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Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients

Clinical and Translational Oncology volume 23, pages 1415–1428 (2021)Cite this article

Abstract

Aims

To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality.

Methods

Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria.

Results

The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively.

At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients.

Conclusions

Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good–excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

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Fig. 1
Fig. 2

Abbreviations

ASTRO:

American Society for Radiation Oncology

AIRO:

Associazione Italiana di Radioterapia e Oncologia Clinica

BC:

Breast cancer

CI:

Confidence intervals

CT:

Computed tomography

CTV:

Clinical target volume

EORTC:

European Organization for Research and Treatment of Cancer

FU:

Follow-up

G1:

Grade 1

G2:

Grade 2

G3:

Grade 3

HF-WBRT:

Hypofractionated whole-breast radiotherapy

IMRT:

Intensity-modulated radiotherapy

LENT-SOMA:

Late effects normal tissue task subjective, objective, management, and analytic scale

OARs:

Organs at risk

NRS:

Numeric rate scale

PTV:

Planning target volume

RR:

Relative risk

RT:

Radiotherapy

RTOG:

Radiation Therapy Oncology Group

SIB:

Simultaneous integrated boost

TB:

Tumor bed

WB:

Whole breast

WBRT:

Whole-breast radiotherapy

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Acknowledgements

This work was partially supported by a research grant from Accuray Inc. entitled “Data collection and analysis of Tomotherapy and CyberKnife breast clinical studies, breast physics studies and prostate study” and by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds. The sponsors did not play any role in the study design, collection, analysis, and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication.

The author Maria Alessia Zerella, M.D., was supported in part by research Grants from the Fondazione IEO-CCM (project title: “Preclinical study for single fraction ablative preoperative radiation treatment in early-stage breast cancer: a benchmark for clinical investigation”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. S. Dicuonzo and M. C. Leonardi are Co-first authors.

  2. D. P. Rojas and B. A. Jereczek-Fossa are Co-last authors.

Affiliations

  1. Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, via Ripamonti, 435, 20141, Milan, Italy

    S. Dicuonzo, M. C. Leonardi, G. Corrao, M. A. Gerardi, A. Morra, M. A. Zerella, M. Zaffaroni, C. Fodor, D. P. Rojas & B. A. Jereczek-Fossa

  2. Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy

    S. Raimondi

  3. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    G. Corrao, P. Veronesi & B. A. Jereczek-Fossa

  4. Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy

    V. Bagnardi

  5. Unit of Medical Physics, IEO, European Institute of Oncology IRCCS, Milan, Italy

    F. Pansini, F. Cattani & R. Luraschi

  6. Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy

    P. Veronesi

  7. Scientific Directorate, IEO, European Institute of Oncology IRCCS, Milan, Italy

    R. Orecchia

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  1. S. Dicuonzo
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Correspondence to G. Corrao.

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Dicuonzo, S., Leonardi, M.C., Raimondi, S. et al. Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients. Clin Transl Oncol 23, 1415–1428 (2021). https://doi.org/10.1007/s12094-020-02538-w

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Keywords

  • Hypofractionated radiotherapy
  • Simultaneous integrated boost
  • Toxicity
  • Early breast cancer