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Radiotherapeutic Option in Management of Hepatocellular Carcinoma Dr. CK Tang, Tuen Mun Hospital.

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Presentation on theme: "Radiotherapeutic Option in Management of Hepatocellular Carcinoma Dr. CK Tang, Tuen Mun Hospital."— Presentation transcript:

1 Radiotherapeutic Option in Management of Hepatocellular Carcinoma Dr. CK Tang, Tuen Mun Hospital

2 Overview External beam radiotherapy External beam radiotherapy Transarterial radioembolisation Transarterial radioembolisation Aim : Overview of clinical use of external beam radiotherapy in HCC patients Aim : Overview of clinical use of external beam radiotherapy in HCC patients

3 Background Hepatocellular carcinoma HCC Hepatocellular carcinoma HCC 5th most common cancer in the world 5th most common cancer in the world 3rd ranked cause of global cancer mortality 3rd ranked cause of global cancer mortality Worldwide Incidence of HCC

4 Background Multidisciplinary management of HCC Multidisciplinary management of HCC Aggressive treatment Aggressive treatment Increasing interest in radiotherapy as an option of management for HCC Increasing interest in radiotherapy as an option of management for HCC

5 Background Traditionally, radiotherapy is regarded as of limited use Traditionally, radiotherapy is regarded as of limited use Radiation-induced liver disease RILD Radiation-induced liver disease RILD Low dose radiation Low dose radiation Relatively diffuse field Relatively diffuse field “Radio-resistant” “Radio-resistant”

6 Background New technologies : New technologies : Advanced imaging to improve tumour definition Advanced imaging to improve tumour definition 3D conformal treatment planning 3D conformal treatment planning Computer-assisted organ tracking Computer-assisted organ tracking Intensity modulated RT Intensity modulated RT Improved knowledge of partial volume tolerance of liver Improved knowledge of partial volume tolerance of liver

7 Background Greater conformality of the radiation dose cloud around liver tumors Greater conformality of the radiation dose cloud around liver tumors Less radiation delivered to surrounding “normal liver” Less radiation delivered to surrounding “normal liver” Higher radiation dosage could be delivered to tumour up to 70 Gy Higher radiation dosage could be delivered to tumour up to 70 Gy Stereotactic body radiotherapy SBRT Stereotactic body radiotherapy SBRT

8 Clinical Questions Is it useful ? Which patient group are we going to offer to ? What are the outcomes ?

9 Is it useful ?

10 Evidence 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

11 Early results came from experience in palliative care Evidence

12 Evidence Bujold et al. Bujold et al. Phase II prospective series including 102 patients Phase II prospective series including 102 patients High risk High risk Extrahepatic disease Extrahepatic disease Large size HCC up to 7cm Large size HCC up to 7cm Main portal vein thrombosis Main portal vein thrombosis

13 Evidence Bujold et al. Bujold et al. Overall local control at 1 year was 87%. Overall local control at 1 year was 87%. Median overall survival was 17.0 months Median overall survival was 17.0 months 1-year survival rate compared favorably with best supportive care and with sorafenib 1-year survival rate compared favorably with best supportive care and with sorafenib Conclusion : SBRT has substantial local control activity against HCC Conclusion : SBRT has substantial local control activity against HCC

14 Evidence 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 carcinoma Andolino et al % response rate

15 Which patient group are we going to offer radiotherapy to?

16 We don’t know. No RCT No guideline Expert opinion

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20 Preserved liver function Preserved liver function Huge tumour Huge tumour Main portal vein thrombus Main portal vein thrombus

21 Evidence Synergistic effect of TACE with RT Synergistic effect of TACE with RT Direct tumour necrosis Direct tumour necrosis Veno-occlusive effect of RT to surrounding liver tissue Veno-occlusive effect of RT to surrounding liver tissue

22 Preserved liver function Preserved liver function Huge tumour Huge tumour Main portal vein thrombus Main portal vein thrombus

23 What are the outcomes ? Local control activity against HCC Local control activity against HCC And apart from that… And apart from that…

24 Case 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

25 Case 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%

26 Case presentation 1 BeforeAfter

27 Right tri-sectionectomy 6 months after initial diagnosis of HCC

28 Case presentation 1

29 Case presentation 2 Child’s A Presented to us for RUQ pain CT : Huge HCC occupying the right lobe, contained rupture

30 Case 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

31 Case presentation 2 BeforeAfter Right hepatectomy 6 months after initial diagnosis of HCC

32 Combination of Radiotherapy with other modalities Choi SB et al 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

33 Combination of Radiotherapy with other modalities Hung KC et al. 2011

34 Combination of Radiotherapy with other modalities Hung KC et al. 2011

35 Summary Is it useful ? Is it useful ? Level I evidence to support radio-sensitivity of HCC Level I evidence to support radio-sensitivity of HCC Prospective studies to support local control activity in HCC Prospective studies to support local control activity in HCC Whom to select ? Whom to select ? No RCT, no guideline No RCT, no guideline Expert opinion Expert opinion Huge tumour, MPV thrombus, Preserved liver function Huge tumour, MPV thrombus, Preserved liver function

36 Summary What are the clinical outcomes ? What are the clinical outcomes ? Prospective studies support the clinical use of radiotherapy for local control Prospective studies support the clinical use of radiotherapy for local control A few case reports and small case series to support combination of radiotherapy and TACE with surgical resection A few case reports and small case series to support combination of radiotherapy and TACE with surgical resection

37 Summary But still lacking RCTs to provide comparison with other treatment modalities, in terms of survival benefit But still lacking RCTs to provide comparison with other treatment modalities, in terms of survival benefit Relatively new approach with scanty clinical data meanwhile Relatively new approach with scanty clinical data meanwhile Controversy Controversy

38 Future perspective ? Overall survival ? Overall survival ? Disease-free survival ? Disease-free survival Evidence limited to prospective studies, case reports and case studies Evidence limited to prospective studies, case reports and case studies Evidence concentrated in Asia Evidence concentrated in Asia No RCT No RCT Data are emerging Data are emerging China JapanKorea

39 As a Surgeon… Overview only Overview only Share our experience of managing patients with radiotherapy Share our experience of managing patients with radiotherapy As a Surgeon… Multidisciplinary approach in management of HCC Multidisciplinary approach in management of HCC Operation is only a part of it Operation is only a part of it Explore combination of radiotherapy with resection / ablative surgery / liver transplantation Explore combination of radiotherapy with resection / ablative surgery / liver transplantation Ongoing research should be promoted Ongoing research should be promoted

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41 Adverse reactions

42 Limitations Evidence limited to prospective studies, case reports and case studies Evidence limited to prospective studies, case reports and case studies Evidence concentrated at Asia Evidence concentrated at Asia No RCT conducted No RCT conducted Limited to a selected group of patient Limited to a selected group of patient No generalised selection criteria No generalised selection criteria No homogeneous treatment protoccol No homogeneous treatment protoccol

43 Radiation-induced liver disease Radiation hepatitis Radiation hepatitis Fatigue, RUQ pain, ascites, jaundice, elevated liver enzymes Fatigue, RUQ pain, ascites, jaundice, elevated liver enzymes Develops usually 1-2 months after RT (range 2 weeks - 8 months) Develops usually 1-2 months after RT (range 2 weeks - 8 months) Treatment: supportive; most patients recover, but can lead to liver failure and death Treatment: supportive; most patients recover, but can lead to liver failure and death

44 Radiation-induced liver disease Dawson report in 2002 Dawson report in 2002 The mean liver dose is directly proportional to risk of RILD The mean liver dose is directly proportional to risk of RILD 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 ( 100 Gy Small liver volumes ( 100 Gy Difference between normal liver tolerance and HCC liver tolerance Difference between normal liver tolerance and HCC liver tolerance


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