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



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.


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.


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.


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



American Society for Radiation Oncology


Associazione Italiana di Radioterapia e Oncologia Clinica


Breast cancer


Confidence intervals


Computed tomography


Clinical target volume


European Organization for Research and Treatment of Cancer




Grade 1


Grade 2


Grade 3


Hypofractionated whole-breast radiotherapy


Intensity-modulated radiotherapy


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


Organs at risk


Numeric rate scale


Planning target volume


Relative risk




Radiation Therapy Oncology Group


Simultaneous integrated boost


Tumor bed


Whole breast


Whole-breast radiotherapy


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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.

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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 (2021).

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