Management of hepatocellular carcinoma: a case report

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Management of hepatocellular carcinoma a case
report

• Giovanni Brandi

Institute of Hematology end Medical Oncology L e
A Seràgnoli Bologna University
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The patient

• Male, 61 year-old
• Smoker
• Alcohol abuse

In 1999 first ascitic failure
Diagnosis of chronic C hepatitis
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The patient
In 2000 refractory ascitis
Right atrium
Hepatic veins
Transjugular Intrahepatic Portosystemic
Shunt (TIPSS)
TIPSS
Portal Vein
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March 2002
Abdomen ultrasound scan nodular lesion in the
VI hepatic segment.
CT scan negative
?
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June 2004
Abdomen ultrasound scan multiple hepatic
nodular formations.
CEUS HCC nodule in the VI hepatic segment.

CT scan negative
?
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August 2004
MRI HCC nodule in the VII hepatic segment.

December 2004
CT scan HCC nodule in the VIII hepatic segment
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April 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
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?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.

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15 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
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Treatment options Barcellona criteria
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Liver 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
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Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Survival by grade
Zavaglia et al. Am. J. G. 2005
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Predictors of Long-Term Survival After
LiverTransplantation for Hepatocellular
Carcinoma.
Zavaglia et al. Am. J. G. 2005
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Beyond 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
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The patient

• A first nodule of 2 cm
• A second nodule of 1 cm
• No invasion of main hepatic vessels

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Liver Transplant
February 2006
Anastomosis between celiac tripode of the graft
and accessory left hepatic artery of the receiver
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Pathologist 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

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Immunosoppression and other therapies
Immunosoppression protocol

• Norvasc
• Lansox
• Tiklid
• Bactrim forte
• Deursil
• Zyloric
• Eskim
• Torvast
• Aranesp

• Daclizumab
• (Zenapax)
• Tacrolimus

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Adverse event within the immunosoppression/tacroli
mus

• Infections
• Decrease of renal function
• CNS impairment (headache, trembling,
  depression..)
• Cytopenia
• Hirsutism
• Diabetes mellitus
• Increase incidence of lymphoma
• ..

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Follow-up

• Progressive increase of creatinine
• Emerging albuminuria

Dose reduction of Tacrolimus then switch to
Sirolimus
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Nephrologic evaluation
October 2006

• Ecodoppler no thrombosis or stenosis in the main
  renal vessels
• Renal biopsy

Nephropaty with mesangial deposition of IgA
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• Abdomen ultrasound scan

Suspect for hepatic lesion
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CT December 2006
Pet-CT January 2007
Only the largest was seen on FDG-TC-PET.
Multiple microscopic hepatic lesions. One
macroscopic nodule.
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• Colonoscopy was performed in order to exclude a
  large intestine primitive cancer

Negative
Hepatic biopsy
Recurrence of HCC
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Survival for recurrence HCC after OLT
Survival from transplant
P lt 0.0001
Roayaie et al. Liver Trasplantation 2004
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Survival 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
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Survival for recurrence HCC after OLT
Survival from time of recurrence
Presence of bone metastases (P 0.002)
Roayaie et al. Liver Trasplantation 2004
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15 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
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Treatment options Barcellona criteria
July 2008
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Phase 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)

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Eligibility 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)

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• 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

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Hepatic arteriography
Disease progression
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• November 2007 we try to restart with HAI-therapy
  but..

Arteritis (CHT-induced)
Treatment interruption
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15 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
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A 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

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• 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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