QUANTEC: Organ Specific Paper
Radiation Dose–Volume Effects in the Heart

https://doi.org/10.1016/j.ijrobp.2009.04.093Get rights and content

The literature is reviewed to identify the main clinical and dose–volume predictors for acute and late radiation-induced heart disease. A clear quantitative dose and/or volume dependence for most cardiac toxicity has not yet been shown, primarily because of the scarcity of the data. Several clinical factors, such as age, comorbidities and doxorubicin use, appear to increase the risk of injury. The existing dose-volume data is presented, as well as suggestions for future investigations to better define radiation-induced cardiac injury.

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)

  • X. Wei et al.

    Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy

    Int J Radiat Oncol Biol Phys

    (2008)
  • C.W. Taylor et al.

    Cardiac exposures in breast cancer radiotherapy: 1950s–1990s

    Int J Radiat Oncol Biol Phys

    (2007)
  • C.W. Taylor et al.

    Cardiac dose from contemporary tangential breast cancer radiotherapy in the year 2006

    Int J Radiat Oncol Biol Phys

    (2008)
  • S.M. Grundy et al.

    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

    (1999)
  • V. King et al.

    Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease

    Int J Radiat Oncol Biol Phys

    (1996)
  • B.M. Aleman et al.

    Late cardiotoxicity after treatment for Hodgkin lymphoma

    Blood

    (2007)
  • L.E. Rutqvist et al.

    Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer

    Int J Radiat Oncol Biol Phys

    (1992)
  • G. Gagliardi et al.

    Partial irradiation of the heart

    Semin Radiat Oncol

    (2001)
  • F. Eriksson et al.

    Long-term cardiac mortality following radiation therapy for Hodgkin's disease: Analysis with the relative seriality model

    Radiother Oncol

    (2000)
  • Z.A. Carr et al.

    Coronary heart disease after radiotherapy for peptic ulcer disease

    Int J Radiat Oncol Biol Phys

    (2005)
  • C.W. Hurkmans et al.

    Cardiac and lung complication probabilities after breast cancer irradiation

    Radiother Oncol

    (2000)
  • L.B. Marks et al.

    The incidence and functional consequences of RT-associated cardiac perfusion defects

    Int J Radiat Oncol Biol Phys

    (2005)
  • G. Gagliardi et al.

    Prediction of excess risk of long-term cardiac mortality after radiotherapy of stage I breast cancer

    Radiother Oncol

    (1998)
  • L. Mosca et al.

    Evidence-based guidelines for cardiovascular disease prevention in women: 2007 Update

    J Am Coll Cardiol

    (2007)
  • L.W. Jones et al.

    Early breast cancer therapy and cardiovascular injury

    J Am Coll Cardiol

    (2007)
  • P. Van Luijk et al.

    The impact of heart irradiation on dose-volume effects in the rat lung

    Int J Radiat Oncol Biol Phys

    (2007)
  • J.M. Cosset et al.

    Long-term toxicity of early stages of Hodgkin's disease therapy: The EORTC experience. EORTC Lymphoma Cooperative Group

    Ann Oncol

    (1991)
  • C. Burman et al.

    Fitting of normal tissue tolerance data to an analytic function

    Int J Radiat Oncol Biol Phys

    (1991)
  • 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

    (2005)
  • B.M. Aleman et al.

    Long-term cause-specific mortality of patients treated for Hodgkin's disease

    J Clin Oncol

    (2003)
  • R.J. Carmel et al.

    Mantle irradiation in Hodgkin's disease. An analysis of technique, tumour eradication, and complications

    Cancer

    (1976)
  • J. Ragaz et al.

    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

    (2005)
  • L.F. Paszat et al.

    Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: A population-based study in Ontario, Canada

    Int J Radiat Oncol Biol Phys

    (1999)
  • Cited by (527)

    View all citing articles on Scopus

    Conflict of interest: none.

    View full text