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

Abstract

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 (n5128) 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][3][4][5][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 nee...

Analysis of Dose Distribution and Risk of Pneumonitis in Stereotactic Body Radiation Therapy for Centrally Located Lung Tumors

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Stereotactic body radiotherapy with helical TomoTherapy for medically inoperable early stage primary and second-primary non-small-cell lung neoplasm: 1-year outcome and toxicity analysis

“…Unlike these investigators, however, we recorded two cases (12.5%) of acute or late grade $2 RP. The frequency after SBRT for early and/or late grade NSCLN with $2 RP varies (0% and 21%, respectively 3,[14][15][16] ), and few dosimetric risk factors such as a high PTV ($37.7 cm 3 15 ) have been identified when using the linear accelerator as a delivery system. The mean PTV of 53 cm 3 obtained here for patients with grade $2 RP is within the range obtained in other studies.…”

A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain

“…For patient cohorts given localized thoracic radiotherapy, female gender was significantly predictive of radiation pneumonitis in some but not in all studies. [130][131][132][133][134] Another 'bad' aspect identified from this literature review is the high reliance on the lethality end point in the majority of mouse lung studies and where it is used as the primary criteria for evaluating therapeutics. This has, in part, been encouraged by interpretations of the FDA 'Animal Rule' wherein it states, and with some ambiguity, that 'The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity'.…”