SCOTTSDALE, ARIZ. (FRONTLINE MEDICAL NEWS) Oncologists should consider not only age, but also comorbidities and disease extent when deciding whether to offer concurrent chemoradiation to older adults with locally advanced head and neck cancer, suggests a cohort study using data from the National Cancer Data Base.

The study of 4,042 patients aged 71 years or older found that adding chemotherapy to radiation therapy (RT) reduced the risk of death by at least one-fourth overall, according to results reported in a poster session and related press briefing at the Multidisciplinary Head and Neck Cancer Symposium.

In further analysis, benefit was limited to those who were aged 81 years or younger with low comorbidity and more advanced disease.

“Does age matter? The answer to that question is yes and no,” commented senior author Dr. Sana Karam of the University of Colorado at Denver, Aurora. “The physician needs to use his or her clinical judgment.”

“Don’t just look at the age of the patient,” she advised. “In this day and age where patients are healthier and living longer, give them the benefit of curative intent with the addition of chemo. Assess the patient clinically. If they are not healthy; their comorbidity score, KPS, ECOG, whatever you are using in your practice, is poor; or if they have earlier-stage disease, early T, no bulky nodes, then it’s okay to just give RT alone. But the addition of chemotherapy can improve survival dramatically” for other patients.

The new findings are likely to temper those of the pivotal MACH-NC (Meta-Analysis of Chemotherapy in Head and Neck Cancers). That analysis found little to no survival benefit from adding concurrent chemotherapy to radiation therapy in patients aged 71 years or older, but only 4% of the included patients fell into this age-group.

“So it was very underpowered, but yet, it has set our clinical practice guidelines,” Dr. Karam noted at the meeting cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology. “And we know from many of our clinical trials this is a patient population that’s generally heavily underrepresented on clinical trials.”

Press briefing moderator Dr. Christine Gourin of Johns Hopkins University, Baltimore, commented, “Your data are very important because we all know the MACH-NC meta-analysis is used by our colleagues in Europe to support not using chemotherapy in elderly patients,” she added. “And in fact your data suggest it’s really not age, but comorbidity” that should be considered.

Dr. Gourin and colleagues performed a similar analysis, but instead used the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Their results suggested that the impact of adding concurrent chemotherapy to radiation depended on the site: Patients with oropharynx cancer benefited, but those with larynx cancer actually fared worse because of late toxicity.

“Did you find any difference when you drilled down between larynx and hypopharynx and oropharynx?” she asked.

“We found that the overall survival benefit was regardless of the subsite,” Dr. Karam replied, noting that the patient populations in the two cohorts differed somewhat. “Unfortunately, we don’t have clear-cut variables for toxicity, but what we did look at is time to completion of RT, and we found that patients who did get concurrent chemoradiation had a longer time to completion of RT, suggesting perhaps more treatment breaks maybe. … But still, despite the treatment breaks, even after controlling for that, we still found an overall survival advantage, regardless of the subsite.”

At her institution, patients are already being treated with a tailored approach, Dr. Gourin commented. “We have young patients who are so sick that they are not great candidates for chemotherapy, and then we have old patients who are healthier than I am who are great candidates for chemotherapy. So I would say that we have been doing what Dr. Karam suggests, which is looking at age not as a number, but rather comorbidity and the overall functional status of the patient.”

“That’s why I really liked your study: It’s great to see that in writing, because I know that colleagues in other countries that I talk to about health care reform and how to cut costs, they actually use the MACH-NC to define who gets treated and who doesn’t,” she added.

For their analysis, Dr. Karam and colleagues identified patients in the database given a diagnosis of locally advanced cancer of the oropharynx, larynx, or hypopharynx between 1998 and 2011 who were treated with radiation therapy.

Overall, 53% received chemotherapy concurrently, defined as starting it in the 14 days before or 14 days after initiation of the radiation therapy, according to Dr. Karam.

The specific agents given could not be ascertained, she acknowledged. “Unfortunately, the NCDB does not give us data in regard to the type of chemotherapy, and they only started collecting cetuximab data in 2013.”

With a median follow-up of 19 months, the unadjusted 5-year overall survival rate was 15.2% with radiation therapy alone and 30.3% with concurrent chemoradiation (hazard ratio, 0.59; P less than .001). Benefit fell only slightly after multivariate adjustment (HR, 0.63; P less than .001).

Findings were similar in a propensity-matched analysis, which showed an 18.1% survival with radiation therapy alone versus 26.4% with concurrent chemoradiation (HR, 0.73; P less than .001).

On recursive partitioning analysis, chemoradiation was associated with better survival among patients 81 years of age or younger who had low comorbidity based on Charlson-Deyo score and either T1-2,N2-3 disease or T3-4,N0-3 disease.

There was no survival benefit in patients older than age 81. And among patients aged 71-80, there was no benefit for those having less advanced disease (stage T1-2,N1) and low comorbidity, or having more advanced disease (T3-4,N1+ disease) and high comorbidity. m