Detection and monitoring of circulating tumor DNA in adrenocortical carcinoma

Garinet, Simon; Nectoux, Juliette; Néou, Mario; Pasmant, Éric; Jouinot, Anne; Sibony, Mathilde; Orhant, Lucie; Fonseca, Juliana Pipoli da; Perlemoine, Karine; Bricaire, Léopoldine; Groussin, Lionel; Soubrane, Olivier; Dousset, B.; Libé, R.; Letourneur, Franck; Bertherat, Jérôme; Assié, Guillaume

doi:10.1530/erc-17-0467

Cited by 24 publications

(21 citation statements)

References 10 publications

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“…8. In addition to improving treatment, other future research directions may include the use of artificial intelligence in diagnostic work-up of adrenal tumors and the improvement of screening and follow-up procedures using non-invasive techniques such as urine or serum steroid metabolomics (305,306,307,308) or 'liquid biopsies' with circulating tumor cells (309), circulating miRNAs (310,311,312), or circulating cell-free tumor DNA (313,314) for early diagnosis or detection of recurrence. 9.…”

Section: Future Directions and Recommended Researchmentioning

confidence: 99%

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Dekkers

Else

et al. 2018

European Journal of Endocrinology

653

867

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Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

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Section: Future Directions and Recommended Researchmentioning

confidence: 99%

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Dekkers

Else

et al. 2018

European Journal of Endocrinology

653

867

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“…Liquid biopsies represent another perspective for patients' follow-up. Circulating miRNA (99,104,108,109) and circulating tumor DNA (110,111) are measurable in patients' blood. Larger validation cohorts are needed to precise their ability for early detection of recurrence.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Adrenocortical carcinoma: differentiating the good from the poor prognosis tumors

Jouinot

Bertherat

2018

European Journal of Endocrinology

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Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis, the five-years overall survival being below 40%. However, there is great variability of outcomes and we have now a better view of the heterogeneity of tumor aggressiveness. The extent of the disease at the time of diagnosis, best assayed by the European Network for the Study of Adrenal Tumors (ENSAT) Staging Score, is a major determinant of survival. The tumor grade, including the mitotic count and the Ki67 proliferation index, also appears as a strong prognostic factor. The assessment of tumor grade, even by expert pathologists, still suffers from inter-observer reproducibility. The emergence of genomics in the last decade has revolutionized the knowledge of molecular biology and genetics of cancers. In ACC, genomic approaches - including pan-genomic studies of gene expression (transcriptome), recurrent mutations (exome or whole-genome sequencing), chromosome alterations, DNA methylation (methylome), miRNA expression (miRnome) - converge in a new classification of ACC, characterized by distinct molecular profiles and very different outcomes. Targeted measurements of a few discriminant molecular alterations have been developed in the perspective of clinical routine, and thus, may help defining therapeutic strategy. By individualizing patients' prognosis and tumor biology, these recent progresses appear as an important step forward towards precision medicine.

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“…Easier diagnosis, thanks to specific markers detected by noninvasive techniques as micro ribonucleic acids (miRNAs) [ 9-11 ] or circulation tumor DNA [ 12 , 13 ].…”

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confidence: 99%

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

Vaduva

Bonnet

Bertherat

2020

Journal of the Endocrine Society

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This review reports the main molecular alterations leading to development of benign cortisol and/or aldosterone secreting adrenal tumors. Causes of adrenal Cushing can be divided in two groups: multiple bilateral tumors or adenomas secreting cortisol. Bilateral causes are mainly Primary Pigmented Nodular Adrenocortical Disease (PPNAD), most of the time due to PRKAR1A germline inactivating mutations, and Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), that can be caused in some rare syndromic cases by germline inactivating mutations of MEN1, APC and FH and of ARMC5 in isolated forms. PRKACA somatic activating mutations are the main alterations in unilateral cortisol producing adenomas (CPA). In primary hyperaldosteronism (PA), familial forms were identified in 1-5% of cases: familial hyperaldosteronism type I (FH-I) due to a chimeric CYP11B1/CYP11B2 hybrid gene, FH-II due to CLCN-2 germline mutations, FH-III due to KCNJ5 germline mutations, FH-IV due to CACNA1H germline mutations and PA, seizures and neurological abnormalities (PASNA) syndrome due to CACNA1D germline mutations. Several somatic mutations have been found in aldosterone producting adenomas (APAs) in KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1 genes.

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Detection and monitoring of circulating tumor DNA in adrenocortical carcinoma

Cited by 24 publications

References 10 publications

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

MANAGEMENT OF ENDOCRINE DISEASE: Adrenocortical carcinoma: differentiating the good from the poor prognosis tumors

Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome

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