Transcript Prostate Support Group

Prostate Support
Group
Dr Duncan McLaren
Consultant Oncologist
Presentation
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Radiotherapy results
Current RT dose
IGRT
IMRT- Rapid arc
HDR
Q&A session
New Drugs
Q&A
Some good news
80%
2001-6
1996-01
Improved cause specific
survival with radiotherapy
over the last 30 years
70%
35%
1982-92
Some good news
2001-6
1996-01
55Gy
52.5Gy
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
Why dose such a
modest dose
escalation work !
Alpha/Beta for tumour = 10
Alpha/Beta for prostate tumour =1.5-3.0
ALPHA
SF
Alpha/Beta for normal tissue = 5
2Gy per day
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
Current XRT schedules
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Hypo-fractionation
57Gy in 19#
3Gy per day
74Gy equivalent
• 60Gy in 20# future dose
• 78Gy equivalent
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Standard fractionation
74Gy in 37#
2Gy per day
Can treat pelvic nodes
• Future dose 78Gy
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
High dose rate
Permanent
Iodine 125 seeds
Temporary
Iridium 192
Single stop intraoperative
prostate Seeds
Brachytherapy
Live since 2010
First 150 men @ 5yrs
good
Int
95%
80%
55%
poor
P=0.0005
5 year outcomes
5 yr PSA
RFS
52.5Gy
55Gy
Brachy
GOOD
60%
80%
95%
57-60Gy
verses
74Gy
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INT
40%
70%
80%
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POOR
20%
40%
55%
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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
New drugs in metastatic
prostate cancer
How does hormone blockade work?
ZOLADEX
CASODEX
LHRH agonists
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 intratumour
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
Cabazitaxel v Mitoxantrone post Taxotere
progression- TROPIC Trial
positive results
does not =
NHS funding
Median survival benefit 2.4 months
Median survival 15.1 mths
Cabazitaxel v 12.7 mths
Mitoxantrone p=0.04
Thank you