FDA Approval Sought for Lumisight Optical Imaging Agent to Assist in Intraoperative Breast Cancer Detection


A new drug application seeking the approval of Lumisight, an optical imaging agent that detects cancerous tissue during initial lumpectomy to allow for a more complete resection, has been submitted to the FDA.

Barbara Smith, MD, PhD

Barbara Smith, MD, PhD

A new drug application (NDA) seeking the approval of Lumisight, an optical imaging agent that detects cancerous tissue during initial lumpectomy to allow for a more complete resection, has been submitted to the FDA.1

The investigational proprietary onco-fluorescent agent should be used with the Lumicell Direct Visualization System (DVS) to find, view, and guide the resection of residual cancer during the initial surgery.1,2 Lumisight is given preoperatively, on the same day of the procedure, to highlight cancerous cells. Then, a hand-held imaging probe scans inside the breast cavity to find activated Lumisight in residual cancer. Patient-calibrated tumor detection software provides real-time images from the cavity that help guide the surgeon in removing remaining disease.

The NDA is based on information collected from over 700 patients with breast cancer spanning 5 clinical trials. The safety and efficacy of the Lumicell DVS system has been examined in the phase 3 INSITE trial (NCT03686215),3 results of which will be shared at the 2023 American Society of Breast Surgeons Annual Meeting, and a phase 2 feasibility study (NCT03321929).4

“Data has shown that the risk of local recurrence is directly related to incomplete tumor removal. Currently, at least 20% of women having BCS require a second surgery because of positive margins and 6% to 10% of women with breast cancer experience a local recurrence,” Barbara Smith, MD, PhD, director of the Breast Program at Massachusetts General Hospital, professor of surgery at Harvard Medical School, and lead investigator of INSITE, stated in a press release. “As surgeons, technology that helps ensure we are doing everything in our power to remove cancer during the initial lumpectomy gives us and patients greater [peace] of mind and has the potential to support improved outcomes.”

Data from the feasibility study were published in JAMA Surgery in May 2022.5 The nonrandomized, controlled trial enrolled female patients with invasive breast cancer and/or ductal carcinoma in situ and who were at least 18 years of age. If patients had received neoadjuvant therapy, were undergoing margin re-excision after previous breast-conserving surgery (BCS) or were injected with blue dyes for sentinel node mapping prior to completing the procedure with the imaging system, they were excluded.

On the day of the surgery, patients received the Lumisight intravenously at 1 mg/kg over the course of 3 minutes. Following infusion, investigators monitored participants for toxicity for 2 to 6 hours; then, they went on to receive standard BCS, which was defined as resection of the main tumor specimen and any shaved cavity margins needed to obtain grossly negative margins per surgeon assessment.

After the procedure, the handheld probe took pictures of the lumpectomy cavity. If the software detected a region suspected to contain residual disease, the surgeon removed additional shaves from that area. Surgeons were initially limited to 1 shave per orientation; this was amended to 2 shaves following data from the first 127 patients analyzed.

A total of 234 patients were enrolled to the study. All patients received the imaging agent, but 4 patients withdrew before completing the procedure; the remaining 230 patients were analyzed for performance metrics and all 234 patients were examined for safety.

Investigators evaluated the association of the imaging system with shave margin pathology by using the truth standard hierarchy approach. Of the 1091 negative images, 1072 were true negatives, translating to a negative predictive value of 98%. Imaging was positive in 43 of the 62 total positive margins, translating to a sensitivity rate of 69.4%. The false-negative rate of the imaging procedure was 1.2%. Moreover, compared with routine pathology assessment of lumpectomy specimens, the per-margin sensitivity rate with the imaging system was 69.4% vs 38.2%.

The association of the imaging system and final margin status was also examined. Of the 230 total patients, 83.5% achieved negative margins following BCS. In this subset, 115 patients had additional image-guided excisions and 14 patients were found to have residual disease in the additionally excised margins; 11 patients had negative margins at the time of the final pathology assessment.

Moreover, 16.5% of the 230 patients were found to have positive margins after BCS. In this subset, 29 had positive imaging in at least 1 orientation; 23 of these patients had additional image-guided excisions 12 of which with residual disease identified in the final margins. Sixty percent of the 230 patients had additional excisions guided by the imaging system and 19% were found to have residual disease. The false-negative rate of the imaging system was 23.7% on a per-patient level and the sensitivity rate at this level was 76.3%.

Investigators also analyzed the link between the imaging system and re-excision rates. Of the overall population, 12.2% went on to have a second procedure for positive margins and this comprised 24 re-excisions and 4 mastectomies. In 32 patients who underwent excision of imaging-guided shaves, the novel system reduced the need for re-excision for 19% of patients.

Of the 234 patients evaluate for safety, 1 patient had serious anaphylaxis during the administration of Lumisight. This patient received treatment, recovered, and went on to their planned surgery. Notably, the patient was noted to have a history of allergy to iodinated contrast drugs, which had not met exclusion criteria at the time they had been enrolled. Investigators subsequently revised the eligibility criteria for the study in light of this. After the change was made, no additional serious toxicities were observed.

Other adverse effects that were determined to be likely linked with study intervention included superficial thrombophlebitis, transient transaminitis, and post-traumatic stress disorder.

“Submission of the Lumisight NDA is a significant step toward achieving this goal,” Kevin Hershberger, president and chief executive officer of Lumicell, Inc., added in a press release.“We look forward to working with the FDA on acceptance of our Lumisight application for review and submitting the PMA for the Lumicell DVS in the second quarter.”


  1. Lumicell submits new drug application for Lumisight optical imaging agent to US FDA for intraoperative breast cancer detection and removal. News release. Lumicell, Inc. March 21, 2023. Accessed March 21, 2023.
  2. Our platform technology. Lumicell, Inc. website. Accessed March 21, 2023.
  3. Investigation of novel surgical imaging for tumor excision (INSITE). Updated December 16, 2022. Accessed March 21, 2023.
  4. Intraoperative detection of residual cancer in breast cancer. Updated April 1, 2021. Accessed March 21, 2023.
  5. Hwang ES, Beitsch P, Blumencranz P, et al. Clinical impact of intraoperative margin assessment in breast-conserving surgery with a novel pegulicianine fluorescence-guided system: a nonrandomized controlled trial. JAMA Surg. 2022;157(7):573-580. doi:10.1001/jamasurg.2022.1075
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