rt for hcc, sunrising or sunset?
DESCRIPTION
Department of Radiation Oncology, Zhongshan Hospital, Fudan University Zhao-Chong ZengTRANSCRIPT
RT for HCC, sunrising or RT for HCC, sunrising or sunset?sunset?
Department of Radiation Oncology, Zhongshan Hospital, Fudan University
Zhao-Chong Zeng
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 ((Ø Ø 5-7cm) 5-7cm) 4
Vascular InvasionVascular Invasion 5.6 5.6 2 4.1 4.1 2 9.7 9.7 5 11.6 11.6 6
Lung Mt.Lung Mt. 5.6 5.6 2 4.2 4.2 2 16.7 16.7 7 12.3 12.3 8
Lymph node Mt.Lymph node Mt. 5.6 5.6 2 3.2 3.2 2 7.9 7.9 9 10 10 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;26:1011 J Korean Med Sci 2011;26:1011 7.7. Clin Exp Metastases Clin Exp Metastases 2012;29:1978. IJRBP 2009;74:412 9. IJRBP 2005;63:1067 10.10. IJROBP 2010;78:729IJROBP 2010;78:729
Eur J Cancer Eur J Cancer 2012;48(10):1452-65
281 HCC with PVT treated with conventional RT281 HCC with PVT treated with conventional RTKorean Academy Medical Sci 2011;26:1014Korean Academy Medical Sci 2011;26:1014
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.
Only 1 onging trialOnly 1 onging trial
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
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 but Helical Tomotherapy (HT) for confined but unresectalbe HCCunresectalbe HCC
3.3. HT improves long-term survival via increased HT improves long-term survival via increased dose without increase toxicity for HCC with dose without increase toxicity for HCC with macrovascular invasionmacrovascular invasion
A B
C D
Liver
SC
G
lK
rK
PTV
B
C D
A
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 but Helical Tomotherapy (HT) for confined but unresectable HCCunresectable HCC
3.3. HT improves long-term survival via increased HT improves long-term survival via increased dose without increase toxicity for HCC with dose without increase toxicity for HCC with macrovascular invasionmacrovascular invasion
A B
C D
Followup CT after TACE, poorer Lipidol deposit in the larger tumor. Better deposit in the smaller satellite lesion.
LKidneyLKidney
R KidneyR Kidney GastricGastricSCSC LiverLiver
PTVPTV
GastricGastric
GTV/GTV/CTVCTV
LiverLiverKidneyKidney
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
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 ！！
A B C D
E F G
Case 2. large and multiple HCC in the Right Lobe.
A B
C
2011-3-8 2011-3-8
2011-4-19 2011-6-1D E
Case 2
A B C D
E F G
Followup CT after TACE on 2011-7-19
Followup CT after HT on 2011-11-17 (3 M later)
Followup MRI on 2012-4-10
2011-3-4 2011-7-19 2011-10-19
2011-11-17 2012-4-10
Proliferation of left Lob during therapies
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
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
TPS in TomoTPS in Tomo2.8Gy/20Fx2.8Gy/20Fx
PTVPTV
PTVPTV
stomachSmallbowelLiver
Min. Max. Mean
PTV 3DCRT
48.3 66.9 58.0
Tomo 43.2 59.0 57.1
Liver-PTV
3DCRT
0.45 66.9 17.3
Tomo 1.7 58.0 13.6
Stomach
3DCRT
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 DVH Comparison in DVH bwt 3DCRT & Tomobwt 3DCRT & Tomo
PTVPTV
stomachstomachSmallbowelSmallbowel
LiverLiver
Spinal cordSpinal cord
Left kidneyLeft kidney
Right kidneyRight kidney
2012-4-10
2012-2-7
Intrahepatic tumor Intrahepatic tumor response to response to TomotherapyTomotherapyA huge tumor located in A huge tumor located in the left lobe and adhered the left lobe and adhered with stomach. After with stomach. After treated with HT, tumor treated with HT, tumor responded to RT well in responded to RT well in the following CT or MRI the following CT or MRI at the completion after at the completion after 1.5, 3 and 5 months. 1.5, 3 and 5 months.
2012-5-22
2013-3-4
2012-2-7
2012-4-10
2012-5-22
PVT response to PVT response to Tomotherapy in Tomotherapy in following imagingsfollowing imagings
2013-3-4
www.nordridesign.com
Case 2Case 2 ：： IVC tumor IVC tumor thrombi + Intrahepatic thrombi + Intrahepatic T.T.
From Palliative to CureFrom Palliative to Cure
www.nordridesign.com
www.nordridesign.com
11-10-14
11-6-28
AFP declined from 309 to 8μg/L
www.nordridesign.com
PTV
PTV
liverSpinal cordheart
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
0.4
7
57.
2
17.
6
Spin
al
Cord
3DC
RT
0.6 48.
7
18.
5
Tom
o
1.3
5
28.
4
15.
1
Hear
t
3DC
RT
0.9 58.
3
18.
4
Tom
o
2.1
4
57.
2
20.
2
TomoTomo
3DCRT3DCRT
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
GenderFemale 2 3
0.359Male 48 31
HBsAgNegative 7 2
0.238Positive 43 32
KPS
70 1 2
0.2680.268
80 28 13
90 20 19
100 1 0
AFP status (µg/L)≤20 17 9
0.518>20 33 24
Child-Pugh classificationA 48 33
0.797B 2 1
Max. diameter of intrahepatic tumors Average (cm) 8.89 ± 5.36 7.78 ± 3.34 0.298
Intrahepatic tumor numberSolitary 30 15
0.152Multiple 20 19
Thrombus location
PV trunk 21 15
0.929PV 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
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
HT Median OS:13.4mHT Median OS:13.4m
3DCRT Median OS:10.5m3DCRT Median OS:10.5m
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.
Survival & Causes of death for HCC with extrahepatic
metastasesMetastatic sites
Overall Survival(mo)
Cause of Liver FailureRT 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% 66
1.1. IJROBP 2005;63:1067-76IJROBP 2005;63:1067-762.2. 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;2:237-435.5.Cancer 2009;115:2710-20Cancer 2009;115:2710-206.6.JJR under reviewJJR under review
Hereafter Clinical trials: Focus on Intrahepatic tumors
control
SBRT for early stage HCCRT for confined intrahepatic HCCRT for PV branches tumor thrombi
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
Now, no evident to support Now, no evident to support this’s sunrising. We do not this’s sunrising. We do not care this, please enjoy care this, please enjoy beautiful sun scene in this beautiful sun scene in this moment.moment.