Tianjin Medical University Cancer Institute & HospitalHuanhuXi Road, TiYuanBei, He Xi District, Tianjin 300060, PRCTel: +86-22-23340123 Fax: + 86-22-23341405 Web site: www.tmucih.org

STEREOTACTIC BODY RADIATION THERAPY USING CYBERKNIFE® FOR LIVER METASTASES:

A REPORT FROM TIANJIN CANCER INSTITUTE & HOSPITAL

Zhi-Yong Yuan, MD, PhDChun-Lei Liu, MD

Ma0-Bin Meng, MD, PhDCyberKnife Center, Department of Radiation Oncology,Tianjin Medical University Cancer Institute & Hospital

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Background

The liver is the second most common site for metastatic spread of cancer.

Surgical resection is currently considered as the first line measure for the treatment of liver metastatises (LM).

Hess KR, et al. Cancer 2006; 106: 1624-1633.

Timmerman RD, et al. CA Cancer J Clin 2009; 59: 145-170.

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Liver metastasis SBRT report

4Hoyer M, et al. Int J Radiation Oncology Biol Phys 2012; 82: 1047-1057

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Questions and Aims

The optimal dose and fractionation scheme has not yet been determined.

It is still unclear whether it is scientifically rigorous enough to recommend its routine use for curative treatment of LM.

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CyberKnife Treatment System

The present study is aimed at assessing the efficacy and safety of SBRT using CyberKnife on the treatment of LM, It is anticipated that this study will provide additional evidence for clinical practice.

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Inclusion Criteria The inclusion criteria were defined as follows:

Patients of any age; LM Disease confirmed cytologically, pathologically, or

diagnosed through imaging; Patients with KPS ≥ 70; Patients within ≤ 4 LMs and individual tumor diameter <

6 cm; Patient’s life expectancy >3 months; Patient unsuitable for or refractory to surgery and

received CyberKnife treatment; Bilirubin less than 3 mg/dl, albumin greater than 2.5 g/dl,

and serum liver enzymes less than twice the upper limit of normal range.

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The dose constraints of SBRT

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Follow-up and endpoints

The patients were observed at 1 month after completion of treatment, then every 3 months for the first year, and every 6 months thereafter until July 2012.

The primary endpoint was local control (LC)

OS, PFS, distant PFS (DPFS), and adverse events. Local control of LM was assessed at a minimum

of 6 months of follow-up after CyberKnife treatment in order to avoid uncertainty associated with early transient radiographic changes within the high-dose region.

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Patient characteristics

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Summary of SBRT parameters

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Treatment characteristics

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Follow-up patients

Prior to RT 5 Weeks 3 Months 6 Months 13 Months 18 Months 25 Months

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LC rate, PFS, and DPFS

1 year LC: 94.4%2 years LC: 89.7%

Median PFS: 12 monthsMedian DPFS: 37 months

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LC rate by subgroups

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Overall survival

Median OS: 37.5 months1 year OS: 68.6 months2 years OS: 55.9 months

Median OS for favorable patients : Not reachedMedian OS for non-favorable patients: 8.7 months

Note: The favorable patients were defined as primaries originating from colorectal, breast, and stomach cancers, and sarcomas.

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OS rate by subgroups

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Factors associated with OS

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Patterns of failure

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Toxicities The treatment was well tolerated by all patients;

the most common toxicities were grade 1 or 2 fatigue, nausea, vomiting, and changes in liver function tests, which were corrected by routine treatment.

None of the patients developed grade 3 or higher toxicity. In addition, no clinically significant changes were noted in liver function evaluations or physical examinations of LM patients.

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Discussion The RT strategies:

The type of RT should be determined according to the Barcelona Clinic Liver Cancer (BCLC) stage and liver function.

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Discussion The dose and fractionation scheme :

The prescribed dose and fractionation were specified according to lesion Location and Volume in this study.

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Discussion The optimal dose and fractionation scheme :

29 patients: 40 Gy/4f13 patients: 45 Gy/3fLC: 45Gy/3f > 40Gy/4f

Vautravers DC, et al. Int J Radiation Oncology Biol Phys 2011; 81: e39-47

LC: 60Gy/5f > 50Gy/5f >30Gy/3f

Rule WR, et al. Ann Surg Oncol 2011; 18: 1081-1087

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Discussion The BED correlative with LC:

Chang DT, et al. Cancer 2011; 117: 4060-4069

Median prescription dose: 41.7Gy (22-60)Median fractions: 6 fractions (1-6)

Lanciano R, et al. Fron Oncol 2012; 2: 1-8

Median prescription dose/fraction: 12GyMedian fractions: 3 fractions (3-5)

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Discussion The LC correlative with tumor volume:

13 patients: < 60 Gy/3f36 patients: = 60 Gy/3f

Rusthoven KE, et al. JCO 2009; 27: 1572-1578

Median prescription dose/fraction: 12GyMedian fractions: 3 fractions (3-5)

Lanciano R, et al. Fron Oncol 2012; 2: 1-8

≠

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Limitations This is a retrospective study. As record keeping

and bias may influence results, prospective studies of LM must be performed to confirm the efficacy and safety of SBRT with CyberKnife.

LC appears to be excellent with CyberKnife, however, our follow-up is short and the study included a heterogeneous group of patients with various primary tumors, previous treatments, and liver disease statuses, etc.

The optimal dose and fractionation scheme has not yet been determined. Despite these limitations, the study showed that SBRT using CyberKnife can improve LC as well as OS in patients with LM.

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Conclusions

SBRT with CyberKnife is an effective modality with good local control and acceptable toxicity for unresectable or medically inoperable LM.

Such studies will hopefully also help identify the subset of patients most likely to benefit from this therapy.

Further study: Guideline for the SBRT Dose-Fraction for Different Volume and Sites LM lesions (Large number cases and Muticenter needed)

THANKS

Tianjin Medical University Cancer Institute & Hospital

Radiation Oncologist ： Wang Ping, Song Yongchun, Zhuang Hongqing, Meng Maobing

Nerosurgeon ： Wang Xiaoguang, Liuqun

Thoracic Surgeon

Wang Changli, Zhang Zhenfa

Belly Surgeon:

Hao Jihui, Song Tianqiang

Physicist ：Li Fengtong, Dong Yong

TherapistWang Jingsheng, Chen Huaming

The TUMC Cyberknife Team

Acknowledgements F0unndations: NFSC (No. 81201754) and the

Cyberknife Foundation (No. 4-1-3).