Stroke risk high among head and neck cancer survivors in SG

Survivors of head and neck cancer (HNC) in Singapore have a more than twofold increased risk of stroke, regardless of age, cancer subsites, and treatment modalities, among others, according to a study.

The age-standardized incidence rate ratio (SIRR) of stroke (composite of ischaemic and haemorrhagic stroke events) in HNC survivors was 2.46 (95 percent confidence interval [CI], 2.21–2.74) times higher than in the general population. [JAMA Netw Open 2024;7:e2354947]

On average, HNC survivors had about 4 additional strokes per 1,000 people per year (age-standardized incidence rate difference [SIRD], 4.11 [95 percent CI, 3.37–4.85] per 1,000 person-years).

Following HNC diagnosis, the cumulative incidence of stroke was estimated at 3 percent at 5 years and 7 percent at 10 years. The risk of stroke rose dramatically at 5 years postdiagnosis relative to within the first 5 years of diagnosis (SIRR, 3.92, 95 percent CI, 3.36–4.58 vs SIRR, 1.84, 95 percent CI, 1.59–2.14).

“We captured both ischaemic and haemorrhagic stroke events from a national stroke registry,” the investigators noted.

“SIRR represents the relative risk, which is significantly influenced by the baseline rate in the reference population. Conversely, SIRD reflects the absolute difference in risks in terms of the excess number of strokes per 1,000 person-years, which is directly interpretable in terms of health outcomes among survivors. These two metrics should complement each other in revealing distinct risk profiles,” they pointed out.

Stroke risk across subgroups

The increased risk of stroke among HNC survivors was observed consistently across subgroups defined by age, sex, disease histology, cancer subsites, and treatment modalities.

“The SIRR [of stroke] was highest among patients who were diagnosed with HNC when they were younger than 40 years [of age] (SIRR, 30.55, 95 percent CI, 16.24–52.35). SIRR values decreased with increasing age at the diagnosis of HNC, whereas SIRD values showed an increasing trend,” the investigators said.

Male HNC survivors had a higher SIRD than their female counterparts (SIRD, 4.58 strokes per 1,000 person-years, 95 percent CI, 3.62–5.54 vs 2.02 strokes per 1,000 person-years, 95 percent CI, 0.98–3.06). Meanwhile, survivors with nonsquamous vs squamous histology had a higher SIRR of stroke (SIRR, 2.99, 95 percent CI, 2.59–3.44 vs 1.99, 95 percent CI, 1.69–2.34).

Finally, the SIRR and SIRD were significantly higher among survivors who had a primary radiation treatment approach (SIRR, 3.01, 95 percent CI, 2.64–3.43; SIRD, 5.12 strokes per 1,000 person-years, 95 percent CI, 4.18–6.29) than among those who had a primary surgical approach (SIRR, 1.64, 95 percent CI, 1.31–2.05; SIRD, 1.84 strokes per 1,000 person-years, 95 percent CI, 0.92–3.67).

Taken together, “these findings could inform resource allocation for stroke prevention and emphasize the importance of long-term follow-up,” the investigators said.

For the study, the investigators used data from the Singapore Cancer Registry, the Singapore Stroke Registry, and the Registry of Birth and Deaths. A total of 9,803 survivors of HNC (median age 58 years, 73.1 percent men, 86.1 percent Chinese) were included. The most common HNC subsites were nasopharynx (47.7 percent), larynx (12.5 percent), and tongue (10.8 percent). Approximately 4 million people from the Singapore general population serving as the reference group.

In total, 337 HNC survivors (3.4 percent) had stroke over a median follow-up of 42.5 months. Those who had stroke were older and more likely to be men and have nonsquamous cell carcinoma.