Can we deliver the dose distribution we plan in HDR-Brachytherapy of Prostate Cancer?

Transcription

1 Can we deliver the dose distribution we plan in HDR-Brachytherapy of Prostate Cancer? Dimos Baltas 1,3, Natasa Milickovic 1, Nikolaos Zamboglou 2 1 Dept. of Medical Physics & Engineering, 2 Strahlenklinik, Klinikum Offenbach GmbH Offenbach, Germany 3 Nuclear and Particle Physics Section, Physics Department, University of Athens, Panepistimioupolis, Ilisia, Athens, Greece dimos.baltas@klinikum-offenbach.de Slide 1

2 List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 2

3 Modern Radiation Therapy The Field / Beam: ERT BRT 1 3 1: Catheter / Needle 3D 3D Slide 3

4 Modern Radiation Therapy 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 MLC ERT BRT Slide 4

5 Modern Radiation Therapy Beam Shaping: Plane BRT: Catheter/Needle MLC p + / Ions: Raster Scanning 1.0 mm 2.5 mm 5.0 mm 10.0 mm?? mm Raster / Vector Scanning Slide 5

6 Modern Radiation Therapy Dosimetric Kernel ERT 10 : 1 BRT Depth Dose MV MV MV MV Depth (cm) Dose Rate Normalized to 1.0 cm 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 Radial Distance (cm) Slide 6

7 Modern Radiation Therapy Dosimetric Kernel ERT BRT Dose Rate Normalized to 1.0 cm 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 Radial Distance (cm) Slide 7

8 Modern Radiation Therapy Dosimetric Kernel Dose Rate Normalized to 1.0 cm BRT 20 kev 25 kev 30 kev 40 kev 50 kev 60 kev 70 kev 80 kev 90 kev Radial Distance (cm) 100 kev 150 kev 200 kev 300 kev 400 kev 667 kev Radial Dose Fucntion g(r) BRT r -2 = kev kev 1.1 Yb kev Ir kev kev 40 kev kev Radial Distance (cm) Slide 8

9 Modern Radiation Therapy Dose Shaping: Intensity Modulation (2D) MLC : Step & Shoot ERT BRT Bixel/Beamlet/Segment Dwell Position MUs Dwell Time Slide 9

10 Modern Radiation Therapy Dose Shaping ERT Energy Dwell Position (3D) BRT Multi-Spots Relative Depth Dose MeV Protons 192 Ir (400 kev) Depth in Water (cm) Slide 10

11 Dose Shaping: Intensity Modulation (3D) MSS: Step & Shoot Spot K(r ) F( { r }, { t}) D( r ) = F( r, r { t} ) K( ) Slide 11

12 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

13 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 13

14 List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 14

15 Workflow Imaging and Anatomy Definition Pre-Planning Imaging and Implantation and Treatment Plan Treatment Delivery Slide 15

16 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 16

17 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 17

18 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 18

19 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 19

20 List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 20

21 Treatment Delivery: I. Machine +δmachine MLC precision of ± 1.0 mm Complex geometries: MLC accuracy 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 21

22 Treatment Delivery: I. Machine Prostate: 16 catheters & 86 ASDPs ( beamlets/ segments ) Slide 22

23 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 23

24 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 24

25 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 25

26 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 26

27 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 27

28 Treatment Delivery Multi-fractions delivery with a single implant CT-based Use of reference: bony structures Implanted markers Slide 28

29 Treatment Delivery Multi-fractions delivery with a single implant δbeam & δvoi δdose Slide 29

30 Treatment Delivery Multi-fractions delivery with a single implant! Slide 30

31 Treatment Delivery Multi-fractions delivery with a single implant Slide 31

32 Treatment Delivery Multi-fractions delivery with a single implant δbeam Mean shift: f2-f1 = 7.9 mm f3-f1 = 3.9 mm δdose Slide 32

33 Treatment Delivery Multi-fractions delivery with a single implant Slide 33

34 Treatment Delivery Multi-fractions delivery with a single implant Slide 34

35 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 35

36 List of Content BRT versus ERT from Dosimetry Point of View Treatment Planning and Dose Calculation Treatment Delivery Treatment Delivery Verification Slide 36

37 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions Slide 37

38 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs Example Case # 1 50% 100% 150% 200% 300% PTV TLD catheter, 14 x TLDs Rectum Slide 38

39 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs Example Case # 2 Urethra 50% 100% 150% 200% 300% PTV TLD catheter, 14 x TLDs Slide 39

40 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions 5 x cases, 18 x Fractions, 14 x TLDs Dose (cgy) Plato BPS with D ref = 9,5 Gy TLD 1.Fraktion 04/06/ :30 TLD 2.Fraktion 05/06/ :30 TLD 4.Fraktion 06/06/ Distance from catheter tip (mm) Analysis Example Slide 40

41 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions Slide 41

42 Treatment Delivery Verification: Off-Line Procedure CT based 1 x Implant + 4 x Fractions Slide 42

43 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 Imaging 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 43

44 Treatment Delivery Verification: +δvois + δbeams Between: Plan & Delivery During Delivery +δdose Slide 44

45 The Clinical Procedure at Offenbach Clinic Pre-Plan Needle Implantation Treatment Delivery Live plan Slide 45

46 The Clinical Procedure at Offenbach Clinic: The QA-Tools Slide 46

47 The Clinical Procedure at Offenbach Clinic: The QA-Tools (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 47

48 The Clinical Procedure at Offenbach Clinic: The QA-Tools (2) Template-Perineum QA-Tool 2 Slide 48

49 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 49

50 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 50

51 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 51

52 Results: Prostate & OARs Movement δvois VOI Name Type r 21 [mm] r 31 [mm] r 32 [mm] Prostate PTV 0.5±0.6 [ ] 0.6±0.7 [ ] 0.1±0.3 [ ] Urethra OAR Base plane 0.6±0.7 [ ] 1.1±1.3 [ ] 0.4±0.8 [ ] Reference 0.6±0.7 [ ] 0.8±0.9 [ ] 0.3±0.5 [ ] Apex 0.6±0.8 [ ] 0.8±0.9 [ ] 0.3±0.5 [ ] Rectum OAR 0.3±0.4 [ ] 0.4±0.4 [ ] 0.1±0.2 [ ] *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 Slide 52

53 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 53

54 Results: Dosimetric Impact δdose Prostate D 90 [%] Paired t-test: p 12 <0.001 p 13 <0.001 p 23 =0,411 D 90 of: clinical, pre-treatment and post-treatment plan Clinical (1), pre (2)- and post (3)-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 54

55 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 55

56 Results: Dosimetric Impact δdose Slide 56

57 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 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 values 0.78 Slide 57

58 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: PD ( ) PD ( ) Slide 58

59 Radiobiological Evaluation Slide 59

60 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 Control Urethra (U) Stenosis Bladder (B) Rectum (R) Symptomatic contracture, volume loss Proctitis, necrosis, fistula, stenosis Slide 60

61 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 61

62 Results: Dosimetric Impact δdose Slide 62

63 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 63

64 The Clinical Procedure at Offenbach Clinic: The QA-Tools Slide 64

65 Treatment Delivery Verification: An open Issue... Currently double check (4 x eyes)!!!!? Slide 65

66 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 66

67 CLINICAL UNCERTAINTY ANALYSIS FOR BRACHYTHERAPY Slide 67

68 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 68

69 Reproducibility of Treatment Delivery in Offenbach Reproducibility of Treatment Delivery: What does it mean for the individual patient or individual implant? 52 consequent patients with a total of 117 plans and treatment deliveries. Only Live Plans (Treatment Plans delivered are considered). Mean PTV of (38.9 ± 16) cm³ Range cm³ Slide 69

70 Offenbach Dosimetric Constraints Case Monotherapy #1 and Boost Case #2 Prostate (PTV = CTV 1): D % V % V % Urethra: D % V 115% 10% D 0.1cm³ 120 % Rectum & Bladder D 10 75% V 75% 10% D 0.1cm³ 80 % Slide 70

71 How we contour Since the last 7 years We contour also bladder. Thus urethra stops Cranially where bladder begins. Slide 71

72 Reproducibility of Treatment Delivery I. PTV (38.9 ± 16) cm³ Volume [%] N= Dose [%] D 90 = (102.5 ± 2.0)% V 100 = (92.0 ± 1.6)% V 150 = (29.1 ± 3.2)% Prostate (PTV = CTV 1): D % V % V % Slide 72

73 Reproducibility of Treatment Delivery II. Urethra (17.2 ± 3.2) cm³ Volume [%] N= Dose [%] D 10 = (112.9 ± 1.6)% D 0.1cm³ = (114.0 ± 1.3)% D 1.0cm³ = (98.4 ± 13.2)% V 100 = (63.9 ± 9.2)% Urethra: Volume [%] Dose [%] D % V % D 0.1cm³ 120 % Slide 73

74 Reproducibility of Treatment Delivery III. Rectum (33.8 ± 9.6) cm³ Volume [%] Dose [%] Volume [%] N= Dose [%] D 10 = (52.5 ± 4.8)% D 0.1cm³ = (74.9 ± 2.7)% D 2.0cm³ = (58.1 ± 5.3)% Rectum D 10 75% V 75 10% D 0.1cm³ 80 % Slide 74

75 Reproducibility of Treatment Delivery IV. Bladder (28.6 ± 13.4) cm³ Volume [%] Dose [%] Volume [%] N= Dose [%] D 10 = (50.5 ± 8.2)% D 0.1cm³ = (73.8 ± 4.9)% D 2.0cm³ = (53.6 ± 5.7)% Bladder D 10 75% V 75 10% D 0.1cm³ 80 % Slide 75

76 Conclusions Can we deliver the dose distribution we plan? Currently we do not have a close-loop System (Technology) clinically routinely available to answer this for the different localisations (similar to kv-, MV-CBCT in ERT, Industry) We do have data supporting and proving the YES-Answer under specific conditions and scenarios (in the enormous diversity of methods & clinical workflows) We definitively need site-specific guidelines (procedures and action levels) for Treatment Delivery Verification in modern Brachytherapy! Slide 76

77 Thank you very much for your Attention! Slide 77