Identification of Mutations in Cell-Free Circulating Tumor DNA in Adrenocortical Carcinoma: A Case Series

Creemers, Sara G; Korpershoek, Esther; Atmodimedjo, Peggy N.; Dinjens, Winand N.M.; Koetsveld, Peter M. van; Feelders, Richard A; Hofland, Leo J.

doi:10.1210/jc.2017-00174

Cited by 25 publications

(24 citation statements)

References 12 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

656

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

656

867

View full text Add to dashboard Cite

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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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“…For ACC, the knowledge of single mutations in driver genes and copy number variations (CNVs) identified in the primary lesion will be pivotal to guide the analysis of ctDNA in ACC patients. Creemers and coworkers were the first to report the presence of circulating ctDNA in plasma of a metastastic ACC patient following mutation identification in the primary tumor (Creemers et al 2017). However, the same authors were not able to detect in ctDNA the same mutations already characterized in the primary tumor, suggesting that mutation detection in ctDNA using the current approach may be variable between ACC patients.…”

Section: Exosomes and Tumor Microenvironment In Acc Progressionmentioning

confidence: 99%

“…2). This is a novel and minimally invasive technique developed for solid tumors and recently also applied to ACC (Chabre et al 2013, Szabó et al 2014, Creemers et al 2017, Batth et al 2017, Bardelli & Pantel 2017 to identify potential markers to assess malignancy in ACC, even if the predictive power needs to be confirmed on larger cohorts of patients. In addition to its diagnostic/ prognostic value, the liquid biopsy represents a unique tool that can provide informative material to be analyzed and compared to the primary lesion for longitudinal surveillance of clonal evolution and progression of the tumor, also in response to anticancer treatments.…”

Section: The 'Liquid Biopsy' and Circulating Markers Of Malignancymentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

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Identification of Mutations in Cell-Free Circulating Tumor DNA in Adrenocortical Carcinoma: A Case Series

Cited by 25 publications

References 12 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

The next step: mechanisms driving adrenocortical carcinoma metastasis

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