This document summarizes research on using CyberKnife and TomoTherapy for treating liver cancer. It discusses studies from Korea, Taiwan, China, Belgium, and the US on using these technologies for inoperable primary or recurrent hepatocellular carcinoma and liver metastases. Key findings included high response rates and local control. Current research interests discussed standardizing treatment protocols and criteria across countries through guidelines. Future directions may involve regional collaboration on studies to further optimize these radiotherapy approaches for liver cancer.

1. 1
Research Discussion
Moderated by : Professor Jinsil Seong

2. 22
What has been published?

3. 3
CyberKnife for Liver Cancer
Inoperable primary hepatocellular carcinoma
Combined with transarterial chemoembolization (TACE)1
As sole treatment when other local therapies not indicated2
For recurrences3
Cholangiocarcinoma in combination with chemotherapy4
As a bridge to transplant7
Liver metastases
From various primary tumors5
In patients treated multiple times6
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1Choi et al. BMC Cancer 2008;8:351.
2Louis et al. Technol Cancer Res Treat 2010;9:479-487.
3Huang et al. International journal of radiation oncology, biology, physics 2012;84:355-361.
4Park et al. Gut Liver 2010;4:103-105.
5Ambrosino et al. Anticancer Res 2009;29:3381-3384.
6Lanciano et al. Front Oncol 2012;2:23.
7O’Connor et al. Liver Transplant, 2012 Aug;18(8):949-54.

4. 4
CyberKnife for Liver Cancer
 Korea institute of Radiological and Medical Science
SBRT for inoperable HCC as a salvage after incomplete TACE
 Retrospective
 2008-2011, 50 patients (C-P A/B, tumor <10cm, 1-5 TACE before RT)
 Median prescribed dose: 57 Gy in 3 fractions (range, 42-60 Gy)
 Response rate at 6 mo: 76.6% (CR in 38.3%, PR in 38.3%)
 2 Y LC: 94.6%, 2 Y OS: 68.7%
Korea
Kang et al. Cancer. 2012;118:5424-31.
Kwon et al. BMC Cancer. 2010 Sep 3;10:475
 The Catholic Univ. of Korea
Long term effect of SBRT for HCC ineligible for local treatment
 Retrospective
 2004-2007, 42 patients (C-P A/B, tumor <100 cc, without PVTT)
 Median prescribed dose: 33 Gy in 3 fractions (range, 30-39 Gy)
 In-field response rate at 1 mo: 85.8% (CR in 59.6%, PR in 26.2%)
 1Y OS: 92.9%, 3Y OS: 58.6%

5. 5
CyberKnife for Liver Cancer
 National Defense Medical Center
SBRT for inoperable recurrent HCC
 Retrospective
 2008-2009, 36 patients (recurrent tumor after curative treatment)
 Median prescribed dose: 37 Gy in 4-5 fractions (range, 25-48 Gy)
 Response rate: 58.6% (CR in 22%, PR in 36.6%)
 2Y OS: 64%
 Matched-pair analysis with 138 patients given other or no treatment
- 2Y OS: 72.6% in SBRT group, 42.1% in control group (p=0.013)
 National Defense Medical Center
SBRT or 3DRT for PVTT in HCC patients
 Prospective
 2002-2004, 43 patients (22 in SBRT group, 21 in 3DRT group)
 Median prescribed dose- SBRT: 45 Gy in 15 fractions/ 3DRT: 45 Gy in 25 fractions
 Response rate: 79% (CR in 7%, PR in 71%)
 1Y OS: 100% in CR, 56% in PR
Taiwan
Huang et al. IJROBP 2012 Oct 1;84(2):355-61
Lin CS et al. JJCO 2006 Apr;36(4):212-7

6. 6
CyberKnife for Liver Cancer
 Tianjin Cancer Hospital
Radiosurgery for primary HCC
 Retrospective
 2006-2008, 17 patients (stage I-III, 12 patients received local treatment)
 Median prescribed dose: 45 Gy in 3-8 fractions (range, 39-52 Gy)
 Response rate: 100%
China
Liu et al. Zhonghua Zhong Liu Za Zhi. 2010 Mar;32(3):229-33.

7. 7
CyberKnife for Liver Cancer
 University Hospital Domaine Universitaire Sart Tilman, Belgium
SBRT for inoperable HCC
 Retrospective
 25 patients (CP-A/B, single tumor)
 Median prescribed dose: 45 Gy in 3 fractions
 2Y local control: 95%
 1Y OS: 79%, 2Y OS: 52%
 Baylor Univ. Medical center Dallas, USA
Long-Term Outcomes of SBRT in HCC as a Bridge to Transplantation
 Retrospective
 2005-2010, 10 patients
 Median prescribed dose: 51 Gy in 3 fractions (range, 33-54 Gy)
 CR in 27%, 5Y OS & DFS: 100%
Europe / US
Louis et al. TCRT.Volume 9, Number 5, October 2010
Oconnor et al. Liver Transl 2012 Aug;18:949-954

8. 8
CyberKnife for Liver Cancer
 Indiana Univ. School of Medicine, USA
Phase I feasibility trial of SBRT for HCC
 Prospective, Dose escalation
 21 patients (CP-A/B, tumor ≤ 6 cm)
 Protocol scheme:
36 Gy in 3 fractions > planned escalation until reaching MTD
 2Y local control: 100%, 1Y OS: 75%, 2Y OS: 60%
Europe / US
Price et al. Cancer. 2012 Jun 15;118(12):3191-8
Cardenes et al. Clin Transl Oncol. 2010 Mar;12(3):218-25
 Indiana Univ. School of Medicine, USA
Radiosurgery for primary HCC
 Retrospective
 2006-2008, 17 patients (stage I-III, 12 patients received local treatment)
 Median prescribed dose: 45 Gy in 3-8 fractions (range, 39-52 Gy)
 Response rate: 100%

9. 9
CyberKnife for Liver Cancer
 Centre Oscar Lambret, Lille, France
IG-IMRT for unresectable liver metastasis
 Retrospective
 2007-2009, 42 patients
 Median prescribed dose: 40 Gy in 4 fractions/45 Gy in 3 fractions
 1Y LC: 90%, 2Y LC: 86%
 1Y OS: 94%, 2Y OS: 48%
Europe / US
Vautraver et al. IJROBP 2011 Nov 1;81:39-47

10. 10
TomoTherapy for Liver Cancer
• Locally advanced
• Large lesions
• Multiple lesions
• Liver metastases
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11. 11
TomoTherapy for Liver Cancer
 The Catholic Univ. of Korea
Simultaneous multi-target RT for HCC with multiple extrahepatic mets
 Retrospective
 42 patients (152 intra and extrahepatic metastases)
 Median prescribed dose: 33 Gy in 3 fractions (range, 30-39 Gy)
 In-field response rate at 1 mo: 85.8% (CR in 59.6%, PR in 26.2%)
 1Y OS: 92.9%, 3Y OS: 58.6%
 Yonsei Univ. of Korea
Optimal RT technique for locally advanced HCC
 2006-2007, 12 patients, 60 Gy in 30 fractions
 Comparison of plans(3D-CRT, linac-based IMRT and helical tomotherapy)
 Lower irradiated liver volume at 40, 50 and 60 Gy
 Superior tumor coverage
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Korea
Jang et al. IJROBP 2009 Nov 1;81:39-47
Lee et al. JJCO. 2011 Jul;41(7):882-9

12. 12
TomoTherapy for Liver Cancer
 Shin-Kong Memorial Hospital, National Yang-Ming University
Angiogenic blockade and RT in HCC
 Retrospective
 2007-2008, 23 patients, RT + sunitinib
 Median prescribed dose: 52.5 Gy in 15 fractions
 Response rate: 74%
 1Y OS: 70%
 Vrije Univ. Brussel, Belgium
Phase II study in the multidisciplinary Tx of oligometastatic CRC
 24 patients(≤ 5 metastases, in lung, liver, LN)
 Median prescribed dose: 50 Gy in 5 fractions
 Response rate in metastatic lesion: 55%
 1Y LC: 54%, 1Y PFS: 14%, 1Y OS: 78%
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Chi et al. IJROBP. 2010 Sep 1;78(1):188-93
Engels B et al. Radiation Oncology. 2012 Mar 16;7:34

13. 1313
Current Research Interests?

14. 14
HCC studies and protocols
 Korea CK
 led by Kim of Korea Cancer Center Hospital, multi-institution studies
 Incomplete response after TACE? Sample size?
 60Gy in 3?
 2-year local control, OS?
 Taiwan CK
 led by Ren of Tri-Service General Hospital, Taiwan, multi-institution studies
 TACE ineffective or unsuitable, sample size 150
 Randomized, arm A – SABR and/or Thalidomide/Sorafenib, 4.5-6.5 per faction, 1F
per day, 10 fractions, total 45-60Gy; arm B – TACE and/or Thalidomide/Sorafenib or
observation
 Safety profile, local control and PFS, OS in two years
 China CK
 led by Song of Tianjin Cancer Hospital, multi-institution studies
 Naïve patients, sample size 100
 45Gy in 3
 OS at 1 and 2-year; local control, PFS and acute and late toxicities
 Korea TT
 led by Seong of Yonsei University Medical College
 9-13Gy x 4f

15. 1515
Future Research Direction?

16. 16
Standardizing protocol?
Criteria in selecting the patients?
Impact of target delineation strategies?
Dose and fractionation scheme?
The treatment margins for CK or TT?
Ways of image guidance and motion management?
How can we connect the guidelines to medical
associations in different countries?
SBRT (CyberKnife) and IG-IMRT (TomoTherapy)
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17. 17
Future Research and Regional Synergy
Future research areas/direction?
Possible regional collaboration ?
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