Disparate Practice Patterns and Survival Outcomes: The Impact of Centralization of Cancer Care for Adrenocortical Carcinoma in the United States.

PURPOSE: Adrenocortical carcinoma is a rare but aggressive malignancy. While centralization of care to referral centers improves outcomes across common urological malignancies, there exists a paucity of data for low-incidence cancers. We sought to evaluate differences in practice patterns and overall survival in patients with adrenocortical carcinoma across types of treating facilities. MATERIALS AND METHODS: We identified all patients diagnosed with adrenocortical carcinoma from 2004-2016 in the National Cancer Database. The Kaplan-Meier method was used to evaluate overall survival and multivariable Cox regression analysis was used to investigate independent predictors of overall survival. The chi-square test was used to analyze differences in practice patterns. RESULTS: We identified 2,886 patients with adrenocortical carcinoma. Median overall survival was 21.8 months (95% CI 19.8-23.8). Academic centers had improved overall survival versus community centers on unadjusted Kaplan-Meier analysis (p <0.05) and had higher rates of adrenalectomy or radical en bloc resection (p <0.001), performed more open surgery (p <0.001), administered more systemic therapy (p <0.001) and had lower rates of positive surgical margins (p=0.03). On multivariable analysis, controlling for treatment modality, academic centers were associated with significantly decreased risk of death (HR 0.779, 95% CI 0.631-0.963, p=0.021). CONCLUSIONS: Treatment of adrenocortical carcinoma at an academic center is associated with improved overall survival compared to community programs. There are significant differences in practice patterns, including more aggressive surgical treatment at academic facilities, but the survival benefit persists on multivariable analysis controlling for treatment modality. Further studies are needed to identify the most important predictors of survival in this at-risk population.

Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma.

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion. Objective: To assess the prognostic role of VAV2 expression in ACC by investigation of a large cohort of patients. Design, Setting, and Participants: A total of 171 ACC cases (157 primary tumors, six local recurrences, eight metastases) from seven European Network for the Study of Adrenal Tumors centers were studied. Outcome Measurements: H-scores were generated to quantify VAV2 expression. VAV2 expression was divided into two categories: low (H-score, <2) and high (H-score, ≥2). The Ki67 LI retrieved from patients' pathology records was also categorized into low (<20%) and high (≥20%). Clinical and immunohistochemical markers were correlated with progression-free survival (PFS) and overall survival (OS). Results: VAV2 expression and Ki67 LI were significantly correlated with each other and with PFS and OS. Heterogeneity of VAV2 expression inside the same tumor was very low. Combined assessment of VAV2 expression and Ki67 LI improved patient stratification to low-risk and high-risk groups. Conclusion: Combined assessment of Ki67 LI and VAV2 expression improves prognostic prediction in ACC.

Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model.

Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, cytotoxic chemotherapy and mitotane have been utilized with a very modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases using next-generation sequencing (NGS)-based genomic and other '-omic' profiling to guide the precision medicine approach and personalized use of targeted and novel therapies.

Genomic signatures of cancer: basis for individualized risk assessment, selective staging and therapy.

The development of DNA microarray and quantitative real-time polymerase chain reaction technologies has allowed for precise quantitation of RNA expression of hundreds to thousands of genes. These technologies have significantly impacted the study and understanding of cancer in terms of its molecular and genetic characteristics. In this review article, breast cancer, colon cancer, and adrenal carcinoma have been chosen to illustrate the principle and techniques of genomic profiling and to illustrate how such methods may be used to develop genomic signatures for personalized risk assessment and to individualize patient treatment.

Assessment of GH reserve before and after successful treatment of adult patients with Cushing's syndrome.

OBJECTIVE: Several studies have demonstrated impaired GH secretion in patients with active Cushing's syndrome (CS). It has been suggested that persistence of GH deficiency, despite treatment of cortisol excess, may delay the recovery of these patients and therefore temporary treatment with GH may have some benefit. However, the time course of restoration of GH secretion after successful treatment of CS has only been investigated in a limited number of mostly paediatric reports. The aim of the present study was the evaluation of GH reserve in adult patients with CS before and after correction of cortisol excess. DESIGN AND PATIENTS: Sixteen patients (12 females, four males) with CS aged 44.7 +/- 5.05 years were recruited. These included seven patients with Cushing's disease, four patients with ectopic ACTH secretion and five patients with adrenal adenoma. All patients were evaluated before any therapeutic intervention. Twelve patients were successfully treated following appropriate surgery and these were further studied. The combined pyridostigmine/GHRH test was used to assess GH reserve in these patients. In a proportion of cases an insulin tolerance test (ITT) was also used. RESULTS: Before any therapeutic intervention, an impaired GH response to PD/GHRH was noted in all patients. Restoration of GH response at 6 months was observed in six patients (50%); at 12 months in two; at 18 months in one patient. Two of the patients with no restoration of GH response at 12 months did not accept further investigation. Only one patient did not achieve an adequate GH response even when tested 30 months following cure of CS. Restoration of GH reserve was more commonly observed in those patients in whom there was recovery of the HPA axis. There was a good correlation between peak GH levels to PD + GHRH and ITT. No statistically significant difference was revealed in IGF-I levels between pre- and post-treatment evaluation. CONCLUSIONS: Adult patients with active Cushing's syndrome demonstrate a profound suppression of stimulated GH secretion. In the majority of these patients the disruption of GH secretion is normalized within a year after successful treatment of endogenous cortisol excess.

Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.

An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs.

Scintigraphic assessment of therapeutic success in aldosteronomas treated by transcatheter arterial embolization using absolute ethanol.

UNLABELLED: Adrenocortical scintigraphy was examined as an indicator of therapeutic success in aldosteronomas treated by transcatheter arterial embolization (TAE) with absolute ethanol (AE). METHODS: Adrenocortical scintigraphy was performed 7 days after intravenous injection of 37 MBq 131I-6-beta-iodomethyl-19-norcholesterol before and after TAE. Complete or incomplete therapeutic success was determined by periodic measurements of the levels of plasma aldosterone and correlated with the scintigraphic results. RESULTS: The aldosteronoma was visualized as a hot nodule in nine patients and a warm nodule in one patient before TAE. Scintigraphy showed a hot, residual hot or warm nodule on seven occasions (six occasions after the first TAE and one occasion after the second TAE) when the techniques were incompletely successful and disappearance on seven occasions when success was achieved (three occasions after the first TAE and one occasion after the second TAE). Of the seven occasions when TAE was unsuccessful, four patients received the second or third TAE to result in complete destruction of the aldosteronoma; three patients underwent unilateral adrenalectomy. CONCLUSION: Adrenocortical scintigraphy can correctly predict the effect of TAE on aldosteronomas and is a valuable indicator for decisions on the necessity of repeated TAE or adrenalectomy.