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

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 …….

Single nodule Multiple nodules

Prospective DB Todescribenaturalhistoryoftumors Toaddressappropriatenessoflocaltherapies

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

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

Disease free interval,[object Object]

5. Howto deal withnew target therapy – the GIST model

Strikingactivity and efficacy…

Imatinib chemioterapia OS months

2 consequences In localizedsettingwe can take advantagesofitsactivity

Preoperative Therapy for Primary Disease When should preoperative treatment with imatinib be considered ? ,[object Object]

Extendedprocedures (Tospareorgans/fFunction)

Riskofintraoperativetumorrupture and/or bleeding,[object Object]

b. Extended Procedure (ToSpareOrgans/Function) 12 months after imatinib

… 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 ?

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

Overall Survival 2-yr 41% Median 19 mo a. Surgery in the Era BeforeImatinib ,[object Object]

Dematteo et al. (2001), Ann Surg

34 pts with GIST metastatic to the liver

Diagnosed prior to use of IM,[object Object]

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

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

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