Researchers have discovered that the investigational optical imaging agent pegulicianine in fluorescence-guided surgery (pFGS) may have been effective at helping surgeons identify and remove residual tumor tissue in patients with breast cancer during breast-conserving surgery, according to a novel study published by Smith et al in NEJM Evidence. The new findings demonstrated that pFGS may have enabled the removal of residual tumor cells left behind by standard lumpectomy procedures or avoided second surgeries in 10% of the study participants.
Traditionally, tumor margins are evaluated by pathologists after the tumor has been removed from the patient’s cavity by surgeons. However, the tumor specimens are often deformed after they have been excised—making it challenging to evaluate the margin orientation—and the return of results can take several days.
In the pFGS approach, the fluorescent dye pegulicianine is injected prior to breast-conserving surgery and activated to a fluorescent form at the sites of the residual tumor tissue. After surgeons remove the initial tumor specimen, they use a handheld probe to scan the lumpectomy cavity. Image analysis software then displays any of these fluorescent signals on a screen, indicating the location of the tumor tissue and allowing the surgeons to remove it during surgery.
“The goal of our research is to evaluate ways to improve the effectiveness of lumpectomy surgery, reduce the burden on patients, and … help surgeons get to clean margins,” explained lead study author Barbara Smith, MD, PhD, Professor of Surgery at Harvard Medical School as well as Director of the Breast Program and Co-Director of the Women’s Cancers Program at the Mass General Cancer Center. “In our study, this intervention had a favorable effect for 10% of the patients that we studied. By evaluating margins in real time, surgeons can remove additional tissue immediately,” she added.
Study Methods and Results
In the new prospective trial, the researchers enrolled 406 patients who were undergoing lumpectomy for stages I to III invasive breast cancer and/or ductal carcinoma in situ in order to evaluate the efficacy of pFGS. Among the patients who were randomly assigned to receive pFGS, the surgeons performed their standard lumpectomy and then removed residual tumor tissue based on the pFGS guidance.
The researchers detected residual tumor tissue left behind by standard lumpectomy in 7.6% (n = 27/357) of the patients who received pFGS. Among the 17% of patients who had positive margins after standard surgery, 14.5% (n = 9/62) of them had all margins cleared by pFGS—potentially avoiding the need for a second surgical procedure. The researchers further reported that pFGS had few adverse events, and the rate of allergic reactions was low and similar to that of other commonly used imaging agents.
The researchers also assessed the diagnostic performance of pFGS by measuring the percentage of margins with tumor tissue that were pFGS-positive and the percentage of margins with no tumor tissue that were pFGS-negative. They found that the sensitivity was 49.3% across all study margins and 58.6% for margins where direct histopathology comparison was available, and the specificity was 85.2%.
“These results compare favorably with standard-of-care margin assessment,” Dr. Smith emphasized.
The researchers highlighted that the new study met its prespecified thresholds for the removal of residual tumor tissue and specificity; however, it did not meet its prespecified sensitivity goal. This may have been the result of the study’s design, which did not include taking additional margin specimens when there were negative pFGS readings. The researchers plan to continue obtaining additional margin tissue in ongoing studies to calculate sensitivity more precisely. They also hope to further examine how effectively the novel approach is capable of leading to clear margins by comparing outcomes and recurrence rates in those receiving pFGS with those receiving standard surgery.
“Overall, we found that pFGS removed tumor missed by standard lumpectomy and reduced the need for second surgeries for positive margins. Given its potential, pFGS merits evaluation in future trials and studies,” concluded Dr. Smith.
Disclosure: The research in this study was supported by Lumicell and the National Institutes of Health. For full disclosures of the study authors, visit evidence.nejm.org.
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