Can we use a simple blood test to reduce unnecessary adverse effects from radiotherapy by timely identification of radiotherapy-resistant rectal cancers?

Sep 24, 2026

Uploaded by Bulrr

The study protocol evaluates a DNA-methylation diagnostic innovation to enable more selective use of chemoradiation therapy (CRT) for locally advanced rectal cancer. Current CRT reduces local recurrence but can cause significant late harm to surrounding healthy tissue and affects only a minority of patients. A prospective single-centre observational design profiles liquid biopsy DNA methylation in 75 patients receiving neoadjuvant CRT to predict pathological response. Results aim to identify CRT resistance upfront, improving patient selection and reducing unnecessary adverse effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

Background

Chemoradiation therapy standards and limitations

Rationale for patient selection

Methods

Study design and participants

DNA-methylation profiling in liquid biopsies

Discussion

Hypothesis on predictive methylation patterns

Trial registration

Keywords

Mens et al. BMC Cancer (2023) 23:1187 BMC Cancer [https://doi.org/10.1186/s12885-023-11671-y](https://doi.org/10.1186/s12885-023-11671-y) STUDY PROTOCOL Open Access Can we use a simple blood test to reduce unnecessary adverse effects from radiotherapy by timely identification of radiotherapy-resistant rectal cancers? MeDSeq rectal study protocol D. M. Mens 1*, J. M. van Rees 1, S. M. Wilting 1 and C. Verhoef1 Abstract Background Chemoradiation therapy (CRT) followed by surgery is currently the standard of care to treat patients with locally advanced rectal cancer (LARC) . CRT reduces local recurrences, but is associated with significant damage to the surrounding healthy tissue that can severely impact patients quality of life. Additionally, a proportion of patients (hardly) benefit from CRT. We aim to develop a diagnostic innovation, using DNA-methylation, which can enable amore selective and thereby more effective use of the available therapies for rectal cancer patients. Methods MeD-Seq Rectal is a prospective single centre, observational study. 75 patients diagnosed with rectal cancer and will receive CRT as neoadjuvant treatment are will be included. DNA-methylation profiling will be performed on liquid biopsies to predict pathological response to CRT. Discussion To data no clinical or image-based features were found that predict response to CRT. we hypothesize that DNA methylation patterns in liquid biopsies may provide a promising and patient-friendly strategy to predict CRT resistance upfront. Trial registration This trial is registered [at ClinicalTrials.gov](at ClinicalTrials.gov) (NCT06035471) . Keywords Rectal cancer, Chemoradiation, DNA-methylation *Correspondence: D. M. Mens[d.mens@erasmusmc.nl](d.mens@erasmusmc.nl) 1Erasmus MC University Medical Center, Rotterdam, Netherlands © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Mens et al. BMC Cancer (2023) 23:1187 Background Current guidelines in the Netherlands recommend to treat patients with locally advanced rectal cancer (LARC) with pre-operative radiotherapy combined with radiosensitizing low-dose chemotherapy (CRT), followed by surgery. CRT clearly reduces the local recurrence rate in patients with LARC also when combined with newer surgical techniques such as the total mesorectal excision (TME) [1, 2]. However, with these newer surgical techniques the local recurrence rate is already below 10% and CRT only results in an absolute reduction of about ~ 5%. Effects of CRT on the development of distant metastases and overall survival appear to be limited at best. On the other hand, CRT can induce significant damage to the surrounding healthy tissue which may complicate subsequent surgeries and gives rise to late adverse effects severely impacting quality of life in patients treated for rectal cancer [3]. Although these late adver

FAQs

What clinical problem does the protocol address?

CRT for locally advanced rectal cancer reduces local recurrence but can cause significant late adverse effects, while many patients do not benefit. The protocol targets unnecessary harm by improving early prediction of CRT resistance.

How does the study attempt to predict CRT response?

It uses DNA-methylation profiling performed on liquid biopsies to predict pathological response to CRT, aiming to identify radiotherapy-resistant rectal cancers upfront.

What is the study design and sample size?

The study is a prospective single-centre observational study including 75 patients diagnosed with rectal cancer who will receive CRT as neoadjuvant treatment.

Sep 24, 2026

Uploaded by Bulrr