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Prostate Support Group. Dr Duncan McLaren Consultant Oncologist. Presentation. Radiotherapy results Current RT dose IGRT IMRT- Rapid arc HDR Q&A session New Drugs Q&A. Some good news. 80%. 2001-6. 70%. 1996-01.
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Prostate Support Group Dr Duncan McLaren Consultant Oncologist
Presentation • Radiotherapy results • Current RT dose • IGRT • IMRT- Rapid arc • HDR • Q&A session • New Drugs • Q&A
Some good news 80% 2001-6 70% 1996-01 Improved cause specific survival with radiotherapy over the last 30 years 35% 1982-92
Some good news 55Gy 2001-6 52.5Gy 1996-01 50Gy 1982-92
Effect of dose escalation T1-2b Gleason 6 PSA<10 55Gy 80% 60% 52.5Gy P=0.0086 Time to PSA relapse years
T2c or Gleason 7 or PSA >10 55Gy 70% 40% 52.5Gy P<0.0001 Time to PSA relapse Years
T3 or PSA >20 or Gleason grade >8 55Gy 40% 52.5Gy 20% P<0.0001 Time to PSA relapse Years P = 0.0086
Why dose such a modest dose escalation work ! Alpha/Beta for tumour = 10 Alpha/Beta for prostate tumour =1.5-3.0 Alpha/Beta for normal tissue = 5 ALPHA 2Gy per day SF Normal tissue 3Gy per day BETA Prostate Tumour 2 3 4 DOSE per fraction
Advantages of Hypo-fractionation • Shorter number of treatments • Benefits patients and machine capacity • Possible reduced acute toxicity • CHHiP toxicity data supports this • Possible improved efficacy • CHHiP outcome data awaited • In house data very supportive
Potential disadvantages • If alpha beta ratio is wrong then a lower dose is given • It may increase late damage on the rectum or bowel • No evidence of this with in house data • Need to deliver dose very accurately IGRT conformal XRT or IMRT
Hypo-fractionation 57Gy in 19# 3Gy per day 74Gy equivalent 60Gy in 20# future dose 78Gy equivalent Standard fractionation 74Gy in 37# 2Gy per day Can treat pelvic nodes Future dose 78Gy Current XRT schedules
Why we can increase our doses safely Image Guided Radiotherapy IGRT 2009 Fiducial Markers Inserted trans rectally Images true prostate position and software calculates how much to move the field to correct for it
Intensity modulated radiotherapy IMRT Advantages over conformal XRT Much tighter dose to the prostate Reduced dose to normal tissue Further dose escalation Disadvantages Prostate movement Time consuming Irradiated volume
New for 2012! Even better XRT! Varian Novalis Trilogy Linear Accelerator with Rapid Arc
Faster, reduced dose to normal tissues, greater patient throughput and can be used as a standard linear accelerator
2012 research project to use Multi-parametric MRI to fuse with planning CT scan to allow potential prostate tumour boost dose
What is happening in Prostate Brachytherapy? Low dose rate Permanent Iodine 125 seeds High dose rate Temporary Iridium 192
Single stop intraoperative prostate Seeds Brachytherapy Live since 2010
First 150 men @ 5yrs good 95% Int 80% 55% poor P=0.0005
How to improve outcome for high risk disease • Single fraction of HDR brachytherapy and 13 fractions of external beam Brachytherapy External beam
HDR High dose rate prostate brachytherapy Business case 2012
Advantages Very high dose boost single 15Gy fraction Flexibility to ensure dose constraints to rectum and urethra are met by adjusting catheter or source position Reduced irradiated volume 13 fractions of XRT 2 weeks later 2 Gy equivalent dose >100Gy Disadvantages Relatively medically labour intensive GA or spinal Possible overnight stay
How does hormone blockade work? CASODEX ZOLADEX
Degarelix – GnRH antagonist 240mg given as 2 subcutaneous injections of 120mg each (loading) Followed by 80mg maintenance every 28 days
Degarelix - Firmagon SMC approval for advanced prostate cancer January 2011 Locally used for high risk patients with high PSA and very symptomatic e.g. SCC Major benefit is lack of testosterone flare
Abiraterone mode of action - Cyp -17 blocker Blocks body androgens Blocks intra- tumour androgens
Abiraterone Phase III trial results Median Survival benefit = 3.9 months Abiraterone 14.8 mths OS HR 0.65 Placebo 10.9 mths OS
MDV 3100 AFFIRM Trial Androgen receptor signalling blocker Results not yet published but trial closed December 2011 OS 18.4 months MDV 3100 OS 13.6 months placebo HR 0.63 Median survival benefit 4.8 months
Alpharadin- Radium 223 ALYMPSA Trial post Taxotere progression Median survival benefit 4.8 months 16.3 mths 11.5mths
positive results does not = NHS funding Cabazitaxel v Mitoxantrone post Taxotere progression- TROPIC Trial Median survival benefit 2.4 months Median survival 15.1mths Cabazitaxel v 12.7 mths Mitoxantrone p=0.04