Prof. Laura Marcu collaborated with Dr. Gregory Farwell’s group in the Department of Otolaryngology at the UC Davis Cancer Center to translate her work on fluorescence spectroscopy and imaging into a fiber-optic probe that doctors can use to detect tumors at an early stage. The probe can also help surgeons see the margins of a tumor during surgery, allowing them to remove it completely. “This technology gives surgeons an advantage because it can be integrated with surgical instruments to add diagnostic value to existing techniques and instrumentation in the operating room without the need of contrast agents,” Marcu explained. Prof. Marcu demonstrates the probe in this YouTube video. On August 17, Jeffrey Callison interviewed them on his “Insight” radio show on Capital Public Radio. Profs. Marcu and Farwell also discussed their work with The Aggie.
Every hour, one person dies from oral cancer. That number increases when it includes cancers of the oropharynx and larynx. Approximately 43,000 people in the United States are diagnosed with tumors of the oral cavity, pharynx and larynx each year. In addition to smoking, the main risk factor, the rise in cancer of the oropharynx has been linked to human papillomavirus (HPV).
When discovered at an early stage, oral cancers have successful treatments. However, this drops dramatically if the cancer has spread at the time of diagnosis. Currently, only 1/3 of those with oral cavity cancers receive a diagnosis at the earliest stage. Most people are not diagnosed until they have developed a painful sore in the mouth. By this point, the disease has often progressed and requires an aggressive combination of surgery, radiation and chemotherapy.
“People are not as aware of this cancer as they are of other cancer types,” said Dr. Laura Marcu, a professor of biomedical engineering at University of California, Davis. “There’s a lot out there about breast cancer, prostate cancer, and brain cancer, but people are not so aware about oral cancer and its devastating consequences. People don’t think to look for it, and there isn’t any routine screening.”
Therapy for head and neck cancers can have severe, sometimes fatal, side effects. It also often impairs many critical functions, such as speech, swallowing, and taste. Despite advances in reconstructive surgery, facial appearance may remain permanently disfigured. Because tumors can grow back if they have not been removed completely, patients may need more than one surgery. Complete and accurate removal of the tumor results in better patient outcomes and fewer surgeries.
The fiber-optic probe developed in Dr. Marcu’s Lab stimulates the molecules in the patient’s tissues with a laser. Some of these molecules naturally respond by re-emitting fluorescent light. Using sensitive optoelectronic equipment, the devices developed in her lab rapidly detect and analyze this light using a process known as “fluorescence lifetime” or “time-resolved” measurement. The wavelength of the emitted light is determined and the time it takes for the fluorescing molecules to revert to their pre-excited state is measured. The ability to analyze cells immediately resolves around the fact that different metabolic states and biochemical components emit light differently. By analyzing the colors of the emitted light in space and time provides information about the type of molecule present.
The use of fluorescence lifetime contrast in surgical environment is important as the presence of blood can distort the intensity of the fluorescence signal but not the lifetime. Thus surgeons can take more robust measurements of the tumor margins even as they are cutting the tissue. Using this technique, called “time-resolved fluorescence spectroscopy (TR-LIFS)”, Marcu’s lab distinguished cancerous from normal cheek tissue with 100% accuracy in hamsters, and could even begin to investigate the stage of the tumor’s development.
Based on these encouraging results, Marcu and Farwell’s team recruited nine human volunteers from patients who arrived at the University of California, Davis, Medical Center for surgical therapy of the oral cavity, pharynx and larynx. Farwell and Marcu’s team placed the fiber-optic probe perpendicular to the surface of tissue presumed to be healthy, and regions suspicious for carcinoma. They placed the probes in different sites within the mouth and larynx. They collected spectroscopy data and took biopsies from the same locations. When they compared the spectroscopy data with data from the conventional biopsies, they found that the TR-LIFS technique could accurately diagnose the cancer in the surgical environment. The probe is similar to one that Marcu has already developed for use with brain tumors. In clinical trials, surgeons have used her technology to delineate the margins of tumors during surgery.
“As in brain tumor surgery, precision is very important in surgery for oral tumors. The oral cavity performs essential functions, such as eating, breathing, and talking. And the face is such an important part of human identity and communication, that preserving facial appearance is also very important,” Marcu explained.
Using her fiber-optic TR-LIFS probe, Marcu believes surgeons can remove tumors more precisely and more completely. This will help preserve oral and facial features and functions, and lead to a better quality of life for patients after treatment.
Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma. Meier JD, Xie H, Sun Y, Sun Y, Hatami N, Poirier B, Marcu L, Farwell DG. Otolaryngol Head Neck Surg. 2010 Jun;142(6):838-44.PMID: 20493355