The gold standard for oral cancer diagnosis is visual examination followed by biopsy and histological analysis of suspicious lesions. Now, researchers find that the need for biopsies can be halved when chemiluminescent illumination and toluidine blue staining are used in conjunction with visual examination. Significantly, the new approach accurately identified 100% of the abnormal lesions in a multicenter study.
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May 2007This is the first multicenter study to look at this kind of device kit and to have histologic outcomes, said Joel Epstein, DMD, MSD, Director of the Interdisciplinary Program in Oral Cancer Biology, Prevention and Treatment at the Chicago Cancer Center, who led the trial. The results of this study provide additional information on the utility of this adjunctive technology.
The study was designed to determine whether the US Food and Drug Administration-cleared device kit, called ViziLite Plus with TBlue630, could reduce the number of suspicious lesions that required biopsy. Researchers enrolled 84 patients who were already scheduled to have a total of 97 suspicious lesions biopsied. Prior to the biopsy, the investigators used the kit-which includes a disposable chemiluminescent light source, an acetic acid solution, and pharmaceutical grade toluidine blue dye-to visualize the suspected lesions.
Prior to the biopsies, Dr. Epstein and colleagues recorded the brightness, sharpness, texture, and size of each lesion when visualized with the chemiluminescent light source following application of the acetic acid solution. They also scored each lesion for retention of toluidine blue, which adheres more readily to premalignant and malignant cells than to healthy ones.
Subsequent histopathology analysis showed that 43 lesions (44%) were benign, 34 (36%) had mild to moderate dysplasia, seven (7%) had severe dysplasia, four (4%) had carcinoma in situ, and nine (9%) had progressed to invasive squamous cell carcinoma.
When the researchers compared standard visual examination to visualization with the chemiluminescent light, they found that the new method improved the brightness or sharpness of 61% the lesions relative to standard visual examination. For example, 49 lesions appeared brighter with the new approach, of which nine had a serious pathology. Forty-eight lesions had sharper boundaries, of which seven had serious pathology.
Overall, however, the addition of the chemiluminescent visualization did not change the status of any of the lesions. With standard evaluation, there were 77 false positives and 20 true positives. The results with the chemiluminscence were the same, although one sample was missing from the analysis.
The portion of the kit that provided the most additional diagnostic value, said Dr. Epstein, was the use of toluidine blue, which was directly swabbed onto suspect sites after visualization with the chemiluminescent light source, per the kit’s directions. Toluidine blue is thought to bind to sites of putative loss of tumor suppressor genes that have been associated with progression of oral mucosal lesions to cancer and in oral cancer. Of the 96 lesions tested with the dye, 34 were false positives, 20 were true positives, and 42 were true negatives. There were no false negatives. The false positive rate was decreased by 59% with the dye, said Dr. Epstein during his presentation of the trial data at the Multidisciplinary Head and Neck Symposium in January.
Value of the Study
I think the study is valuable, said Ann M. Gillenwater, MD, Associate Professor and Associate Surgeon, at The University of Texas M.D. Anderson Cancer Center in Houston. A lot of the patients and physicians are reluctant to have the biopsy done unless they are really suspicious. A test like this could help tip the balance so that physicians perform only the biopsies that truly need to be done.
The current trial was not designed to determine whether the kit or the dye can detect lesions that would be missed with standard visual exams. That question is key, said Dr. Gillenwater, who is involved in several trials testing other diagnostic devices in oral cancer.
When asked about that issue, Dr. Epstein said that several trials designed to answer that very question are ongoing. In those studies, the toluidine blue dye will be used as an oral rinse rather than applied directly to suspect lesions. One of the multicenter trials is testing the approach in individuals at high risk for oral cancer but who have not yet been diagnosed with the disorder. Participants in the trial must be over 45 years of age, and smoke cigarettes or drink alcohol. Other trials are testing the approach in patients who have been previously treated for premalignant or malignant lesions and are being followed to look for new lesions or recurrence.
In the meantime, the current trial data suggest that the diagnostic kit can reduce the need for biopsies of lesions already identified by visual and chemiluminescent examination.
Dr. Epstein is on the medical advisory board of Zila, Inc. The trial was funded by Trylon Corp Inc. Both companies have financial ties to the ViziLite Plus device kit.
©2007 The Triological Society
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