Does Previous Head and Neck Irradiation Increase Vascular Complications in Free Autologous Reconstruction?

Abstract

Sir:FigureWe read with interest the recent article “Free Flap Reconstruction in the Head and Neck Region following Radiotherapy: A Cohort Study Identifying Negative Outcome Predictors.”1 This is an important article because there are still contradicting data regarding microsurgical complications associated with previous radiotherapy. The topic is also of general interest outside the plastic surgery community because there is an increasing population of cancer survivors for whom the long-term side effects of radiotherapy have to be considered. In fact, a growing body of clinical evidence has recently shown that radiotherapy is an independent risk factor for cardiovascular disease (i.e., myocardial infarction and stroke) at previously irradiated sites. This is further supported by molecular evidence that radiotherapy clearly exerts a detrimental effect on blood vessels, especially the endothelium.2 However, in the context of microvascular surgery, we lack a more detailed description of vascular complications related to radiotherapy. A relationship between previous chest wall irradiation and different vascular complications during free flap surgery was recently clearly shown in 1026 free flaps by Fosnot et al.,3 but this finding did not affect the free flap failure rates. The association shown by Fosnot et al., between radiotherapy and perioperative vascular complications, would be interesting to study in the cohort presented by Bourget et al., where the radiotherapy dose is higher (median, 64.5). Both studies concluded that radiotherapy is not associated with increased free flap failure rates. However, this could be explained by the fact that even relatively large clinical cohorts suffer with regard to statistical power as a result of low free flap failure rates, because it is difficult to detect an association with a limited sample size. In an attempt to overcome this, we presented a review of the literature where free flap outcome had been described in relation to previous radiotherapy. No association had been found between previous radiotherapy and complete free flap failure in any of the single studies, but a significant relationship between previous radiotherapy and free flap failure was clearly seen when all of the material was analyzed together (p < 0.0019; odds ratio, 1.72; 95 percent confidence interval, 1.22 to 2.44).4 There are several studies, outside the microsurgical field, that have been able to show that radiotherapy is associated with a prothrombotic response where the radiotherapy dose seems to be of importance.1,5 Fosnot et al. described that their results may be explained by endothelial dysfunction and prothrombotic characteristics seen in irradiated recipient veins, previously presented by us and others.6 Our group has over the past few years been studying radiation-induced gene expression in head and neck recipient arteries and veins and found an inflammatory and prothrombotic response even years after radiotherapy exposure.6,7 We believe that vascular complication is a more sensitive endpoint, compared with free flap failure, when radiotherapy shall be studied as a risk factor for microvascular surgery. Clinical studies on radiotherapy-related thrombosis during microsurgery in both arteries and veins may also contribute to increased general knowledge about radiation-induced vasculopathy, an area recently pointed out as an important field for future research in cancer survivors.1 Martin Halle, M.D., Ph.D. Filip Farnebo, M.D., Ph.D. Karolinska University Hospital, Stockholm, Sweden