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Radiotherapeutic Option in Management of Hepatocellular Carcinoma

Radiotherapeutic Option in Management of Hepatocellular Carcinoma. Dr. CK Tang, Tuen Mun Hospital. Overview. External beam radiotherapy Transarterial radioembolisation Aim : Overview of clinical use of external beam radiotherapy in HCC patients. Background. Hepatocellular carcinoma HCC

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Radiotherapeutic Option in Management of Hepatocellular Carcinoma

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

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

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

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

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

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

  7. Background • Greater conformality of the radiation dose cloud around liver tumors • Less radiation delivered to surrounding “normal liver” • Higher radiation dosage could be delivered to tumour up to 70 Gy • 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. Evidence • Early results came from experience in palliative care

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

  13. Evidence • Bujold et al. • Overall local control at 1 year was 87%. • Median overall survival was 17.0 months • 1-year survival rate compared favorably with best supportive care and with sorafenib • 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. 2011 • 85-95% response rate

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

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

  17. Preserved liver function • Huge tumour • Main portal vein thrombus

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

  19. Preserved liver function • Huge tumour • Main portal vein thrombus

  20. What are the outcomes ? • Local control activity against HCC • And apart from that…

  21. 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

  22. 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%

  23. Case presentation 1 Before After

  24. Case presentation 1 • Right tri-sectionectomy 6 months after initial diagnosis of HCC

  25. Case presentation 1

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

  27. 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

  28. Case presentation 2 • Right hepatectomy 6 months after initial diagnosis of HCC Before After

  29. Combination of Radiotherapy with 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

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

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

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

  33. What are the clinical outcomes ? 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 Summary

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

  35. Korea China Japan Future perspective • ? Overall survival • ? Disease-free survival • Evidence limited to prospective studies, case reports and case studies • Evidence concentrated in Asia • No RCT • Data are emerging

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

  37. Adverse reactions

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

  39. Radiation-induced liver disease • Radiation hepatitis • Fatigue, RUQ pain, ascites, jaundice, elevated liver enzymes • 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

  40. Radiation-induced liver disease • Dawson report in 2002 • The mean liver dose is directly proportional to risk of RILD • 5% risk of RILD for whole liver RT is at 32 Gy • Small liver volumes (<25%) can tolerate doses >100 Gy • Difference between normal liver tolerance and HCC liver tolerance

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