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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

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) 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 Disease Indolent Disease

Multidisciplinary Team y

Oncologic Oncologic g IR IR

Radiofrequency Radiofrequency

• Tumoral tissue heating

(60° - 100° C) ( )

• Cell death

(thermocoagulation necrosis) (thermocoagulation necrosis) Molecules ionic collision Heat production Heat production (coagulative necrosis)

Microwaves Microwaves

Tumoral tissue heating

• Tumoral tissue heating

(65° - 150° C) C ll d th

• Cell death

(thermocoagulation necrosis) No corrent flow through the patient

Cryoablation Cryoablation

El t ti Electroporation

HAI

(Hepatic Arterial I f i ) Infusion)

• Transfemoral access

Transfemoral access

• Angiography
• GDA obstructed

C th t l d i t

• Catheter placed into

common hepatic artery

TACE / TAE TACE / TAE

• High selective
• Less Data

SIRT SIRT

(Selective Internal ( Radiation Therapy)

90

• Y

90

• glass spheres

resin spheres

• resin spheres

Li M t t Liver Metastases

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 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 OS

• f pts with non resectable CRC LM

p

Minimally Invasive Therapy

RF TACE MWA MWA HIFU HIFU SIRT HAI TAE HAI

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

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

It li Ph III Italian 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

TACE TACE

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 pre y p September 2014 post September 2014 post

Post Pre

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

Ablation Therapy

Negative Prognostic Factors

• 4 or more liver lesions

f

• Diameter of the lesion > 5cm
• Safety halo < 1cm

Safety halo < 1cm

• High levels of CEA

Ablation Therapy

Lung Metastases

B k d Background

Most cited primary malignancy: colorectal cncer Most cited primary malignancy: colorectal cncer Main Actor: clinical oncologist

Background Background

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

Mortality rate less than 2 5%

y 41% and 56% (median 48%)

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

Best Candidate: Surgery Best Candidate: Surgery

• Prolonged disease free internal between primary and metastases

N l CEA

• Normal CEA
• No nodal involvement
• Single metastases

New Trend: Surgery New Trend: Surgery

The beginning The beginning

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

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

Need for comparative trials Need 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 function respiratory function

More than surgery g 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)

Conclusion Conclusion

• Lack of phase III trials

ac o p ase a s

• Surgery: largest series and longer follow up

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?

C l i Conclusion

Ablation Therapy Embolization

• Minimally invasive

Rapid execution

• Effective in second line

and 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

g progress

• First choice in lung

metastases?

Grazie Grazie