The evaluation of radiation induced radiological changes of the lung and its association between clinical and dosimetric factors in breast cancer patients treated with radiotherapy

Purpose To perform a detailed analysis of radiotherapy (RT) induced radiological changes of the lung, to grade the radiation pneumonitis/fibrosis (RP/F) and to investigate its association between clinical and treatment related factors of breast cancer patients treated with RT. Methods From 2005 to 2013, 76 breast cancer patients treated at Ege University Faculty of Medicine Department of Radiation Oncology were retrospectively reviewed. During follow-up, patients were examined for radiation pneumonitis (RP). Mediastinal window with 350/50 Hounsfiel Unit (HU) and parenchymal window with 1200/-600, 800/-800, 1800/-600 HUs were used for the evaluation of 116 follow-up thorax CTs of 76 patients. Thorax CT scans were analyzed for ground glass opacity, septal thickening, consolidation/patchy pulmonary opacity/alveolar infiltrates, subpleural air cyst, air bronchogram, parenchymal bands, traction bronchiectasis, pleural/subpleural thickening and pulmonary volume loss. The scoring of radiological RP/F was made according to Nishioka classification system. The scoring includes Grade 0, no significant changes in the radiation field; Grade 1, only pleural thickening in the radiation field; Grade 2, pulmonary changes (plaque-like or heterogeneous density) in <50% of the area of the radiation field; Grade 3, pulmonary changes in >50% of the area of the radiation field. Descriptive statistics and correlation analysis with Spearman's correlation coefficient were done with IBM SPSS 22.0 software. Correlation coefficient was between -1 and +1; whereas p<0,05 was considered statistically significant. Results Patients' median age was 53, of whom 70% had modified radical mastectomy, 58% had invasive ductal carcinoma histology and 93% of them had stage II-III disease. All patients were treated with breast/chest wall plus regional lymphatic irradiation. During 49 months of follow-up, none of the patients were diagnosed with oxygen or steroids requiring clinical RP. For all follow-up periods ground glass opacity was the most common radiological finding followed by pleural/subpleural thickening and septal thickening. Regarding 1-6 months follow-up thorax CT scan evaluation, patients older than 53 years of age or patients taking aromatase inhibitors had more severe Nishioka RP/F grades (rs=0,42 and rs=0,663; p=0,012 and p=0,000) in univariate analysis. Among dose volume histogram (DVH) parameters of 13- 18 months follow-up thorax CT scan, ipsilateral lung V5>%30 (rs=0,73 and p=0,000) and >%44 (rs=0,49 and p=0,025); V20>%15 (rs=0,56 and p=0,01), >%20 (rs=0,64 and p=0,002), >%30 (rs=0,51 and p=0,02) and >%33 (rs=0,48 and p=0,02); V40>%24 (rs=0,51 and p=0,02) and mean lung dose was (MLD)>16 Gy (rs=0,51 and p=0,02) was related with more severe Nishioka RP/F grades. Moreover, after an 18 months period follow-up of thorax CT scans evaluation, Nishioka RP/F grade was more severe in cases with V5 >%30 (rs=0,37 and p=0,037) or V20 >%15 (rs=0,39 and p=0,028). Conclusions In the study regarding 1-6 months follow-up thorax CT scans, advanced age or aromatase inhibitors as clinical factors were related with more severe Nishioka RP/F grading. Regarding DVH parameters; V5, V20, V40 and MLD are found to be important factors in relation to the Nishioka RP/F grades. These DVH parameters, already used in daily clinical practice, are predictive for late term (>12 months) RT-induced radiological lung changes. Keywords Radiotherapy; radiation pneumonitis/fibrosis; Nishioka grading system