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Cancers Oct 2021Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a... (Review)
Review
Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%-local recurrence, 19% ( = 65)-distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival ( < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.
PubMed: 34771430
DOI: 10.3390/cancers13215266 -
Cancers Oct 2021Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this... (Review)
Review
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3-6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3-6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.
PubMed: 34638485
DOI: 10.3390/cancers13195001 -
The Journal of Urology Jan 2021Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of...
PURPOSE
Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines.
MATERIALS AND METHODS
PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria.
RESULTS
There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years.
CONCLUSIONS
After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.
Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Adrenergic alpha-Antagonists; Biopsy; Endocrinology; Humans; Magnetic Resonance Imaging; Medical Oncology; Patient Preference; Pheochromocytoma; Positron-Emission Tomography; Practice Guidelines as Topic; Radiology; Tomography, X-Ray Computed; Urology; Watchful Waiting
PubMed: 32856984
DOI: 10.1097/JU.0000000000001342 -
Radiation Oncology (London, England) May 2020Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Surgical resection is the standard treatment for localized ACC, but the local recurrence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Surgical resection is the standard treatment for localized ACC, but the local recurrence remains high. Adjuvant radiation (ART) has been proposed as a means to reduce recurrence rates in ACC after surgery with conflicting results from nonrandomized studies. We performed a retrospective study and a meta-analysis to determine the impact of ART on survival outcomes.
METHODS
A retrospective study of the adrenocortical cancer database in Peking Union Medical College was conducted. We selected postoperative ACC patients with or without ART. A meta-analysis is also performed to compare the outcomes between ART and only surgical resection in ACC patients. The obtained data were analyzed using SPSS 23.0 and Stata 15.0 statistical software. Differences between two groups were compared using the log-rank test for retrospective analysis and estimated by calculating the odds ratio (OR) and 95% confidence interval (CI) for meta-analysis.
RESULTS
Of a total of 75 patients available in the database, 12 patients underwent postoperative ART and were matched one to one to patients with only surgical resection. There was no significant difference on overall survival between ART group and control group (log-rank P = 0.149). Locoregional recurrence was diagnosed in 2 of the ART group, and in 4 of the control group (P = 0.64). A total of 238 participants were selected for the meta-analysis, of which 111 and 127 patients underwent ART after surgical resection and only surgical resection, respectively. Overall survival is significantly higher in ART group, with an odds ratio (OR) of 2.41 (95% CI of 1.33, 4.38; P = 0.004). Besides, meta-analysis significantly favored ART for locoregional recurrence-free survival and disease-free survival, with an OR of 4.08 and 2.27, respectively.
CONCLUSIONS
Our results show that compared to only surgical resection, ART is an effective postoperative treatment for ACC.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Adult; Aged; Disease-Free Survival; Female; Humans; Male; Middle Aged; Radiotherapy, Adjuvant; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 32448148
DOI: 10.1186/s13014-020-01533-3 -
AJR. American Journal of Roentgenology Feb 2020The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this...
The objective of this systematic review was to determine the number and quality of reports of adrenocortical carcinoma (ACC) containing macroscopic fat; this information may inform guidelines for diagnosis and management of ACC. A comprehensive search of databases of published studies was performed. Two reviewers independently selected original research, case series, or case reports of ACC with macroscopic fat on imaging and extracted data. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Three case reports and one retrospective study comprising a total of seven cases of ACC (lesion size: range, 6.5-22 cm) with macroscopic fat were included. ACC was symptomatic in all patients; neither locally invasive features nor metastases were reported. Four cases had less than 5% macroscopic fat on imaging, and the percentage fat on imaging was not reported for the remaining three cases. With regard to the risk of bias, one case had high risk for the index test domain because of potentially unreliable determination of macroscopic fat (i.e., no pathologic confirmation). All seven cases (from four studies) had unclear risk for the reference standard domain because there was insufficient information about the reference standard to determine whether ACC was correctly diagnosed. All studies were at low risk of bias in the flow and timing domain. There are few reports of macroscopic fat in ACC detected on imaging studies; among the reports of macroscopic fat in ACC, tumors were large (> 6 cm) and had a small proportion of gross fat (< 5%). The reliability of reported cases is questionable primarily because of insufficient details about pathologic diagnosis. Based on this information, a change in guideline recommendations may not be warranted. However, consideration of follow-up or biopsy of patients with large symptomatic tumors (> 6 cm) containing a small proportion of fat (< 5%) may be appropriate.
Topics: Adipose Tissue; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Humans
PubMed: 31691613
DOI: 10.2214/AJR.19.21851 -
Journal of Cancer Research and... Mar 2019Historically, the role of adjuvant radiotherapy (RT) for patients with adrenocortical carcinoma (ACC) has been controversial. The objective of this research is to review... (Meta-Analysis)
Meta-Analysis
PURPOSE
Historically, the role of adjuvant radiotherapy (RT) for patients with adrenocortical carcinoma (ACC) has been controversial. The objective of this research is to review systematically the literature evaluating the role of adjuvant RT in patients with ACC undergone a surgical resection.
MATERIALS AND METHODS
The electronic databases were searched for articles published until July 2017 without language restriction: Lilacs, Medline, Embase, and the Cochrane. Two reviewers independently appraised the eligibility criteria and extracted data. When possible, a fixed-effect meta-analysis was done. The systematic review (SR) followed all the criteria of the MOOSE guideline.
RESULTS
Overall, 382 citations were identified. After the screening of titles and abstracts, 12 articles (eight case series [48 patients] and 4 cohort studies [136 patients]) were included in the final analysis. For the local recurrence, the pooled relative risk (RR) was RR = 0.46 (95% confidence interval: 0.28-0.75), in favor of adjuvant RT when compared with surgery alone. Concerning overall mortality and disease recurrence, no significant difference between adjuvant RT and surgery was detected, RR = 0.77 (CI 95% 0.49-1.22, P = 0.27), and RR = 0.95 (IC 95% 0.74-1.24, P = 0.67). In all cohort studies, the acute toxicities were graduated as mild and self-limited with nausea and fatigue being the most common symptoms. Only one case (1/50) of impairment of kidney function was detected as late toxicity in these studies.
CONCLUSIONS
This SR and meta-analysis indicate that adjuvant RT dramatically reduces the local recurrence of ACC after surgery. Moreover, the treatment has a low acute and late toxicity, resulting in a high therapeutic index. Further, prospective studies are needed to confirm or refute the role of RT on survival and disease recurrence.
Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Fatigue; Humans; Nausea; Neoplasm Recurrence, Local; Observational Studies as Topic; Prospective Studies; Radiotherapy, Adjuvant; Treatment Outcome
PubMed: 30900615
DOI: 10.4103/jcrt.JCRT_996_15 -
The American Surgeon Jan 2019Metastatic adrenocortical carcinoma (ACC) is associated with a poor 5-year survival rate and high rate of recurrence. Outcomes after resection for patients with limited...
Metastatic adrenocortical carcinoma (ACC) is associated with a poor 5-year survival rate and high rate of recurrence. Outcomes after resection for patients with limited disease remain poorly described. We conducted a PubMed search for articles published between 1950 and 2017 using the terms "ACC," "recurrence," and "surgery." Patients with metastatic ACC at any anatomic site who had undergone surgical resection were included. Thirteen studies met the criteria. Patients were grouped according to the recurrence site. Pulmonary metastasectomy was reported in 50 patients with moderate complications and without perioperative mortality. Disease recurrence rates range from 25 to 42 per cent, with median overall survival of 40 to 50 months. Hepatic metastasectomy was reported in 108 patients with a single perioperative mortality. Disease recurrence rates range from 65 to 100 per cent, with median disease-free survival (DFS) and OS of five to nine months and 22 to 76 months. Peritoneal cytoreduction and heated intraperitoneal chemotherapy have been reported for 10 patients with minimal morbidity and without perioperative mortality. The disease recurrence rate was 70 per cent, with DFS of 19 months. For selected patients with recurrent ACC in the lungs, liver, or peritoneum, metastasectomy is safe and can be associated with prolonged survival. However, subsequent disease recurrence is common, and patients should be counseled accordingly.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Humans; Neoplasm Recurrence, Local
PubMed: 30760340
DOI: No ID Found -
European Journal of Endocrinology Dec 2018Objective Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis. Many publications in ACC report on risk factors for a poor outcome; one risk factor... (Meta-Analysis)
Meta-Analysis Review
Objective Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis. Many publications in ACC report on risk factors for a poor outcome; one risk factor studied is hormonal hypersecretion (cortisol, sex-hormones, steroid precursors or aldosterone). The aim of this systematic review was to study the association between hormonal secretion and recurrence or mortality in ACC. Design Systematic review and meta-analysis. We searched PubMed, EMBASE and The Cochrane library (January 2018) for cohort studies examining the association between hormonal secretion on overall or recurrence-free survival in ACC. Methods A random-effects model meta-analysis was performed to obtain a weighted relative risk comparing cortisol-secreting and/or androgen-secreting ACCs to non-secreting tumours regarding overall and recurrence-free survival. Risk of bias assessment was performed for all studies included. Results Nineteen publications were included representing a total of 3814 patients. Most studies were generally considered low/intermediate risk of bias. Meta-analysis showed higher mortality risk for cortisol-secreting ACCs, weighted relative risk 1.71 (95% CI: 1.18-2.47) combining studies that adjusted for tumour stage; also a higher recurrence risk was found for cortisol producing ACCs, relative risk 1.43 (95% CI: 1.18-1.73). Androgen secretion was not clearly associated with survival (RR: 0.82, 95% CI: 0.60-1.12). Conclusion This systematic review and meta-analysis show that cortisol-secreting ACCs are associated with a worse overall survival; future research is needed to establish whether this association points to negative effects of cortisol action, whether it signifies a more aggressive ACC subtype or whether cortisol is merely a prognostic marker.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Cohort Studies; Humans; Hydrocortisone; Survival Rate
PubMed: 30325179
DOI: 10.1530/EJE-18-0450 -
BioMed Research International 2018The adjuvant use of mitotane on adrenocortical carcinoma (ACC) has always been in controversy. We aimed to assess the prognostic benefits of adjuvant mitotane after... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The adjuvant use of mitotane on adrenocortical carcinoma (ACC) has always been in controversy. We aimed to assess the prognostic benefits of adjuvant mitotane after resection of ACC in patients without distant metastasis.
METHODS
The PubMed, WoS, Embase, and Cochrane Library databases were systematically searched. Recurrence-free survival (RFS) and overall survival (OS) were adopted as measurements. A meta-analysis was conducted based on hazard ratio (HR) with 95% confidence interval (CI). A study was included only if the enrolled patients underwent resection of ACC without adjuvant chemotherapy except mitotane.
RESULTS
A total of 5 retrospective studies reporting on 1249 patients were included for this meta-analysis. The meta-analysis showed that adjuvant mitotane was significantly associated with prolonged RFS (HR = 0.62; 95%CI, 0.42-0.94; P < 0.05) and prolonged OS (HR = 0.69; 95%CI, 0.55-0.88, P < 0.05).
CONCLUSION
After comprehensive review, current evidence suggests that adjuvant mitotane significantly decreases the recurrence rate and mortality after resection of ACC in patients without distant metastasis, but these findings need further demonstration from prospective controlled trials.
Topics: Adolescent; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Female; Humans; Male; Middle Aged; Mitotane; Neoplasm Recurrence, Local; Prospective Studies; Retrospective Studies; Young Adult
PubMed: 29967789
DOI: 10.1155/2018/9362108 -
Molecular and Cellular Endocrinology Jul 2018Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with a poor prognosis. Diagnosis and treatment of this tumor remains challenging. The Weiss...
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with a poor prognosis. Diagnosis and treatment of this tumor remains challenging. The Weiss score, the current gold standard for the histopathological diagnosis of ACC, lacks diagnostic accuracy of borderline tumors (Weiss score 2 or 3) and is subject to inter observer variability. Furthermore, adjuvant and palliative systemic therapy have limited effect and no proven overall survival benefit. A better insight in the molecular background of ACC might identify markers that improve diagnostic accuracy, predict treatment response or even provide novel therapeutic targets. This systematic review of the literature aims to provide an overview of alterations in DNA methylation, histone modifications and their potential clinical relevance in ACC.
Topics: Adrenocortical Carcinoma; Animals; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Histones; Humans; Protein Processing, Post-Translational
PubMed: 28830787
DOI: 10.1016/j.mce.2017.08.009