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IR Therapies for the Treatment of Colorectal Liver Metastases


Title: MSK Teaching File Author: Semaan, Dominic Last modified by: lejam01 Created Date: 6/8/2012 12:29:49 AM Document presentation format: On-screen Show – PowerPoint PPT presentation

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Title: IR Therapies for the Treatment of Colorectal Liver Metastases

IR Therapies for the Treatment of Colorectal
Liver Metastases
Laurie M. Vance, MD Vascular and Interventional
Radiologist Department of Diagnostic Radiology
Providence Hospital Southfield, MI
Financial Disclosures
  • I have nothing to disclose.

  • -Colorectal cancer is the second most common
    cause of cancer death in the Western World.
  • -Colorectal liver metastases (CLM) are detected
    at the time of diagnosis of the bowel primary in
    20-25 of cases. A further 40-45 of patients
    will subsequently develop CLM 1.
  • -Without treatment, prognosis is poor, with
    median survival of 1 year, and few survivors
    beyond 3 years.
  • -Surgical resection is the gold standard, but
    majority are not eligible for this.
  • -60-70 of liver metastases are unresectable at
  • -Central location or bilobar disease
  • -Major vascular/biliary involvement
  • -Unresectable extrahepatic disease
  • -Liver dysfunction/cirrhosis 2

  • Radiology plays an important role in the
    multidisciplinary care of patients with CLM.
  • Imaging
  • Detection and characterization of liver
  • Assists in surgical/locoregional treatment
  • Treatment
  • Portal Vein Embolization
  • Ablative therapies
  • Liver directed arterial therapies
  • Understanding the timing and role of locoregional
    techniques is critical.

Imaging Recommendations for Colorectal Carcinoma
  • -Staging
  • -Contrast enhanced CT
  • -Normal parenchyma enhances, mets are
  • -Peripheral enhancement may be present
  • -Questionable lesions ? MR or PET
  • -Surveillance
  • -PET/CT
  • -Foci of increased radiotracer activity within
    the liver
  • -False negative with highly mucinous mets

Liver Segmental Anatomy- Couinaud

Portal Vein Embolization
Portal Vein Embolization (PVE)
  • -Embolization of the PV branches supplying the
    liver segments to be resected, redirects blood
    flow to the nondiseased liver.
  • -This redistribution induces hypertrophy of the
    future liver remnant (FLR), making it possible to
    safely undergo major hepatectomy.
  • -Indications
  • Patients with primary/metastatic liver disease,
    who are otherwise hepatic resection candidates,
  • Cirrhosis/Advanced fibrosis and future liver
    remnant (FLR)/total liver volume (TLV) lt40
  • Extensive chemotherapy and and FLR/TLV lt30
  • Normal underlying liver and an FLR/TLV lt20

  • Contraindications
  • Absolute
  • Overt clinical portal HTN
  • Extensive invasion of the portal vein precluding
    safe catheter manipulation
  • Complete lobar portal vein occlusion
  • Relative
  • Extrahepatic metastatic disease
  • Tumor extension to the FLR
  • Tumor precluding safe access into the portal
    venous system
  • Biliary dilatation of the FLR
  • Mild portal HTN
  • Uncorrectable coagulopathy
  • Renal insufficiency

  • Preprocedure preparation
  • CT
  • IV antibiotic prophylaxis
  • Ceftriaxone 1 gram IV
  • Consider General Anesthesia
  • Procedure
  • Ipsilateral approach
  • Puncture peripheral portal venous branch
  • Portography
  • If segment 4 embo required, ideally performed
  • Microcatheter, embo with particles, small then
    large, then deposit coils in the more proximal
  • Final portography in main portal vein
  • Embolize tract with coils as exiting
  • Contralateral approach
  • Pros Allows for antegrade catheterization
    without sharp angles
  • Cons If any injury to left sided portal vein
    occurs, patient is no longer surgical candidate

  • Results
  • Get CT 3-4 weeks post-embo to assess degree of
    FLR hypertrophy (DH)
  • Degree of hypertrophy is used as a predictor of
    postoperative course
  • DH lt5 ? Higher post-op complication rate
  • Recent study
  • 112 patients
  • Average increase in FLR volume 9
  • Complications
  • Subcapsular hematoma, hemobilia, pneumothorax, AV
    fistula, arterioportal shunt, sepsis, nontarget
    embolization, portal HTN.

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CT Volumetric for PVE
Chemical/Thermal Ablation
  • Chemical Ablation
  • Involves percutaneous direct infusion into the
    tumor of a denaturing materal (EtOH or Acetic
    acid), usually under CT guidance
  • Limited success and not routinely used anymore
  • Thermal Ablation
  • Involves killing of tissue by freezing it
    (cryoablation) or heating it (microwave, laser or
  • Many institutions world wide have employed RF
    ablation, which has proven more effective at
    local control of tumor burden and fewer treatment

Thermal Ablation
  • Performed by directing an alternating current
    (460kHz) to create local agitation at the
    molecular level, heat and irreversible cellular
  • Procedure is done percutaneously under image
    guidance (CT or US) and involves insertion of a
    needle-tip electrode with an insulated shaft and
    an active uninsulated tip into the tumor
  • May also be performed intraoperative

Thermal Ablation
  • Can be used as stand-alone therapy or in
    conjunction with other treatments
  • Reserved for treatment of focal or multifocal
    lesions that are unresectable
  • Treatment success
  • Varies with the size of lesion and surrounding
    normal liver
  • Studies have shown 80-90 complete tumor necrosis
    (while some patients required more than one
  • With larger lesions, a study of 126 patients
    showed only 48 complete tumor necrosis (mean
    size 5.4 cm)
  • As with surgical resection, immediate complete
    tumor necrosis does not equate with long-term
  • NO definite criteria for use of thermal ablation,
    but factors to consider
  • Lesion size
  • Individual lesions should be no larger than 5 cm
  • Number of Lesions
  • Fewer than 3 lesions
  • Degree of underlying hepatic impairment
  • Typically Child-Pugh class A or B
  • Ideal objective is a 1cm margin of ablation
    around the mass, similar to surgical resection

Thermal Ablation
  • Advantages
  • Repeatability
  • High local efficacy
  • Sparing of normal liver
  • Low complication/cost
  • Complications
  • Pain/Nausea
  • Hemorrhage
  • Coagulopathy and ascites increase the risk of
    uncontrolled bleeding and should be corrected
    prior to treatment
  • Abscess
  • There should be no active infection
  • Higher risk in patients with a choledochojejunal
  • Tumor seeding the tract
  • Thermal injury of adjacent organs
  • Usually a problem with peripheral tumors
  • Especially Gallbladder and adjacent ribs

Transcathether Arterial Therapies
  • Therapeutic advantage due to the dual blood
    supply to the liver and the propensity for masses
    to derive their blood supply from arterial
  • Developed for patients who are ineligible for
    more definitive treatment of HCC
  • Problem is that most have such severe liver
    dysfunction that they are usually not candidates,
    as they cannot tolerate any additional stress on
    the surrounding liver
  • Patients with Child-Pugh class C are ineligible
    and referred for systemic therapy
  • Comorbidities can add substantially to the risk
  • Severe thrombocytopenia or leukopenia
  • Cardiac or renal insufficiency
  • Uncorrectable coagulopathy
  • Ascites
  • Portal vein occlusion with hepatofugal flow
  • Atypical or diseased arterial anatomy that
    increases the risk of injury to adjacent
    gastrointestinal organs from non-target

Selective Chemoembolization (TACE)
  • Catheter based treatment where the
    chemotherapeutic agent is injected into the
    vessels feeding the mass
  • Usually combined with an embolization or
    sclerotic agent (spheres or EtOH)

Selective Chemoembolization (TACE)
  • Tumors known to respond
  • HCC
  • Mets from
  • Colorectal
  • Neuroendorcine
  • Ocular melanoma
  • Gastrointestinal sarcoma
  • Exclusion criteria
  • Clinically apparent jaundice
  • Hepatic encephalopathy
  • Hepatofugal portal vein flow
  • Liver rupture or tumor penetration of liver
  • Biliary obstruction
  • WBC lt 2.5
  • Platelet count lt 60k
  • Pregnancy
  • Clinical considerations
  • Portal vein patency
  • Can use low dose if partially occluded
  • No extrahepatic tumors that will potentially kill
    the patient within 3 months
  • Adequate residual uninvolved liver and adequate
  • No consensus on a numberstudies vary from 50
  • Want serum bilirubin lt3 mg/dL
  • Multiple treatments may be needed
  • F/U CT Scans in 1d, 1m, 3m, 6m and 1y
  • Tumor markers drawn before and after treatment

Selective Chemoembolization (TACE)
  • Various chemo agent and embolization protocols
    have be used in TACE
  • Embospheres (typically 300-500um)
  • Epirubicin (50mg), doxorubicin (50mg), cisplatin
    (100mg), mitomycin (10mg)
  • Ethiodol helps achieve concentration of the
    drugs in the tumor bed
  • Technical Consideration ?Should you completely
    embolize the feeding artery?
  • Pros
  • You obtain tissue ischemia, leading to cell death
  • Anoxia causes an increase in tissue permeability
    and local concentration of the chemo
  • Blocking inflow delays washout of the chemo agent
  • Cons
  • Evidence of hypoxia causing angiogenesis
  • Permanent occlusion preclude subsequent

Selective Chemoembolization (TACE)
  • Inadvertant Uptake
  • Lung not uncommon
  • Usually of no clinical consequence
  • Lobar collapse is usually a result of pain and
    resultant hypoventilation
  • Celiac Artery Branches
  • Pancreas Uncommon and can cause pancreatitis
  • GDA Can coil prior to embolization
  • Gastric Uptake
  • Uncommon and patients usually asymptomatic
  • Gallbladder
  • Uncommon
  • Usually asymptomatic, but can cause emphysematous
    cholecystitis or infarction
  • Spleen
  • Very uncommon, but can cause infarction

Selective Internal Radiation Therapy
  • External beam radiation if delivered in
    sufficient doses is lethal to neoplastic tissue,
    with normal hepatocytes having an even lower
  • However, when the whole liver is exposed to EBRT
    at a mean radiation dose of 43 Gy, more than 50
    of patient develop liver dysfunction
  • Stereotactic radiation can be used to deliver
    much higher doses to more focal areas, however
    this is difficult in CLM where many patients have
    multifocal masses that are irregular in
  • Isotope bearing microspheres, unlike EBRT, are
    point sources of radiation that preferentially
    localize in the peritumoral and intratumoral
    arterial vasculature
  • Thus you can deliver very high doses of radiation
    to tumors, while radiation exposure to the normal
    hepatic parenchyma remains within tolerable

Selective Internal Radiation Therapy
  • Delivery of radioactive material into the
    arterial blood supply
  • Much more involved and patients must undergo
    preprocedure angiography/mapping
  • Various isotopes have been used, with yttrium 90
    (y-90) most commonly used in the United States
  • B-emitting isotope
  • 64.2 hour half-life (94 in 11 days)
  • Decays to stable Zirconium 90
  • Tissue penetration of 0.25 cm 1.1 cm

Selective Internal Radiation Therapy
  • Delivery is via nonbiodegradable glass or resin
    microspheres that have embedded radioisotope,
    which like TACE the microspheres are injected
    into the arterial blood supply
  • Two Commercially available microspehere devices
  • Glass beads ? Thera-Sphere
  • Resin ? SIR-Spheres
  • The spheres are neither metabolized nor excreted
    but remain in the liver as a permanent implant
  • Contraindications
  • Absolute
  • Exaggerated hepatopulmonary shunting
  • Reflux into arteries that supply the
    gastroduodenal region
  • Relative
  • Subsequent to EBRT, as the effects of internal
    radiation after EBRT has not been studied
  • Treatment with capecitabine can increase toxicity
  • Ascites indication of decreased hepatocellular
  • Increased Bilirubin (gt2)
  • Portal venous thrombosis (package insert warning,
    but studies show it can be done)

Selective Internal Radiation Therapy
  • Therapy Planning
  • Initial workup should include
  • CT or MRI of the liver for assessment of tumor,
    normal liver volume and patency of portal vein
  • Check of presence of extrahepatic disease
  • Labs
  • Serum bilirubin level should be less than 2mg/dL
  • Check for renal insufficiency to limit amount of
    contrast used
  • Arteriography for Hepatopulmonary Shunt
  • May need to coil accessory arteries to prevent GI
    deposition of the spheres
  • MAA is injected during this arteriogram, used as
    a sphere surrogate
  • HP shunt fraction greater than 20 of injected
    dose or when shunt fraction indicates potential
    exposure of the lung to an absorbed dose of more
    than 30 Gy should preclude the patient
  • SPECT done 30 hrs after treatment

Selective Internal Radiation Therapy
  • Results (Therasphere)
  • Initial studies largely took place in Canada
  • 100Gy well tolerated by patients
  • Increased survival
  • 635 days vs 323 days
  • 20 response rate
  • Studies in the US have shown similar favorable
  • US studies also demonstrated safety for patients
    with portal vein thrombosis
  • Ongoing studies showing similar favorable results
    in metastatic colorectal cancer, even in those
    that showed no response to chemo
  • Complications
  • Low incidence
  • GI complications less than 5
  • Pancytopenia, as a result of bone marrow
    suppression from leaching of the isotope
  • Life-threatening complication of progressive
    pulmonary insufficiencynever reported in the US
  • Cholecystitis, inject distal to cystic artery

  • Presenting newly diagnosed patients at
    multidisciplinary tumor board is the key to
    providing optimum treatment.
  • Locoregional therapies may limit unnecessary
    resections, contributing to the preservation of
    patient quality of life.
  • Interventional Radiologic therapies allow the
    physician to manage the unresectable patient, to
    extend disease-free periods and overall survival,
    as well as convert some patients to resection for
    possible cure.

Thank you
  • Radio-frequency Ablation of Liver Tumors
    Assessment of Therapeutic Response and
    Complications. October 2001 RadioGraphics, 21,
  • Yttrium-90 Microsphere Therapy for Hepatic
    Malignancy Devices, Indications, Technical
    Considerations, and Potential ComplicationsOctober
    2005 RadioGraphics, 25, S41-S55.