Relation between radiation-induced whole lung functional loss and regional structural changes in partial irradiated rat lung.
ABSTRACT Radiation-induced pulmonary toxicity is characterized by dose, region, and time-dependent severe changes in lung morphology and function. This study sought to determine the relation between the structural and functional changes in the irradiated rat lung at three different phases after irradiation.
Six groups of animals were irradiated to 16-22 Gy to six different lung regions, each containing 50% of the total lung volume. Before and every 2 weeks after irradiation, the breathing rate (BR) was measured, and at Weeks 8, 26, and 38 CT was performed. From the computed tomography scans, the irradiated lung tissue was delineated using a computerized algorithm. A single quantitative measure for structural change was derived from changes of the mean and standard deviation of the density within the delineated lung. Subsequently, this was correlated with the BR in the corresponding phase.
In the mediastinal and apex region, the BR and computed tomography density changes did not correlate in any phase. After lateral irradiation, the density changes always correlated with the BR; however, in all other regions, the density changes only correlated significantly (r(2) = 0.46-0.85, p < 0.05) with the BR in Week 26.
Changes in pulmonary function correlated with the structural changes in the absence of confounding heart irradiation.
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ABSTRACT: To quantify the influence of treatment- and patient-related factors on the severity of early local pulmonary injury and to establish whether regional differences are present for local dose-effect relations for early radiation-induced pulmonary injury. Forty-two patients with malignant lymphoma and 40 breast cancer patients were examined prior to and 3 months after radiotherapy. The lymphoma patients were irradiated with mantle fields to an average dose of 38 Gy and the breast cancer patients were irradiated with internal mammary node fields with or without tangential breast fields to an average dose of 50 Gy. Dose-effect relations for local perfusion, ventilation and density changes were determined using correlated single photon emission computed tomography (SPECT) and CT data. A multivariate analysis was performed to study the influence of irradiated volume, chemotherapy (CMF and MOPP/ABV), smoking, age and gender. In addition, dose-effect relations for different regions in the lung were determined. A similar and almost linear increase of early functional changes as a function of radiation dose was observed for perfusion and ventilation, whereas the shape of the dose-effect relation and the magnitude of early structural changes were different for density. For the three end-points studied, regional differences in radiosensitivity could not be demonstrated. For the posterior lung region compared to the anterior lung region, however, a difference was observed, which could be attributed to a gravity-related effect in the measuring procedure. Local structural changes (density) were significantly smaller for smokers (P = 0.002) and young patients (P = 0.007), whereas the CMF chemotherapy regimen given after radiotherapy (P = 0.017) significantly increased the amount of functional changes (perfusion). The magnitude of local pulmonary changes was independent of the irradiated volume, the MOPP/ABV chemotherapy regimen and gender. The dose-effect relations for early radiation-induced local pulmonary changes were independent of the irradiated volume, MOPP/ABV, gender and lung region. CMF, smoking and age influenced the magnitude of early pulmonary changes and should be taken into account in dose-escalation protocols.Radiotherapy and Oncology 08/1998; 48(1):33-43. · 4.52 Impact Factor
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ABSTRACT: To assess the recovery from early local pulmonary injury after irradiation and to determine whether regional differences exist. For 110 patients treated for breast cancer or malignant lymphoma, single photon emission computed tomography (SPECT) perfusion and ventilation scans and CT scans were made before, 3, 18, and 48 months after radiotherapy. Dose-effect relations for changes in local perfusion, ventilation, and density were determined for each individual patient using spatially correlated SPECT and CT data sets, for each follow-up period. Average dose-effect relations for both subgroups were determined, as well as dose-effect relations for different regions. In general, partial improvement of local pulmonary injury was observed between 3 and 18 months for each of the three endpoints. After 18 months, no further improvement was seen. Patients with breast cancer and malignant lymphoma showed a similar improvement (except for the perfusion parameter), which was attributed to a recovery from the early radiation response and could not be explained by contraction effects of fibrosis of lung parenchyma. No regional differences in radiosensitivity 18 months after treatment were observed, except for the dorsal versus ventral region. This difference was attributed to a gravity-related effect in the measuring procedure. For all patients, a partial recovery from early local perfusion, ventilation, and density changes, was seen between 3 and 18 months after radiotherapy. After 18 months, local lung function did not further improve (lymphoma patients).International Journal of Radiation OncologyBiologyPhysics 08/2000; 47(5):1201-8. · 4.52 Impact Factor
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ABSTRACT: To study regional differences in lung radiosensitivity by evaluating the incidence of radiation pneumonitis (RP) in relation to regional dose distributions. Registered chest CT and single photon emission CT lung perfusion scans were obtained in 106 patients before curative or radical radiotherapy for non-small-cell lung cancer. The mean lung dose (MLD) was calculated. The single photon-emission CT perfusion data were used to weigh the MLD with perfusion, resulting in the mean perfusion-weighted lung dose. In addition, the lungs were geometrically divided into different subvolumes. The mean regional dose (MRD) for each region was calculated and weighted with the perfusion of each region to obtain the mean perfusion-weighted regional dose. RP was defined as respiratory symptoms requiring steroids. The incidence of RP for patients with tumors in a specific subvolume was calculated. The normal tissue complication probability (NTCP) parameter values for the TD(50), and an offset NTCP parameter for tumor location were fitted for both lungs and for each lung subvolume to the observed data using maximum likelihood analysis. The incidence of RP correlated significantly with the MLD and MRD of the posterior, caudal, ipsilateral, central, and peripheral lung subvolumes (p between 0.05 and 0.002); no correlation was seen for the anterior, cranial, and contralateral regions Similarly, a statistically significant correlation was observed between the incidence of RP and the perfusion-weighted MLD and perfusion-weighted MRD for all regions, except the anterior lung region. For this region, the dose-effect relation improved remarkably after weighting the local dose with the local perfusion. A statistically significant difference (p = 0.01) in the incidence of RP was found between patients with cranial and caudal tumors (11% and 40%, respectively). Therefore, a dose-independent offset NTCP parameter for caudal tumors was included in the NTCP model, improving most correlations significantly, confirming that patients with caudal tumors have a greater probability of developing RP. The incidence of RP correlated significantly with the MLD and MRD of most lung regions, except for the anterior, cranial, and contralateral regions. Weighting the local dose with the local perfusion improved the dose-effect relation for the anterior lung region. Irradiation of caudally located lung tumors resulted in a greater risk of RP than irradiation of tumors located in other parts of the lungs.International Journal of Radiation OncologyBiologyPhysics 12/2004; 60(3):748-58. · 4.52 Impact Factor