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Multidisciplinary

approach of
colorectal cancer
liver metastases
GIAMMARIA FIORENTINI, DONATELLA SARTI,
CAMILLO ALIBERTI, RICCARDO CARANDINA,
ANDREA MAMBRINI, STEFANO GUADAGNI
INTRODUCTION
– Colorectal cancer (CRC) in an increasing global health issue with 1,4
million newly diagnosed CRC each year,and mortality rate up to 10%.

– CRC patients have a > 50% probability of liver metastases


development; with CRC-LM resectability considerably improves
outcomes, resulting in 5 and 10-year survival rates of 40% and 25%
respectively.
– Neoadjuvant chemotherapy allow initially unresectable colorectal
cancer-liver metastase (CRC-LM) patients to have long term survival
similar to those of resectable patients.

– CRC-LM patients need a multidisciplinary team for treatment


decision.
PERIOPERATIVE EVALUATION
– A dedicated multidisciplinary team should assess co-morbidities and
patient’s performance status in order to decide a future treatment
plan.

– Complete blood examination should be performed before surgery,


to assess liver function, coagulation profile, bilirubin, creatinine and
carcinoembryonic antigen (CEA).
– Exclusion criteria for surgery include advanced age, male gender, low
serum albumin, presence of liver disease, ascites, kidney or
cardiologic impairment, bleeding syndromes, and chronic
obstructive pulmonary disease (COPD).

– Schroeder et al reported Morbidity and mortality rates are around


61% and 11%; after liver resection is often due to inadequate
function of remnant liver, leading to liver failure.
– Morbidity and mortality after liver resection may be improved by
measuring the intake of 99mTc mebrofenin of tumor-free liver of functional
liver needs to be highly considered for selection of surgical method..

– Most chemotherapeutic agents can result in hepatic damage and


modification of liver regeneration. Severely compromised metastase livers,
on the contrary, cannot tolerate even a minor hepatectomy
RADIOLOGICAL ASSESSMENT
CRC-LM for surgical resectability can be performed with :

1. CT Scan;
2. MRI- contrast;
3. Positron Emission Tomography (PET) scan;
4. Intraoperative Ultrasound (IOUS)
CRITERIA FOR RESECTABILITY
CRC-LM for surgical resectability by The American Hepato-Pancreato-
Biliary Association (APHBA) are:

– Presence of disease confined to the liver as identified after surgery


of primitive cancer;
– Disease in a single hepatic lobe are < 3 nodules; the largest size of
nodules < 5 cm in diameter;
– Margin Future Liver Remnant (FLR) > 1 cm
Fong et al criteria for resectability CRC-LM with worse prognosis
prediction after resection using Clinical Risk Score (CRS) with each
point score 1 are :

1. Disease Free interval from primary to metastase <12 month;


2. Largest hepatic tumor > 5 cm in diameter;
3. Node-positivity;
4. Number of lesions > 1;
5. CEA > 200 ng/mL
House et al requirements for LM resection are :
1. R0 resection achievement of intrahepatic and extra hepatic
disease;
2. Adequate Free Liver Remnant (FLR) > 2 adjacent liver segments
to be spared with blood and bile inflow and outflow
preservation

Nagashima et al recommend for LM resection importance to the


volume and function of the future liver remnant (FLR),
TIMING OF COLON AND LIVER RESECTION
1. The classic surgical method is “primary first”;

2. “synchronous resection of LM and primary CRC”;

3. “Alternative staged liver-first”


CHEMOTHERAPY FOR RESECTABLE CRC-LM
EXTRA HEPATIC DISEASE (EHD)

– Extra hepatic disease (EHD) has a poor prognosis.

– Most common sites of EHD are lymph nodes, lungs, peritoneum,


brain and bone; is currently no longer a contraindication to
metastasis resection.
EXTRA HEPATIC DISEASE (EHD)

– Adam et al reported EHD with Celiac or aorto-caval lymph node


resections are associated with a worse outcome when compared to
hepatic pedicle nodes, and mediastinal lymph nodes have a worse
median survival than intrathoracic ones; high number of lymph
nodes positive for metastases have also a poor outcome
LOCO-REGIONAL THERAPIES
RADIO FREQUENCY ABLATION (RFA)
Radio Frequency ablation (RFA) is widely used and allows the application of
extreme temperature to ablate the lesion with minimal toxicity (< 1%) in the
surrounding liver tissue.

RFA disadvantage is the recurrence rate that is higher when the tumor is > 3
cm or when treatment is delivered percutaneously.
– Microwave ablation uses high frequency microwave radiation to
induce coagulation with necrosis of lesions.
Martin et al reported this method show a 6% local recurrence rate
using microwave ablation for CRC-LM.

– External Beam RadioTherapy (EBRT) is safe with low therapeutic


window (at 60 Gy) and toxicity is effective for liver tumors in general
and in selected patient
HEPATIC ARTERY INFUSION
– Hepatic Artery Infusion (HAI) is indicated for patients with
unresectable lesions.

– The comparison of OS between HAI therapy and systemic


therapy alone (15.9 mo vs 12.4 mo) doesn’t show any difference,
however, there was a great response rate in favor of HIA (43% vs
18%)
Trans-arterial chemoembolization (TACE)
– Fiorentini et al reported TACE with irinotecan (DEBIRI) are better
in terms of OS, PFS, time to extra-hepatic progression, and
quality of life compared with systemic chemotherapy (FOLFIRI).

– Aliberti et al reported more than 80% cases using TACE


irinotecan and doxorubicin with Polyethylene Glycol (PEG)
microspheres (Lifeperals,Terumo) found 63% CR and 37% PR.
Radioembolization
– Radioembolization (RE) with Yttrium 90 (Y90) used for refractory CRC-LM to
chemotherapy.

– Cosimelli et al reported Objective tumor response rates of RE are 33%-48%


in second line and 10%-48% in third line treatment. Survival and
progression free survival are also improved after RE application as third line
treatment.
MULTIDISCPLINARY TEAM

The involvement of a multidisciplinary approach includes


– Liver surgeons;
– Medical oncologist;
– Interventional radiologists specialized in hepatobiliary disease;
– Pathologist;
– Case manager nurse
CONCLUSION
– Recent improvements of CRC-LM treatment allows the down-staging of several
patients, resulting in increased number of patients cured or living with longer
disease control.

– The neoadjuvant chemotherapy is widely accepted as up front treatment.


The use of chemotherapy may lead to disease regression for unresectable CRC-
LM, allowing resection and cure;
Surgical resection can be performed if the complete removal of cancer is
achievable leaving an adequate FRL.

– The application of loco-regional therapies is increasing, resulting in high tumor


response, however, they aren’t recommended as first-line treatment in case of
unresectable CRC-LM.
THANK YOU