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7 th July CRH talk

7 th July CRH talk

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7 th July CRH talk

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  1. 7th July CRH talk Dr George Hruby Senior Staff Specialist Sydney Cancer Centre

  2. Outline of Talk • IGRT (Image Guided Radiation Treatment) as applied to prostate cancer • Update the Sydney Cancer Centre HDR (high dose rate) brachytherapy programme

  3. 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

  4. CT simulation

  5. CT sim

  6. Dual energy Linac with MLC

  7. 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

  8. treatment

  9. EBRT

  10. Reducing target uncertainty • Rectal balloon • Flatus tubes Image Guidance • Trans-abdominal ultrasound (BAT) • Cone beam CT • Fiducial markers Brachytherapy

  11. 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

  12. Fiducial marker insertion • Picture of Probe/Insertion

  13. $ 200

  14. Rectal Gas

  15. Loss Gas between AP and Lat

  16. Image “matched” to bone

  17. Matched to fiducials

  18. 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)

  19. 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

  20. TRUS

  21. Setting up

  22. HDR brachytherapy

  23. HDR Brachytherapy

  24. 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.

  25. 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

  26. 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)

  27. 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)

  28. 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)

  29. 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

  30. 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

  31. 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)

  32. 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.

  33. 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.

  34. 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)

  35. 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)

  36. 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)

  37. 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%)

  38. 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)

  39. 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)

  40. Planning CT scout

  41. Pre treatment Film