A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.

Autor: Roesel R; Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland., Epistolio S; Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland., Molinari F; Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland., Saletti P; Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland.; Medical Oncology Clinic, Clinica Luganese Moncucco, Lugano, Switzerland.; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland., De Dosso S; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.; Istituto Oncologico della Svizzera Italiana, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Valli M; Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Franzetti-Pellanda A; Service of Radiotherapy, Clinica Luganese Moncucco, Lugano, Switzerland., Deantonio L; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.; Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Biggiogero M; Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland., Spina P; Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.; Department of Health Sciences, University of Eastern Piedmont, Novara, Italy., Popeskou SG; Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland., Cristaudi A; Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland., Mongelli F; Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland., Mazzucchelli L; Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland., Stefanini FM; Faculty of Science and Technology-ESP, University of Milan, Milano, Italy., Frattini M; Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland., Christoforidis D; Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.; Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Frontiers in oncology [Front Oncol] 2022 Jun 28; Vol. 12, pp. 900945. Date of Electronic Publication: 2022 Jun 28 (Print Publication: 2022).
DOI: 10.3389/fonc.2022.900945
Abstrakt: Introduction: Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management.
Materials and Methods: Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T 0 , T end ), at 4 (T 4 ), 7 (T 7 ) weeks after radiotherapy, on the day of surgery (T op ), and 3-7 days after surgery (T post-op ). On the day of surgery, a mesenteric vein sample was also collected (T IMV ). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored.
Results: We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the T op .
Conclusions: ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Roesel, Epistolio, Molinari, Saletti, De Dosso, Valli, Franzetti-Pellanda, Deantonio, Biggiogero, Spina, Popeskou, Cristaudi, Mongelli, Mazzucchelli, Stefanini, Frattini and Christoforidis.)
Databáze: MEDLINE
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