7th July CRH talk
Dr George Hruby
Senior Staff Specialist
Sydney Cancer Centre
Outline of Talk
• IGRT (Image Guided Radiation Treatment)
as applied to prostate cancer
• Update the Sydney Cancer Centre HDR
(high dose rate) brachytherapy
programme
Introduction
Dose escalation confers significant disease control
benefit in localised prostate cancer. 7 RCTs
show 10-20% improvement in FFF with
increased dose. Caveat…
- EBRT – landmark MD Anderson trial – FFF 78%
in 78Gy arm v 59% for 70Gy
- HDR brachytherapy as a boost
CT simulation
CT sim
Dual energy Linac with MLC
Conformal Radiation
treatment
Up until recently, EBRT has relied on a single planning CT
“snap-freeze” taken before treatment starts.
Regular X-rays (port films) were performed to ensure the
pelvic bony anatomy was in the same position
But
– required bigger margins to account for organ motion
- Could not visualize the prostate itself or its relationship to
OAR (organs at risk) eg rectum/bladder
treatment
EBRT
Reducing target uncertainty
• Rectal balloon
• Flatus tubes
Image Guidance
• Trans-abdominal ultrasound (BAT)
• Cone beam CT
• Fiducial markers
Brachytherapy
Prostate: EBRT
Fiducials
• In house feasibility trial of fiducial markers 2007/8
• Ethics approved for 25 patients
• 1st 5 patients – feasibility alone
• Current 20 – daily “on line” localization
• Feasibility study completed early 2008
• Standard practice since early 2008
Fiducial marker insertion
• Picture of Probe/Insertion
$ 200
Rectal Gas
Loss Gas between AP and Lat
Image “matched” to bone
Matched to fiducials
Results
• Slightly more invasive
• Very Feasible (even with prosthetic hip)
• RTs enthusiastic, if 3mm or greater mismatch in any 1 plane, we correct in all 3
planes
• Adds about 5 mins to 5 field prostate
treatment (OTT in bunker from 9 to 14
mins)
Where to next ?
Fiducials
• Now our standard treatment for intact
prostate
• Daily “on-line” seed matching allows
tighter margins in all 3 planes
hence
• safe dose escalation to 78Gy with 3D-CRT
• Same process crucial for IMRT 80Gy
TRUS
Setting up
HDR brachytherapy
HDR Brachytherapy
RPA experience
• First Case: January 2003
• 100th patient treated 28.11.2007
• Over 200 implants since technique
introduced.
• Team: ROs (Hruby, Patanjali), Urologists,
Anaesthetics (JL), RTs, physics, nursing.
Benefits of HDR
• Conformality (and effects on normal tissues)
• Radiobiologic advantage (low alpha/beta ratio of
prostate cancer suggests hypofractionated
treatment could improve response)
• Shorter overall treatment time (patient
convenience)
• Recent systematic review of 3 modalities of dose
escalation showed superiority of HDR as a boost
(vs IMRT or seed brachy boost) – Pieters 2009
Study Methods
• Data collected prospectively (outcomes,
toxicity, QOL)
• Patients were considered for HDR boost if
they had localised prostate cancer with
intermediate or high risk features, AND
were suitable for anaesthesia with a
reasonable life expectancy (~10years)
Radiation Technique
• First 67 patients: 6.5Gy x 3#
• Since then 2 separate implants for all
patients
• Dose escalation over last few yrs: 8.5 Gy x
2, 9 Gy x2, currently 9.5 Gy x2
• EBRT: 46Gy in 23# (prostate and seminal
vesicles only)
Failure
• Biochemical failure defined by Phoenix
definition (PSA nadir + 2)
OR clinical failure, any of
• Radiological evidence lymphatic or distant
disease
• LR on DRE, imaging or biopsy
• Need for salvage treatment (LHRH)
Patient Characteristics
• Median age 68 (46-79)
• Median PSA = 12 (3 – 43)
• 31, 58, and 11 men had Clinical T1, 2 and
3 disease, respectively
• GS 3+4 (36), 4+3 (42)
• Intermediate risk: n=65
• High risk: n=35
Androgen Ablation
• 95 patients received neo-adjuvant and/or
concomitant hormones
• 80 for 6 months
• 14 for 12 to 24 months
• 1 patient 3 months only
Results
• Median F-up 49 months (17 to 85)
• No data beyond 2 years for 3 patients
• OS 99% (one patient died of an MI)
Results continued
• 15 patients failed – 7 biochemical and 8 clinical.
• DFS rate
intermediate risk = 90.8%
high risk = 74.3%
• To date, no patients have developed clinically
apparent LR or metastatic disease.
Kaplan-Meier survival estimate
1.00
0.75
0.50
0.25
0.00
0
12
100
98
36
24
Time from Rx (months)
48
60
41
20
Number at risk
96
68
Acute toxicity
• Acute effects: 69% of patients had grade
1-2 acute urinary toxicity; 54% GI effects
(no grade 3 or 4)
• Three patients had post op PEs; another
patient was admitted to CCU with post op
AF.
Late toxicity
• GU – rate of urethral stricture 8% (only one of
these pts required more than one intervention)
• GI – 8% mild (gd 1) toxicity, 3% grade 2, No
grade 3 or 4.
• Erectile function preservation rate 72% (53/75
patients who were potent at baseline had
satisfactory EF post treatment)
How do the results compare?
• Comparable to large international series
(the largest pooled analysis Galalae
reported DFS of 69% and 88% for high
and int risk respectively at 5yrs)
• Toxicity also similar to that reported
elsewhere (including Sullivan’s data on
urethral strictures and most prostatectomy
data)
Discussion points
• Young cohort, median age 68
- Good preservation of EF (age and
microvasc disease recently proven to be
risk factors in post RT ED)
- PSA bounce – tends to occur in younger
patients, probably reflecting testosterone
recovery (6% in our cohort)
Change in toxicity Profile
• Shift in radiation related toxicity from
rectum to urethra
- MD Anderson gd 2+ rectal toxicity 26% in
high dose arm (vs 13% in std arm)
- Rates of urethral stricture comparable to
other studies but still higher than seed
brachy (up to 5.5%) EBRT (1-4%) and
IMRT (3%)
High risk patients
• 74% DFS
• However patients with more than one
adverse feature (T3+, PSA>20, GS 8-10)
all failed - Micro-mets ?
• Individualisation of treatment – androgen
deprivation and radiation volumes
(? treating pelvic nodes in these pts)
Evolution of Protocol
• Shift from 3 fractions to 2 (out-patient tmt,
eliminates problem of inter-fraction catheter
displacement, ?better for patients – patient
survey analysis pending)
• Dose escalation (19Gy in 2#; ? 15Gy in 1#)
• Fiducial markers – to quantify and account for
intra-fraction catheter displacement (may be
some time before we see if this translates into
improved toxicity profile)
Planning CT scout
•
Pre treatment Film
•