Majety Priyanka, Groysman Anna, Seery Virginia, Shea Meghan, Hou Runhua
Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
Cureus. 2022 Jul 14;14(7):e26859. doi: 10.7759/cureus.26859. eCollection 2022 Jul.
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.
引言 近年来,免疫疗法的出现彻底改变了癌症治疗方式。使用针对检查点分子的单克隆抗体进行免疫治疗,包括程序性死亡(PD)-1、PD配体(PD-L)1和细胞毒性T淋巴细胞相关抗原4(CTLA)-4,已成为癌症治疗的基石。然而,由于检查点分子在预防自身免疫中的生理作用,免疫相关不良事件(irAEs)已成为常见并发症。随着免疫疗法使用的增加,需要更好地了解irAEs以及用于及时诊断和管理的筛查工具。
材料和方法 我们向本机构的肿瘤学医护人员提出了10个问题,以评估他们对内分泌irAEs的诊断和管理知识以及舒适度。我们专门为肿瘤相关内分泌病创建了内分泌科转诊单,并创建了一种用于诊断这些内分泌病的筛查工具。我们与肿瘤学医护人员进行了三次不同的为时一小时的会议。在我们首次会议六个月后发出了干预后调查问卷,以评估参与者知识和舒适度的变化。我们还查阅了电子病历系统中内分泌科新转诊的数量。
结果 共有27名(N)参与者回复了初始调查问卷,六个月后有14名(n)参与者回复了后续调查问卷。根据初始调查问卷,只有少数(26%)受访者对诊断和管理(15%)免疫疗法相关肾上腺功能障碍感到放心,而更多受访者对诊断(55%)和管理(56%)甲状腺功能障碍感到放心。大多数(67%)受访者知道哪些免疫疗法通常与垂体炎有关,但其中只有42%的人知道其后续管理步骤。我们注意到干预后自我报告的诊断(p<0.05)和管理(p<0.05)肾上腺疾病的舒适度有显著提高。参与者在诊断和管理甲状腺功能障碍、垂体炎的管理以及与甲状腺功能障碍有关的免疫疗法方面的舒适度也有改善趋势,但这些变化未达到统计学意义。在这种情况下,他们对与垂体炎有关的免疫疗法以及甲状腺功能障碍自然史的知识没有显著变化。在我们干预后的六个月内,转诊至内分泌科的患者中有30%(n=21)患有免疫相关内分泌病,而在干预前的类似时间段内这一比例为19%(n=7)。21名患者中有16名患者有转诊至内分泌科就诊的时间数据,平均(±标准差)内分泌科就诊时间为2.66(±1.95)周。21名转诊患者中有9名(43%)在两周内就诊于内分泌科。
结论 虽然免疫相关内分泌病很少致命,但它们对患者的生活质量有重大影响。内分泌病通常通过及时识别和治疗是可控制的。但其细微和非特异性表现使诊断过程具有挑战性。标准化和实用的筛查工具有助于及时诊断这些不良事件,必要时寻求专科护理,还可能有助于降低医疗相关成本。