Comparison between existing brachytherapy techniques 2012 November 23

“Comparison between existing brachytherapy techniques” 2012 November 23 th, Mallorca, Spain Janusz Skowronek, MD, Ph. D, Ass. Prof. Brachytherapy Department, Greater Poland Cancer Centre, Poznań, Poland; www. wco. pl/zb

Permanent LDR brachytherapy and temporary HDR brachytherapy are competitive techniques for clinically localized prostate radiotherapy. PDR – where are you?

Mark K. Buyyounouski et al. A survey of current clinical practice in permanent and temporary prostate brachytherapy: 2010 update. Brachytherapy 11 (2012) 299 - 305 Years of respondents’ experience with LDR and HDR brachytherapy. LDR = low-dose-rate; HDR = high-dose-rate.

USA 2004 – 81850 pts (seeds) http: //www. rtanswers. org/statistics/aboutradiationtherapy. aspx 4

Patterns of care for brachytherapy in Europe: Updated results 2002 - 2007 Ferran Guedea, Jack Venselaar, Peter Hoskin, Taran Paulsen Hellebust, Didier Peiffert, Bradley Londres, Montse Ventura, Jean-Jacques Mazeron, Erik Van Limbergen, Richard Pötter, Gyorgy Kovacs Radiotherapy and Oncology 97 (2010) 514– 520 Prostate cancer Nr of patients Nr of centers LDR MDR PDR HDR Total 7940 806 5890 (74. 2%) 223 (2. 8%) 45 (0. 6%) 1782 (22. 4%) Group I 7224 Group II 672 Group III 44 133 5808 192 (2%) 45 Austria, Belgium, Denmark, Finland, France, Germany, Greece, (0. 6%) (80. 4%) Iceland, Ireland, Italy, Luxembourg, Monaco, The Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom 38 (5. 7%) 31 (4. 6%) 0 Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Slovakia, Slovenia. Albania, Armenia, Belarus, Bosnia and Herzegovina, 0 1 44 (100%) 0 Bulgaria, Croatia, Georgia, Israel, Macedonia, Moldova, Montenegro, Romania, Serbia, Turkey 1179 (16. 3%) 603 (89. 7%) 0

NCCN brachytherapy guidelines brachytherapy LDR • Permanent low-dose rate (LDR) brachytherapy as monotherapy is indicated for patients with low-risk cancers. • For intermediate-risk cancers consider combining brachytherapy with EBRT (40 -50 Gy) ± 4 -6 mo neoadjuvant/concomittant/adjuvant ADT. • Patients with high-risk cancers may be treated with a combination of EBRT (40 -50 Gy) and brachytherapy ± 4 -6 mo neoadjuvant/concomitant/adjuvant ADT. • Patients with a very large prostate or very small prostate, symptoms of bladder outlet obstruction (high IPSS), or a previous transurethral resection of the prostate (TURP) are more difficult to implant and may sufler increased risk of side effects. • Neoadjuvant androgen deprivation therapy may be used to shrink the prostate to an acceptable size.

NCCN brachytherapy guidelines brachytherapy • Post-implant dosimetry should be performer to dokument the quality of the implant. • The recommended prescribed doses for LDR monotherapy are 145 Gy for 125 -Iodine and 125 Gy for 103 -Palladium. • The corresponding boost dose after 40 -50 Gy EBRT are 110 Gy and 90 -100 Gy, respectively. HDR • High-dose rate (HDR) brachytherapy can be used in combination with EBRT (40 -50 Gy) instead of LDR. • Commonly used boost regiment include 9. 5 -10. 5 Gy x 2 fractions, 5. 5 -7. 5 Gy x 3 fractions, and 4. 0 -6. 0 Gy x 4 fractions.

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AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. Inclusion Criteria: Clinical Stage: T 1 -T 3 b and selected T 4 T 1 b-T 2 c and selected T 3 Gleason Score: Gleason score 2 -10 Gleason scores 2 -10 PSA: No upper limit, but in almost all cases, patient does not have documented distant metastasis (Tx. N 0 M 0) In almost all cases, a PSA≤ 50 ng/m. L No pathologic evidence of pelvic lymph node involvement No distant metastases

AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. Patient Selection Criteria: Monotherapy: Clinical T 1 b-T 2 b and Gleason score ≤ 7 and PSA ≤ 10 ng/m. L • Clinical stage T 1 b-T 2 b and Gleason score ≤ 6 and PSA ≤ 10 ng/m. L • Select higher risk patients • Salvage of select radiation therapy failures Boost: • Patients with high risk features such as T 3 -T 4, Gleason score 7 -10, and/or PSA > 10 ng/m. L • Selected patients with “bulky” T 1 -2 b tumor (inadequate information exists to clearly define bulky tumor based on DRE, TRUS, percentage positive biopsies) ≥ clinical stage T 2 c and/or Gleason score ≥ 7 and/or PSA > 10 ng/m. L Special clinical situations: Inadequate information exists to recommend supplemental XRT based on perineural invasion, percent positive biopsies and/or MRI-detected extracapsular penetration

AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. Exclusion Criteria: Relative Contraindications: Severe urinary irritative/obstructive symptomatology • Extensive TURP defect • Substantial median lobe hyperplasia • Prostate dimensions larger than the grid (i. e. , > 60 mm in width and > 50 mm in height) • Severe pubic arch interference • Gross seminal vesicle involvement • Prior pelvic radiotherapy • Inflammatory bowel disease • Pathologic involvement of pelvic lymph nodes • • Severe urinary obstructive symptoms • Extensive TURP defect or TURP within 6 month • Collagen vascular disease Absolute Contraindications: • Unable to undergo anesthesia (general, spinal, epidural, or local) • Unable to lay flat • Distant metastases • Life expectancy < 5 years

AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. Doses Monotherapy Pd-103 125 Gy (110 -120 Gy) I-125 145 Gy (140 -160 Gy) Cs-131 115 Gy 10. 5 Gy x 3 8. 5 -9. 5 Gy x 4 6. 0 -7. 5 Gy x 6 BT + EBRT 15 Gy x 1 (with 36 -40 Gy XRT) 9. 5 -10. 5 Gy x 2 (with 40 -50 Gy XRT) 5. 5 -7. 5 Gy x 3 (with 40 -50 Gy XRT) 4. 0 -6. 0 Gy x 4 (with 36 -50 Gy XRT) Pd-103 Boost (with 41. 4 – 50. 4 Gy EBRT) 90 -100 Gy I-125 Boost (with 41. 4 – 50. 4 Gy EBRT) 108 -110 Gy

AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. PTV The definition of volumes will be in accordance with ICRU Report 58: Dose and Volume Specification for reporting interstitial therapy. • Clinical Target Volume (CTV) is defined by the physician on the treatment planning scan. • For T 1 c-T 2 b, the brachytherapy CTV includes the prostate only • For T 3 a-T 3 b, the brachytherapy CTV includes the prostate and extra-capsular extension. • PTV = CTV. • Prostate with margin • Seminal vesicles • Prostate minus non-cancerous regions of the gland (e. g. , anterior base) • Image-guided target volumes such as indium-111 or MR spectroscopy

AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Eric Vigneault MD, Jean Pouliot, Ph. D August, 2008 AMERICAN BRACHYTHERAPY SOCIETY PROSTATE LOW-DOSE RATE TASK GROUP Gregory S. Merrick, M. D. , Michael J. Zelefsky, M. D. , John Sylvester, M. D. , Subir Nag, M. D. , William Bice, Ph. D. Recommended evaluated postoperative dosimetric parameters: The prescription dose will be given only to the PTV. • The goal is to deliver the prescription dose to at least 90% of the PTV (V 100 prostate >90%). • The volume of bladder and rectum receiving 75% of the prescription dose should be kept to less than 1 cm 3 (V 75 rectum and V 75 bladder < 1 cm 3) • the volume of urethra receiving 125% of the prescription dose should be kept to less than 1 cm 3 (V 125 urethra < 1 cm 3). • V 100 • V 150 • V 200 • D 90 • Urethral doses - should include UV 125, UV 150, UD 30, UD 5 and/or maximum and minimum dose • Rectal doses - cubic centimeters of rectum which received ≥ prescription dose (RV 100) •

Brachytherapy dose inhomogeneity • Differential dose volume histograms (d. DVH) for 125 I, 103 Pd and 192 Ir from average patient-derived data. Note that for the 192 Ir HDR brachytherapy DVH, the dose scale is ‘percent dose’ because different dose fraction sizes can be prescribed. • Note how heterogeneous and ‘hot’ these DVH are, particularly for 125 I and 103 Pd. Christopher R. King. LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models. Brachytherapy 1 (2002) 219– 226

HDR „Virtual planning” 20

HDR „Real-time planning” 21

LDR „Real-time planning” 22

HDR 23

HDR

LDR

Seeds LDR brachytherapy Advantages over HDR • Large worldwide clinical experience and longterm data available, • Patient and MD convenience, • High patient turnover in OR, • Ideal for patients with pre-existing ED or comorbidities precluding prolonged bedrest, • Ideal for patients with AUA scores of <12.

Seeds LDR brachytherapy Disadvantages over HDR • Dosimetric uncertainties regarding final seeds distribution and dosimetry (gland swelling, seeds migration, clumping), • No accurate post-implant plan in the OR since individual seed position identification is not yet possible, • Dosimetry is performed after patient leaves the OR, • Real implant dosimetry varies with time from procedure (“cold implants” until prostate edema subsides, seeds migration/clumping may add to dose inhomogeneity over effective treatment time (6 months for I-125).

Seeds LDR brachytherapy Disadvantages over HDR • Operator-dependent and patient volume-dependent to maintain expertise • Longer resolution of urinary symptoms Acute urinary toxicity “The Dribbler” Popular beer bar near Seattle Prostate Institute Courtesy of John Blasko

Seeds LDR brachytherapy Disadvantages over HDR • Less likely to preserve erectile function

Seeds LDR brachytherapy Bottom line • Both HDR and LDR work well in properly selected patients, • The differences in toxicity are minimal and the outcome is excellent with both, • No matter what you chose, get good at it! • If you like golf, tennis or dinner with family, go for seeds!

Seeds LDR brachytherapy Bottom line • If you have time to spare, • or you are an obsessive-compulsive type of guy • and a few millimeters or a few lost seeds would give you nightmares or heartburn, go for HDR

Seeds LDR brachytherapy Bottom line • In the end, what physicists or vendors try to convince you regarding precision, accuracy and sophistication with new HDR or LDR brachy extravaganza, take it with a grain of salt… It may not be clinically relevant after all.

Conclusions At present, the available clinical data with these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates.

Conclusions Will be a randomized trial be conducted comparing these two forms of brachytherapy?

Our choice… Thank you

Real problem! Radical prostatectomy Laparoscopic prostatectomy Robotic surgery or Conventional external beam 3 -D IMRT Conformal external beam IGRT Proton High-dose conformal Dose escalation High dose rate Brachytherapy Low dose rate HIFU Nerve sparing prostatectomy Hypofractionation Brachytherapy/external beam Any of the above with androgen deprivation RITA Cryotherapy