These three toxicities are discussed together as they are all primarily consequences of supraclavicular and/or axillary irradiation in the treatment of breast cancer.
Arm edema or lymphedema in breast cancer patients is caused by an interruption ofthe normal filtration process that occurs between capillaries, interstitial tissue, and lymphatic vessels in the arm. Under normal circumstances, capillary pressures force fluid into the interstitium and reabsorption pressures pull most ofthe fluid back into the capillary at the venous side. The remainder of the filtered fluid and protein are removed by lymphatic vessels. Without the functioning lymphatic system, protein, cells and non-reabsorbed fluid remain in the interstitial tissue. The stasis of fluid in the subcutaneous tissues of the arm leads to increased weight and girth of the extremity. Patients with arm edema secondary to breast cancer therapy can experience difficulty performing skills at home or work because of functional impairment, psychological distress as a result of the change of body image, and chronic pain, leading to significantly reduced QOL.96'97'98 The primary treatment factors contributing to arm edema are the extent of axillary node dissection and nodal irradiation. There are multiple other clinical factors that have been associated with an increased subsequent risk of lymphedema, of these, infection100'101 and obesity116 are frequently reported.
Until recently, axillary node dissection was a standard part ofthe surgical management of invasive breast cancer regardless of tumor size or nodal involvement. The incidence of subsequent lymphedema in several studies is shown in Table 11 and averages about 13%. Studies with longer follow-up tend to show a greater incidence of arm edema. Increased rates of lymphedema have been reported with more extensive dissection,103'104 greater number of nodes removed,105'107'108 and splitting the pectoralis muscle.107 Sentinel lymph node biopsy has resulted in significantly less morbidity with estimates of subsequent lymphedema being <1—3%.110'111
The addition of supraclavicular and/or axillary radiation following a dissection results in a higher incidence of lymphedema. The incidence of lymphedema following axillary node dissection and nodal irradiation ranges from 9% to 58% in the studies presented in Table 12. Increased rates of lymphedema have been described in association with both the British Columbia and the Danish Breast Cancer Cooperative Group (DBCG) 82B and 82C randomized trials that reported a survival advantage with the addition of chest wall and comprehensive nodal RT following mastectomy and chemotherapy. In the British Columbia trial, symptomatic lymphedema was reported in 9% of those irradiated versus 3% in the non-RT arm.72 Hojris reported 14% lymphedema from
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