Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging

Purpose To apply a previously designed framework for predicting radiation pneumonitis by using pretreatment lung function heterogeneity metrics, anatomic dosimetry, and functional lung dosimetry derived from 2 imaging modalities within the same cohort. Methods and Materials Treatment planning computed tomography (CT) scans were co-registered with pretreatment [99mTc] macro-aggregated albumin perfusion single-photon positron emission tomography (SPECT)/CT scans and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans of 28 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥2 (Common Terminology Criteria for Adverse Events, v. 4). Anatomic dosimetric parameters (mean lung dose [MLD], volume receiving ≥20 Gy [V20]) were collected from treatment planning scans. Baseline functional lung heterogeneity parameters and functional lung dose-volume parameters were calculated from pretreatment SPECT/CT and FDG PET/CT scans. Functional heterogeneity parameters calculated over the tumor-subtracted lung included skewness, kurtosis, and coefficient of variation from perfusion SPECT and FDG PET and the global lung parenchymal glycolysis and mean standardized uptake value from FDG PET. Functional dose-volume parameters calculated in regions of highly functional lung, defined on perfusion (p) or SUV (s) images, included mean lung dose (pMLD, sMLD) and V20 (pV20, sV20). Fraction of integral lung function receiving ≥20 Gy (pF20, sF20) was also calculated. Equivalent doses in 2 Gy per fraction (EQD2) were calculated to account for differences in treatment regimens and dose fractionation (EQD2Lung). Results Two anatomic dosimetric parameters (MLD, V20) and 4 functional dosimetric parameters (pMLD, pV20, pF20, sF20) were significant predictors of grade ≥2 pneumonitis (area under the curve >0.84; P < .05). Dose-independent functional lung heterogeneity metrics were not associated with pneumonitis incidence. At thresholds of 100% sensitivity and 65% to 91% specificity, corresponding to maximum prediction accuracy for pneumonitis, these parameters had the following cutoff values: MLD = 13.6 Gy EQD2Lung, V20 = 25%, pMLD = 13.2 Gy EQD2Lung, pV20 = 15%, pF20 = 17%, and sF20 = 25%. Significant parameters MLD, V20, pF20, and sF20 were not cross-correlated to significant parameters pMLD and pV20, indicating that they may offer independently predictive information (Spearman ρ < 0.7). Conclusions We reported differences in anatomic and functional lung dosimetry between patients with and without pneumonitis in this limited patient cohort. Adding selected independent functional lung parameters may risk stratify patients for pneumonitis. Validation studies are ongoing in a prospective functional lung avoidance trial at our institution. To apply a previously designed framework for predicting radiation pneumonitis by using pretreatment lung function heterogeneity metrics, anatomic dosimetry, and functional lung dosimetry derived from 2 imaging modalities within the same cohort. Treatment planning computed tomography (CT) scans were co-registered with pretreatment [99mTc] macro-aggregated albumin perfusion single-photon positron emission tomography (SPECT)/CT scans and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans of 28 patients who underwent definitive thoracic radiation. Clinical radiation pneumonitis was defined as grade ≥2 (Common Terminology Criteria for Adverse Events, v. 4). Anatomic dosimetric parameters (mean lung dose [MLD], volume receiving ≥20 Gy [V20]) were collected from treatment planning scans. Baseline functional lung heterogeneity parameters and functional lung dose-volume parameters were calculated from pretreatment SPECT/CT and FDG PET/CT scans. Functional heterogeneity parameters calculated over the tumor-subtracted lung included skewness, kurtosis, and coefficient of variation from perfusion SPECT and FDG PET and the global lung parenchymal glycolysis and mean standardized uptake value from FDG PET. Functional dose-volume parameters calculated in regions of highly functional lung, defined on perfusion (p) or SUV (s) images, included mean lung dose (pMLD, sMLD) and V20 (pV20, sV20). Fraction of integral lung function receiving ≥20 Gy (pF20, sF20) was also calculated. Equivalent doses in 2 Gy per fraction (EQD2) were calculated to account for differences in treatment regimens and dose fractionation (EQD2Lung). Two anatomic dosimetric parameters (MLD, V20) and 4 functional dosimetric parameters (pMLD, pV20, pF20, sF20) were significant predictors of grade ≥2 pneumonitis (area under the curve >0.84; P < .05). Dose-independent functional lung heterogeneity metrics were not associated with pneumonitis incidence. At thresholds of 100% sensitivity and 65% to 91% specificity, corresponding to maximum prediction accuracy for pneumonitis, these parameters had the following cutoff values: MLD = 13.6 Gy EQD2Lung, V20 = 25%, pMLD = 13.2 Gy EQD2Lung, pV20 = 15%, pF20 = 17%, and sF20 = 25%. Significant parameters MLD, V20, pF20, and sF20 were not cross-correlated to significant parameters pMLD and pV20, indicating that they may offer independently predictive information (Spearman ρ < 0.7). We reported differences in anatomic and functional lung dosimetry between patients with and without pneumonitis in this limited patient cohort. Adding selected independent functional lung parameters may risk stratify patients for pneumonitis. Validation studies are ongoing in a prospective functional lung avoidance trial at our institution.