Transition to Heterogeneity Corrections Eric E. Klein, M.S., Washington University, St. Louis, MO Craig Stevens, M.D., Ph.D., MD Anderson Cancer Center, Houston, TX Nikos Papinikolou, Ph.D., University of Arkansas, Little Rock, AR AAPM 2004 Annual Meeting Why have accurate dose algorithms? Effectiveness of radiation therapy depends on maximum TCP and minimum NTCP. Both of these quantities are very sensitive to absorbed dose We learn how to prescribe from clinical trials and controlled studies. Their outcome depends on the accuracy of reporting data History of Prescriptive Changes Brought Forth by Physics TG-43 changes to S k based on NIST Calibration updates. Gamma Knife (Elekta) found a 8% discrepancy in 4 mm output. End result, Direct Prescription change of 8%. Change from LDR to HDR GYN Brachytherapy. Depends on institution. IMRT Too early to advise if excessive hot spots (EUD concept) matters Inhomogeneity Corrections Clinical Examples Orton et al (1998) Developed benchmark test case Reviewed 322 patients in RTOG 88-08 Results Benchmark lung corrections Measured: 1.14 (Co-60)-1.05 (24 MV) Calculated: 1.17 (Co-60)-1.05 (24 MV) Patients: 0.95-1.28, mean=1.05, SD=0.05 For lateral fields: mean=1.11, SD=0.08 Conclusion Lung corrections lead to significant variations Density corrections will help reduce these variations 1
Inhomogeneity Corrections Clinical Examples Mah & Van Dyk (1991) reviewed 100 thoracic patients Conclusions Within lung, corrections are significant (0.95-1.24) Target dose corrections are significant (0.95-1.21) Substantial variation over patients (-5% to +21%) Dose uniformity reduced in corrected distributions In 80% patients, probability of lung damage underestimated by >5% (up to 19%) if corrections not applied Density Determination Van Dyk IJORBP 1983 Assumed Density Dose Correction Factor % Difference from real density calculation CT Based real 1.40 0 CT Measured 0.26 1.45 +4 (total lung) CT Measured 0.35 1.39-1 (average lung) Age Related Best 0.31 1.42 +2 Fit Age Related Best 0.38 1.37-2 Fit (+ 1 SD) Age Related Best 0.24 1.47 +5 Fit (-1 SD) Emphysema 0.06 1.59 +14 Metastases 0.60 1.23-12 Dose Correction Factors Based on Different Lung Density Assumptions Physics of Photon Dose Calculation Problem TISSUE INHOMOGENEITY CORRECTIONS FOR MEGAVOLTAGE PHOTON BEAMS Report of Task Group 65 of the Radiation Therapy Committee of the American Association of Physicists in Medicine Nikos Papanikolaou University of Arkansas, Little Rock, Arkansas, USA Jerry J. Battista London Regional Cancer Centre, London, Ont., Canada Arthur L. Boyer Stanford University, Stanford, California, USA Constantin Kappas University of Thessaly, Medical School, Larissa, Hellas Eric Klein Mallinckrodt Institute of Radiology, St Louis, MO, USA T. Rock Mackie University of Wisconsin, Madison, Wisconsin, USA Jeff V. Siebers Virginia Commonwealth University, Richmond, Virginia Michael Sharpe Princess Margaret Hospital, Toronto, Canada Jake Van Dyk London Regional Cancer Centre, London, Ont., Canada Incident photons (spectrum) Scattered photons Scattered electrons 2
Energy transfer to electrons Photon energy T mean R CSDA (cm) (MeV) muscle lung bone 1.25 0.59 0.23 0.92 0.14 2 1.06 0.44 1.76 0.26 4 2.4 1.2 4.8 0.72 6 3.86 1.9 7.6 1.16 assumes lung =0.25 g/cc bone =1.85 g/cc T mean = h e tr e Photon scatter Depth (cm) Magnitude of Effects Field size (cm) Scatter (% of total dose) Co-60 6 MV 18 MV 5 5 x 5 12 8 7 10 10 x 10 24 18 14 20 25 x 25 48 38 27 Range of scattered electrons Range Energy Co-60 6 MV 18 MV Forward (cm) 0.5 1.5 3.0 Lateral (cm) 0.2 0.4 0.8 Algorithms used for dose calculation Measurement based Algorithms Model based Algorithms Rely on measured data in water, coupled with empirically derived correction factors to account for patient contour, internal anatomy and beam modifiers (Clarkson, ETAR) Use measured data to derive the model parameters. Once initialized, the model can very accurately predict the dose based on the physical laws of radiation transport (convolution, MC) How many Dimensions? Dimension of anatomy Dimension of scatter inclusion Where will the scatter go? (photons, electrons) z=-1 z=0 z=1 A dose cloud displayed on a 3D rendered volume does Not necessarily suggest a 3D algorithm 3
Local Energy Deposition - No Electron Transport Ratio of Tissue-Air Ratios (RTAR) Handles primary accurately (electronic equilibrium) Partial correction for scatter (modified depth in TAR) Nothing about size, shape or location Local Energy Deposition - No Electron Transport Power Law (Batho) T ( d1, W ) ICF = T ( d 2, W ) 1 2 1 2 d 1 2 d Local Energy Deposition - No Electron Transport Power Law (Batho) Adapted to CT planning by Webb et al layers, multiplicative factors sensitive to depth from surfaces (changes primary & scatter) not sensitive to width better than RTAR under corrects < 1.0, over corrects > 1.0 under predicts for large fields improves with TPR instead of TAR problems when d i lie in build up region O Connor s Scaling Theorem Dose at A = Dose at B d x and w x are equal 4
Local Energy Deposition - No Electron Transport Equivalent Tissue Air Ratio (ETAR) T ( d', ~ r ) ICF = T ( d, r) Uses O Connor s scaling theorem d & r are depth & radius of equivalent field d ' & ~ r are scaled versions of d & r ~ r = r ~ ~ = i j k i j k w ijk w ijk ijk Inhomogeneity Corrections Measured and Calculated Data Mackie et al (1985) Effects of electron transport High energy Predicted by convolution Non Local Energy Deposition - Electron Transport Convolution - Point Kernel D = dxdydz 3 ( x, y, z) K ( x, y, z) D pt Convolution: Dose Computation muscle =1 gr/cm 3 lung =0.25 gr/cm 3 5
Convolution Lung Calculation Convolution/Superposition Homogeneous Scatter Homogeneous Primary and Scatter MDAH History 5 years ago transferred CT info to simulator films by hand. CT not in Rx position "at least" 1cm from tumor edge to block edge dose calculated to midplane in a homogeneous patient Now GTV contoured on Rx planning CT, with FDG PET to identify LN CTV based on the literature (8mm). PTV tumor motion measured in ALL patients (ITV). Set up uncertainty measured (2SD=7mm) then block edge (~7mm) GTV to block edge 8+7+7=22mm Rx 95% of PTV gets Rx dose. 6
Now Able to do this on a service with 8 attendings 2 physicists 6 dosimetrists (that rotate) 12 Rx machines About 100 therapists All while implementing IMRT and other new technologies But we've never done it before. But the changes to the isocenter are small, while coverage of the PTV becomes MUCH better. Planning Characteristics GTV -> CTV 8 mm (Giraud et al., 2000) CTV -> PTV 10 mm PTV -> Block edge 10 mm Beam geometries and prescription (60-66 Gy) were those used for initial treatment. All beams 6MV x-rays Planning Assumptions Plan 1: calculate dose to iso, homogeneous Plan 1H: monitor units from 1, heterogeneous Plan 3: adjust beam weights so that 95% of PTV treated to target dose. 7
Case 1 T1 Goal 66Gy Case 1 What was planned in 3D Case 1 Case 1 1 1H 1H 3 8
Case 1 Monitor units Plan 1 Plan 1H Plan 3 AP 123 123 160 PA 178 178 135 total 301 301 295 Why? Tumor more anterior Lung posterior Case 2 T2 tumor Goal dose 66 Gy to iso Therefore, weighting should be more AP 9
Case 2 Case 2 What the dose distribution looks like in 3D 1 1H Case 2 Case 2 1H 3 10
Dose to GTV Case 2 Case 2 18MV 2 Gy 3 % 1 1H Case 2 18MV Patient Characteristics 1 29 patients with 30 tumors Stage I or Stage II CTV range: 15-359 cm 3 PTV range: 73-760 cm 3 1H 11
Planning Characteristics GTV -> CTV 8 mm (Giraud et al., 2000) CTV -> PTV 10 mm PTV -> Block edge 10 mm Beam geometries and prescription (60-66 Gy) were those used for initial treatment. Planning Assumptions Plan 1: calculate dose to iso, homogeneous Plan 2: monitor units from 1, heterogeneous Plan 3: adjust beam weights so that 95% of PTV treated to target dose. Isocenter Dose Isocenter Dose Dose (Gy) Number of patients Mean difference 3% Plan 1H Plan 3 % Difference Plan 3 - Plan 1H 12
CTV Minimum CTV Maximum CTV Minimum Dose Dose (Gy) Dose (Gy) Number of patients Plan 1H Plan 3 Plan 1H Plan 3 % Difference Plan 3 - Plan 1H CTV Maximum Dose PTV Minimum PTV Maximum Number of patients Dose (Gy) Dose (Gy) % Difference Plan 3 - Plan 1H Plan 1H Plan 3 Plan 1H Plan 3 13
PTV Minimum Dose PTV Maximum Dose Number of patients Number of patients % Difference Plan 3 - Plan 1H % Difference Plan 3 - Plan 1H % PTV Coverage Plan 1H % PTV Coverage 95% of PTV to Goal Dose Number of patients Number of patients p=0.05 % Coverage to Goal Dose % Coverage to Goal Dose 14
Summary Beam arrangement for IMRT plan Monte Carlo is very similar to convolutionsuperposition with heterogeneity Hetero plans are close to Monte Carlo On average PTV coverage is better. Case-by-case can be quite different And it's not hard. But block margin, weighting, and energy will be chosen more accurately Pencil Beam calculations Transverse plane isodose comparison 0.25 cm 0.5cm 1cm 2cm EGS4-BEAM calculations on 2100C Inhomogeneous Calculation accounts for varying tissue densities Homogeneous Calculation assumes all tissue has water density Inhomogeneous with Homogeneous calc MUs Calculation accounts for varying tissue densities but forces the MU from Homogeneous calc Note the difference in coverage in absolute dose between plans 15
GTV Adenopathy Lt. Lung Soft Tissue Dose comparison and Ratio Homogeneous Calculation Max. Dose cgy 5399.71 5420.27 5392.60 5420.27 Mean Dose cgy 5348.06 5341.31 1056.51 292.801 Inhomogeneous Calculation Max. Dose cgy 5428.59 5451.35 5451 5456.66 Mean Dose cgy 5383.83 5399.08 1076.57 299.35 Inhomogeneous w/ Homogeneous MU s Max. Dose cgy 5091.50 5109.21 5110.07 5114.79 Mean Dose cgy 5044.67 5048.74 1011.98 276.946 Ratio of Inhomogeneous w/ Homog. MU s and Homogeneous Max. Dose Ratio in % -5.71-5.74-5.24-5.64 Mean Dose Ratio in % -5.67-5.48-4.21-5.42 Under-dose of 5% or more is introduced by the monitor units as calculated by the homogenous plan TG-65 Recommendations The physicist needs to understand the algorithm(s) within the TPS and MU calculation programs. The physicist is strongly advised to test the planning system to ascertain if the system can predict common trends. The physicist is advised to measure benchmark data for their own beam and compare with the calculated (planning system or hand calculations) data. If possible, the physicist may also use Monte Carlo calculations to support measured data. TG-65 Recommendations The physicist should understand the dose calculation resolution grid, due to volumetric averaging. The physicist should maintain an open dialogue with clinicians and be clear on limitations of the TPS. For each clinical site (eg. left breast, right lung, larynx etc), there should be 5-10 treatment plans generated, with & without inhomogeneity corrections. The dose prescription should be the same for both cases. TG-65 recommends energies of 12 MV or less for lung radiotherapy. TG-65 Recommendations The physicist should keep abreast of new algorithms. The vendors should provide clear documentation of the inhomogeneity correction methods implemented. When physicists teach residents, tissue inhomogeneity effects on doses should be discussed. The physicist should finally confirm that the method to calculate treatment time or monitor units, whether it is derived by the treatment planning software, or with an alternative method, is accurate to deliver the planned absolute dose to the point of interest. 16
Implementation Recommendations In addition, planning volume margins may be affected according the algorithms ability to calculate penumbra in the presence of inhomogeneous media, particularly lung. Classic beam arrangements may need to be scrutinized due to the impact of increased exit dosing observed with corrections applied. 17