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 mis-

match 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.

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100 98 96 68 41 20 Number at risk

0 12 24 36 48 60Time from Rx (months)

Kaplan-Meier survival estimate

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

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Pre treatment Film

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