Purpose/Objective(s)
Stereotactic body radiotherapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort, and to identify predictive dosimetric parameters.
Methods and Materials
We identified patients who received SBRT for central tumors according to either of two definitions. Local failure (LF) was estimated using a competing-risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity, and applied Cox proportional hazard analysis and logrank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.
Results
One hundred twenty-five patients received SBRT for NSCLC (n=103) or metastatic (n=22) lesions using IMRT. The most common dose was 45Gy in 5 fractions. Median followup was 17.4 months. Incidence of grade ≥ 3 toxicity was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced grade ≥2 esophageal toxicity, including 50% of patients where PTV overlapped the esophagus. There were two treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥ 80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” or NFZ) correlated with grade ≥ 2 pulmonary toxicity. There was no difference in pulmonary toxicity between central tumors located inside the NFZ, and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.
Conclusion
Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.
Background and Purpose
Stereotactic body radiotherapy (SBRT) to central lung tumors can cause esophageal toxicity, but little is known about the incidence or risk factors. We reviewed central lung SBRT patients to identify dosimetric factors predictive of esophageal toxicity.
Material and Methods
We assessed esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with α/β=10 Gy (BED10), dose-volume histogram variables for the esophagus (Dv and Vd) were assessed for correlation with grade ≥2 acute toxicity.
Results
Incidence of grade ≥2 acute toxicity was 12% (n=15). Highly significant logistic models were generated for D5cc and Dmax (p<0.001). To keep the complication rate < 20%, the model requires that D5cc ≤ 26.3 BED10. At 2 years, the probability of complication with BED10 D5cc > 14.4 Gy was 24%, compared to 1.6% if ≤14.4 Gy.
Conclusions
This novel analysis provides guidelines to predict acute esophageal toxicity in lung SBRT. Dose to the hottest 5cc and Dmax of the esophagus were the best predictors of toxicity. Converting the BED10 limits to physical doses, D5cc to the esophagus should be kept less than 16.8, 18.1 and 19.0 Gy for 3, 4, and 5 fractions, respectively, to keep the acute toxicity rate < 20%.
SynopsisThe interfacial reaction between a liquid polyfunctional aromatic isocyanate and a diol was studied using infrared spectroscopy to follow the reduction in concentration of the isocyanate group. It was shown that the product polyurethane formed a gel layer around dispersed isocyanate droplets which were swollen by the diol but not by fhe isocyanate. A model for the process is suggested based on the reaction occuring at the interface of a diminishing droplet surface. It is suggested that the reaction is controlled by the reaction kinetic parameters and the mass transfer by diffusion of the diol through the product layer. Quantitative evaluation is based on steady and nonsteady state diffusion theories.
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