A multi-center clinical trial led by Mass General Cancer Center has produced promising results for a new technique designed to assist surgeons in identifying and removing residual tumor tissue during breast-conserving surgery. The trial evaluated Lumicell’s investigational optical imaging agent pegulicianine in fluorescence-guided surgery (pFGS).
Pegulicianine is activated to a fluorescent form at sites of residual tumor in pFGS, allowing surgeons to identify remaining tumor cells during breast cancer surgery. The study found that pFGS enabled removal of residual tumor cells left behind by standard lumpectomy procedures or avoided second surgeries in 10% of patients. The results have been published in NEJM Evidence.
The aim of the research is to improve the effectiveness of lumpectomy surgery, reduce patient burden, and assist surgeons in achieving clean margins. Real-time evaluation of margins allows surgeons to remove additional tissue immediately. Traditional methods of evaluating tumor margins involve pathologists evaluating the tumor after it has been removed, which can take several days.
The pFGS approach involves injecting pegulicianine, a fluorescent dye, prior to surgery. After the initial tumor specimen is removed, surgeons use a hand-held probe to scan the lumpectomy cavity for additional tumor tissue. Image analysis software displays any fluorescent signal on a screen, indicating remaining tumor tissue for removal.
In a prospective trial led by Smith and her colleagues, 406 patients were enrolled at 14 U.S. sites to evaluate the effectiveness of pFGS. Patients with stages 1 to 3 invasive breast cancer and/or ductal in situ carcinoma (the earliest form of breast cancer) undergoing lumpectomy were included in the study. Patients who were randomized to receive pFGS had their standard lumpectomy followed by additional tissue removal based on pFGS guidance.
Of the patients who underwent pFGS, tumor tissue left behind by standard lumpectomy was detected in 7.6% (27 out of 357 patients). Nine out of 62 patients with positive margins after standard surgery had all their margins cleared by pFGS, avoiding a second surgical procedure. The rate of allergic reactions to pFGS was low and comparable to other commonly used imaging agents.
The study also measured the diagnostic performance of pFGS by determining the sensitivity and specificity of the technique. The sensitivity was 49.3% for all study margins and 58.6% for margins where direct histopathology comparison was available. The specificity was 85.2%.
Smith stated that “these results are comparable to standard-of-care margin assessment.”
While the trial met the prespecified thresholds for removal of residual tumor and specificity, it did not meet its sensitivity goal. This may be due to the trial’s design, which did not include taking additional margin specimens when there were negative pFGS readings. To address this issue, Smith and her team are conducting ongoing studies that will obtain additional margin tissue to calculate sensitivity more precisely. They will also be comparing the effectiveness of pFGS in clearing margins to that of standard surgery, and evaluating rates of recurrence.
Smith acknowledged that “pFGS removed tumor missed by standard lumpectomy and reduced the need for second surgeries for positive margins.” She added that “given its potential, pFGS merits evaluation in future trials and studies.”
Source: Mass General Brigham