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Systemic therapy used frequently in elderly patients with head, neck cancer
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The use of systemic therapy with definitive radiotherapy is common among elderly patients with head and neck cancer and is associated with improved OS, according to a National Cancer Data Base analysis.
These data appear to diverge from available prospective evidence about the benefit of systemic therapy in older patients, according to the researchers.
“Because of surgical morbidity, locally advanced tumors of the pharynx and larynx are commonly treated with definitive radiotherapy with or without sensitizing systemic therapy,” Matthew C. Ward, MD, resident in the department of radiation oncology at the Taussig Cancer Institute of Cleveland Clinic, and colleagues wrote. “These regimens can be physically challenging even for fit patients. Elderly patients are at an increased risk for acute toxicity with the addition of systemic therapy to definitive radiotherapy.”
A previous meta-analysis failed to show a survival benefit from concurrent chemotherapy in patients aged older than 70 years. However, these studies were performed before recent advances in treatment and supportive care, which limits their application to modern patients, the researchers wrote.
Because a previous analysis of SEER data showed systemic therapy increased toxicity without a survival improvement in older patients, Ward and colleagues analyzed the National Cancer Data Base (NCDB) to evaluate practice patterns and outcomes associated with the use of systemic therapy with definitive radiotherapy in 30,399 patients with stage III to IVB squamous cell carcinoma of the nasopharynx, oropharynx, larynx or hypopharynx treated between 2004 and 2012. Of these patients, 4,165 were aged older than 70 years.
Median follow-up was 35 months (range, 0-132) for the entire cohort and 26 months (range, 1.8-125) for elderly patients.
Overall, 80.4% (n = 3,347) of elderly patients were treated with systemic therapy. Ninety percent of patients aged 70 years or younger received systemic therapy; however, that rate decreased to 79% for patients aged 71 to 80 years and to 41% for patients aged 90 years.
The percentage of elderly patients who received systemic therapy increased from 64% in 2004 to 86% in 2012. Single-agent systemic therapy use increased from 23% to 68%, whereas multi-agent use decreased from 33% to 14%.
Multivariate logistic regression analysis showed that older age, female sex, black race, laryngeal primaries, lower radiotherapy doses and conventional radiotherapy were associated with less frequent administration of systemic therapy.
Elderly patients treated with systemic therapy achieved longer median survival than those treated without systemic therapy (43.7 months vs. 24.5 months; P < .0001).
After the researchers accounted for radiotherapy treatment duration and the inverse probability–weighted propensity score, the omission of systemic therapy increased risk for mortality among elderly patients (HR = 1.46; 95% CI, 1.31-1.62).
Overall, elderly patients demonstrated a 3-year OS rate of 51.6% (95% CI, 50-53.2).
The absolute difference in 3-year OS among all patients remained consistent throughout each age group and ranged from 8.9% to 14.5%. The researchers were unable to identify an age threshold above which systemic therapy was no longer associated with improve survival.
The researchers recommended that these results should be validated with additional population-based data sets. They also recommended that prospective trials specifically investigate the role of systemic therapy in elderly patients.
“Elderly patients were underrepresented in previous clinical trials, and the frequency of treating elderly oropharynx and larynx patients with definitive radiotherapy and chemoradiotherapy is increasing,” Ward and colleagues wrote. “A threshold age eliminating the need for systemic therapy could not be identified, and the decision to administer systemic therapy should be patient specific.” – by Kristie L. Kahl
Disclosure: The researchers reported no relevant financial disclosures.
Perspective
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Ward and colleagues published data from National Cancer Data Base examining contemporary trends in curative intent treatment approaches for patients with head and neck cancer who are 71 years of age or older. Their results demonstrate a temporal increase in the use of systemic therapy among older patients and, more importantly, an improvement in OS among patients receiving chemotherapy compared with those who did not, controlling for potential confounders. The researchers were unable to identify an age threshold beyond which there was no apparent benefit to systemic chemotherapy.
These findings address a clinical dilemma that will be increasingly more common as our population ages. The challenge of balancing acute treatment related toxicities, optimizing oncologic outcomes, and considering the cost or value of therapy among older patients is all too familiar to medical oncologists.
In the MACH-NC meta-analysis, there was no observed benefit to the addition of chemotherapy among patients aged older than 71 years. But as the researchers point out, this older dataset may have limited applicability today, since our radiation techniques, systemic agents and supportive care have evolved significantly in the interim.
The researchers appropriately describe the caveats of observations generated from nonrandomized registry data, underscoring the need for generating prospective data in this growing patient population. Overall, this large dataset supports the use of physiologic — rather than chronologic — age and careful patient selection in therapeutic decision-making for elderly patients.
Pignon JP, et al. Radiother Oncol. 2009;doi:10.1016/j.radonc.2009.04.014.
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