Title: Management of hepatocellular carcinoma: a case report
1Management of hepatocellular carcinoma a case
report
Institute of Hematology end Medical Oncology L e
A Serà gnoli Bologna University
2The patient
- Male, 61 year-old
- Smoker
- Alcohol abuse
In 1999 first ascitic failure
Diagnosis of chronic C hepatitis
3The patient
In 2000 refractory ascitis
Right atrium
Hepatic veins
Transjugular Intrahepatic Portosystemic
Shunt (TIPSS)
TIPSS
Portal Vein
4March 2002
Abdomen ultrasound scan nodular lesion in the
VI hepatic segment.
CT scan negative
?
5June 2004
Abdomen ultrasound scan multiple hepatic
nodular formations.
CEUS HCC nodule in the VI hepatic segment.
CT scan negative
?
6August 2004
MRI HCC nodule in the VII hepatic segment.
December 2004
CT scan HCC nodule in the VIII hepatic segment
7April 2005
Abdomen ultrasound scan multiple nodular
lesion, the largest in the VI hepatic segment.
May 2005
CT scan Nodular HCC between V and VI hepatic
segment, a second lesion in the II segment and a
third in the VII segment
8?FP always within the normal range
- July 2005 chemoembolization of the
- largest nodule (3,4 cm).
- CEUS complete response in
- the lesion treated 2 residual
- lesions in the remaining
- parenchyma. Multiple
rigenerative - nodules.
915 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Which is the best treatment for this patient?
Select between
Liver transplant
Surgical resection
Termoablation
Yttrium
10Treatment options Barcellona criteria
11Liver trasplant indications
Milanos criteria
- Solitary nodule with less than 5 cm of diameter
or - Less than 3 nodules with each less than 3 cm of
diameter and - No gross vascular invasion and
- No ilums nodes involvement
Mazzaferro V. et al. NEJM 1996
12Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Survival by grade
Zavaglia et al. Am. J. G. 2005
13Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Zavaglia et al. Am. J. G. 2005
14Beyond Milanos criteria ?
Mazzaferro V. et al. Lancet 2009
- From june 2006 to april 2007, 1556 patients
transplanted, 1112 exceeding Milanos criteria - Median size of largest nodule 40 mm
- Median numbers of nodule 4
- 41 of microvascular invasion()
- 5-years OS 53 vs 73 in patient meet criteria
worst prognostic factor
15The patient
- A first nodule of 2 cm
- A second nodule of 1 cm
- No invasion of main hepatic vessels
16Liver Transplant
February 2006
Anastomosis between celiac tripode of the graft
and accessory left hepatic artery of the receiver
17Pathologist exam of the explanted liver
- Solitary HCC nodule, almost necrotic (the one
treated by chemoembolization) - Multiple rigenerative nodules
- Diffuse, microscopic vascular invasion
- HCC G2-G3 by Edmodson degrees
18Immunosoppression and other therapies
Immunosoppression protocol
- Norvasc
- Lansox
- Tiklid
- Bactrim forte
- Deursil
- Zyloric
- Eskim
- Torvast
- Aranesp
- Daclizumab
- (Zenapax)
-
- Tacrolimus
19Adverse event within the immunosoppression/tacroli
mus
- Infections
- Decrease of renal function
- CNS impairment (headache, trembling,
depression..) - Cytopenia
- Hirsutism
- Diabetes mellitus
- Increase incidence of lymphoma
- ..
20Follow-up
- Progressive increase of creatinine
-
- Emerging albuminuria
Dose reduction of Tacrolimus then switch to
Sirolimus
21Nephrologic evaluation
October 2006
- Ecodoppler no thrombosis or stenosis in the main
renal vessels - Renal biopsy
Nephropaty with mesangial deposition of IgA
22Suspect for hepatic lesion
23CT December 2006
Pet-CT January 2007
Only the largest was seen on FDG-TC-PET.
Multiple microscopic hepatic lesions. One
macroscopic nodule.
24- Colonoscopy was performed in order to exclude a
large intestine primitive cancer
Negative
Hepatic biopsy
Recurrence of HCC
25Survival for recurrence HCC after OLT
Survival from transplant
P lt 0.0001
Roayaie et al. Liver Trasplantation 2004
26Survival for recurrence HCC after OLT
Survival from time of recurrence
Time from transplant to recurrence of
hepatocellular carcinoma (P 0.0015)
Roayaie et al. Liver Trasplantation 2004
27Survival for recurrence HCC after OLT
Survival from time of recurrence
Presence of bone metastases (P 0.002)
Roayaie et al. Liver Trasplantation 2004
2815 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Which is the best treatment for this patient,
now?
Select between
Chemotherapy
Surgical resection
Experimental treatment
Termoablation
29Treatment options Barcellona criteria
July 2008
30Phase I/II trial of continuous hepatic arterial
infusion (HAI) of Irinotecan in patients with
hepatocellular carcinoma (HCC).
- Efficacy of irinotecan on HCC cell lines
- Low efficacy of intravenous irinotecan in HCC (
Boige V et al 2006) - HCC nodules are supplied only by arterial flow
- Possibility to deliver a higher amount of drug
into tumoral vasculature - Higher conversion of CPT-11 in SN-38 during HAI
vs IV administration ( Van Riel JHM, 2002) - Lower systemic toxicity in HAI vs IV CHT
administration - Irinotecan is a phase specific drug prolonged
infusion increase fractional cell kill, produces
lower peak-plasma drug concentration avoiding
carboxylestease saturation and theoretically
increasing glucoronation of SN-38 with reduced
systemic toxicity (Gerrits CJ 1997)
31Eligibility criteria
- INCLUSION
- Pts with HCC on Child-Pugh A/B cirrhosis not
eligible for curative treatment according to
Barcelona consensus criteria - Absent or incomplete portal vein thrombosis or
present in only one branch - Pts untreated with systemic CHT
- or submitted to previous TAE, RF
- with at least 1 measurable active lesion
- leuko/neutro gt3000/1300
- plateletsgt 75000 Hbgt 10
- Bilir up to 3.0 Pt gt50
- EXCLUSION (main)
- HCC without cirrhosis
- Child-Pugh C
- Complete portal vein thrombosis
- Metastatic disease
- History of differents neoplasias..
- Recent AMI pregnancy.
- DLT
- One G4 haematological and/or
- Two G3 non-haematological toxicities (exepting
nausea, vomiting, alopecia) - Liver function impairment (Child C)
32- June 2007 First infusion of CPT-11 (20mg/m²).
- July 2007 second infusion
- August 2007 third infusion then
- Hospitalization for worsening of chronic kidney
failure
33 Hepatic arteriography
Disease progression
34- November 2007 we try to restart with HAI-therapy
but..
Arteritis (CHT-induced)
Treatment interruption
3515 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
OKand now?
Select between
Systemic chemotherapy
Antiangiogenic therapy
Experimental treatment
Yttrium
36A phase II trial of metronomic capecitabine in HCC
Inclusion criteria
Exclusion criteria
- Diagnosis of HCC by histology or Barcellonas
criteria - Child-pugh cirrhosis A (or B)
- Unfit for surgery or local treatment
- Life expectancy gt 3 months
- Bilirubin serum level lt 3 mg/dl
- Child-pugh cirrhosis C
- Chronic heart failure
- Chronic kidney failure
- No bone marrow impairment
- Hypersensitivity at 5-FU
37- In december 2007 the patients starts with Xeloda
1000 mg/daily (500mg500mg) without interruption - In march 2009 he completed the XIVth cicle of
therapy - This is the CT of revaluation
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39ECOGlt0