L’Interventisica Locoregionale:L Interventisica Locoregionale: Quale ruolo specie nella malattia biologicamente

indolente?

Florindo Laurino Fac Medicina e Psicologia SapienzaFlorindo Laurino, Fac. Medicina e Psicologia, SapienzaAz. Osp. Sant’Andrea, Roma

Metastatic Colorectal Cancer:Metastatic Colorectal Cancer:the magnitude of the problem in Europe Colorectal Cancer: 450.000 per year (the second most frequent cancercancer

• 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) th 330 000 f RCR• more than 330.000 of mRCR new cases per year

Liver Metastases:• 85% of metastases are located in the liver

Indolent DiseaseIndolent Disease

Multidisciplinary Teamy

Oncologic Oncologic ggIRIR

RadiofrequencyRadiofrequency• Tumoral tissue heating

(60° - 100° C)( )• Cell death

(thermocoagulation necrosis)(thermocoagulation necrosis)

Molecules ionic collision

Heat productionHeat production(coagulative necrosis)

MicrowavesMicrowaves

Tumoral tissue heating• Tumoral tissue heating (65° - 150° C)C ll d th• Cell death (thermocoagulation necrosis)

No corrent flow through the patient

CryoablationCryoablation

El t tiElectroporation

HAI(Hepatic Arterial

I f i )Infusion)

• Transfemoral accessTransfemoral access

• Angiography

• GDA obstructedC th t l d i t• Catheter placed into

common hepatic artery

TACE / TAETACE / TAE

• High selective

• Less Data

SIRTSIRT(Selective Internal (Radiation Therapy)

90• Y

90

• glass spheres

resin spheres• resin spheres

Li M t tLiver MetastasesLiver 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 l li f ti ll b t l i• Normal liver: preferentially by portal vein

*Weiss L et al., J Pathol 1986, 150:195-203

New terapies have determined an increase of OSof pts with non resectable CRC LMp

Minimally Invasive Therapy

RF TACE

MWAMWA

HIFUHIFU

SIRTHAI

TAEHAI

TACETACERationale

• 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 mCRCthe systemic treatment of mCRC

• Increase of local concentration of drug has always given a benefit when compared with IV administration

Dc Beads it is possible to load chemotherapyDc Beads, it is possible to load chemotherapy into the Beads

It li Ph IIIItalian Phase III

P i bj ti i 2 OS b 40%• Primary objective: increase 2-yr OS by 40%

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

TACETACE

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

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

Single metastasis

Embolization

May 2014 prey p

September 2014 postSeptember 2014 post

PostPre

Ablation Therapy

Indications

• 3 or less liver lesions (< 3cm)• 3 or less liver lesions (< 3cm)

• Poor response to CTPoor response to CT

• Residual cancer after CT

• Pts unsuitable for resection

• Associated to resection

Ablation Therapy

Negative Prognostic Factors

• 4 or more liver lesions

f• Diameter of the lesion > 5cm

• Safety halo < 1cmSafety halo < 1cm

• High levels of CEA

Ablation Therapy

Lung MetastasesB k dBackground

Most cited primary malignancy: colorectal cncerMost cited primary malignancy: colorectal cncer

Main Actor: clinical oncologist

BackgroundBackground

• 5-years survival between • 17 studies, 1684 patients

Mortality rate less than 2 5%

y41% and 56% (median 48%)

• Mortality rate less than 2,5%• Single metastasis: better

outcome

Best Candidate: SurgeryBest Candidate: Surgery

• Prolonged disease free internal between primary and metastases

N l CEA• Normal CEA

• No nodal involvement

• Single metastases

New Trend: SurgeryNew Trend: Surgery

The beginningThe beginning

• 4 patients with 5 metastases

• Not suitable for surgery (comorbidity, refusal, etc.)

Ablation: the firstAblation: the first prospective studyprospective 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

Need for comparative trialsNeed for comparative trials

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 functionrespiratory function

More than surgeryg y

S h t t d ?So what to do?

• > 50 pts, > 24 months follow up

• 27 studies: 4 RFA, 23 surgery (no SRBT eligible)

ConclusionConclusion

• Lack of phase III trialsac o p ase a s

• Surgery: largest series and longer follow up

Trials OngoingTrials Ongoing

No comparative or randomised trials at the momentNo comparative or randomised trials at the moment

Ethical implications?Ethical implications?Long lasting recruiting time?

Population dimension?

C l iConclusionAblation Therapy Embolization

• Minimally invasiveRapid execution

• Effective in second lineand further• Rapid execution

• Low rate of complications,bidi d li

and further• First line?

morbidity and mortality• Low cost (Day Hospital)

• + systemic CTx?• Waiting for SIRT trials in

• High rate of effectiveness• First choice in lung

gprogress

• First choice in lungmetastases?

GrazieGrazie