Dr. Barbara Smith removing the initial tumor specimen, using a hand-held probe to scan the lumpectomy cavity looking for additional tumor to remove. Image analysis software then displays any fluorescent signal on a screen, indicating remaining tumor tissue for removal.
Newswise — A fresh method intended to enable surgeons to detect and excise leftover tumor tissue during breast-conserving surgery demonstrated encouraging outcomes in a multi-center study led by researchers from the Mass General Cancer Center, a member of Mass General Brigham. The clinical study, which received partial funding from Lumicell, Inc., examined Lumicell's investigational optical imaging agent pegulicianine in fluorescence-guided surgery (pFGS). In pFGS, pegulicianine becomes fluorescent at residual tumor sites, permitting surgeons to recognize any remaining tumor cells in the surgical site during breast cancer surgery. Investigators discovered that pFGS facilitated the elimination of residual tumor cells that were left behind after standard lumpectomy procedures or prevented the need for a second surgery in 10% of study participants. Findings are published in NEJM Evidence.
"Our aim with this research is to assess methods for enhancing the efficacy of lumpectomy surgery, lessening the burden on patients, and assisting surgeons in achieving clean margins," explained Barbara Smith, MD, PhD, the corresponding author and the director of the Breast Program at Mass General Cancer Center, as well as the head of the Breast Section in the Department of Surgery. "In our study, this intervention had a positive impact on 10% of the patients we examined. By assessing margins in real-time, surgeons can promptly remove any remaining tissue."
The conventional method of evaluating tumor margins entails pathologists examining the excised tumor after it has been removed from the patient's cavity by surgeons. However, tumor specimens are frequently distorted after removal, making it difficult to assess margin orientation, and results can take several days to be returned. In contrast, the pFGS approach involves injecting a fluorescent dye called pegulicianine before surgery. Following the removal of the primary tumor specimen, surgeons employ a hand-held probe to scan the lumpectomy cavity in search of any remaining tumor to excise. Image analysis software subsequently displays any fluorescent signal on a screen, indicating residual tumor tissue that requires removal.
Smith and her colleagues conducted a prospective trial to assess the effectiveness of pFGS. They enrolled 406 patients at 14 U.S. sites, all of whom were undergoing lumpectomy for stage 1 to 3 invasive breast cancer and/or ductal in situ carcinoma (considered the earliest form of breast cancer). In the group randomized to receive pFGS, surgeons conducted the standard lumpectomy procedure and then excised any additional tissue based on pFGS guidance.
The study showed that pFGS detected residual tumor tissue in 27 out of 357 patients (7.6 percent) who underwent the procedure, which had been left behind by standard lumpectomy. In the group of patients who had positive margins after standard surgery, 9 out of 62 (17 percent) had all margins cleared by pFGS, potentially negating the need for a second surgical procedure. The pFGS approach was associated with few safety issues, as the rate of allergic reactions was low and comparable to that of other commonly used imaging agents.
The team also evaluated the diagnostic performance of pFGS by determining the percentage of margins that tested positive for residual tumor tissue (sensitivity) and the percentage of margins that tested negative for residual tumor tissue (specificity). Sensitivity was found to be 49.3 percent for all margins evaluated in the study and 58.6 percent for
“These results compare favorably with standard-of-care margin assessment,” said Smith.
Although the trial met prespecified benchmarks for specificity and removal of residual tumor tissue, it did not meet the prespecified sensitivity goal. This may be attributed to the study design, which did not entail taking additional margin specimens when pFGS readings were negative. Smith and her colleagues are involved in ongoing research that will involve taking additional margin tissue to more accurately determine sensitivity. They will also conduct a more comprehensive assessment of the efficacy of pFGS in clearing margins, comparing outcomes to standard surgery and recurrence rates.
Smith stated that, on the whole, the study showed that pFGS was effective in removing residual tumor tissue that was not detected by standard lumpectomy and in decreasing the necessity for second surgeries due to positive margins. Based on its potential, Smith believes that pFGS warrants further evaluation in future clinical trials and studies.
olleagues conducted a prospective trial, enrolling 406 patients at 14 U.S. sites. All patients were undergoing lumpectomy for stages 1 to 3 invasive breast cancer and/or ductal in situ carcinoma (considered the earliest form of breast cancer). Among patients who were randomized to receive pFGS, surgeons performed their standard lumpectomy and then removed additional tissue based on pFGS guidance.
In 27 of 357 patients (7.6 percent) who underwent pFGS, the technique detected tumor tissue that had been left behind by standard lumpectomy. In the 17 percent of patients who had positive margins after standard surgery, 9 of 62 had all margins cleared by pFGS, potentially avoiding a second surgical procedure. pFGS had few safety events—the rate of allergic reactions was low and similar to that of other commonly used imaging agents.
The team also assessed diagnostic performance of pFGS by measuring the percentage of margins with tumor that were pFGS positive (sensitivity) and the percentage of margins with no tumor that were pFGS negative (specificity). Sensitivity was 49.3 percent across all study margins, and 58.6 percent for margins where direct histopathology comparison was available. Specificity was 85.2 percent.
“These results compare favorably with standard-of-care margin assessment,” said Smith.
The trial met prespecified thresholds for removal of residual tumor and specificity but did not meet its prespecified sensitivity goal, which may be due to the trial’s design, which did not include taking additional margin specimens when there were negative pFGS readings. Smith and colleagues are involved in ongoing studies that will obtain additional margin tissue to calculate sensitivity more precisely. They will also look in greater detail at how effectively pFGS clears margins, comparing outcomes to standard surgery and rates of recurrence.
“Overall, we found that pFGS removed tumor missed by standard lumpectomy and reduced the need for second surgeries for positive margins,” said Smith. “Given its potential, pFGS merits evaluation in future trials and studies.”
Disclosures: Author disclosures and other supplementary materials are available at evidence.nejm.org.
Funding: Supported by Lumicell, Inc. and the National Institutes of Health (grant number 1R44CA211013-01).
Paper cited: Smith BL et al. “Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery” NEJM Evidence DOI: 10.1056/EVIDoa2200333
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