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LInterventisica Locoregionale: L Interventisica Locoregionale: Quale ruolo specie nella malattia biologicamente indolente? Florindo Laurino Fac Medicina e Psicologia Sapienza Florindo Laurino, Fac. Medicina e Psicologia, Sapienza Az. Osp.

  1. L’Interventisica Locoregionale: L Interventisica Locoregionale: Quale ruolo specie nella malattia biologicamente indolente? Florindo Laurino Fac Medicina e Psicologia Sapienza Florindo Laurino, Fac. Medicina e Psicologia, Sapienza Az. Osp. Sant’Andrea, Roma

  2. Metastatic Colorectal Cancer: Metastatic Colorectal Cancer: the magnitude of the problem in Europe Colorectal Cancer: 450.000 per year (the second most frequent cancer cancer • 200.000 deaths/y about • The CRC-related 5-year survival : 60% • the m-CRC -related 5-year survival: only 6% Metastases Occurence: • 75% of pts will have metastasis (25% at diagnosis,50% during the desese) • more than 330.000 of mRCR new cases per year th 330 000 f RCR Liver Metastases: • 85% of metastases are located in the liver

  3. Indolent Disease Indolent Disease

  4. Multidisciplinary Team y

  5. Oncologic Oncologic g IR IR

  6. Radiofrequency Radiofrequency • Tumoral tissue heating (60° - 100° C) ( ) • Cell death (thermocoagulation necrosis) (thermocoagulation necrosis) Molecules ionic collision Heat production Heat production (coagulative necrosis)

  7. Microwaves Microwaves • Tumoral tissue heating Tumoral tissue heating (65° - 150° C) • Cell death C ll d th (thermocoagulation necrosis) No corrent flow through the patient

  8. Cryoablation Cryoablation

  9. Electroporation ti t El

  10. HAI (Hepatic Arterial I f Infusion) i ) • Transfemoral access Transfemoral access • Angiography • GDA obstructed • Catheter placed into C th t l d i t common hepatic artery

  11. TACE / TAE TACE / TAE • High selective • Less Data

  12. SIRT SIRT (Selective Internal ( Radiation Therapy) 90 90 Y • • glass spheres • resin spheres resin spheres

  13. Li Liver Metastases M t t Liver is usually the firs site of metastases • Hematogenic spread: portal vein -> liver -> lung -> other organs (1541 CRC necropsies *) ( p ) Vascolarization: Vascolarization: CRLM: almost exclusively by hepatic artery (e.p. if > 3cm) • N Normal liver: preferentially by portal vein l li f ti ll b t l i • *Weiss L et al., J Pathol 1986, 150:195-203

  14. New terapies have determined an increase of OS of pts with non resectable CRC LM p

  15. Minimally Invasive Therapy RF TACE MWA MWA HIFU HIFU TAE SIRT HAI HAI

  16. TACE TACE Rationale • Irinotecan is a major drug for the treatment of • Irinotecan is a major drug for the treatment of metastatic colorectal cancer • Anti - angiogenetic agents have shown an efficacy in the systemic treatment of mCRC the systemic treatment of mCRC • Increase of local concentration of drug has always given a benefit when compared with IV administration

  17. Dc Beads it is possible to load chemotherapy Dc Beads, it is possible to load chemotherapy into the Beads

  18. It li Italian Phase III Ph III • Primary objective: increase 2-yr OS by 40% P i bj ti i 2 OS b 40% Fiorenitini G, et al. Anticancer Research 2012;32:1387-96

  19. Fiorenitini G, et al. Anticancer Research 2012;32:1387-96 TACE TACE

  20. DEBIRI: a high level of evidence, a need for standardization

  21. Single metastasis Embolization

  22. May 2014 pre y p September 2014 post September 2014 post

  23. Post Pre

  24. Ablation Therapy Indications • 3 or less liver lesions (< 3cm) • 3 or less liver lesions (< 3cm) • Poor response to CT Poor response to CT • Residual cancer after CT • Pts unsuitable for resection • Associated to resection

  25. Ablation Therapy Negative Prognostic Factors • 4 or more liver lesions • Diameter of the lesion > 5cm f • Safety halo < 1cm Safety halo < 1cm • High levels of CEA

  26. Ablation Therapy

  28. Lung Metastases B Background k d Most cited primary malignancy: colorectal cncer Most cited primary malignancy: colorectal cncer Main Actor: clinical oncologist

  29. Background Background • 5-years survival between y • 17 studies, 1684 patients 41% and 56% (median 48%) • Mortality rate less than 2,5% • Single metastasis: better Mortality rate less than 2 5% outcome

  30. Best Candidate: Surgery Best Candidate: Surgery • Prolonged disease free internal between primary and metastases • Normal CEA N l CEA • No nodal involvement • Single metastases

  31. New Trend: Surgery New Trend: Surgery

  32. The beginning The beginning 4 patients with 5 metastases • Not suitable for surgery (comorbidity, refusal, etc.) •

  33. Ablation: the first Ablation: the first prospective study prospective study • Multi-centric, single arm, prospective trial • 73 metastatic patients • Patient selection: unsuitable for surgery SBRT and CT • Patient selection: unsuitable for surgery, SBRT and CT • Overall survival: 66% and 64% at 2 years for CRM and other metastases respectively

  34. Need for comparative trials Need for comparative trials

  35. Ablation: Ablation: today • Overall survival rate 51% at 5-years as per the major surgical series • 24% of retreatments up to 4 times with no change in respiratory function respiratory function More than surgery g y

  36. S So what to do? h t t d ? • > 50 pts, > 24 months follow up • 27 studies: 4 RFA, 23 surgery (no SRBT eligible) Conclusion Conclusion • Lack of phase III trials ac o p ase a s • Surgery: largest series and longer follow up

  37. Trials Ongoing Trials Ongoing No comparative or randomised trials at the moment No comparative or randomised trials at the moment Ethical implications? Ethical implications? Long lasting recruiting time? Population dimension?

  38. C Conclusion l i Ablation Therapy Embolization • Effective in second line • Minimally invasive and further and further • Rapid execution Rapid execution • First line? • Low rate of complications, morbidity and mortality bidi d li • + systemic CTx? • Low cost (Day Hospital) • Waiting for SIRT trials in g progress • High rate of effectiveness • First choice in lung • First choice in lung metastases?

  39. Grazie Grazie

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