- Email: [email protected]
Toward Individualized Fractionation Schedule for Lung Cancer Radiation Therapy
S542
International Journal of Radiation Oncology Biology Physics
Conclusions: Results indicate that the proposed biomechanical model achieves superior performance and provides significant improvement in registration accuracy compared to the uniform model. With estimation of elastic parameters, the proposed model allows for a patient-specific, location-specific and direction-specific mater property distribution, which is more suitable for physically realistic simulation of lung deformation. Author Disclosure: M. Li: None. E. Castillo: None. H. Luo: None. X. Zheng: None. R. Castillo: None. D. Meshkov: None. L. Tan: None. Y. Wu: None. S. Zhang: None. T. Guerrero: None.
2889 The Dependence of Optimal Fractionation Scheme on Dose Distribution, Tissue Damage Model, and Prescription Dose in Radiation Therapy of Lung Cancer Y. Fan; Baystate Health Systems, Inc., Springfield, MA Purpose/Objective(s): The optimal fractionation scheme is crucial in improving the quality of radiation therapy of lung cancer as the hypofractionated SBRT has been widely implemented. Its dependence on spatial dose distribution has been addressed in recent articles but the dependence on tissue damage model has not been fully studied. The purpose of this work is to investigate its dependence on both spatial dose distribution and tissue damage model and provide a better understanding and guidance for optimal fractionation choice. Materials/Methods: Various equivalent fractionation schemes with same equivalent dose in 2 Gy fractions (EQD2) to tumor were obtained with the linear quadratic (LQ) model. The correspondent spatial distributions of EQD2 to normal lung were calculated for typical DVHs in lung cancer treatments including AP/PA, 3D conformal, IMRT and SBRT from the literature. The EQD2-Volume-Histograms of normal lung were compared for equivalent fractionation schemes. The local dose effect by EQD2 to each volume unit vi of lung as parallel functional subunit (FSU) was determined through FSU damage probability (pi) model with parameters derived from best-fit to whole lung irradiation data. The total lung complication probability is then expressed as S v i pi. Results: First, illustration was made that there is a certain isodose level at which the EQD2s to normal lung are the same for all fractionation schemes with same EQD2 to tumor. This relative isodose level is determined by the ratio of a/b of normal tissue to a/b of tumor which is 30% corresponding to a fractionation-equivalent dose FED Z 45 Gy for a typical 60 Gy in 3 fraction SBRT treatment. Fewer fractions results in lower EQD2 to the part of lung receiving dose lower than FED, but higher EQD2 to the part of lung receiving dose higher than FED. Secondly, the optimal fractionation choice based on minimum total lung toxicity is shown to be dependent on the location of the FSU damage curve - below or above FED. As the damage-sensitive dose range is around D50w20-30 Gy of the FSU damage curve, which is below 45 Gy, fewer-fraction scheme is preferred. Although fewer fractions results in higher EQD2 to the part of lung receiving higher than 45 Gy, it does not contribute to whole lung complication as full inactivation (pi Z 1) in this part has been reached. Conclusions: The optimal fractionation depends not only on spatial dose distribution but also on normal tissue damage model and prescription dose. Hypo-fractionation in current SBRT protocols causes less lung toxicity than traditional or hyper-fractionation while delivering same EQD2 to the tumor. FSU based local dose effect model is more adequate than MLD/ EUD based whole lung dose effect model when higher dose is delivered to an already fully inactivated area. Author Disclosure: Y. Fan: None.
2888 Toward Individualized Fractionation Schedule for Lung Cancer Radiation Therapy N. Xiao,1,2 F. Kong,3,4 I. Chetty,1 J. Burmeister,2,5 M. Joiner,2 and J. Jin1; 1 Henry Ford Hospital, Detroit, MI, 2Wayne State University, Detroit, MI, 3 University of Michigan, Ann Arbor, MI, 4Veteran’s Hospital, Ann Arbor, MI, 5Karmanos Cancer Center, Detroit, MI Purpose/Objective(s): In light of the wide range of fractionation regimens in lung cancer treatment (from conventional RT of 2 Gy/fx to single fraction of 34 Gy), this study aims to compare the relative damaged volume (RDV) of the dose-limiting normal structure (normal lung, in this study) for various fractionation regimens while giving the same biologically equivalent dose (BED) to tumor. A smaller RDV value represents lower normal tissue complication probability (NTCP) and higher therapeutic ratio. Materials/Methods: The RDV was computed for 4 typical lung cancer cases for 17 different fractionation regimens (1-8, 10, 12, 15, 20, 25, 30, 35, 40, and 50 fractions). Conventional 35 x 2 Gy fractionation was used as the tumor control probability (TCP) reference. The linear quadratic model with a correction for tumor regrowth effect (Tpot) was used to determine BED to tumor, assuming a/b ratios of 3 and 10 for normal lung and tumor, respectively. The RDV was calculated from the patient’s BED-corrected lung DVH using the following equation, P RDVZ EðBEDi Þ ,vi ; where EðDÞZ D1L50 2 is a logistic local 1þð D Þ i response function, and DL50, the dose required to produce 50% local damage in the conventional fractionation, was converted to BEDL50 in the calculation. Various Tpot (5-30 days) and DL50 (20-50 Gy) values were used to calculate RDV for each patient. Results: The minimum RDV among 17 studied fractionation regimens varied from case to case, and with Tpot and BEDL50. The table below shows the optimal number of fractions and the% reduction in RDV from conventional 35 x 2 Gy fractionation regimen for an example patient (Patient #3). Overall, the optimal number of fractions varied between 1 and 3 for low DL50 (20 Gy) and Tpot (5 days), between 5 and 10 for medium DL50 (30 Gy) and Tpot (10-20 days), and further increases to 25-40 range for large DL50 and Tpot values. Greater than 20% RDV reductions were achieved in some situations. Conclusions: This computational study predicts that an optimal fractionation regimen may exist for each patient using a model based on basic radiobiological principles. An individualized fractionation scheme, such as hypofractionation vs conventional fractionation, may be determined by using a patient’s DVH, DL50, and Tpot to improve the therapeutic ratio. Author Disclosure: N. Xiao: None. F. Kong: None. I. Chetty: None. J. Burmeister: None. M. Joiner: None. J. Jin: None.
2890 Deep Inspiration Breath-Hold Radiation Therapy for Advanced Stage Lung Cancer Is Feasible and Facilitates Lung Toxicity Reduction M. Josipovic, G.F. Persson, K. Ha˚kansson, S. Damkjær, G. Westman, J. Bangsgaard, L. Specht, and M. Aznar; Rigshospitalet, Copenhagen, Denmark
Poster Viewing Abstract 2888; Table
Optimal fraction # and % reduction in RDV from conventional 35X2 Gy fractionation regimen
Fx # for min RDV (RDV Reduction %)
DL50 Z 20 Gy
Tpot Tpot Tpot Tpot
Z Z Z Z
5 days 10 days 20 days 30 days
1 1 1 1
(24%) (11%) (6%) (5%)
DL50 Z 25 Gy 3 5 5 10
(23%) (9%) (3%) (2%)
DL50 Z 30 Gy 5 5 15 20
(24%) (7%) (2%) (1%)
DL50 Z 35 Gy 5 10 20 25
(24%) (7%) (1%) (0%)
DL50 Z 40 Gy 5 10 20 30
(24%) (6%) (1%) (0%)
DL50 Z 45 Gy 5 15 25 35
(24%) (5%) (1%) (0%)
DL50 Z 50 Gy 5 15 25 40
(23%) (5%) (0%) (0%)
International Journal of Radiation Oncology Biology Physics
Conclusions: Results indicate that the proposed biomechanical model achieves superior performance and provides significant improvement in registration accuracy compared to the uniform model. With estimation of elastic parameters, the proposed model allows for a patient-specific, location-specific and direction-specific mater property distribution, which is more suitable for physically realistic simulation of lung deformation. Author Disclosure: M. Li: None. E. Castillo: None. H. Luo: None. X. Zheng: None. R. Castillo: None. D. Meshkov: None. L. Tan: None. Y. Wu: None. S. Zhang: None. T. Guerrero: None.
2889 The Dependence of Optimal Fractionation Scheme on Dose Distribution, Tissue Damage Model, and Prescription Dose in Radiation Therapy of Lung Cancer Y. Fan; Baystate Health Systems, Inc., Springfield, MA Purpose/Objective(s): The optimal fractionation scheme is crucial in improving the quality of radiation therapy of lung cancer as the hypofractionated SBRT has been widely implemented. Its dependence on spatial dose distribution has been addressed in recent articles but the dependence on tissue damage model has not been fully studied. The purpose of this work is to investigate its dependence on both spatial dose distribution and tissue damage model and provide a better understanding and guidance for optimal fractionation choice. Materials/Methods: Various equivalent fractionation schemes with same equivalent dose in 2 Gy fractions (EQD2) to tumor were obtained with the linear quadratic (LQ) model. The correspondent spatial distributions of EQD2 to normal lung were calculated for typical DVHs in lung cancer treatments including AP/PA, 3D conformal, IMRT and SBRT from the literature. The EQD2-Volume-Histograms of normal lung were compared for equivalent fractionation schemes. The local dose effect by EQD2 to each volume unit vi of lung as parallel functional subunit (FSU) was determined through FSU damage probability (pi) model with parameters derived from best-fit to whole lung irradiation data. The total lung complication probability is then expressed as S v i pi. Results: First, illustration was made that there is a certain isodose level at which the EQD2s to normal lung are the same for all fractionation schemes with same EQD2 to tumor. This relative isodose level is determined by the ratio of a/b of normal tissue to a/b of tumor which is 30% corresponding to a fractionation-equivalent dose FED Z 45 Gy for a typical 60 Gy in 3 fraction SBRT treatment. Fewer fractions results in lower EQD2 to the part of lung receiving dose lower than FED, but higher EQD2 to the part of lung receiving dose higher than FED. Secondly, the optimal fractionation choice based on minimum total lung toxicity is shown to be dependent on the location of the FSU damage curve - below or above FED. As the damage-sensitive dose range is around D50w20-30 Gy of the FSU damage curve, which is below 45 Gy, fewer-fraction scheme is preferred. Although fewer fractions results in higher EQD2 to the part of lung receiving higher than 45 Gy, it does not contribute to whole lung complication as full inactivation (pi Z 1) in this part has been reached. Conclusions: The optimal fractionation depends not only on spatial dose distribution but also on normal tissue damage model and prescription dose. Hypo-fractionation in current SBRT protocols causes less lung toxicity than traditional or hyper-fractionation while delivering same EQD2 to the tumor. FSU based local dose effect model is more adequate than MLD/ EUD based whole lung dose effect model when higher dose is delivered to an already fully inactivated area. Author Disclosure: Y. Fan: None.
2888 Toward Individualized Fractionation Schedule for Lung Cancer Radiation Therapy N. Xiao,1,2 F. Kong,3,4 I. Chetty,1 J. Burmeister,2,5 M. Joiner,2 and J. Jin1; 1 Henry Ford Hospital, Detroit, MI, 2Wayne State University, Detroit, MI, 3 University of Michigan, Ann Arbor, MI, 4Veteran’s Hospital, Ann Arbor, MI, 5Karmanos Cancer Center, Detroit, MI Purpose/Objective(s): In light of the wide range of fractionation regimens in lung cancer treatment (from conventional RT of 2 Gy/fx to single fraction of 34 Gy), this study aims to compare the relative damaged volume (RDV) of the dose-limiting normal structure (normal lung, in this study) for various fractionation regimens while giving the same biologically equivalent dose (BED) to tumor. A smaller RDV value represents lower normal tissue complication probability (NTCP) and higher therapeutic ratio. Materials/Methods: The RDV was computed for 4 typical lung cancer cases for 17 different fractionation regimens (1-8, 10, 12, 15, 20, 25, 30, 35, 40, and 50 fractions). Conventional 35 x 2 Gy fractionation was used as the tumor control probability (TCP) reference. The linear quadratic model with a correction for tumor regrowth effect (Tpot) was used to determine BED to tumor, assuming a/b ratios of 3 and 10 for normal lung and tumor, respectively. The RDV was calculated from the patient’s BED-corrected lung DVH using the following equation, P RDVZ EðBEDi Þ ,vi ; where EðDÞZ D1L50 2 is a logistic local 1þð D Þ i response function, and DL50, the dose required to produce 50% local damage in the conventional fractionation, was converted to BEDL50 in the calculation. Various Tpot (5-30 days) and DL50 (20-50 Gy) values were used to calculate RDV for each patient. Results: The minimum RDV among 17 studied fractionation regimens varied from case to case, and with Tpot and BEDL50. The table below shows the optimal number of fractions and the% reduction in RDV from conventional 35 x 2 Gy fractionation regimen for an example patient (Patient #3). Overall, the optimal number of fractions varied between 1 and 3 for low DL50 (20 Gy) and Tpot (5 days), between 5 and 10 for medium DL50 (30 Gy) and Tpot (10-20 days), and further increases to 25-40 range for large DL50 and Tpot values. Greater than 20% RDV reductions were achieved in some situations. Conclusions: This computational study predicts that an optimal fractionation regimen may exist for each patient using a model based on basic radiobiological principles. An individualized fractionation scheme, such as hypofractionation vs conventional fractionation, may be determined by using a patient’s DVH, DL50, and Tpot to improve the therapeutic ratio. Author Disclosure: N. Xiao: None. F. Kong: None. I. Chetty: None. J. Burmeister: None. M. Joiner: None. J. Jin: None.
2890 Deep Inspiration Breath-Hold Radiation Therapy for Advanced Stage Lung Cancer Is Feasible and Facilitates Lung Toxicity Reduction M. Josipovic, G.F. Persson, K. Ha˚kansson, S. Damkjær, G. Westman, J. Bangsgaard, L. Specht, and M. Aznar; Rigshospitalet, Copenhagen, Denmark
Poster Viewing Abstract 2888; Table
Optimal fraction # and % reduction in RDV from conventional 35X2 Gy fractionation regimen
Fx # for min RDV (RDV Reduction %)
DL50 Z 20 Gy
Tpot Tpot Tpot Tpot
Z Z Z Z
5 days 10 days 20 days 30 days
1 1 1 1
(24%) (11%) (6%) (5%)
DL50 Z 25 Gy 3 5 5 10
(23%) (9%) (3%) (2%)
DL50 Z 30 Gy 5 5 15 20
(24%) (7%) (2%) (1%)
DL50 Z 35 Gy 5 10 20 25
(24%) (7%) (1%) (0%)
DL50 Z 40 Gy 5 10 20 30
(24%) (6%) (1%) (0%)
DL50 Z 45 Gy 5 15 25 35
(24%) (5%) (1%) (0%)
DL50 Z 50 Gy 5 15 25 40
(23%) (5%) (0%) (0%)