Brachytherapy: Clinical implementation LDR/HDR Kent A. Gifford, Ph.D.

Prostate seed LDR (PPI) Advantages Dose conformity, normal tissue sparing Continuous LDR delivery Monotherapy can ablate prostate cancer cells “One and done” procedure No concerns about EBRT motion, setup uncertainties

Prostate seed LDR (PPI) Disadvantages Rapid falloff of ~25keV photon sources Edema of implant Variability of manufacture and activity of sources Interseed and Intraseed attenuation Subject to skill/experience of brachytherapist (art??)

Prostate seed LDR (PPI) Seed properties Radionuclide Cs-131 I-125 Pd-103 Half-life (days) 9.65 59.4 16.97 Average Energy (keV) 29 27 21 Λ (cGy hr-1 U-1) 1.05 0.96-1.04 0.69 Half-value layer (mm) 0.035 0.025 0.008

Monotherapy and boost doses Isotope Cs-131 I-125 Pd-103 Monotherapy dose (cGy) 100-115 140-160 115-130 Boost (cGy) 70-80 100-110 80-110

Treatment Guidelines Seeds I-125: Nycomed-Amersham Model 6711 (NIST 99) Pd-103: Theraseed Model 200 (NIST 99) Activities used at MD Anderson I-125: .391 mCi = .497 U (used in planning software) Pd-103: 1.4 mCi= 1.810 U Will use 1 week decayed sources with a 7.77% decay; .361 mCi= .457 U

Treatment Guidelines Cont. Doses are given as the total dose given over the life of the radioactive seed (decayed to 0 mCi) Planned dose - TG 43 Full Dose: Brachytherapy only I-125: 145 Gy Pd-103: 115 Gy External Beam + Brachytherapy XRT 45 Gy + I-125 110 Gy XRT 45 Gy + Pd-103: 100 Gy

Advantages and Disadvantages of Seed Types NIST Traceable Calibration Well Characterized dosimetry Rapid Strands available Disadvantages Relatively long half life Rounded seed ends makes them mobile Very anisotropic dose distribution Pd-103 Advantages Short Half Life Cupped seed ends tend to anchor seeds Seed activities within +/- 5% Disadvantages No calibration standard Dosimetry based on only two studies Activity decays 4% a day

Which to use? I-125 or Pd-103 Generally use Pd-103 for higher grade tumors The disadvantage is Pd-103 short half life – may miss the slower growing tumor cells.

Pd-103 Seed in comparison with I-125 Seed

Prostate Implants at MD Anderson Modified Peripheral Loading based on Seattle technique Pre-Plan/ Pre-loaded technique Use I-125 seeds, Pd-103, Cs-131 Pre-Implant Ultrasound Volume Study performed 2 weeks to a month before actual implant by the Radiation Oncologist and Resident Plan based on ultrasound images acquired during volume study

Implants at MD Anderson Cont. Varian Variseed computer software used for planning Implant performed under anesthesia as an outpatient procedure Post Implant CTs performed on Day 1 and Day 30 (2 wks potentially for Pd-103, Cs-131)

Pre-Implant US Volume Study 2 weeks to a month before actual implant scheduling ordering of seeds Done in Urology with the patient awake Procedure time: 20-30 min. Patient positioned in stirrups similar to those in the operating room Transrectal Ultrasound (TRUS) used to acquire images

TRUS Imaging Diagram

Pre-Implant US Volume Study Without a good volume study a good plan can not be designed Oncologist draws target volume, tissue that is identified to be treated on each 5 mm slice Prostate Volume is determined from the prostatic margin The target volume includes the prostate volume and some of the surrounding tissue Ultrasound study is done in Urology Considered an art to find prostate margins on US although the imaging with new units has improved significantly over the years The target may appear outside of the prostate margin but due to uncertainty of margins this is OK Take slices 5 cm caudal to the apex and 5 cm cephalad to the base Do a sagittal image

Pre-Implant US Volume Study

Pre-Implant US Volume Study KY Jelly or Ultrasonic Gel used as medium for ultrasound transmission Condom placed over the probe Standoff cap used for prostates that lie posteriorly Requirements for adequate ultrasound images complete contact between transducer and the medium absence of air in the medium good contact with the rectal wall absence of gas or stool in the rectum

Pre-Plan

Variseed Software: Template Registration 3 Point Method 1.) Lower Left Location: A 1.0 2.) Lower Right Location: G 1.0 3.) Designated Row: Any Hole (usually row 5) Template (in red)

Contours

Source Placement Set Reference Plane to Base Slice (0.00 cm) Right Click on image when highlighted in big window

Planning Guidelines Pre-Implant US Volume Study ultrasound images used Modified Peripheral Loading Technique Base Pattern- basic pattern of needles that begin at the base of the prostate Implant small letters (a,b,c,d…) and whole integers (1.0, 2.0, 3.0…) starting with the base slice Place needles and seeds in the template locations in the prostate or within 1/2 cm from prostatic capsule delineated by the contour Continue pattern every 1 cm

Base Pattern Base Slice 0.5cm Slice 1.0cm Slice 1.5 cm Slice

0.0 cm Slice (base)

1.0 cm Slice

2.0 cm Slice

3.0 cm Slice

Planning Guidelines Cont. Patching Pattern- On the slices with a retraction of a 1/2 cm from the previous pattern- Implant at the big letters (A,B,C,D…) and the half-integers (1.5, 2.5, 3.5,…) Place needles and seeds in the template locations in the prostate or within a 1/2 cm from the prostatic capsule delineated by the contour Avoid the “Big D” column due to the position of the urethra Continue pattern every 1 cm Modify central needles for urethral sparing remove complete needles if 100% isodose line sufficiently covers the prostate Remove central seeds in the needles- leave seeds at base and apex

Patching Pattern Base Slice 0.5cm Slice 1.0cm Slice 1.5 cm Slice

0.5 cm Slice

1.5 cm Slice

2.5 cm Slice

3.5 cm Slice (apex)

Remove seeds from “c,d” between rows 2 and 3 0.0 cm slice 2.0 cm slice Urethral Sparing Remove seeds from “c,d” between rows 2 and 3 1.0 cm slice 3.0 cm slice

Remove seeds from “C & D” between rows 2.5 and 3.5 0.5 cm slice 1.5 cm slice Urethral Sparing Remove seeds from “C & D” between rows 2.5 and 3.5 2.5 cm slice 3.5 cm slice

Considerations when Planning Dipping of the 150% isodose line down the center of the gland - urethral sparing Don’t compromise the 100% isodose line for urethral sparing

Dipping of 150% Isodose Line Urethral Area 150% Line 150% Line

Considerations when Planning Dipping of the 150% isodose line down the center of the gland - urethral sparing Don’t compromise the 100% isodose line for urethral sparing No needles can have less than 2 seeds Try to keep the needle count < 30 Optimal prostate sizes to implant: 20-50 cc The length of the urethra that receives more than 400 Gy for I-125 should be kept as low as possible

Considerations when Planning Plan with sufficient dose at the base loose periprostatic tissue has a high probability of causing seed migration a more extended lithotomy position during implant causes the base slice to be larger decreases total number of slices area with most cold spots, due to anatomical position Load posteriolateral aspects of the prostate light location of neurovascular bundles seed migration very likely Symmetry is important for uniform dose

Considerations when Planning Solutions for prostates that lie posteriorly drop the needles in the “big letter (A,B,..)” columns from the half-integers (1.5,2.5,…) to the whole integer (1.0,2.0,…) rows below them follow loading guidelines despite modifications Avoid the rectum as much as possible by loading the central template locations cooler (“big” C-E) Rectal dose should not exceed 100 Gy Do not implant or include the seminal vesicles due to unreliable source placement

Considerations when Planning Mid-gland- generous coverage laterally and anteriorly, no margin posteriorly because of the rectum Recommended to load 70% on the periphery and 30% on the interior Hot spots in the interior of 200-250 Gy can be expected 145 Gy line should extend 3-5 mm beyond the margin drawn

Final Plan Images 1 - 4 Images 5 - 8 Images 9 - 10

Seed Assay and Loading 10% of seeds assayed and then sterilized Loaded under a sterile environment Seeds loaded according to VariSeed computer printouts seed positions with correct orientation most needles loaded with a seed to begin with and then a seed at every cm with a spacer in between each seed each needle ends with a seed due to doctor preference Once all the needles are finished then a verification film must be taken to assure that the needles are loaded correctly

Prostate Seed Implant Needle QA Films

Needle Loading Box Based on the plan and template location, the needles are placed in the needle box after verification and taken up to the Operating Room the following day

Operating Room Procedures In the Operating Room the patient will be returned to the same position as they were in for the pre-plan (a catheter will be placed with contrast in the Foley balloon) Fluoroscopy used The Physician will need the pre-planning US to check for patient position for the implant Need patient plan, loading diagram, small lead pig, calculator, NaI detector, Geiger-Mueller detector and any radiation safety forms you may need should the patient require a stay in the hospital over night

Operating Room Setup

OR Procedures Coordinates of the needle and retraction of the needle are read from the treatment plan When all the needles have been loaded, the extra needles will be used to fill in at the apex and any “cold” spots This is done using fluoroscopy as well as ultrasound The urologist will do a cystoscopy to ensure there are no seeds in the bladder, if there are seeds they will be retrieved and put in the little lead pig

OR Procedures Make a note in the patient chart with total seeds and needles, total activity, and survey meter reading of the patient with the Geiger detector You must remain in the OR until every seed has been accounted for!!! Once the patient has left the room, use the NaI detector to survey EVERYTHING. X-ray taken of last fluoroscopic image to verify the number of seeds implanted (verification)

Verification Fluoroscopy Image

Post-Implant Dosimetry Seed Identification- 5 mm CT scan example

Post-Implant Dosimetry 3-D Dose Reconstruction with Dose 100% isodose cloud (2 different cases)

Post-Implant Dosimetry Timing of CT Scans Edema Average swelling- 20%-50% post implant (Range: 0-96%) calculated by interseed spacing prostate border delineation not as accurate of a measurement T 1/2 = 10 days D90 increases 30 % from day 1 to day 21 Anderson’s experience- prostate back to normal by day 30 Volume increase results in average of 10% underestimate of dose Suggested Timing between 2 post-implant scans: Pd-103- 2 weeks, I-125- 4 weeks

Post-Implant Dosimetry Dose Evaluations Isodose Distributions 2-D distributions on sequential slices of target Recommended isodose lines: 200%, 150, 100, 90, 80, and 50. Dose Volume Histograms (DVH) Cumulative DVH recommended Percent volume of prostate that receives greater than or equal to dose delivered Report following: D100, D90, D80 (dose that 100% of the prostate receives)

Implementation, QA, physicist responsibilities- TG-56 Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.

Implementation, QA, physicist responsibilities Nath et al., Med. Phys. 24(10) 1557-98 1997.