Pulsed Dose Rate for GYN Brachytherapy

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1 Pulsed Dose Rate for GYN Brachytherapy Firas Mourtada,, Ph.D. Department of Radiation Physics

2 Dose equivalency to LDR Brief Introduction Radiobiology Dose Distribution: Radial dose function Source anisotropy LDR/PDR 17 patient dose comparison Effect of applicator perturbation (Monte Carlo studies)

3 The Current Practice of ICRT Control of cervical tumors is based on successful integration of EBRT and ICRT. Uterus and vagina are well suited for placement of applicators and sources centered in the tumor. Traditional ICRT was delivered at LDR with Ra-226, Cs-137 and Co-60. Recent years clinicians have moved away from LDR to HDR, PDR. 85% of practice in US still use LDR

4 LDR Practice at MDACC UTMDACC 4 Selectron LDR 137 Cs afterloaders for gynecological cases Average 3 cases per week Principal replacement for 226 Ra Manually afterloaded 137 Cs sources for small number of cases

5 Intracavitary Irradiation for Cervix Cancer Most institutions in the U.S. that currently use either LDR and/or HDR intracavitary brachytherapy for the treatment of cervix cancer use some form of the Manchester System for dose prescribing. The Manchester System relies on the dose rate to point A as the prescription point for intracavitary implants.

6 Review of Historical Definition of Points A and B Point A, is 2 cm superior from the lower end of the intrauterine radium tubes (from the mucous membrane of the lateral fornix) and then 2 cm lateral from the center of the uterine canal Point B, is 3 cm lateral of Point A B 3 cm 2 cm A A Point A is the point where the uterine vessels cross the ureter B 2 cm Point B signified the location of the obdurate nodes Original definition of A and B, according to the Manchester system.

7 Review of Classical Manchester Dosing In the absence of EBRT a total of 8000 R to point A in 140 hours was prescribed Dose rate at point A remained constant at 54 cgy/hr for all allowed applicator combinations and loadings. Point A With the dose rate at point A remaining constant at 54 cgy/hr with loadings varying from mg, TIME was the determining factor for intracavitary implants The ovoid contribution to point A was limited to 1/3 of the total dose

8 The M. D. Anderson System for Intracavitary Implants The system used at MDACC for intracavitary treatment of cervix cancer is not based upon point A as the prescription point, nor upon the dose rates to point A, the bladder, or the rectum. In the Textbook of Radiotherapy, Dr. Fletcher describes several conditions that have to be met for successful intracavitary implants. Note: The M.D. Anderson experience for treatment of gynecological l malignancies is is based upon results obtained using Radium-226 as the radioactive isotope for intracavitary insertions ( Ra-226 tubes with a physical length of of 22.0 mm, an active length of of 15 mm, and 1.0 mm of Platinum filtration.)

9 The M. D. Anderson System for Intracavitary Implants These conditions are: The geometry of the radium (now cesium) sources must be such that the dose distribution is relatively even, to prevent overdosed and/or underdosed regions on and around the cervix. Adequate dose has to be delivered to the most distant point of the tumor - the paracervical areas. Mucosal tolerance has to be respected.

10 MDAH Dose Specification Dose is specified in mgraeq-hr , 10-10, 10, in 48 hours, 3120 mgraeq-hr Dose is based on a volume effective dose The adequacy of the treatment is evaluated on the shape of the isodose curve representing this dose. (3150 cgy line)

11 Radium to Cesium Ra tube sources, 22 mm PL, 14 mm AL 137 Sources spaced uniformly tip to flange 3 mm spacers used, if required Loadings w/o spacers, sources loading Loadings w spacers, inches loading 137 Cs tube sources, 20 mm PL, 13.5 mm AL 2 mm spacers, sources loading 5 mm spacers, inches loading No spacers, short sources loading

12 Radium Tube Sources to Cesium Selectron Pellets in the Tandem 25.0 mm = Ra-226 tube source with 3mm spacer 22.0 mm = Ra-226 tube 2.5 mm tip screw mm 2.5 mm Center of 1st tube source Note: each active pellet has a nominal activity of 5 mgraeq

13 Ra to Selectron LDR Afterloaders 226 Ra treatment plans historical tandem and ovoids treatments Selectron loadings for same dose distribution Tables translate 226 Ra to Selectron, sources and inches tandem loadings MDACC ovoids - 33mm

14 Quantification of MD Anderson GYN Brachytherapy Effectiveness Results were presented at 1999 ASTRO meeting and published in 2000 in Red Journal Dr Angela Katz took 396 patients 808 insertions % received Nucletron LDR Selectron ALTO, the rest were manually loaded Cs tube sources IJROBP, v48(5) , 2000

15 Characteristics of Cervical Cancer Treatment Total doses to reference points - MDACC Reference point Dose ± S.D. Point A 87 ± 8 Gy Bladder 70 ± 9 Gy Rectum 70 ± 8 Gy Vaginal surface 125 ± 15 Gy Katz et al

16 Cervical cancer: Results of treatment with radiation at MDACC ( ) Central disease control 100 Central recurrence: IB1: 1 2% IB2 II: 10 15% III: 25 30% IB1 IB2 IIA IIB III Time (years) Katz

17 Cervical cancer: Results of treatment with radiation at MDACC ( ) Disease-Specific Survival 100 Death from disease: IB1: 10 15% IB2 II: 30 40% III: 50 60% IB1 IB2 IIA IIB III Time (years) Katz

18 Conclusions - Katz Clinical outcome yielded high rates of central disease control with acceptable normal tissue complication It does however require following the guidelines for placement and loading precisely!

19 MDACC Cervical Carcinoma Tx Approach

20 Why change? Desire an intracavitary LDR brachytherapy program with remote afterloader. After 2009 Nucletron will not support the Selectron LDR remote afterloader. Manual 137 Cs sources are more difficult to obtain. PDR remote afterloader, potential solution MDACC radiation oncologists do not favor HDR (<5% of our cases only)

Selectron LDR Afterloader 4 channels 1 for tandem 1 for each ovoid 1 spare 48 pellets, 2.5 mm dia. 20 active 5mgRaeq (36.

21 Selectron LDR Afterloader 4 channels 1 for tandem 1 for each ovoid 1 spare 48 pellets, 2.5 mm dia. 20 active 5mgRaeq ( U) nominal 137 Cs on surface of 1.5mm ceramic (borosilicate) bead, 0.5mm SS encapsulation 28 inactive pellets Ferromagnetic, 304 stainless steel

22 Nucletron PDR Afterloader Physical construction identical to Nucletron mhdr v2 192 Ir stepping source Source activity GBq ( Ci) at installation Treatment Control Station software specific for PDR

23 PDR Afterloader Advantages Nursing care provided between pulses Patient has more certainty when treatment finishes Visitors between pulses (must keep door opened) Computerized optimization 3D imaging, planning, volumetric information required for true optimization

24 BrachyVision- Contoured Applicators Rt. Ovoid Tandem Lt. Ovoid Foley Balloon

25 LDR to PDR Prescriptions Geometry based Point A dose 3D planning

26 Dose equivalency to LDR Brief Introduction Radiobiology Dose Distribution: Radial dose function Source anisotropy LDR/PDR 17 patient dose comparison Effect of applicator perturbation (Monte Carlo studies)

27 CLDR vs PDR Schedule Simulates LDR with higher activity source exposed a fraction of each hour PDR source steps through the implant during irradiation pulse

28 the question is? 137 Cs/LDR 192 Ir/PDR 3D DD w/ + w/o shield BED T 1/2 a/b It is all about the radiobiology

29 Typical Loadings from MDACC Database

30 Pulse Width needed to match Cs-137 LDR Loadings Ci mpdr Pulse width (40mgRaEq), min Pulse width (60mgRaEq), min Pulse width (80mgRaEq), min Pulse Width, min min max pulse width desired by physician Days T pulse Pulse width (40mgRaEq), min Pulse width (60mgRaEq), min Pulse width (80mgRaEq), min Day PDR, Ci Sk microgy m2/hr

31 Pulsed Brachytherapy There is always some loss of thx eff when dose rates increased RE increases more for late complications than for tumor cell kill Question is How much if a continuous LDR of say 0.5 cgy/hr is divided into 30 min pulses of 1Gy/hr, or 15 min pulses of 2Gy/hr, or 10min pulses of 3Gy/hr, etc.

32 Tx time and pulse width and freq to yield similar biological to LDR? A pulse width of 10 min with a period between pulses of 1 hr would be appropriate for all cell lines considered. This produced up to 2% increase in late- effect probability Acceptable for the small volumes irradiated in interstitial brachy

35 IJROBP, v 43(1) pp , 1999 To analyze the outcome and complication rates for patients treated with curative-intent intent PDR and EBRT for uterine cervical carcinoma (n=52) Median effective dose rate of 0.55 Gy per pulse per hr and 84.1 Gy to point A Concluded that PDR is a safe and effective brachytherapy method in the treatment of cervix carcinoma. Further FU required, it it appears to provide outcome which compares favorably to other methods of brachytherapy delivery, and results in a low rate of complications

BED Models BED LDR = NRt 1 + 2R β 1 e 1 μ α μ t μt LDR BED PDR 2R β 1 = NRt 1 + 1 Y μ α Npulse μ Tpulse S = 2 N + 1 N ( N K K N K Z + K Z ) ( 1 K Z ) 2 [ ] 2 N Y S PDR K =

36 BED Models BED LDR = NRt 1 + 2R β 1 e 1 μ α μ t μt LDR BED PDR 2R β 1 = NRt Y μ α Npulse μ Tpulse S = 2 N + 1 N ( N K K N K Z + K Z ) ( 1 K Z ) 2 [ ] 2 N Y S PDR K = exp[-u *X], X is time interval w/o irradiation between pulses. X= [Tperiod - Tpulse] (x) (t) Eq 3 from Fowler and Mount, IJROBP, Vol 23, pp , 1992 (Dale s Eq 1, BJR 61, 1988)

$TD== total dose per fraction DR==Dose-rate$

37 BED PDR ±5% of BED LDR is OK? TD== total dose per fraction DR==Dose-rate FTT==fraction total time

38 Dose equivalency to LDR Brief Introduction Radiobiology Dose Distribution: Radial dose function Source anisotropy LDR/PDR 17 patient dose comparison Effect of applicator perturbation (Monte Carlo studies)

39 LDR to PDR Dose Distribution: 3 factors considered Radial dose function 137 Cs vs. 192 Ir Anisotropy Ovoid shielding Other factors Source position Dwell weight optimization

40 1.06 Radial dose function Cs-137 vs. Ir-192 g(r) comparison g( r) Ir-192 g( r) Cs-137 Ratio (Ir/Cs) Radial distance (cm) g(r) accounts for the effects of absorption and scatter in tissue along the perpendicular bisector of the source

41 Anisotropy Accounts for anisotropy of dose distribution around the source, including effects of absorption and scatter in medium, i.e., self filtration in source, oblique filtration in walls, scattering and absorption in tissue

42 mpdr (mhdr V2) Source Geometry Single 192 Ir source, 0.5, 1.0 or 2.0 Ci capsule 0.9 mm diameter, 4.5 mm long Ir pellets: 0.6 mm diameter, 0.6 mm long Stainless steel capsule Special weld to drive cable

43 mpdr (mhdr v2) Source

44 Anisotropy Cs pellet is isotropic 192 Ir source is anisotropic 192 Asymmetric due to stainless steel cable Iridium the 2 nd most densest material

45 What is the influence of these two factors on abs dose distribution? 17 LDR patients retrospective analysis TG-43 in water dosimetry (BrachyVision TPS) w/o shields Same source distribution in tandem and ovoid Assumed 1Ci Ir source, adjust dwell time to yield similar Cs LDR loading

46 Case1: mini-ovoids With orthogonal films

47 Case1: Mini-ovoids Mini Ovoids Enter Source Activity= Aapparent= 1 Ci 1000 mci Air kerma constant= cgy cm2/hr / mci for mhdr v2 (PDR source) Air kerma strength= 4082 cgy cm2/hr Reed-15deg/7.5mRe Cs137 Strength, cgy cm2/hr Time, hr cgy cm2 hr PDR hrs Ovoid Tandem

48 Patient Case1: Mini Ovoids PDR LDR 1) Radial dose function 2) Anisotropy Effect

49 Patient Case: Mini Ovoids PDR LDR

50 Patient Case: Mini Ovoids PDR LDR

51 Case1: Mini-Ovoids PDR LDR Alt Art Aave Blt Brt Bave Rectum Bladder LDR, cgy PDR, cgy PDR/LDR

52 LDR to PDR: 3) Ovoid Shielding effect Applicators: are they different?

53 BrachyVision- 3D CT study (n=9) Rt. Ovoid Tandem Lt. Ovoid Foley Balloon

54 Selectron LDR Fletcher-Suit-Delclos Ovoids small ovoids - one ovoid with medium cap mini ovoids 30 degree short small ovoid ovoid - 33 mm long large cap short ovoid - 28 mm long medium cap 15 degree small ovoid short large cap 15 degree mini ovoid 30 degree small ovoid

55 SolidWorks CAD Model of FSD Ovoid with 137 Cs pellets Imported directly from Solidworks into Attila Half Ovoid shown for visualization

56 137 Cs Selectron ALTO Small Ovoid Geomtery Anterior (Bladder) Shield Posterior (Rectal) Shield Courtesy of K Gifford

57 Ovoid Shielding Effect on 137 Cs Dose Distribution in Water Courtesy of K Gifford

58 MCNPX Results Pt#1 With Ovoid Shield Without Ovoid Shield Courtesy of K Gifford

59 MCNPX Results: Patient #1 Courtesy of K Gifford

60 Results: Patient#1 Dose Points MCNPX MCNPX Brachyvision(cGy) Shielded(cGy) Unshielded(cGy) Art Alt Brt Blt bladder * 949 rectum ** 740 max bladder max rectum *17% lower bladder dose **26% lower rectum dose Courtesy of K Gifford

61 PDR/HDR Tandem and Ovoid Applicators (Fletcher/Williamson) Ovoid Shielding HDR Tandem HDR Small Ovoids HDR Mini Ovoids no shields

62 PDR/HDR: Fletcher-Williamson Ovoids PDR/HDR Applicator from Nucletron Surface doses shown on critical structures Mourtada et al, AAPM Dose calc by Attila

Rectal Shield Geometry Rectal Rectal PDR LDR FW (PDR) FSD (LDR) ID, mm 4 8 OD, mm 18 18 thickness, mm 2.

63 Rectal Shield Geometry Rectal Rectal PDR LDR FW (PDR) FSD (LDR) ID, mm 4 8 OD, mm thickness, mm Total surface, mm Largest face surface, mm Total shield volume, mm * Material for both FW and FSD is Densimet 17 (17 g/cm 3 )

267 296 Largest face surface, mm 2 91 58 Total shield volume, mm 3

64 Bladder Shield Geometry Bladder Bladder PDR LDR FW (PDR) FSD (LDR) Height, mm 7 5 OD, mm thickness, mm 2 5 Total surface, mm Largest face surface, mm Total shield volume, mm * Material for both FW and FSD is Densimet 17 (17 g/cm 3 )

65 Ovoid Study Conclusions Successfully modeled the Nucletron FW applicator / 192 Ir PDR/HDR source utilizing the MCNPX MC package. Equivalent 137 Cs treatments using FW and FSD applicators deliver dose rates within 10% difference for regions away from shields and up to 60% difference in regions proximal to shields in clinically relevant planes Similar but not equivalent

66 Conclusion PDR provides equivalent radiobiology to CLDR for pulse period chosen Differences due to radial dose function and anisotropy are within 5% Differences due to applicator perturbation is much greater, up to 60% near shields Dose distribution is fairly sensitive to source position relative to shield(s) Current TPS do not have accurate accounting for shield perturbation

Regulatory Guidelines and Computational Methods for Safe Release of Radioactive Patients II. Brachytherapy

Regulatory Guidelines and Computational Methods for Safe Release of Radioactive Patients II. Brachytherapy Firas Mourtada, Ph.D., DABR Chief of Clinical Physics Helen F. Graham Cancer Center Christiana