Clinical investigation
Lung
Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates

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Purpose: To define clinical and dosimetric parameters correlated with the risk of clinically relevant radiation pneumonitis (RP) after thoracic radiotherapy.

Methods and Materials: Records of consecutive patients treated with definitive thoracic radiotherapy were retrospectively reviewed for the incidence of RP of Grade 2 or greater by the Common Toxicity Criteria. Dose-volume histograms using total lung volume (TL) and TL minus gross tumor volume (TL-G) were created with and without heterogeneity corrections. Mean lung dose (MLD), effective lung volume (Veff), and percentage of TL or TL-G receiving greater than or equal to 10, 13, 15, 20, and 30 Gy (V10–V30, respectively) were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated to estimate RP predictive values.

Results: Twelve cases of RP were identified in 92 eligible patients. Mean lung dose, V10, V13, V15, V20, and Veff were significantly correlated to RP. Combinations of MLD, Veff, V20, and V30 lost significance using TL-G and heterogeneity corrections. Receiver operating characteristic analysis determined V10 and V13 as the best predictors of RP risk, with a decrease in predictive value above those volumes.

Conclusions: Intrathoracic radiotherapy should be planned with caution when using radiotherapy techniques delivering doses of 10 to 15 Gy to large lung volumes.

Introduction

Thoracic radiotherapy is often used in the treatment of neoplastic diseases of the chest and upper abdomen. As with all oncologic therapies, radiotherapy has potential adverse effects, which include asymptomatic laboratory or radiographic alterations, severe morbidity, and even death (1, 2, 3, 4, 5). When radiotherapy is used to treat tumors within or adjacent to the thorax, the dose-limiting organs of primary concern are the lungs and the spinal cord. The lungs are sensitive to the effects of radiation in both the short and long term and are sensitive at a lower dose than other structures in the chest, such as the esophagus, heart, and spinal cord (2, 5).

Despite the dependence of radiotherapy treatment planning on a correct estimate of the tolerance of the normal lung to ionizing radiation, the exact sensitivity of normal lung tissue to potential radiation injury remains imperfectly quantified. The risk of radiation pneumonitis (RP) developing after radiotherapy has been reported to be dependent on the volume of lung irradiated, the dose received by the lung (2), and the percentage of total lung volume minus the planning target volume exceeding 20 Gy (6, 7).

In the present study, the dosimetric data of patients treated with conventionally fractionated radiotherapy for neoplastic lung processes were examined in relation to the incidence of clinically apparent RP. Demographic and clinical characteristics and dosimetric parameters were identified and their correlation with the development of clinically relevant RP was studied. Treatment planning calculations involving lung tissue have historically not been performed using tissue inhomogeneity corrections, although many institutions have now incorporated this method into their routine clinical practice (8, 9, 10, 11). Therefore, this study was also performed with and without inhomogeneity corrections to investigate this effect.

Section snippets

Patients

We retrospectively reviewed the records of 99 consecutive patients treated for lung cancer between January 2001 and June 2003 at Mayo Clinic in Rochester, Minnesota. Eligible patients had lung neoplasms and received conventionally fractionated radiotherapy of curative intent. Patients were eligible with or without concurrent or sequential chemotherapy. Approval from the Mayo Foundation Institutional Review Board was obtained before initiation of the study.

Radiotherapy

Radiotherapy simulation was performed

Results

Of the 99 patients who met the inclusion criteria, 7 were excluded—6 because of incomplete follow-up data, and 1 patient died (due to cerebrovascular accident) during the course of radiotherapy. Twelve cases of RP were identified in the remaining 92 patients. Table 1 details patient characteristics. Results of logistic regression analysis for combinations of TL and TL-G with heterogeneity corrections “off” or “on” are reported in Table 2. For TL without heterogeneity corrections, MLD, V10, V13,

Discussion

Radiation pneumonitis is one of the dose-limiting potential adverse effects of thoracic radiotherapy that has been associated with death in a small percentage of patients (2, 5). Thus, the ability to administer curative doses of radiotherapy, either alone or in combination with chemotherapy, is greatly hindered. Advances in computing power have allowed for the relative ease of analyzing radiation doses with respect to electron densities in the lung and other organ volumes as determined by CT

Conclusions

Radiation pneumonitis is a clinically relevant adverse effect of radiotherapy whose incidence is significantly correlated with dose-volume metrics. This correlation, specifically with V10, V13, and V15, is more significant when dose-volume parameters are calculated using heterogeneity corrections and GTVs are subtracted from TL. The areas under the ROC curves in the present study reinforce the concept that larger volumes of lung treated to lower doses (10, 13, or 15 Gy) may be more critical in

Acknowledgments

Editing, proofreading, and reference verification were provided by the Section of Scientific Publications, Mayo Clinic.

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