High-Intensity Local Treatment May Improve Head and Neck Cancer Survival

The addition of high-intensity primary tumor ablation in addition to systemic chemotherapy may improve the survival of patients with metastatic head and neck squamous cell carcinoma.

The addition of high-intensity primary tumor ablation in addition to systemic chemotherapy may improve the survival of patients with metastatic head and neck squamous cell carcinoma (HNSCC). Results of a National Cancer Data Base analysis showed that patients who underwent systemic therapy plus local treatment had improved survival compared to those who were given systemic therapy alone.

“We believe that the role of combined high-intensity local therapy and systemic therapy in HNSCC patients presenting with distant metastases warrants a prospective evaluation, particularly for patients with oligometastatic disease,” wrote Zachary S. Zumsteg, MD, of the department of radiation oncology at Cedars-Sinai Medical Center, New York, and colleagues, in a study published in Cancer.

Prior research has shown that with some malignancies, locoregional treatment for patients with distant metastases undergoing systemic chemotherapy may improve outcomes compared with systemic treatment alone.

Therefore, Zumsteg and colleagues conducted this National Cancer Data Base analysis of 3,269 patients with HNSCC undergoing systemic therapy. Of the included patients, 45.7% received high-intensity therapy, 19.9% received low-intensity therapy, and 34.4% received systemic treatment alone. High-intensity treatment included radiation (n = 1,299), surgery (n = 121), or both (n = 75).

The median follow-up was 51.5 months. Patients who underwent local therapy and systemic therapy had a 2-year overall survival of 34.2% compared with 20.6% for those who underwent systemic treatment alone (P < .001). Looking at the subgroups of high-intensity compared with low-intensity local therapy, only high-intensity treatment was associated with the significant gains in overall survival. Survival was similar for patients receiving low-intensity local therapy and no local therapy at all.

“There are several explanations for a beneficial effect from locoregional treatment for patients with head and neck cancers who present with distant metastases ,” the researchers wrote. “Perhaps the simplest explanation is that, because this region contains structures that facilitate breathing, eating, and speaking in addition to blood vessels and nerves necessary for survival, locoregional progression represents the most imminent source of mortality for many patients with metastatic HNSCC.”

The researchers found that timing of high-intensity therapy also affected outcomes. Receipt within the first 6 months after diagnosis had a stronger effect on survival (adjusted hazard ratio, 0.255; 95% CI, 0.210–0.309; P < .001) compared with more than 6 months after diagnosis (adjusted HR, 0.622; 95% CI, 0.561–0.689; P < .001).

“This is likely due in part to the fact that virtually all patients in this cohort eventually experienced systemic progression,” the researchers wrote. “In addition, both immortal-time bias, whereby patients needed to survive long enough to complete high-intensity local treatment, and selection bias, whereby patients having good responses to systemic therapy were more likely to receive high-intensity local therapy, could have contributed to the larger effect size observed for high-intensity local therapy during the first 6 months.”

Therefore, the researchers also performed landmark analyses of 1-, 2-, and 3-year survivors and found continued overall survival benefit for patients who underwent high-intensity treatment.

“We believe that these data support a benefit of high-intensity local treatment for metastatic head and neck cancer, but we favor using the 38% relative decrease in mortality observed beyond 6 months of follow-up as a conservative estimate of its magnitude because of the greater potential for bias at earlier time points,” the researchers wrote.