Speak, Hear, Swallow, Listen

Multidisciplinary teams of physicians and scientists balance the need to battle head and neck cancer aggressively against the treatments’ often-dramatic impact on quality of life.

by Alicia Di Rado

When Blair Franks recently took his first bite into a hamburger and gulped down the patty, the ketchup and even the bun, it was a major victory. “It’s a real joy to be able to taste food again,” he says. Franks, age 56, has survived throat cancer, one of myriad malignancies known collectively as head and neck cancer. These tumors arise in the mouth, throat, sinuses, nasal cavity, voice box or salivary glands, or even skin surrounding the mouth. Those in the mouth are often called oral cancers.

or those who have undergone treatment for these cancers, eating is just one of the everyday parts of life that may go awry after therapy. Surgery can interfere with chewing, while radiation can stunt the glands’ ability to make saliva, as well as confuse the taste buds. Chemotherapy can sap the appetite. Even swallowing and speaking become a challenge because surgery and radiation may damage vital throat muscles.

Some difficulties are unavoidable, admit surgeons at the Keck School of Medicine of USC. But they can be minimized if treatment is done with care; and sometimes, physicians can offer treatment options that cause fewer side effects. Keck School cancer specialists believe in a balance: They weigh the need to battle head and neck cancer aggressively against the treatments’ often-dramatic impact on quality of life.

That concern for patients translates to the laboratory, where Keck School scientists look for ways to reduce side effects while packing the most effective punch into chemotherapy and radiation. It shows in support groups that provide hope to survivors. And through population studies underway at USC, the caring shows in quality-of-life research that seeks eventually to improve patients’ outcomes—and perhaps help prevent the cancers in the first place.

Head and neck cancers do not attract as much public attention as some other cancers, but the diseases do have the full attention of USC scientists: They are uniting experts who span a spectrum of disciplines in a major thrust to advance desperately needed genetic, preventive, therapeutic and rehabilitative research.

“Some of the most basic functions we count on, the things that make us human, can be taken away by these tumors and the treatments we currently have for them,” says Uttam K. Sinha, M.D., chief and program director in the Department of Otolaryngology/Head and Neck Surgery at the Keck School, who specializes in head and neck cancer surgery and complex reconstruction. “We would like to significantly improve the survival rate for these cancers, and through rehabilitation, significantly enhance the quality of life for survivors. At the same time, we want to reduce the incidences of head and neck cancers in the first place.”

Group think

Two dozen men and women sit side-by-side in a circle, chatting and hugging; many have scars that are familiar to head and neck cancer survivors.

Scars stand as visible reminders of the cancer experience. Unfortunately, disfigurement or an altered voice may deter survivors from reuniting with friends, seeking support from others or even just going out in public. After surgery, head and neck cancer patients may withdraw, become isolated and fall into depression.

But at the Keck School’s Head and Neck Surgery Clinic located in the Healthcare Consultation Center II, a new support group brings survivors into the open and provides an outlet for those with a cancer once hidden in shadows.

Only a few centers across the country offer support groups for people with head and neck cancers; most are at academic medical centers such as USC. Yet experts estimate that about 60,000 Americans each year are diagnosed with head and neck cancers—comprising about 5 percent of all cancer cases. Internationally, these cancers hit 900,000 people each year, making them, collectively, the world’s sixth most common cancer.

“I operate on about 20 patients with these cancers every month,” Sinha says. “What is important for these patients is to receive not only treatments that have the greatest chance of success, but also those that maintain their quality of life. Having the support of other patients, as well as getting regular information from health professionals, is critical to upholding that quality of life.”

Sinha attends the support group, which was created in August 2005 by Stanley “Zack” Cherry, a licensed psychotherapist and head and neck cancer patient, and USC speech pathologist Brenda Villegas.

At the meetings, survivors share similar stories: They discover they cannot tolerate the taste of their favorite food. Or perhaps nothing smells as it used to. Some struggle to open their jaws to eat.

As Sinha explains, when cancer surgeons and oncologists see evidence that cancer has spread beyond the original tumor, they recommend radiation or chemotherapy (or both) in addition to surgery. However, these therapies can damage salivary glands and surrounding tissue.

As a result, saliva can be a rare commodity for those with head and neck cancer, resulting in dry mouth, cavities and more. But in the support group, survivors talk about their “spit troubles” with a sense of humor and share solutions.

Jim Franchino, a tongue cancer survivor, attended a recent meeting. “Six months ago was the day I had surgery and the day we got rid of our cancer,” he announces, his wife beside him. In the meantime, he has undergone reconstruction of his tongue, coaches his son’s soccer team, and has begun therapy to improve his swallowing.

“To me, it’s about having the right frame of mind—thinking positive,” Franchino says. “It’s about doing what you can—and a little bit more.”

Stop the spread

Fortunately, most head and neck cancers are highly curable when caught early.

Once they spread, though, the chance of survival drops. So Keck School researchers are studying what makes cancer spread—and how to stop it.

Sinha oversees the translational laboratory research efforts and works closely with Rizwan Masood, Ph.D., assistant professor of research in otolaryngology at the Keck School. “Surgery and other treatments for head and neck cancers are improving the quality of life for patients, but survival rates aren’t improving. In fact, they haven’t changed much in 20 years,” Sinha says.

Squamous cell carcinomas, which comprise most of the cancers of the head and neck, typically arise as one primary tumor that, if left untreated, metastasizes to the lymph nodes of the neck. But for some reason, some of the carcinomas metastasize early in their growth, when they still appear small, while others can grow quite large before metastasizing.

At the same time, some carcinoma cells that appear quite abnormal under a microscope are slow to spread, while others that look more like normal cells are quick to spread, Masood says.

Sinha and Masood theorize that rather than a tumor’s size or grade, perhaps its genetics plays a major part in the cancer’s metastasis.

Using tumor and lymph node samples from patients, the researchers are studying genes found in both the cancer cells and normal cells. They have several suspects and hope to uncover other candidate genes using microarray technology, which can comb through about 46,000 genes at a time. The duo want to determine if expression of any of the genes is linked to cancer spread to the lymph nodes.

Ultimately, if the researchers can figure out the key genetic players in the cancers’ spread, they may develop therapies against them. They may also be able to use the genes as markers to detect the spread of head and neck cancer earlier—and treat it more successfully.

In addition to metastasis, Sinha explains that physicians often worry that cancerous head and neck tumors will come back even after surgery and radiation. And they have good reason: The cancer returns in its original site in the majority of patients.

“When these cancers come back, they are very aggressive,” Sinha says. “These are cancers that have survived radiation.”

Sinha and his colleagues are looking for the genes linked to aggressiveness. If they can identify the genes and inhibit them, they may be able to deter high-risk cancers from returning.

Life after cancer

The researchers also team with fellow scientists and health professionals on studies to improve the quality of life of head and neck cancer patients.

For one, speech pathologist Villegas and Sinha are evaluating a U.S. Food and Drug Administration-approved product called VitalStim, which uses electrodes to stimulate the swallowing muscles of the larynx and the base of the tongue. Villegas places the electrodes on the front part of the patient’s neck and electrical signals contract muscles, which facilitates swallowing.

Because radiation hurts the healthy functioning of the muscle tissue, the researchers believe that strengthening muscles using VitalStim before and during radiotherapy can help protect swallowing function. Currently, USC is the only site in the nation with a clinical protocol evaluating VitalStim for head and neck cancer patients. VitalStim is funding the study.

In another study funded by the department, the researchers seek to determine if inhibiting the function of a key gene can make head and neck cancer cells more vulnerable to radiation, which would allow them to use lower doses of radiation in therapy, reducing the lasting side effects of treatment.

But the laboratory and clinic are not the only areas where researchers are attacking head and neck cancers.

pidemiologist Lihua Liu, Ph.D., research scientist in the Department of Preventive Medicine at the Keck School, is sifting through population-based cancer registry data on head and neck cancer cases to examine incidence patterns by demographic characteristics, tumor location and cell types.

Los Angeles County and other areas throughout the nation track cancer diagnoses and deaths, Liu explains. USC preventive medicine researchers oversee local data through the Los Angeles County Cancer Surveillance Program. “The Cancer Surveillance Program is a centralized, population-based database that helps identify risk patterns and generate hypotheses regarding the causes of these diseases,” Liu says. In addition, she says, observations obtained at the population level help guide the focus of basic science research for maximum efficiency.

With support from the National Cancer Institute (NCI) and its Surveillance Epidemiology and End Results program, Liu and Sinha are conducting a survey of Los Angeles County patients diagnosed with tongue cancer in the 12 months after March 2005. Researchers at the Detroit Cancer Registry are collaborating by following cases in their area.

The epidemiologists are surveying the cancer patients to ask about lifestyle factors, such as smoking, that might have raised cancer risk. They also seek to find out how quality of life after cancer may be associated with the type of treatment patients received.

“Each surgeon has a personal way to treat tongue cancer,” Sinha explains. “They lack specific, researched guidelines on the most effective treatments for various subgroups of tongue cancer patients, and often rely on instinct or experience when recommending a therapy plan.” By studying outcomes, he says, researchers may begin to better understand the effects of various surgical, radiation and chemotherapy treatments.

Liu is also conducting an NCI-supported study to examine how carefully pathologists describe characteristics of tongue cancer tumors in pathology reports, something that can help determine the course of patients’ treatments.

It is all part of a drive to push for more effective care for head and neck cancer patients while maintaining their quality of life. “Head and neck cancers are under-investigated, yet they take the lives of so many and leave a lasting effect on basic human functions,” says Sinha. “Our goal is to establish an international-level program here to change that.”

 

WORD OF MOUTH

Before USC School of Dentistry faculty and students arrived, several dozen people had already lined up for their free oral cancer screening. By the time the four-hour effort was done, more than 550 people had been checked for the disease.

Rita Potter, who had her first oral cancer screening that day, talked her friend into having one, too. “It was easy,” she says. “It’s a much needed service in this community. A lot of people don’t go to doctors.”

Tobacco use and excessive use of alcohol are the biggest known risk factors for oral cancer, while sunshine increases the risk of lip cancer.

One of every four oral cancer patients do not smoke or drink, though studies suggest that certain strains of human papilloma virus may account for the recent increase of cases seen in young, non-smoking victims of cancers of the mouth and pharynx who do not fall into typical high-risk groups. Even so, for those with or without risk factors, “it is important that we get the word out that early detection can save lives,” says Mahvash Navazesh, D.M.D., chair of the division of diagnostic sciences at the dentistry school. “In its early stages, oral cancer may not have symptoms that are painful or obvious to the patient.”

Navazesh, who organized USC’s participation in the Oral Cancer Foundation-sponsored event, says an annual screening by a qualified professional, such as a physician or dentist, is essential to catching the disease early.

The School of Dentistry also teamed with the USC School of Pharmacy to provide about 60 free screenings for USC faculty, staff and students. Dentistry faculty also hosted lectures and training sessions on early detection.

The screening efforts were so successful that the Oral Cancer Foundation will expand them to other cities, and USC faculty members hope to increase local participation even further in 2006.

For more information about oral cancer, including risk factors, symptoms and treatments, visit www.oralcancerfoundation.org.