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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

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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 Presentation Transcript

    • Modelsofsurgery in rare tumors
      Alessandro Gronchi
      alessandro.gronchi@istitutotumori.mi.it
    • Whathavewelearntfrom rare tumors
    • 1. Howtodefinesurgicaladequacy
    • LR
      Intralesional 100%
      Marginal 60-80%
      Wide 10-30%
      Radical < 5%
    • “Cabeza de Vaca” - Andres Serrano
    • Radicalityachievedby more limitedsurgery + RT
      Rosenberg et al. : 43 pts. (NCI) AnnSurg, 1982.
    • 2. Prospectivedatabases
      6167 pts, collectedfrom 1982
    • Prospective DB
      Todescribenaturalhistoryoftumors
    • Adult type soft tissue sarcoma
      UPS SINOVIALSA LIPOSA LEIOMIOSA MPNST
      …….
    • DSS
      DM
    • Single nodule
      Multiple nodules
    • Prospective DB
      Todescribenaturalhistoryoftumors
      Toaddressappropriatenessoflocaltherapies
    • LR
      DM
    • LR
      DM
    • Riskofdeath
      3.7 for LR afteroptimalsurgery
    • Prospective DB
      Todescribenaturalhistoryoftumors
      Toaddressappropriatenessoflocaltherapies
      Topredict the outcome ( nomograms)
    • Prospective DB
      Todescribenaturalhistoryoftumors
      Toaddressappropriatenessoflocaltherapies
      Topredict the outcome ( nomograms)
      Tounderstand the impact ofnewapproaches/treatment modalities on outcome
    • Improvedlocalcontrol, thanksto:
      Tailoredapproaches
      LargeuseofpreoperativeTx in high riskpopulation
      Improvementofreconstructivetechniques, whichallowedbettermargins at a better price
    • 3. Multidisciplinarity
      Rarityofdiseases
      Anatomicalvariability
    • The multidisciplinaryapproach
      Technical
      Plastic reconstructivesurgery
      Vascularsurgery
      Nerverepair
      Boneresection
      PreopTx
      CT and or RT
      ILP
    • Free flaps
    • Vasculargrafts
    • Nervegrafts
    • CT-RT can maximize downstaging
      4 courses CT (E.I.) + RT (50 Gy)
    • When RT alone can be effective
      Myxoid liposarcoma
      EBRT 50 Gy
    • 4. Surgery and metastaticdisease
    • Cancer 1992;69:662
    • AnnSurg 1999;5:602
    • J Am CollSurg 2000;191:184
      • Numberoflesions
      • Disease free interval
    • ?!
    • 5. Howto deal withnew target therapy – the GIST model
    • Strikingactivity and efficacy…
    • Imatinib
      chemioterapia
      OS
      months
    • but…
    • …limitedovertime…
    • 2 consequences
      In localizedsettingwe can take advantagesofitsactivity
    • Preoperative Therapy for Primary Disease
      When should preoperative treatment with imatinib be considered ?
      • Inoperable disease
      • Extendedprocedures (Tospareorgans/fFunction)
      • Riskofintraoperativetumorrupture and/or bleeding
    • a. Inoperable Disease
      6 months after imatinib
    • b. Extended Procedure (ToSpareOrgans/Function)
      12 months after imatinib
    • 6 monthsafter IM
    • … verylimitedsurgicalresection…
      … isitworthwile ?…
    • c. RiskofIntraoperativeTumorRupture and/or Bleeding
      12 months after imatinib
    • Reductionoftumorsizein neoadjuvantimatinib
      Longer treatment – smaller tumor
      Haller, Ann Surg Oncol. 2006;14:526-532
    • 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
    • 2 consequences
      In localizedsettingwe can take advantagesofitsactivitytolimit the extentofsurgery
      In metastaticsetting, couldweprolongitsefficacy ?
    • There are believers
    • a.Tumor bulk does correlate with PFS and OS (notwithresponse)
    • AIM of SURGERY
      Reduce the tumor burden
      Prevent secondary mutations
      Prolong time to progression
      Increase the rate of patients with durable response (cure ?)
    • b. No solidtumor in metastaticphase can becuredwithout complete remission
    • …and unbelievers
    • Overall Survival
      2-yr 41%
      Median 19 mo
      a. Surgery in the Era BeforeImatinib
      • Gold et al. (2007), Ann Surg Oncol
      • 119 pts with advanced GIST
      • Diagnosed prior to use of IM
      • Dematteo et al. (2001), Ann Surg
      • 34 pts with GIST metastatic to the liver
      • 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
    • c.Response to Imatinib Correlates with Surgical Result
    • d. Imatinib interruption is detrimental even after surgical complete remission
    • Wesimply don’t knowtowhichextentsurgeryprolong the durationof IM activity in respondingpatients
    • the ideal way togetananswer
      Imatinib
      FollowforPFS & OS
      Metastatic GIST in response on IM
      Imatinib + surgery at best response (within 1 yr)
    • 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.
    • … in isolated progression…
    • Median time to secondary progression 6-12 months
    • …it can delayswitchtoanother TKI
    • Median time to secondary progression 6.3 months
    • …inbrief
    • 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
    • … alessandro.gronchi@istitutotumori.mi.it