Radiotherapy Is Associated with an Accelerated Risk of Ischemic Stroke in Oral Cavity Cancer Survivors after Primary Surgery

Kuan, Feng‐Che; Lee, Kuan-Der; Huang, Shiang‐Fu; Chen, Ping‐Tsung; Huang, Cih-En; Wang, Ting-Yao; Chen, Min-Chi

doi:10.3390/cancers12030616

Cited by 8 publications

(8 citation statements)

References 20 publications

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“…For these reasons, several studies have attempted to elucidate the relationship between these two diseases. Previous studies have described that patients who underwent radiotherapy alone or in combination with other treatments showed a strong relationship with incident ischemic stroke events, but we could not find any studies regarding the increased risk of hemorrhagic stroke related to the radiotherapy [10][11][12][13][14][15][16].…”

Section: Introductioncontrasting

confidence: 63%

The Risk of Ischemic and Hemorrhagic Stroke in Head and Neck Cancer: A Longitudinal Cohort Study

Kim

2023

Cancers

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Several studies have shown that head and neck cancer is associated with an increased risk of stroke incidence. However, investigations of the association between the two diseases based on a matching cohort dataset are still limited. Therefore, we identified the incidence and risk of stroke in patients with head and neck cancer using a nationwide population-based cohort dataset. A total of 5248 individuals without cancer and 1312 with cancer were enrolled from the dataset after a 4:1 propensity score matching. We found that the incidence of overall stroke (per 1000 person years) was 19.29 for those with head and neck cancer, consisting of 17.32 as ischemic type and 2.74 as hemorrhagic type. Additionally, patients with head and neck cancer had a significantly increased risk of overall and ischemic stroke development but not hemorrhagic stroke. Moreover, the risk of stroke development over time was relatively high within the first year after the diagnosis of head and neck cancer. However, in the subgroup analysis, oral cavity cancer survivors showed an increased risk of both ischemic and hemorrhagic strokes. Therefore, our nationwide population-based cohort study suggests that clinicians should closely monitor patients with head and neck cancers for the early detection of stroke.

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Section: Introductioncontrasting

confidence: 63%

The Risk of Ischemic and Hemorrhagic Stroke in Head and Neck Cancer: A Longitudinal Cohort Study

Kim

2023

Cancers

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“…These effects were also found to be reversed by Cx43-plasmid, demonstrating that miR-206 protected against γ-radiation-stimulated neuroinflammation by regulating Cx43 expression. Radiotherapy may cause several long-term complications, such as secondary intracranial tumors, hypopituitarism and stroke (6)(7)(8). Although radiation therapy is one of the causes of ischemic stroke among patients with pituitary adenoma, the underlying mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…It is estimated that 80% of cancers may regress following radiation treatment ( 5 ). However, radiotherapy may result in a series of long-term systemic and local side effects, such as secondary intracranial tumors ( 6 ), pituitary dysfunction ( 7 ) and stroke ( 8 ). When radiotherapy is used to treat pituitary adenomas, it may increase the risk of ischemic stroke, and neuroinflammation is the main pathological process.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑206 relieves irradiation‑induced neuroinflammation by regulating connexin 43

Zeng

2021

Exp Ther Med

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Radiation therapy has been widely used for the treatment of various types of cancer; however, it may cause neuroinflammation during the pathological process of the disease. Astrocytes, the most abundant cell type in the central nervous system, have been confirmed to play vital roles in various diseases. Connexin (Cx)43, the main Cx type in astrocytes, which has been identified as a direct target gene of microRNA (miR)-206, was found to be involved in diseases pathologies in regions with astrocytes. The aim of the present study was to investigate the mechanism through which γ-radiation may cause astrocyte neuroinflammation and determine the specific mechanism underlying the effects of miR-206 in irradiation-induced HA-1800 cells. A dual-luciferase reporter system was used to predict and verify the target binding site between Cx43 and miR-206. HA-1800 cell viability and apoptosis were determined using a MTT assay and flow cytometry, respectively. In addition, the HA-1800 cells were induced by γ-radiation, then the protein and mRNA expression levels of Cx43, miR-206 and cleaved-caspase-3 were determined using western blot and reverse transcription-quantitative PCR analyses, respectively. ELISA was also performed to evaluate the concentrations of different inflammatory cytokines (TNF-α, IL-β, IL-6 and IFN-γ). The dual-luciferase reporter system indicated that Cx43 was a direct target of miR-206. miR-206 mimics increased the expression level of miR-206 in the astrocytes. Irradiation suppressed cell proliferation, increased apoptotic cells and enhanced cleaved-caspase-3 expression and inflammatory cytokines secretion in astrocytes. Furthermore, miR-206 was found to be downregulated and its expression was inversely associated with that of Cx43 in γ-radiation-induced astrocytes.Overexpression of miR-206 enhanced miR-206 and suppressed Cx43 expression, while Cx43 was upregulated in HA-1800 cells transfected with miR-206 mimic + Cx43-plasmid. However, the expression level of miR-206 was not significantly different in the Cx43-plasmid transfected group. In addition, it was found that miR-206 mimics relieved irradiation-induced neuroinflammation, which was confirmed by increased cell viability, and reduced cell apoptosis and cleaved caspase-3 protein expression, as well as decreased inflammatory cytokine secretion. Furthermore, all the effects of miR-206 mimics on γ-radiation-induced astrocytes were reversed by Cx43-plasmid. In summary, the results of the present study indicated that miR-206 may relieve irradiation-induced neural damage by regulating Cx43, which may provide a novel research direction and a potential therapeutic target for the clinical treatment of inflammation-associated neuronal injury following irradiation.

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“…In addition, RT can cause local inflammation, oxidative stress, fibrosis and in-field cardiovascular disease[ 12 ]. Several studies have reported that RT increased the risk of ischemic stroke in patients with head and neck cancers[ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Risk of critical limb ischemia in long-term uterine cancer survivors: A population-based study

Chen¹,

Chang²,

Chen³

et al. 2022

World J Clin Cases

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BACKGROUND The risk of critical limb ischemia (CLI) which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer (UC) survivors remains unclear, especially in Asian patients, who are younger at the diagnosis of UC than their Western counterparts. AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors. METHODS UC survivors, defined as those who survived for longer than 5 years after the diagnosis, were identified and matched at a 1:4 ratio with normal controls. Stratified Cox models were used to assess the risk of CLI. RESULTS From 2000 to 2005, 1889 UC survivors who received surgery alone or surgery combined with radiotherapy (RT) were classified into younger (onset age < 50 years, n = 894) and older (onset age ≥ 50 years, n = 995) groups. While compared with normal controls, the younger patients with diabetes, hypertension, and receiving hormone replacement therapy (HRT) were more likely to develop CLI. In contrast, the risk of CLI was associated with adjuvant RT, obesity, hypertension, and HRT in the older group. Among the UC survivors, those who were diagnosed at an advanced age (> 65 years, aHR = 2.48, P = 0.011), had hypertension (aHR = 2.18, P = 0.008) or received HRT (aHR = 3.52, P = 0.020) were at a higher risk of CLI. CONCLUSION In this nationwide study, we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group, but positive in the older group. Among the survivors, hypertension, advanced age, and HRT were more hazardous than RT. Secondary prevention should include CLI as a late complication in UC survivorship programs.

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Radiotherapy Is Associated with an Accelerated Risk of Ischemic Stroke in Oral Cavity Cancer Survivors after Primary Surgery

Cited by 8 publications

References 20 publications

The Risk of Ischemic and Hemorrhagic Stroke in Head and Neck Cancer: A Longitudinal Cohort Study

The Risk of Ischemic and Hemorrhagic Stroke in Head and Neck Cancer: A Longitudinal Cohort Study

MicroRNA‑206 relieves irradiation‑induced neuroinflammation by regulating connexin 43

Risk of critical limb ischemia in long-term uterine cancer survivors: A population-based study

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