CHICAGO — Chemoradiation therapy (CRT) for head and neck cancer is overused at some centers in patients with early-stage laryngeal cancer, and more care should be taken not to overtreat patients with therapy that can have toxic effects, said invited lecturer Jonas Johnson, MD, at the Annual Meeting of the Triological Society, held here on April 29 as part of the Combined Otolaryngology Spring Meetings.
There has been such a rush to use the therapy that Dr. Johnson, professor and chair of otolaryngology at the University of Pittsburgh School of Medicine, called the last decade “the era of chemoradiation.”
Findings from 1991’s landmark Department of Veterans Affairs Laryngeal Cancer Study Group (N Engl J Med. 324(24):1685-1690) showed that it is possible in patients with limited laryngeal cancer to save 60 percent of the organs without surgery using CRT, but such findings may have given rise to excessive use, Dr. Johnson said.
“There’s a great tendency among doctors to generalize,” Dr. Johnson said. “I think perhaps it’s because they don’t always read the fine print. In some centers, I find, (they) are offering CRT to most patients with head and neck cancer. That’s wrong. Chemoradiation is too much therapy for early-stage disease. And, quite frankly, … T4 tumors were largely excluded in the big prospective randomized trials. You understand that when an investigator puts together a trial he tries not to hurt people…. They figured it wouldn’t work. And by the way, it doesn’t.”
Toxicities
Dr. Johnson said he does believe that CRT should be the standard of care in T3 laryngeal cancer. But he pointed to a review of the data in three major radiation therapy oncology group trials on chemoradiation (J Clin Oncol. 2008;26(21):3582-3589), which found that in the 230 assessable patients out of the 479 in the trial, “severe toxicities” were found in 43 percent of them.
“So what that means is that in this exuberant chase to preserve function, we’re failing,” Dr. Johnson said. “We fail because some patients are not cured. But we also fail because this treatment is in fact very toxic. It’s true that a great deal of effort is being made to find ways to avoid or prevent these toxicities, (but) they remain an issue.”
In early laryngeal cancer cases with T1 and T2 lesions, he said, “we need to avoid overtreatment.” Dr. Johnson said such patients don’t need two treatment modalities. “Either take it out or you irradiate it,” he said. “And maybe you can give it chemo…. Cancer control is excellent. These patients do great. They have good voice, they swallow well, and they rarely have excessive toxicity from treatment.”
The Case for Chemo
Dr. Johnson said data on using CRT in patients with T1 and T2 disease are “interesting but not convincing, in my mind.”
In a study of results for 519 patients by the University of Florida’s William Mendenhall, MD, in 2001, which Dr. Johnson said is still the best available data on the subject, T1 cancer cases had a 98 percent ultimate control rate with irradiation, and T2 cases had a 96 percent control rate (J Clin Oncol. 2001;19(20):4029-4036).
But only 82 percent of T2a cases and 76 percent of T2b cases preserved their larynxes after five years, Dr. Johnson noted.
“It means something between 18 and 24 percent of the larynxes were taken out … to get to this ultimate control rate,” Dr. Johnson said. “If you have a T2 patient, and you’re going to send them for irradiation, he’d better understand that there is some significant chance he will end up with a laryngectomy.”
Settling on a therapy for T2 laryngeal cancer is “a tough one,” he said. “Do you want to have a procedure that will probably leave you with anterior web and some changes in your voice and almost certain tumor control, or would you rather take a chance and go with irradiation?” he said.
Dr. Johnson discussed data from Pittsburgh showing how cancer recurrence was related to the number of nodes. Patients with four or five nodes were at great risk, although cancer can recur even with none at all.
“So the question remains: How many nodes represents indication for adjuvant therapy?” he said. “In Pittsburgh, I can tell you, we use three or more. I know others use other numbers. Here’s the problem: How much risk are you willing to accept before you add irradiation and chemotherapy? And, of course, when you add therapy you add toxicity.”
Decreased Survival Rates
The difficulties with laryngeal cancer are highlighted in stark fashion by the data from the Surveillance, Epidemiology, and End Results (SEER) database.
“Of the 24 cancers that are monitored by the SEER database, the only cancer group to experience a decline in cure is those with laryngeal cancer,” Dr. Johnson said. “So what’s wrong? How does that happen? Well, ladies and gentlemen, our therapies are not very effective. We’re uncertain about which therapy is best. And the toxicities of our treatment are not always acceptable. Pretty straightforward.”
Lack of Evidence
Making matters more difficult, there is no good evidence to guide doctors on surgery, he said.
“The best data, the Level I evidence, is all about irradiation and chemotherapy,” he said. “There is no Level I evidence in surgery. What are we going to do about it? Well, we need articulate leadership. We need Level I evidence.”
He complimented a plan recently discussed by Randal Weber, MD, FACS, of the M.D. Anderson Cancer Center in Houston, to formally develop clinical investigators. But that alone won’t be enough, Dr. Johnson said.
“I think it’s great—I think the major medical centers should do that,” he said. “But I think it’s too late. If we wait until Randy Weber makes clinical investigators for us, we will not know how to do the procedures that need to be done to save people from chemoradiation. We have to collaborate today. We have to talk about it, figure it out, and do it.”
Dr. Mendenhall, a professor at the University of Florida College of Medicine in Gainesville who specializes in head and neck cancer, recently wrote an editorial for Cancer on the same topic.
“I agree completely with Dr. Johnson,” he said. “Organ preservation, for advanced laryngeal and hypopharyngeal cancer in particular, is being overused with, in cases of high-volume cancers, resultant poor cure rates and bad functional outcomes,” he said. “There are other outcomes of importance in addition to overall survival.”