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Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy

British Journal of Cancer volume 129, pages 1619–1624 (2023)Cite this article

Subjects

Abstract

Background

Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC).

Methods

We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS).

Results

One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively.

Conclusion

Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.

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Fig. 1: Kaplan–Meier curves of disease-free survival (DFS) in the exploratory cohort.
Fig. 2: Kaplan–Meier curves of disease-free survival (DFS) in the validation cohort.

Data availability

Datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy

    Andrea Pretta, Pina Ziranu, Giovanna Pinna, Clelia Donisi, Francesco Loi, Giulia Deias, Enrico Palmas, Francesca Semonella, Stefano Mariani, Valeria Pusceddu, Marco Puzzoni, Eleonora Lai, Cinzia Solinas & Mario Scartozzi

  2. Medical Oncology Unit, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy

    Riccardo Giampieri & Rossana Berardi

  3. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

    Giovanni Randon, Federica Morano & Filippo Pietrantonio

  4. UOC Anatomia Patologica, AOU Cagliari, University of Cagliari, Cagliari, Italy

    Alberto Ravarino & Gavino Faa

  5. Science Department, King’s School Hove, Hangleton Way, Hangleton, East Sussex, BN3 8BN, UK

    Gianluca Pretta

  6. UOC Radioterapia Oncologica, Azienda Ospedaliera “Brotzu”, Cagliari, Italy

    Maria Assunta Deidda & Raffaele Barbara

  7. Department of General Surgery, University Hospital and University of Cagliari, Cagliari, Italy

    Angelo Restivo & Luigi Zorcolo

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  1. Andrea Pretta
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Contributions

AP: conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing—original draft, writing—review and editing, visualization. PZ and RG: resources, data curation, formal analysis, writing—original draft, writing—review and editing. G Pinna and CD: resources, data curation, writing—original draft. GR, FL, GD, EP, FM and FS: resources, data curation. AR, SM, MAD, VP, MP, EL, AR, LZ, R Barbara, and R Berardi: resources. G Pretta and CS: writing—review and editing. GF: resources, data curation, writing—original draft, writing—review and editing. FP: resources, data curation, writing—original draft, writing—review and editing. MS: methodology, validation, formal analysis, investigation, resources, data curation, writing—original draft, writing—review and editing.

Corresponding author

Correspondence to Andrea Pretta.

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The authors declare no competing interests.

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Ethics Committee approval was obtained for the study (Protocol number 2020/10912—code: EMIBIOCCOR) from Cagliari Independent Ethics Committee and written informed consent was obtained from all participants for their tissues to be utilized for this work. This study was performed in accordance with the study protocol, the ethical principles stated in the Declaration of Helsinki as well as those indicated in the International Conference on Harmonization (ICH) Note for Guidance on Good Clinical Practice (GCP; ICH E6, 1995), and all applicable regulatory requirements. All patients signed a written informed consent before study entry. Adequate information was given to eligible patients by the principal investigator or co-investigators in accordance with local regulations. The declaration of informed consent was personally signed and dated by the subject, and by the investigator/person designated by the investigator to conduct the informed consent discussion.

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Pretta, A., Ziranu, P., Giampieri, R. et al. Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy. Br J Cancer 129, 1619–1624 (2023). https://doi.org/10.1038/s41416-023-02444-2

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