Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of breast cancer: a prospective study

David Pasquier,Benoit Bataille,Eric Lartigau,Frederik Crop,Alexandre Escande,Franck Darloy,Emmanuelle Tresch,Hélène Langin,Florence Le Tinier,Damien Carlier,Raoudha Bennadji

doi:10.1038/s41598-021-83159-3

Abstract

ORCID: 0000–0001-6019–7309. In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). Comparisons with conventional radiotherapy have shown that IMRT is associated with lower frequencies of acute and late-onset AEs. Here, we extended a prospective, observational, single-center study of the safety of IMRT to a second investigating center. Patients scheduled for adjuvant IMRT after partial or total mastectomy were given a dose of 50 Gy (25 fractions of 2 Gy over 5 weeks), with a simultaneous integrated boost in patients having undergone conservative surgery. 300 patients were included in the study, and 288 were analyzed. The median follow-up period was 2.1 years. The 2-year disease-free survival rate [95% CI] was 93.4% [89.2–96.0%]. Most AEs were mild. The most common AEs were skin-related—mainly radiodermatitis [in 266 patients (92.4%)] and hyperpigmentation (in 178 (61.8%)). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Only 4 patients presented with a grade 3 event (radiodermatitis). Smoking (odds ratio) [95% CI] = 2.10 [1.14–3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27–0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001–1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters.Trial registration: ClinicalTrials.gov NCT02281149.

Highlights

D2% Dose received by 2% of the volume D50% Dose received by 50% of the volume D95% Dose received by 95% of the volume D98% Dose received by 98% of the volume EORTC QLQ-BR23 European Organisation for Research and Treatment of Cancer Breast Cancer-Specific
The project was initially set up as a single-center study at the Centre Oscar Lambret cancer center (Lille, France), and the preliminary results in 114 patients have been r eported[16]; we found that quality of life (QoL) was well maintained, and that acute esophageal toxicity was associated with a number of dosimetric factors
Two-center study of 288 patients treated for breast cancer with Intensity-modulated radiation therapy (IMRT) (including 225 (78.3%) with axillary node involvement), we found that skin adverse events were very common but rarely severe

Summary

Introduction

In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Smoking (odds ratio) [95% CI] = 2.10 [1.14–3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27–0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001–1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters. Questionnaire ESTRO European Society for Radiotherapy and Oncology IMRT Intensity-modulated radiation therapy OAR Organs at risk OR Odds ratio PTV Planning target volume. QoL Quality of life SBR Scarff-Bloom and Richardson SD Standard deviation SIB Simultaneous integrated boost V95% Volume receiving 95% of the dose WHO World Health Organization

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Conclusion