Background: Cancer survivors can be at risk of stroke because of either their malignancy or treatment. Identification of cancer treatment-related risk factors for stroke among patients with lung cancer is crucial for clinical decision-making and stroke prevention.
Objectives: To systematically synthesize existing literature and identify cancer treatment-related risk factors for stroke among patients with lung cancer.
Methods: A systematic search of Ovid MEDLINE, Embase, and Web of Science from inception to March 5, 2025, was conducted according to PRISMA guidelines. We included experimental and observational studies published in English and reporting the association between any cancer treatment and the incidence of stroke among patients with lung cancer. The titles and abstracts screening, full-text review, and quality assessment were performed by two independent researchers, and discrepancies were resolved through consensus.
Results: The search resulted in 1,616 distinct records. After the title and abstract screening, 68 records were retrieved for full-text review, and 19 studies published between 2013 and 2024 were included in the final analysis. All 19 studies were retrospective, observational studies, including cohort (n=16), case-control (n=2), and cross-sectional design (n=1). The risk for postoperative cerebral infarction (PCI) was found to be significantly increased in patients undergoing segmentectomy (OR=24.3; 95% CI=3.9- 150.2), wedge resection (OR=7.0; 95% CI=1.4- 35.0), or combined surgical approach (two surgical approaches) (OR=29.9; 95% CI=1.5- 616.5) compared to patients undergoing lobectomy. One study found that compared to surgery only, the risk of ischemic stroke (IS) was significantly higher for surgery plus chemotherapy (adjusted hazard ratio (aHR)=1.4; 95% CI: 1.1-1.6) and surgery plus chemotherapy plus radiotherapy (aHR=2.1; 95% CI: 1.6-2.8) recipients but was not significantly different for surgery plus radiotherapy (aHR=1.4; 95% CI: 0.9-2.2) recipients. Another study found that stroke incidence did not differ between post-operative radiotherapy (PORT) users and non-users (3.4% vs. 2.7%, p=0.313). However, a separate study reported a high risk of IS in PORT patients versus the surgery alone patients (aHR=4.2; 95% CI:1.4- 12.2). One study found that in advanced lung cancer, the risk of IS was higher in the first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) versus first-line chemotherapy users (aHR=2.0, 95% CI: 1.2-3.5), and another study found that TKI users had a higher risk of IS compared to non-users (aHR=1.3, 95% CI: 1.2-1.4) in non-small cell lung cancer (NSCLC). Additionally, a study reported no significant difference in non-fatal stroke between immune checkpoint inhibitors (ICIs) and non-ICI users (0.9% vs. 0.0%, p=0.280) among lung cancer patients.
Conclusions: This systematic review identified several potential cancer treatment-related risk factors for stroke in patients with lung cancer. Adequate risk mitigation strategies are warranted for patients under these treatments.
