FLARE™ Surgical Illuminations
"FLARE™ (Fluorescence-Assisted Resection and Exploration) is a novel imaging system that uses near-infrared (NIR) light to help surgeons better see cancers - while they are performing surgeries. Developed by
John Frangioni, MD, PhD, cofounder of BIDMC's Center for Molecular Imaging, FLARE™ has, for the first time, been successfully utilized during surgery to efficiently identify sentinel lymph nodes in breast cancer patients. The pilot study currently appears on-line in the Annals of Surgical Oncology.
"If a surgeon can find cancer faster and more effectively and make smaller incisions to remove it, it benefits patients in terms of lower morbidity rates and fewer complications," said Frangioni, the study's senior author.
As the body's first line of defense, lymph nodes are the most likely place for cancer cells to migrate once they have moved from the primary tumor. Therefore, in breast cancer patients, doctors typically remove the lymph nodes following initial treatment, to determine if the cancer has spread.
"The problem," says Frangioni, "is that until now, there was no way of knowing which lymph nodes were at highest risk. There are 30 lymph nodes under a woman's arm, and removing too many can leave the patient with lymphedema, a painful and debilitating swelling of the arm."
However, he adds, if surgeons can focus in only on the sentinel lymph nodes - the first underarm nodes that receive drainage from the area surrounding the breast cancer - they can avoid unnecessary surgery and related complications.
The FLARE™ imaging system, invented in 2001 in the Frangioni Laboratory, improves mapping of sentinel lymph nodes during surgery. FLARE™ utilizes NIR light in combination with a specially designed fluorescing dye that targets lymph nodes and that can be injected into patients. While invisible to the naked eye, the dye can be seen when exposed to NIR light from the FLARE™ system. The image of the fluorescing sentinel lymph nodes is then overlaid on a color image of the surgical site on a video monitor; the surgeon is able to view the lymph nodes fluoresce in real time and remove them.
"This is a phenomenal new technology, and we felt this was a very successful first attempt at using the FLARE™ system for surgery on patients," said Susan Troyan, MD, who performed the lymph node surgeries on the six participants of this study. Dr Troyan is the study's first author as well as director of Breast Care Program at BIDMC.
Presently, in sentinel lymph node surgery, patients are often injected with radioactive dye prior to surgery. The surgeon then uses a scanner to find the sentinel lymph nodes containing the radioactive dye and removes the nodes, which are then examined for the presence of cancer cells.
In this pilot study, the first published clinical trial using the FLARE™ system, nine sentinel lymph nodes were detected by FLARE™ and removed. In addition to the NIR-fluorescent dye, the patients were injected with radioactive dye so both detection methods could be compared. In four of the six patients, they revealed the same result. In one patient, the FLARE™ system identified a sentinel lymph node that was not detected by the radioactive dye. In another, the FLARE™ system discovered one of two sentinel lymph nodes, both of which were detected by the radioactive dye.
Future studies will continue to refine the accuracy of the FLARE™ system and optimize its imaging capabilities. A clinical trial was just completed using FLARE™ in breast reconstruction surgery after mastectomy for breast cancer, and another is underway mapping sentinel lymph nodes in lung cancer.
To further this work, Dr. Frangioni's lab is currently examining ways to engineer various NIR-fluorescing dyes so that they can attach to specific cancer cells. This would be useful in breast cancer surgeries, for example, where surgeons remove the cancerous tumor as well as what appears to be normal tissue surrounding it. That "margin" of normal tissue is then examined by pathologists to determine if any of the cancerous tumor cells are seen at the edge of the tissue. It takes three to five days to receive the pathology results; if cancerous cells are found at the margin, additional surgery is required to remove it.
"Imaging gets a bad reputation in the health care system for driving up costs," said Dr. Frangioni, who also co-directs the Center for Molecular Imaging and the Longwood Small Animal Imaging Facility (LSAIF) at BIDMC. "However, imagine the cost savings if the 25 percent of women who have to go back for a second breast cancer surgery do not have to go back to have more cancer removed. That is hundreds of millions of dollars saved in one procedure."
"If a dye could attach to breast cancer cells, a surgeon could remove only the NIR-fluorescing tissue visible through the FLARE™ system. "We would be able to direct surgery more accurately with greater precision, fewer surgeries, and a better cosmetic result," said Dr. Troyan. "Recurrence of breast cancer could decrease because we would be able to remove cancerous areas on the margins of tumors that could have previously been missed."
The FLARE™ system is capable of simultaneously displaying two independent colors of NIR-fluorescing light. This is a valuable tool for surgeries that require removal of one tissue, such as a tumor, while avoiding other tissues, such as nerves and blood vessels, and has potential applications in complex cancer surgeries like prostate cancer.
This study was supported by a multi-year Bioengineering Research Partnership grant from the National Institutes of Health (NIH) designed to translate technology into clinical settings, and a NIH R21 Quick Trials in Imaging grant designed for the first-in-human testing of the FLARE™ imaging system in women undergoing sentinel lymph node mapping for breast cancer.
Coauthors include BIDMC scientists Vida Kianzad, PhD, Summer L. Gibbs-Strauss, PhD, Sylvain Gioux, MEng, Aya Matsui, MD, PhD, Rafiou Oketokoun, MEng, Long Ngo, PhD, and Fred Azar, PhD.