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Radiotherapeutic Option Radiotherapeutic Option in Management of in Management of Hepatocellular CarcinomaHepatocellular Carcinoma
Dr. CK Tang, Tuen Mun HospitalDr. CK Tang, Tuen Mun Hospital
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OverviewOverview
External beam External beam radiotherapyradiotherapy
Transarterial Transarterial radioembolisationradioembolisation
Aim :Aim : Overview Overview of clinical of clinical use of external beam use of external beam radiotherapy in HCC radiotherapy in HCC patientspatients
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BackgroundBackground
Hepatocellular carcinomaHepatocellular carcinoma HCCHCC
5th5th most common most common cancer in the worldcancer in the world
3rd 3rd ranked cause of ranked cause of global cancer mortalityglobal cancer mortality
Worldwide Incidence of HCC
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BackgroundBackground
MultidisciplinaryMultidisciplinary management of HCCmanagement of HCC
AggressiveAggressive treatment treatment
Increasing interest in Increasing interest in radiotherapy as an option radiotherapy as an option of management for HCCof management for HCC
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BackgroundBackground
Traditionally, radiotherapy Traditionally, radiotherapy is regarded as of is regarded as of limitedlimited useuse
Radiation-induced liver Radiation-induced liver disease RILDdisease RILD
Low dose radiationLow dose radiation Relatively diffuse fieldRelatively diffuse field ““Radio-resistant”Radio-resistant”
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BackgroundBackground
New technologies :New technologies :
Advanced imaging to improve Advanced imaging to improve tumour definitiontumour definition
3D conformal treatment 3D conformal treatment planningplanning
Computer-assisted organ Computer-assisted organ trackingtracking
Intensity modulated RTIntensity modulated RT Improved knowledge of Improved knowledge of
partial volume tolerance of partial volume tolerance of liverliver
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BackgroundBackground
Greater conformalityGreater conformality of of the radiation dose cloud the radiation dose cloud around liver tumorsaround liver tumors
Less radiation delivered Less radiation delivered to surrounding “normal to surrounding “normal liver”liver”
Higher radiation dosage Higher radiation dosage could be delivered to could be delivered to tumour up to 70 Gytumour up to 70 Gy
Stereotactic body Stereotactic body radiotherapy SBRTradiotherapy SBRT
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Clinical Questions
Is it useful ?
Which patient group are we going to offer to ?
What are the outcomes ?
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Is it useful ?
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EvidenceEvidence
Radiotherapy for hepatocellular carcinoma: Systematic review of radiobiology and modeling projections indicate reconsideration of its use
Wigg et al 2010
Level I evidence that HCC is radiosensitive
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Early results came from experience in palliative care
EvidenceEvidence
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EvidenceEvidence Bujold et alBujold et al.. Phase II prospective seriesPhase II prospective series including including 102 102 patientspatients High riskHigh risk
Extrahepatic diseaseExtrahepatic disease Large size HCC up to 7cmLarge size HCC up to 7cm Main portal vein thrombosisMain portal vein thrombosis
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EvidenceEvidence Bujold et alBujold et al..
Overall local control at 1 year was Overall local control at 1 year was 87%.87%. Median overall survival was Median overall survival was 17.0 months17.0 months 1-year survival rate1-year survival rate compared favorably with best supportive care and with compared favorably with best supportive care and with sorafenibsorafenib Conclusion : SBRT has Conclusion : SBRT has substantial local control activitysubstantial local control activity against HCC against HCC
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EvidenceEvidence Feasibility and efficacy of high-dose three-dimensional-conformal
radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma non-eligible for curative therapies – mature results of the French phase II RTF-a trial
Mornex et al 2006
Stereotactic body radiotherapy for primary hepatocellular carcinomaAndolino et al. 2011
85-95% response rate
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Which patient group are we going to offer radiotherapy to?
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We don’t know. No RCT No guideline Expert opinion
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Preserved liver functionPreserved liver function Huge tumourHuge tumour Main portal vein thrombusMain portal vein thrombus
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EvidenceEvidence
Synergistic effect of TACE with RTSynergistic effect of TACE with RT Direct tumour necrosisDirect tumour necrosis Veno-occlusive effect of RT to surrounding liver tissueVeno-occlusive effect of RT to surrounding liver tissue
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Preserved liver functionPreserved liver function Huge tumourHuge tumour Main portal vein thrombusMain portal vein thrombus
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What are the outcomes ?
Local controlLocal control activity against activity against HCCHCC
And apart from that…And apart from that…
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Case presentation 1Case presentation 1 55 year-old gentleman Attended TMH Non-Hep B, non-Hep C HCC AFP 1085 Child’s A CT : 10.4cm HCC at right lobe BCLC stage C
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Case presentation 1Case presentation 1 TACE to RHA, then stereotactic radiotherapy 4 Gy x 9 Follow-up CT : Interval decrease in size of HCC to
6.2cm, with hypertrophy of left lateral section CT volumetry : 57%
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Case presentation 1Case presentation 1
BeforeBefore AfterAfter
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Case presentation 1Case presentation 1 Right tri-sectionectomy 6 months after initial diagnosis of
HCC
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Case presentation 1Case presentation 1
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Case presentation 2Case presentation 2 Child’s A Presented to us for RUQ pain CT : Huge HCC occupying the right lobe, contained
rupture
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Case presentation 2Case presentation 2 TACE, then stereotactic radiotherapy 4 Gy x 8 Follow-up CT : Interval decrease in size of HCC from
13.4cm to 9cm Hypertrophy of left lateral section
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Case presentation 2Case presentation 2
BeforeBefore AfterAfter
Right hepatectomy 6 months after initial diagnosis of HCC
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Combination of Radiotherapy Combination of Radiotherapy with other modalitieswith other modalities
Choi SB et al. 2009 Case series 16 patients with HCC greater than 5 cm in size TACE and radiation therapy, then resection Median survival 13.3 months 5 patients had survived more than 2 yr and 2 patients who had survived more
than 5 yr
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Combination of Radiotherapy Combination of Radiotherapy with other modalitieswith other modalities
Hung KC et al. 2011
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Combination of Radiotherapy Combination of Radiotherapy with other modalitieswith other modalities
Hung KC et al. 2011
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SummarySummary
Is it useful ?Is it useful ? Level I evidenceLevel I evidence to support to support radio-sensitivityradio-sensitivity of HCC of HCC Prospective studies Prospective studies to support local control activity in to support local control activity in
HCCHCC
Whom to select ?Whom to select ? No RCT, no guidelineNo RCT, no guideline Expert opinionExpert opinion
Huge tumour, MPV thrombus, Preserved liver functionHuge tumour, MPV thrombus, Preserved liver function
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SummarySummary
What are the clinical outcomes ?What are the clinical outcomes ? Prospective studiesProspective studies support the clinical use of support the clinical use of
radiotherapy for radiotherapy for local controllocal control A few A few case reportscase reports and and small case seriessmall case series to support to support
combination of radiotherapy and TACE with surgical combination of radiotherapy and TACE with surgical resectionresection
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SummarySummary
But still But still lacking RCTslacking RCTs to provide comparison with other to provide comparison with other treatment modalities, in terms of treatment modalities, in terms of survivalsurvival benefit benefit
Relatively new approach with Relatively new approach with scanty clinical data scanty clinical data meanwhilemeanwhile
ControversyControversy
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Future perspectiveFuture perspective ? Overall survival? Overall survival ? Disease-free survival ? Disease-free survival
Evidence limited to Evidence limited to prospective studies, case prospective studies, case reports and case studiesreports and case studies
Evidence concentrated in Evidence concentrated in AsiaAsia
No RCTNo RCT
Data are emergingData are emerging
ChinaChinaJapanJapan
KoreaKorea
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As a Surgeon…As a Surgeon…
Overview onlyOverview only Share our experience of managing patientsShare our experience of managing patients with with
radiotherapyradiotherapy
As a Surgeon…As a Surgeon…
MultidisciplinaryMultidisciplinary approach in management of HCC approach in management of HCC Operation is only a part of itOperation is only a part of it Explore Explore combinationcombination of radiotherapy with resection / of radiotherapy with resection /
ablative surgery / liver transplantationablative surgery / liver transplantation Ongoing research should be promotedOngoing research should be promoted
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Adverse reactionsAdverse reactions
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LimitationsLimitations
Evidence limited to prospective studies, case reports Evidence limited to prospective studies, case reports and case studiesand case studies
Evidence concentrated at AsiaEvidence concentrated at Asia No RCT conductedNo RCT conducted
Limited to a selected group of patientLimited to a selected group of patient No generalised selection criteriaNo generalised selection criteria No homogeneous treatment protoccolNo homogeneous treatment protoccol
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Radiation-induced liver diseaseRadiation-induced liver disease
Radiation hepatitisRadiation hepatitis Fatigue, RUQ pain, ascites, jaundice, elevated liver Fatigue, RUQ pain, ascites, jaundice, elevated liver
enzymesenzymes Develops usually 1-2 months after RT (range 2 weeks Develops usually 1-2 months after RT (range 2 weeks
- 8 months) - 8 months) Treatment: supportive; most patients recover, but can Treatment: supportive; most patients recover, but can
lead to liver failure and death lead to liver failure and death
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Radiation-induced liver diseaseRadiation-induced liver disease
Dawson report in 2002 Dawson report in 2002 The mean liver dose is directly proportional to risk of The mean liver dose is directly proportional to risk of
RILDRILD 5% risk of RILD for whole liver RT is at 32 Gy 5% risk of RILD for whole liver RT is at 32 Gy Small liver volumes (<25%) can tolerate doses >100 Small liver volumes (<25%) can tolerate doses >100
Gy Gy Difference between normal liver tolerance and HCC Difference between normal liver tolerance and HCC
liver toleranceliver tolerance