SCOTTSDALE, ARIZ.-Because the toxicity of concurrent chemoradiation is greater than radiation therapy alone for definitive head and neck cancer treatment, many clinicians have reservations about offering chemoradiotherapy for elderly head and neck cancer patients.
But a new study shows that combining chemotherapy with radiation therapy improves survival rates for those head and neck cancer patients ages 71 to 79 years who have low comorbidity scores and advanced disease stage, with survival rates similar to that of younger patients.
The study, which used data from the National Cancer Data Base (NCDB), suggests elderly patients are being underrepresented in prospective clinical trials that have defined standards of care for head and neck cancer.
"In the era of improved radiation techniques, improved systemic therapy, and better supportive care, we found that chemoradiotherapy does, in fact, improve survival for a large segment of this population," said Sana Karam, MD, PhD, Assistant Professor of Radiation Oncology at the University of Colorado School of Medicine in Aurora, and senior author on the study.
"These findings challenge historical data demonstrating no benefit of chemoradiotherapy for patients older than 70 years," Karam said.
The study was presented at the 2016 Multidisciplinary Head & Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology (ASTRO) and the American Society of Clinical Oncology (ASCO). First author is Arya Amini, MD, a fourth-year resident in the Department of Radiation Oncology at the University of Colorado School of Medicine.
Before the meeting, Karam discussed the study in an online audio preview for the press.
She said current guidelines for treatment of elderly head and neck cancer are based on trials that are included in the MACH-NC meta-analysis of 16,485 patients in 87 randomized trials (Radiotherapy and Oncology 2009;92:4-14).
While the meta-analysis confirmed a benefit of concomitant chemotherapy in locally-advanced head and neck cancer greater than the benefit with induction chemotherapy, it showed those benefits decreasing with age with no overall survival benefit for patients age 71 and above.
"But only 4 percent of the patients in this meta-analysis were age 71 and above, compared with 9 percent of the 2010 U.S. Census," Karam pointed out. "The meta-analysis was underpowered, yet it has set our clinical practice guidelines."
The researchers examined records from the NCDB for patients older than between 1998 and 2011. From 1998-2011, 23 percent of patients in the database were over age 70. Cases for these elderly patients were stratified by whether or not they received chemotherapy concurrent with radiotherapy.
All patients received definitive radiotherapy (66.0-81.6 Gy in 1.2-2.0 Gy fractions). Concurrent chemoradiation was defined as beginning a course of chemotherapy 14 days before or after the start of radiotherapy.
Karam said 68 percent of the patients received radiotherapy alone, and 32 percent received chemoradiotherapy.
Five-Year Survival Improved If Comorbidity Low
The study showed that five-year survival in head and neck cancer patients ages 71 to 79 years was 30.3 percent with concomitant chemotherapy and radiotherapy, versus 15.2 percent for radiotherapy alone.
"Our results showed clearly a significant overall survival benefit with the addition of chemotherapy to radiation therapy," Karam said.
Chemoradiotherapy was associated with improved survival when patients had comorbidity scores of zero or one, and advanced disease stage.
The researchers also found an overall survival benefit of chemoradiotherapy for patients treated with intensity modulated radiotherapy.
But patients who did not see an overall survival benefit from chemoradiotherapy tended to be ages 79 or older, had a comorbidity score of two or greater, or presented with T-I or T-II disease.
The trend toward worse overall survival for patients with multiple comorbidities was only marginally significant, Karam added.
"These findings may aid clinicians in discussing treatment options with their elderly head and neck cancer patients, and they could guide future prospective trials to confirm the benefit of multimodality treatment in elderly patients, not only for head and neck cancer, but for other cancer sites as well," Karam said.
Comorbidity, Not Age
In an online audio preview of the meeting for the press, moderator Christine G. Gourin, MD, Associate Professor of Narratology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, said, "These data show us that the key factor is not age, but comorbidity. As we age, we collect comorbidities, and that's what is probably more significant."
Gourin commented on the MACH-NC meta-analysis, "that we all know is used by our colleagues in Europe to support not using chemotherapy in elderly patients.
She said her own research using the SEER (Surveillance, Epidemiology and End Results) Medicare database found survival results can differ by tumor site-chemoradiation is superior to radiation in oropharyngeal cancer in terms of survival, she said; but in larynx cancer, overall survival is actually worse for chemoradiation.
Those differences were due to late toxicity of treatment, aspiration pneumonia, and dyspepsia.
Karam said her research also found differences between those two tumor sites, but that chemoradiotherapy improved overall survival for both subsets nonetheless.
"There are many differences in the data sets between the NCDB and SEER Medicare databases, including the historic staging analysis. The patient populations are a little different; our reviewers picked up on that when we were submitting the manuscript.
"Unfortunately, we don't have a clear cut variable for toxicity, but we did look at time to completion of radiotherapy. We found that patients who got concurrent chemoradiation had a longer time to completion of radiotherapy, suggesting perhaps more treatment breaks.
"But even after controlling for treatment breaks, we still saw an overall survival advantage regardless of the subset, except for the very elderly and those with multiple comorbidities," Karam said.