Fluorescent guide can help detect tumour left behind after surgery

A new technique designed to allow surgeons to identify and remove residual tumour tissue during breast-conserving surgery is said to have shown promising results in a multi-centre trial led by investigators from the Mass General Cancer Center.

The clinical trial, involving 406 patients across 14 US sites, evaluated Lumicell’s investigational optical imaging agent pegulicianine in fluorescence-guided surgery (pFGS). In pFGS, pegulicianine is activated to a fluorescent form at sites of residual tumour, allowing surgeons to identify tumour remaining in the surgical site during breast cancer surgery.

Investigators found that pFGS enabled removal of residual tumour cells left behind by standard lumpectomy procedures or avoided second surgeries in 10% of study patients. The trial was funded in part by Lumicell, Inc, and the results are published in NEJM Evidence.

“The goal of our research is to evaluate ways to improve the effectiveness of lumpectomy surgery, reduce the burden on patients and to help surgeons get to clean margins,” said corresponding author Barbara Smith, MD, PhD, the director of the Breast Program at Mass General Cancer Center (a member of Mass General Brigham) and head of the Breast Section in the Department of Surgery.

“In our study, this intervention had a favourable effect for 10% of the patients that we studied. By evaluating margins in real time, surgeons can remove additional tissue immediately.”

Traditionally, tumour margins are evaluated by pathologists after the tumour has been removed from the patient’s cavity by surgeons. Tumour specimens are often deformed after they have been excised, making it challenging to evaluate margin orientation, and the return of results can take several days.

The pFGS approach involves injecting pegulicianine, a fluorescent dye, prior to surgery. After surgeons remove the initial tumour specimen, they use a handheld probe to scan the lumpectomy cavity looking for additional tumour to remove. Image analysis software then displays any fluorescent signal on a screen, indicating remaining tumour tissue for removal.

All 406 patients involved in the trial 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 randomised to receive pFGS, surgeons performed their standard lumpectomy and then removed additional tissue based on pFGS guidance.

In 27 of 357 patients (7.6%) who underwent pFGS, the technique detected tumour tissue that had been left behind by standard lumpectomy. In the 17% 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 tumour that were pFGS positive (sensitivity) and the percentage of margins with no tumour that were pFGS negative (specificity). Sensitivity was 49.3% across all study margins and 58.6% for margins where direct histopathology comparison was available. Specificity was 85.2%.

“These results compare favourably with standard-of-care margin assessment,” Smith said.

The trial met prespecified thresholds for removal of residual tumour but did not meet its prespecified sensitivity rate, which may be due to the trial’s design, which did not include taking additional margin specimens when there were negative pFGS readings, said Massachusetts General Hospital in a statement. 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 tumour missed by standard lumpectomy and reduced the need for second surgeries for positive margins,” Smith said. “Given its potential, pFGS merits evaluation in future trials and studies.”

Image caption: iStockphoto.com/NoSystem images