Department of Radiation Oncology, Zhongshan Hospital, Fudan University Zhao-Chong Zeng

1. RT for HCC, sunrising orRT for HCC, sunrising or
sunset?sunset?
Zeng.zhaochong@zs-hospital.sh.cnZeng.zhaochong@zs-hospital.sh.cn
Department of Radiation Oncology,
Zhongshan Hospital, Fudan University
Zhao-Chong Zeng

2. Asia-Pacific regionAsia-Pacific region ChinaChina KoreaKorea
SorafenibSorafenib PlaceboPlacebo RTRT RTRT
IntrahepaticIntrahepatic++TACETACE 29.7 (29.7 (Ø≤Ø≤7cm)7cm) 1
＞＞ 29.7 (29.7 (Ø≤Ø≤7cm)7cm) 1 25.8 3 32 ((ØØ 5-7cm)5-7cm) 4
Vascular InvasionVascular Invasion 5.65.6 2
4.14.1 2
9.79.7 5
11.611.6 6
Lung Mt.Lung Mt. 5.65.6 2
4.24.2 2
16.716.7 7
12.312.3 8
Lymph node Mt.Lymph node Mt. 5.65.6 2
3.23.2 2
7.97.9 9
1010 10
Comparison btw Sorafenib and RT for intermediate/advanced HCCComparison btw Sorafenib and RT for intermediate/advanced HCC
References:
1 Eur J Cancer 2011;47:2117
2 Eur J Cancer 2012;48(10):1452-65.
3 IJRBP 2011;81(S2):352
4 Liver Int 2005;25:1189
55 Cancer SCI 2008;99:2510Cancer SCI 2008;99:2510
6.6. J Korean Med Sci 2011;26:1011J Korean Med Sci 2011;26:1011
7.7. Clin Exp MetastasesClin Exp Metastases 2012;29:197
8. IJRBP 2009;74:412
9. IJRBP 2005;63:1067
10.10. IJROBP 2010;78:729IJROBP 2010;78:729

3. Eur J CancerEur J Cancer 2012;48(10):1452-65

4. 281 HCC with PVT treated with conventional RT281 HCC with PVT treated with conventional RT
Korean Academy Medical Sci 2011;26:1014Korean Academy Medical Sci 2011;26:1014

5. Comparison of cost-efficient btw. Sorafenib & RT
Sorafenib EBRT
Survival prolong 1.5 months 7.4 months
Cost for survival
benefit per-month
29, 866$ 2,297$
Level of EBM A C
It is very important to do the RCT for HCC using EBRT
Sorafenib: 8,000$/per monthSorafenib: 8,000$/per month××5.6 months=44,800$5.6 months=44,800$
5.6-4.1=1.5 months prolong survival. 44,800$/1.5=29,866$/per mo.5.6-4.1=1.5 months prolong survival. 44,800$/1.5=29,866$/per mo.
RT: 11.6-4.2 =7.4 months prolong survival. 17,000$/7.4=2,297$/per mo.RT: 11.6-4.2 =7.4 months prolong survival. 17,000$/7.4=2,297$/per mo.

8. Only 1 onging trialOnly 1 onging trial

9. Lancet Oncol. 2009 Jan;10(1):25-34.Lancet Oncol. 2009 Jan;10(1):25-34.
N Engl J Med. 2008 Jul 24;359(4):378-90.N Engl J Med. 2008 Jul 24;359(4):378-90.
312 clinical trials312 clinical trials
Siemens
Varian
Elekta
Clinical Trial of RT for HCC: only 1
supported by Bayer.
Sharp TrialSharp Trial
Oriental TrialOriental Trial
One boy is a boy, two boys half boy, three boys no boyOne boy is a boy, two boys half boy, three boys no boy

10. Clinical practice in RT for HCCClinical practice in RT for HCC
1.1. SBRT for Early stage HCCSBRT for Early stage HCC
2.2. Helical Tomotherapy (HT) for confined butHelical Tomotherapy (HT) for confined but
unresectalbe HCCunresectalbe HCC
3.3. HT improves long-term survival via increasedHT improves long-term survival via increased
dose without increase toxicity for HCC withdose without increase toxicity for HCC with
macrovascular invasionmacrovascular invasion

11. A B
C D

12. Liver
SC
G
lK
rK
PTV

13. B
C D
A

14. Clinical practice in RT for HCCClinical practice in RT for HCC
1.1. SBRT for Early stage HCCSBRT for Early stage HCC
2.2. Helical Tomotherapy (HT) for confined butHelical Tomotherapy (HT) for confined but
unresectable HCCunresectable HCC
3.3. HT improves long-term survival via increasedHT improves long-term survival via increased
dose without increase toxicity for HCC withdose without increase toxicity for HCC with
macrovascular invasionmacrovascular invasion

15. A B
C D
Followup CT after TACE, poorer Lipidol deposit in the larger tumor. Better deposit in the
smaller satellite lesion.

16. LKidneyLKidney
R KidneyR Kidney GastricGastric
SCSC LiverLiver
PTVPTV
GastricGastric
GTV/GTV/CTVCTV
LiverLiver
KidneyKidney
SCSC
三 3DCRT ， GTV 60Gy conventional dose ， gastric 53Gy ， liver V35 40% 。 Palliative RT
HT ， GTV 59.5 Gy/17Fx ，≈ 76Gy Conventional dose ， gastric 23Gy ， liver V35 18% 。 Curable RT

17. 11-6-3 11-8-24AFP=205 AFP=50
AFP=8.0 11-12-2211-10-25
From palliative to cure——a great leapFrom palliative to cure——a great leap ！！

18. A B C D
E F G
Case 2. large and
multiple HCC in the
Right Lobe.

19. A B
C
2011-3-8 2011-3-8
2011-4-19 2011-6-1D E
Case 2

20. A B C D
E F G
Followup CT
after TACE on
2011-7-19

22. Followup CT
after HT on
2011-11-17 (3 M
later)

24. Followup MRI on
2012-4-10

25. 2011-3-4 2011-7-19 2011-10-19
2011-11-17 2012-4-10
Proliferation of left Lob during therapies

26. Clinical practice in RT for HCC
1. SBRT for Early stage HCC
2. Helical Tomotherapy (HT) for confined
but unresectalbe HCC
3. HT improves long-term survival via
increased dose without increase toxicity
for HCC with macrovascular invasion

27. 2012-2-7
Case 1. A huge tumor located in the left lobe and adhered with stomach.Case 1. A huge tumor located in the left lobe and adhered with stomach.
2012-2-7

28. TPS in TomoTPS in Tomo
2.8Gy/20Fx2.8Gy/20Fx

29. PTVPTV
PTVPTV
stomach
SmallbowelLiver
Min. Max. Mean
PTV 3DCR
T
48.3 66.9 58.0
Tomo 43.2 59.0 57.1
Liver-
PTV
3DCR
T
0.45 66.9 17.3
Tomo 1.7 58.0 13.6
Stomac
h
3DCR
T
5.2 59.1 42.3
Tomo 8.2 57.3 34.3
stomach 3DCRT TOMO
V50 28% 4.9%
V55 10.4% 0.45%
Comparison in DVHComparison in DVH
bwt 3DCRT & Tomobwt 3DCRT & Tomo
PTVPTV
stomachstomach
SmallbowelSmallbowel
LiverLiver
Spinal cordSpinal cord
Left kidneyLeft kidney
Right kidneyRight kidney

30. 2012-4-10
2012-2-7
Intrahepatic tumorIntrahepatic tumor
response toresponse to
TomotherapyTomotherapy
A huge tumor located inA huge tumor located in
the left lobe and adheredthe left lobe and adhered
with stomach. Afterwith stomach. After
treated with HT, tumortreated with HT, tumor
responded to RT well inresponded to RT well in
the following CT or MRIthe following CT or MRI
at the completion afterat the completion after
1.5, 3 and 5 months.1.5, 3 and 5 months.
2012-5-22
2013-3-4

31. 2012-2-7
2012-4-10
2012-5-22
PVT response toPVT response to
Tomotherapy inTomotherapy in
following imagingsfollowing imagings
2013-3-4

32. www.nordridesign.com
Case 2Case 2 ：： IVC tumorIVC tumor
thrombi + Intrahepaticthrombi + Intrahepatic
T.T.
From Palliative to CureFrom Palliative to Cure

33. www.nordridesign.com

34. www.nordridesign.com
11-10-14
11-6-28
AFP declined from 309 to 8μg/L

35. www.nordridesign.com
PTV
PTV
liverSpinal cord
heart
liverheartSpinal cord
Min. Ma
x.
Mea
n
PTV 3DC
RT
50.9 59.
2
54.8
Tom
o
48.8 58.
0
55.6
Liver-
PTV
3DC
RT
0 58.
4
21.1
Tom
o
0.47 57.
2
17.6
Spina
l
Cord
3DC
RT
0.6 48.
7
18.5
Tom
o
1.35 28.
4
15.1
Heart 3DC
RT
0.9 58.
3
18.4
Tom
o
2.14 57.
2
20.2
TomoTomo
3DCRT3DCRT

36. VariablesVariables 3D-CRT(n=50)3D-CRT(n=50) HT(n=34)HT(n=34) P-valuesP-values
Age(yr) Average 53.56 ± 11.88 53.79 ± 12.36 0.931
Gender
Female 2 3
0.359
Male 48 31
HBsAg
Negative 7 2
0.238
Positive 43 32
KPS
70 1 2
0.268
0.268
80 28 13
90 20 19
100 1 0
AFP status (µg/L)
≤20 17 9
0.518
>20 33 24
Child-Pugh classification
A 48 33
0.797
B 2 1
Max. diameter of intrahepatic tumors Average (cm) 8.89 ± 5.36 7.78 ± 3.34 0.298
Intrahepatic tumor number
Solitary 30 15
0.152
Multiple 20 19
Thrombus location
PV trunk 21 15
0.929
PV branch 18 12
IVC 8 6
IVC + PV 3 1
Volume of normal liver Average (mm3
) 1079.48 ± 397.48 1028.36 ± 258.76 0.511
Baseline characteristics in 84 HCC patients with tumor thrombi who received 3D-CRT or HTBaseline characteristics in 84 HCC patients with tumor thrombi who received 3D-CRT or HT

37. Variables 3D-CRT (n=50) HT (n=34) P-values
Radiation Dose (Gy)
Total 50.54 ± 7. 93 57.79 ±6.51 <0.01
BED* 59.44 ±7.76 71.83 ± 9.88 0.011
Dose of normal liver
Mean (Gy) 20.77 ± 4.44 22.41 ± 4.31 0.098
V5 (%) 69.28 ± 15.57 83.21 ± 14.45 <0.01
V10(%) 60.98 ± 15.59 66.53 ± 15.80 0.118
V15(%) 51.17 ± 14.29 55.21 ± 13.75 0.204
V20(%) 43.98 ± 12.85 44.64 ± 11.00 0.810
V30(%) 31.88 ± 10.91 31.35 ± 10.04 0.823
Intrahepatic tumor control after
EBRT
controlled 36(72.0%) 31(91.2%)
0.032
uncontrolled 14(28.0%) 3 (8.8%)
Tumor thrombus control after EBRT
Response or stable 41(82.0%) 33(97.1%)
0.036
progressive 9(18.0%) 1(2.9%)
Toxicity
0 11(22%) 16(47.1%)
0.016I-II 39(78%) 18(52.9%)
III-IV 0 0
Overall radiation fractions Average 25.48±3.80 19.44±4.09 <0.010
Overall survival Median 10.5 13.4
Effect and toxicity of EBRT in 84 HCC patients with macrovascular invasionEffect and toxicity of EBRT in 84 HCC patients with macrovascular invasion
* BED=nd(1+d/* BED=nd(1+d/αα//ββ)) ;; αα//ββ=12 for HCC=12 for HCC

38. HT Median OS:13.4mHT Median OS:13.4m
3DCRT Median OS:10.5m3DCRT Median OS:10.5m

39. Conclusion
In comparison to 3D-CRT, HT improves the
therapy response and survival for HCC
with macrovascular invasion, which could
deliver higher dose in shorter therapy
period with acceptable toxicity.

40. Survival & Causes of death for
HCC with extrahepatic
metastases
Metastatic
sites
Overall Survival(mo) Cause of Liver
Failure
RT Non-RT
Lymph
node
8.9 1
3 1
61.5%61.5% 22
Lung 17 3
8 4
67.5%67.5% 44
Bone 7.4 5
88.5%88.5% 55
Adrenal 13.6 6
83.3%83.3% 661.1. IJROBP 2005;63:1067-76IJROBP 2005;63:1067-76
2.2. Clin Transl Oncol 2013;Feb.Clin Transl Oncol 2013;Feb.
3.3. Clin Exp Metastasis 2012;29:197-205Clin Exp Metastasis 2012;29:197-205
4.4.Hepatol Int 2008;2:237-43Hepatol Int 2008;2:237-43
5.5.Cancer 2009;115:2710-20Cancer 2009;115:2710-20
6.6.JJR under reviewJJR under review

41. Hereafter Clinical trials: Focus
on Intrahepatic tumors control
SBRT for early stage HCC
RT for confined intrahepatic HCC
RT for PV branches tumor thrombi

42. HCC
PS 0~2 PS 3~4
Child-Pugh A/B Child-Pugh C
PS
Liver function
Extrahepatic M - +
Vascular inv.
Intrahep. T
Tumor Size
- +
≤3cm ＞ 3cm
≥4 nodules2~3 nodules
Stage I IIa IIb IIIa IIIb IVbIVa
•Support
care
•Support
care
•LT
(UCSF)
•TACE
•RT
•+Sorafenib
•TACE
•resection
•+RF
•resection
•TACE
•LT
(UCSF)
•resection
•RF≤3cm
•LT
(UCSF)
Treatment
Choice
•TACE
•resection
•RT
•+sorafenib
Solitary
Do you believe it?
>65 ％ pt. Need RT

43. Now, no evident to supportNow, no evident to support
this’s sunrising. We do notthis’s sunrising. We do not
care this, please enjoycare this, please enjoy
beautiful sun scene in thisbeautiful sun scene in this
moment.moment.
Zeng.zhaochong@zs-hospital.sh.cnZeng.zhaochong@zs-hospital.sh.cn