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Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers
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Rare Solid Cancers: An Introduction - Slide 12 - A. Gronchi - Models of surgery in rare cancers

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  • 1. Modelsofsurgery in rare tumors
    Alessandro Gronchi
    alessandro.gronchi@istitutotumori.mi.it
  • 2. Whathavewelearntfrom rare tumors
  • 3. 1. Howtodefinesurgicaladequacy
  • 4. LR
    Intralesional 100%
    Marginal 60-80%
    Wide 10-30%
    Radical < 5%
  • 5. “Cabeza de Vaca” - Andres Serrano
  • 6. Radicalityachievedby more limitedsurgery + RT
    Rosenberg et al. : 43 pts. (NCI) AnnSurg, 1982.
  • 7. 2. Prospectivedatabases
    6167 pts, collectedfrom 1982
  • 8. Prospective DB
    Todescribenaturalhistoryoftumors
  • 9. Adult type soft tissue sarcoma
    UPS SINOVIALSA LIPOSA LEIOMIOSA MPNST
    …….
  • 10.
  • 11.
  • 12.
  • 13. DSS
    DM
  • 14.
  • 15.
  • 16. Single nodule
    Multiple nodules
  • 17.
  • 18. Prospective DB
    Todescribenaturalhistoryoftumors
    Toaddressappropriatenessoflocaltherapies
  • 19.
  • 20.
  • 21.
  • 22. LR
    DM
  • 23. LR
    DM
  • 24.
  • 25. Riskofdeath
    3.7 for LR afteroptimalsurgery
  • 26.
  • 27.
  • 28. Prospective DB
    Todescribenaturalhistoryoftumors
    Toaddressappropriatenessoflocaltherapies
    Topredict the outcome ( nomograms)
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35. Prospective DB
    Todescribenaturalhistoryoftumors
    Toaddressappropriatenessoflocaltherapies
    Topredict the outcome ( nomograms)
    Tounderstand the impact ofnewapproaches/treatment modalities on outcome
  • 36.
  • 37. Improvedlocalcontrol, thanksto:
    Tailoredapproaches
    LargeuseofpreoperativeTx in high riskpopulation
    Improvementofreconstructivetechniques, whichallowedbettermargins at a better price
  • 38. 3. Multidisciplinarity
    Rarityofdiseases
    Anatomicalvariability
  • 39. The multidisciplinaryapproach
    Technical
    Plastic reconstructivesurgery
    Vascularsurgery
    Nerverepair
    Boneresection
    PreopTx
    CT and or RT
    ILP
  • 40. Free flaps
  • 41. Vasculargrafts
  • 42. Nervegrafts
  • 43. CT-RT can maximize downstaging
    4 courses CT (E.I.) + RT (50 Gy)
  • 44. When RT alone can be effective
    Myxoid liposarcoma
    EBRT 50 Gy
  • 45.
  • 46. 4. Surgery and metastaticdisease
  • 47.
  • 48. Cancer 1992;69:662
  • 49. AnnSurg 1999;5:602
  • 50. J Am CollSurg 2000;191:184
  • 51.
    • Numberoflesions
    • 52. Disease free interval
  • ?!
  • 53.
  • 54. 5. Howto deal withnew target therapy – the GIST model
  • 55. Strikingactivity and efficacy…
  • 56. Imatinib
    chemioterapia
    OS
    months
  • 57. but…
  • 58.
  • 59. …limitedovertime…
  • 60. 2 consequences
    In localizedsettingwe can take advantagesofitsactivity
  • 61. Preoperative Therapy for Primary Disease
    When should preoperative treatment with imatinib be considered ?
    • Inoperable disease
    • 62. Extendedprocedures (Tospareorgans/fFunction)
    • 63. Riskofintraoperativetumorrupture and/or bleeding
  • a. Inoperable Disease
    6 months after imatinib
  • 64. b. Extended Procedure (ToSpareOrgans/Function)
    12 months after imatinib
  • 65. 6 monthsafter IM
  • 66. … verylimitedsurgicalresection…
    … isitworthwile ?…
  • 67. c. RiskofIntraoperativeTumorRupture and/or Bleeding
    12 months after imatinib
  • 68. Reductionoftumorsizein neoadjuvantimatinib
    Longer treatment – smaller tumor
    Haller, Ann Surg Oncol. 2006;14:526-532
  • 69. 2 consequences
    In localizedsettingwe can take advantagesofitsactivity, but:
    Do not miss the best time point to operate
    Imatinib does not work infinitely
    The patient might get biased towards continuing medical treatment instead of operative treatment
    Neoadjuvant therapy and efficacy might otherwise have been in vain
  • 70. 2 consequences
    In localizedsettingwe can take advantagesofitsactivitytolimit the extentofsurgery
    In metastaticsetting, couldweprolongitsefficacy ?
  • 71. There are believers
  • 72. a.Tumor bulk does correlate with PFS and OS (notwithresponse)
  • 73.
  • 74. AIM of SURGERY
    Reduce the tumor burden
    Prevent secondary mutations
    Prolong time to progression
    Increase the rate of patients with durable response (cure ?)
  • 75. b. No solidtumor in metastaticphase can becuredwithout complete remission
  • 76. …and unbelievers
  • 77. Overall Survival
    2-yr 41%
    Median 19 mo
    a. Surgery in the Era BeforeImatinib
    • Gold et al. (2007), Ann Surg Oncol
    • 78. 119 pts with advanced GIST
    • 79. Diagnosed prior to use of IM
    • 80. Dematteo et al. (2001), Ann Surg
    • 81. 34 pts with GIST metastatic to the liver
    • 82. Diagnosed prior to use of IM
  • b. Front-lineSurgeryDoesNotImprove PFS in Metastatic GIST in Imatinib Era
    R2/No surgery before IM onset
    Surgical complete remission before IM onset
    54 pts
    99 pts
    Bui B et al. Do patients with initially resected metastatic GIST benefit from 'adjuvant' imatinib (IM) treatment? Results of the prospective BFR14 French Sarcoma Group randomized phase III trial. ASCO Annual Meeting 2006. Abstract 9501
  • 83. c.Response to Imatinib Correlates with Surgical Result
  • 84. d. Imatinib interruption is detrimental even after surgical complete remission
  • 85. Wesimply don’t knowtowhichextentsurgeryprolong the durationof IM activity in respondingpatients
  • 86. the ideal way togetananswer
    Imatinib
    FollowforPFS & OS
    Metastatic GIST in response on IM
    Imatinib + surgery at best response (within 1 yr)
  • 87. Allocation by pt. will
    Imatinib
    FollowforPFS & OS
    Metastatic GIST in response on IM
    Imatinib + surgery
    at best response
    Providingadequateinformedconsentisgiven and eligibilitycriteria are met
    Benjamin et al. Proc Am Soc Clin Oncol. 2003;22:814. Abstract 3271.
    Rankin et al. Proc Am Soc Clin Oncol. 2004;23:815. Abstract 9005.
    Verweij et al. Proc Am Soc Clin Oncol. 2003;22:814. Abstract 3272.
  • 88. … in isolated progression…
  • 89.
  • 90. Median time to secondary progression 6-12 months
  • 91. …it can delayswitchtoanother TKI
  • 92. Median time to secondary progression 6.3 months
  • 93. …inbrief
  • 94. Surgeryfor rare tumorshasforcedto
    Describecriteriaforsurgicaladequacy
    Set up prospective data basestounderstandnaturalhistory and underlyingbiologyotherwisestillobscureof rare diseases
    Foster collaborationbetweendifferentdisciplines in localized and metastaticsettings
    Deal withnew target therapies in solidtumors and help establishingnewparadigms
  • 95.
  • 96. … alessandro.gronchi@istitutotumori.mi.it

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