Correlation of Perfused Lung Heterogeneity and Dosimetry With Incidence of Radiation Pneumonitis

Abstract

In patients undergoing radiation treatment to the thorax, baseline lung function and functional lung dosimetry may play an important role in modulating pneumonitis risk. We evaluated features of perfused lung heterogeneity and dosimetry for correlation to incidence of radiation-induced pneumonitis. Pre-treatment 99mTc-MAA perfusion SPECT/CT scans were co-registered to planning CT scans in 28 patients who received definitive-dose thoracic radiotherapy: 20 patients with non-small cell lung cancer, 5 with small cell lung cancer, and 3 with lung metastasis. Eleven patients underwent IMRT or 3DCRT, 7 SBRT, and 10 proton RT. Two patients had clinical grade 2, one patient had grade 3, and two patients had grade 4 radiation pneumonitis defined by CTCAE version 4. Anatomic GTV-subtracted total lung (TL-GTV) mean dose (MLD) and dose-volumes were extracted. Threshold percentages of maximum perfusion (10-90%) within TL-GTV defined functional lung volumes, from which mean perfused lung doses (pMLD10-90%) were calculated. Dose-function histogram quantiles, defined as the fraction of integral lung perfusion receiving a given dose or higher (FGy), were recorded. Heterogeneity in baseline lung perfusion was assessed by intensity histogram distribution moments (coefficient of variation, skewness, kurtosis). Doses were voxelwise converted to EQD2a/b=3and GyRBE to account for fractionation variability and proton therapy dosing, respectively. Logistic regression characterized the predictive accuracy of features for incidence of grade 2 or higher pneumonitis (G2+ PNM). Anatomic mean lung dose was significantly higher in G2+ PNM patients following Mann-Whitney testing (14.6 vs. 9.3 GyEQD2, p=0.003). Patients with G2+ PNM demonstrated significantly higher pMLD70% (19.3 vs. 5.6 GyEQD2, p=0.02). MLD (p=0.002), pMLD70% (p=0.02) and F25Gy (p=0.009) were predictive of G2+ PNM under univariate logistic regression (AUC>0.79). Patients at high risk for pneumonitis presented with MLD>13.6 GyEQD2, pMLD70%>13.2 GyEQD2 and F25Gy>16% (100% sensitivity, >74% specificity). Baseline perfused lung distribution coefficient of variation, skewness and kurtosis did not correlate with G2+ PNM incidence. Perfused lung dose and dose-function histogram parameters were statistically associated with incidence of grade 2 or higher radiation pneumonitis. Validation of these functional lung planning constraints is underway within a prospective functional lung avoidance trial.