Anal ca vakalis

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  1. 1. ANAL Ca
    VOLOS GREECE2010
    VAKALIS XENOFON
    401 General MilitaryHospital ofAthens
  2. 2.

    4%
    (5300 2009, 700 )
    1980

    (1.4/100.000 , 1.7/100.000 )
    HIV- ~37/100,000
    60-65
  3. 3.
    ( < 2cm )
    ,(, )
    HPV
    ( 90% 60% )( - Human papilloma virus (HPV-16, 18 & 31) )

    ( 10-30 , HIV-positive 50
    str82/100.000gay male 35/100.000 gay male HIV+ 60/100.000)

    , high grade VIN (vulvar intraepithelial neoplasia)
  4. 4.







  5. 5.
  6. 6.


    Anal intraepithelial neoplas (AIN)
    74%



    19%
    4%
    3%
    50% , 30-40% 10-20%
  7. 7. Anal intraepithelial neoplas (AIN)
  8. 8.



    ( )
    .
    CT MRI .
    PET ?
  9. 9. PET
  10. 10. TNM
    T
    T0
    Tis
    T1 2 cm 5 cm
    T4
    N
    N0
    N1
    N2
    N3
    M
    M0
    M1 .
    (Hansen and Roach, 2007)
  11. 11. AJCC
    0
    Tis, N0, M0
    I
    T1, N0, M0
    II
    T2, N0, M0
    T3, N0, M0
    IIIA
    T1, N1, M0
    T2, N1, M0
    T3, N1, M0
    T4, N0, M0
    IIIB
    T4, N1, M0
    T, N2, M0
    T, N3, M0
    IV
    T,
    ON, M1
  12. 12.
    -,
    -
  13. 13. -
  14. 14.
    26% 50%
    • 15.
  15. &
  16. 16.
  17. 17. -
    Transition Zone
    Glandular Tissue
    Squamous Cells
  18. 18. (anal verge,anal margin)
  19. 19. (anal verge,anal margin)
  20. 20. (anal verge,anal margin)
  21. 21. (anal verge,anal margin)
  22. 22.
    • 1950
    • 23. 1970
    • 24. 1990 -
    • 25. 2000 .
    • 26. 2010 -


    • 40-60%
    • 27. 5- 30-70%
    • 28. -



  23. 29.
    > 70%, (6,000 cGy)
  24. 30. ( > 60 Gy) (1984-96)
    .
    5-

    *
  25. 31.
    20 Gy
    • Iridium: 15 -20 Gy
    • 32. T < 5 cm
    10 Gy
  26. 33. NCCN Guidelines
  27. 34.
    > 70% ,

    . 45 Gy 60 Gy
  28. 35. Ca


    Adjuvant
    -
  29. 36.



  30. 37.
  31. 38.
  32. 39. -
  33. 40.
  34. 41.
    ACT 1585 CRT vs. RT
    EORTC110 CRT vs. RT
    RTOG/ECOG 291Role of MMC
    RTOG 98-11 644Role of NACT/cisplat
    ACCORD-03 307Role of NACTcisplat/RT dose
    ACT 2940Role of cisplat vs. MMC
    + maintenance cisplat
    EORTC 85Role of 5FU vs. CDDP
    22011-40014not extended to phase III
  35. 42. EORTC 1987-1994
    110 pts randomised RT vschemoRT
    45Gy/25#
    mitomycin C 15 mg/m2 d 1 5FU 750 mg/m2 d 1-5
    UKCCCR 1987-1991 ACT1
    577 patients randomised
    45Gy/20-25# gap 6/52 boost 15Gy in 6# or 25Gy in 2-3 days by implant
    mitomycin C 12 mg/m2 d 1 5FU 1000 mg/m2 d 1-4 and #21-25
    -
    1: Lancet 348: 1049-1054, 1996
    2: Bartelink et al, JCO, 15:2040-2049, 1997
  36. 43. -vs
    More recent data from the UKCCCR with 12 years median FU confirm that the difference is maintained
    Beyond 5 years only 11 patients have relapsed with locoregional disease
    (UKCCCR, 1996; Bartelink et al., 1997)
  37. 44. EORTC Colostomy-freeSurvival
    JCO,1997
    years
    32% improvement in Colostomy-free survival at 5 years
  38. 45. -
    EINAI




    JCO, Vol 15, No 5, 1997
  39. 46. UKCCCR ACT 1 .
    • 40% (265/577)
    • 47. , 58% salvage
    • 48. 42%
    • 49. 50% 5
    .
    , , ,
  40. 50.
    ACT 1585 CRT vs. RT
    EORTC110 CRT vs. RT
    RTOG/ECOG 291Role of MMC
    RTOG 98-11 644Role of NACT/cisplat
    ACCORD-03 307Role of NACTcisplat/RT dose
    ACT 2940Role of cisplat vs. MMC
    + maintenance cisplat
    EORTC 85Role of 5FU vs. CDDP
    22011-40014not extended to phase III
  41. 51. mitomycin c ?



    (HUS)

  42. 52.
  43. 53. RTOG 8704 /ECOG 1289 trial( mitomycinfluoruracil)
    RT and 5-FURT and 5-FU and MMC
    Positive biopsy14%8%
    5 year LR36%17%
    5 year DFS50%67%
    5 year 22%11%
    colostomy rate
    5 year OS65%67%
    acute gr 4 toxicity7%22%
    Flam 1996
  44. 54. mitomycin c ?


    cisplatin?
  45. 55. cisplatin
    Intergroup Anal Cancer ph III trial RTOG 98-11
  46. 56. cisplatin
    RTOG 98-11: Disease-free survival
  47. 57. cisplatin
    RTOG 98 11: Overall survival and treatment failure
  48. 58.
  49. 59. cisplatin
    Mitomycin C


    5-FU / MITOMYCIN C +

  50. 60. ACT II
    ? Cisplatin better than MMC
    ? Maintenance therapy beneficial
    OXI
  51. 61. Cisplatin Maintenance therapy
  52. 62. ACT II
    ? Cisplatin better than MMC
    ? Maintenance therapy beneficial
    OXI
    OXI
  53. 63.
    ACT 1585 CRT vs. RT
    EORTC110 CRT vs. RT
    RTOG/ECOG 291Role of MMC
    RTOG 98-11 644Role of NACT/cisplat
    ACCORD-03 307Role of NACTcisplat/RT dose
    ACT 2940Role of cisplat vs. MMC
    + maintenance cisplat
    EORTC 85Role of 5FU vs. CDDP
    22011-40014not extended to phase III
  54. 64. Neoadjuvant chemotherapy
    RTOG 98-11{ 65% DFS 5 }
    682 patients randomised between
    cycles of 5-FU (1000 mg/m2x4 + mitomycin-C 10 mg/m2 d 1,29, 57, 85chemoRTstarting day 57
    OR
    cycles of 5-FU (1000 mg/m2x4+ cisplatin 75 mg/m2 d1,29,57,85chemoRTstarting day 57
    End point of study DFS and secondary end point OS, colostomy free survival at 2 years and local recurrence
    5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28
  55. 65.
    Neoadjuvant
  56. 66. ()
    T4N3
  57. 67. Neo-adjuvant* / palliative chemotherapy
    MMC
    5FU (capecitabine)
    Cisplatin
    * And then surgery or chemoradiotherapy
  58. 68. Capecitabine (Xeloda)
    Replacing 5FU in the ACT-II schedule with oral capecitabine, n=31
    RT 50.4 Gy/28#/ 38 days in two phases
    Capecitabine in RT treatment days 825 mg/m2 b.d
    Full compliance with chemo 68%
    Full compliance with RT 81%
    No treatment-related deaths
    4 w following CRT 77% clinical CR and 16% PR
    3 loco-regional relapses in first 14 m
    Glynne-Jones et al 2008 IJROBP; 72:119-126
  59. 69. Capecitabine (Xeloda)
    EXTRA Phase II trial
    Phase II multicentre trial
    Same RT dose and technique as in ACTII
    Mitomycin C 12mg/m2day 1, capecitabine825mg/m2 b.d on radiotherapy days (5 days per week)
    End points CR at 4 weeks, 6 month local control and toxicity
  60. 70. Cetuximab (Erbitux)
  61. 71. ERBITUX, XELODA, ELOXATIN
  62. 72.
    endpoint : colostomy-free survival (CFS) at 3 years
    CFS was: A= 83%, B= 85%, C= 86%, D= 80%
    with no significant difference of ICT nor HDRT
  63. 73.
  64. 74. RT+5Fu/Mitomycin
  65. 75.
  66. 76.
  67. 77.
  68. 78. Multicenter experience with IMRT for anal cancer
    53 patients treated at three academic medical centers with IMRT andchemotherapy for definitive treatment of anal cancer.
    Toxicity
    58% completed treatment without interruption
    Improved GI toxicity rates and severity
    Grade 3 in 15% with no Grade 4
    RTOG 98-11: 34% of patients had Grade 3 - 4
    Dermatologic, Grade 3 in 38%
    Similar to studies with 2-wk treatment breaks
    Better than the 48% in RTOG 98-11
    Hematologic toxicities were severe and common
    Grade 3 and 4 in 58% of patients as worst
    Similar to RTOG 98-11 rates of 60%
    (Salama et al., 2007)
  69. 79. Multicenter experience with IMRT for anal cancer
    53 patients treated at three academic medical centers with IMRT andchemotherapy for definitive treatment of anal cancer.
    Response
    Complete response in 92%
    Local recurrence rate 13% @ 18 months
    18-month colostomy free survival 83.7%
    18-month distant recurrence free survival 92.3%
    (Salama et al., 2007)
  70. 80. IMRT in anal cancer
    New application gaining support
    Early studies show reduced toxicity rates with comparable local control and survival statistics.
    Area of active study
    Radiation Therapy Oncology Group is currently enrolling for a phase II trial (RTOG 0529).
  71. 81. IMRT trial anal Ca
  72. 82.
  73. 83.
  74. 84.
  75. 85.
  76. 86.
  77. 87.
    -
    • ACT II ,Constantinouset al, 1997: 5 40 (86% vs 60%, p=0.14).
    • 88. Neoadjuvant ( ) &
    ;
    (gaps split therapy)
  78. 89. ?
  79. 90.

    Margin uT3
    -

    N+
    -
    -
    +
    +
    +

    +
    FOLLOW UP
    -

  80. 91. 75 N3
  81. 92. BOOST
    • 93.
    • 94.
  82. Anal margin cancer