Medical treatment of Cushing’s disease: Overview and recent findings

Cushing’s disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing’s disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing’s disease

Changes in Stage Distribution and Disease-Specific Survival in Differentiated Thyroid Cancer with Transition to American Joint Committee on Cancer 8th Edition: A Systematic Review and Meta-Analysis

BACKGROUND: Recent revision significantly changed the American Joint Committee on Cancer (AJCC) staging criteria for differentiated thyroid cancer (DTC). To quantitatively evaluate resulting changes in patient stage distribution and the associated disease-specific survival (DSS) incorporating diverse populations, we performed a meta-analysis of studies comparing the AJCC 7th edition (AJCC-7) with 8th edition (AJCC-8) staging for DTC. MATERIALS AND METHODS: After PROSPERO registration (#CRD42019123657), publications in English reporting DSS of DTC with AJCC-7 and AJCC-8 from inception to June 2019 were identified by search of MEDLINE and PubMed. Random-effects meta-analyses were conducted to compare differences in survival between AJCC-7 and AJCC-8. Pooled hazard ratios, 10-year DSS, and corresponding interval estimates were calculated for AJCC subgroups. Differences in survival between editions were assessed using subgroup analysis with nonoverlapping confidence intervals indicating statistical significance. RESULTS: Final analysis included six studies with 10,850 subjects and median follow-up from 55 to 148 months. Use of AJCC-8 shifted classification to earlier stages: stage I, from 60% to 81%; stage II, from 5% to 13%; stage III, from 21% to 2%; stage IV, from 10% to 3%. Ten-year DSS was significantly lower in AJCC-8 versus AJCC-7 in patients with stage II (88.6%, 95% confidence interval [CI] 82.7-94.6% vs. 98.1%, 95% CI 96.6-99.6%, respectively) and stage III disease (70.5%, 95% CI 59.1-83.9% vs. 96.8%, 95% CI 94.1-99.64%, respectively). CONCLUSION: Meta-analysis of revised AJCC staging for DTC, incorporating diverse populations, demonstrates redistribution of patients toward earlier clinical stages and better stratification of disease-specific mortality risk, specifically among patients now classified with stage II and III disease. IMPLICATIONS FOR PRACTICE: This study provides updated estimates of disease-specific survival for patients with differentiated thyroid cancer determined by the American Joint Committee on Cancer staging system that are generalizable to broader populations and support improved stratification using the recently revised criteria

Changes in Stage Distribution and Disease-Specific Survival in Differentiated Thyroid Cancer with Transition to American Joint Committee on Cancer 8th Edition: A Systematic Review and Meta-Analysis.

BackgroundRecent revision significantly changed the American Joint Committee on Cancer (AJCC) staging criteria for differentiated thyroid cancer (DTC). To quantitatively evaluate resulting changes in patient stage distribution and the associated disease-specific survival (DSS) incorporating diverse populations, we performed a meta-analysis of studies comparing the AJCC 7th edition (AJCC-7) with 8th edition (AJCC-8) staging for DTC.Materials and methodsAfter PROSPERO registration (#CRD42019123657), publications in English reporting DSS of DTC with AJCC-7 and AJCC-8 from inception to June 2019 were identified by search of MEDLINE and PubMed. Random-effects meta-analyses were conducted to compare differences in survival between AJCC-7 and AJCC-8. Pooled hazard ratios, 10-year DSS, and corresponding interval estimates were calculated for AJCC subgroups. Differences in survival between editions were assessed using subgroup analysis with nonoverlapping confidence intervals indicating statistical significance.ResultsFinal analysis included six studies with 10,850 subjects and median follow-up from 55 to 148 months. Use of AJCC-8 shifted classification to earlier stages: stage I, from 60% to 81%; stage II, from 5% to 13%; stage III, from 21% to 2%; stage IV, from 10% to 3%. Ten-year DSS was significantly lower in AJCC-8 versus AJCC-7 in patients with stage II (88.6%, 95% confidence interval [CI] 82.7-94.6% vs. 98.1%, 95% CI 96.6-99.6%, respectively) and stage III disease (70.5%, 95% CI 59.1-83.9% vs. 96.8%, 95% CI 94.1-99.64%, respectively).ConclusionMeta-analysis of revised AJCC staging for DTC, incorporating diverse populations, demonstrates redistribution of patients toward earlier clinical stages and better stratification of disease-specific mortality risk, specifically among patients now classified with stage II and III disease.Implications for practiceThis study provides updated estimates of disease-specific survival for patients with differentiated thyroid cancer determined by the American Joint Committee on Cancer staging system that are generalizable to broader populations and support improved stratification using the recently revised criteria

Endocrinopathies with use of cancer immunotherapies

BackgroundImmunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%.ObjectiveTo describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies.DesignRetrospective cohort study.PatientsA total of 388 patients aged ≥18&nbsp;years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution.MeasurementsBiochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies.ResultsFifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients).ConclusionsOver 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs