Dynamic imaging of the changes in the lymphatics of head and neck patients in response to surgery and radiation

418 Objectives While the lymphatic vasculature may mediate immunosuppression, lymph node metastases, and targeted radiation-induced immune responses in head and neck cancer, the role of lymphatic transport before, during, and following surgery and radiation remains unclear. We sought to longitudinally image the lymphatics of head and neck cancer patients before surgery and longitudinally throughout their treatment to visualize changes in the anatomy and function of the lymphatic vasculature. Methods Near-infrared fluorescence lymphatic imaging was performed in an observational study of head and neck patients before and after surgery, lymph node dissection, and fractionated radiotherapy in order to determine whether transient changes in lymphatic function occur. Following informed consent, each subject received four intraoral injections containing 25ug of ICG and imaging was subsequently performed to assess the drainage through the internal lymphatics. After imaging for approximately 10 minutes, six intradermal injections of 25ug ICG in 0.1 cc were administered, with injections fore and aft each ear and bilaterally along the mid jawline. Imaging sessions were designed to be repeated after surgery, after radiation and subsequently over approximately one year. Results Of the eighteen subjects who underwent baseline imaging, eight subjects were imaged three or more times. In eight of the 18 subjects, we observed lymphatic drainage following the intraoral injections in at least one imaging session. In several subjects, submandibular, internal jugular, and cervical lymph nodes were detected after intraoral injections. Pre-treatment, patients with unilateral disease exhibited impaired cervical lymphatic drainage as compared to their contralateral, uninvolved side. All 7 patients who underwent both lymph node dissection and radiotherapy developed lymphatic dermal backflow on treated lateral sides ranging from days after the start of radiotherapy to weeks after its completion, while contralateral regions not associated with lymph node dissection but also treated with radiotherapy, experienced no such changes in functional lymphatic anatomies. Figure 1 shows (A) the progressive changes in lymphatic anatomy on the left lateral side that had extensive lymph node dissection and 60Gy fractionated radiation as compared to (B) the right side which was treated with 60 Gy fractionated radiation. The time course of treatment is shown in (C). Of the 7 subjects showing this type of aberrant lymphatic architecture, one patient was clinically diagnosed with head and neck cancer lymphedema, a disorder which has few objective diagnostic criteria. Conclusions The functional lymphatic vasculature is altered by cancer involvement and undergoes transient changes during, and weeks after, post-surgery radiotherapy. While radiation treatment profoundly impacts the lymphatic system, it remains to be determined how combination of immunotherapy with radiotherapy will further impact the lymphatic vasculature of head and neck cancer survivors.