hcc egyptian guidelines overview prof ezz elarab
TRANSCRIPT
Egyptian HCC Guidelines
Overview Presented By
Mohamed A. Ezzel Arab MD
Head of the HCC & Intervention Unit
National Hepatology & Tropical Medicine Research Institute
Treasurer of the Egyptian Society of Liver Cancer
(ESLC)
Confirmation and collecting these points were done using live voting system.
The final draft had been completely endorsed by the ESLC to be applied for the Egyptian HCC patients.
ESLC invited most of experts with different specialties in HCC management all over the country, to discuss the new guidelines taking into consideration basically the international guidelines (level I evidence based), and in parallel considering as well the local factors in Egypt, in addition to their own experience
)level III, expert opinion (in those points which could not be applicable in Egypt, provided that it is based on reliable international publications.
INTRODUCTION
HCC EGYPTIAN GUIDELINES 2011
Primary Prevention
Secondary Prevention
Tertiery Prevention
• Prevention of chronic HBV and HCV infection by:
- Safe injection practices.- Screening of donated blood for the presence of hepatitis viruses.
- Passive immunization with hyperimmune –globulin has a role in preventing HBV after acute exposure.
- Antiviral therapeutic agents. - Immunization against HBV is a valuable step in the prevention of
hepatocellular carcinoma.
- Avoid Aflatoxin B1 exposure. - Prevention of dietary iron overload by westernization of the cooking
habits and tools.
HCC EGYPTIAN GUIDELINES 2011
Secondary Prevention
• Venesection for cases with high iron overload.
Tertiery Prevention
• Prevention of progression of the cirrhosis to HCC is done by treating the hepatitis B and C virus infections .
• Preventing HCC caused by alcoholic cirrhosis by avoiding alcohol
• Prevention of Non alcoholic steato-hepatitis.
Screening
Diagnosis
Staging
Treatment
Treatment decision making, and determining prognosis
Accurate diagnosis of HCC
Selection of appropriate therapy
Early detection of cases with hepatic nodule or elevated AFP
HCC EGYPTIAN GUIDELINES 2011
HCC EGYPTIAN GUIDELINES 2011
Non-cirrhotic patients: HBV infection (carrier)
All cirrhotic patients: HBV HCV (Metavir score 3 or 4) NASH Alcoholic Haemochromatosis
Screening for HCC should be done for all high risk patients with AFP and abdominal U/S with time interval every 4 months
Screening should be preformed to all high risk groups:
Screening
High risk patient with HFL and either serum AFP is ≥ 200 ng/ml,
or triphasic CT-scan abdomen shows typical criteria for HCC then, it has to be diagnosed as HCC.
Diagnosis should be made as follow:
(NB: Radiological criteria of HCC is in the form of early enhancement during arterial phase followed by rapid washout of contrast in delayed phase)
Diagnosis
HCC EGYPTIAN GUIDELINES 2011
HCC EGYPTIAN GUIDELINES 2011
Diagnosis
Senario (1)
High risk patient with HFL < 1cm, AFP < 200 ng/ml, then follow up every 2 months by abdominal U/S and serum
AFP is recommended. If the lesion increases in size then, reassess with triphasic CT-scan abdomen
High risk patient with HFL ≥ 1cm, AFP has normal level or < 200 ng/ml and triphasic CT-scan abdomen shows
atypical criteria for HCC then, a dynamic contrast MRI (with magnet strength≥ 1.5 tesla) is recommended. If MRI
is not available or its result is not satisfactory then targeted liver biopsy is recommended.
Senario (2)
HCC EGYPTIAN GUIDELINES 2011
Diagnosis
Senario (3)
High risk patient with serum AFP ≥ 200 ng/ml and no HFL could be detected neither by abdominal U/S nor
trisphasic CT-scan abdomen then, a dynamic MRI study (≥ 1.5 tesla) is recommended.
HCC EGYPTIAN GUIDELINES 2011
The recommended Workup for HCC patient at time of diagnosis is:
- Full History (concerning the risk factor, occupation, exposure to toxins, chemical …etc).
- Physical Examination.- CBC.- Bleeding profile (PT, INR and PTT).- Liver function tests and LDH.- Kidney function tests.- AFP.- Etiologies of liver cirrhosis: (HBsAg, HBcAb, HCV-Ab).- ECG.
Triphasic spiral CT-scan abdomen or MRI ≥1.5 tesla whenever indicated
HCC EGYPTIAN GUIDELINES 2011
Indications for HCC metastatic workup are:• Clinical suspicion.• Prior to transplant.
Screening for HCC metastasis is performed with:• Chest/Pelvis CT with contrast.• Bone scan on clinical suspicion or in symptomatic patients.
Staging of HCC
It should include the proper assessment of different views covering; the patient clinical state, liver state, tumor size,
number, site, vascular invasion and extrahepatic disease.
Tumor
1. Llovet JM. J Gastroenterol. 2005;40:225-235; 2. Marrero JA, et al. Clin Liver Dis. 2006;10:339-351; 3. Bruix J, et al. J Hepatol. 2001;35:421-430;
Patient
Liver
ECOGPST
TNMChild-Pugh
BCLC4
Okuda6
CLIP8
JIS9
CUPI7
GRETCH5
BCLC Staging System
End StageAdvanced StageIntermediate StageEarly Stage
Surgical TreatmentLocal Ablation
SorafenibTACE
HCC
(30%)Potentially Curative
Treatments 5-y Survival: 40%-70%
(50%-60%)Randomized Trials
Median Survival If Untreated: 6-16 mo
(10%)BSC
Survival <3 mo
TACE = transarterial chemoembolization; BSC = best supportive care.Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.
HCC EGYPTIAN GUIDELINES 2011
Surgical Resection:Patient who is fit for surgical resection should fulfill the following conditions:
• Child Pugh score < 6 (Child A).• Good performance status.• Site is anatomically accessible(cases with subcapsular HCC
are good candidates for surgical resection while deep lesions should be assessed first for the possibility of ablative
therapies).• Serum bilirubin < 1.5 mg/dl.• Localized HCC.• No vascular invasion.• Absence of extrahepatic spread (EHS).• Absence of portal hypertension.
HCC EGYPTIAN GUIDELINES 2011
N.B: Criteria predicting portal hypertension are:• Platelets count < 100,000 /mm3.• Splenomegaly.• Upper GIT endoscopy showing either esophageal varices or
signs of portal hypertensive gastropathy.• Hepatic Venous Wedge Pressure (HVWP > 10 mmHg).
Large HCC lesion is not a contraindication for liver resection provided an adequate residual volume of the cirrhotic liver after proper metastatic workup.
N.B: operative theatres for liver surgery should be fully equipped with all facilities and equipments required especially operative ultrasound machine and capability of operative ablative therapy.
HCC EGYPTIAN GUIDELINES 2011
HCC EGYPTIAN GUIDELINES 2011
Liver transplantation will be beneficial forrecurrent HCC within Milan criteria after liver resection with the following criteria:
• No micro-vascular invasion.• Well differentiated HCC.• Acceptable AFP < 1000 ng/ml.
HCC EGYPTIAN GUIDELINES 2011
HCC EGYPTIAN GUIDELINES 2011
In bridging or downstaging of HCC either by surgical resection or locoregional therapy, liver transplantation could be done if:
serum AFP is < 1000 ng/ml.Adequate radiological response (Partial and complete responders) according to modified RECIST criteria after locoregional therapy.Absence of disease progression during time period of 3 months.
HCC EGYPTIAN GUIDELINES 2011
Local recurrence of HCC after liver transplantation may be treated with surgery if it is resectable or with loco-regional therapy if it is unresectable.
While Sorafenib is the only available systemic therapy indicated in distant recurrent HCC.
HCC EGYPTIAN GUIDELINES 2011
Locoregional Therapy:HCC ≤ 4 cm, away from main bile ducts or intestinal loops, without vascular invasion or extrahepatic spread in Child-Pugh A or B patients neither candidate for surgery nor ready for liver transplantation, are candidates for Radiofrequency (RFA) or Microwave ablation.
HCC ≤ 4 cm close to a great vessel, without vascular invasion or extrahepatic spread in Child-Pugh A or B patients neither candidate for surgery nor ready for liver transplantation, are candidates for Microwave ablation.
HCC EGYPTIAN GUIDELINES 2011
RFA and Microwave ablation are contraindicated in lesions located in close contact with main bile ducts or intestinal loops. So, the best clue for these patients with Child Pugh Class A or B, neither fit for resection nor transplantation, is Percutanous Ethanol Injection (PEI) in lesions < 3 cm or combined Transarterial Chemoembolization (TACE) + PEI for lesions 3 – 6 cm.
Also intra operative RFA could be an alternative for patient who is fit for surgery with single HCC ≤ 4cm close to intestinal loops.
HCC EGYPTIAN GUIDELINES 2011
HCC measuring 4 – < 6 cm, away from main bile ducts or intestinal loops without vascular invasion or extra-hepatic spread in Child A or B patient neither candidate for surgery nor ready for transplantation, are candidates for combined therapy of Heat ablation (with RFA or Microwave ablation) + TACE.
HCC measuring ≥ 6 cm or multifocal lesions, without vascular invasion or extra-hepatic spread in Child A and early B and not candidate for surgical management, could be treated with TACE.
Addition of Sorafenib is optional, to act against the rising serum level of VEGF which occur especially during the first week after embolization.
HCC EGYPTIAN GUIDELINES 2011
Ablation therapy could be performed as a potentially curative modality for up to 3 lesions, however, cases with more than 3 lesions are not an absolute contraindication for ablation and should be discussed on a case by case basis.
HCC EGYPTIAN GUIDELINES 2011
Single or multifocal HCC with portal vein invasion in Child Pugh Class A or early B patient are candidates for Sorafenib.
Furthermore, in respect to the rising promising data coming to support the use of Selective Internal Radiotherapy (SIRT) with Y-90 in advanced HCC especially in case of portal vein thrombosis.
Radioembolization with Y-90 could be recommended as a second line of treatment for those patients in the following situations:
- Progressive disease inspite of full dose Sorafenib.- Patient who can’t tolerate the adverse events of
Sorafenib.
HCC EGYPTIAN GUIDELINES 2011
Systemic treatment:Sorafenib is the standard systemic therapy indicated for treatment of HCC in the following conditions:
• Extrahepatic spread (such as lymph node, lung or suprarenal metastasis).
• Vascular invasion (such as malignant portal vein or hepatic vein invasion).
• In patients with post-transarterial chemoembolization (TACE) progressive disease.
HCC patient who is candidate for Sorafenib should have Child A liver cirrhosis or early B (score≤7), good performance status, and serum bilirubin ≤ 2 mg/dl.
The standard daily oral dose of Sorafenib is 800 mg/day (divided into two doses per day) one hour before meals or two hours after meals.
HCC EGYPTIAN GUIDELINES 2011
Systemic treatment:Clinical follow up of patients on Sorafenib should be performed twice monthly after beginning of treatment then monthly on a regular basis. While assessment of radiological response with modified RECIST criteria is accepted with triphasic spiral CT-scan or MRI (≥ 1.5 tesla) every three months.
Addition of external beam radiotherapy is amenable in case of bone metastasis together with Sorafenib
Finally, ESLC is aware of the plethora of targeted therapies that are in progress in phase II and III clinical trials. Therefore in case of Sorafenib failure in patients who are still maintaining child score A and good performance status, they could be included into clinical trials.
HCC EGYPTIAN GUIDELINES 2011
Best Supportive Care: It is the only line of treatment indicated for end stage HCC which is defined by; poor performance score or child C liver cirrhosis who are not eligible for transplantation.
Best supportive care should cover the following states:• Treatment of portal hypertension.• Nutritional management.• Pain management.• Psychological management.• Control of ascites.
HCC EGYPTIAN GUIDELINES 2011Post-therapeutic monitoring for HCC patients:•Clinical:Reassessment of the patient’s general condition and his Performance status is mandatory.•Serological:
• AFP (if elevated at baseline).• CBC.• LFTs (especially S. bilirubin).• KFTs (especially S. uric acid).• PT and INR
•Radiological:It is recommended to perform tri-phasic CT-scan abdomen one month after initial treatment, then every 3 months during the first year after therapy. Then every 6 months if the patient does not develop recurrence or disease progression ,meanwhile he should enter in the screening program by abdominal U/S and serum AFP / 4 months ,aiming early detection of new HCC.
Close to intestinal loops
Laparoscopic RFA
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