Abstract 2052: Assessing lymphatic response to treatments in head and neck cancer using near-infrared fluorescence imaging
Authors: Tan I-Chih , Karni Ron J. , Rasmussen John C. , Sevick-Muraca Eva M. 
Published: May 2015

Abstract
Radiation toxicity is a major obstacle to effective head and neck (HN) cancer treatment. Treatment-related toxicity to lymphatic tissues in the HN region could significantly diminish patient's quality-of-life, with lymphedema resulting in more than half of HN cancer patients who undergo surgery and radiotherapy. Impairment of lymphatics due to radiotherapy may be expected because radiation exposures could cause tissue fibrosis and loss of capillary lymphatics. In this pilot study, we sought to visualize lymphatic architecture and contractile function before and after cancer treatments using near-infrared fluorescence (NIRF) lymphatic imaging. The approach allowed us to longitudinally assess the effect of radiation or surgery on the lymphatics in HN cancer patients.
Human subjects, who were diagnosed with HN squamous cell carcinoma and scheduled for radiotherapy or combination of surgery/radiotherapy, were recruited in this ongoing study under FDA approval (IND 102,765). Imaging sessions are conducted before and as late as one year after the treatments at several time points. After informed consent, ten injections of 12.5-25 mcg indocyanine green (off-label use) in 0.05-0.1 c.c. saline were each administered bilaterally in the oral cavity, oropharynx, and on the face (posterior auricular, preauricular, and submandibular) in each imaging session. Immediately after injections, the skin surface was illuminated with a diffused excitation light of 785 nm, and sequences of NIRF lymphatic images of 0.2 sec exposure time at 2 frames/sec were collected using a custom-built imaging system. Imaging was typically performed for an hour. While subject recruitment continues, NIRF images in all 13 subjects show the lymphatic draining vessels and nodes in the face and neck. Images acquired before treatment, post-surgery, and then post-radiation allowed us to document the change of lymphatics and investigate the response of lymphatics to the treatments. Propulsion of lymph in collecting lymphatic vessels were seen in some of subjects both pre- and post- surgery as well as after radiotherapy. To date, no major impairment of lymphatics has been noted in the first 13 subjects. Longitudinal imaging was accomplished for 3 out of 13 subjects. Extra-lymphatic leakage around the incision line was seen in some subjects post surgery. In one subject, lymphatic propulsion was seen before treatment and post- radiation, but not post-surgery. Preliminary results show the reformation of lymphatic architecture after surgery and radiotherapy.
In conclusion, we have employed NIRF imaging to assess lymphatics in HN cancer patients, who underwent radiotherapy and/or surgery, and to visualize the response to the treatments. While longitudinal studies continue, the preliminary results show the reorganization of lymphatics after the treatments.
Citation Format: I-Chih Tan, Ron J. Karni, John C. Rasmussen, Eva M. Sevick-Muraca. Assessing lymphatic response to treatments in head and neck cancer using near-infrared fluorescence imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2052. doi:10.1158/1538-7445.AM2014-2052