jaffrain-Rea, Claire Briet, Florina Luca, Marion Lapoirie, Flavius Zoicas, Isabelle Simoneau, Alpha M Diallo, Ammar Muhammad, Fahrettin Kelestimur, Elena Nazzari, Rogelio Garcia Centeno, Susan M Webb, Marie-Laure Nunes, Vaclav Hana, Véronique Pascal-Vigneron, Irena Ilovayskaya, Farida Nasybullina, Samia Achir, Diego Ferone, Sebastian J C M M Neggers, Brigitte Delemer, Jean-Michel Petit, Christof Schöfl, Gerald Raverot, Bernard Goichot, Patrice Rodien, Bernard Corvilain, Thierry Brue, Franck Schillo, Luaba Tshibanda, Dominique Maiter, Jean-François Bonneville and Albert Beckers
GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.