Creating a new oral tradition
NEW YORK—Patients with oral cancer may have more targeted, personalized treatment options available to them if a new clinical study successfully identifies genomic markers in tumors that predict if an oral cancer is likely to metastasize to the neck.
The study, the work of the NYU College of Dentistry and the Helen Diller Family Comprehensive Cancer Center at the University of California-San Francisco (UCSF), was recently awarded a two-year grant from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). More funding is needed to advance the trial, but the study's leaders are confident that they will be able to harness the power of genomics to yield groundbreaking results for oral cancer patients, for whom current treatment options are limited.
Oral cancer, a subtype of head and neck cancer, is any cancerous tissue growth located in the oral cavity. Oral cancers may originate in any of the tissues of the mouth, and most commonly involve the tongue—but the disease may also occur on the floor of the mouth, cheek lining, gums, lips or palate.
"People don't realize that oral cancer is an incredibly difficult-to-treat cancer," says Dr. Brian L. Schmidt, professor of oral and maxillofacial surgery at the NYU College of Dentistry, former faculty member at UCSF and a leader of the study. "Head and neck and oral cancers have a lot of DNA mutations, so it is a very tricky cancer when you compare it to other cancers. People don't realize they can die from this, but in fact, survival is very poor, with about half of patients surviving only five years after diagnosis. One of the things that drew me to treating patients with oral and head and neck cancer is that they often have a low quality of life. They can have a lot of pain or disfigurement, so this is a group that needs a lot of attention."
Oral cancer is often fatal if it spreads to the neck and remains untreated. Nearly all cancers within the oral cavity must be surgically removed in a neck dissection, which may also be performed to remove lymph nodes if there is any clinical or radiographic evidence of neck metastasis. Current clinical and radiographic examination provides limited information for diagnosis of early neck metastasis of oral cancer.
"We currently have no reliable methods of detecting whether a patient already has metastasized disease. The instruments we have cannot detect small metastasis," says Schmidt. "When I finished my fellowship in 2002 [in head and neck cancer at Legacy Emanuel Hospital and Health Center in Portland, Ore.], the Human Genome Project was just being completed. I realized there was the potential that this could be used to somehow predict which patients might develop metastasis."
Enter his colleague, Dr. Donna G. Albertson, a professor at the UCSF Helen Diller Family Comprehensive Cancer Center. Albertson, one of the pioneers in the development of fluorescent in-situ hybridization (FISH) and its applications in single-copy gene mapping in the human, is working to develop microarray technology for measurement of DNA copy number alterations, and applications of this technology in medical genetics and studies of genomic alterations in cancer.
"We had a project to see if we could find genomic copy number alterations that were biomarkers for metastasis of oral cancer," Albertson says. "If you can use a brush or swab to take a sample of cells from the cancer, you can isolate DNA from that material and carry out the assay for the biomarker. Such a test could be performed during routine office visits prior to surgery, and one could have the answer back quickly—in time to plan surgical treatment. Use of the swab or brush looks very promising."
Grant funding has been used to develop that assay, but there is more work to be done and other problems to solve—and thus, more funding to obtain. Patients who present with no evidence of metastasis in the neck often undergo a preemptive neck surgery, because untreated occult metastasis reduces life expectancy by half.
"Right now, we just throw everything we can at the patient, assuming the patient is going to have the worst possible outcome," says Schmidt. "Many people are receiving neck dissections to remove the lymph nodes, but they are not necessarily benefitting from it. These are significant surgeries. There is morbidity associated with it, including a high rate of stroke compared to other surgeries. In addition, patients have a long recovery time and have to spend extra time in the hospital and delay going back to work, so there are significant downsides to performing neck dissections when it comes to patient productivity and healthcare time and costs."
In a larger confirmation study, Schmidt and Albertson will work to validate genomic markers that will ultimately be used to rule out neck dissection in oral cancer patients with no clinical evidence of neck metastasis and who have tumors containing specific genomic profiles.
Schmidt will conduct the clinical portion of the study through the NYU Bluestone Center for Clinical Research, which he directs, recruiting subjects, enrolling patients and collecting specimens. The samples will then be sent to Albertson's laboratory at UCSF, where her team will process and analyze the samples.
Ultimately, Schmidt and Albertson foresee improved care for oral cancer patients once their newly identified genomic marker is validated.
"It has taken us eight years of research to converge on a genomic marker that could be used to tailor treatment for oral cancer patients," says Schmidt. "We look forward to testing this marker in a clinical study, and this funding will help up us to develop the appropriate laboratory test for such a trial."