Radiation-induced lymphedema refers to the development of lymphedema following radiation treatment.

The incidence of radiation-induced lymphedema varies depending on the radiation method and design, but it is estimated to be as low as 3.1% without regional nodal radiation, around 20%-24% when regional nodal radiation is delivered, and as high as 33% when both regional nodal radiation and axillary nodal dissection are completed. It may occur months to years after radiation.

The pathophysiology of radiation-induced lymphedema is thought to be due to the destruction of lymphatics and interstitial fibrosis compressing lymphatic vessels, resulting in mechanical insufficiency of lymphatic drainage. It may be associated with a higher risk of infection and malignancy. The extremities are most commonly affected, but the breast or chest wall may also be involved.

Several risk factors have been identified:

• Breast cancer, especially when lymph node dissection is performed, is linked to upper limb lymphedema. Gynecological malignancies, such as ovarian, vulvar, and endometrial cancers, are associated with lower limb lymphedema, particularly following pelvic and inguinal node dissections. Sarcoma and malignant melanoma are also associated with radiation-induced lymphedema.
• Certain anatomic locations are at higher risk of lymphedema development from radiation. Specifically, upper axillary nodal basins at level I between the latissimus dorsi to the lateral aspect of the pectoralis minor and level II posterior to the pectoralis minor are high-risk locations due to a high concentration of lymph nodes.
• The methods of radiation delivery matter. For breast cancer, tangential photon radiation is associated with a higher risk for lymphedema compared to diffuse chest wall electron beams. Overlapping radiation fields and posterior axillary boost radiation may also increase risk of lymphedema. For lower extremity lymphedema, external beam radiation carries a higher risk for lymphedema compared with vaginal brachytherapy.
• Risk is dose-dependent in the setting of axillary radiation; a higher total dose of radiation is associated with a higher risk of radiation-induced lymphedema.
• Obesity is a risk factor (in a patient with a body mass index higher than 30).
• Postoperative complications or infection of the surgical site, ipsilateral venous compromise (in the setting of thrombosis, indwelling venous port, pacemaker, or dialysis catheter), advanced or recurrent cancer, trauma, taxane-based chemotherapy, high number of positive lymph nodes (greater than 8), and capsular invasion by a tumor are risk factors for radiation-induced lymphedema.

Clinical staging of lymphedema: Based on clinical findings in a physical examination, the International Society of Lymphology (ISL) developed a staging system that divides lymphedema into 4 stages:

• Stage 0 (subclinical) – Swelling is not evident. Heaviness and discomfort.
• Stage 1 (spontaneously reversible) – Swelling relieved by limb elevation. Includes pitting edema.
• Stage 2 (spontaneously irreversible) – Swelling not improved by limb elevation. May or may not include pitting edema.
• Stage 3 (lymphostatic elephantiasis) – Swelling not improved by limb elevation. Skin hardening, nonpitting edema, verrucous changes, and recurrent soft tissue infections.

Complications of chronic lymphedema include predisposition to cellulitis, recurrent cellulitis, and ulceration. Lymphangiosarcoma (Stewart-Treves syndrome) is a rare yet serious complication of longstanding chronic lymphedema associated with radical mastectomy.