HCC EMBOLIZATION

  • View
    305

  • Download
    0

Embed Size (px)

Text of HCC EMBOLIZATION

  • Embolization of HCC:Cocktails, Beads, Hot, or Bland-Does it make any difference?vs.

    Moretti Italian Glass beads , Ruby Flowers, by Amy Bland

  • DisclosuresGuerbet LLC, BTG consultant, researchMERIT Medical medical monitor, HiQUALITY trialSirtex speaker, proctorCambridge University Press - royalties

  • Monday...

  • www.io-central.org

  • Lipiodol HistoryDiscovered in 1901 by Guerbet and LafayUsed as a vector of Iodine for tuberculosis, syphilis, rheumatoid arthritis, and goiterIn 1926 Lipiodol becomes the first iodinated contrast medium used in radiology

  • Lipiodol History1951, development of Lipiodol UltraFluid (ethyl esters of Lipiodol)1957, used in endemic goiter (IM injection) and for lymphography1986, oral Lipiodol for goiter

  • Lipiodol in the Liver

    Portal Vein Idezuki Y, Sugiura M, Hatano S, Kimoto S. Hepatography for detection of small tumor masses in the liver; experiences with oily contrast medium. Surgery 1966;60:572Intraoperative injection of Lipiodol into SMV tributary in 37 patients, followed by xrays +/- tomography on Day 0, 3, 7, and 14. Hepatograms were succcessfully used in the diagnosis of space-occupying lesions in the liver.Hepatic ArteryLaval-Jeantet M, Tristant H, Guerbet M, et al. Une nouvelle mthode d'hpatographie lipiodole par voie intra-artrielle. J Radiol Electrol 1972; 53:29-34.Twelve clinical cases let appear the value of the method in the detection of intra-hepatic tumoral masses.

  • Lipiodol in the LiverFirst use of Lipiodol for chemoembolizationIn 1981, Prof. Konno who used for the first time lipiodol, said that if we injected Lipiodol directly into the hepatic artery of patients with hepatocellular carcinoma, it binds selectively to the tumor and accumulates for prolonged periods up to several months.Bonnemai B, Guerbet M. Histoire du Lipiodol (1901-1994) ou Comment un mdicament peut voluer avec son temps. In: Revue d'histoire de la pharmacie, 83e anne, N. 305, 1995. pp. 159-170.

    1983 - First publications of diagnostic and therapeutic Lipiodol via the hepatic artery for HCC.

  • In-vivo videomicroscopy studies have demonstrated that the hepatic arterial blood feeding tumors actually passes through numerous presinusoidal shunts into the terminal portal vessels and sinusoids before entering the tumor, particularly through the peribiliary capillary plexus. This has important implications for chemoembolization.

  • Particulate embolics occlude arteries 200 microns or larger, proximal to the level of the pre-sinusoidal shunts, allowing portal blood flow to continue to the tumor and daughter nodules. Oily agents occlude the pre-sinusoidal shunts, but may wash out with time. Oil followed by particulate embolics causes the greatest and most durable tumor ischemia.

  • Tumor Necrosis: Oil +/- ParticleRate of complete tumor necrosis on explant:Takayasu K, RAD 1987;163:345-51

    Main TumorDaughter NodulesDox/Lipiodol/Gelfoam83%53%Dox/Lipiodol13%6%Lipiodol only0%0%

  • Survival: Particle +/- Oil

    Nakamura H, RAD 1989;170:783-86

    SurvivalDox/Gelfoam/LipiodolDox/GelfoamN = 100N = 1041 year54%45%2 year33%16%3 year18%4%

  • Hydrophilic vs. Lipophilic Drugs

    Most chemotherapeutic drugs used for adenocarcinomas are lipophobic, and remain in the aqueous phase of the emulsion, which can wash out while the oil stays behind. Lipophilic drugs will be taken up by the oily micelles and remain in the tumor.

  • Water-in-Oil EmulsionSpecific gravity of contrast adjusted to match Lipiodol Ultra-Fluide 8.5ml Conray 43 + 1.5ml sterile waterMix at oil:chemo ratio of 1-2:1

  • Lipiodol as a Drug Carrier

    OilW/OO/W

  • Copyright 2011 by the American Roentgen Ray SocietyTakayasu, K. et al. Am. J. Roentgenol. 2000;175:699-704Lipiodol is - Tumor selective- A drug carrier- An imaging biomarker for response... + Dox in resected HCC @ 1-2 mo

    who needs ADC maps or mRECIST?

  • ...and Survival!El Khaddari S, Gastroenterol Clin Biol. 2002;26:728-34.

    Figure 4. Courbe de survie selon la fixation lipiodole.Survival curve according to lipiodol tumor uptake.

    validated imaging response marker correlating to survival.>50% oil uptake improves med survival from 10 to 30 months.

  • Oil Retention vs. Survival

    Kim, AP&T 2012;35:1343

  • Lipiodol Chemoembolization of HCC: Randomized TrialsLo et al., Hepatology 2002

    80 Patients, 80% hep. B +, 7 cm tumors (60% multifocal)

    2) Llovet et al., Lancet 2002 112 Patients, 80% hep. C +, 5 cm tumors (70% multifocal)

    Survival1 year2 years3 yearsTACE57%31%26%BSC32%11%3%

    Survival1 year2 yearsTACE82%63%BSC63%27%

  • What about bland?

    1515Llovet, Lancet 2002

    1-year2-year3-yearHRControl63%27%17%Chembo82%63%29%0.47 [0.25-0.91] p=0.02Bland75%50%29%0.57 [0.31-1.04] p=0.07

  • Bland vs ChemoembolizationHCC all-comers US population

    16N=3221 yr 66%2 yr 46%3 yr 33%N = 2061 yr64%2 yr39%3 yr 28%Microspheres (MSKCC)Maluccio, JVIR 2008;19:862CAM/Lip/PVA (U Penn)Weiss, WCIO 2008

  • GIDEON 2nd Interim AnalysisGeschwind et al, ASCO GI 2012 J Clin Oncol 30, 2012 (suppl 4; abstr 317)

  • DEB Chemoembolization of HCC:Randomized Trials - Precision V

    99Lammer, CVIR 2010p = 0.116-month Imaging Response

  • DEB Chemoembolization of HCC:Randomized Trials - DEB vs. BlandMajor hepatic complications: DEB 17% vs. bland 2%Relative risk of biloma/infarct DEB vs. oil 9.8:1Malagari, CVIR 2010;33:541-51; Guiu, J Hepatol 2012;56:609

    BlandN = 41DEBN = 436 mo100%100%9 mo95%97.5%12 mo86%85%

  • MRI of Iron-labeled DEBs 300-500 micronSource: Journal of Vascular and Interventional Radiology 2008; 19:1490-1496 (DOI:10.1016/j.jvir.2008.06.008 )Copyright 2008 SIR Terms and Conditions

    Axial T2*-weighted MR image of the liver after embolization with 300500-m IOEs. Less intense and partially distributed signal void at the rim of the tumor (arrowhead) is seen without signal void inside the tumor. Note the intense signal void with blooming artifact (white arrow) caused by the clustered IOEs within the left hepatic artery located at a significant distance from the tumor bed.

  • MRI of Iron-labeled DEBs 100-300 micronSource: Journal of Vascular and Interventional Radiology 2008; 19:1490-1496 (DOI:10.1016/j.jvir.2008.06.008 )Copyright 2008 SIR Terms and Conditions

    Axial T2*-weighted MR image (field of view, 16 16; matrix size, 256 160; repetition/echo time, 200/15 msec; flip angle, 45) of the liver after embolization with 100300-m IOEs. Note the multiple punctate signal voids inside the tumor (arrowheads) and circumferentially distributed at the rim of the tumor (white arrows), showing the ability of MR imaging to track the distribution of IOEs in tumor bed.

    Source: Journal of Vascular and Interventional Radiology 2010; 21:259-267 (DOI:10.1016/j.jvir.2009.10.026 )Copyright 2010 SIR Terms and ConditionsFluorescence Imaging of Doxorubicin Eluting Bead

    Doxorubicin quantitative mapping in the tissue around DEBs. Left: unstained tissue section of a vessel occluded by four doxorubicin DEBs (100300 m, day 28). Right: fluorescence microspectroscopy image of free doxorubicin around the same vessel. Scale bar: 50 m.

  • 2626

  • DEB Adverse Events:Hepatobiliary necrosis due to dox in normal tissueNon-target injuries due to lack of image guidance*Malagari CVIR 2011;34:774 ** Brown JVIR 2012;23:287

    N = 267DEB*SIR QI**Guidelinesgrade 4-5 hepatobiliary injury5.5%4%cholecystitis5.5%

  • Retrospective Cohort Analysis:Y-90 vs. CE of HCC

    Overall Survival, p=0.78AFP & Imaging response equivalentNo difference in morbidityMedian TTP:

    Y-90 13.3 mo vs. CE 8.4 mo p=0.046Salem, Gastro 2011;140:497

  • Is anything better than cTACE?

    18DEBY90sorafenib

  • Hepatic Embolotherapy:Cocktails, Beads, Hot, or Bland-Does it make any difference?Probably notCaveats:Cardiac, hematologic, renal insufficiency- blandExtrahepatic collaterals - blandLimiting PES a priority (frail, caretaker) - Y-90Whipple/ biliary stent - Y-90

  • Moretti Italian Glass beads , Ruby Flowers, by Amy BlandIn-vivo videomicroscopy studies have demonstrated that the hepatic arterial blood feeding tumors actually passes through numerous presinusoidal shunts into the terminal portal vessels and sinusoids before entering the tumor, particularly through the peribiliary capillary plexus. This has important implications for chemoembolization.Particulate embolics occlude arteries 200 microns or larger, proximal to the level of the pre-sinusoidal shunts, allowing portal blood flow to continue to the tumor and daughter nodules. Oily agents occlude the pre-sinusoidal shunts, but may wash out with time. Oil followed by particulate embolics causes the greatest and most durable tumor ischemia.Most chemotherapeutic drugs used for adenocarcinomas are lipophobic, and remain in the aqueous phase of the emulsion, which can wash out while the oil stays behind. Lipophilic drugs will be taken up by the oily micelles and remain in the tumor. who needs ADC maps or mRECIST?validated imaging response marker correlating to survival.>50% oil uptake improves med survival from 10 to 30 months.Axial T2*-weighted MR image of the liver after embolization with 300500-m IOEs. Less intense and partially distributed signal void at the rim of the tumor (arrowhead) is seen without signal void inside the tumor. Note the intense signal void with blooming artifact (white arrow) caused by the clustered IOEs within the left hepatic artery located at a significant distance from the tumor bed.Axial T2*-weighted MR image (field of view, 16 16; matrix size, 256 160; repetition/echo time, 200/15 msec