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Neuroendocrine pulmonary tumors in people with Cushing syndrome (CS) are associated with increased nodal metastasis, higher recurrence, and lower disease-free survival compared with quiescent bronchopulmonary tumors, according to results from an observational case series published in JAMA Network Open. Researchers said their study shows these tumors are not biologically aggressive and underlying carcinoid biology may not be as important as symptomatic hormonal physiology. Patients (n=68) with CS who underwent curative-intent pulmonary surgery at the National Cancer Institute (NCI) between 1982 and 2020 were retrospectively reviewed for clinical outcomes on the basis of tumor etiology. Outcomes were compared among groups of patients with adrenocorticotropic hormone-secreting carcinoid tumors who were treated at the National Institutes of Health in 2021 (n=68), Hôpital Européen Georges-Pompidou in 2011 (n=14), the Mayo Clinic in 2005 (n=23), and Massachusetts General Hospital in 1997 (n=7). Patients who underwent surgery at the NCI were aged median 41 years (range, 17-80 years), 42.6% were men, 81.8% were White, and mean follow-up after surgery was 16 months (range, 0.1-341 months). Most patients had T status 1a (55.9%). The pathological stages were IA1 (37.3%), IA2 (23.7%), IA3 (1.7%), IIB (16.9%), IIIA (20.3%), or unknown (13.2%). The patients with typical carcinoid tumors (83.8%) underwent lobectomy (70.2%), wedge (22.8%), segmentectomy (5.3%), and pneumonectomy (1.7%) surgical approaches. Patients with atypical carcinoid tumors (16.2%) underwent lobectomy (72.7%) and wedge (27.3%) approaches. Stratified by surgical approach, lobectomy recipients were younger (P =.01) and more had node-positive atypical carcinoid tumors (P =.01). After surgery, morbidity occurred among 19.1% of patients; overall mortality was 1.5%. Disease-free survival at 5 years following surgery was 73.4% (95% CI, 48.7%-87.6%) and 55.1% (95% CI, 26.3%-76.5%) at 10 years. Disease-free survival was 75.4% (95% CI, 49.2%-89.3%) at 5 years and 50.2% (95% CI, 18.3%-75.7%) at 10 years for typical carcinoid tumors and remained stable at 75.0% among those with atypical carcinoid tumors. Median follow-up after surgery was 16 months (range, 0.1-341 months). At the time of last follow-up, 76.4% of the patient population was alive and tumor free. The overall incidence of persistence/recurrence was 16.2%. Recurrent disease occurred in 7 patients and persistent disease in 4 patients. Only one of this group had an atypical carcinoid tumor. Mean time to recurrence in patients with recurrent disease was 76 months with a median of 55 months. The adrenocorticotropic hormone-secreting carcinoid cohort from multiple institutions was aged median 39 years, 46.4% were men, 72.3% underwent lobectomy or pneumonectomy, 18.7% had morbidity, and 0.9% mortality. The majority of these groups had typical carcinoid tumors (83.9%) with a mean size of 1.1 cm (range, 0.1-10 cm) and 39.4% had lymph node positivity. Recurrence occurred among 12.6% of patients and persistence among 5.4% of patients. Among the recurrence cohort, 85.7% had typical carcinoid tumors. Time to recurrence was >6 years. Disease-free survival was 73% at five years and 55% at 10 years. This study was limited by the small group sizes, however, due to the rarity of this cancer it was not possible to include more individuals. “Ectopic adrenocorticotropic hormone secreting carcinoid tumors with Cushing syndrome appear to be associated with increased metastasis to lymph nodes, higher recurrence (mostly local), and lower overall disease-free survival at 5 and 10 years than quiescent bronchial carcinoid tumors, irrespective of histologic subtype,” the researchers wrote. “Nevertheless, we contend these tumors are not biologically aggressive since these patients have distinct, prolonged survival and delayed time to recurrence.” The researchers also noted that “the current staging system applied to these tumors raises questions about prognostic accuracy. Extrapolation may suggest that the underlying carcinoid biology may not be as important as the symptomatic hormonal physiology.” They suggested future studies may test “whether a lung-sparing surgical approach coupled with routine lymphadenectomy is an optimal intervention in this scenario when normal endocrine functioning is restored and CS sequelae resolve.” Reference Seastedt KP, Alyateem GA, Pittala K, et al. Characterization of outcomes by surgical management of lung neuroendocrine tumors associated with Cushing syndrome. JAMA Netw Open. 2021;4(9):e2124739. doi:10.1001/jamanetworkopen.2021.24739 From https://www.endocrinologyadvisor.com/home/topics/general-endocrinology/cushing-syndrome-and-lungs-and-neuoendocrine-tumors/