Predictors of radiotherapy induced bone injury (RIBI) after stereotactic lung radiotherapy

Abstract

Background: The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy.

Methods: Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created.

Results: 46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 - 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 - 40 m). The mean maximum point dose in non-fractured ribs (n=1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n=41) 48.5 Gy ± 24.3 Gy (p<0.0001). On univariate analysis, age, dose to 0.5 cc of the ribs (D0.5), and the volume of the rib receiving at least 25 Gy (V25), were significantly associated with RIBI. As D0.5 and V25 were cross-correlated (Spearman correlation coefficient: 0.57, p<0.001), we selected D0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 - 1.21, p=0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 - 11.68, p=0.003), and rib D0.5 (odds ratio: 1.0009, 95% CI: 1.0007 - 1.001, p<0.0001) were significantly associated with rib fracture.Using D0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D0.5 of 60 Gy.

Conclusions: Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.

Figure 1

Anatomic locations of 41 fractured ribs in 17 patients with RIBI.

Figure 2

Kaplan Meier curve for fractured rib as an event (n = 46 patients). Dashed lines indicate 95% confidence intervals.

Figure 3

Grading of chest wall pain (n = 21 patients with reports of chest wall pain > 0) and rib fractures (n = 17 patients, 43 fractures) based on CTCAE criteria.

Figure 4

Maximum likelihood curve for fractured ribs. Dx: Absolute dose to a certain volume (0.5-10 cc) of the ribs. Vx: Absolute volume receiving certain dose (15-50 Gy) of the ribs.

Figure 5

a: D_0.5 for patients with fractured ribs (pink triangle) and without fractured ribs (Green diamond); calculated probability of fracture (blue diamond) at the median follow up of 25 months based on D_0.5 . b: Distribution of 17 patients with fractured rib per D_0.5 dose groups (10 Gy bin size), and calculated probability of fracture (blue diamond).

Figure 6

RIBI nomogram based on gender, age and D_0.5 in 46 patients treated with SBRT at Princess Margaret Hospital (Estimating risk of rib fracture at median follow up of 25 month). Risk of rib fracture in a 75 year old lady treated with 54 Gy in 3 fractions and D0.5 of 60 Gy (within a median FU of 2 years)is about 65%.