Patients With Head/Neck Cancer See Lower Stroke Risk With Initial Surgery

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

A population-based study of U.S. veterans treated for OPSCC found 23% lower stroke risk for those who underwent up-front surgery compared with patients who received definitive (chemo)radiotherapy, reported Lova L. Sun, MD, of the University of Pennsylvania in Philadelphia, and colleagues.

“These findings present an important additional risk-benefit consideration to factor into treatment decisions and patient counseling and should motivate future studies to examine cardiovascular events in this high-risk population,” Sun and her colleagues wrote in JAMA Otolaryngology — Head & Neck Surgery.

Across 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%-13.25%) at 10 years; the cumulative incidence of death was 43.80% (95% CI 42.82%-44.77%) at 5 years and 57.32% (95% CI 56.24%-58.38%) at 10 years.

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

Subgroup analysis showed that this effect was seen across all subgroups, with the exception of patients with a history of hypertension.

The veterans diagnosed in this study, whose de-identified records were made available by the Veterans Health Administration, were diagnosed with OPSCC in the period from 2000 to 2020. Their median age was 61, 99% were men, 13% Black, and 75% white.

“As expected, patients treated with up-front surgery had lower stage disease, lower Charlson comorbidity index, and better ECOG performance status,” the authors reported. Given these baseline differences, they noted it was “unsurprising” that patients treated with up-front surgery had better overall survival (OS) than those treated with nonsurgical therapy (median OS 109.9 vs 61.3 months).

The majority (7,719) of patients received nonsurgical definitive radiotherapy or chemoradiotherapy, while the remaining 2,717 had up-front surgery with or without radiation/chemotherapy. Most of the patients who had surgery had adjuvant radiotherapy or chemoradiotherapy.

“More than a quarter of up-front surgery patients avoided chemotherapy and radiotherapy altogether, and the remainder underwent shorter courses of radiotherapy and chemotherapy than nonsurgical patients treated with definitive (chemo)radiotherapy,” Sun and colleagues observed. “The observed stroke risk reduction associated with up-front surgery may reflect a combination of treatment avoidance as well as some observed de-escalation of chemotherapy and radiotherapy.”

The authors acknowledged several limitations to the study.

They pointed out, for example, that the U.S. veterans population is not necessarily generalizable to the OPSCC population overall, particularly with the higher rates of tobacco and alcohol consumption in veterans with head and neck squamous cell carcinoma. Additionally, practically all patients in the study were men. Also, the authors did not have hard data on chemotherapy or radiation doses, instead using duration of therapy as a proxy for treatment intensity.

“Given the aforementioned limitations, these hypothesis-generating results merit validation in other large databases,” Sun and co-authors wrote. “As important next steps, these findings highlight the importance of cardiovascular risk mitigation efforts in survivors of head and neck cancer and provide support for future de-escalation trials that may explicitly investigate cardiovascular and cerebrovascular outcomes in treatment groups.”

In a commentary accompanying the study, William G. Albergotti, MD, and colleagues noted that patients should be counseled according to the toxicity profiles of both definitive radiation therapy and definitive surgery. For example, while there is likely to be a higher risk of stroke with radiotherapy, patients treated with transoral surgery have a likely higher risk of fatal hemorrhage.

As for patients who receive radiotherapy, “the traditional risk factors of diabetes, hyperlipidemia, smoking, hypertension, and so on, should be medically managed and/or optimized,” the editorialists wrote. “Surveillance with yearly carotid artery ultrasound is reasonable to do, and we arbitrarily recommend including this as part of the survivorship plan starting at 5 years after radiotherapy.”