Head and neck cancer patients found to have lower stroke risk through primary surgery

In oropharyngeal squamous cell carcinoma (OPSCC), the type of initial treatment appears to influence the likelihood of stroke in subsequent years, researchers say.

A Population-based study of U.S. veterans treated for OPSCC found a Patients who underwent upfront surgery had a 23 percent lower risk of stroke compared with patients, and colleagues.

“These findings raise an important additional risk-benefit consideration to factor into treatment decisions and patient counseling, and should motivate future research examining cardiovascular outcomes in this high-risk population incident,” Sun and her colleagues wrote in JAMA Otolaryngology-Head and Neck Surgery.

In the entire cohort of 10,436 veterans, the cumulative incidence of stroke was 7.37% (95% CI 6.87%-7.90%) at 5 years and 12.52% (95% CI 11.81%) at 10 years -13.25%); 5-year cumulative mortality was 43.80% (95% CI 42.82%-44.77%), and 10-year cumulative mortality was 57.32% (95% CI 56.24%-58.38%).

After propensity score and inverse probability weighting, the hazard ratio for stroke associated with surgical treatment was 0.77 (95% CI 0.66-0.91).

Subgroup analysis showed that this effect was present in all subgroups except those with a history of hypertension.

Veterans diagnosed in this study, whose de-identification records were provided by the Veterans Health Administration, were diagnosed with OPSCC during the period from 2000 to 2020. Their median age was 61 years, 99% were male, 13% were black, and 75% were white.

“As expected, patients who underwent upfront surgery had lower disease stage, lower Charlson comorbidity index, and better ECOG performance status,” the authors report. Given these baseline differences, they noted that it was “not surprising” that patients treated with upfront surgery had better overall survival (OS) than those treated with nonsurgical treatment (median OS, 109.9 vs. 61.3 months).

Most (7,719) patients received nonsurgical curative radiation or chemoradiation, while the remaining 2,717 patients received prior surgery with or without radiation/chemotherapy. Most patients who underwent surgery received adjuvant radiation or chemoradiation.

“More than a quarter of patients with upfront surgery avoided chemotherapy and radiotherapy completely, and the remainder received a shorter course of radiotherapy and radiotherapy. Consistent with non-patients receiving definitive (chemo)radiation compared with surgical patients,” Sun and colleagues observed. “The observed reduction in stroke risk associated with prior surgery may reflect a combination of avoidance of treatment and some de-escalation observed with chemotherapy and radiation.”

The authors acknowledge some limitations

They point out, for example, that the US veteran population does not necessarily apply to the overall OPSCC population, especially in the context of higher rates of tobacco and alcohol consumption among veterans of the head and squamous cell carcinoma of the neck. Additionally, nearly all patients in the study were men. Furthermore, the authors do not have exact data on chemotherapy or radiation doses, but use treatment duration as a proxy for treatment intensity.

“Given the above limitations, these assumptions yield results worthy of validation in other large databases,” Sun and coauthors wrote. “As an important next step, these findings underscore the importance of reducing cardiovascular risk in head and neck cancer survivors and provide support for future de-escalation trials that may definitively investigate cardiovascular and cerebrovascular outcomes in treatment groups.”

In a comment accompanying the study, William G. Albergotti, MD, and colleagues state that patients should be counseled based on the toxicity profile of definitive radiation therapy and definitive surgery. For example, while radiation therapy may be associated with a higher risk of stroke, patients treated with oral surgery may be at higher risk of fatal bleeding.

As for patients receiving radiation therapy, “traditional risk factors for diabetes, hyperlipidemia, smoking, hypertension, etc., should be medically managed and/or optimized,” the editorial wrote. “Annual carotid ultrasound surveillance is reasonable and we arbitrarily recommend it as part of a survival plan starting 5 years after radiotherapy.”

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  Mike Bassett is a Staff writer focusing on oncology and hematology. He lives in Massachusetts.

Disclosure

There was no external funding for this study. Sun did not disclose any information. Other co-authors report on industry relationships.

Edit not disclosed.