Novel Intraoperative Fluorescence Guidance Identifies Residual Tumor During Lumpectomy

In 2018, researchers at Massachusetts General Hospital first described a novel pegulicianine fluorescence-guided system (pFGS) designed to improve the approach to breast conservation surgery. It evaluates the entire lumpectomy cavity intraoperatively in about one minute, allowing the surgeon to identify and remove residual tumor in real time rather than wait for a pathology report.

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Barbara Smith, MD, PhD, co-director of the Women's Cancers Program at the Mass General Cancer Center, Michele Gadd, MD, assistant visiting surgeon here, and colleagues recently completed INSITE, a prospective, multicenter trial of pFGS co-sponsored by Lumicell, Inc. and the National Institutes of Health.

As they report in NEJM Evidence, the results of pFGS evaluation met prespecified goals for excision of residual tumor and for specificity (sparing of normal tissue), but fell short of the goal for sensitivity (cancer detection).

Methods

406 women enrolled in the trial at 14 U.S. sites between November 4, 2019 and September 15, 2021. All received pegulicianine before surgery. Patients were randomly assigned 10:1 to have pFGS guidance or not; the only purpose of the control group was to discourage surgeons from performing smaller than standard lumpectomy in anticipation of pFGS assistance. Group allocation was revealed only after the surgeon declared lumpectomy was completed.

14 patients were withdrawn before randomization, leaving 357 in the pFGS group and 35 controls. Each patient undergoing pFGS served as her own control; analyses compared margin pathology after standard lumpectomy with margin pathology after standard lumpectomy plus pFGS guidance.

Primary Outcomes

The three co-primary outcomes were:

• Percentage of patients for whom pFGS identified cancer left behind after standard lumpectomy, with success defined as a lower bound of the 95% CI >3%: The result was 27 of 357 patients (7.6%; 95% CI, 5.0%–10.8%)
• Sensitivity (percentage of margins with tumor, read as pFGS-positive), with success defined as a lower bound >40%: The result was 49.3% (95% CI, 37.0%–61.6%)
• Specificity (percentage of tumor-negative margins read as negative by pFGS-negative), with success defined as a lower bound >60%: The result was 85.2% (95% CI, 83.7%–86.6%)

Other Findings

22 of the 27 patients with residual cancer identified by pFGS had "negative" margins on standard-of-care evaluation. This tumor would have been left behind if pFGS had not been used.

62 patients had at least one positive margin after lumpectomy and before pFGS. In nine of them, excision of additional margins under pFGS guidance converted all positive margins to final negative margins, allowing patients to avoid a second surgery.

Based on these results the FDA has granted priority review designation to pegulicianine and accepted a premarket approval application for the pFGS, now called the Lumicell Direct Visualization System.

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