Abdominal imaging treatment of inoperable hcc p kwok

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Abdominal imaging treatment of inoperable hcc p kwok

  1. 1. Traitement  du  CHC  inopérable  :     le  scenario  de  Hong  Kong       Treatment  of  Inoperable  Hepatocellular  Carcinoma:   the  Hong  Kong  Scenario       Philip  CH  KWOK   Queen  Elizabeth  Hospital     Hong  Kong  SAR,  CHINA  
  2. 2. HCC  in  Hong  Kong   •  Worldwide  750000  new  cases  HCC  diagnosed   in  2008   •  High  prevalence  in  HK  :  chronic  hepa;;s  B   infec;on   •  Worldwide:  6th  most  prevalent  cancer,  3rd   cause  of  cancer  death   •  3rd  leading  cause  of  cancer  death  in  HK   –  4th  commonest  cancer  in  men   –  7th  commonest  cancer  in  women  
  3. 3. Cura;ve  treatment  for  HCC   •  HK  has  high  standard  and  advanced  skill  of   surgical  resec;on   •  Play  a  leading  role  in  HCC  research   •  Include:   –  Surgical  resec;on   –  Transplanta;on   –  Local  abla;on  with  various  means  
  4. 4. Treatment  for  Inoperable  HCC   •  HCC  is  a  combina;on  of  2  diseases  :  cancer  +   liver  cirrhosis  (mostly)   •  Successful  cura;ve  treatment   1.  remove  the  tumor  +  some  surrounding   noncancerous  ;ssue   2.  +  Enough  and  func;oning  residual  liver  ;ssue  to   sustain  life  
  5. 5. Treatment  for  Inoperable  HCC   •  Inoperability  due  to:   –  Too  much  tumor  ;ssue,  either  in  one  lobes,    or  in   both  lobes,  or  outside  the  liver   –  Inadequate  func;oning  liver  ;ssue  leT  behind   aTer  tumor  resec;on/  abla;on  
  6. 6. Tools  for  inoperable  HCC   •  •  •  •  Transarterial  chemoemboliza;on  (TACE)   Transarterial  radioemboliza;on  (TARE  or  RE)   External  radiotherapy   Target  therapy  (Sorafenib)  
  7. 7. Tools  for  Unresectable  HCC   •  Unresectable  ≠   Inoperable   •  Tools  for  unresectable   tumors:   –  Radiofrequency  abla;on   (RFA)   –  Microwave  abla;on   (MWA)   –  Percutaneous  alcohol   injec;on  (PEI)   –  Cryoabla;on  
  8. 8. More  Aggressive  way:     RFA,  ar;ficial  ascites  
  9. 9. More  Aggressive  way:     RFA,  transpleural  with  ar;ficial  pneumothorax  
  10. 10. More  Aggressive  way:     RFA,  transpleural  with  ar;ficial  pneumothorax  
  11. 11. More  Aggressive  way:     RFA,  blood  flow  control,  percutaneous  or  open   Pringle  manoeuvre  
  12. 12. Percutaneous  Alcohol  Injec;on  (PEI)   PEI:  S'll  has  a  role  for  tumors  near  cri'cal  loca'ons  or  vital  structures  ,     where  thermal  abla'on  is  dangerous  or  ineffec've  
  13. 13. Do  we  have  a  Guideline  to  follow?   •  Currently  no  local  consensus,  we  will  have  one   very  soon   •  Commonly  quoted  :   –  Barcelona  Clinic  Liver  Cancer  (BCLC)  staging   system  and  management   –  Asian  Pacific  Associa;on  for  the  Study  of  the  Liver   (APASL)  
  14. 14. BCLC  staging  
  15. 15. BCLC  staging   •  There  are  more  treatment  modali;es   available  than  men;oned  in  the  “guideline”     •  Not  up-­‐to-­‐date  
  16. 16. APASL  Guidelines  for  HCC   Management  
  17. 17. APASL  guideline   •  More  closely  reflect  the  local  prac;ce  
  18. 18. China  An;-­‐cancer  Society  
  19. 19. China  An;-­‐cancer  Society   •  In  2009  
  20. 20. J-­‐HCC  Guidelines  
  21. 21. J-­‐HCC  Guidelines   •  Different  prac;ce  in  Japan  
  22. 22. Hong  Kong  Guideline  on  Treatment  of   HCC   •  Consensus  Mee;ng  in  2013   •  Will  come  out  soon   •  A  group  of  local  specialists  led  by  Prof  Ronnie   TP  POON   –  Surgeons   –  Oncologists   –  Interven;onal  Radiologists   –  Hepatologists  
  23. 23. Treatment  aim   •  For  inoperable  HCC,  the  treatment  aim  is   mainly  pallia;ve  
  24. 24. HCC  Treatment   •  Pallia;ve   –  Transarterial  chemoemboliza;on  (TACE)   •  lipiodol  +  chemotherapeu;c  agent(s)   •  Drug  elu;ng  beads   –  Transarterial  radioemboliza;on  (TARE)   •  Ymrium-­‐90    
  25. 25. Conven;onal  TACE   •  The  commonest  treatment  for  inoperable  HCC  in  Hong   Kong   •  About  500  TACE    per  year  in  a  single  ins;tute   •  The  standard  treatment  in  most  centers  for  inoperable   HCC   •  Emulsion  of  lipiodol  +  single/  mul;ple   chemotherapeu;c  agents   •  Oily  emulsion  can  reach  500  um   •  Effect  proven  by  mul;ple  studies  and  2  RCT  (Llovet,  Lo)  
  26. 26. Conven;onal  TACE   •  TACE  given  once  every  2  months  or  3  months   •  Usually  through  the  hepa;c  artery   •  Also  possible  through  other  extrahepa;c   arteries   •  Assess  the  response  aTer  every  TACE  
  27. 27. TACE   Defect  of  lipiodol  reten.on  
  28. 28. TACE,  inferior  phrenic  artery  
  29. 29. TACE  
  30. 30. Conven;onal  TACE   •  Stop  TACE   –   when  the  tumor(s)  do  not  respond,  either  there  is   inadequate  uptake,  or  the  tumor(s)  enlarge   –  When  the  liver  func;on  gets  worse  aTer  TACE   –  When  the  supplying  artery  is  occluded   –  When  there  are  other  complica;ons  of  TACE,  e.g.   biliary  necrosis  
  31. 31. TACE  –  induced  biliary  Injury     •  ATer  6  sessions  of  TACE  
  32. 32. Conven;onal  TACE   •  TACE  can  be  cura;ve,  though  it  is  oTen   considered  a  pallia;ve  treatment   •  So,  stop  TACE  also  when   –  THE  DISEASE  IS  CURED!   •  This  is  oTen  the  situa;on  when   –   TACE  is  performed  superselec;vely   –  TACE  is  performed  for  a  small  lesion  inapproachable   by  other  local  abla;ve  treatment  e.g.  RFA  for  a  lesion   near  another  organ  (gall  bladder)  
  33. 33. Conven;onal  TACE   •  Variants:   –  Superselec;ve  TACE  with  microcatheter   •  Overflow  of  emulsion  to  portal  venules   –  (Balloon  occluded  TACE  )   •  Not  yet  available  locally  
  34. 34. Superselec;ve  TACE  with  overflow  to   portal  venules   •  Matsui  O.   •  Superselec;ve  TACE  with  microcatheter   •  Lipiodol  flows  to  the  portal  venules  through   peribiliary  plexus   •  Enhances  treatment  effect  
  35. 35. Superselec;ve  TACE  with  overflow  to   portal  venules   •  The  3-­‐year   local   recurrence   rate  for   grade  0,  1,  2:   74%,  42%,  19%  
  36. 36. Balloon-­‐occluded  TACE  
  37. 37. B-­‐TACE   •  3Fr  microballoon   catheter   •  Reduce  the  arterial   stump  pressure   •  Increase  lipiodol   emulsion   accumula;on  inside   the  tumor  
  38. 38. Conven;onal  TACE   •  Side  effects  are  common   •  Related  to  early  systemic  release  of  chemo   agents   –  Nausea,  vomi;ng,  alopecia,  renal  impairment,   marrow  suppression,  etc.   •  Liver  parenchymal  damage   –  Liver  func;on  impairment,  liver  failure,  liver   abscess,  biliary  duct  injury  and  biloma  
  39. 39. Drug  elu;ng  beads-­‐TACE/DEB-­‐ TACE   •  Replace  lipiodol  with   microspheres   (100-­‐300um)   •  Slow  release  of  drugs   •  Enhances  local   therapeu;c  efficacy   •  Less  systemic  side   effects  
  40. 40. DEB-­‐TACE   –  Two  randomized  controlled  trials  showed  bemer   control  of  disease  progression  but   –  no  sta;s;cal  significant  in  survival  rate  due  to   short  follow-­‐up  period  and  small  sample  size    
  41. 41. DEB-­‐TACE   –  PRECISION  V  study  recruited  217  pa;ent  showed  that   DEB  had  a  disease  control  rate  of  63.4%  and   conven;onal  TACE  had  a  disease  control  rate  of  51.9%   (P=0.11).     –  Pa;ent  with  Child-­‐Pugh  B,  ECOG  1,  bilobar  disease,   and  recurrent  disease  showed  a  significant  increase  in   objec;ve  response  (P=0.038)  compared  to  cTACE.     –  DC  Bead  was  associated  with  improved  tolerability,   with  a  significant  reduc;on  in  serious  liver  toxicity   (P=0.001)  and  a  significant  lower  rate  of  doxorubicin-­‐ related  side  effects  (P=0.0001).  
  42. 42. DEB  5-­‐yr  survival   Malagari  K,    et  al.  (CVIR  2012)   173  pa;ents,  Child  A,  B   Mean  lesion  diameter  7.6  +/-­‐  2.1cm   Mean  overall  survival  was  43.8  months  (range   1.2–64.8)   •  Overall  survival  at  1,  2,  3,  4,  and  5  years  was   93.6,  83.8,  62,  41.04,  and  22.5  %,   •  •  •  • 
  43. 43. Malagari  K,  et  al  CVIR  2012  
  44. 44. DEB-­‐TACE   •  Used  more  frequently  in  private  hospitals  than   public  hospitals  due  to  the  high  costs  
  45. 45. TARE   •  Transarterial   Radioemboliza;on   •  Ymrium-­‐90  is  beta   emitng   •  On  resin  or  glass  beads   (20-­‐60um)   •  2mm  range   bachytherapy   •  Half  life  64  hours   •  Usually  perform  once  
  46. 46. TARE   •  Can  be  performed  in  3  public  hospitals  and  2   private  hospitals  in  Hong  Kong   –  Exper;se  required   –  Great  demand  on  several  special;es  working   together  as  a  team   –  Currently  Hospital  Authority  only  approved  and   reimbursed  its  use  in  HCC  >  8cm  diameter,  or   there  is  portal  vein  invasion  
  47. 47. TARE   •  In  Western  countries,  TARE  is  used  mainly  for   liver  dominant  colorectal  metastases   •  Not  in  HK  public  hospitals  
  48. 48. TARE   •  large-­‐scale  phase  II  studies  show,  when   compared  with  cTACE,   –   less  side  effects,  bemer  tolerance,     –  bemer  response  rate  and  longer  ;me  to  disease   progression   •  No  definite  survival  benefit  when  compared   with  cTACE   •  Maybe  related  to  its  use  in  moderate  to   advanced  disease  
  49. 49. TARE   •  Benefit  in  HCC   with  portal   vein  invasion   •  Kulik  LM,  et  al.   (Hepatology   2008)   •  PR:  42.2%   (WHO);  70%   (EASL)  
  50. 50. TARE   Salem  and  Lewandowski.  Clin  Gastroenterol  and  Hepatol  2013  
  51. 51. TACE  +  RFA   •  In  HB  cirrhosis,  there  may  be  lots  of  nodules   •  HCC  focus  seen  in  CT  or  MR,  but  not  seen   under  ultrasound   •  Perform  TACE  once,  then  RFA  under  CT   guidance  
  52. 52. TACE  +  RFA S7  lesion  seen  in  MR Selec;ve  TACE  to  RHA  once
  53. 53. TACE  +  RFA CT  guided  RFA  with  mul;planar  recon CT  post  RFA  1  month
  54. 54. LR  therapies  +  others   •  cTACE  +  RFA  has  bemer  response  rate,  bemer   1-­‐year  and  3-­‐year  survival  than  either   monotherapy   •  Metaanalysis  of  6  papers   –  Ni  JY  et  al.  (J  Cancer  Res  Clin  Oncol  2013)  
  55. 55. cTACE  +  RFA   •  TACE  plus  PRFA  had   significantly  bemer   effec;veness  on  1-­‐  and  3-­‐year   overall  survival  rate   –  odds  ra;o  [OR]  1-­‐year  =  4.61,   95  %  confidence  interval  [95  %   CI]  2.26–9.42,  P  <  0.0001   –  OR  3-­‐year  =  2.79,  95  %  CI  1.69– 4.61,  P  <  0.0001   •  and  3-­‐year  recurrence-­‐free   survival  rate   –  [OR]  3-­‐year  =  3.00,  [95  %  CI]   1.75–5.13,  P  <  0.0001   •  1-­‐year  recurrence-­‐free  survival   rate:  no  significant  difference  
  56. 56. Locoregional  therapies  +  Sorafenib   •  cTACE  or  DEB-­‐TACE  +  Sorafenib  (kinases   inhibitor)   –  Inves;ga;onal   –  Timing  and  dose  of  Sorafenib  needed  to  be   determined  with  clinical  studies  
  57. 57. Image  guided  Radiotherapy  for  HCC   •  Previously  overlooked  because  of  fatal  liver   toxicity  at  doses  lower  than  therapeu;c  doses   •  Recently,  precise  delivery  of  focused  high-­‐ dose  on  targeted  volume  of  the  liver   –  3D  conformal  RT   –  Intensity  modulated  RT  (IMRT)   –  Stereotac;c  body  RT  (SBRT)   –  Image  guided  RT  (IGRT)   –  Proton  therapy  
  58. 58. IGRT  and  BCLC  stages   •  Stage  A:  nonsurgical   cura;ve  therapy.   •  Stage  B:  can  be   combined  with  other   treatments  such  as   TACE.     •  Stage  C:  prolong  the   survival  ;me  in   selected  pa;ents  with   locally  advanced  HCC   associated  with  portal   vein  invasion  but  not   distant  metastasis.   •  Stage  D:  pallia;on.   Lee  IJ  et  al.  Gut  Liver  2012  
  59. 59. Thanks

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