Feasibility of 4D IMRT Delivery for Hypofractionated High Dose Partial Prostate Treatments

Transcription

1 Feasibility of 4D IMRT Delivery for Hypofractionated High Dose Partial Prostate Treatments R.A. Price Jr., Ph.D., J. Li, Ph.D., A. Pollack, M.D., Ph.D.*, L. Jin, Ph.D., E. Horwitz, M.D., M. Buyyounouski, M.D., C-M. Ma, Ph.D. Fox Chase Cancer Center, Philadelphia, PA *University of Miami Miller School of Medicine, Miami, FL

2 Proposed IMRT Dose Escalation Trial Intermediate Risk Stratify PSA Gleason ±STAD R a n d o m i z e SIMRT 76 Gy in 38 (2.0 Gy) fxs SIMRT + IMRT Boost Boost bulky tumor 76 Gy in 38 (2.0 Gy) fxs + 10 Gy Boost (single fraction)

3 Rationale Local persistence after RT remains a problem, even at high doses Confirmed by prostate biopsy Appears related to dominant lesion (hypoxia?) Builds on prior FCCC randomized trial

4 FCCC Experience with 10 Gy/fx In-house protocol; 46 Gy to pelvis (IMRT) Gy HDR boost weeks 1 & 3 ~45 men over last 9 years <10% risk of rectal bleeding/urethral strictures Same short-term term side effects as IMRT

5 We need advanced imaging for Targeting (what part(s) ) of the prostate do we need to boost) Treatment Planning (we need to reduce PTV margins to stay below critical structure tolerances) Treatment Delivery (we need to know where the target(s) ) are during treatment delivery, e.g. tracking)

6 MRS of Prostate Citrate Cho Cr Citrate levels with prostate Ca PPM 3 2 Cho Cr Citrate Choline levels with prostate Ca High (choline+creatine)/citrate ratio Cancer PPM 3 2 Courtesy of Radka Stoyanova, Ph.D. (original data from UCSF)

7 MRS Correlate MRS findings with high tumor density regions prior to treatment planning May define based on palpation Additionally, use non-invasive MRS in lue of 2-2 year follow-up biopsy (initially we ll correlate results with biopsies)

8 Hypointense regions (indicative of Ca) choline choline citrate choline Courtesy of Radka Stoyanova, Ph.D.

9 Problems Limiting dose to rectum during the 1 st 76 Gy Limiting dose to rectum during the 10 Gy boost Evaluating rectal constraints during the planning of the 10 Gy boost Evaluating the rectal constraints of the composite plan

10 DVH Acceptance Criteria PTV 95 % 100% Rx R 65 Gy 17%V R 40 Gy 35%V B 65 Gy 25%V B 40 Gy 50%V FH 50 Gy 10%V Good DVH R 40 = 22.7% PTV 95 = 100% R 65 = 8.3% R 40 = 19% B 65 = 8.4%

11 Good plan example (axial) 100% 90% 80% 70% 60% 50% CTV Effective margin The 50% isodose line should fall within the rectal contour on any individual CT slice The 90% isodose line should not exceed ½ the diameter of the rectal contour on any slice

12 R65 with PTV reduction 25 38cc prostate 3mm PTV 66cc prostate mm PTV 79cc prostate 3mm PTV Percent of Rectum at 65 Gy cc prostate 3mm PTV 127cc prostate 3mm PTV 214cc prostate 3mm PTV Theoretically, we can limit dose to the rectum by decreasing PTV margins & using Calypso beacons for active tracking

13 Prostate IMRT Rectal Values Rectal Volume (%) Average Values Max Values Min Values Average Prescription 79.2 Gy (78-80) Average Rectal Volume 50.4 cc ( ) 14.3 R40 R65 R75 R80 Rectal Dose Cutpoints (Gy)

14 Equivalent dose at 2Gy/fx EQD2 = D[(d + (α/β( ))/(2 + (α/β( ))] D = total dose given with a fraction size of d

15 Assumptions Overall tx time is relatively unchanged; 76 Gy in 38 fractions followed by a boost of 10 Gy in a single fraction EQD 2 are additive If we limit the R 65 to 17% Vol in fxs our results hold α/β = 2Gy (prostate); α/β = 4Gy (rectum) 10Gy boost 2Gy/fx (prostate( prostate); = 106 Gy

16 Prostate S Prostate I Boost Target Boost Target 76 Gy, 68, 61, 53, 46, Gy, 68, 61, 53, 46, 38

17 Boost 10 Gy, 9, 8, 7, 6, 5 10 Gy, 9, 8, 7, 6, 5 EQD2 = D[(d + ( / ))/(2 + ( / ))] = 30 Gy { / 30 Gy, 27, 24, 21, 18, 15 prostate 30 Gy, 27, 24, 21, 18, 15 = 2.0 Gy}

18 Prostate spillover 30 Gy, 27, 24, 21, 18, 15 Boost target Issues of note -spillover dose into non-boost prostate volume (will result in increased overall dose at time of composite plan generation) -there are systems that allow the optimization on previously delivered dose (what happens to the boost dose/fraction?) -compressed dose gradient has been used for critical structure sparing (rectum) -this plan is for evaluation of target(s) only (α/β prostate = 2.0 Gy) -this plan cannot be used to evaluate the rectum (α/β rectum = 4.0 Gy)

19 106 Gy, 95, 85, 76, 65, 55 Increased overall dose to both targets: 85 Gy 95 Gy 106 Gy 95% of Prostate PTV ~84 Gy (vs 76 Gy) 95% of Boost PTV ~107 Gy (vs 106 Gy) 76 Gy

20 Volume-based scaling (initial plan) Our normal PTV margins (8 & 5 mm) result in dose-volume limit of 17% rectum receiving 65 Gy. 65 Gy/38 fx = 1.71 Gy/fx EQD Gy limit P R 65 Gy

21 Volume-based scaling (initial plan) P R Gy With decreased margins (3mm) 17% rectum receives ~ Gy in 38 fractions resulting in a dose/fx of Gy. Therefore EQD Gy (from the rectum s s perspective)

22 Rectal DVH with PTV Change PTV 5mm posteriorly (original) PTV 3mm PTV 3mm (rectum EQD2 scaled) 17% Rectal Volume 70 Prostate Volume (%) Rectum 5mm post margin 3mm post margin 20 17% rectal volume Dose (Gy)

23 Rectal dose limit for boost plan The 10 Gy boost plan yields 3.09 Gy to 17% of the rectal volume EQD Gy Gy (EQD 2 initial) Gy (EQD 2 boost) = Gy; well below the Gy limit Composite plan: Gy

24 Composite to 106 Gy 110 Prostate PTV 100 Prostate Boost Target PTV Percent Volume Target data taken from composite plan generated using prostate α/β = 2.0 Gy 17% Vol receiving Gy Boost Target Rectum Rectal data taken from composite plan generated using rectum α/β = 4.0 Gy Dose (Gy)

25 Summary Single fraction high dose boosts to the prostate should be possible (dosimetrically( dosimetrically) Important issues with targeting & radiobiology PTV reduction is necessary (but is a 3mm margin necessary? Remember, 17% of rectum at Gy only)

26 Dose Escalation Barriers Goals Highly Conformal Radiation Therapy Use reduced margins Uncertainty of Target Delineation Setup Error Patient and Organ Motion Target Deformation Uncertainty of Beam Delivery System Improve Disease Control Reduce Complications

27 3D Localization Techniques for Prostate Treatment Skin Markers with portal image verification Ultrasound images BAT, I-BEAMI etc. In room CT/MRI -- CT-on on-rails and Cone beam CT, Tomotherapy,, cobalt machine with MRI Implanted Fiducial markers with OBI Implanted Beacon transponders with Calypso 4D localization system

28 4D Localization Techniques for Prostate Treatment Orthogonal X-rayX images with implanted fiducial markers Calypso 4D localization system with Implanted Beacon transponders

29 Calypso 4D Localization Wireless miniature Beacon Electromagnetic Transponders Accurate, objective guidance for target localization and continuous, real-time tracking Actual size: Length = ~8.5mm Diameter = 1.8mm System Beacon Electromagnetic Transponder

30 Clinical Procedure for Calypso Patient 1. MRI scan patient 2. Implant Beacon Transponders 3. CT scan patient at least a week later 4. Complete treatment planning, input isocenter coordinates and transponder coordinates into the Calypso system Medium frequency High frequency low frequency Unique Frequencies Identify Location

31 Electromagnetics Locate and Track Continuously GPS for the Body Step 1 Step 2 Excitation Waveform Response Waveform Source Coil Current Resonator Current Excitation Phase Ring Down Phase

32 Calypso System Prostate Localization Prostate rotation monitoring Prostate real-time motion tracking

33 Advantages and disadvantages of the Calypso system Advantages 4D, real-time tracking Localization Fast feed back Less operator dependence No additional dose Efficient workflow Can be used for gating Disadvantages Invasive implant Lack of anatomic information MRI artifacts Limited patient population Anti-coagulant or anti-platelet drug therapy Hip prosthesis, prosthetic implants Patients with large AP separation

34 Comparison with OBI for patient localization A. OBI images were taken when Calypso motion tracking was on B. Calypso readings were corrected by the amount of the average isocenter offset from morning QA results in the same period C. The OBI based-shifts shifts were then compared with the corrected Calypso offset reading Lateral Longitudinal Vertical FCCC patients 3 2 Difference (mm

35 Error of skin marker based prostate localization lat long vert 20 Setup errorr(mm Number of setup L-R I-S P-A FCCC patients Mean (mm) (mm) σ (mm) More than 65% of patients had > 5mm misalignment at setup based on skin markers

36 Beacon migration and prostate size change Ratio of distance between transponders Apex-RB RB-LB Ratio Apex-LB Apex-RB 0.8 RB-LB 0.7 Apex-LB number of patients Ratio of intertransponder distance relative to the planning CT The First Treatment Apex-LB 0.97 Apex-RB 0.97 LB-RB 0.99 FCCC patients; can be >2mm The Last Treatment

37 Intrafractional motion Offset (cm Lateral Long Vertical Time (min) Offset (cm Lateral Long Vertical Time (min) Lateral Long Vertical Offset (cm Time (min) FCCC patients 3 patients 3 diff fractions

38 Intrafractional motion (775 fractions of 105 patients) Percentage of fractions that need intervention 29.3% for 3mm threshold 4.8% for 5mm threshold Percentage of time prostate is off the base line 13.4% for 3mm threshold 1.8% for 5mm threshold

39 Prostate Rotation Frequency(% Mean= -1.5 degree SD = 6.4 degree Rotation angle around the lateral axis (degree) Frequency (% Frequency (% Rotation angle around longitudinal axis (degree) Rotation angle around vertical axis (degree) Mean= 0.0 degree, SD = 2.9 degree Mean= -0.2degree, SD = 1.9 degree FCCC patients

40 Translational Error Caused by Prostate Rotation θ x FCCC patients Rotated contour (20 patients) and found translational error when matching to planning CT Translational Error (mm y= x x Rotation Angle (Degree)

41 How much does motion tracking help during prostate treatment? - Quantitative analysis of potential PTV reduction

42 Population-Based Margin Calculation (CTV to PTV) m * = σ + S PTV Total systematic error = 2 del + 2 int er + 2 int ra + 2 mtd + 2 rot + 2 bds +L Total random error σ = σ 2 int er + σ 2 int ra + σ mtd + σ rot + σ bds +L Total mean S = S del + S inter + S intra + S mtd + S rot + S bds + * Stroom JC et al, Int. J. Rad. Onc. Biol. Phys 43(4) pp ,1999 With a criteria of D 99 of CTV > 95% of the nominal dose on average

43 Geometrical Uncertainties 1. Delineation Error (C. Rasch et al) (del) L-R 1.7mm; S-I 2-3.5mm; A-P 2mm; 2. Geometrical Uncertainty of the beam delivery system (bds) bds = 0.5mm, δ bds = 0.7mm 3. Uncertainty of localization and motion tracking system (mtd) 4. Uncertainty caused by Beacon migration and prostate size change -- not included in the margin calculation 5. Geometrical Uncertainty Caused by Prostate Rotation (rot) 6. Setup residual error included in the intrafractional motion 7. Geometrical Uncertainty caused by intrafractional motion

44 Geometrical Uncertainty Including Intrafractional Motion and Resultant PTV Margins 105 patients with no intervention (mm) Mean (S) Left Right 0.19 Sup 0.25 Inf 0.91 Ant 0.47 Post 0.55 (total) σ (total) Margin How to reduce the effects of intrafractional motion?

45 Threshold-based Intrafractional Intervention Lateral Long Vertical Offset (cm Beam Off Time (min) 1. Beam off (gated treatment) 2. Move prostate back to the base line by moving the table Lateral Long Vertical Lateral Long Vertical Offset (cm Time (min) Offset (cm Time (min)

46 4D treatments moving the couch and/or using DMLC 1. Correction of the translational error only 2. Correction of the translational error plus rotation

47 PTV Margins for Various Uncertainty Conditions 105 patients with/without intervention (mm) No intervention Left 5.3 Right 5.6 Sup 8.1 Inf 8.8 Ant 8.8 Post 8.8 5mm threshold mm threshold D Tx D Tx + Rotation Correction

48 Intrafractional motion (61 fractions of 7 patients who exhibited the largest intrafractional motion) The percentage time of prostate off the base line 41% for 3mm threshold 15% for 5mm threshold

49 PTV Margins 7 patients with/without intervention (mm) No intrafractional motion considered Left 5.2 Right 5.9 Sup 7.0 Inf 10.0 Ant 7.4 Post mm threshold (intra rotation not considered) 3mm threshold (intra rotation not considered) 4D Tx (additional uncertainty for tracking added; MLC tracking, couch) 4D Tx + Rotation Correction (all uncertainties added)

50 Conclusions Calypso 4D localization system is an accurate and convenient system for prostate localization and real-time motion tracking The prostate translational intrafractional motion is not a major contributor to the geometrical uncertainty for the general patient population and motion tracking during treatment plays a small role in treatment margin reduction. A small fraction of patients who have large intrafractional motion can benefit significantly from real-time motion tracking and threshold- based intervention. Effects caused by prostate rotation are more significant than the translational intrafractional motion. Rotation correction could help more on treatment margin reduction. One should use caution when reducing the treatment margins even with prostate motion tracking.