Source: www.medscape.com
Author: Fran Lowry

Modest changes in the 2011 National Comprehensive Cancer Network (NCCN) Head and Neck Cancers Guidelines will refine and improve the treatment of these complex, challenging, and relatively rare cancers, according to the panel chief reporting here at the NCCN 16th Annual Conference.

One of the main changes is a new “suggestion” that the workup for cancer of the oropharynx include testing of the tumor for human papillomavirus (HPV).

“Immunohistochemical testing for HPV p16 is recommended,” said David G. Pfister, MD, from Memorial Sloan-Kettering Cancer Center in New York City, and chair of the NCCN Head and Neck Cancers Guidelines Committee. “Although not used to guide treatment, HPV testing is valuable prognostically. The results should not change management decisions,” he emphasized.

HPV-related oropharyngeal cancer appears to be a new and distinct disease entity, and is associated with better survival than non-HPV head and neck cancers, Dr. Pfister noted.

HPV Has a Clear Impact on Prognosis

“Our understanding of the human papillomavirus as a risk factor for head and neck cancer has evolved. Now we see that it has a clear impact on prognosis,” Dr. Pfister said in an interview with Medscape Medical News.

Because of their improved prognosis, these patients might require different treatment, he said. “There is a great interest in better understanding HPV-related cancers and how we treat the disease down the road. Right now we have insufficient data to change how we treat these patients, but clinical trials are being designed to assess the optimal treatment for this group.”

The incidence of HPV-related oropharyngeal cancer has increased noticeably in recent years. In one study, conducted in Sweden, researchers found a progressive proportional increase in HPV detected in biopsies taken to diagnose oropharyngeal cancer, from 23.3% in the 1970s, to 29% in the 1980s, 57% in the 1990s, 68% in 2000 to 2002, 77% in 2003 to 2205, and 93% in 2006 and 2007 (Int J Cancer. 2009:125:362-366).

Jury Still Out on Induction Chemotherapy

Another area of interest in the 2011 guidelines is the issue of induction chemotherapy.”As locoregional control has improved, distant metastases have increased. Induction chemotherapy allows early treatment of microscopic distant disease. Also, as the morbidity of concurrent chemoradiotherapy is increasingly appreciated, induction chemotherapy allows time to optimize the patient’s medical status,” Dr. Pfister said.

Induction chemotherapy is also useful to triage patients to appropriate local treatment. “So what’s not to like?” he asked.

But concerns about induction chemotherapy persist. Although it might decrease distant metastases, overall survival in randomized clinical trials has been disappointing. Plus, induction chemotherapy adds 2 to 4 months to the duration of treatment and might adversely affect compliance.

“The discussion on induction is still highly contentious,” Dr. Pfister noted. “The recommendations are basically similar to the previous year. While we wait for the randomized trials, we are trying to get a sense of the settings that seem to be most likely to lead to benefit.

For more advanced disease, the recommendation for induction chemotherapy is a category 2b; for less advanced disease, it is category 3. “This reflects major disagreement among the panel,” Dr. Pfister said.

The DeCIDE trial, which is currently ongoing, should give some definitive answers about the benefit of induction chemotherapy, he said. DeCIDE is a phase 3 randomized trial of docetaxel-based induction chemotherapy in patients with N2/N3 locally advanced head and neck cancer. The trial’s principal investigator is Everett E. Vokes, MD, from the University of Chicago, Illinois.

Clarification and Simplification a Goal

Some parts of the guidelines dealing with patient management have been streamlined to make them more user friendly, Dr. Pfister said.

Updating the staging to reflect the 7th (2010) edition of the American Joint Committee on Cancer staging manual and revising the order of the primary site algorithms are 2 examples.

In addition, the workup sections in the guidelines have been made more consistent and a Principles of Surgery section has been added.

There is also a suggestion that patients with hypopharynx cancer be evaluated and started on speech therapy as soon as possible. “These patients often can have severe speech impairment, and that investment up front will pay huge dividends down the road,” said Dr. Pfister.

Communicating new information in a timely way is important, but equally important is how that information is packaged, he noted.

“The consumer of the guidelines has to find them easy to understand. Most clinicians in real-life practice will not see the same number and variety of patients that clinicians in academic centers see. They see these cancers once in a while. If you don’t do a good job communicating what the real take-home messages are, they can get buried with the detailed information,” Dr. Pfister explained.

That’s why we spent a lot of time and effort to streamline our recommendations.

“That’s why we spent a lot of time and effort to streamline our recommendations for workup and monitoring patients. We didn’t want to confuse the consumer with stuff that may be based on much less robust evidence or may reflect inconsistencies in how the panel synthesized things,” Dr. Pfister said.

The lack of blockbuster recommendations in the 2011 version of the Head and Neck Cancers Guidelines reflect the nature of the disease, he added. “Head and neck cancer is a little different than other tumors in terms of numbers of randomized trials, which are the ones that really drive our data and recommendations. They are just less frequent than they are for the other more common cancers.”

Emphasis on HPV in Oropharyngeal Cancer

Asked to comment on the update to the guidelines, Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at Ohio State University, Columbus, and a member of the NCCN Head and Neck Cancer Guidelines panel, emphasized the role of HPV in head and neck cancers. The NCCN felt that they had to acknowledge the fact that HPV is the most important factor determining whether patients live or die from their cancer, she told edscape Medical News.

In her experience, patients with oropharyngeal cancer are now demanding to be tested for HPV.

“This patient population is very well informed and tends to be highly educated, so they get on the internet,” she said. “If you are diagnosed with oropharynx cancer and you know that there is one test that can determine whether you have a 90% survival or a 35% survival, would you want the test?”

In addition to determining prognosis, HPV testing will now be used to determine eligibility for clinical trials that are looking for the best way to treat these patients, and for stratification in clinical trials.

Quality-of-life issues that patients with HPV-positive oropharyngeal cancer face once they finish treatment include difficulty swallowing, loss of their sense of taste, and hearing loss. Some patients are left with feeding-tube dependence, needing to be fed through a tube in their stomach. Others have to change their diet, eat very slowly, and eat foods of certain consistencies, and become prone to choking. As a result, they become less likely to go out with friends and be sociable.

“This patient population is young, and now the big research question is whether it is possible for them to be treated with a less toxic therapy and still have the same good outcome,” Dr. Gillison said.

HPV Vaccine for Head and Neck Cancer?

Currently, the HPV vaccine is being marketed for use in young girls to prevent cervical cancer. Dr. Gillison agreed that prevention of head and neck cancer is an equally important reason, if not more so, for vaccination.

In fact, Dr. Gillison told Medscape Medical News that she received research funding from Merck after lobbying them for 4 years to do a vaccine trial to look at whether their vaccine would protect against oral infections that can lead to head and neck cancer. However, Merck later cancelled that trial.

“I worked with some very talented young people, all of whom I knew during my training at Hopkins and Harvard. We worked as collaborators for 3 years and we had the trial designed. We were 6 weeks from opening the trial and enrolling the first subject when Merck cancelled it last February,” she said.

Screening for cervical cancer in the United States is extraordinarily effective, but there is no screening for head and neck cancer caused by HPV. “The vaccine might be even more important in that setting,” she said. However, neither of the manufacturers — Merck and GlaxoSmithKline — are funding trials to see if the HPV vaccine can be used to protect against HPV-positive head and neck cancer.

Dr. Pfister has have disclosed no relevant financial relationships.

National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented March 10, 2011