RADIATION-INDUCED CARDIAC TOXICITY AFTER THERAPY FOR BREAST CANCER: INTERACTION BETWEEN TREATMENT ERA AND FOLLOW-UP DURATION

Purpose: Cardiac toxicity after breast radiotherapy (RT) has been widely described in older RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more modern RT trials have shown less cardiac toxicity. The comparisons between the older and modern trials are confounded by the longer follow-up time in the older trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. Methods and Materials: The published data were surveyed using PubMed to identify studies using breast cancer, irradiation/radiotherapy, cardiac/heart, and toxicity/morbidity/mortality in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as older (patient accrual start year before 1980) and modern (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. Results: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically <= 10 years and did not report an excess toxicity risk. The modern studies lacked longer follow-up. Conclusion: Additional follow-up is needed to ensure that modern methods effectively reduce cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent. (C) 2009 Elsevier Inc.