Circulating cell-free DNA for adrenal masses discrimination: a pilot study

Lorenzo Tucci; Oskar Podstawka; Ana Crastin; Alessandro Prete; Miriam Asia; Yasir S. Elhassan; Vasileios Chortis; Dalmazi Guido Di; Cristina L. Ronchi

doi:10.1530/endoabs.107.004

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Endocrine Abstracts (2024) 107 004 | DOI: 10.1530/endoabs.107.004

IACS9 9th International Adrenal Cancer Symposium 2024 Abstracts (18 abstracts)

Circulating cell-free DNA for adrenal masses discrimination: a pilot study

Lorenzo Tucci ^1,2,3 , Oskar Podstawka ⁴ , Ana Crastin ¹ , Alessandro Prete ^1,5,6 , Miriam Asia ⁶ , Yasir S. Elhassan ⁶ , Vasileios Chortis ^1,6 , Guido Di Dalmazi ^2,3 & Cristina L. Ronchi ^1,6

Author affiliations

¹Department of Metabolism and Systems Science, University of Birmingham, Birmingham, UK ²Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy ³Endocrinology and Diabetes Prevention and Care Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy ⁴Cancer Clinical Trials Unit, University of Birmingham, Birmingham, UK ⁵NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK ⁶Department of Endocrinology, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, UK

Background: Ruling out malignancy in adrenal masses (AM) can be a clinical challenge, which may require numerous and/or invasive investigations. Recently, we showed that circulating cell-free DNA concentrations (ccfDNA-C) are higher in patients with adrenocortical carcinoma (ACC) compared to healthy subjects. However, ccfDNA is still poorly explored in other AM.

Objectives: To explore the usefulness of ccfDNA-C measurement for AM discrimination.

Methods: We enrolled 74 patients with adrenocortical adenoma (ACA, n =56), other benign AM (OB, n =4, oncocytic adenoma, ganglioneuroma, adrenal cyst, renal schwannoma), ACC (n =11), and adrenal metastases (MET, n =3, primary: papillary thyroid cancer, leiomyosarcoma, renal cell cancer). Clinical data, radiological parameters and blood samples were collected at the time of AM diagnosis. AM with initially indeterminate radiology (heterogenous appearance, unknown plain Hounsfield Units or plain Hounsfield Units > 10) and not associated with Cushing syndrome, primary aldosteronism, androgen excess or mixed hormonal secretion were labelled as “undefined AM” (n =31/74, 18 ACA, 4 OB, 6 ACC, 3 MET). ccfDNA was isolated with Cell3™ Xtract kit (Nonacus) and ccfDNA-C were measured with Quantus™ Fluorometer (Promega). We tested the diagnostic performance of our previously published ccfDNA-C healthy-derived cut-off (0.146 ng/μl) with logistic regression, positive (PPV) and negative predictive value (NPV) for recognition of malignant AM (ACC+/-MET).

Results: Malignant AM as a whole (ACC+MET) showed higher ccfDNA-C compared to benign AM (P = 0.03). However, only ACC ccfDNA-C were higher than other AM types (P = 0.003). ccfDNA-C ≥0.146 ng/μl predicted ACC+MET (Odds Ratio (95% Confidence of Interval) (OR 3.884 (95%CI 1.146-13.171), P = 0.025), with PPV = 32.1% and NPV = 89.1%, and ACC (OR 10.421 (95%CI 2.054-52.864), P = 0.001), PPV = 32.1%, NPV = 95.7%. Among undefined AM, ccfDNA-C were comparable between benign and malignant lesions (P = 0.078). However, ccfDNA-C were higher in ACC than each adrenal tumour type when considering all groups separately (P = 0.003). ccfDNA-C ≥0.146 ng/μl predicted ACC+MET (OR 5.333 (95%CI 1.000-28.435), P = 0.042), with PPV=32.1% and NPV=95.7%, but it did not predict ACC (P = 0.998).

Conclusions: In AM, high ccfDNA-C seems to be an ACC-specific characteristic and ccfDNA-C ≥0.146 ng/μl is confirmed to be a useful cut-off for discrimination of ACC. Further comparisons among larger cohorts of adrenal and non-adrenal tumours are needed.