Dermal Backflow, Detected by Near-infrared Fluorescence Lymphatic Imaging, Is an Early Prognostic Marker of Breast Cancer-related Lymphedema

Abstract

Breast cancer-related lymphedema (BCRL) is a complication for millions of patients receiving chemotherapy, axillary lymph node dissection (ALND), and radiation therapy (RTx). Ipsilateral arm swelling of 5% to 10% over baseline, at least 3 months after RTx, is commonly used as a BCRL diagnostic, yet this criteria may only be realized after significant, permanent, lymphatic damage has occurred. As timely complete decongestive treatment has been shown by others to stall or even prevent BCRL, “catching it early” could optimize patient outcomes. We sought to evaluate whether longitudinal near-infrared fluorescence lymphatic imaging (NIRF-LI) of lymphatic dysfunction provides an early predictor of BCRL in advanced breast cancer patient undergoing ALND and RTx. In an ongoing clinical study (NCT02949726), patients with breast cancer were imaged before and after ALND, as well as at 6, 12, and 18 months after RTx, NIRF-LI to visualize dysfunctional lymphatics. Perometer readings of arm volumes were recorded at each imaging session to provide objective diagnosis of BCRL from arm swelling of >5% at or after 6 months after RTx. Perometer readings were compared to pretreatment baseline measurements. Dermal backflow, an NIRF-LI pattern indicating lymph that either fails to enter primary lymphatics and progress to collector vessels, or counterfluxes from collector vessels, appeared in 23 out of 24 women thus far diagnosed with BCRL at time of this report (August 27, 2021). Dermal backflow occurred at the time of diagnosis in 39% of patients, or prior to BCRL diagnosis (mean, 10.4 months; range, 6-25.5 months) in the remaining 61% patients. Of all BCRL diagnoses, 34% were diagnosed at 6 months after RTx. Prior to 6 months after RTx, dermal backflow, but not >5% arm volume increases, were predictive of BCRL. One patient taking biologics for treatment of previously diagnosed rheumatoid arthritis was diagnosed with BCRL prior to appearance of dermal backflow. Another patient developed dermal backflow at study end point and thus, could have developed BCRL beyond the study end point. From a total of 32 patients who have completed the study, NIRF-LI dermal backflow had a specificity and sensitivity of 89% and 96% and an overall accuracy for predicting or detecting BCRL of 97%. Preliminary results show that longitudinal screening of patients with breast cancer with NIRF-LI enables earlier diagnosis of BCRL that could enable optimized outcomes, healthcare cost savings, and improved quality of life for breast cancer survivors. NIRF-LI screening during the first six months after RTx could detect those patients developing lymphatic dysfunction before onset of arm swelling can be used as a benchmark to prescribe complete decongestive treatment.