A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA

Margaret Ottaviano; Mario Giuliano; Marianna Tortora; Evelina La Civita; Antonietta Liotti; Michele Longo; Dario Bruzzese; Michele Cennamo; Vittorio Riccio; Pietro De Placido; Fernanda Picozzi; Sara Parola; Bruno Daniele; Gerardo Botti; Pietro Formisano; Francesco Beguinot; Sabino De Placido; Daniela Terracciano; Giovannella Palmieri

doi:10.3389/fonc.2020.602153

A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA

Front Oncol. 2021 Feb 4:10:602153. doi: 10.3389/fonc.2020.602153. eCollection 2020.

Authors

Margaret Ottaviano^{1

2

3}, Mario Giuliano^{1

2}, Marianna Tortora^{2

4}, Evelina La Civita⁴, Antonietta Liotti⁴, Michele Longo⁴, Dario Bruzzese⁵, Michele Cennamo⁴, Vittorio Riccio¹, Pietro De Placido¹, Fernanda Picozzi¹, Sara Parola¹, Bruno Daniele³, Gerardo Botti^{2

6}, Pietro Formisano⁴, Francesco Beguinot⁴, Sabino De Placido^{1

2}, Daniela Terracciano⁴, Giovannella Palmieri²

Affiliations

¹ Department of Clinical Medicine and Surgery, Università degli Studi di Napoli "Federico II", Naples, Italy.
² CRCTR Rare Tumors Coordinating Center of Campania Region, Naples, Italy.
³ Oncology Unit, Ospedale del Mare, Naples, Italy.
⁴ Department of Translational Medical Sciences, Università degli Studi di Napoli "Federico II", Naples, Italy.
⁵ Department of Public Health, Università degli Studi di Napoli "Federico II", Naples, Italy.
⁶ Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.

Abstract

Background: Thymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.

Methods: From July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.

Results: We found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).

Conclusions: To the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.

Keywords: biomarkers; circulating cell-free DNA; circulating tumor DNA; stage system; thymic carcinoma; thymic epithelial tumors; thymoma.

Copyright © 2021 Ottaviano, Giuliano, Tortora, La Civita, Liotti, Longo, Bruzzese, Cennamo, Riccio, De Placido, Picozzi, Parola, Daniele, Botti, Formisano, Beguinot, De Placido, Terracciano and Palmieri.