Intraoperative Assessment of Surgical Lumpectomy Margins

Institution: John Wayne Cancer Institute
Investigator(s): Armando Giuliano, M.D. -
Award Cycle: 2006 (Cycle 12) Grant #: 12IB-0120 Award: $268,810
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure

Initial Award Abstract (2006)
Approximately 20-30 percent of patients who undergo lumpectomy (removal of breast primary tumor), require re-operation because of tumor involvement at the edges of the removed tissue (tumor positive margins) indicating that some breast cancer was left within the breast itself. Lumpectomy, even with radiation, is less likely to be successful in controlling breast cancer when even small amounts of tumor cells are left at the margin of surgical removal compared to complete tumor removal. There currently is no good means to intraoperatively detect tumor at the margin of surgery. The emotional and financial cost of re-operation is great, and often mastectomy is performed for positive lumpectomy margins.

A new beta probe, which has been shown to detect tumor cells after a FDG {imaging agent for PET (positron emission tomography imaging)} scan, may be able to identify tumor left behind at lumpectomy margins during operation. This handheld probe used during the operation could enable the surgeon to take slightly more tissue at the initial procedure, thereby avoiding positive margins and the need for subsequent surgery, thus preventing disease recurrence.

Our study will include patients undergoing injection with FDG within 3 hours before lumpectomy. The tumor will be surgically removed and examined to determine whether the PET beta probe can detect tumor around the margins and in the breast cavity during the operation. The margins of the lumpectomy specimen will be examined and correlations made between probe detection and microscopic detection of tumor by the pathologist. In addition, sensitive molecular tumor marker tests will be performed to improve detection over current pathology. Subsequently, once the probe accuracy is demonstrated, it will be used to detect tumor during the operation and to alter the extent of surgery to avoid positive (tumor present) margins, avoid subsequent surgery, and render a patient breast tumor-free in one operation.

Currently there is no accurate way to intraoperatively detect residual tumor cells at the surgical margins. This project is innovative in its application of a unique beta probe to identify tumor <1 mm away. Another novel aspect of the study is the applied combination of ultra-sensitive detection of cancer in the breast. Examination of lumpectomy margins with molecular assays has never been performed and could result in a more rational way to detect cancer and make decisions regarding surgical management.

Final Report (2009)
The overall purpose of this project was to determine the feasibility of a beta probe for the intraoperative assessment of the surgical margins of a lumpectomy for breast cancer. Lumpectomy often results in residual tumor margins of resection requiring re-operation or mastectomy. Techniques to determine tumor involvement of the margins intraoperatively have not been successful. We attempted to identify tumor at the margins of resection by injecting patients with radioactive glucose (FDG) which is the same agent used for whole body positron emission tomography (PET scanning). Our hypothesis was that tumor cells would take up glucose more avidly than the surrounding normal breast tissue, and these cells could be detected with the probe just as metastases are detected on PET scan. A total of 7 patients were tested with the initial probe developed by our physicist. We found that the probe as designed lacked the sensitivity to identify small amounts of tumor at the margin. However, we showed that the concept of tumor detection with the intraoperative FDG and the beta probe was valid by examining the lumpectomy specimen itself. We bisected lumpectomy specimens and saw that the probe could detect within the specimen.

Attempt was then made by our physicist to modify the probe by altering the shielding. However, after testing 5 more patients, we found that even this modified probe lacked sensitivity. We then went from a probe to a camera. Our hypothesis at this time was that the camera could accumulate counts from radioactive tumor cells, and this accumulation of counts could magnify the difference between tumor and background, and we would detect small amounts of tumor. Two patients were then tested with the camera, and again there was not sufficient sensitivity to detect small amounts of tumor at the margin. The tumor margins from the lumpectomies were also examined with molecular oncology markers. We identified 2 markers that could be effective in detecting breast cancer.

Overall, we validated the concept of the beta probe for intraoperative detection of primary tumors in breast cancer. However, we have yet to overcome the barrier of probe sensitivity. By identifying molecular markers, we are focusing our future efforts on the use of intraoperative molecular marker detection of tumor-involved margins while awaiting improvements in probe technology.