Gender Disparity in Cardiovascular Mortality following Radiation Therapy for Hodgkin's Lymphoma: A Systematic Review

Background Radiation-induced coronary artery disease (R-CAD) has become an increasingly recognized phenomenon. Although the clinical relationship between radiation therapy and CAD risk is well known, there is minimal investigation of the gender relationship to radiation-induced CAD events and resulting cardiovascular (CV) mortality. We study the gender variation in the incidence of CV events/mortality related to R-CAD in Hodgkin’s Lymphoma (HL) patients. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis. OVID, Cochrane Central Register of Controlled Trials via the Wiley Interface, Web of Science Core Collection, MEDLINE, EMBASE, and Google Scholar were investigated to identify prospective and retrospective observational studies comparing women and men following radiation treatment for Hodgkin's lymphoma. 10 studies were included (4 prospective, 6 retrospective). The primary outcome was incidence of cardiovascular events and mortality. The secondary outcome was all-cause mortality. Meta-regression for age was also performed. Results Of 13,975 patients including 41% females and 59% males, CV events/mortality was noted to be significantly higher in women compared to men (OR 3.74, 95% CI 2.44-5.72, p <0.001). All-cause mortality was also higher in women compared to men (OR 1.94, 95% CI 1.10-3.44, p <0.023). On meta-regression analysis, elderly populations have a higher rate of mortality which was even higher for women than men (coefficient = 0.0458, p=0.0374). Conclusions Women have a higher rate of CAD related CV events/mortality and all-cause mortality compared to men in radiation treated patients. These data highlight the need for increased surveillance to better monitor for CAD in female patients treated with mantle or mediastinal radiation.