Second malignant neoplasms and cardiovascular disease following radiotherapy

Abstract

Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.

Figure 1

Selected cancer risks by radiation dose. A) Breast cancer risk according to radiation dose to the breast. From Inskip et al. (165). Reprinted with permission. Copyright 2008 American Society of Clinical Oncology. All rights reserved. B) Relative risk of subsequent glioma and meningioma within the Childhood Cancer Survivor Study cohort by radiation dose (open boxes, mean observed relative risk for meningioma; closed boxes, mean observed relative risk for glioma; solid line, fitted line for meningioma risk; hatched line, fitted line for glioma risk). P < .001 (likelihood ratio test, two-sided). From Neglia et al. (157). Reprinted with permission from Oxford University Press. C) Thyroid cancer risk by radiation dose in case subjects and control subjects after adjustment for first cancer. From Sigurdson et al. (166). Reprinted from Lancet 2005;365:2014–2023, with permission from Elsevier. Error bars represent 95% confidence intervals. ORs = odds ratios.

Figure 2

Cumulative incidence of cardiac disorders among childhood cancer survivors by average cardiac radiation dose. From Mulrooney et al. (9), with permission from BMJ Publishing Group Ltd. cGy = centigray.