Radiotherapy Exposure in Cancer Patients and Subsequent Risk of Stroke: A Systematic Review and Meta-Analysis

Abstract

Background: Cancer patients who have undergone radiotherapy may have an increased risk of subsequent stroke. A clear and detailed understanding of this risk has not been established.Methods: A search for research articles published from January 1990 to November 2017 in the English language was conducted. Subsequent stroke risk in cancer survivors was compared using relative risk (RR) and 95% confidence intervals (CI) according to whether or not radiotherapy was given.Results: A total of 12 eligible studies were identified including 57,881 total patients. All studies were retrospective, as no prospective studies were identified. The meta-analysis revealed a higher overall risk of subsequent stroke in cancer survivors/patients given radiotherapy compared to those not given radiotherapy (RR: 2.09, 95% CI: 1.45, 3.16). In addition, compared to patients not given radiotherapy, there was an increased risk of subsequent stroke for radiotherapy treated patients with Hodgkin's lymphoma (RR: 2.81, 95% CI: 0.69, 4.93) or head/neck/brain/nasopharyngeal cancer (RR: 2.16, 95% CI: 1.16, 3.16), for patients younger than 40 years (RR: 3.53, 95% CI: 2.51, 4.97) or aged 40–49 years (RR: 1.23, 95% CI: 1.09, 1.45) and for patients treated in Asia (RR: 1.88, 95% CI: 1.48, 2.29), the United States (RR: 1.62, 95% CI: 1.01, 2.23), or in Europe (RR: 4.11, 95% CI 2.62, 6.45).Conclusions: The available literature indicates an approximate overall doubling of the subsequent stroke risk in cancer patients given radiotherapy. The elevated risk was generally statistically significant according to cancer type, baseline patient age and region or country where treatment was given. Caution is required in interpreting these findings due to the heterogeneity of populations represented and lack of standardization and completeness across published studies. Further, if real, we cannot conclude the extent to which patient, treatment and/or investigational factors are responsible for this apparent elevated risk. An objective and more detailed understanding of the risks of radiotherapy, and how to prevent them, is urgently required. It is the responsibility of all who provide cancer services to ensure that the experience of all their patients is documented and analyzed using quality registries.

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

“…In addition, newly developed therapies based on high linear energy transfer (LET) particles, including protons and heavy ions such as carbon ions, are being used in cancer treatments [22][23][24][25] . However, with the increased usage of radiation not only in cancer treatment but also in medical examination globally, the adverse influence of radiation on the human body has attracted much attention in the public and scientific community, including the subsequent secondary cancer risks and damage to normal tissues after radiotherapy 26 . Indeed, advances in radiation and radiotherapy are contributing substantially to winning the battle against cancer [27][28][29] .…”

“…RR leads to cancer relapse, poor treatment response, poor prognosis, decreased quality of life, and increased disease treatment burden. Furthermore, RR induces damage to canceradjacent normal tissues, disrupting the physiological and biochemical functions of normal tissue, resulting in symptoms, including radiation-related diarrhea, rectal bleeding, and radiation dermatitis [39][40][41] , as well as an increased risk of subsequent secondary cancer 26,[42][43][44] or chronic noncommunicable diseases including type II diabetes 45,46 or cardiovascular diseases 47 . Over the past century, to remove the barrier of RR, many studies have been carried out to investigate RR-related regulatory genes, molecules, and signaling pathways to uncover the underlying mechanisms of RR and to develop radiation sensitizers 48,49 .…”

Emerging Challenges of Radiation-Associated Cardiovascular Dysfunction (RACVD) in Modern Radiation Oncology: Clinical Practice, Bench Investigation, and Multidisciplinary Care

“…Clinically, the overall incidence of RACVDs is rare but substantially encountered in irradiated patients with mediastinum lymphoma (8,44,66), head and neck (10,45), esophagus (63), lung (13,61,62), and breast (12,21,56,64) cancers. High-risk features of RACVD development are as follows: left-side breast irradiation (21, 65), combination with anthracycline-based chemotherapy (65), and vulnerable patient populations [e.g., pre-existing cardiac risk factors/heart disease (21, 57) and BRCA1/2 mutation carriers (60)].…”

“…As a result, when these therapies are prescribed concurrently or sequentially with RT, the risk of RACVD is increased substantially, especially in vulnerable pediatric (40,41) or elderly cancer patients (42,43). Besides, other RT-associated adverse events may occur with RACVD, such as ischemic stroke (44,45) and lung fibrosis (46,47), which may further impair patients' survival and life quality.…”

Analysis of lncRNA and mRNA Transcriptomes Expression in Thyroid Cancer Tissues Among Patients With Exposure of Medical Occupational Radiation

“…[5][6][7] Radiation is commonly used in modern medication and numerous novel radiology procedures have been introduced. 8 There are about 2,3 million diagnostic radiology professionals worldwide and the number is rapidly increasing. 9 Ionizing radiation, in the forms of x-rays, g rays, and radon gas, is a known carcinogen.…”