Characteristics of Lymphedema in Patients Treated with Mammalian Target of Rapamycin Inhibitors

Abstract

Purpose: To investigate the characteristics of lymphedema in patients treated with mammalian target of rapamycin (mTOR) inhibitors and delineate complex decongestive therapy (CDT) outcomes. Methods and Results: We retrospectively analyzed 24 patients with mTOR inhibitor-induced lymphedema and 7 lymphedema patients (control) not treated with mTOR inhibitors, who visited the lymphedema clinic of the department of rehabilitation medicine from March 2016 to December 2019. We comprehensively reviewed clinical features, medication history, associated diseases, lymphoscintigraphy, lower extremity computed tomography venography (LE CTV), and the effect of CDT. By using ImageJ program, we measured the cross-sectional area (CSA) of muscle and subcutaneous fat of mid-thigh image in LE CTV and compared them to a control group not treated with mTOR inhibitors. Seventeen patients on sirolimus and seven patients on everolimus were included, with an approximately equal distribution of stages 2 and 3 lymphedema, and most with pitting edema. Ten patients had breast or gynecological cancer and underwent lymph node dissection. Lymphedema developed after mTOR inhibitor initiation, not postoperatively. Lymphoscintigraphy revealed decreased lymph node uptake and dermal backflow. LE CTV revealed subcutaneous honeycomb-shaped trabecular areas in the affected limbs of seven patients. Patients treated with mTOR inhibitors had a larger mean subcutaneous fat CSA and a smaller mean muscular CSA than controls. Lymphedema improved or remained unchanged after initial CDT. Daily CDT adequately controlled 11 cases, but exacerbation occurred in 5 of 7 poorly compliant patients, and cellulitis occurred in 6 patients. Conclusion: Physicians should identify mTOR inhibitor-related lymphedema early and discuss medication alternatives and CDT with patients.