Chemoradiation Improves OS for Elderly Patients With Head and Neck Cancers

Sana Karam, MD, PhD

Concurrent chemoradiation significantly improved overall survival (OS) compared with radiation therapy alone for elderly patients with locally advanced head and neck cancers, according to a large analysis of the National Cancer Data Base (NCDB) presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

In the study, the 5-year OS rate was 30.3% with chemoradiation versus 15.2% with radiation alone for patients >70 years (HR, 0.59; 95% CI, 0.55-0.63, P <.001). In a propensity score matching analysis, the 5-year OS rate was 26.4% for chemoradiation versus 18.1% with radiation alone (HR, 0.73; 95% CI, 0.66-0.80; P <.001).

“The addition of chemotherapy can improve survival dramatically, even for those who are elderly,” senior study author Sana Karam, MD, PhD, an assistant professor of radiation oncology at the University of Colorado School of Medicine in Aurora, Colorado, said during a presentation of the data. “Our results clearly show that there is a significant overall survival benefit with the addition of concurrent chemoradiation.”

In the study, data were examined from 5265 patients treated with definitive radiation therapy alone (n = 3604) or in combination with chemotherapy (n = 1661). Radiation was delivered in 1.2 to 2.0 Gy fractions, for a total of 66 to 81.6 Gy. Patients were eligible for the chemoradiation arm if they had started chemotherapy within 14 days of receiving radiation. The NCDB did not provide the type of chemotherapy administered.

All patients examined in the study had stage III and IV tumors of the oropharynx, larynx, and hypopharynx. All tumors were either node positive T1-2 or T3-4, N0-3. The median age in the chemoradiation arm was 75 years (range, 71-90). In the radiation alone arm, the median age was 77 years (range, 71-90).

OS was assessed using univariate and multivariate cox regression analysis. Additionally, propensity score matching and recursive partitioning analyses were conducted on the data to rule out any confounding factors, such as age, Charlson comorbidity score, T-stage, and N-stage.

In the recursive partitioning analyses, improvement in OS was associated with patient age of ≤81 years, a low comorbidity (CD) score, and either T1-2/N2-3 or T3-4/N0-3 disease. “The patients who benefit the most are those younger than age 80 with early T stage but advanced nodal or advanced T stage and any nodal and they have to be healthy,” said Karam.

According to the abstract from the meeting, in a multivariate subgroup analysis, those aged <79 years experienced a 20% reduction in the risk of death with chemoradiation versus radiation alone (HR, 0.80; P = .001). Those below age 79 with a CD score of 0-1 had a 16% reduction in risk (HR, 0.84; P = .002), and those with stage III/IV disease had a 23% reduction in the risk of death with chemoradiation (HR, 0.77; P <.001).

OS was not improved with the addition of chemotherapy for those over the age of 81. Additionally, OS was not improved in patients aged 71 to 80 with T1-2/N1 tumors and a CD score of 0-1 and those aged 71 to 80 with T3-4/N1+ tumors with a CD score of more than CD1. Patients aged ≥79 years with a CD score of ≥2 experienced a trend toward worse OS when treated with chemoradiation versus radiation alone (HR, 2.36; P = .923).

The HR was 0.93 for those aged ≥79 years treated with chemoradiation versus radiation alone (P = .369). For those with a comorbidity score of ≥2, the HR was 1.00 between the two treatments (P = .992). A benefit was also not experienced by patients with stage I/II tumors (HR, 1.09; P = .448).

Outside of patient characteristics, those treated with intensity modulated radiation therapy experienced an improvement in OS (HR, 0.76; P = .002). However, three-dimensional radiation was not associated with an OS benefit (HR, 1.02; P = .923).

The addition of chemotherapy to radiation is associated with increased toxicity; however, as radiation, chemotherapy, and supportive care techniques have improved, these adverse events have become more manageable. Unfortunately, this aspect could not be analyzed, as the NCDB does not provide clear-cut data for toxicity, Karam said.

“We found that patients who did get concurrent chemoradiation had a longer time to completion of radiation therapy, suggesting more treatment breaks. We couldn't look at aspiration pneumonia,” she said. “Despite treatment breaks, even after controlling for that, we found an overall survival advantage across subsites.”

Prior to the database analysis, studies had suggested that patients >70 years of age had worse survival outcomes with chemoradiation. In general, however, this elderly population represented just 4% of patients analyzed, which underpowered the data. Findings from the database study could be instrumental in changing the standard of care for elderly patients, specifically outside of the United States.

“The main takeaway is that you should not just look at the age of the patient,” said Karam. “In this day and age, when patients are healthier and living longer, give them the benefit of curative intent with the chemo.”

Amini A, Jones B, McDermott J, et al. Does Age Matter? Survival Outcomes with the Addition of Concurrent Chemotherapy for Elderly Head and Neck Cancer Patients Undergoing Definitive Radiation Using the National Cancer Data Base. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 100.

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