Genomics has not yet been integrated into the clinical practice of Radiation Oncology. Liquid biopsy is a non-invasive tool based on the study of circulating tumor DNA (ctDNA), mainly applied to advanced cancer patients treated with chemotherapy. This work assesses the utility of liquid biopsy in early-stage/oligometastatic cancer patients undergoing stereotactic body radiation therapy (SBRT).
Next-generation sequencing (NGS) genomic panels were used to analyse germline, tissue biopsy and liquid biopsy samples from 24 cancer patients with lung lesions undergoing SBRT: 16 lung cancer primaries and 8 lung oligometastases from other primaries. Personalized tumor biomarkers were selected from NGS data for longitudinal ctDNA analysis in serial liquid biopsies collected from the patients during treatment and follow-up.
Genomic panels revealed potential follow-up ctDNA biomarkers for all patients thanks to the integration of the different genomic tests which enabled to determine the origin of the variants identified, essential for successful biomarker selection; 1/3 of the genomic variants identified by the liquid biopsy panel were real tumor variants. Targeted ctDNA analysis showed that ctDNA detection before treatment was significatively associated with progression-free survival (12 months). In addition, 16 patients showed detectable levels of ctDNA during treatment, while no ctDNA signal was detected in 8 cases. In 14/16 ctDNA-positive patients, follow-up ctDNA signal was consistent with clinical status in both good responders and disease-progression cases. Liquid biopsy detected clinical relapse before imaging tests in 3/6 patients with progression. Besides, the genomic panels identified genetic alterations associated with potential targeted therapeutic alternatives (16/24 patients) and hereditary predisposition to cancer (2/24).
Genomics provides complementary and relevant information for patients undergoing SBRT. Liquid biopsy stands as a promising tool for tailoring SBRT treatments and surveillance protocols, as it can provide prognostic and predictive information.
The authors.
Fundación María Cristina Masaveu Peterson.
All authors have declared no conflicts of interest.