Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours

Objective

The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0–1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours.

Methods

Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose–volume histograms (DVHs) were constructed to identify the incidence of RP.

Results

The median follow-up period was 12 months (range, 6–45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5–30 Gy (V5–30) and mean lung dose were significant factors differentiating between grade 0–1 and grade 2 RP, and V15–30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0–1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0–1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0–2 RP.

Conclusions

Grade 0–2 RP was dose–volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0–2 RP. However, incidences of V15–30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.Previously, we investigated the clinical and dosimetric factors that correlate with severe radiation pneumonitis (RP) in patients with lung tumours treated with stereotactic body radiotherapy (SBRT) 1]. We found that, among a variety of factors, only a short latent period was a significant correlate of severe RP.Other reports 2-6] have also analysed the clinical and dosimetric factors correlated with RP after SBRT. Various dosimetric factors were reported to significantly correlate with RP after SBRT, which included the mean dose in the ipsilateral lung, V7 and V10 by Kyas et al 2], normal tissue complication probability (NTCP) by Ricardi et al 3], lung volumes treated with doses higher than 2.5–50 Gy (V2.5–50) by Guckenberger et al 4], mean lung dose by Barriger et al 5] and contralateral V5 by Ong et al 6].We found a discrepancy in the significant clinical and dosimetric factors between the results of these five studies on low-grade RP 2-6] and our study on severe RP 1]. We speculated that the mechanism underlying the development of grade ≥3 RP might be different from that of grade 2 RP. Additionally, the treatment of grade ≥3 RP was much more critical than that of grade 2 RP. Most patients with grade ≥3 RP needed to be admitted to hospital and steroids or oxygen therapy were administered. By contrast, patients with grade 2 RP were simply followed up carefully without administration of medication as outpatients.In the present study, to ascertain this discrepancy, we analysed the clinical and dosimetric factors that correlated with RP after SBRT among patients with grade 0–1, grade 2 and grade 3 RP in the same sample of patients as that included in our previous study 1].