Egyptian HCC Guidelines Overview Presented By Mohamed A. Ezzel Arab MD Head of the HCC & Intervention UnitNational Hepatology & Tropical Medicine Research Institute Treasurer of the Egyptian Society of Liver Cancer (ESLC)
INTRODUCTIONESLC invited most of experts with differentspecialties in HCC management all over the country, to discuss the newguidelines taking into consideration basically the international guidelines(level I evidence based), and in parallel considering as well the localfactors in Egypt, in addition to their own experience(level III, expert opinion) in those points which could not be applicablein Egypt, provided that it is based on reliable international publications.Confirmation and collecting these points were done using livevoting system.The final draft had been completely endorsed by the ESLC to be appliedfor the Egyptian HCC patients.
HCC EGYPTIAN GUIDELINES 2011 Primary Prevention• Prevention of chronic HBV and HCV infection by: - Safe injection practices. - Screening of donated blood for the presence of hepatitis viruses. Secondary Prevention - Passive immunization with hyperimmune –globulin has a role in preventing HBV after acute exposure. - Antiviral therapeutic agents. - Tertiery Prevention HBV is a valuable step in the prevention of Immunization against 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.
HCC EGYPTIAN GUIDELINES 2011 Screening Early detection of cases with hepatic nodule or elevated AFP Diagnosis Accurate diagnosis of HCC Staging Treatment decision making, and determining prognosis Treatment Selection of appropriate therapy
HCC EGYPTIAN GUIDELINES 2011 Screening Screening should be preformed to all high risk groups: All cirrhotic patients: Non-cirrhotic patients: HBV HBV infection (carrier) HCV (Metavir score 3 or 4) NASH Alcoholic HaemochromatosisScreening for HCC should be done for all high risk patients with AFP and abdominal U/S with time interval every 4 months
HCC EGYPTIAN GUIDELINES 2011 Diagnosis Diagnosis should be made as follow: 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.(NB: Radiological criteria of HCC is in the form of earlyenhancement during arterial phase followed by rapidwashout of contrast in delayed phase)
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 Senario (2) 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.
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 2011The recommended Workup for HCC patient attime 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 teslawhenever 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 HCCIt should include the proper assessment of different views covering; the patient clinical state, liver state, tumor size,number, site, vascular invasion and extrahepatic disease. Patient 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; ECOG PST BCLC4 GRETCH5 Okuda6 Child- Pugh CUPI7 TNM CLIP8 JIS9 Liver Tumor
BCLC Staging System HCC Early Stage Intermediate Stage Advanced Stage End Stage Surgical Treatment TACE Sorafenib Local Ablation (30%) (50%-60%) (10%) Potentially Curative Randomized Trials BSC Treatments 5-y Median Survival If Untreated: 6-16 mo Survival <3 mo Survival: 40%-70%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 thefollowing 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 2011In bridging or downstaging of HCC either by surgicalresection or locoregional therapy, liver transplantationcould 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 2011Local recurrence of HCC after liver transplantation may betreated with surgery if it is resectableor with loco-regional therapy if it is unresectable.While Sorafenib is the only available systemic therapyindicated in distant recurrent HCC.
HCC EGYPTIAN GUIDELINES 2011Locoregional 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 norready for liver transplantation, are candidates forRadiofrequency (RFA) or Microwave ablation.HCC ≤ 4 cm close to a great vessel, without vascularinvasion or extrahepatic spread in Child-Pugh A or Bpatients neither candidate for surgery nor ready for livertransplantation, are candidates for Microwave ablation.
HCC EGYPTIAN GUIDELINES 2011RFA and Microwave ablation are contraindicated in lesionslocated in close contact with main bile ducts or intestinalloops. So, the best clue for these patients with Child PughClass A or B, neither fit for resection nor transplantation, isPercutanous Ethanol Injection (PEI) in lesions < 3 cm orcombined Transarterial Chemoembolization (TACE) + PEIfor lesions 3 – 6 cm.Also intra operative RFA could be an alternative for patientwho is fit for surgery with single HCC ≤ 4cm close tointestinal loops.
HCC EGYPTIAN GUIDELINES 2011HCC measuring 4 – < 6 cm, away from main bileducts or intestinal loops without vascular invasion orextra-hepatic spread in Child A or B patient neithercandidate for surgery nor ready for transplantation, arecandidates for combined therapy of Heat ablation(with RFA or Microwave ablation) + TACE.HCC measuring ≥ 6 cm or multifocal lesions, withoutvascular invasion or extra-hepatic spread in Child A andearly B and not candidate for surgical management, couldbe treated with TACE.Addition of Sorafenib is optional, to act against the risingserum level of VEGF which occur especially during thefirst week after embolization.
HCC EGYPTIAN GUIDELINES 2011Ablation therapy could be performed as a potentiallycurative modality for up to 3 lesions, however, caseswith more than 3 lesions are not an absolutecontraindication for ablation and should be discussedon a case by case basis.
HCC EGYPTIAN GUIDELINES 2011Single or multifocal HCC with portal vein invasionin Child Pugh Class A or early B patient are candidates forSorafenib.Furthermore, in respect to the rising promising datacoming to support the use of Selective InternalRadiotherapy (SIRT) with Y-90 in advanced HCC especiallyin case of portal vein thrombosis.Radioembolization with Y-90 could be recommended as asecond line of treatment for those patients in the followingsituations: - Progressive disease inspite of full dose Sorafenib. - Patient who can’t tolerate the adverse events of Sorafenib.
HCC EGYPTIAN GUIDELINES 2011Systemic treatment:Sorafenib is the standard systemic therapy indicated fortreatment 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 haveChild A liver cirrhosis or early B (score≤7), goodperformance 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 ortwo hours after meals.
HCC EGYPTIAN GUIDELINES 2011Systemic treatment:Clinical follow up of patients on Sorafenib should be performedtwice monthly after beginning of treatment then monthly on aregular basis. While assessment of radiological response withmodified 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 ofbone metastasis together with SorafenibFinally, ESLC is aware of the plethora of targeted therapiesthat are in progress in phase II and III clinical trials.Therefore in case of Sorafenib failure in patients who are stillmaintaining child score A and good performance status, theycould be included into clinical trials.
HCC EGYPTIAN GUIDELINES 2011Best Supportive Care:It is the only line of treatment indicated for end stage HCCwhich is defined by; poor performance score or child C livercirrhosis 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 Performancestatus 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 onemonth after initial treatment, then every 3 months during the firstyear after therapy. Then every 6 months if the patient does notdevelop recurrence or disease progression ,meanwhile he shouldenter in the screening program by abdominal U/S and serum AFP / 4months ,aiming early detection of new HCC.