Cardiac and pulmonary side-effects of radiotherapy in early breast cancer

Abstract: The purpose of this thesis was to study early and late side-effects to lung and heart in adjuvant locoregionalradiation therapy (LRRT) of early breast cancer (BC). Papers I-III were intervention studies aiming to reduce symptomatic/ radiological pneumonitis and functional changes after LRRT by applyingthe ipsilateral lung dose volume constraint V20 ≤ 30 %. The results were compared with a previoustreatment series. Papers IV-V evaluated the long-term cardio-pulmonary effects of BC RT. In paper I, 66 patients were followed for signs of post-RT pneumonitis and changes on chest computer tomography (CT) 4 months post-RT. Lung subvolumes with radiological changes were contoured and the mean doses were calculated. Few cases of symptomatic pneumonitis were diagnosed. The mean ipsilateral lung V20 was higher in symptomatic than in unaffected patients, 29 % vs 24 % (p=0.04). Mild/moderate radiological changes were detectable on chest CT in subvolumes with average doses > 30 Gy. In paper II, patients were examined with chest X-ray and CT pre- and 4-5 months post-RT and compared to the outcome of our previous trial. The use of lung dose volume constraints significantly reduced moderate/severe radiological changes on chest X-ray compared with our earlier study (p< 0.001). Lung changes on CT were also limited in the present series and related to ipsilateral V13. In paper III, changes in pulmonary function tests (PFTs) were studied. The applied constraints appeared to lower short-term changes in PFTs. Pre-RT chemotherapy affected DLCO at baseline. In paper IV, a long-term follow-up of irradiated women with BC, i.e. median 11 years, was undertaken. We assessed late changes in PFTs and radiological abnormalities with chest CT. The median matched VC, FEV1, and TLC were reduced 15, 9, and 7 %, respectively, compared to pre-RT values (p<0.001). DLCO, however, appeared to recover from baseline probably due to transient chemotherapy-induced lung toxicity. The median matched percentage of the predicted DLCO 11 years after RT was, however, only 86 %, indicating a chronic therapy-induced reduction also of this metric. The observed radiological and PFTs changes 4 months after RT were, thus, still detectable after a median follow-up of 11 years. In paper V, the risk of developing ischaemic heart disease, through incidental heart irradiation, was examined in a population-based case-control study of 2,100 women, who underwent RT for BC during 1958-2001. Individual patient data were obtained and doses to the entire heart and left anterior descending coronary artery were estimated. Exposure of the heart to ionizing radiation during RT increased the subsequent rate of ischaemic heart disease. The increase was proportional to the mean dose to the heart, began within a few years after exposure, and continued for at least 20 years. In conclusion, our aims to minimize incidental dose to lung in LRRT of BC lowered the short-term pulmonary side-effects and should therefore be utilized. The long-term studies showed that side-effects to lung and heart after adjuvant RT in BC with older techniques were of clinical relevance still after several years.