ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer

J Cancer Res Clin Oncol. 2024 Sep 22;150(9):428. doi: 10.1007/s00432-024-05944-7.

Abstract

Background: Liquid biopsy is a minimally invasive procedure investigating tumor mutations.

Methods: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations.

Results: In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen.

Conclusion: ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations.

Keywords: Liquid biopsy; Locally advanced rectal cancer; Neoadjuvant therapy; Radiotherapy; ctDNA.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Circulating Tumor DNA* / blood
  • Circulating Tumor DNA* / genetics
  • Female
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy* / methods
  • Rectal Neoplasms* / genetics
  • Rectal Neoplasms* / pathology
  • Rectal Neoplasms* / therapy
  • Retrospective Studies

Substances

  • Circulating Tumor DNA
  • Biomarkers, Tumor