Risk Factors For Radiation-Induced Lung Injury After Hypofractionated Radiotherapy In Breast Cancer

Purpose:This study analysed the incidence and differences between hypofractionated radiotherapy（HFRT）and conventional radiotherapy（CFRT）in breast cancer,aimed to identify potential risk factors related to the radiation pneumonia（RP）and radiation-induced lung fibrosis（RILF）of the ipsilateral lung,and investigate probability of the dose reductions from DIBH in left lung and the heart.Patients and MethodsPart-1We retrospectively reviewed female patients of breast cancer accepted postoperative radiotherapy（PMRT）in the Department of Radiation Oncology of Xiangya Hospital from January 2018 to April 2020,and screened finally out 173 patients who had a repeated chest CT within 6 months and 2 years after radiotherapy,including 63 patients in the HFRT group,and 110 patients in the CFRT group;Patients were monitored for symptoms of RILI 1,3,6,12 and 24 months after radiotherapy（RT）and data on covariates were collected prospectively.The outcome was compared with Baseline chest CT before radiation therapy.RP（within 6 months following completion of irradiation）was graded using common terminology criteria for RTOG and RILF（occurs 6 months after treatment）was graded using CTCE5.0 lung fibrosis criteria.Meanwhile,the correlated clinical and physical factors were collected;The degree of lung fibrosis was estimated by measuring the fibrosis volume.The comparison between hypofractionation group and conventional fractionation group was performed using the Student t-test.Univariate and Logistic regression analyses were conducted to assess the risk factors of RP and RILF in patients with BC.The predictors threshold were estimated using receiver operating characteristic curve analysis.We used the SPSS 26.0 statistical software for statistical analysis.P < 0.05 indicates that the difference was statistically significant.Part-2A total of 7 female patients receiving radiotherapy for left-sided breast cancer in DIBH were enrolled in this study,admitted to Departments of Pathology in Xiangya Hospital Since mastered the DIBH technology in October 2021.Collect radiotherapy dose parameters for the left lung and heart under DIBH and FB states;Radiation doses to the lung and cardiac structures were compared between the DIBH and FB techniques and the dose reductions with DIBH were correlated to the lung expansion using Spearman’s rank correlation coefficient（ρ）.P<0.05 indicates that the difference was statistically significant.ResultsPart-11.A total of 173 breast cancer patients were evaluated,the median follow-up time was 5.6 months,the results showed that the incidence of grade 1 RP was 64.54%（71 patients）in the CFRT group and 55.55%（35 patients）in the HFRT group;four patients（3.63%）of CFRT group developed grade 2 RP,two patients（3.17%）of HFRT group developed grade 2 RP;for grade 3 RP,only one patient（0.9%）of CFRT group,two patients（3.17%）of HFRT group.But there was no significant difference between the two groups（P=0.459）.2.Finally,the median follow-up time of RILF was 26.2 months,the results showed that the incidence of grade 1 RILF was 51.81%（57patients）in the CFRT group and 57.14%（36 patients）in the HFRT group;For the occurrence of grade 2 RILF,there is 6 patients（5.45%）of CFRT group and 3 patients（4.7%）of the HFRT group;there is not occurrence of ≥ grade 3 RILF in two group.No statistically significant incidence between the two groups（P=0.930）.3.For all 173 patients,ipsilateral lung V₁₇ is independent predictors for ≥ grade 2 RP（odds ratio = 1.16,p = 0.013）,With 32% as the optimal V₁₇ threshold for ≥ grade 2 RP;The Vf ranged from 51 to 58 mL（median 65.2ml）,ipsilateral lung V₄₀ was independent predictor of ≥ grade 2 RILF（odds ratio = 1.148,p = 0.043）.With 21% as the optimal threshold for V₄₀ for ≥ grade 2 RILF.Part-2A total of 7 patients were evaluated,the mean volumes of the left lung increased in 55.8% compared to FB,DIBH effectively reduced doses to the left lung,whole lung and the heart,but the degree of dose reductions was variable across different structures,especially V₂₀（p=0.032）and V₃₀（p=0.019）.Spearman’s rank correlation coefficient demonstrated that the expansion of the left lung with DIBH as compared with FB was significantly correlated with the relative dose reductions in most of the left,especially V₁₇（p=0.007）and V₂₀（p=0.036）.ConclusionsIn the study,hypofractionated radiotherapy had similar toxicities to conventional fractionated radiotherapy in breast cancer even in the context of modern comprehensive treatment.V₁₇ is an independent predictor of radiation pneumonia and V₄₀ of radiation pulmonary fibrosis,so dose restrictions on the lungs should be taken into account when developing radiotherapy plans.In addition,the use of BIDH technology to reduce the dose of left lung radiation in patients with left breast cancer play a limited role,and large-sample prospective randomized studies are still needed to confirm the optimal applicability of the population.