Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients

Purpose: Radiation pneumonitis (RP) is one of the most severe toxicities experienced by patients with breast cancer after radiotherapy (RT). RT fractionation schemes and techniques for breast cancer have undergone numerous changes over the past decades. This study aimed to investigate the incidence of RP as a function of such changes in patients with breast cancer undergoing RT and to identify dosimetric markers that predict the risk of this adverse event. Methods and Materials: We identified 1,847 women with breast cancer who received adjuvant RT at our institution between 2015 and 2017. The RT technique was individually tailored based on each patient's clinicopathological features. Deep inspiration breath hold technique or prone positioning were used for patients who underwent left whole-breast irradiation for cardiac sparing, while those requiring regional lymph node irradiation underwent volumetric-modulated arc therapy (VMAT). Results: Of 1,847 patients who received RT, 21.2% received the conventional dose scheme, while 78.8% received the hypofractionated dose scheme (mostly 40 Gy in 15 fractions). The median follow-up period was 14.5 months, and the overall RP rate was 2.1%. The irradiated organ at risk was corrected concerning biologically equivalent dose. The ipsilateral lung V30 in equivalent dose in 2 Gy (EQD2) was the most significant dosimetric factor associated with RP development. Administering RT using VMAT, and hypofractionated dose scheme significantly reduced ipsilateral lung V30. Conclusions: Application of new RT techniques and hypofractionated scheme significantly reduce the ipsilateral lung dose. Our data demonstrated that ipsilateral lung V30 in EQD2 is the most relevant dosimetric predictor of RP in patients with breast cancer.

[1]  K. Keum,et al.  Long-term survival outcomes following internal mammary node irradiation in stage II-III breast cancer: results of a large retrospective study with 12-year follow-up. , 2013, International journal of radiation oncology, biology, physics.

[2]  S. Naganawa,et al.  Development of the breast immobilization system in prone setup: The effect of bra in prone position to improve the breast setup error , 2017, Journal of applied clinical medical physics.

[3]  John R Yarnold,et al.  Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. , 2006, The Lancet. Oncology.

[4]  H. Struikmans,et al.  Regional Nodal Irradiation in Early-Stage Breast Cancer. , 2015, The New England journal of medicine.

[5]  I. Yeung,et al.  Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[6]  M. Martel,et al.  Radiation dose-volume effects in the lung. , 2010, International journal of radiation oncology, biology, physics.

[7]  Roger Owen,et al.  Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[8]  Joanne S Haviland,et al.  The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. , 2013, The Lancet. Oncology.

[9]  J. Yarnold,et al.  Estimating the volume of lung irradiated during tangential breast irradiation using the central lung distance. , 1995, The British journal of radiology.

[10]  F. Vicini,et al.  Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. , 1991, International journal of radiation oncology, biology, physics.

[11]  Masahiro Endo,et al.  Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. , 2003, International journal of radiation oncology, biology, physics.

[12]  M. Bonab randomised trial , 2022 .

[13]  N. Mendenhall,et al.  Is radiation treatment volume a predictor for acute or late effect on pulmonary function? A prospective study of patients treated with breast‐conserving surgery and postoperative irradiation , 1994, Cancer.

[14]  J R Yarnold,et al.  The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial , 2008, The Lancet.

[15]  Laurence Collette,et al.  Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. , 2015, The New England journal of medicine.

[16]  Anthony Fyles,et al.  Long-term results of hypofractionated radiation therapy for breast cancer. , 2010, The New England journal of medicine.

[17]  H. Park,et al.  External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence , 2018, Radiation oncology journal.

[18]  J. Bradley,et al.  The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation. , 2002, International journal of radiation oncology, biology, physics.

[19]  B. Wennberg,et al.  Radiation pneumonitis and pulmonary function with lung dose–volume constraints in breast cancer irradiation , 2013, Journal of radiotherapy in practice.

[20]  J. Yarnold,et al.  The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial , 2008, The Lancet. Oncology.

[21]  Joos V Lebesque,et al.  Regional differences in lung radiosensitivity after radiotherapy for non-small-cell lung cancer. , 2004, International journal of radiation oncology, biology, physics.

[22]  K. Keum,et al.  The deep inspiration breath hold technique using Abches reduces cardiac dose in patients undergoing left-sided breast irradiation , 2013, Radiation oncology journal.

[23]  B. Fowble,et al.  Lung and heart dose volume analyses with CT simulator in radiation treatment of breast cancer. , 1998, International journal of radiation oncology, biology, physics.

[24]  Ik Jae Lee,et al.  Three-dimensional analysis of patterns of locoregional recurrence after treatment in breast cancer patients: Validation of the ESTRO consensus guideline on target volume. , 2017, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  R. Clough,et al.  Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. , 2002, International journal of radiation oncology, biology, physics.

[26]  E. Hall,et al.  Radiation-induced second cancers: the impact of 3D-CRT and IMRT. , 2003, International journal of radiation oncology, biology, physics.

[27]  K. Boda,et al.  The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients. , 2007, International journal of radiation oncology, biology, physics.

[28]  I. Vogelius,et al.  A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis , 2012, Acta oncologica.

[29]  Chen Hu,et al.  Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. , 2019, The Lancet. Oncology.

[30]  D. Groheux,et al.  Regional Nodal Irradiation in Early-Stage Breast Cancer. , 2015, The New England journal of medicine.