Researchers at the Perelman School of Medicine at the University of Pennsylvania (Penn Medicine) say physicians and patients with head and neck cancer should consider upfront surgery to lower the risk of stroke following treatment. The recommendation follows a large, in-depth analysis of the health records of more than 10,000 military veterans diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) between 2000 and 2020. The results from the study were presented at the 2022 American Society of Clinical Oncology Annual Meeting (Abstract 6057).
In the "era of treatment de-intensification" for the disease, the researchers "sought to quantify the cumulative incidence of stroke in patients with non-metastatic OPSCC and evaluate whether patients who received upfront surgery have decreased risk of stroke compared to non-surgical treatment."
Their analysis of the veterans' health records revealed that patients who underwent initial surgery lowered the risk of stroke in the decade following treatment by nearly one-fourth when compared to patients who received non-surgical treatments, including radiotherapy and chemoradiotherapy.
The researchers also found a link between upfront surgery and lower stroke risk in different age groups, as well as patients with and without hypertension, those with high cholesterol, and others with diabetes, suggesting surgery, as opposed to other risk factors, accounted for the lower risk of stroke revealed in the analysis.
OPSCC has high morbidity and mortality rate of about 20 percent with the increased risk of stroke following non-surgical treatments likely being due to the damage the therapies do to arteries that deliver blood and oxygen to the brain, shown in previous studies.
The majority of the patients in the Penn Medicine analysis (7,719) had received non-surgical definitive radiotherapy or chemoradiotherapy, and 2,717 had surgery either with or without perioperative definitive radiotherapy or chemoradiotherapy.
The veterans included in the study were males with non-metastatic OPSCC. One in eight patients had a stroke in the decade following their initial treatment with the non-surgical therapies, qualifying them as a high-risk group, according to the researchers.
Propensity score weighting methods were used to factor out differences between the two patient cohorts in the study, which led to further revelations, such as better outcomes in patients who received shorter courses of chemo and radiation, most likely due to less tissue damage incurred during treatment.
Lova L. Sun, MD, MSCE, the study's lead author and Assistant Professor of Medicine at the Hospital of the University of Pennsylvania, shared additional insight into the background, discoveries, and implications of the head and neck cancer study.
Oncology Times: What inspired you to investigate this research?
Sun: "Cardiovascular events are often underemphasized causes of morbidity and mortality in patients with head and neck cancer, who often have shared risk factors, including smoking, that predispose to both cancer and cardiovascular disease.
"While treatment toxicities, including dysphagia and xerostomia, are extensively studied and discussed in the debate between surgery and radiation for oropharynx cancer, the risk of cardiovascular events, including stroke, has not directly been compared between these two treatment modalities.
"Since radiation to the neck has been associated with vascular injury and carotid artery stenosis, we hypothesized that patients undergoing upfront surgery, who can often avoid full-dose chemotherapy and radiation, may have lower long-term stroke risk."
Oncology Times: What were the most important findings in the study and what was surprising?
Sun: "In the overall cohort of veterans with head and neck cancer, we found that the risk of stroke at 10 years was 12.5 percent. In addition, our propensity-matched analysis showed that getting upfront surgery was associated with a 23 percent lower risk of stroke compared to getting radiation-based therapy. The 10-year risk of stroke in the entire cohort regardless of treatment modality was quite high and really underscores that this is a population with a high burden of cardiovascular risk factors. For instance, over half of our population had a diagnosis of hypertension at baseline."
Oncology Times: Is there anything others might miss or misunderstand about your findings?
Sun: "It's important to note that this study was conducted in a U.S. veteran population who may not be completely representative of the oropharynx cancer population as a whole; for instance, almost all of the patients in this study were men. Also, these results should not be interpreted as a recommendation for upfront surgery over radiation in oropharynx cancers in general, [as] there are multiple disease and patient factors that go into this treatment decision, and stroke risk may be one additional risk-benefit consideration that this study helps to inform."
Oncology Times: What are the clinical implications of your research and what further research needs to be done?
Sun: "For patients with oropharynx cancer in whom either surgery or radiation-based treatment are reasonable upfront treatment options, this study provides one important risk-benefit consideration to factor into treatment decisions and patient counseling. In addition, the high risk of stroke overall underscores the importance of mitigating cardiovascular risk factors in patients with head and neck cancer in general.
"Further research into the impact of cardiovascular risk factors and how they interact with cancer treatment, as well as interventions to mitigate risk factors and reduce cardiovascular events, will help to optimize survivorship and long-term health outcomes in this high-risk patient population."
Chuck Holt is a contributing writer.
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