brachytherapy in carcinoma prostate

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Brachytherapy in carcinoma prostate Dr Sailendra Senior resident Dept of radiotherapy Maulana azad medical college

Transcript of brachytherapy in carcinoma prostate

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Brachytherapy in carcinoma prostate

Dr SailendraSenior resident

Dept of radiotherapyMaulana azad medical college

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rationale

• prostate adenocarcinoma has a low α/β-ratio of 1.2–3.0 Gy

• Late reacting tiisues are more sensitive to higher does per fraction

• It is a form of conformal radiotherapy that avoids dose to normal structures

• Shorter duration of treatment

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History of brachytherapy

1910 - Young used urethral radium for treatment of prostate cancer

1930 - Flocks first injected radioactive gold liquid into prostate

1970 -Whitmer et al. at MSKCC in New York first performed prostate seed implants using iodine seeds

1983 - Holm performed the first closed implant,using needles and ultrasound guidance

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INCLUSION CRITERIA

PATIENT FACTORS• Life expectancy >5 years• IPSS <15• Prostate volume <60 cm3• No defect if previous TURP• Minimal pubic arch

interference

TUMOUR FACTORS• Monotherapy: T1–T2b,

Gleason score ≤7, PSA ≤15a• Boost therapy: ≥T2 c,

Gleason score ≥7, PSA ≥10

IPSS , International Prostate Symptom Score

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TYPES

• LDR– CLASSIC LDR– ULTRA LDR

• HDR

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TYPES

LDR(0.4-2Gy/hr)LDR brachytherapy or ‘seed’ implant involves the insertion of permanent radioactive sources directly into the prostate.

HDR(>12Gy/hr)HDR brachytherapy also involves radioactive material being placed directly into the prostate but, unlike LDR seeds, the placement of the material is temporary and for shorter periods – usually for a day or two at a time

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TYPES OF PERMANENT IMPLANTS

Classic LDR• 222Rn seeds, 198Au seeds

• Half-lives of a few days

• High-energy γ-rays emitted by these sources

• Monoenergetic

• The patient must be confined to the hospital until the source strength decays to a safe level (two to three half-lives or about 10 days)

Ultra LDR• 103Pd, 125I and 131Cs

• Uses longer half life

• Low-energy photon emitters• cascade of rays with different energy

• The patient’s tissues or a thin lead foil are sufficient to reduce ambient exposure rates to negligible levels, eliminating the need to hospitalize

• Reduce radiation exposure to operating room personnel

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TYPES OF SEEDS

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Loose seeds Vs stranded seeds• Stranded seeds are fabricated with absorbable spacer

material,which fix the distance of 1 cm between the centers of two serial seeds.

• capability of minimizing the risk for seed loss• Loose seeds can migrate through the venous system to the lungs,

abdomen and pelvis or are excreted with urine or ejaculated• Most of the seeds get lost within 30days of PSI• Loose seeds are used in centre to prevent higher dose to urethra • Stranded seeds can be used in cases where margin is required

around prostate

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Factors predicting seed loss• Number of needles

• Number of seeds

• Preoperative prostate volume

• Expertise of the brachytherapy team

• Surprisingly, overall seed loss was more frequent in the patient group with stranded seeds, which might be biased by low patient number (n = 40) or wrong technique.

Miyazawa et al. 2012; Kono et al. 2010

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PROCEDURE OF LDR

• Preplanned interstitial implant• Intraoperative interstitial implant

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Preplanned interstitial implant

• Patient selection• Ultrasound simulation and volume assesment• Treatment planning• Implant process• Post-implant dosimetry• Follow-up

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Ultrasound simulation and volume assesmentTRUS imaging is obtained before the planned procedure to assess the prostate volume

Treatment planningA computerized plan is generated from the transverse ultrasound images, producing isodose distributions and the ideal location of seeds within the gland to deliver the prescription dose to the prostate.

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THINGS TO ENSURE PRIOR TO THE IMPLANT PROCEDURE

• Patient is admitted the night prior to the day of the procedure

• Enema to clear bowel prior to the procedure

• Preanesthetic check up should be done

• Fasting for atleast 6hrs before the procedure

• Shaving the hair from the genital area

• Medication that need to stop before the procedure, e.g. anticoagulants, anti-inflammatories, herbal or complementary supplements

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IMPLANT PROCESS• Done under general anaesthetia or spinal anaesthesia

• Patient in lithotomy position

• Patient is catheterised

• Real time TRUS guided

• 60-100 small radioactive seeds are placed inside the prostate

• Seeds are inserted using Needles or Mick applicator guided by a template placed over the perineum according to the coordinates determined by the preplan

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Mick applicator

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POST IMPLANT DOSIMETRY• Post implant CT scan is done and images transferred to TPS

• At first, the actual number of seeds in the target area is detected.

• If there are missing seeds, a chest X-ray is recommended.

CONTOURING – CTV-P (prostate)– CTV-PM (prostate + 3mm margin)– Rectum (“r”)– intraprostatic urethra (“u”)

• The detection of the seeds in the CT / MRI images is performed by the automatic seed finder feature of the planning software

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TARGET DELINEATION• The clinical target volume (CTV) is defined as the whole prostate as

seen in rectal ultrasound • The seminal vesicles are not usually included within the clinical

target volume. • A margin of 2–3 mm is added to generate the planning target

volume (PTV).• In high risk prostate cancer, the PTV may consist of the prostate

gland with a 5 mm margin (posteriorly 2 mm).• The proximal 1 cm of the seminal vesicles should also be included

in the planning target volume in high risk cases(Bittner et al. 2012)• The whole plan is then correlated with the pre plan for

verification.

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Does prescription

The dose constraints for the PTV (prostate plus margin) are:– pD90 > 100 % of prescribed dose(PD) – pV100 ≥95 %,– pV150 ≤50 %

• Rectum– rD2cc ≤ PD and rD0.1cc<200 Gy

• Prostatic urethra – uD10 <150 % of PD – uD30 <130 % of PD

The GTV should be encompassed by the 150 % isodose.

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Post procedure

• Antibiotics to prevent infection.• Stool softeners to avoid constipation• Can resume eating and drinking once patient is awake• Barrier contraception is recommended for use for the

first two months after implantation• Patient is advised to come after 1month for follow up• it is important to remember that………………. the seeds

are radioactive, you are not

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Intraoperative Planning• An ultrasound probe is positioned in the rectum and the prostate and

normal anatomies are identified.

• Needles are inserted through the perineal template

• The prostate is subsequently scanned from apex to base, and these 0.5-cm images are transferred to the treatment-planning system

• On the computer monitor, the prostate contours and the urethra are digitized on each axial image.

• Needle positions are identified on each image, and their coordinates are incorporated into a genetic algorithm optimization program.

• After the optimization program identifies the optimal seed-loading pattern and the dose calculations are completed

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LDRadvantage

• Usually only requires one night in hospital

• Less invasive procedure than prostatectomy

• Repeated treatments not required

• Lesser risk of long term effects to normal tissues (rectum, bladder, urethra)

• Probably better preservation of erectile function

disadvantage

• Not available in all centres

• Urinary side effects may occur which might last over several weeks or months

• Anaesthetic and surgical procedure required

• You will have minor temporary changes to lifestyle as a result of radioactive implant

• Costly

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Rationale for HDR Brachytherapy• Higher dose per fraction as carcinoma prostate behaves as a

late responding tissue

• Without unacceptable dosimetric changes caused by source migration and tissue deformity as in LDR implants

• No intrafraction motions as in EBRT

• Temporary HDR BRT is not limited by positioning uncertainties as the target is immobilized by the implanted catheters and treated within very short treatment times.

• Since there is no permanent implant with HDR, no long-term radiation protection issues exist as in the case of LDR BRT

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Brachytherapy Techniques

• performed under spinal or general anesthesia• Patient in lithotomy position• Real-time TRUS-guided implantation• Treatment planning after TRUS-guided

implantation is commonly performed using either CT or TRUS imaging

• Perineal template to aid catheter placement

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• For CT based planning, 3 mm slice thickness in the axial plane is used

• Imaging should extend the prostate in the craniocaudal extension and should include sufficient normal anatomy for meaningful normal tissue dosimetry

• PTV is defined as the entire prostate gland without margins

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• Based on the acquired 3D anatomy, the appropriate virtual needle positions are generated, the needle source dwell positions located within the PTV are activated, and the radioactive source dwell times are calculated using an intraoperative treatment planning system

• If the pre-planning dosimetry parameters fulfill the dosimetric protocol, TRUSguided implantation of catheters is performed at the previously determined positions

• After completion of implantation, a final 3D TRUS data set is acquired for intraoperative real-time treatment planning.

• Real needle positions are reconstructed and dwell positions located within the PTV are activated ensuring the 3D dose distribution fulfills the dosimetric protocol

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• Irrespective of the imaging modality for interventional guidance or treatment planning, HDR is performed using a remote afterloading system.

• Iridium 192 is the most commonly used isotope with an average energy of 380 keV, a half-life of 73.8 days and a half value layer of 2.5 mm of lead

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DEMERITS OF CT BASED AND TRUS BASED PLANS

CT PLANNING

• The potential disadvantages of CT dosimetry are the need to move the patient and the time it takes to go from one location to another to perform serial functions.

• There may occur changes in catheter positions during transfer

TRUS PLANNING

• The image distortions (“shadows”) produced by the posterior (dorsal) catheters can obscure the view of more anterior (ventral) catheters during treatment planning, and the catheters themselves can obscure the prostate contour especially near the apex.

• Definition of contours of the rectum and to a lesser extent the bladder may be less accurately rendered with real time TRUS planning than with CT-based planning.

• Newer 3D ultrasound probes will likely reduce some of these technical difficulties

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D. Jeffrey Demanes, Michel I. Ghilezan

High-dose-rate brachytherapy as monotherapy for prostate cancer

Brachytherapy, Volume 13, Issue 6, 2014, 529–541

Fig. 1. CT-based dosimetry. Transverse, sagittal, coronal, and three-dimensional views.

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D. Jeffrey Demanes, Michel I. Ghilezan

High-dose-rate brachytherapy as monotherapy for prostate cancer

Brachytherapy, Volume 13, Issue 6, 2014, 529–541

Fig. 2. Ultrasound-based dosimetry. Coronal, transverse, sagittal, and 3D views with 100% isodose lines and 3D cloud (red). 3D = three-dimensional. (For interpretation of the references to color in this figure legend, the reader is referred to the web version ...

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DOSE SCHEDULES

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HDRADVANTAGES

• Shorter course of treatment

• Usually minimal side effects are experienced around the time of treatment

• Minimal post procedure recovery time required

DISADVANTAGES

• Needs hospitalisation

• Not available in all centres

• Having to lie flat while the implant catheters are in place, sometimes overnight, which can be uncomfortable.

• Side effects affecting bladder, bowel and erectile function can occur in the longer term

• Costly

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TOXICITY

• URINARY TOXICITY

• RECTAL TOXICITY

• ERECTILE DISFUNCTION

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URINARY TOXICITY• Acute urinary retention• urinary frequency• Urgency• occasional urge incontinence.

• Depending on the isotope used, these symptoms often peak at 1 to 3 months after the procedure and subsequently gradually decline over the ensuing 3 to 6 months.

• Most patients benefit with the use of an α-blocker, which ameliorates such symptoms in 60% to 70% of patients.

• Most urinary symptoms resolved within 12 months after the procedure, and significant residual toxicity was unusual.

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Multivariate analysis demonstrated that the

– use of androgen-deprivation therapy before implantation

– High prostate volume– higher baseline IPSS– use of higher number of needles

was associated with increased rate of grade 2 acute toxicity

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RECTAL TOXICITY• Symptoms manifest as rectal bleeding or increased

mucous discharge.• The onset of symptoms often peaks at 8 to 12 months

and is self-limited in natureERECTILE DYSFUNCTION• Erectile dysfunction after brachytherapy has been

reported to occur in from 20% to 80% of patients.• Excellent responses were observed with sildenafil citrate

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