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

國防醫學中心National Defense Medical Center

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

Stereotactic Body RTversus ---

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

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.

腦部 脊椎 鼻咽部 肝 肺 胰 腎臟 攝護腺 其他0

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200

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治療部位

Case N

um

ber

個案

數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

248209

EXPERIENCES USING SABR AT TRI-SERVICE GENERAL

HOSPITAL, TAIPEI

肝癌LIVER CANCER

SABR OF LIVER CANCER

Fiducial CT sim SABRGTV + 1-3 mm = PTV 10 Gy x 5 fractionsV15 of normal liver 700 mlV20 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

SABR IN RECURRENT LIVER CANCER

Before SABR After SABR

Before SABR 3 months after SABR

68 y/o malea 2.3-cm recurrent tumorComplete response after SBRT

Newly diagnosed HCC

2 years after subsequent hepatectomy with NED

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

Eligibility criteria Recurrence after prior treatment with

curative intent Unresectable or medically inoperable ECOG performance status of 0-2

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

days.

Tumor response

41/42 lesions evaluable (One patient died of brain metastasis before follow-up study)

CR, 22%

PR, 37%

SD, 39%

PD, 2%

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%

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

三軍總醫院治療門靜脈栓塞經驗TSGH Experience Treating

HCC with Portal Vein Thrombosis

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

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

PATIENTS

53 from June 2008 to June 2011 with 68 lesions

Unresectable or medically inoperable HCC, patients

ECOG ≦2, Child-Pugh class A or BPatients who had failed with TACE

or 17 patients with main portal vein thrombosis which precluded TACE.

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.

SURVIVAL

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

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

Cyberknife Stereotactic Radiosurgery for Other Cancers

2012.11.16Before SABR

2013.4.5after SABR

Pancreas Cancer

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

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

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?

QUESTIONS

Patient selectionWhen should SABR be given to patients

after TACE?What exactly is the optimal dose-

fractionation?

THOUGHTS FOR THE FUTURE

Add thalidomide or nexavar after SABRNimorazole trialRandomized clinical trial

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

祝健康愉快