Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment

Autor: Lorenzo Gervaso, Davide Ciardiello, Giuliana Gregato, Lorenzo Guidi, Carmine Valenza, Liliana Ascione, Laura Boldrini, Samuele Frassoni, Chiara Alessandra Cella, Francesca Spada, Luigi Funicelli, Giuseppe De Roberto, Wanda Petz, Simona Borin, Marianna Alessandra Gerardi, Luca Bottiglieri, Darina Tamayo, Emilio Bertani, Uberto Fumagalli Romario, Vincenzo Bagnardi, Giuseppe Curigliano, Francesco Bertolini, Nicola Fazio, Maria Giulia Zampino
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Therapeutic Advances in Medical Oncology, Vol 16 (2024)
Druh dokumentu: article
ISSN: 1758-8359
17588359
DOI: 10.1177/17588359241249602
Popis: Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10–1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02–1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63–8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35–4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.
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