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

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

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