International Journal of Radiation Oncology*Biology*Physics
QUANTEC: Organ Specific PaperRadiation Dose–Volume Effects in the Heart
Section snippets
Clinical Siginificance
Radiation-associated cardiac disease is seen in patients treated for lymphoma, breast cancer, seminoma, peptic ulcer disease, and lung cancer, as well as in atomic bomb survivors. Acute injury, often manifest as pericarditis, is usually transient but can be chronic. Late injury, often manifest as congestive heart failure (CHF), ischemia, coronary artery disease (CAD), or myocardial infarction (MI) several months to years post-radiation treatment (RT), is more clinically significant. In some
Endpoints
Both clinical and subclinical endpoints describe the spectrum of RT-induced heart disease (Table 1). The latency of RT-associated cardiac effects ranges from months (pericarditis) to decades (CAD, MI). The most clinically significant endpoints analyzed are morbidity (e.g., CHF and ischemic events such as MI) and cardiac deaths. Since these events occur at a relatively high rate in patients who have not undergone irradiation, the best data are derived from randomised clinical trials, or
Challenges in Defining Volumes
Delineation of the clinically relevant subregions of the heart is challenging because their structural definition through the current devices used in treatment planning (e.g., computed tomography [CT]) is imprecise. No imaging modality clearly shows these structures. The heart border may be difficult to differentiate from liver and diaphragm, but the segmenting of the superior border with the large vessels can be more challenging. The heart moves with the respiratory and cardiac cycles: the
Review of Dose/Volume Factors
The risk of cardiac events is probably related to both dose and irradiated volume. For example, as breast cancer treatment techniques have evolved to reduce cardiac exposure, there has been a steady decline in the RR for RT-associated events (32). In the Stanford HL series, the RR of death from cardiac causes (other than MI) was decreased with use of subcarinal blocking from 5.3 to 1.4 (17). In the large study in the Netherlands, the risk of valvular dysfunction was higher in the group
Factors Affecting Risk
Evidence suggests that the risk of RT-associated heart disease may be affected by baseline patient cardiac risk factors and cardiotoxic chemotherapy. All of these investigations are retrospective in design.
Mathematical/Biological Models
Table 2, Table 3, Table 4 summarize dose–volume constraints and normal tissue complication probability (NTCP) parameter values for pericarditis, cardiac mortality, and perfusion defects, respectively.
Special Situations
Several aspects, both general and heart specific, have to be considered when applying NTCP models and dose–volume constraints to clinical treatment planning.
First, there are anatomical and functional considerations in defining the organ or parts of the organ at risk, e.g., heart vs. pericardium vs. coronary vessels. For example, applying pericarditis NTCP parameters obtained from the pericardium dose distribution to the whole heart is more acceptable in a calculation and/or comparison exercise
Recommended Dose/Volume Limits
Radiation-induced cardiac complications have different significance and implications depending on the clinical scenario. As such constraints/NTCP values can be used only for guidance; they must always be considered in relation to probability of tumor control and the specific patient situation. Nevertheless, the following broad dose/volume guidelines are suggested.
In patients with breast cancer, it is recommended that the irradiated heart volume be minimized to the greatest possible degree
Future Toxicity Studies
Improved toxicity prediction requires prospective clinical trials based on 3D dosimetric data and careful long-term follow-up of patients who have received potentially cardiotoxic chemotherapy and RT. Prospective cardiac mortality studies are unlikely to be numerous. Hopefully, the few existing dose–volume predictors for cardiac mortality will be modified by new retrospective analyses based on larger data sets, in which dose to the left descending artery will also be considered. Future
Toxicity Scoring
We recommend that the LENT-SOMA system (64) be considered to describe cardiac effects, as it explicitely addresses clinical, radiological, and functional assessments of cardiac dysfunction.
Acknowledgment
Supported in part by grants from the NIH (CA69579) and the Lance Armstrong Foundation (LBM).
References (66)
- et al.
Postoperative radiotherapy in breast cancer - long term results from the Oslo study
Int J Radiat Oncol Biol Phys
(1986) - et al.
A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer
Radiother Oncol
(2007) - et al.
Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective cohort study of about 300,000 women in US SEER cancer registries
Lancet Oncol
(2005) - et al.
Morbidity and mortality of ischemic heart disease in high-risk breast cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: Analysis of DBCG 82b and 82c randomized trials
Lancet
(1999) - et al.
Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: The role of irradiated heart volume
Int J Radiat Oncol Biol Phys
(2007) - et al.
Morbidity of ischemic heart disease in early breast cancer 15–20 years after adjuvant radiotherapy
Int J Radiat Oncol Biol Phys
(1994) - et al.
Cardiac lesions after mediastinal irradiation for Hodgkin's disease
Radiother Oncol
(1994) - et al.
Asymptomatic cardiac disease following mediastinal irradiation
J Am Coll Cardiol
(2003) - et al.
Respiratory motion of the heart and positional reproducibility under active breathing control
Int J Radiat Oncol Biol Phys
(2007) - et al.
Fraction size and dose parameters related to the incidence of pericardial effusions
Int J Radiat Oncol Biol Phys
(1998)
Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy
Int J Radiat Oncol Biol Phys
Cardiac exposures in breast cancer radiotherapy: 1950s–1990s
Int J Radiat Oncol Biol Phys
Cardiac dose from contemporary tangential breast cancer radiotherapy in the year 2006
Int J Radiat Oncol Biol Phys
AHA/ACC scientific statement: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology
J Am Coll Cardiol
Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease
Int J Radiat Oncol Biol Phys
Late cardiotoxicity after treatment for Hodgkin lymphoma
Blood
Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer
Int J Radiat Oncol Biol Phys
Partial irradiation of the heart
Semin Radiat Oncol
Long-term cardiac mortality following radiation therapy for Hodgkin's disease: Analysis with the relative seriality model
Radiother Oncol
Coronary heart disease after radiotherapy for peptic ulcer disease
Int J Radiat Oncol Biol Phys
Cardiac and lung complication probabilities after breast cancer irradiation
Radiother Oncol
The incidence and functional consequences of RT-associated cardiac perfusion defects
Int J Radiat Oncol Biol Phys
Prediction of excess risk of long-term cardiac mortality after radiotherapy of stage I breast cancer
Radiother Oncol
Evidence-based guidelines for cardiovascular disease prevention in women: 2007 Update
J Am Coll Cardiol
Early breast cancer therapy and cardiovascular injury
J Am Coll Cardiol
The impact of heart irradiation on dose-volume effects in the rat lung
Int J Radiat Oncol Biol Phys
Long-term toxicity of early stages of Hodgkin's disease therapy: The EORTC experience. EORTC Lymphoma Cooperative Group
Ann Oncol
Fitting of normal tissue tolerance data to an analytic function
Int J Radiat Oncol Biol Phys
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials
Lancet
Long-term cause-specific mortality of patients treated for Hodgkin's disease
J Clin Oncol
Mantle irradiation in Hodgkin's disease. An analysis of technique, tumour eradication, and complications
Cancer
Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-Year results of the British Columbia randomized trial
J Natl Cancer Inst
Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: A population-based study in Ontario, Canada
Int J Radiat Oncol Biol Phys
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