0
Hepatocellular Carcinoma                  Ahmed ZeeneldinAssociate Professor of Medical Oncology/Hematology               ...
Risk factors    — Hepatitis B and/or C ,    — External sources:        — alcohol , aflatoxin,    — Particular comorbiditie...
3   Ahmed Zeeneldin
4   Ahmed Zeeneldin
HCC and Cirrhosis    — Risk factors for HCC are also risk factors for liver cirrhosis.    — 60%-80% of HCC have cirrhosis ...
6   Ahmed Zeeneldin
7   Ahmed Zeeneldin
Screening for HCC    — Aim: Early asymptomatic curable    — China:       — Hepatitis B or history of chronic hepatitis    ...
Screening methods    — AFP and US    — US > AFP but operator dependednt    — Both are better                              ...
Indications for screening     — Patients at risk for HCC:         — Cirrhosis           — Hepatitis B, C           — Alcoh...
Screening11   Ahmed Zeeneldin
Clinical picture     — Symptoms     — Signs     — Paraneoplastic syndromes         — hypercholesterolemia,         — eryth...
Blood supply of the liver     — Normal:         — 1-portal vein         — 2 Hepatic artery         — 3 hepatic vein     — ...
Imaging of hepatic tumors     — Triphasic CT, MRI, US*         — 1-arterial phase (malignancy)         — 2-portal venous p...
CT normal liver     A eraly arterial, Hepatic artery opacified     B late arterial, portal vein opacified     C potal veno...
HCC CT     CT evaluation of the liver during the early arterial (2a), late arterial (2b), and portal     venous (2c) phase...
HCC US                       (a) RT hepatic lobe hypoechoic FL                       (b) Dynamic contrast enhanced US     ...
HCC MRI       (A) shows the arterial phase of the MRI, indicating an arterially       enhancing mass in the right lobe of ...
HCC MRI       (B) shows the 3-minute delayed image of the hepatic mass. The mass       appears hypointense compared with t...
HFL in US     — Size >2cm         — One imaging modality (triphasic CT, MRI, US)         — Classic = HCC         — None cl...
Needle biopsy     — Sampling error, particularly 1-2 cm.     — Negative biopsy : follow up closely21   Ahmed Zeeneldin
HCC staging     — M1: Distant metastasis     — N1: Regional lymph node metastasis     — T1: Solitary tumor without vascula...
Serum biomarkers     — AFP: not a sensitive or specific.     — Diagnosis of HCC should not be based solely on the AFP     ...
Serum biomarkers     — AFP: not a sensitive or specific.     — Diagnosis of HCC should not be based solely on the AFP     ...
workup     — HP     — Hepatic function?     — Portal ypertension?     — Is there hepatitis B/C?     — Comorbidities?     —...
Assessments     — liver function tests:         — Bilirubin         — Aspartate transaminase (AST),         — alanine tran...
Child-Pugh classification     Measure             1 point    2 points          3 points           units     Bilirubin (tot...
Child-Pugh classification     — Advantages         — Simple         — Includes clinical parameters (ascites, encephalopath...
Model for End-Stage Liver Disease (MELD)     — MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] +       9.57[Ln seru...
Pathology of HCC     — Gross         — Nodular (Cirrohsis): well           circumscribed nodules.         — Massive (nonci...
31   Ahmed Zeeneldin
Histology     Cirrhotic nodules in upper left and   Hepatocellular carcinoma     lower right areas, separated by a     fib...
33   Ahmed Zeeneldin
Prognostic Factors in HCC:     — Tumor: stage, aggressiveness and growth rate:         — AJCC TNM staging     — Patient: g...
Other systems     — Okuda system:         — based on tumor size, ascites, jaundice and serum albumin     — The French clas...
Management of HCC            =MULTIDICIPLINARY36   Ahmed Zeeneldin
HCC management     — Patient, liver, tumor     — Multidiscplinary         — hepatologists,         — pathologists         ...
Modalities     — Surgery     — Local Regional Therapy         — Bland embolization and chemoembolization         — Conform...
Surgery     — Partial Hepatectomy         — Early-stage HCC who are eligible to undergo the procedure.           — solitar...
Surgery     — Liver Transplantation         — Potentially curative for early HCC.            — 4 y OS: 85% and 4-y RFS: 92...
Surgery     — Bridge therapy         — Locoregional treatment of HCC as a bridge to liver            transplantation in el...
Local Regional Therapy     — Aim: selective tumor necrosis,     — categories: ablation or embolization.     — They are not...
Local Regional Therapy     — Ablation: inducing direct necrosis         — Chemical : ethanol (PEI), acetic acid         — ...
RFA: Needle and effect44   Ahmed Zeeneldin
PEI vs RFA     HCC <= 4cm     RCT     Complete tumor necrosis was defined as persistent hypoattenuation of the tumor     o...
PEI vs RFA     Cirrhosis, child A/B, 1-3 Tumors, 1.5-3 cm     RCT                             Brunello et al, Scand J Gast...
PEI Vs RFA     Cirrhosis, child A/B, 1-3 Tumors, <= 3 cm     RCT                                Shiina et al, Gastroentero...
Resection Vs RFA     Cirrhosis, child A/B, solitary Tumors, <= 5 cm     RCT                                             Ch...
Ablation limitations     — Dome     — Capsule     — Near major blood vessel or bile duct or abdominal organ49   Ahmed Zeen...
Embolization     — Aim: selective catheter-based infusion of particles targeted to the       arterial branch of the hepati...
A celiac angiogram showing the blood vessels of the      liver with multiple HCC tumors before (left) and after      (righ...
Bland embolization (TAE)     chemoembolization (TACE)     — Particles to block arterial flow. :         — Gelatin sponge, ...
Bland embolization (TAE)     chemoembolization (TACE)     — Complications:         — acute portal vein thrombosis,        ...
TAE Vs TACE Vs BSC     Unresectable HCC, Child A and B, Okuda I and II     RCT     HR of death for TACE vs BSC =0.47 (S)  ...
TACE Vs BSC     Unresectable HCC,     RCT     TACE q 2-3 months     HR of death for TACE vs BSC =0.49 (S)                 ...
Radioembolization     — Agents:         — Microspheres embedded with yttrium-90 (beta radiation            emitter)     — ...
Combinations of local therapies     TAE then RFA     — Aim: focused heat delivery of RFA may be enhanced by vessel       o...
TAE-> RFA Vs resection     Retrospective     1-3 lesions, size ,<= 3 cm, or single tumor ,<= 5cm     Child A, no vascular ...
TAE-> RFA/PEI Vs resection     Retrospective , single author experience     single tumor ,<= 7cm                          ...
Radiotherapy!!     — Conformal or stereotactic     — Focused, thus limiting the risk of radiation-induced liver       dama...
Systemic therapy61   Ahmed Zeeneldin
Doxorubicin: NO!     Combination: NO!     — Low RR     — No OS advantage     — Yeo et al, J Natl Cancer Inst. 2005;97:1532...
Tamoxifen!!!     — ???63   Ahmed Zeeneldin
Sorafinib (NEXAVAR)64   Ahmed Zeeneldin
Sorafinib mechanism of action                       oral multikinase inhibitor which suppresses                         tu...
SHARP trial     — Llovet et al, N Engl J Med. 2008;359:378-390.     — Patient inclusion criteria included         — Histol...
67   Ahmed Zeeneldin
68   Ahmed Zeeneldin
69   Ahmed Zeeneldin
70   Ahmed Zeeneldin
71   Ahmed Zeeneldin
72   Ahmed Zeeneldin
COST     — One box(m)$ 5000 = 5000 x 5.5 = 27,500 LE     — Duration of therapy         — Until no longer clinically benefi...
Sharp trial summary                       Sorafinib         BSC     MOS (S)           10.7 m            7.9 m     TTP (S) ...
Asia-Pacific Sorafinib trial                                     Sorafinib                        BSC                     ...
Take home message     — Risk factors for HCC     — Screen high-risk subjects by US and AFP     — Classic appearance in CT,...
Upcoming SlideShare
Loading in...5
×

Hepatocellular carcinoma

2,283

Published on

Comprehensive overview of Hepatocellular carcinoma: etiology, staging, diagnosis and treatment

0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
2,283
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
273
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide

Transcript of "Hepatocellular carcinoma"

  1. 1. Hepatocellular Carcinoma Ahmed ZeeneldinAssociate Professor of Medical Oncology/Hematology NCI, Egypt
  2. 2. Risk factors — Hepatitis B and/or C , — External sources: — alcohol , aflatoxin, — Particular comorbidities or conditions: — inherited errors of metabolism: hereditary hemochromatosis, porphyria cutanea tarda, α1-antitrypsin deficiency, and Wilson’s disease, — autoimmune hepatitis and primary biliary cirrhosis. — non-alcoholic fatty liver disease and steatohepatitis [NASH]2 Ahmed Zeeneldin
  3. 3. 3 Ahmed Zeeneldin
  4. 4. 4 Ahmed Zeeneldin
  5. 5. HCC and Cirrhosis — Risk factors for HCC are also risk factors for liver cirrhosis. — 60%-80% of HCC have cirrhosis — Cirrhosis is a prerequisite for HCC in inherited metabolic diseases and autoimmune D. — annual incidence rate of HCC in hepatitis C-related cirrhosis: 2-8%.5 Ahmed Zeeneldin
  6. 6. 6 Ahmed Zeeneldin
  7. 7. 7 Ahmed Zeeneldin
  8. 8. Screening for HCC — Aim: Early asymptomatic curable — China: — Hepatitis B or history of chronic hepatitis — Screening: AFP and US q 6m — <60% completed the screening program (5-10 times). — biannual screening reduced HCC mortality by 37% — Zhang et al, J Cancer Res Clin Oncol. 2004;130:417-422. Screening Control N 9,373 9,443 Total HCC n 86 67 Subclinical HCC n 52 (60%) 0 Small HCC 39 (45%) 0 Resection 40 (47%) 5 OS at 1,3,5y 66, 53, 46% 31,7,0% (S) Death 32 54 (S)8 Ahmed Zeeneldin
  9. 9. Screening methods — AFP and US — US > AFP but operator dependednt — Both are better HCC No-HCC test + True + False + PPV=TP/TP+FP AFP: 5% AFP: 3% US : 3% US : 7% Both: 7% Both: 3% - False – True – NPP= TN/TN+FN Sensitivity: TP/TP+FN Specificity: TN/TN+FP AFP: 70% US : 85% Both: 92%9 Ahmed Zeeneldin
  10. 10. Indications for screening — Patients at risk for HCC: — Cirrhosis — Hepatitis B, C — Alcohol — Genetic hemochromatosis — Auto immune hepatitis — Non-alcoholic steatohepatitis — Primary biliary cirrhosis — Alpha1-antitrypsin deficiency — Without cirrhosis — Hepatitis B carriers — Non-alcoholic steatohepatitis10 Ahmed Zeeneldin
  11. 11. Screening11 Ahmed Zeeneldin
  12. 12. Clinical picture — Symptoms — Signs — Paraneoplastic syndromes — hypercholesterolemia, — erythrocytosis, — hypercalcemia, and — hypoglycemia.12 Ahmed Zeeneldin
  13. 13. Blood supply of the liver — Normal: — 1-portal vein — 2 Hepatic artery — 3 hepatic vein — Malignant: — 1-Hepatic artery — 2-portal vein — 3- hepatic vein13 Ahmed Zeeneldin
  14. 14. Imaging of hepatic tumors — Triphasic CT, MRI, US* — 1-arterial phase (malignancy) — 2-portal venous phase (normal) — 3-venous phase after a delay — How classic HCC look in triphasic imaging — Arterial phase: intense arterial uptake or enhancement (White) — Delayed veous phase: washout or hypointensity (Grey)14 Ahmed Zeeneldin
  15. 15. CT normal liver A eraly arterial, Hepatic artery opacified B late arterial, portal vein opacified C potal venous phase: middle hepatic vein opacified15 Ahmed Zeeneldin
  16. 16. HCC CT CT evaluation of the liver during the early arterial (2a), late arterial (2b), and portal venous (2c) phases of enhancement. The mass in segment III (white arrow) demonstrates the classic pattern of enhancement for HCC.16 Ahmed Zeeneldin
  17. 17. HCC US (a) RT hepatic lobe hypoechoic FL (b) Dynamic contrast enhanced US with SonoVue. The early arterial phase : peripheral tumoural vessels (arrows) with enhancement filling from the periphery. (c) The arterial phase : homogeneous tumoural enhancement with a small hypoechoic area (arrow). (d) In the portal phase, the HCC (arrows) became relatively hypoechoic to the surrounding enhanced liver parenchyma.17 Ahmed Zeeneldin
  18. 18. HCC MRI (A) shows the arterial phase of the MRI, indicating an arterially enhancing mass in the right lobe of the liver near the dome (arrow), with an enhancing rim around the mass.18 Ahmed Zeeneldin
  19. 19. HCC MRI (B) shows the 3-minute delayed image of the hepatic mass. The mass appears hypointense compared with the rest of the liver (arrow), consistent with a marked decrease in arterial blood supply to the mass. This process is called “washout of contrast.”19 Ahmed Zeeneldin
  20. 20. HFL in US — Size >2cm — One imaging modality (triphasic CT, MRI, US) — Classic = HCC — None classic: Bx — Size 1-2 cm — 2 imaging modalities: — Both classic = HCC — One classic: biopsy — None classic: Bx — Size <1cm — One imaging modality q3-4 m — Stable for 18 m: imaging q 6-12 — Enlarging as before20 Ahmed Zeeneldin
  21. 21. Needle biopsy — Sampling error, particularly 1-2 cm. — Negative biopsy : follow up closely21 Ahmed Zeeneldin
  22. 22. HCC staging — M1: Distant metastasis — N1: Regional lymph node metastasis — T1: Solitary tumor without vascular invasion — T2: Solitary tumor with vascular invasion OR multiple tumors none more than 5 cm — T3: Multiple tumors more than 5 cm OR tumor involving a major branch of the portal or hepatic vein(s) — T4: direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum — F0: Fibrosis score 0-4 (none to moderate fibrosis) — F1: Fibrosis score 5-6 (severe fibrosis or cirrhosis)22 Ahmed Zeeneldin
  23. 23. Serum biomarkers — AFP: not a sensitive or specific. — Diagnosis of HCC should not be based solely on the AFP level, regardless of how high it may be. — AFP in conjunction with other tests. — Additional imaging studies (ie, CT/MRI) with a rising serum AFP level in the absence of a liver mass23 Ahmed Zeeneldin
  24. 24. Serum biomarkers — AFP: not a sensitive or specific. — Diagnosis of HCC should not be based solely on the AFP level, regardless of how high it may be. — AFP in conjunction with other tests. — Rising serum AFP level in the absence of a liver mass suggests additional imaging studies (ie, CT/MRI) — If still no masses: more frequent AFP and Imaging q 3 m — Mass > 2 cm with classic imaging , AFP > 200 ng/ml: is diagnostic of HCC24 Ahmed Zeeneldin
  25. 25. workup — HP — Hepatic function? — Portal ypertension? — Is there hepatitis B/C? — Comorbidities? — Is there metastasis? — lung, abdominal lymph nodes and the bone.25 Ahmed Zeeneldin
  26. 26. Assessments — liver function tests: — Bilirubin — Aspartate transaminase (AST), — alanine transaminase (ALT), — Alkaline phosphatase, lactate dehydrogenase (LDH), — albumin, and protein. — kidney function tests: BUN and creatinine — Others: PT/PC or INR and CBCD26 Ahmed Zeeneldin
  27. 27. Child-Pugh classification Measure 1 point 2 points 3 points units Bilirubin (total) <34 (<2) 34-50 (2-3) >50 (>3) μmol/l (mg/dl) Serum albumin >35 28-35 <28 g/l INR <1.7 1.71-2.20 > 2.20 no unit Ascites None Mild Severe no unit Grade I-II (or Hepatic Grade III-IV (or None suppressed with no unit encephalopathy refractory) medication) One year Two year Points Class survival survival 5-6 A 100% 85% 7-9 B 81% 57% 10-15 C 45% 35%27 Ahmed Zeeneldin
  28. 28. Child-Pugh classification — Advantages — Simple — Includes clinical parameters (ascites, encephalopathy) — Disadvatages — Lacks data on portal hypertension (esophagogastric varices, splenomegaly, abdominal collaterals) — Clinical data are subjective — Interpretation — Class A: compensated cirrhosis — Class B and C: decompensated cirrhosis28 Ahmed Zeeneldin
  29. 29. Model for End-Stage Liver Disease (MELD) — MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43 — Predict death within 3 months after (TIPS) surgery transjugular intrahepatic portosystemic shunt — 40 or more — 100% mortality — 30–39 — 83% mortality — 20–29 — 76% mortality — 10–19 — 27% mortality — <10 — 4% mortality — Advantage: — Includes renal function — No subjectivity — Prioritize liver transplant29 Ahmed Zeeneldin
  30. 30. Pathology of HCC — Gross — Nodular (Cirrohsis): well circumscribed nodules. — Massive (noncirrhotic): large area with or without satellite nodules — Diffuse: small indistinct tumor nodules throughout the liver.30 Ahmed Zeeneldin
  31. 31. 31 Ahmed Zeeneldin
  32. 32. Histology Cirrhotic nodules in upper left and Hepatocellular carcinoma lower right areas, separated by a fibrous band,32 Ahmed Zeeneldin
  33. 33. 33 Ahmed Zeeneldin
  34. 34. Prognostic Factors in HCC: — Tumor: stage, aggressiveness and growth rate: — AJCC TNM staging — Patient: general health — ECOG PS — Karnofsky PS — Liver: functions — Child-Pugh, MELD — Treatments34 Ahmed Zeeneldin
  35. 35. Other systems — Okuda system: — based on tumor size, ascites, jaundice and serum albumin — The French classification (GRETCH) system — Karnofsky performance , measurements of liver function and serum AFP — Cancer of the Liver Italian Program (CLIP) — Child-Pugh stage, tumor morphology, alpha-fetoprotein (AFP), and portal vein thrombosis. — Barcelona Clinic Liver Cancer (BCLC),35 Ahmed Zeeneldin
  36. 36. Management of HCC =MULTIDICIPLINARY36 Ahmed Zeeneldin
  37. 37. HCC management — Patient, liver, tumor — Multidiscplinary — hepatologists, — pathologists — cross-sectional radiologists, — Interventional radiologists, — transplant surgeons, — surgical oncologists, — medical oncologists,37 Ahmed Zeeneldin
  38. 38. Modalities — Surgery — Local Regional Therapy — Bland embolization and chemoembolization — Conformal or stereotactic radiation therapy — Systemic therapy — Best supportive care38 Ahmed Zeeneldin
  39. 39. Surgery — Partial Hepatectomy — Early-stage HCC who are eligible to undergo the procedure. — solitary tumors without major vascular invasion. — 3 or fewer tumors of 3 cm or less (debateable) — Child-Pugh A, No portal HT, adequate reserve — Low operative morbidity and mortality (5% or less). — 5 year OS: ~ 50% — 5 year recurrences: ~70% — Hepatic reserve (HR) — Future liver remnant (FLR) — HR=FLR/total liver volume-Tu — =>20 % if no cirrhosis — =>30-40 % if cirrhosis39 Ahmed Zeeneldin
  40. 40. Surgery — Liver Transplantation — Potentially curative for early HCC. — 4 y OS: 85% and 4-y RFS: 92% — Removes detectable and undetectable lesions, — treats underlying cirrhosis — Avoids complications of small FLR. — United Network for Organ Sharing (UNOS)/Milan criteria — Patient has a tumor 5 cm in diameter or 2-3 tumors 3 cm each — No macrovascular involvement — No extrahepatic disease — Child-Pugh B and C — These patients may be resected if transplantation not feasible Mazzaferro et al , N Engl J Med 1996;334(11):693-700.40 Ahmed Zeeneldin
  41. 41. Surgery — Bridge therapy — Locoregional treatment of HCC as a bridge to liver transplantation in eligible patients waiting for the procedure. — radiofrequency ablation (RFA), — Chemoembolization — radioembolization41 Ahmed Zeeneldin
  42. 42. Local Regional Therapy — Aim: selective tumor necrosis, — categories: ablation or embolization. — They are not comparable to that of liver resection or transplantation. — should not be used in place of resection or transplantation for eligible patients42 Ahmed Zeeneldin
  43. 43. Local Regional Therapy — Ablation: inducing direct necrosis — Chemical : ethanol (PEI), acetic acid — Physical: radiofrequency ablation [RFA], microwave ablation, cryoablation — laparoscopic, percutaneous or open approaches. — Indications: local disease only completely amenable to ablative therapy according to the size and location of the tumor(s). — Major complications 5%, mortality 0% — Tumor necrosis is assessed by CT/MRI at intervals an no contrast uptake43 Ahmed Zeeneldin
  44. 44. RFA: Needle and effect44 Ahmed Zeeneldin
  45. 45. PEI vs RFA HCC <= 4cm RCT Complete tumor necrosis was defined as persistent hypoattenuation of the tumor on helical CT 4 months after the most recent ablation therapy Lim et al, Gastroenterology. 2004 Dec;127(6):1714-23. Conventional PEI Higher dose PEI RFA 52 (64 tumors) 53 (56 T) 52 (61T) Complete necrosis (NS) 88% 92% 96% Sessions More More Fewer (S) 1,2,3 OS (S) 85%, 61%, 50% 88%, 63%, 55% 90%, 82%, 74% 1,2,3 DFS (S) 61%, 42%, 17% 63%, 45%, 20% 78%, 59%, 37%45 Ahmed Zeeneldin
  46. 46. PEI vs RFA Cirrhosis, child A/B, 1-3 Tumors, 1.5-3 cm RCT Brunello et al, Scand J Gastroenterol. 2008;43(6):727-35. Conventional PEI RFA 69 70 1-y CR (S) 36% 66% HR OS (NS) 1 0.8846 Ahmed Zeeneldin
  47. 47. PEI Vs RFA Cirrhosis, child A/B, 1-3 Tumors, <= 3 cm RCT Shiina et al, Gastroenterology. 2005 Jul;129(1):122-30. Conventional PEI RFA 114 118 Sessions (S) 6.4 2.1 4-y OS (S) 57% 74% Recurrence/progression (S) higher Lower47 Ahmed Zeeneldin
  48. 48. Resection Vs RFA Cirrhosis, child A/B, solitary Tumors, <= 5 cm RCT Chen et al, Ann Surg. 2006;243:321-328. Surgery resection RFA 90 71 (19 withdrew consent) complications () More and severer 1,2,3,4-y OS (NS) 93.3%, 82.3%, 73.4%, 95.8%, 82.1%, 71.4%, 64.0% 67.9% 1,2,3,4-y DFS(NS) 85.9%, 69.3%, 64.1%, 86.6%, 76.8%, 69%, 46.4% 51.6%48 Ahmed Zeeneldin
  49. 49. Ablation limitations — Dome — Capsule — Near major blood vessel or bile duct or abdominal organ49 Ahmed Zeeneldin
  50. 50. Embolization — Aim: selective catheter-based infusion of particles targeted to the arterial branch of the hepatic artery feeding the tumor leading to ischemia. T:HA, NL: PV — Types: — bland embolization, — chemoembolization — radioembolization) — Caution: — arterial anatomy outlined — embolization is limited to a segment, subsegment, or lobe — Indications: — All HCC tumors are embolizable if the arterial supply is isolated. — Used in unresectable/inoperable tumors not amenable to ablation (>5cm), alone or followed by ablation50 Ahmed Zeeneldin
  51. 51. A celiac angiogram showing the blood vessels of the liver with multiple HCC tumors before (left) and after (right) treatment showing loss of vascularity and response to therapy.51 Ahmed Zeeneldin
  52. 52. Bland embolization (TAE) chemoembolization (TACE) — Particles to block arterial flow. : — Gelatin sponge, — polyvinyl alcohol, and — polyacrylamide microspheres — Chemotherapeutic agents: — Doxorubicin and/or Cisplatin — Containdications to TACE: — Child C — Portal v thrombosis — Bilirubin > 3 mg/ml: liver abscess — Biliary enteric bypass: liver abscess52 Ahmed Zeeneldin
  53. 53. Bland embolization (TAE) chemoembolization (TACE) — Complications: — acute portal vein thrombosis, — cholecystitis, and — bone marrow suppression, — post-embolization syndrome — fever, — abdominal pain, — and intestinal ileus — Mortality: <5 %53 Ahmed Zeeneldin
  54. 54. TAE Vs TACE Vs BSC Unresectable HCC, Child A and B, Okuda I and II RCT HR of death for TACE vs BSC =0.47 (S) Terminated early TAE Vs TACE ?? Llovet et al, Lancet. 2002;359:1734-1739. BSC TAE TACE 35 37 40 1,2-y OS (S) 63% and 27% 75% and 50% 82% and 63%*S RR 34% PortalV inasion Less54 Ahmed Zeeneldin
  55. 55. TACE Vs BSC Unresectable HCC, RCT TACE q 2-3 months HR of death for TACE vs BSC =0.49 (S) Lo et al, Hepatology. 2002;35:1164-1171. BSC TACE (Cisplatin) 40 40 1,2, 3-y OS (S) 32, 11, 3% 57, 31, 26% Death from liver failure more55 Ahmed Zeeneldin
  56. 56. Radioembolization — Agents: — Microspheres embedded with yttrium-90 (beta radiation emitter) — tumor necrosis is more likely to be induced by radiation rather than ischemia. — PRR: 42% — Complications: — cholecystitis and — abscess formation.56 Ahmed Zeeneldin
  57. 57. Combinations of local therapies TAE then RFA — Aim: focused heat delivery of RFA may be enhanced by vessel occlusion by TAE — Use 3-5 cm tumors who are not eligible for liver resection or transplantation57 Ahmed Zeeneldin
  58. 58. TAE-> RFA Vs resection Retrospective 1-3 lesions, size ,<= 3 cm, or single tumor ,<= 5cm Child A, no vascular invasion, no mets, Yamakado et al, Radiology. 2008;247:260-266 TAE/RFA Resection 104 62 1,2, 5-y OS (NS) 98%, 94%, 75% 97%, 93%, 81% 1,2, 5-y DFS (NS) 92%, 64%, 27% 89%, 69%, 26%58 Ahmed Zeeneldin
  59. 59. TAE-> RFA/PEI Vs resection Retrospective , single author experience single tumor ,<= 7cm Yamakado et al, Radiology. 2008;247:260-266 TAE/RFA/PEI Resection 33 40 1,2, 5-y OS (NS) 97%, 77%, 56% 81%, 70%, 58%59 Ahmed Zeeneldin
  60. 60. Radiotherapy!! — Conformal or stereotactic — Focused, thus limiting the risk of radiation-induced liver damage — unresectable/inoperable due to performance status or comorbidity e.g. if PEI, RFA, TACE, TAE is not feasible60 Ahmed Zeeneldin
  61. 61. Systemic therapy61 Ahmed Zeeneldin
  62. 62. Doxorubicin: NO! Combination: NO! — Low RR — No OS advantage — Yeo et al, J Natl Cancer Inst. 2005;97:1532-1538. — Unresectable HCC doxo Cisp-INF-Doxo-FU PIAF MOS (NS) 6.8 m 8.7m RR 10% 20% Toxicity higher62 Ahmed Zeeneldin
  63. 63. Tamoxifen!!! — ???63 Ahmed Zeeneldin
  64. 64. Sorafinib (NEXAVAR)64 Ahmed Zeeneldin
  65. 65. Sorafinib mechanism of action oral multikinase inhibitor which suppresses tumor cell proliferation and angiogenesis,65 Ahmed Zeeneldin
  66. 66. SHARP trial — Llovet et al, N Engl J Med. 2008;359:378-390. — Patient inclusion criteria included — Histologically proven HCC — Advanced HCC — (ECOG PS) 0-2 — ≥1 measurable untreated lesions — Child-Pugh class A (mild hepatic impairment) — No prior systemic treatment66 Ahmed Zeeneldin
  67. 67. 67 Ahmed Zeeneldin
  68. 68. 68 Ahmed Zeeneldin
  69. 69. 69 Ahmed Zeeneldin
  70. 70. 70 Ahmed Zeeneldin
  71. 71. 71 Ahmed Zeeneldin
  72. 72. 72 Ahmed Zeeneldin
  73. 73. COST — One box(m)$ 5000 = 5000 x 5.5 = 27,500 LE — Duration of therapy — Until no longer clinically benefiting from therapy or until unacceptable toxicity occurs — For OS of 10.7 m: — 10.7 x 27, 500= 294, 250 — For PFS of 5.5 m — 5.5 x 27, 500= 151, 25073 Ahmed Zeeneldin
  74. 74. Sharp trial summary Sorafinib BSC MOS (S) 10.7 m 7.9 m TTP (S) 5.5 m 2.8 m Toxicity Hand-foot diarrhea Cost 150-294, 000 LE Child A >90% * PS 0-1 >90%*74 Ahmed Zeeneldin
  75. 75. Asia-Pacific Sorafinib trial Sorafinib BSC 150 76 MOS (S) 6.2 m 4.1 m MTTP (S) 2.8m 1.4 m Child A >97% * PS 0-1 >90%* Cheng et al., J Clin Oncol 26: 2008 (May 20 suppl; abstr 4509)75 Ahmed Zeeneldin
  76. 76. Take home message — Risk factors for HCC — Screen high-risk subjects by US and AFP — Classic appearance in CT, MRI, tri-US: arterial uptake and venous washout — Liver function assessment and reserve — Patient, liver, tumor — Surgery: resection and transplant — Local regional therapy: ablation, emobolization — Systemic therapy = sorafinib76 Ahmed Zeeneldin
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×