Background and purpose: The literature on dose-volume parameters and pneumonitis is extensive. The results are inconsistent

both for the best predictive metrics and significant comorbid factors. This study aimed to investigate a prospective functional equivalent uniform dose (fEUD) with perfusion single photon emission computed tomography (SPECT) images as predictors of radiation pneumonitis (RP) in patients undergoing curative radiotherapy (

RT). Methods: Functional lung imaging was performed using SPECT for perfusion imaging. Perfusion factors were defined as the mean percentile perfusion levels of the 4 areas

top to 75%

75% to 50%

50% to 25%

25% to 0%

respectively. fEUD was calculated from perfusion factors and standard dose-volume parameters extracted from treatment planning computed tomography (CT) scans. Total lung (TL)

ipsilateral (IL) and contralateral lung (CL) volumes minus gross tumor volume (GTV)

whole-lung V

5

V

20

whole lung fEUD

IL and CL fEUD

and general equivalent uniform dose (gEUD) were analyzed to evaluate correlations between RP using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Statistical significance was defined as P0.05. Results: A total of 15 patients treated with intensity modulated RT or 3D conformal RT were analyzed

grades≥3 RP were observed in 6 patients. There was only a trend toward significance for unilateral (UL) fEUD of higher dose side (P=0.007). Whole-lung V

5

V

20

were almost identical between patients who developed pneumonitis and patients who did not

as the values were below the recommended thresholds from published papers. Unilateral fEUDs were linear with unilateral gEUDs (t=0.815

P=0.000). Conclusion: SPECT-based equivalent uniform dose appears to be a better predictor of RP compared to standard dose-volume parameters. Planning constraints should aim to keep unilateral fEUD below 21 Gy.