The Role of Lymph Node Irradiation in the Pathogenesis of Acquired Lymphedema

The prevalence of acquired lymphedema in the cancer survivor population underscores the intimate relationship between cancer therapeutics and lymphatic vascular dysfunction. ¹ While the contributory role of radiotherapies to this outcome is widely acknowledged, ² the dysfunction that is directly attributable to radiation damage to the nodal structures has not been directly identified. Furthermore, despite importance of radiation damage to the pathogenesis of cancer-related lymphedema, the incorporation of radiation into experimental animal models of lymphedema has been infrequent.

Both of these issues are addressed by Baker et al. in the current issue of Lymphatic Research and Biology. ³ Using a model of popliteal node radiotherapeutic disruption in rabbits, the authors demonstrated that radiation of the intact nodes decreased lymph transport at both early and late time points. Irradiation of a single popliteal lymph node reduced the lymphatic to blood transport of the lymph flow tracer to about a third of that observed in non-irradiated controls. Comparable functional defects following radiation, with our without surgical excision, suggest that radiation itself is capable of playing a predominant role. The authors postulate that the abnormal pressure-flow relationships observed in all treatment groups relates, at least in part, to the fibrosis and thickening of the nodal capsules and trabeculae. Furthermore, angiogenic responses and formation of lymphaticovenous anastomoses suggest that endogenous development of alternative drainage pathways is feasible.