41 Retrospective analyses on toxicity in esophageal cancer patients Introduction Over the last decade, increasing numbers of oesophageal cancer patients have been treated with radiotherapy, either in the neo-adjuvant setting followed by surgery or as definitive treatment. Due to neo-adjuvant CRT, cure rates have improved [1,2]. As a consequence, the number of oesophageal cancer survivors at risk of developing late toxicity is has risen correspondingly. Traditionally, radiotherapy planning for these patients has aimed at adequate target coverage while focussing on dose limitation for the spinal cord and lungs in order to prevent radiation-induced toxicities. In recent years, there has been an increasing awareness of radiation-induced cardiac toxicity. In breast cancer patients, prediction models for cardiac toxicity [3,4] indicate a linear increase of the risk of major coronary events by 7.4% per Gray. However, in the radiotherapy treatment of oesophageal cancer the radiation dose to the heart is generally much higher and oesophageal cancer patients generally have less favourable cardiovascular risk profiles. Therefore, prediction models describing the relationship between dose parameters and cardiac events developed in breast cancer patients cannot be automatically extrapolated to oesophageal cancer patients. Limited data currently exists for radiation-induced cardiac toxicity in oesophageal cancer patients. Grade III cardiac toxicities are observed in about 10 percent of these cases and occur relatively early after treatment. Numerous dose volume parameters of the heart are significantly associated with a variety of cardiac toxicity endpoints. However, multivariable prediction models for cardiac toxicity are not available and it remains unclear which threshold dose levels should be used in routine clinical practice [5–9]. Nevertheless, in some studies, including of patients with lung and oesophageal cancer, significant associations were found between cardiac dose and OS, suggesting that cardiac toxicity is a relevant and possibly underestimated problem in the treatment of these patients [10–16]. Even with modern photon techniques, such as IMRT and VMAT, attempts to reduce cardiac dose is generally accompanied by higher dose levels to the lungs, thus increasing the risk of pulmonary toxicity. The optimal balance between cardiac and pulmonary toxicity and its influence on overall survival remains to be determined. 4
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