Adrenocortical carcinoma (ACC): When and why should we consider germline testing?

Petr, Elisabeth Joye; Else, Tobias

doi:10.1016/j.lpm.2018.07.004

Cited by 30 publications

(21 citation statements)

References 41 publications

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“…Overall, the pathogenesis is not completely understood [ 10 ]. A subgroup of pediatric ACC is frequently associated with Li Fraumeni syndrome (LFS), a familial genetic cancer predisposition caused by a germline mutation in the TP53 tumor suppressor gene [ 11 ]. Thus far, no international consensus has been reached on the best therapeutic approach to ACC beyond surgery, which is the first-line treatment in most patients.…”

Section: Introductionmentioning

confidence: 99%

Adrenocortical Carcinoma in Childhood: A Systematic Review

Riedmeier¹,

Decarolis

Haubitz³

et al. 2021

Cancers

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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% (n = 65)—distant metastases at relapse. Patients <4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 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.

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Section: Introductionmentioning

confidence: 99%

Adrenocortical Carcinoma in Childhood: A Systematic Review

Riedmeier¹,

Decarolis

Haubitz³

et al. 2021

Cancers

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“…Despite intense efforts to improve management of ACC, both with preclinical and clinical studies, prognosis remains overall limited, although it has been recently recognized that ACC is a very heterogeneous disease and harbors a variety of morphological, clinical, and genetic variants that have a prognostic value [2, 3]. ACC is mostly sporadic, although it can be diagnosed within hereditary syndromes, such as Li-Fraumeni and Lynch syndromes, associated with specific germline mutations in TP53 gene or in various mismatch repair genes, respectively [4].…”

Section: Introductionmentioning

confidence: 99%

Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma

Fiorentini

Grisanti

Cosentini

et al. 2019

Journal of Oncology

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Adrenocortical carcinoma (ACC) is a rare, highly aggressive cancer, often insensitive to conventional chemotherapeutics agents. Early diagnosis, followed by radical surgical resection plus/minus adjuvant mitotane therapy, is nowadays the only valuable option. Unfortunately, one out of four patients has metastatic disease at diagnosis and most of radically resected ACC patients are destined to recur with local or metastatic disease. Numerous efforts aimed at identifying molecular alterations crucial for ACC pathogenesis have been extensively conducted, with the hope to develop new treatments. Indeed, multiple genes and pathways have been identified as potentially targetable in ACC patients; however, despite the strong preclinical rationale, translational findings to clinical trials led to date to disappointing results. The immunotherapeutic intervention targeting T-cell checkpoint molecules has been proposed as well, but results obtained in early studies indicate that ACC patients would be unlikely to benefit from immunotherapy. Genetic alterations of different pathways involved in ACC carcinogenesis are also known substrates of resistance to immunotherapy. Among them, β-catenin gene CTNNB1 and TP53 gene are frequently mutated in ACC samples. Overactivation of the β-catenin pathway and loss of p53 protein function are potential tumor-intrinsic factors that, impacting on the ability of ACC cells to recruit dendritic cells, leading to T-cell exclusion, put this tumor among those that are potentially resistant to immunotherapy. Moreover, the steroid phenotype, which implies glucocorticoids hypersecretion in a subset of ACC, contributes to generating an immunosuppressive microenvironment. Here, we review clinical results of immunotherapy in ACC and we highlight molecular mechanisms driving immunotherapy failure in ACC, suggesting possible approaches to overcome resistance.

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“…Any child with ACT should be evaluated for the presence of a cancer susceptibility syndrome. A detailed family history and thorough evaluation of patient to detect any evidence of these syndromes is mandatory 26 …”

Section: Discussionmentioning

confidence: 99%

Adrenocortical tumours in children: a review of surgical management at a tertiary care centre

Ardicli

User

Çiftçi

et al. 2021

ANZ Journal of Surgery

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Background Adrenocortical tumours (ACT) are rare tumours of childhood usually presenting with endocrine dysfunction. This retrospective study is designed to review our institutional experience in surgical management. Methods Records of children treated for ACT between 1999 and 2019 were reviewed retrospectively. Results The median age of 24 children was 78 months. Fourteen patients had adrenocortical carcinoma, nine had adrenocortical adenoma and one had neuroendocrine differentiation of ACT. Endocrine dysfunction was noted in 79% of the patients. Five patients had preoperative chemotherapy but none had a decrease in tumour size. Transabdominal approach was used in all but two patients who had thoracoabdominal incision for excision of giant tumours and ipsilateral lung metastases. Two patients had visceral excision to achieve R0 resection. Five patients, four of whom had spillage and one with partial resection died of widespread disease. Two patients with stage 4 adrenocortical carcinoma are still on chemotherapy. All patients with stage I–III disease who had total excision without spillage (n = 17) are disease‐free for 2–170 months. Conclusions Our results show the importance of excision in ACT without spillage for survival. However, multicentre prospective studies should enhance the knowledge of children about ACT and develop alternative therapies for stage III and IV cases.

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Adrenocortical carcinoma (ACC): When and why should we consider germline testing?

Cited by 30 publications

References 41 publications

Adrenocortical Carcinoma in Childhood: A Systematic Review

Adrenocortical Carcinoma in Childhood: A Systematic Review

Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma

Adrenocortical tumours in children: a review of surgical management at a tertiary care centre

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