Research Discussion

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Research Discussion Moderated by : Professor Jinsil Seong

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What has been published?

3#XXXXXXX — Company Confidential

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 metastasesFrom various primary tumors5

In patients treated multiple times61Choi 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.

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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%

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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

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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.

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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

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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%

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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


TomoTherapy for Liver Cancer

• Locally advanced• Large lesions• Multiple lesions • Liver metastases



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

Korea

Jang et al. IJROBP 2009 Nov 1;81:39-47

Lee et al. JJCO. 2011 Jul;41(7):882-9



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%

Chi et al. IJROBP. 2010 Sep 1;78(1):188-93

Engels B et al. Radiation Oncology. 2012 Mar 16;7:34

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Current Research Interests?

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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

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Future Research Direction?


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)


Future Research and Regional Synergy

Future research areas/direction? Possible regional collaboration ?

Health & Medicine

Research Discussion