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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 -
Cancers Feb 2024Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC)... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10-19%, I = 0%), and the DCR was 43% (95% CI = 37-50%, I = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85-23.05), and the median PFS was 2.8 months (95% CI = 1.8-5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care.
PubMed: 38473262
DOI: 10.3390/cancers16050900 -
European Urology Focus Feb 2016Controversy exists regarding the choice for surgical approach and the role of lymph node dissection (LND) in adrenocortical carcinoma (ACC) treatment. ACC surgery is... (Review)
Review
Surgical Management of Adrenocortical Carcinoma: Impact of Laparoscopic Approach, Lymphadenectomy, and Surgical Volume on Outcomes-A Systematic Review and Meta-analysis of the Current Literature.
CONTEXT
Controversy exists regarding the choice for surgical approach and the role of lymph node dissection (LND) in adrenocortical carcinoma (ACC) treatment. ACC surgery is increasingly advocated to be performed in specialist referral centres.
OBJECTIVE
To review systematically the evidence of oncologic outcomes for ACC surgery by open adrenalectomy (OA) or laparoscopic adrenalectomy (LA), and for concomitant LND. The influence of surgical volume is also analysed.
EVIDENCE ACQUISITION
A systematic review of Ovid Medline, Embase, and the Cochrane Library was performed in June 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Twenty-six publications were selected for inclusion in the analysis. Meta-analyses were performed when appropriate.
EVIDENCE SYNTHESIS
Included studies reported on oncologic outcomes after surgical treatment of ACC (11 studies), compared different surgical approaches (7 studies), evaluated the role of LND (3 studies), and analysed the effect of surgical volume on outcome (5 studies). From the available studies and the meta-analysis, no differences were found in the rate of positive surgical margins, disease-free survival, and overall survival between OA and LA in localised disease. In patients with histologically proven positive lymph nodes, a shorter time to recurrence was seen when no proper LND was performed. A trend for better recurrence-free survival and disease-specific survival after LND was found. In high-volume centres, more aggressive and open surgery was performed. In low-volume centres, higher local recurrence and distant metastases rates, and a shorter time to recurrence were seen. Our findings are limited due to the low level of evidence of selected studies, patient and disease heterogeneity, and heterogeneous surgeon populations.
CONCLUSIONS
After adequate clinical staging for localised disease, LA is as effective and oncologically safe as OA, as long as oncologic principles are respected. LA should be performed by surgeons with extensive experience in laparoscopic adrenal surgery in high-volume centres. Patients with locally advanced disease and metastatic disease, for debulking purposes, should be operated on extensively with open surgery with adequate margins and concomitant LND to optimise staging, which may contribute to survival in locally advanced disease.
PATIENT SUMMARY
Laparoscopic surgery for localised adrenocortical carcinoma is safe and effective when performed by expert surgeons in high-volume centres. Patients with more extensive tumours should be operated with open surgery; lymph node dissection is mainly applied to determine the stage of the disease.
PubMed: 28723392
DOI: 10.1016/j.euf.2015.12.001 -
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 -
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 -
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 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 -
Clinical Nuclear Medicine Aug 2016Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical... (Review)
Review
Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Humans; Magnetic Resonance Imaging; Molecular Imaging; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 26825212
DOI: 10.1097/RLU.0000000000001112 -
European Journal of Endocrinology Aug 2016To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy.
METHODS
Medline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate.
RESULTS
We included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6-11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5-3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively.
CONCLUSIONS
Evidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.
Topics: Adrenal Gland Diseases; Adrenal Gland Neoplasms; Adrenal Glands; Biopsy; Female; Humans; Male; Middle Aged; Neoplasm Metastasis
PubMed: 27257146
DOI: 10.1530/EJE-16-0297 -
Contemporary Clinical Trials Sep 2016Adrenal tumors are quite rare in infancy and childhood with the exception of neuroblastoma. In fact, adrenocortical tumors (ACT) account for only 0.2% of all malignant... (Review)
Review
Adrenal tumors are quite rare in infancy and childhood with the exception of neuroblastoma. In fact, adrenocortical tumors (ACT) account for only 0.2% of all malignant cancers in children and adolescents. According to a multicenter registry investigation, the median interval between first endocrine symptoms and the diagnosis of ACT is 5months, and death is seen in 38% of patients, who suffer from tumor progression following the diagnosis in about 2½years. The prognosis of pediatric ACC is poor with a 5-year event-free survival of 54%. To face this dreadful scenario, a few decades ago the International Pediatric Adrenocortical Tumor Registry (IPACTR) was established. Moreover, Children's Oncology Group (COG) and National Cancer Institute (NCI) have approved several clinical trials designed to investigate new treatment options in pediatric ACT. In this systematic review, we summarize the diagnostic histopathologic criteria, bio-markers, and clinical trials of this challenging diagnosis. Eleven pediatric ACT trials were reviewed in our investigation. Two out of 11 studies were conducted in Brazil showing apparently an increased rate of germline mutation-related pediatric ACT. A heterogeneous methodology was evident with four non-randomized clinical trials, three prospective cohort studies, and four retrospective case-control studies limiting higher statistical approach. Tumor histology remains the backbone to diagnose ACT creating a common investigative platform and potentially supporting studies aiming to increase international collaborative research, which is crucial for this challenging disease.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Biomarkers, Tumor; Child; Clinical Trials as Topic; Humans; Neoplasm Staging; Prognosis; Research Design; Survival Rate
PubMed: 27424218
DOI: 10.1016/j.cct.2016.07.011