Monitoring Endocrine Complications of Immunotherapy: A Screening Tool

Abstract

Introduction The advent of immunotherapy has revolutionized cancer therapy in recent years. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T-lymphocyte antigen 4 (CTLA)-4, has become a cornerstone in cancer therapy. However, due to the physiologic role of checkpoint molecules in preventing autoimmunity, immune-related adverse events (irAEs) have emerged as frequent complications. As the use of immunotherapy increases, a better understanding of irAEs and screening tools for timely diagnosis and management are needed. Materials and methods We surveyed oncology providers at our institution with 10 questions assessing their knowledge, and comfort levels in diagnosing and managing endocrine irAEs. We created an endocrine clinic referral order specifically for oncology-related endocrinopathies and created a screening tool for diagnosing these endocrinopathies. We met with our oncology providers in three different hour-long sessions. A post-intervention survey was sent out six months after our initial meeting to assess changes in the participants' knowledge and comfort levels. We also reviewed the electronic medical records system for the number of new referrals to endocrinology clinic. Results A total of 27 (N) participants responded to the initial survey and 14 (n) responded to the subsequent survey six months later. Based on the initial survey, only a minority (26%) of respondents were comfortable diagnosing and managing (15%) immunotherapy-related adrenal dysfunction whereas more respondents were comfortable diagnosing (55%) and managing (56%) thyroid dysfunction. The majority (67%) of the respondents knew which immunotherapies commonly are implicated in hypophysitis but only 42% of them were aware of the next steps of its management. We noted a significant increase in self-reported comfort levels in diagnosing (p < 0.05) and managing (p < 0.05) adrenal disorders post-intervention. There was also a trend of improvement in participants' comfort levels regarding diagnosing and managing thyroid dysfunction, management of hypophysitis, and immunotherapies implicated in thyroid dysfunction but the changes did not reach statistical significance. There was no significant change in their knowledge regarding immunotherapies implicated in hypophysitis and natural history of thyroid dysfunction in this setting. In the six months following our intervention, 30% (n=21) of the patients referred to the endocrine clinic were for immune-related endocrinopathies compared to 19% (n=7) of patients over a similar duration before the intervention. Data on the time between referral and endocrinology appointment was available for 16 out of the 21 patients and the mean (±SD) time to endocrine clinic appointment was 2.66 (±1.95) weeks. Nine (43%) of the 21 referred patients were seen in endocrinology clinic within two weeks. Conclusions Although immune-related endocrinopathies are rarely fatal, they have a significant impact on patients' quality of life. Endocrinopathies are typically manageable with prompt recognition and treatment. But the subtle and non-specific manifestations make the diagnostic process a challenge. Standardized and practical screening tools can help in diagnosing these adverse events promptly, seeking specialized care if needed and may also aid in reducing healthcare-related costs.

Keywords: endocrinopathies; immune checkpoint inhibitors; immune-related adverse events; immunotherapy; screening tool.