Liver cancer treatments OLT Treatment of choice for HCC, especially in cirrhotics Milan criteria: one lesion up to 5 cm, or up to 3 lesions, each up to 3 cm. No vascular invasion or mets 5-year survival ~70% Resection Treatment of choice for HCC in non-cirrhotics Any size lesion if limited to one lobe, PV invasion OK 5-year survival ~50% RFA Treatment of choice in non-operative candidates with limited disease Effective in lesions up to 3-5 cm, up to 3 or 4 lesions 5-year survival ~40% TACE Treatment of choice in non-operative candidates with intermediate stage HCC (large or numerous tumors) Give chemotherapy-eluting particles directly into arteries feeding the tumor 5-year survival ~20% Nexavar Treatment of choice in advanced HCC (extrahepatic spread or vascular invasion) Tyrosine kinase inhibitor with proven survival benefit in RCT Median survival 10 months (vs 7 months with placebo)
Transarterial chemoembolizationRationale HCC takes its blood supply almost exclusively from the hepatic artery Surrounding normal liver has dual blood supply (with portal vein) Chemotherapy + embolic agent administered into hepatic artery should selectively kill tumor while sparing normal liver
TACETechnique1. Conscious sedation2. Common femoral artery access3. Catheter to select hepatic artery4. Microcatheter to superselect tumor-bearing artery5. Embolize to near-stasis or stasis • Conventional TACE: Chemotherapy (doxorubicin, cisplatin, mitomycin C) with Lipiodol, followed by Gelfoam or Embospheres • DEB-TACE: Doxorubicin-eluting LC beads • Chemo elutes more slowly than with Lipiodol • Reduced liver toxicity • Less side effects6. Arterial closure7. Overnight admission
TACELlovet and Lo, 2002 RCT of TACE vs. symptomatic treatment for unresectable HCC Llovet: 112 patients 3-year survival: 29% with TACE 17% with supportive care Lo: 80 patients 3-year survival: 26% with TACE 3% with supportive care
TACEConsensus statement “TACE is first-line non-curative therapy for non- surgical patients with large or multifocal HCC who do not have vascular invasion or extrahepatic spread (level I evidence).” American Association for Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).
Radiofrequency ablationRationale RF current induces thermal coagulation necrosis around an electrode • Complete ablation rates >80% for small to medium HCC • Local recurrence uncommon (1-12%) Disadvantages • Relies on thermal conduction (limited ablation size) Best for tumors <3 cm Increasing technical failure and local recurrence for tumors >3 cm • Heat sink effect • Slow McWilliams J, et al. Percutaneous ablation of hepatocellular carcinoma: current status. J Vasc Interv Radiol 2010;21:S204-S213. Hinshaw J. The role of image-guided tumor ablation in the management of liver cancer. Cancer News review article.
RFATechnique1. General anesthesia (usually)2. Ultrasound used to guide 1-3 needles into tumor3. CT to confirm and/or adjust position4. Ablation performed (3-5 cm burn possible)5. Adjust needle position and repeat as necessary6. Needle removal with tract cauterization7. Contrast CT to confirm adequate treatment8. MRI after anesthesia wears off9. Discharge same day (ideally)
Percutaneous ablationConsensus statement “Local ablation is safe and effective therapy for patients who cannot undergo resection, or as a bridge to transplantation.” American Association for Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).
Post-embo and post-ablationmanagementGeneral principles
General PrinciplesPost-embolization syndrome (PES) Occurs in 80-90% of patients who undergo embolization (TACE, UFE, etc) Within 24 hours of embolization, tissue and cell death begins, and breakdown products are released into the circulation • Pain – At site of embolization, may be severe • Nausea/vomiting – About 1/3 of patients • Fever – 15-30% of patients, up to 104 degrees • Leukocytosis – 15-30% of patients, can exceed WBC 20k • Fatigue – Most patients, can last for weeks Some or all of these symptoms may not manifest until after patient discharge Post-ablation syndrome consists of the same symptoms, but is less frequent (<1/3 of patients) Most symptoms resolve by 72 hours (except fatigue, and sometimes pain)
General PrinciplesPain Can occur during the procedure, but often does not occur until post-procedure Referred visceral pain from the liver is often found in the right shoulder Opioid analgesia is treatment of choice for severe pain • Dilaudid or morphine • PCA is often best method of delivery NSAIDs can be useful for minor pain, but generally avoid in liver patients Tylenol is OK but limit to 1.5 grams/day in liver patients
General PrinciplesNauseaOften multifactorial• PES• Chemotherapy• Opioid useZofran works great (4 mg q4 or 8 mg q8)Can add dexamethasone in non-diabetics (12 mg on day oftreatment)Compazine or droperidol for breakthrough nausea
General PrinciplesFever15-30% of patients develop fever after intervention• Usually at 24-48 hours• May be up to 104, but usually <102Leukocytosis is normal• Can exceed 20kLow grade or moderate fever in first few days aftertreatment should not warrant fever work-upDifferentiating infection vs. PES is difficult• Gas in embolized area on CT is normal, not abscess• Fevers beyond 48 hours may require work-up• Abscess usually occurs at 2-4 weeks
General PrinciplesFatigue Extremely common after embolization, and to a lesser extent, ablation Peaks several days after treatment Can last for days or weeks Risk factors • Baseline fatigue • High dose of chemo used
Post-embo and post-ablationmanagementThe specifics
TACEPost-procedure managementFluids/Diet• IV hydration NS ~250 cc/hr x 5 hours• Advance diet as tolerated (do not start with Salisbury steak)ActivityPain controlNausea controlAntibioticsPuncture siteLabs
TACEPost-procedure managementFluids/DietActivity• Bed rest at least 2 hours (closure device)• Bed rest at least 6 hours (manual compression)• Bed rest overnight (higher risk patients)Pain controlNausea controlAntibioticsPuncture siteLabs
TACEPost-procedure managementFluids/DietActivityPain control• PCA (almost everyone)• If pain stays controlled, switch to PO Vicodin/Percocet/Oxycodone the next AMNausea controlAntibioticsPuncture siteLabs
TACEPost-procedure managementFluids/DietActivityPain controlNausea control• Dexamethasone 6 hours post-procedure (if non-diabetic)• Zofran (4 mg q4 hours, or 8 mg q8 hours)• If ineffective, can use Phenergan or Droperidol or ReglanAntibioticsPuncture siteLabs
TACEPost-procedure managementFluids/DietActivityPain controlNausea controlAntibiotics• No data prove their necessity or effectiveness post-TACE• Used empirically by some operators, especially in higher risk patients• Cipro +/- Flagyl x 7 daysPuncture siteLabs
TACEPost-procedure managementFluids/DietActivityPain controlNausea controlAntibioticsPuncture site• First 2 hours post-procedure are critical• Groin checks and vitals q15 min x 4, then q30 min x 2• The most dangerous bleeds are not externally obviousLabs
TACEPost-procedure managementFluids/DietActivityPain controlNausea controlAntibioticsPuncture siteLabs• AST and ALT• Total bilirubin• Creatinine• Sodium
TACEComplications Liver failure • Risk factors: Child B/C, total bili >3.0, albumin <2.0, ECOG >2 • Mechanism: TACE-related injury to “normal” liver parenchyma (poor reserve in cirrhotic livers) • Incidence: 13% of TACE patients suffer some degree of liver failure. • Diagnosis: Elevated bilirubin/INR, jaundice, itchiness, dark urine, light stool • Avoidance strategy: Superselective embo • Treatment: Supportive care • Outcome: Most recover. 30-day TACE-related mortality from liver failure is 2%
TACEComplications Bleeding (puncture site) • Risk factors: Low platelets, high INR, obesity, closure device failure, uncooperative patient • Mechanism: Platelet plug does not form or dislodges • Incidence: Minor groin hematoma <10%. Major intramuscular or retroperitoneal bleed is rare but devastating. • Diagnosis: Groin swelling/pain (not if retroperitoneal), tachycardia, hypotension, orthostasis, pallor, dizziness, lightheadedness, weakness • Avoidance strategy: Careful access and closure, bed rest with leg straight • Treatment: Pressure. IVF. Stat type/cross and transfuse. Stat CT. Consider angio. • Outcome: Depends on blood loss.
TACEComplications Bleeding (variceal) • Risk factors: Presence of varices, previous variceal bleed, low platelets, high INR • Mechanism: Increased portal HTN in setting of periprocedural liver insult (varices) • Incidence: <1%, anecdotal • Diagnosis: Hematemesis, shock • Avoidance strategy: Pre-TACE banding? Superselective TACE • Treatment: IVF. Type/cross and transfuse. Immediate endoscopy with banding. Consider emergent TIPS if no other options. • Outcome: High mortality rate.
TACEComplications Nontarget embolization • Risk factors: Lobar (nonselective) treatment • Mechanism: Embolic material passes into gallbladder, stomach or intestine • Incidence: <<10% • Diagnosis: Ulceration, perforation, pain, bleeding • Avoidance strategy: Superselective embo • Treatment: NPO. Hydration. PPI. Prolonged observation. Consider surgery if bowel necrosis. • Outcome: Most recover with supportive care alone.
TACEComplications Acute renal failure • Risk factors: High baseline creatinine (CRI), diabetes, dehydration • Mechanism: Nephrotoxic contrast, nephrotoxic chemotherapy, tumor lysis syndrome • Incidence: <1-8% • Diagnosis: Rising creatinine, peaking 2-3 days after insult; oliguria • Avoidance strategy: IV hydration. Minimize contrast. Bicarbonate/Mucomyst. • Treatment: IV hydration. Temporary dialysis if necessary. • Outcome: 1/3 require permanent dialysis. 2/3 recover.
RFA/MWAPost-procedure managementFluids/Diet• IVF (gentle)• Advance as tolerated (most had general anesthesia)ActivityPain controlNausea controlAntibioticsPuncture siteLabs
RFA/MWAPost-procedure managementFluids/DietActivity• Ad libPain controlNausea controlAntibioticsPuncture siteLabs
RFA/MWAPost-procedure managementFluids/DietActivityPain control• Usually PO narcotics suffice (Vicodin, Percocet)• PCA or IV morphine/dilaudid if pain is severeNausea controlAntibioticsPuncture siteLabs
RFA/MWAPost-procedure managementFluids/DietActivityPain controlNausea controlAntibiotics• Little evidene to support its use in routine ablation• Cipro +/- Flagyl if chance of biliary/bowel injury or high risk patientPuncture siteLabs
RFA/MWAPost-procedure managementFluids/DietActivityPain controlNausea controlAntibioticsPuncture site• Usually nothing to see• Rare skin burnsLabs
RFA/MWAComplications Hemorrhage • Risk factors: Low platelets, high INR, multiple needle placements, ascites • Mechanism: Arterial injury by needle, or persistent oozing from liver puncture • Incidence: ~1% clinically significant hemorrhage rate • Diagnosis: Hypotension, tachycardia, pallor, pain, dizziness, orthostasis • Avoidance strategy: Tract cauterization, FFP/platelet support • Treatment: IVF resuscitation. Transfuse. Stat CTA (look for active extravasation). Hepatic angiography and embolization. • Outcome: Depends on blood loss.
RFA/MWAComplications Liver failure • Risk factors: Child B/C, total bili >3.0, albumin <2.0, ECOG >2, large ablation zone, multiple ablations • Mechanism: Ablation of “normal” liver parenchyma (poor reserve in cirrhotic livers) • Incidence: 12% risk of death from liver failure in ablation of Child C patients; <1% risk for Child A or B • Diagnosis: Elevated bilirubin/INR, jaundice, itchiness, dark urine, light stool • Avoidance strategy: Staged ablation • Treatment: Supportive care • Outcome: Recovery is less likely than in TACE as liver is permanently damaged with ablation
RFA/MWAComplications Nontarget ablation • Risk factors: Target tumor near stomach, bowel, bile ducts, gallbladder • Mechanism: Nontarget tissues lie within ablation zone • Incidence: 2% • Diagnosis: Bowel or gallbladder perforation, bile leak or obstruction • Avoidance strategy: Hydrodissection, positioning • Treatment: Surgery or supportive care • Outcome: Mortality is high for bowel injury in this population
RFA/MWAComplications Infection/abscess • Risk factors: Hepatojejunostomy, biliary drainage tube • Mechanism: Colonized biliary system seeds the necrotic treated ablation zone • Incidence: <5% with normal sphincter of Oddi; 30-80% if compromised • Diagnosis: Pain, fever • Avoidance strategy: Periprocedural antibiotics, bowel prep • Treatment: Antibiotics and drainage • Outcome: Most recover
RFA/MWAComplications Tumor seeding • Risk factors: Multiple needle insertions, concomitant biopsy • Mechanism: Tumor cells on needle seed tract as needle is removed • Incidence: <1% • Diagnosis: Imaging • Avoidance strategy: Tract ablation/cauterization with needle removal • Treatment: Ablation or surgery • Outcome: Most are detected on follow up and treated
TG 39 y/o female Fibrolamellar HCC diagnosed in 2001Left lobe resection of 9 x 11 cm mass in 2001 Recurrence 2007 with partial right lobe resection CT 4/9/2010: At leastPresents with multifocal recurrence 2/2010 10 hypervascular liver masses Not a surgical or transplant candidate Presented at tumor board and referred for locoregional therapy
TACE 5/3/2010 100 mg doxorubicin on LC beads 2 weeks later, returns with fevers, RUQ pain
CT 5/19/2010: near- complete tumor necrosis Prolonged CT 8/6/2010: Biloma Percutaneous biloma catheter resolved, but drainage drainage intrahepatic recurrence and new lung nodule. To study drug
Fibrolamellar hepatocellular carcinoma Status post left lobectomy and partial right lobectomy No longer a surgical candidate OLT? RFA? TACE? Chemotherapy?
Liver cancer treatments OLT Treatment of choice for HCC, especially in cirrhotics Milan criteria: one lesion up to 5 cm in size, or up to 3 lesions, each up to 3 cm in size. No vascular invasion and no mets. RFA Place ablation needle into lesion (under CT/US guidance) and cook it Effective in lesions up to 3 cm (sometimes larger), up to 3 or 4 lesions Damage to adjacent bile ducts or bowel can be a concern TACE CFA access, catheterize hepatic artery and subselect tumor feeders Give chemotherapy-eluting particles Block blood flow Release tumoricidal chemotherapy Targeted chemotherapy Nexavar (tyrosine kinase inhibitor) – extends survival in advanced HCC Avastin (monoclonal VEGF inhibitor) – promising but unproven
Liver cancer treatmentsOLT Too many lesions to qualify (outside Milan criteria) Can consider Milan exception if we can decrease her disease burdenRFA Too many lesions to effectively treat, and marginal location increases risk for bowel/stomach injuryTACE SuitableTargeted chemotherapy Suitable, if TACE fails
Status post 100 mg doxorubicin on 100-300 and 300-500 micron LC beads
Discharged home the next day, doing well2 weeks later, having persistent high fevers to 103 and night sweats