Can we deliver the dose distribution we plan in HDR-Brachytherapy of Prostate Cancer? Dimos Baltas Dept. of Medical Physics & Engineering, Strahlenklinik, Klinikum Offenbach GmbH 63069 Offenbach, Germany E-mail: dimos.baltas@sana.de Slide 1
List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 2
Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel Delivery Technology Dose Distribution Slide 3
Modern Radiation Therapy BRT versus ERT Similarities and Differences The Field / Beam: 2 ERT 1 BRT 3 Slide 4
Modern Radiation Therapy BRT versus ERT Similarities and Differences Beam Shaping: Plane Field Catheter/Needle/Applicator MLC 2.5 mm or 5.0 mm or 10.0 mm 1.0 mm 2.5 mm 5.0 mm 10.0 mm?? mm MSS ERT BRT Slide 5
Depth Dose Dose Rate Normalized to 1.0 cm Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel ERT 10 : 1 BRT 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 4 MV 6 MV 18 MV 10 MV 0 5 10 15 20 25 30 35 Depth (cm) 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 20 kev 25 kev 30 kev 40 kev 50 kev 60 kev 70 kev 80 kev 90 kev 100 kev 150 kev 200 kev 300 kev 400 kev 667 kev 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Radial Distance (cm) Slide 6
Dose Rate Normalized to 1.0 cm Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel ERT BRT 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 20 kev 25 kev 30 kev 40 kev 50 kev 60 kev 70 kev 80 kev 90 kev 100 kev 150 kev 200 kev 300 kev 400 kev 667 kev 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Radial Distance (cm) Slide 7
Dose Rate Normalized to 1.0 cm Radial Dose Fucntion g(r) Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 BRT 20 kev 25 kev 30 kev 40 kev 50 kev 60 kev 70 kev 80 kev 90 kev 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Radial Distance (cm) 100 kev 150 kev 200 kev 300 kev 400 kev 667 kev 1.6 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 20 kev BRT Yb-169 Ir-192 30 kev 60 kev 40 kev 100 kev 0 2 4 6 8 10 12 14 16 Radial Distance (cm) 1/r 2 = 0.007 80 kev 50 kev Slide 8
ERT BRT Modern Radiation Therapy BRT versus ERT Similarities and Differences Dose Shaping: Intensity Modulation (2D) MSS: Step & Shoot Bixel Dwell Position MUs Dwell Time Slide 9
Relative Depth Dose Depth Dose Modern Radiation Therapy Dose Shaping ERT BRT Spot Spot Energy Dwell Position (3D) 1.5 1.4 1.3 1.2 159 MeV Protons 192 Ir (400 kev) 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Depth in Water (cm) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 4 MV 6 MV 18 MV 10 MV 0 5 10 15 20 25 30 35 Depth (cm) Slide 10
Relative Depth Dose Modern Radiation Therapy Dose Shaping ERT Energy Dwell Position (3D) BRT Multi-Spots 1.5 1.4 1.3 1.2 159 MeV Protons 192 Ir (400 kev) 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Depth in Water (cm) Slide 11
Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel Particles (Spot) Delivery Technology IMRT (X, P) (Modulation, Dose-Volume-Prescriptions) Dose Distribution SRS / SBRT (Inhomogeneity) Slide 12
Modern Radiation Therapy Dose Inhomogeneity SRS BRT Slide 13
Modern Radiation Therapy Dose Inhomogeneity 10% 10% 50% 30% 30% SRS 100% 110% 50% BRT 125% Slide 14
Modern Radiation Therapy Dose Inhomogeneity 10% 30% 50% SRS BRT V100 = 93% D90 = 103% Slide 15
Modern Radiation Therapy BRT versus ERT Similarities and Differences Dosimetric Kernel Particles (Spot) Delivery Technology IMRT (X, P) (Modulation, Dose-Volume-Prescriptions ) Dose Distribution SRS / SBRT (Inhomogeneity) Slide 16
Modern Radiation Therapy The Field / Beam: ERT BRT Set-Up of the anatomy (Reconstruction) at the 3D-Reference System of the LINAC. Position of Beams and their configuration (MLC-settings) can then be automatically tracked based on integrated technology into the LINAC (electronics, EPID, kv- or MV-CBCT, ) Anatomy: is reconstructed relative to the Imager Coordinate System (DICOM). Beams: Catheters/needles/Applicators have to be placed and reconstructed by user-driven actions relative to DICOM (Anatomy). ASDPs (MLC) are not tracked automatically but this assumes firstly the reconstruction of the catheters/applicators. There is no Imaging of ASDPs delivery with respect to anatomy. Slide 17
List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 18
Workflow Imaging and Anatomy Definition Pre-Planning Imaging and Implantation and Treatment Plan Treatment Delivery Slide 19
Current Treatment Planning The Role of Imaging in Anatomy Definition and related uncertainty effects can be assumed similar to ERT with the following exceptions: Image distortion due inserted applicators (e.g. MR and metallic needles, seed artefacts in CTimaging,...) For BRT there exists the following specific issue: Imaging is also used for Identification and Reconstruction of the Catheters/Needles/Applicators (ERT: Beams). Based on their geometry the possible SDPs and required ASDPs are extracted (ERT: MLC settings, beamlets) Slide 20
Sources of Uncertainties Imaging, Fusion/Registration, Contouring Imaging, Fusion/Registration, RTP: Beam - Reconstruction +δvois Treatment Delivery +δvois +δbeams +δbeams +δrtp +δmachine Treatment Delivery: Machine + Anatomy + Beams RTP: Dose Calculation Slide 21
Treatment Planning Imaging, Fusion/Registration, RTP: Beam - Reconstruction +δbeams δdose e.g. Gynaecological Implants: 5% in D 2cm³ per mm offset for bladder & rectum < 4% per mm offset for CTV (D 90, D 100 ) Data available limited to gynaecological and prostate implants! Slide 22
RTP: Dose Calculation +δrtp Beam Data Entry (TG-43) Source Strength S K TG-43 Tables Dose Calculation Clinic measures S K (k=1): 1.3% for LDR low Energy 1.5% for HDR high Energy Total Dose Calculation TG-43 (k=1): 4.4% for low Energy 3.4% for high Energy All values for Best practice Uncertainties Slide 23
List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 24
Treatment Delivery: I. Machine +δmachine MLC precision of ± 1.0 mm Complex geometries: MLC accuracy 2.5 4.5 mm By courtesy of University of Vienna Attention: Dose distribution Depends not only on the position but also on the orientation (vector) of the sources Slide 25
Treatment Delivery: I. Machine Prostate: 16 catheters & 86 ASDPs ( beamlets/ segments ) Slide 26
Treatment Delivery: I. Machine Prostate: 16 catheters & 86 ASDPs ( beamlets/ segements ) δbeams (Reconstruction) Reconstruction uncertainty of 1.0 mm (...) and 2.0 mm (---) + δmachine MLC / source positioning uncertainty of 1.5 mm along catheter (...) : 2% up to 200%, 5% above 200% (---) : 3% up to 150%, 9% above 150% Even in that case, the impact on DVH calculations is 3% Pantelis E, Papagiannis P, et al. Phys. Med. Biol. 49, 55-67, 2004 Slide 27
Treatment Delivery: I. Machine +δmachine MU - dwell time accuracy of 30 ms Effect of Rounding: less than 1% Effect of MLC travelling finite speed of source drive < 1% Slide 28
Treatment Delivery: II. Anatomy and Catheters/Applicators +δvois + δbeams Between: Plan & Delivery During Delivery Fraction to Fraction (Interfractional: single implant & multiple fractions) + δdose Delivery Slide 29
Treatment Delivery Almost all published data available are based on pretreatment imaging for the purpose of investigating anatomy & implant changes and thus of potential errors for following workflows (mainly gynaecological and prostate implants): Multi-fractions delivery with a single implant Multi-implants with single or multi factions delivery per implant Slide 30
Treatment Delivery Multi-fractions delivery with a single implant Implant U/S Plan U/S 1 st Delivery Imaging N th Delivery Plan CT 1 st Delivery N th Delivery Slide 31
Treatment Delivery Multi-fractions delivery with a single implant CT-based Use of reference: bony structures Implanted markers Slide 32
Treatment Delivery Multi-fractions delivery with a single implant δbeam & δvoi δdose Slide 33
Treatment Delivery Multi-fractions delivery with a single implant! Slide 34
Treatment Delivery Multi-fractions delivery with a single implant Slide 35
Treatment Delivery Multi-fractions delivery with a single implant δbeam Mean shift: f2-f1 = 7.9 mm f3-f1 = 3.9 mm δdose Slide 36
Treatment Delivery Multi-fractions delivery with a single implant Slide 37
Treatment Delivery Multi-fractions delivery with a single implant Slide 38
Treatment Delivery Multi-fractions delivery with a single implant δbeam Median shift: 7.5 mm [2.9, 23.9] Median t between CT & delivery 254 min [81, 367]! Slide 39
List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 40
Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions Slide 41
Example Case # 1 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs 50% 100% 150% 200% 300% PTV TLD catheter, 14 x TLDs Rectum Slide 42
Example Case # 2 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs 50% 100% 150% 200% 300% Urethra PTV TLD catheter, 14 x TLDs Slide 43
Dose (cgy) Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs 1600 1400 1200 Plato BPS 14.2.2 with D ref = 9,5 Gy TLD 1.Fraktion 04/06/2002 15:30 TLD 2.Fraktion 05/06/2002 08:30 TLD 4.Fraktion 06/06/2002 08.30 1000 800 600 400 200 0 0 10 20 30 40 50 60 70 80 90 Distance from catheter tip (mm) Analysis Example Slide 44
Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions Slide 45
Imaging Treatment Delivery Verification: Plan Currently common/published/realised CT imaging based Verification of anatomy and implant geometry before repeated Treatment Delivery for the same Implant Delivery From CT-Imaging to Treatment Delivery there exist in the majority of the cases a patient transportation (CT-Imaging room Treatment Room). No verification under Treatment Delivery conditions or no verification of dose delivery (except some efforts for a reliable in-vivo dosimetry). Slide 46
Treatment Delivery Verification: +δvois + δbeams Between: Plan & Delivery During Delivery +δdose Slide 47
The Clinical Procedure at Offenbach Clinic Pre-Plan Needle Implantation Treatment Delivery Live plan Slide 48
The Clinical Procedure at Offenbach Clinic: The QA-Tools 1 1 1 3 2 1 Slide 49
The Clinical Procedure at Offenbach Clinic: The QA-Tools 1 1 1 (1) Intraoperative Real Time Treatment Planning System Oncentra Prostate using 2D- and 3D- Ultrasound Imaging. Ultrasound probe remains in place during treatment enabling 2D and 3D verification at any time during the procedure. 1 Slide 50
The Clinical Procedure at Offenbach Clinic: The QA-Tools (2) Template-Perineum QA-Tool 2 Slide 51
The Clinical Procedure at Offenbach Clinic: The QA-Tools 3 (3) Measurement of Free Length of the needles is utilized for both reconstruction purposes (reconstruction of needle tip) and for quality control purposes for checking needle shifts during the treatment procedure Slide 52
Materials The mean volume of prostate (PTV) for the 25 cases is 35.8cm³ with minimum volume of 17.4cm³ and maximum of 59.6cm³ Average time spent between the clinical (1) and the pre-irradiation (2) 3D acquisition was 51.2 ± 7.1min*, and between the pre- (2) and post-irradiation (3) acquisition 19.3 ± 2.2min**. *as a teaching hospital, we regularly provide the residents training, that increases the time between the clinical set acquisition and irradiation **irradiation time that depends on the source activity and the prostate volume Slide 53
Results: Prostate & OARs Movement δvois Prostate The prostate movement in the Z direction (DICOM) was equal to 0mm for each of our acquisitions BASE plane remained unchanged. The movement in X (horizontal) and Y (vertical) directions was measured compared to the prostate gravity center on the reference plane. Urethra The shift of urethra was measured on the base, reference and apex plane. Rectum and Bladder By rectum and bladder, we have not noticed significant movements. Slide 54
Results: Prostate & OARs Movement δvois VOI Name Type r 21 [mm] r 31 [mm] r 32 [mm] Prostate PTV 0.5±0.6 [0.0 2.1] 0.6±0.7 [0.0 2.1] 0.1±0.3 [0.0 1.1] Urethra OAR Base plane 0.6±0.7 [0.0 2.7] 1.1±1.3 [0.0 5.1] 0.4±0.8 [0.0 3.4] Reference 0.6±0.7 [0.0 2.3] 0.8±0.9 [0.0 2.9] 0.3±0.5 [0.0 1.7] Apex 0.6±0.8 [0.0 3.3] 0.8±0.9 [0.0 2.8] 0.3±0.5 [0.0 1.7] Rectum OAR 0.3±0.4 [0.0 1.4] 0.4±0.4 [0.0 1.4] 0.1±0.2 [0.0 0.6] *The significance test for the observed differences is always done using the student paired t-test, two sided statistical method. For the paired t-tests the significance level was 0.05. Slide 55
Results: Catheter Changes/Movement δbeams The shifts of the catheters on base, reference and apex plane is measured between the clinical and pre-irradiation; clinical and postirradiation and pre- and post- irradiation plan. In all but one case, is the maximum needle movement less than 1.5 mm Slide 56
Results: Dosimetric Impact δdose Prostate D 90 [%] 110 105 100 95 Paired t-test: p 12 <0.001 p 13 <0.001 p 23 =0,411 1 2 3 Clinical (1), pre (2)- and post (3)-treatment plan D 90 of: clinical, pre-treatment and post-treatment plan There are only three (of 25) pre- irradiation plans with D 90 values of 97.5, 97.7 and 97.8 and thus below 100%. The minimum value for D 90 for the post- irradiation plan was 96.2%. There are five (of 25) post- irradiation plans with D 90 value less than 100% with values within range of [96.2 to 98.3] %. Slide 57
General finding There is much more sense in observing the influence of the relative shift of catheters with reference to prostate on the DVH and also radiobiological parameters than the influence of absolute dislocation of needles and/or OARs separately. The cases that showed large absolute prostate and catheter displacements, showed small relative displacement and fulfilled the clinical protocol. Slide 58
Results: Dosimetric Impact δdose Slide 59
Results: Dosimetric Impact δdose COIN 0,95 0,90 0,85 0,80 0,75 Paired t-test: p 12 <0,001 p 13 <0,001 p 23 =0,409 1 2 3 COIN for: clinical, pre- and post-treatment plan Clinical (1), pre (2)- and post (3)-treatment plan The COIN values for all preirradiation plans remain above 0.8. For 1 of 25 post- irradiation plans the COIN drops below 0.8 with a value of 0.78 Slide 60
Radiobiological Evaluation The radiobiological quantities P + and D were employed to evaluate the effectiveness of the examined dose distributions. P + is the probability of complication-free tumor control and can be approximated by: P + = P B - P I where P B and P I are the total probability of tumor control and injury, respectively and D is the biologically effective uniform dose, which is the dose that causes the same tumor control or normal tissue complication probability as the actual dose distribution, D given to the patient and it can be iteratively determined from: P( D) P( D) Slide 61
Radiobiological Evaluation Slide 62
Radiobiological Evaluation Summary of the model parameter values for the examined prostate cancer cases. D 50 is the 50% response dose, γ is the maximum normalized value of the dose-response gradient and s is the relative seriality, which characterizes the volume dependence of the organ. Radiobiological Model D 50 (Gy) γ s α/β Endpoint PTV 70.0 4.0 3.0 Control Urethra (U) 120.0 3.0 0.03 3.0 Stenosis Bladder (B) 80.0 3.0 0.3 3.0 Rectum (R) 80.0 2.2 0.7 3.0 Symptomatic contracture, volume loss Proctitis, necrosis, fistula, stenosis Slide 63
Results: Dosimetric Impact δdose The average DVHs of the prostate gland (red), urethra (black), bladder (pink) and rectum (blue) are presented for the three HDR treatment plans, namely 1: after implantation (clinical acquisition) (solid), 2: just before starting the treatment execution (preirradiation acquisition) (dashed) and 3: just after finishing the treatment delivery (postirradiation acquisition) (dotted-dashed). Here, the total dose of 34.5 Gy delivered by three fractions of 11.5 Gy is considered to be the total prescription dose (100%). Slide 64
Results: Dosimetric Impact δdose Slide 65
Paper Conclusions The measured mean shift of anatomy and needles ( beams ) is as low as 1.0mm For high modulated plans as those in HDR brachytherapy such small shifts result in dosimetric changes which are in general lower than 5%. These results demonstrate that quality assurance procedures have to be clinically implemented to guarantee anatomy and implant stability of the order of 1mm. This can only be realized without any manipulation of the implant and anatomy as done, for example, in the case of removing the US-probe before treatment delivery (Presentation by Dr. Milickovic on Monday)! Slide 66
The Clinical Procedure at Offenbach Clinic: The QA-Tools 1 1 1 3 2 1 Slide 67
Treatment Delivery Verification: An open Issue... Currently double check (4 x eyes)!!!!? Slide 68
Treatment Delivery Verification: The dose-fluence pattern incident verification, that will enable the real 3Ddose reconstruction (analogue to on-line fluence measurement in ERT), assumes the on-line Beamlets & MU Tracking: source dwell positions & dwell times. ERT Advance in-vivo dosimetry systems could partly support this. Currently we have to build on: Anatomy Reconstruction & Tracking Catheter Reconstruction & Tracking OCTAVIUS III by PTW Freiburg, Germany Under delivery conditions / during delivery! Slide 69
CLINICAL UNCERTAINTY ANALYSIS FOR BRACHYTHERAPY Slide 70
CLINICAL UNCERTAINTY ANALYSIS FOR BRACHYTHERAPY HDR 192 Ir temporary brachytherapy implants for prostate (Monotherapy or Boost) In this example, the relative dosimetric uncertainties are considered with the respect to the D 90 and V 150 dosevolume parameters for the prostate/ptv. Slide 71
Dose / Volume Parameter Value (%) Volume [%] Volume [%] Volume [%] Reproducibility of Dose Prescription: Aimed versus planned Dose: Offenbach 100 90 80 70 60 50 40 30 20 10 Prostate 0 0 50 100 150 200 250 Dose [%] 100 90 80 70 60 50 40 30 20 10 Urethra 0 0 20 40 60 80 100 120 140 Dose [%] 100 90 80 70 60 50 40 30 20 10 Rectum 0 0 10 20 30 40 50 60 70 80 90 100 Dose [%] 120 100 80 60 Prostate Urethra Rectum PTV = (38.9 ± 16)cm³ Range 15-97cm³ D 90 = (102.5 ± 2.0)% 40 20 0 D 90 V 100 V 150 D 10 D 0.1c D 1c V 100 D 10 D 0.1c D 2c V 100 = (92.0 ± 1.6)% V 150 = (29.1 ± 3.2)% Slide 72
Dose / Volume Parameter Value (%) Reproducibility of Dose Prescription: Aimed versus planned Dose: UCLA In IMBRT-treatment planning using Inverse Optimization: UCLA 120 100 D 90 10% higher than PD 80 60 Prostate Urethra Rectum 40 20 0 D 90 V 100 V 150 D 10 D 0.1c D 1c V 100 D 10 D 0.1c D 2c Slide 73
Reproducibility of Dose Prescription: Aimed versus planned Dose: UCLA individually planned D 90 aimed Prescription Dose 100% Slide 74
Thank you very much for your Attention! Slide 75