Clinical and dosimetric factors impacting radiation pneumonitis in isotoxically dose-escalated NSCLC


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Sindu Vivekanandan1,David Landau2,Nicholas Counsell3,Daniel Warren1,Laura Farrelly4,Yenting Ngai4,Maria Hawkins1,John Fenwick5

1University of Oxford,2Guy’s Hospital, London,3UCL Clinical Trials Unit,4UCL trials Unit,5University of Liverpool

Abstract

Background

Radiation pneumonitis (RP) has been related to various clinical and radiation dosimetric factors such as mean lung equivalent dose in 2Gy fractions (ML-EQD2). Here we test the hypothesis that other factors impact grade 2 or higher RP within 6 months of radiotherapy (RT) (≥G2RP) when ML- EQD2 is controlled.

Method

We analyzed 114 patients treated to 63-73Gy in 30 fractions in a prospective isotoxically escalated RT trial. An initial prescribed tumor dose (PD) was selected to achieve ML-EQD2 of 18.2Gy. Dose volume histograms (DVHs) were extracted for these structures: Whole lung minus GTV (L-GTV), lung on contralateral (CL) and ipsilateral (IL) sides of the tumor, CL and IL split into equal thirds (upper, middle and lower). 95% of variance between L-GTV DVHs was represented by principal components (PC). Maximum RP scores within 6 months of RT were collated. Univariable logistic regression analysis (UVA) was performed to ascertain associations of clinical factors, L-GTV PCs and ML-EQD2 with ≥G2RP risk. The best multivariable (MV) model was obtained from these factors via stepwise selection using Akaike information criterion. The significant L-GTV PC in the MV model was replaced by the L-GTV and CL/IL section volumes irradiated to the dose levels represented by that PC for further localization.

Results

Mean PD was 67.1Gy. ML-EQD2 mean was 14.4Gy. The ≥G2RP rate was 26%. On UVA, there was no evidence that ML-EQD2 mean was associated with ≥G2RP risk, but ≥G2RP risk increased with poor PS and high L-GTV PC5 (representing greater L-GTV volumes receiving 4-9Gy, L-GTV4-9). L-GTV PC5, poor PS, and high baseline FVC (FVC0) were significantly associated with ≥G2RP risk. L-GTV6-9 and CL lower segment receiving 4-9Gy (CLL4-9) were significantly associated with ≥G2RP risk when they replace L-GTV PC5.

Conclusion

Poor PS, high FVC0 and greater lung volumes receiving 4-9Gy were associated with increased ≥G2RP risk.