Impact of Fractionation and Dose in a Multivariate Model for Radiation-Induced Chest Wall Pain.

Purpose: To determine the role of patient/tumor characteristics, radiation dose, and fractionation using the linear-quadratic (LQ) model to predict stereotactic body radiation therapy-induced grade ≥ 2 chest wall pain (CWP2) in a larger series and develop clinically useful constraints for patients treated with different fraction numbers.
Methods and Materials: A total of 316 lung tumors in 295 patients were treated with stereotactic body radiation therapy in 3 to 5 fractions to 39 to 60 Gy. Absolute dose-absolute volume chest wall (CW) histograms were acquired. The raw dose-volume histograms (α/β = ∞ Gy) were converted via the LQ model to equivalent doses in 2-Gy fractions (normalized total dose, NTD) with α/β from 0 to 25 Gy in 0.1-Gy steps. The Cox proportional hazards (CPH) model was used in univariate and multivariate models to identify and assess CWP2 exposed to a given physical and NTD.
Results: The median follow-up was 15.4 months, and the median time to development of CWP2 was 7.4 months. On a univariate CPH model, prescription dose, prescription dose per fraction, number of fractions, D83cc, distance of tumor to CW, and body mass index were all statistically significant for the development of CWP2. Linear-quadratic correction improved the CPH model significance over the physical dose. The best-fit α/β was 2.1 Gy, and the physical dose (α/β = ∞ Gy) was outside the upper 95% confidence limit. With α/β = 2.1 Gy, VNTD99Gy was most significant, with median VNTD99Gy = 31.5 cm(3) (hazard ratio 3.87, P<.001).
Conclusion: There were several predictive factors for the development of CWP2. The LQ-adjusted doses using the best-fit α/β = 2.1 Gy is a better predictor of CWP2 than the physical dose. To aid dosimetrists, we have calculated the physical dose equivalent corresponding to VNTD99Gy = 31.5 cm(3) for the 3- to 5-fraction groups.
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