Late cardiotoxicity of mediastinal irradiation

Reviewer: S. Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 1, 2003

Presenter: JM Adams
Presenter's Affiliation: University of Rochester
Type of Session: Scientific


    Most patients with childhood Hodgkin's Disease (HD) survive long-tem and many are treated with mediastinal irradiation (RT). Mediastinal RT is known to cause cardiac fibrosis and possibly increase the risk of fatal myocardial infarctions; however, less is known regarding other cardiovascular (CV) effects of mediastinal irradiation. A study examining the cardiac toxicities of mediastinal RT in long-term survivors of childhood HD was conducted.

Materials and Methods

  • 48 patients treated for HD between 1970-1991 were prospectively assessed for CV toxcity.
  • All patients had received mediastinal RT (median dose 40 Gy, range 27.0-51.7) at a median age of 16.5 yrs (6.4-25.0 yrs)
  • 4 patients were treated with anthracyclin chemotherapy which has know long-term cardiac toxicities
  • All patients were evaluated with an echocardiogram, electrocardiogram, and exercise stress test as well as evaluated for quality of life (QoL).
  • Median follow-up was 14.3 yrs.


  • 68% of patients had trivial to moderate cardiac valvular defects including 21% with mitral valve regurgitation and 19% with aortic valve regurgitation (AR). These were both significantly increased compared to an age- and gender-matched population.
  • Patients with AR had a significant decrease in physical component score (p=0.01)
  • 60% had conduction defects including 9% with QTc prolongation and 15% with QRS axis deviation. 1 patient experienced complete heart block.
  • Autonomic dysfunction defined as persistant tachycardia or blunted hemodynamic response was seen in 62% of patients.
  • Statistically significant increase in restrictive cardiomyopathy (CM) was seen compared to a matched control population.
  • Average peak myocardial oxygen uptake during exercise (a known predictor of mortality in heart failure) was seen in 30%.
  • All patients rated themselves as good or excellent on self-assessment for overall health; however, 67% reported significant fatigue and 40% reported significant shortness of breath.
  • Average physical function score was in the bottom 25th percentile compared to a matched control population

Author's Conclusions

  • Unsuspected clinically significant CV abnormalities were common in long-term survivors of HD treated with mediastinal RT
  • Defects include restrictive CM, ischemia, valvular defects, autonomic dysfunction, and conduction defects
  • Although patients often reported being asymptomatic, they had clinically significant symptoms upon more detailed questioning

Clinical/Scientific Implications

    This study shows a high rate of clinically significant symptoms from cardiac toxicity due to mediastinal RT. Serial screening of cardiac status is necessary in the long-term follow-up of these patients. These findings are likely expandable to other patients receiving significant cardiac radiation dose, such as patients treated for spinal tumors; however, further studies are needed for validation. Some care must be taken when viewing the results of this trial as the methods of delivering radiation have changed significantly during the time in which the patients were treated. A careful examination of the dose distribution to the heart may better delineate specific risks of cardiac toxicities due to RT.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.

From the National Cancer Institute