The Association Between the Mean Heart Dose, Mean Lung Dose, Tumor Location and RT-associated Heart and Lung Toxicity

Reviewer: Chika Madu, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 18, 2005

Presenter: L.B. Marks
Presenter's Affiliation: Radiation Oncology, Duke University Medical Center, Durham, NC
Type of Session: Scientific


One of the side effects of lung irradiation is radiation pneumonitis, which can be manifested as dyspnea. However, dyspnea can be one of the presenting symptoms of cardiac disease and might cause confusion in diagnosis following lung irradiation. The purpose of this study was to evaluate the association between heart and lung doses, tumor location, with the development of heart/lung toxicity following irradiation.

Materials and Methods

  • Between 1991 and 2001, 215 patients were enrolled in a prospective clinical study to define predictors of RT-induced lung toxicity
  • All included patients had at least 6 months of follow up
  • Patients with dyspnea secondary to progression of intra-thoracic tumor <6months following XRT were excluded
  • CT-based 3D external beam radiation was used and the heart was contoured from the inferior pulmonary artery down to the diaphragm
  • Doses received by non-involved lung tissue and the heart were calculated
  • Toxicity was scored via the NCI common toxicity criteria
  • Lung toxicity ≥ grade 2 and RT-associated heart toxicity (mainly pericarditis) were calculated
  • Patients were divided into subgroups based on mean heart and lung doses
  • Rate of toxicity and patient subgroups were compared via Fisher exact test
  • Wilcoxon rank sum was used to evaluate the effect of tumor location on mean heart dose (MHD) and mean lung dose (MLD)


  • One hundred and eighty three patients were evaluated out of 215
  • 19% of the evaluated patients developed ≥ grade 2 lung injury and 4% developed heart injury
  • The relative incidence of heart vs. lung toxicity was associated with the ration of MHD and MLD (p=0.01)
  • When MHD was >MLD, there was a comparable heart and lung toxicity rate, but when MLD was >MHD, lung toxicity predominated
  • The incidence of heart injury was 11% and 1% for MHD >25Gy and MHD <25Gy respectively (p=0.01)
  • The MHD in patients with heart injury was 33Gy, while it was 17Gy in patients without heart injury (p=0.009)
  • There was no difference in the MHD in patients with left or right sided tumors (16Gy vs. 19Gy)
  • Lower/middle lobe lung lesions was associated with a higher MHD than upper lobe lesions (23Gy vs. 14Gy; p=0.0001), however, this was not associated with the presence of dyspnea

Author's Conclusions

  • Incidence of RT-associated heart toxicity increases with increasing MHD
  • RT-associated dyspnea is not associated with MHD
  • The ratio of MHD and MLD can be correlated with the incidence of heart and/or lung toxicities
  • Further analysis of doses to different heart chambers currently underway

Clinical/Scientific Implications

This paper addresses one of the very common problems seen in patients who are status post lung irradiation. In patients presenting with dyspnea, it is difficult in certain cases to separate lung from heart etiologies. This study has looked at the MHD received from radiation and has found no correlation with dyspnea, although there is a correlation between MHD and heart toxicities such as pericarditis, myocardial infarction. As such, RT-induced toxicity is more likely to present with symptoms other than dyspnea according to this study. This study did not look at patient hemoglobin levels to evaluate for any correlations. Previous mouse/rat studies have shown a higher incidence of radiation pneumonitis after irradiation to lower lobe tumors. This has also been shown in human studies. What is unclear is why this is the case. Is this due to an intrinsic higher sensitivity of the basal lung to radiation or is it because the lower lobes are larger and more relied upon for respiration? Further studies are needed to clarify this issue. In the mean time, all patients should undergo a complete clinical/laboratory work-up if there is any doubt regarding the etiology of their dyspnea following lung irradiation.