Analysis of Radiation Pneumonitis (RP) Incidence in a Phase I Stereotactic Body Radiotherapy (SBRT) Dose Escalation Study for Multiple Metastases

Abstract

Purpose/Objective(s)To determine the relation between the incidence of RP and the SBRT dose distribution in a Phase I dose escalation study of multiple metastases.Materials/MethodsPatients with 1-5 sites of metastatic cancer with a life expectancy of >3 months and good performance status received escalating doses of radiation to all known sites of cancer with SBRT. Twenty-eight patients with 50 lesions in the lung were evaluated for this study. All patients underwent 4DCT simulation and FDG PET (if possible) for internal target volume (ITV) delineation on 4DCT images. Planning target volumes (PTV) varied from 5.7cc to 265.6cc and received 24 Gy to 48 Gy in 3 fractions. In addition, one of the patients received a dose fractionation of 10 x 5 Gy and another one 30 x 2 Gy to one of their lung sites, respectively. Optimized SBRT plans with 9-15 coplanar/noncoplanar beam arrangements were designed using a treatment planning system with convolution/superposition algorithm and tissue heterogeneity corrections. The gated SBRT treatments were delivered between July 2005 and December 2008. Dose volume histograms (DVH) were calculated for the total lung excluding the gross tumor and converted to normalized total dose (NTD) at 2 Gy fractions by using the linear quadratic model with α/β ratio of 3 Gy. Normal tissue complication probabilities (NTCP) were evaluated using the Lyman model as per Kwa et al. (1998). Late toxicities were scored using the NCI Common Terminology Criteria for Adverse Events v3.0.ResultsA 61% local control was achieved with 39% of patients surviving in this cohort at the time of study. Seven patients out of 28 experienced grade 2 or higher RP. An increasing RP rate with increasing NTDmean was observed to be significant with a mean NTD of 1514±402c Gy for >grade 2 versus 854±508c Gy for < grade 2 (p = 0.004). The Lyman NTCP modeling with the parameters NTD50 = 30.5 Gy and m = 0.30 produced a well-defined NTCP curve with mean values of 6.0±4.0% for >grade2 and 2.0±3.4% for <grade 2 (p = 0.048). One patient data was an outlier (grade 1, NTmean = 1013 c Gy, NTCP = 3.8%) which happened to be the patient with the largest PTV of 265 cc treated to 3x8 Gy. Other dosimetric indices such as the ratios of prescription isodose volumes (PIV) to PTV (PIV/PTV) were consistent with plan complexity for large and multiple lesions but not significant between the groups with RP grade > or < 2 (p = 0.086).ConclusionsThe dose-effect relation between the NTDmean and RP established for standard fractionated treatments of lung may be extended to the SBRT treatments of multiple lung lesions up to 3x16 Gy as a predictor of lung toxicity. This tool can facilitate the SBRT treatment planning and analysis process in a dose fractionation regimen not well experienced. Purpose/Objective(s)To determine the relation between the incidence of RP and the SBRT dose distribution in a Phase I dose escalation study of multiple metastases. To determine the relation between the incidence of RP and the SBRT dose distribution in a Phase I dose escalation study of multiple metastases. Materials/MethodsPatients with 1-5 sites of metastatic cancer with a life expectancy of >3 months and good performance status received escalating doses of radiation to all known sites of cancer with SBRT. Twenty-eight patients with 50 lesions in the lung were evaluated for this study. All patients underwent 4DCT simulation and FDG PET (if possible) for internal target volume (ITV) delineation on 4DCT images. Planning target volumes (PTV) varied from 5.7cc to 265.6cc and received 24 Gy to 48 Gy in 3 fractions. In addition, one of the patients received a dose fractionation of 10 x 5 Gy and another one 30 x 2 Gy to one of their lung sites, respectively. Optimized SBRT plans with 9-15 coplanar/noncoplanar beam arrangements were designed using a treatment planning system with convolution/superposition algorithm and tissue heterogeneity corrections. The gated SBRT treatments were delivered between July 2005 and December 2008. Dose volume histograms (DVH) were calculated for the total lung excluding the gross tumor and converted to normalized total dose (NTD) at 2 Gy fractions by using the linear quadratic model with α/β ratio of 3 Gy. Normal tissue complication probabilities (NTCP) were evaluated using the Lyman model as per Kwa et al. (1998). Late toxicities were scored using the NCI Common Terminology Criteria for Adverse Events v3.0. Patients with 1-5 sites of metastatic cancer with a life expectancy of >3 months and good performance status received escalating doses of radiation to all known sites of cancer with SBRT. Twenty-eight patients with 50 lesions in the lung were evaluated for this study. All patients underwent 4DCT simulation and FDG PET (if possible) for internal target volume (ITV) delineation on 4DCT images. Planning target volumes (PTV) varied from 5.7cc to 265.6cc and received 24 Gy to 48 Gy in 3 fractions. In addition, one of the patients received a dose fractionation of 10 x 5 Gy and another one 30 x 2 Gy to one of their lung sites, respectively. Optimized SBRT plans with 9-15 coplanar/noncoplanar beam arrangements were designed using a treatment planning system with convolution/superposition algorithm and tissue heterogeneity corrections. The gated SBRT treatments were delivered between July 2005 and December 2008. Dose volume histograms (DVH) were calculated for the total lung excluding the gross tumor and converted to normalized total dose (NTD) at 2 Gy fractions by using the linear quadratic model with α/β ratio of 3 Gy. Normal tissue complication probabilities (NTCP) were evaluated using the Lyman model as per Kwa et al. (1998). Late toxicities were scored using the NCI Common Terminology Criteria for Adverse Events v3.0. ResultsA 61% local control was achieved with 39% of patients surviving in this cohort at the time of study. Seven patients out of 28 experienced grade 2 or higher RP. An increasing RP rate with increasing NTDmean was observed to be significant with a mean NTD of 1514±402c Gy for >grade 2 versus 854±508c Gy for < grade 2 (p = 0.004). The Lyman NTCP modeling with the parameters NTD50 = 30.5 Gy and m = 0.30 produced a well-defined NTCP curve with mean values of 6.0±4.0% for >grade2 and 2.0±3.4% for <grade 2 (p = 0.048). One patient data was an outlier (grade 1, NTmean = 1013 c Gy, NTCP = 3.8%) which happened to be the patient with the largest PTV of 265 cc treated to 3x8 Gy. Other dosimetric indices such as the ratios of prescription isodose volumes (PIV) to PTV (PIV/PTV) were consistent with plan complexity for large and multiple lesions but not significant between the groups with RP grade > or < 2 (p = 0.086). A 61% local control was achieved with 39% of patients surviving in this cohort at the time of study. Seven patients out of 28 experienced grade 2 or higher RP. An increasing RP rate with increasing NTDmean was observed to be significant with a mean NTD of 1514±402c Gy for >grade 2 versus 854±508c Gy for < grade 2 (p = 0.004). The Lyman NTCP modeling with the parameters NTD50 = 30.5 Gy and m = 0.30 produced a well-defined NTCP curve with mean values of 6.0±4.0% for >grade2 and 2.0±3.4% for <grade 2 (p = 0.048). One patient data was an outlier (grade 1, NTmean = 1013 c Gy, NTCP = 3.8%) which happened to be the patient with the largest PTV of 265 cc treated to 3x8 Gy. Other dosimetric indices such as the ratios of prescription isodose volumes (PIV) to PTV (PIV/PTV) were consistent with plan complexity for large and multiple lesions but not significant between the groups with RP grade > or < 2 (p = 0.086). ConclusionsThe dose-effect relation between the NTDmean and RP established for standard fractionated treatments of lung may be extended to the SBRT treatments of multiple lung lesions up to 3x16 Gy as a predictor of lung toxicity. This tool can facilitate the SBRT treatment planning and analysis process in a dose fractionation regimen not well experienced. The dose-effect relation between the NTDmean and RP established for standard fractionated treatments of lung may be extended to the SBRT treatments of multiple lung lesions up to 3x16 Gy as a predictor of lung toxicity. This tool can facilitate the SBRT treatment planning and analysis process in a dose fractionation regimen not well experienced.