任益民 Yee-Min Jen, MD, PhD Department of Radiation Oncology, Tri-Service General Hospital 國防醫學院三軍總醫院 放射腫瘤部 2013.5.31

1. 任益民 Yee-Min Jen, MD, PhD
Department of Radiation Oncology,
Tri-Service General Hospital
國防醫學院三軍總醫院
放射腫瘤部
2013.5.31
Stereotactic Ablative Radiotherapy
for Liver Cancer:
Report from Tri-Service General
Hospital, Taiwan

4. 國防醫學中心
National Defense Medical Center

5. 5
民國56年改制成立三軍總醫院
內湖國醫中心占地面積 43公頃
員工總數 3,239人
主治醫師 254人
護理人員 1,325人
專科數 26科
病床數 1,895床(含加護病房107床及特殊病床)
附設護理之家 228床
101年平均醫療服務量：
營業額 6.9億元/月
住院 4,015 人次/月
門診 6,092 人次/日
急診 304 人次/日

6. Stereotactic Body RT
versus ---
Blomgren H, Lax I, Naslund I, Svanstrom R.
Stereotactic high dose fraction radiation
therapy of extracranial tumors using an
accelerator: clinical experience of the first
thirty-one patients.
Acta Oncol 1995

7. SABR vs. SBRT
 Discov Med. 2010 May;9(48):411-7.
 Stereotactic body radiation therapy (stereotactic
ablative radiotherapy) for stage I non-small cell lung
cancer--updates of radiobiology, techniques, and
clinical outcomes.
 Hadziahmetovic M, Loo BW, Timmerman RD, Mayr
NA, Wang JZ, Huang Z, Grecula JC, Lo SS.
 Department of Radiation Oncology, Arthur G. James
Cancer Hospital, Ohio State University, Columbus,
OH 43210, USA.

8. 0
100
200
300
400
500
600
700
腦部 脊椎 鼻咽部 肝 肺 胰 腎臟 攝護腺 其他
CaseNumber
個案數
治療部位
Cyberknife Case Distribution, Tri-Service General Hospital
(2007/8-2013/4)
Brain Spinal cord NP Liver Lung Pancreas Kidney Prostate Others
Total: 1362, cranial= 696, body=666
248
209

9. EXPERIENCES USING SABR
AT TRI-SERVICE GENERAL
HOSPITAL, TAIPEI

10. 肝癌
LIVER CANCER

11. SABR OF LIVER CANCER
Fiducial CT sim SABR
GTV + 1-3 mm = PTV
10 Gy x 5 fractions
V15 of normal liver  700 ml
V20 of normal liver  30%
The dose was prescribed to the isodose
curve that encloses 100% of the GTV and
more than 95% of the PTV.
7 days 7-10 days

12. SABR IN RECURRENT LIVER CANCER

13. Before SABR After SABR

14. Before SABR 3 months after SABR
68 y/o male
a 2.3-cm recurrent tumor
Complete response after SBRT

18. Newly diagnosed HCC
2 years after subsequent hepatectomy with NED

19. Recurrent HCC
 2008.1 - 2009.12
 Study Group: 36 patients with 42 lesions
 Control Group: 138 patients with
recurrent HCC in Tri-Service General
Hospital with other or no treatments

20. Eligibility criteria
 Recurrence after prior treatment with
curative intent
 Unresectable or medically inoperable
 ECOG performance status of 0-2

21. 放療劑量
 Median does: 37 Gy (25-48 Gy)
 4-5 fractions in 4-5 consecutive working
days.

22. Tumor response
 41/42 lesions evaluable (One patient
died of brain metastasis before follow-up
study)
CR, 22%
PR, 37%
SD, 39%
PD, 2%

23. Local Control and Failure
 Local failure pattern
- in-field: 15%
- out-field: 56%
1-year in-field failure-free rate: 87.6%
2-year in-field failure-free rate: 75.1%

24. Acute Toxicities
 No grade 4-5 toxicity
 Most common sequelae - fatigue, anorexia
(56%)
 No SBRT interruption due to intolerable side
effects.
SBRT is tolerable.
Acute toxicities in patients undergoing SBRT
(N = 36)
Case No.
Gr. 1 Gr. 2 Gr. 3
Nausea/Vomiting 2 3 0
Anorexia 5 4 0
Abdominal pain 1 1 0
Gastric ulcer 0 1 1
Fatigue 12 1 0
Musculoskeletal 1 0 0

25. 三軍總醫院治療門靜脈栓塞經驗
TSGH Experience Treating
HCC with Portal Vein Thrombosis

26. PVT Result
 16 SBRT patients
 All patients completed planned
radiotherapy.
 No ≧Gr. 3 toxicity
 1 CR, 7 PR, 3 SD, 2 PD (3 no FU image)
 Median survival: 8.2 m

28. 立體定位放射治療用於原發肝癌
SABR for Primary Liver Cancer

29. PATIENTS
53 from June 2008 to June 2011 with 68
lesions
Unresectable or medically inoperable HCC,
patients
ECOG ≦2, Child-Pugh class A or B
Patients who had failed with TACE
or 17 patients with main portal vein thrombosis
which precluded TACE.

30. LOCAL CONTROL
The median follow-up period for all
patients was 13.1 months (range, 1-41
months) and for living patients 18.1
months ( range, 2-41 months ).
1- and 2-year in-field failure free rate
of 73.3% and 66.8% respectively.
 Out -field intra-hepatic recurrence
was the main cause of treatment
failure and occurred in 28/52 patients.

31. SURVIVAL
The 1- and 2- year OS was 70.1% and
45.4% respectively.

32. Acute toxicities in patients undergoing SABR (n = 53)
Toxicity
N0. of patients (%)
Grade 1 Grade 2 Total
Fatigue/Malaise 12 ( 22.6) 3 (5.7) 15 (28.3)
Nausea/vomiting 0 6 (11.3) 6(11.3)
Abdominal distension 2 (3.8) 0 2 (3.8)
Abdominal pain 2 (3.8) 1 (1.9) 3 (5.7)
Anorexia 3 (5.7) 3 (5.7) 6 (11.3)
Gastritis 0 1 (1.9) 1 (1.9)
Gastric ulcer
0 1 (1.9) 1(1.9)
Abbreviations: SABR, stereotactic ablative radiotherapy

33. Cyberknife Stereotactic
Radiosurgery for Other Cancers

34. 2012.11.16
Before SABR
2013.4.5
after SABR
Pancreas Cancer

35. HYPOXIA IN SABR
The presence of tumor hypoxia is a
major negative factor in limiting the
curability of tumors by SABR at
radiation doses that are tolerable to
surrounding normal tissues.
Brown M et al. Int J Radiat Oncol Biol Phys 78: 323-327, 2010

36. HYPOXIA IN SABR
However, this could be overcome by
the addition of clinically tolerable
doses of the hypoxic cell
radiosensitizer etanidazole.
Brown M et al. Int J Radiat Oncol Biol Phys 78: 323-327, 2010

37. CONCLUSIONS
9-12 Gy x 5 fractions over 5 consecutive
days.
Cyberknife SABR is effective and very safe
for liver cancer.
Local recurrence is a problem.
Is hypoxic cell radiosensitizer worth a trial?

38. QUESTIONS
Patient selection
When should SABR be given to patients after
TACE?
What exactly is the optimal dose-fractionation?

39. THOUGHTS FOR THE FUTURE
Add thalidomide or nexavar after SABR
Nimorazole trial
Randomized clinical trial

40. 三總放腫與電腦刀團隊
Department of Radiation
Oncology & SRS Center

41. 祝
健康愉快