Incidence Of Adrenocortical Carcinoma Research Articles

FRI191 Changes In The Incidence And Geographical Distribution Of Adrenocortical Carcinoma: A Retrospective Analysis Of A State Cancer Registry

Abstract Disclosure: V.B. Brondani: None. A.M. Griffin: None. T.J. Owen: None. K.W. Merriman: None. J.M. Varghese: None. C. Jimenez: None. S.G. Waguespack: None. P.H. Graham: None. M.T. Campbell: None. M.M. Hassan: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of 0.102 cases per 100,000 persons per year in the United States. At our tertiary cancer center, we have observed increasing numbers of cases, but to date there has been no study exploring ACC incidence at a populational level to validate our observations. Furthermore, the possibility of geographic ACC clusters has not been studied. Our objectives were to evaluate the incidence and geographical distribution of ACC cases in Texas. Methods: Cases of ACC between 2000 and 2018 were retrospectively identified from the Texas Cancer Registry (TCR). Cases were registered in 110 of Texas' 254 counties (43.3%), representing 92.74% of the total population of Texas. SEER Stat software was used to pool demographic and clinical characteristics and calculate incidence rates. Kaplan-Meier overall survival curve and Pearson's correlations were calculated using SPSS. P values < .05 were considered significant. ACC county-level heatmaps were created with Tableau software to identify clusters. Breast, prostate, lung cancer incidences and their geographic distribution were compared to ACC data. Results: TCR registered 448 cases of ACC in the study period, with a median of 23 new cases/year (range 14-33). Thirty-three (7.4%) patients were aged 19 years or younger (15 were under 5 years), 293 (65.4%) patients were between 20 and 64 years, and 122 (27.23%) were 65 years or older. The majority were female (270 cases [60.3%]), and White (393 [87.7%]). One hundred (22.3%) patients were Hispanic. In 155 evaluable cases, the proportions of patients with stage I, II, III, and IV disease at diagnosis were 7.7%, 27.7%, 16.1%, and 48.4%, respectively. The median overall survival was two years (range, 0-19 years). The mean adjusted population ACC incidence rate was 0.104 per 100,000 per year (std = 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each (median, 34 cases per county; range, 11-66) and a median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county (median, 1 case; range, 1-9 cases). The highest SIRs (corresponding to >10, range, 11.2-30.8) were found in counties with a median population of fewer than 14,000 and with only one reported case. We could not detect any geographic clustering of ACC. Counties with a high frequency of breast, prostate, lung cancer cases also had more cases of ACC (Pearson correlation .982, .981, and .982, respectively; P < .01 for all tests). Conclusion: The incidence of ACC in Texas remained relatively stable through the years and consistent with the US annual incidence. We did not observe any obvious ACC cluster, and SIRs may not be useful for analyzing this rare disease. Presentation: Friday, June 16, 2023

OR16-04 Androgen Deprivation Restricts Anti-tumor Immunity In Adrenocortical Carcinoma

Abstract Disclosure: K.M. Warde: None. L. Smith: None. C.J. Stubben: None. P.W. Willet: None. G. Castaneda-Hernandez: None. L. Liu: None. K. Basham: None. Adrenocortical carcinoma (ACC) is a rare cancer that is often diagnosed late and progresses rapidly, resulting in routinely poor outcomes. Through The Cancer Genome Atlas (TCGA) and other genomic studies, homozygous loss of ZNRF3 was newly identified as a frequent genetic alteration in human ACC tumors. ZNRF3 is an E3 ubiquitin ligase that negatively regulates Wnt signaling by degrading Wnt receptors. To examine the role of ZNRF3 in adrenal biology, we generated a Znrf3 conditional knockout (cKO) mouse model. Despite roust early hyperplasia, we found that Znrf3 cKO mice only develop adrenal tumors with advanced aging. Moreover, tumors emerge in a sex dimorphic manner whereby males, who exhibit a high myeloid immune response, predominately get benign tumors and females, who have a dampened myeloid response, develop metastatic ACC. This phenomenon is reflected clinically in patients whereby the incidence of ACC is up to 2.5x higher in women compare to men. In human ACC patients, females exhibit a lower myeloid signature compared to males. Moreover, a low myeloid response signature is associated with shorter progression-free and overall survival. These data suggest a potential relationship between anti-tumor immunity and sex in ACC, yet the underlying mechanisms remain unclear. Sex differences are common in cancer, and although there are many potential factors, gonadal hormones including androgens and estrogens, have been implicated as major biological drivers. Previous studies of the adrenal cortex highlight a specific role for androgens in repressing stem cell recruitment and proliferation. We hypothesized androgens promote anti-tumor immunity to help protect against ACC. To test this hypothesis, we castrated male Znrf3 cKO mice to lower androgen levels. We found that androgen deprivation significantly reduced myeloid cell infiltration, resulting in significantly larger adrenals in castrated as compared to sham controls. RNA-seq analysis revealed a decrease in immune activation pathways and monocyte-derived myeloid cell populations. Additionally, pro-inflammatory cytokines, including TNF, INFG, and IL-6, were significantly inhibited in castrated animals compared to controls. These data support a protective role for androgens in ACC through driving an intra-adrenal myeloid immune response. Consistent with these results, analysis of the TCGA-ACC patient cohort demonstrated that high androgen receptor expression is associated with better overall survival. Taken together, our results reveal an important role for androgens in promoting anti-tumor immunity in a mouse model of ACC, and we highlight the prognostic value of androgen receptor expression in patients. Further understanding of androgen signaling and downstream biological mechanisms that regulate the immune response may ultimately offer novel therapeutics and improve patient outcomes in ACC. Presentation: Friday, June 16, 2023

Trends in the incidence of adrenocortical carcinoma and pheochromocytoma/paraganglioma in Taiwan

Abstract Background Adrenal malignancies are rare endocrine tumors. Recent epidemiological studies suggest that incidence rates of adrenal malignancies are increased in certain countries. In this study, we aimed to analyze temporal trends in the incidence of adrenocortical carcinoma and pheochromocytoma/paraganglioma (PPGL). Methods Cases of adrenal malignancies were identified from the Taiwan cancer registry, and age-standardized incidence rates (ASRs) were calculated. Annual percent change (APC) or average APC was obtained using joinpoint regression models. Results The ASRs of adrenocortical carcinoma ranged from 0.021 to 0.135 per 100,000 person-years. The average APC between 1995 and 2020 was 6.633% (95% confidence interval, 2.740 to 9.403). The ASRs of PPGL ranged from 0.005 to 0.056 per 100,000 person-years before 2017, and because of changes in diagnostic criteria, the median ASR of PPGL rose to 0.314 per 100,000 person-years after 2017. The APC between 1996 and 2016 was 3.554% (95% confidence interval, −1.103 to 8.264). Conclusions The annual incidence of adrenocortical carcinoma has significantly increased in Taiwan over the past two decades. The incidence of malignant PPGL remained stable over this period.

The Characteristics and Trends in Adrenocortical Carcinoma: A United States Population Based Study.

BackgroundAdrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Data on the incidence of ACC, however, are scarce and not recent. The purpose of this study was to characterize the tumor and the patients developing ACC over the last four decades using a large population based database.MethodsWe identified all cases of ACC diagnosed between 1973 - 2014 from the Surveillance, Epidemiology, and End Results-18 registry. Descriptive analyses were used for all extracted demographic, clinical, pathological, therapeutic and survival data, and were compared between the four time periods of 1973 to 1984, 1985 to 1994, 1995 to 2004 and 2005 to 2014 using Chi-square tests for categorical variables and one-way analysis of variance for continuous variables.ResultsThere were a total of 2,014 cases of ACC between 1973 and 2014 with an age-adjusted incidence of 1.02 per million populations. The median age at diagnosis was 55 years with the majority of them being females and whites. The proportion of cases by different genders, races and age at diagnosis had not changed significantly over time. These malignancies were mostly the only primary malignancy, unilateral and of high grades at diagnosis. Surgical resection of the tumor remained the mainstay of treatment. However, there was a significant increase in the use of adjuvant radiotherapy, adjuvant chemotherapy and chemotherapy alone in recent times. The median survival time was 17 months, but continues to decrease in recent time periods.ConclusionsACC continues to be a rare malignancy in the United States. However, most cases continue to be diagnosed only in advanced stages and are associated with poor survival. These findings underline the need for specific diagnostics tools with new and more effective treatment options.

Laparoscopic trans- and retroperitoneal adrenal surgery for large tumors.

BACKGROUND:Laparoscopic adrenalectomy for tumors larger than 6 cm is currently a matter of controversial discussion because of difficult mobilization from surrounding organs and a possible risk of capsule rupture.MATERIALS AND METHODS:Data of consecutive patients undergoing laparoscopic adrenalectomy between 1/1994 and 7/2012 were collected and analysed retrospectively. Intra- and postoperative morbidity in patients with tumors ≤6 cm (group 1, n = 227) were compared to patients with tumors >6 cm, (group 2, n = 52).RESULTS:Incidence of adrenocortical carcinoma was significantly higher in group 2 patients (6.3% vs. 0.4%, P = 0.039) whereas the incidence of aldosterone-producing adenoma was lower (2% vs. 25%, P = 0.001). Mean duration of surgery was longer (105 min vs. 88 min, P = 0.03) and the estimated blood loss was higher (470 mL vs. 150 mL) in group 2 patients. Intraoperative bleeding rate (5.7% vs. 0.8%, P = 0.041), and the conversion rate were significantly higher (5.7% vs. 1.3%, P = 0.011) in group 2. Also, postoperative complication rate was significantly higher in group 2 (11.5% vs. 3.0%, P = 0.022). However, only two major complications occurred, one in each group.CONCLUSION:Minimally invasive adrenal surgery can be performed by an experienced surgeon even in patients with large tumors (>6 cm) with an increased but still acceptable intra- and postoperative morbidity.

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated.