Risk of ischemic heart disease in women after radiotherapy for breast cancer.

BACKGROUND: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. METHODS: We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. RESULTS: The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. CONCLUSIONS: Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

Long-term functional and radiological pulmonary changes after radiation therapy for breast cancer.

BACKGROUND: We assessed late functional and radiological pulmonary changes in breast cancer patients after a median of 11 years following radiotherapy (RT). MATERIAL AND METHODS: Seventy women who received adjuvant loco-regional RT for breast cancer during November 1994-May 1998 accepted to participate in this follow-up study. Pulmonary function tests (PFTs) (n = 56) were compared to pre-RT examinations and diagnostic computer tomography (CT) of the lungs (n = 70) were performed and compared to four months post-RT examinations. RESULT: The median-matched vital capacity (VC), forced expiratory volume in one second (FEV1), and total lung capacity (TLC) were reduced 15%, 9%, and 7%, respectively, at the long-term follow-up (p < 0.001). We could not, however, detect a correlation between ipsilateral V20 and VC-changes. Diffusion capacity (DLCO) appeared to improve compared with the pre-RT baseline level probably due to transient chemotherapy-induced 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. According to the Arriagada classification, ipsilateral V20 and long-term CT-changes showed a significant correlation (rs: 0. 57; p < 0.001) in a small subset of the women. CONCLUSION: A chronic clinically significant reduction of PFTs compared to pre-RT values and CT-changes four months after RT were still detectable after a median follow-up of 11 years. There was a statistical correlation between V20 and abnormalities on CT but no statistical correlation between V20 and VC-changes.

ROC curves and evaluation of radiation-induced pulmonary toxicity in breast cancer.

PURPOSE: To study clinical, radiologic, and physiologic pulmonary toxicity in 128 women after adjuvant radiotherapy (RT) for breast cancer in relation to dosimetric factors. METHODS AND MATERIAL: The patients underwent pulmonary function testing before and 5 months post-RT. Similarly, computer tomography of the chest was repeated 4 months post-RT and changes were scored with a semiquantitative system. Clinical symptoms were registered and scored according to Common Toxicity Criteria. All patients underwent three-dimensional dose planning, and the ipsilateral lung volume receiving > or = 13 Gy (V13), V20, and V30 were calculated. Multiple logistic or regression analyses were used for multivariate modeling. The relation between the dosimetric factors and side effects was also analyzed with receiver operating characteristic (ROC) curves. RESULTS: V20 was, according to multivariate modeling, the most important variable for the occurrence of the three studied side effects (p < 0.01). Age was also related to symptomatic and radiologic pneumonitis. Reduced pre-RT functional level was more common in patients developing symptomatic toxicity. The ROC areas for symptomatic pneumonitis in relation to V13, V20, and V30 were 0.69, 0.69, and 0.67, and for radiologic pneumonitis 0.85, 0.85, and 0.81. CONCLUSIONS: Our results support the use of three-dimensional planning aimed at minimizing the percent of incidentally irradiated lung volume to reduce pulmonary toxicity. Age was also correlated with post-RT side effects. According to ROC analysis, V20 could well predict the risk for radiologic pneumonitis for the studied semiquantitative model.

Reduction of radiation pneumonitis by V20-constraints in breast cancer.

INTRODUCTION: Adjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women. METHODS: 88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V13, V20, V30 and mean dose were calculated and QoL was assessed before and 4 months after RT. RESULTS: The use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V13 (Spearman Rank Correlation: p < 0.05). CONCLUSIONS: The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V13 alone was correlated with occurrence of lung changes on CT.

Quantitative assessment of lung density changes after 3-D radiotherapy for breast cancer.

Our aim was to reduce the rates of clinical and radiological pneumonitis in local-regional radiotherapy (RT) for breast cancer compared to a previous treatment series by applying a pre-planned lung dose volume constraint. 3-D dose planning was performed in 66 women with the aim of not exceeding an ipsilateral V20 of 30%. The patients were followed for short-term signs/symptoms of post-RT pneumonitis and radiological changes on chest CT 4 months after RT. Radiological abnormalities were scored with a CT-adapted modification of a semi-quantitative classification system originally proposed by Arriagada which accounts for severity and affected lung regions. The abnormal subvolumes were contoured and the mean doses were calculated. Three cases of mild and one case of moderate symptomatic pneumonitis were diagnosed. The mean V20 was higher in symptomatic than in unaffected patients, 29% vs. 24% (p =0.04). Mild/moderate radiological changes were frequently observed on CT in regions with average doses >30 Gy. According to multivariate modeling, a trend for association was found between the studied dosimetric factors V13, V20, V30 and mean lung dose, and moderate-severe changes on CT but not with patient specific covariates, e.g. chemotherapy or tamoxifen exposure. 3-D planned local-regional RT with a preplanned lung dose volume constraint of V20 <30% resulted in few cases of moderate symptomatic pneumonitis. Mild/moderate radiological changes were still detectable on CT in subvolumes receiving doses >30 Gy. Long-term follow-up for evaluation of possible late morbidity is warranted.