Combining Radiation, Surgery Increases Head and Neck Cancer Survival

A large-scale study showing improved survival rates for patients with node-positive head or neck cancer who undergo post-surgical radiation therapy could have a particularly significant impact on patients classified as N1, researchers said.

Johnny Kao, M.D. Mount Sinai School of Medicine

"Radiation therapy increased the likelihood of survival by 22 percent in the N1 group. That is the big impact here," said Johnny Kao, M.D., the study's lead author and an assistant professor of radiation oncology at the Mount Sinai School of Medicine in New York. "Maybe historically we would think many of these patients wouldn't need radiation, but this study provides evidence that radiation should be considered after surgery for most head and neck cancer patients with positive lymph nodes. I'd use this information to consider radiation more strongly for those with N1 disease."

The study was published in the June 2008 issue of the International Journal of Radiation Oncology * Biology * Physics. Researchers analyzed 5,297 patients at least 21 years old, with a median age of 59, all of whom were diagnosed with node-positive head and neck squamous cell carcinoma and were treated with surgery with or without adjuvant radiation therapy. The patients were all treated between 1998 and 2001.

Few Studies Have Examined Survival

While radiation therapy is frequently used in combination with surgery to treat some head and neck cancers—as data have shown radiation therapy improves locoregional control—very few studies have been conducted to determine the impact on survival, researchers said.

"We were surprised that, for a treatment used so widely, there was not much research into survival rates," said Dr. Kao. "The fact that radiation is increasing survival for these people was always suspected, but not really proven. This study was a way to get an answer to the question, 'Is giving radiation—a very complex treatment—a worthwhile endeavor?'"

To answer that question, Dr. Kao and colleagues turned to the Surveillance, Epidemiology, and End Results (SEER) database. Collecting information from 17 cancer registries covering 26 percent of the population in the U.S., SEER is said to be representative of the country.

While the database originally included more than 40,000 patients, most were excluded from the study for a variety of reasons. Those rejected included patients with nasopharyngeal cancer, because the primary locoregional treatment is radiation rather than surgery, and those with salivary gland tumors, because the majority of these are likely nodal metastases from squamous cell carcinoma of the skin. Others excluded were patients with metastatic disease of unknown stage, in situ carcinoma, no pathologic confirmation, preoperative or intraoperative radiotherapy and unknown administration of radiotherapy.

Patients were considered to have had radiotherapy if they received external beam radiation, brachytherapy or both, said researchers. Those patients who received radioisotopes only were not considered to have received adjuvant radiation.

"Once we had the database narrowed down, we looked at the different subgroups, N1 to N3, by how advanced their lymph nodes were," Dr. Kao said. "In all of these groups, radiation did increase survival."

Radiation Typically Recommended for only N2 and N3 Patients

Reprinted from the International Journal of Radiation Oncology * Biology * Physics 71:362-370, Kao, et. al., "Adjuvant Radiotherapy and Survival for Patients With Node-Positive Head and Neck Cancer: An Analysis by Primary Site and Nodal Stage," © 2008, with permission from Elsevier.

Patients were surveyed approximately 4.4 years after treatment. Researchers found that adding radiation to surgery improved the patients' survival rate by about 25 percent in all nodal stages, including N1 stage patients. Radiation is more often recommended only for N2 and N3 stage patients.

"I think the impact on decision making will be on the N1 category of patients," said Shiv Khandelwal, M.D., an associate professor in the Department of Radiation Oncology at the University of Virginia in Charlottesville, who was not involved in the study. "We can't tell by looking at this database why some patients got radiation and some didn't, so we could be missing something that could affect the outcomes here. Either way, there are some who tend to avoid doing radiation in N1 cases and this study tells us we need to look harder at radiating those patients."

Those with N1 nodes constitute a very small percentage of patients, Dr. Khandelwal noted. "That's why it's difficult to do a controlled, complete study," he said. "This is an interesting one and the authors justifiably point out some of its weaknesses. However, none of the studies out there had shown that we improve survival rates with radiation, until this one. I think it's an important study."

Drs. Kao and Khandelwal said the side effects of treating head and neck cancer with radiation, particularly when using intensity-modulated radiation therapy (IMRT), have been greatly reduced over the years. However, the side effects can still be significant in some cases—even with this study, radiation oncologists will have to weigh the risks, researchers said.

Approximately 6 percent of all U.S. cancers are classified as head and neck, according to the SEER database. About 85 percent of these patients receive radiation therapy, said Dr. Kao. While this study is not definitive, by any means, it does answer the question it set out to answer, he said.

"It shows that, in a very large population of patients, radiation can improve survival," Dr. Kao said. "What is reassuring is that we aren't just giving it, but it is helping people."