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De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study

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Abstract

Purpose

Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10–89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life.

Methods

The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years.

Conclusion

This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST.

Trial registration: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).

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Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

BCS:

Breast conserving surgery

BCT:

Breast conserving therapy

CESM:

Contract-enhanced spectral mammography

DCIS:

Ductal carcinoma in situ

FDG-PET CT:

Fluorodeoxyglucose-positron emission tomography computed tomography

HER2:

Human epidermal growth factor Receptor 2

HR:

Hormone receptor

LR:

Local recurrence

LRR:

Locoregional recurrence

LVI:

Lymphovascular invasion

MRI:

Magnetic resonance imaging

Mx:

Mastectomy

NST:

Neoadjuvant systemic therapy

OS:

Overall survival

pCR:

Pathologic complete response

QOL:

Quality of life

TN:

Triple negative

XMG:

Mammograph

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Acknowledgements

Special thanks to BOOG (Borstkanker Onderzoek Groep) Study Center, IKNL (Integraal Kankercentrum Nederland) and BVN (Borstkanker Vereniging Nederland) for their support in designing and conducting the DESCARTES study.

Funding

This work was supported by a research Grant from the Dutch Cancer Society (KWF, project 13761).

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Authors and Affiliations

  1. Department of Surgical Oncology, Netherlands Cancer Institute—Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Annemiek K. E. van Hemert, Josefien P. van Olmen, Emiel J. Th. Rutgers, Marie-Jeanne T. F. D. Vrancken Peeters & Frederieke H. van Duijnhoven

  2. Department of Radiation Oncology (Maastro), Maastricht University Medical Centre+ - GROW School for Oncology and Reproduction, Universiteitssingel 40, 6229 ER, Maastricht, The Netherlands

    Liesbeth J. Boersma

  3. Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    John H. Maduro

  4. Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Nicola S. Russell

  5. Department of Medical Oncology, Jeroen Bosch Ziekenhuis, Henri Dunantstraat 1, 5223 GZ, ‘S-Hertogenbosch, The Netherlands

    Jolien Tol

  6. Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute—Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Ellen G. Engelhardt

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  1. Annemiek K. E. van Hemert
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Contributions

FHvD conceived the DESCARTES study, participated in the design of the study and supervised the drafting of this manuscript. AKEvH participated in the design of the study and drafted the first version of this manuscript. JPvO, LJB, JHM, NSR, JT, EGE, EJTR and MTFDVP participated in the design of the study and critically reviewed the previous versions of this manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Frederieke H. van Duijnhoven.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study protocol is examined and approved by the accredited Medical Research Ethics Committee of The Netherlands Cancer Institute Antoni van Leeuwenhoek (reference: METC21.1046/M21CAR).

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Informed consent of all individual participants will be obtained before inclusion in the study.

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van Hemert, A.K.E., van Olmen, J.P., Boersma, L.J. et al. De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study. Breast Cancer Res Treat 199, 81–89 (2023). https://doi.org/10.1007/s10549-023-06899-y

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