A tumor-specific fluorescent tracer improved the detection of breast tumor margins during surgery and may help surgeons remove cancer cells that would otherwise be missed, according to the first part of a Phase 2 study.
The study, “Implementation and benchmarking of a novel analytical framework to clinically evaluate tumor-specific fluorescent tracers,” was published in the journal Nature Communications.
The complete removal of a tumor during surgery is crucial to avoid additional surgeries, cancer relapse, and lower overall survival. Currently, the distinction of cancer and healthy tissue during surgery mainly depends on visual inspection and palpation by the surgeon — a method with undetermined accuracy.
Surgeons routinely remove an extra centimeter of tissue around the tumor to reduce the chances of leaving any cancer cells behind. Still, one in five patients requires a second procedure to remove the remaining tumor tissue. Thus, there is an unmet need to improve the specific detection of tumor margins during surgical procedures.
Fluorescence-guided surgery, which combines imaging techniques and tumor-specific fluorescent tracers — fluorescent compounds that bind to tumors – has the potential to provide highly specific real-time detection of tumor margins during surgery, illuminating cancer cells that once evaded standard detection.
Despite the increasing number of clinical studies evaluating tumor-specific fluorescent tracers to detect cancer during surgical procedures, there is still no consensus on the gold standard to determine their effectiveness.
Researchers in the Netherlands and China developed a platform to evaluate the effectiveness of fluorescent tracers in the detection of a tumor and its margins during surgery and in post-surgery analyses.
It consists of an analysis of the macroscopic imaging (image and video) of the tumor during fluorescence-guided surgery in combination with the microscopic fluorescence images of the freshly removed tissue.
They used this platform in an open-label Phase 2 study (NCT02583568) to assess the effectiveness of a tumor-specific fluorescent tracer, called bevacizumab-800CW, in patients with invasive primary breast cancer.
Bevacizumab-800CW combines a cancer therapy called Avastin (bevacizumab) — which binds to and blocks VEGF, a protein highly present in cancer cells that allows them to grow blood vessels to survive — and a fluorescent protein called 800CW. It was previously shown to specifically target VEGF in breast cancer patients.
Between October 2015 and February 2017, researchers enrolled 26 patients with early-stage invasive breast cancer, scheduled for breast cancer surgery. In the trial’s first part, three patients received 4.5 mg, 10 patients 10 mg, 10 patients 25 mg, and three patients 50 mg of bevacizumab-800CW three days before surgery.
Because this study was not designed to change standard of care, surgeons could not remove additional tissue based on remaining positive fluorescence signals (after tumor removal).
The results showed that fluorescence-guided surgery with bevacizumab-800CW improved the detection of tumor margins by 88%. It detected remaining cancer cells that were missed by standard methods in seven of eight patients who had lingering tumor cells.
“Because the tumor-involved surgical margins could be detected intraoperatively in real time, these patients might have avoided additional surgery or therapy,” the researchers wrote.
However, bevacizumab-800CW also showed fluorescent signals post-surgery in two patients (7.6%) that were later found to be non-cancerous, which the researchers believe may be due to specific features observed in the surrounding tissue of these tumors.
“This indicates the clinical value of intraoperative molecular fluorescence imaging in breast cancer patients and supports a paradigm shift in the future treatment of breast-conserving surgery,” they concluded.
The team noted, however, that additional clinical studies are necessary to evaluate the definitive clinical impact of bevacizumab-800CW-guided surgery and define the optimal threshold of fluorescence intensities that define the real detection of cancer cells for decision making during surgery.
No serious adverse events were reported in this first part of the trial. In its second part, the two doses of bevacizumab-800CW producing the best results will be further assessed in 10 new breast cancer patients each.