Vakalis - RT for prostate cancer

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Vakalis - RT for prostate cancer

  1. 1. Ε. ΑΝΔΡΙΩΤΗΣ Νεώτερα δεδομζνα ςτην ακτινοθεραπεία του καρκίνου του προςτάτη 2ο Συμπόσιο Κλινικής Ογκολογίας Ρόδου Ακτινοθεραπευτήσ Ογκολόγοσ Euromedica – Αθήναιον Α & Ιατρικό Κζντρο Αθηνών
  2. 2. Cancer Cases in 2013
  3. 3. Cancer Deaths in 2013
  4. 4. ΚΙΝΔΥΝΟΣ ΕΜΦΑΝΙΣΗΣ
  5. 5. Male Cancer Mortality Rates 1930 to 2009 prostate colorectal stomach lung
  6. 6. CaPSURE: Risk Category at Diagnosis 0 20 40 60 80 100 1989 1990 1991 1992 1993 1994 1995 1996 1997 1999 2000 2001 2002 Patients(%) High risk Intermediate risk Low risk 30.2% 37.3% 32.5% 25.1% 38.5% 36.4% 16.0% 37.2% 46.8% 36.6% 33.8% 29.5% Reprinted with permission from Cooperberg MR et al. J Urol. 2003;170:S21
  7. 7. Treating prostate cancer Surgery? Radiation? Or Watchful Waiting?
  8. 8. Καηεςθύνζειρ για ηην θεπαπεία ηοπικήρ νόζος Ιαηπικά πποβλήμαηα αζθενούρ Νοζηπόηηηα Ca πποζηάηος Πποζδόκιμο επιβίυζηρ (αναμενόμενη) • Δνδοκατική νόζορ (Σ1/Σ2), Gleason score (< 7) & PSA(<10) - Ρηδηθή πξνζηαηεθηνκή ή αθηηλνζεξαπεία ή παξαθνινύζεζε • Σοπικά πποσυπημένη νόζορ (Σ3/Σ4) – Αθηηλνζεξαπεία + Οξκνληθόο απνθιεηζκόο (LHRH αλάινγα)
  9. 9. bRFS in pts with favorable tumors (T1-T2A, bGS< 6, iPSA< 10 ng/ml) Kupelian PA, JCO 2002
  10. 10. bRFS in pts with unfavorable tumors (T2b-T2c, bGS> 6, iPSA>10 ng/ml) Kupelian PA, JCO 2002
  11. 11. Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer The Prostate Cancer Outcomes Study (PCOS), comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis • Urinary Incontinence: worse with surgery at 2 and 5 years but the same by 15 years • Erectile Dysfunction: worse with surgery at 2 and 5 years but the same by 15 years • Bowel Urgency: worse with radiation at 2 and 5 years' but by 15 years' the same N Engl J Med 2013; 368:436-445
  12. 12. Η ΑΚΘ ΒΔΛΣΙΩΝΔΙ ΣΗΝ ΔΠΙΒΙΩ΢Η;
  13. 13. ΝΑΙ ! Η ΑΚΘ βειηηώλεη ηελ 10-εηή επηβίσζε Warde P et all Lancet 2011 Widmark A et all Lancet 2009
  14. 14. ΣΟΠΙΚΗ ΤΠΟΣΡΟΠΗ – ΓΟ΢Η ΑΚΣΙΝΟΘΔΡΑΠΔΙΑ΢
  15. 15. Χακειή δόζε
  16. 16. ηο ππόβλημα λύνεηαι με Αύξηζη ηηρ δόζηρ
  17. 17. Σςσαιοποιημένερ μελέηερ πος δείσνοςν ηο όθελορ από ηην αύξηζη ηηρ δόζηρ (συπίρ IMRT και οπμονοθεπαπεία) RCT N Comparison Result Pollack (MDA) 2007 update 301 70Gy/35 vs. 78Gy/39 59% vs. 78% bPFS at 5 years Zietman 2005 393 70.2Gy vs. 79.2Gy (proton boost) 61% vs. 80% bPFS at 5 years Peeters (Dutch) 2006 664 68Gy/34 vs. 78Gy/39 54% vs. 64% FFF at 5 years Dearnaley (RTO1) 2007 843 64Gy/32 vs. 74Gy/37 60% vs. 71% bPFS at 5 years Hoskin (Mt Vernon) 2007 220 55Gy/20 vs. 35.75Gy/13 + HDR 8.5Gy x 2 64% vs. 80% bPFS at 5 years bPFS=biochemical progression free survival FFF= freedom from failure
  18. 18. Low Risk T1-2, GS ≤6, PSA ≤10 Memorial Sloan Kettering Cancer Center IMRT Dose Escalation Zelefsky MJ, Chan H, et. Al. Journal of Urology Vol. 176, 1415-1419, Oct 2006
  19. 19. Intermediate Risk Memorial Sloan Kettering Cancer Center IMRT Dose Escalation Zelefsky MJ, Chan H, et. Al. Journal of Urology Vol. 176, 1415-1419, Oct 2006 T1-2, GS 6, PSA > 10 T1-2, GS >6, PSA  10 T3, GS  6, PSA  10
  20. 20. High Risk GS >6, PSA >10 Memorial Sloan Kettering Cancer Center IMRT Dose Escalation Zelefsky MJ, Chan H, et. Al. Journal of Urology Vol. 176, 1415-1419, Oct 2006
  21. 21. Improving the Results of Radiotherapy Dose escalation– increasing the dose of radiation by 10% can increase local control by 20% (level 1 evidence) 3D Conformal, IMRT, HDR Brachytherapy boost Combination treatment with radiotherapy and androgen suppression
  22. 22. Αύξηζη ηηρ δόζηρ – Σοξικόηηηα
  23. 23. Απώηεπη Σοξικόηηηα ζηιρ μεγάλερ μη- IMRT μελέηερ αύξηζηρ ηηρ δόζηρ Γαζηπενηεπική Σοξικόηηηα Σοξικόηηηα από Οςποποιηηικό Grade 2 Grade 3 Grade 2 Grade 3 Κλαζζική Γόζη 8 – 23% 1 – 2% 6 – 28% 1 – 8% Ττηλή Γόζη (Μη-IMRT) 7 – 30% 1 -7% 10 – 30% 1 – 15 % 2 θοπέρ μεγαλύηεπορ κίνδςνορ ζοβαπήρ ηοξικόηηηαρ !
  24. 24. Evolving Radiation Technology
  25. 25. ΣΔΥΝΙΚΔ΢ ΑΚΣΙΝΟΘΔΡΑΠΔΙΑ΢
  26. 26. J Urol 2001; 166: 876 ≥ Grade 2 Απώηεξε Σνμηθόηεηα από Οξζό 3D-CRT: 14% IMRT: 2% p= 0.005
  27. 27. Γαζηπενηεπική Σοξικόηηηα Σοξικόηηηα Οςποποιηηικού Grade 2 Grade 3 Grade 2 Grade 3 Κλαζζική Γόζη 8 – 23% 1 – 2% 6 – 28% 1 – 8% Ττηλή Γόζη (Μη-IMRT) 7 – 30% 1 -7% 10 – 30% 1 – 15 % Ττηλή Γόζη (IMRT) 1 – 2% 0 – 3% 9 – 23% 0 – 6% Απώηεπη Σοξικόηηηα ζηιρ IMRT μελέηερ αύξηζηρ ηηρ δόζηρ Κίνδςνορ ζοβαπήρ ηοξικόηηηαρ Υαμηλή δόζη συπίρ IMRT = Ττηλή δόζη με IMRT
  28. 28. Μέηπια Τποκλαζμαηοποίηζη 8 εβδομάδερ θεπαπείαρ είναι απαπαίηηηερ; Οι κλινικέρ μελέηερ
  29. 29. • Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer • Hypothesis: hypofractionated radiotherapy schedules for localised prostate cancer will improve the therapeutic ratio by either: a) Improving tumour control b) Reducing normal tissue side effects CHHiP Trial
  30. 30. T1B - T3A N0 M0 Estimated Risk of SV involvement ≤ 30% PSA ≤ 30ng/ml Randomise Group 1 74Gy / 37F 7.5 weeks (Standard) Group 2 60Gy / 20F 4.0 weeks (Hypofractionation) Group 3 57Gy / 19F 3.8 weeks (Hypofractionation) Trial Schema CHHiP Trial
  31. 31. T1c-2a GS <7 PSA <10 73.8 Gy/41 Fx 70 Gy/28 Fx RTOG 0415 Schema n=800 Endpoint is 5 Year BFFF Non-inferiority margin 7% (Control 85%, Exp 78%)
  32. 32. Cyberknife
  33. 33. SBRT cheaper but more toxic than IMRT for Prostate Cancer The study results were published online March 10 in theJournal of Clinical Oncology.
  34. 34. CT scan is obtained at the time of the Simulation Fiducials may be inserted before this step. CT images are then imported into the treatment planning computer
  35. 35. bladder Radiation zone prostate rectum Goal = radiation zone precisely around the prostate cancer with small margin
  36. 36. IMRT (intensity modulated radiation therapy) using 7 different beams to target the prostate The computer can determine the optimal number of beams to deliver the radiation dose to hit the target and avoid other structures
  37. 37. Prostate Seminal Vesicles Courtesy: Chester Ramsey Prostate Seminal Vesicles Alignment on markers Alignment on mid gland prostate Κίνηςη του προςτάτη
  38. 38. AP  4.15 mm SI  3.14 mm RL  1.92 mm
  39. 39. There is significant movement of the prostate gland based on daily gas in rectum Planned target Rectal gas No Rectal gas Planned target, missed badly if rectal gas pushes the prostate forward
  40. 40. Rectal balloon
  41. 41. After IMRT was established then IGRT (image guided) was introduced
  42. 42. Lower Risk of Side Effects with Image Guided IMRT compared to IMRT
  43. 43. Is there ever a need for radiation after a man has already had his prostate removed PostOp Radiation (Adjuvant Therapy) if the pathology report from the surgery raises the concern: “was the cancer completely removed?” Salvage Radiation
  44. 44. Οπιζμοί • Άκεζα κεηεγρεηξεηηθή (adjuvant) – Με αληρλεύζηκν PSA κεηεγρεηξεηηθά – Α/ζ ζε 3-12 κήλεο (αθνύ βειηησζεί ε αθξάηεηα) • Αθηηλνζεξαπεία δηάζσζεο (salvage) – Αληρλεύζηκν PSA κεηεγρεηξεηηθά – ↑ ηνπ PSA αθνύ πξώηα κεδεληζηεί
  45. 45. NCCN Advice on PostOp Radiation RP (radical prostatectomy) PLND (pelvic lymph node dissection) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
  46. 46. Adverse Features 1.Positive Surgical Margins 2.Invasion into the Seminal Vesicles 3.Extracapsular Extension 4.Detectable PSA (after surgery the PSA should fall to undetectable by a few weeks)
  47. 47. Impact of Path Reporting Positive Surgical Margins Risk Group + Margins - Margins Low risk 5.1% 0.4% Intermediate 17% 6.5% High 43% 21.5% Odds of a PSA Relapse J Urol. 2010;183(1):145.
  48. 48. PostOp Radiation…does it work? SWOG 8794 Trial path (425 men) = extraprostatic extension after surgery 10 Year PSA Cure Rate (seminal vesicle) Surgery Only 12% Surgery Plus Radiation 36% EORTC (1005 men) 5 Year Cure Rate if Positive Margins Surgery Only 49% Surgery Plus Radiation 78% German Study (Wiegel, 268 men) 5 Year Cure Rate all T3 Surgery Only 54% Surgery Plus Radiation 72%
  49. 49. Survival Benefits from PostOp Radiation for High Risk Patients RT RTRT No RT No RTNo RT
  50. 50. Άμεζα μεηεγσειπηηική ή α/θ διάζυζηρ;
  51. 51. Is it Better to Treat PostOp for High Risk Features or to Wait and Treat later if the PSA starts rising (salvage)? 8 Year Specific Survival by Group and Therapy Immediate RT Delayed Positive Margins 91% 67% Extra-capsular Spread 92% 75% Gleason 7 88% 72% Node Metastases 88% 68% Role of postoperative radiotherapy after pelvic lymphadenectomy and radical retropubic prostatectomy: a single institute experience of 415 patients Cozzarini. IJROBP 2004;59:674
  52. 52. Υπόνορ έναπξηρ ηηρ άμεζηρ α/θ ≥ 3 επειζόδια ακράηειας : ζηοσς 6 μήνες: 33%, ζηοσς 12 μήνες: 18%, ζηοσς 24-60 μήνες: 15% ΢ηα πεξηζζόηεξα θέληξα 3-12 κήλεο κεηεγρ/θά αθνύ απνθαηαζηαζεί ε εγθξάηεηα • Δελ θαίλεηαη λα επεξεάδεη ηελ λόζν • Η πνιύ πξώηκε έλαξμε → ↑ ηνπ % απώηεξεο ηνμηθόηεηαο από ην νπξνπνηεηηθό Feng et al, IJROBP, 2005
  53. 53. Salvage Radiation: if months or years after surgery the PSA blood tests starts rising again
  54. 54. Salvage Radiation…does it work? Depends… Original Pathology What was the Gleason? Where the surgical margins clear? Did the cancer involve the seminal vesicles or lymph nodes? Was there extra-capsular spread? How long ago was the surgery? How fast is the PSA rising (doubling time)? How high the did PSA get before deciding to try radiation? How high a dose of radiation will be used?
  55. 55. http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools
  56. 56. http://nomograms.mskcc.org/Prostate/SalvageRadiationTherapy.aspx
  57. 57. http://nomograms.mskcc.org/Prostate/SalvageRadiationTherapy.aspx
  58. 58. Does Salvage Radiation Improve Survival? Mayo (2657) No improvement in 10 y mortality (70% versus 69%) Hopkins (635) Improved cancer mortality at 10 years 86% versus 62% Duke (519) All cause mortality at 11 years was reduced by 47% J Urol. 2009;182(6):2708 JAMA. 2008;299(23):2760.
  59. 59. ΑΚΣΙΝΟΘΔΡΑΠΔΙΑ ΢ΣΟΝ ΠΡΩΙΜΟ ΚΑΡΚΙΝΟ ΣΟΤ ΠΡΟ΢ΣΑΣΗ • Δξυηεπική ακηινοθεπαπεία (EBRT) – ΢ύμμοπθη ηξηζδηάζηαηε αθηηλνζεξαπεία (3 Dimensional Conformal Radiotherapy – 3D CRT) – Σξηζδηάζηαηε αθηηλνζεξαπεία διαμοπθούμενηρ ένηαζηρ (Intensity Modulated Radiation Therapy – IMRT/VMAT-IGRT) – Αθηηλνζεξαπεία κε ππυηόνια (Proton Beam Radiation Therapy) – ΢ηεπεοηακηική αθηηλνζεξαπεία ηνπ πξνζηάηε (Stereotactic Radiotherapy) • Βπασςθεπαπεία – Μόληκα εκθπηεύκαηα ρακεινύ ξπζκνύ δόζεο(LDR) (seeds I-125 ή Pd-103) – Πξνζσξηλά εκθπηεύκαηα πςεινύ ξπζκνύ δόζεο (HDR) (Iridium-192 sources)
  60. 60. ΔΜΦΤΣΔΤ΢Η ΚΟΚΚΩΝ
  61. 61. ΔΝΓΔΙΞΔΙ΢ ΒΡΑΥΤΘΔΡΑΠΔΙΑ΢ ΣΟΤ ΠΡΟ΢ΣΑΣΗ (LDR) RECOMMENDED OPTIONAL INVESTIGATIONAL Do well Fair Do poorly PSA (ng/ml) <10 10-20 >20 Gleason Score 5-6 7 8-10 Stage T1c - T2a T2b - T2c T3 IPSS 0 - 8 9 - 19 >20 Prostate Volume (g) <40 40 - 60 >60 Q max mls/sec >15 15 - 10 <10 Residual Volume cc >200 TURP +/- + ESTRO/EAU/EORTC recommendations on seed implantation for localized prostate Cancer. Ash D et al. Radiother Oncol; 2000: 57, 315-321
  62. 62. HDR brachytherapy
  63. 63. 88 HDR
  64. 64. ηελεςηαίερ ζκέτειρ Εμσηεξηθή Αθηηλνζεξαπεία αζθαιήο θαη δξαζηηθή • βειηηώλεη ηελ επηβίσζε κε απνδεθηή ηνμηθόηεηα ζε πςεινύ θηλδύλνπ θαη ηνπηθά πξνρσξεκέλν Ca • αύμεζε ηεο δόζεο πξνθαιεί θαιύηεξν έιεγρν (level 1 evidence) Σερλνινγία πνπ δηαηίζεηαη ζηελ ΑΚΘ πνιύ πξνρσξεκέλε • απμάλεη ηε ζπλνιηθή δόζε • ρνξεγεί πςειή δόζε αλά ζπλεδξία • κεηώλεη ηνλ ζπλνιηθό ρξόλν ζεξαπείαο • παξαθνινπζεί ηε θίλεζε ηνπ πξνζηάηε θη εληνπίδεη αθξηβώο ην ζηόρν Είλαη ππεπζπλόηεηα ησλ γηαηξώλ λα γλσξίδνπλ πνηεο πεξηνρέο λα αθηηλνβνιήζνπλ, πώο λα ζρεδηάζνπλ ηε ζεξαπεία θαη πόηε πξέπεη λα αθηηλνβνιήζνπλ

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