1. 03 Clinical results of Boron neutron capture therapy
2014/06/18
13:30-15:10 Parallel Clinical 1 (Pa C1)
Pörssisali 03
Clinical results of Boron neutron capture therapy
for the patients with malignant meningioma
Shinji Kawabata (Japan), et al.
Osaka Medical College, Department of Neurosurgery

2. Meningioma
Meningiomas are a diverse set of tumors arising from the meninges, the membranous layers surrounding the whole central nervous system.
These tumors are usually benign in nature; however, a small percentage are malignant.
Meningiomas can usually be surgically resected (partially removed) and result in a permanent cure if the tumor is superficial on the dural surface and easily accessible.

3. Malignant Meningioma 1-2% of all meningiomas WHO grade 3
80 % of the cases recurs within 5 years
Median TTP:２ years
PFS for 5 years even after GTR:39%
Uncontrollable tumors with modern treatment regimen.
Kaplan Myer の出典 3

4. 2014 Experiebce of BNCT in Osaka Medical College
Osaka Medical College, Neurosurgery
Experiebce of BNCT in Osaka Medical College
Total number of patients : 148
(BNCT: 167)
2002 ~ 2014; OMC
fresh
N = 64
Meningioma
N = 32
Female
N = 75
Glioma
N = 115
Male
N = 73
recurrent
N = 75

5. Our Challenge for MM with BNCT
Our initial chgallenge for MM with BNCT were already published in JNS and Neurosurgery, 2006 and 2007.
J Neurosurg 105: , 2006
Neurosurgery 61:82-91, 2007 5

6. 2014 Osaka Medical College, Neurosurgery Case Age/Sex PET (T/N)
Prior to BNCT
1st BNCT Dose
(Gy-Eq)
Max　 　　Min
BNCT (times) 1
Papillary 29 F
5.0
SRSx5, OPx3
93.9
39.7 3 2
Anaplastic 48
2.8
EBRT, SRS, OPx5
73.2
44.2 60 -　
SRS, OPx5
49.0
32.0 4 67 M
EBRT, OPx2
71.8
22.1 5 77
4.5
SRSx4, OPx3
86.0
37.2 6
Atypical 72
2.0
SRS, OPx2
65.6
19.0 7
Sarcoma 57
2.7
SRSx2, OPx4
48.3
14.3 8
Rabdoid 26 -
EBRT, OPx3
75.8
18.8 9 62
4.4
111.5
50.7 10 56
3.9
77.3
26.0 11 38
88.9
28.8 12
3.5
EBRT, OPx4
58.0 13 65
3.6
EBRT, SRSx2, OPx3
50.2
24.2 14 75
4.0
SRSx3, OPx1
72.9
42.3 15 79
3.7
SRT, OPx5
61.0
57.2 16 68
SRSx2, OPx2
67.0
52.0 17 49
SRS, OPx6
68.5
15.0 18 50
SRSx4, OP3
100.0
59.0 19 63
69.5
31.0 20 41
3.0
SRSx4, OPx5
80.2 21
anaplastic 69
6.3
SRSx2+1, OPx2
72.0
48.0 22 45
4.7
　78.4
30.0 23
SRSx1, OPx3
65.0　
50.0　 24
atypical 52
OPx2
62.0 25 66
2.4
SRSx2, OPx3
57.5
51.3
60.5
9.5 27 46
EBR, SRS, OPx3
37.0 28
SRS x 3, OP
SRS x 1, SRT x 4, OPx2
84.7
67.1 30
2.9
SRS, SRS, OPx3
53.0
45.0 31 64
4.3
SRS, EBRT
91.0
40.0
We treated 20 MM including 4 cases of atypical meningiomas. All cases received multiple operations and iiradiations prior to BNCT.

7. Absorbed Dose by BNCT in Case 1
2014
Osaka Medical College, Neurosurgery
Absorbed Dose by BNCT in Case 1 80 8 70 40 30 60 6 50 20 4 10 2
This is PC simulation of absorbed dose in case 1 for normal and tumor tissue, respectively.
You can see almost 9 times higher dose could be applied for the tumor in comparison with normal brain, by PC simulation.
Normal brain
Tumor tissue
9 times higher dose could be applied for the tumor
in comparison with normal brain 7

8. 2014 Dose- volume histogram analysis of BNCT
Osaka Medical College, Neurosurgery
Dose- volume histogram analysis of BNCT
(Case 1)
Also you can see very good dose volume histogram for this case by BNCT. 8

9. Effect of BNCT in Case 1　　　　　
1 week prior
To BNCT
65.6 cm3
2 weeks after
BNCT
49.0 cm3
4 months after
BNCT
25.4 cm3
This is effect of BNCT for case 1.
This is 1 week prior to BNCT. The tumor volume became double for one month, waiting for BNCT
This is 2 weeks after, and this is 4 month after BNCT.
You can see the rapid shrincage of the mass. One week after BNCT, she could walk again.
The tumor volume became double for one month, waiting for BNCT,
which induced hemiparesis. One week after BNCT, she could walk again. 9

10. Typical Shrinkage of the Mass by BNCT
18F-BPA PET
Treatment compound BPA is fluororide labelled and used as a tracer for PET imaging.
Good accumulation of the tracer ensures the promising effects of BNCT, prior to neutron irradiaion.
These are the typical shrinkage of the mass.
Ave. L/N = 3.8 (n=31) 10

11. 2014 Ave. tumor volume; 52.2 (+/-45.3) mL Tumor size after BNCT
Osaka Medical College, Neurosurgery
Tumor size after BNCT
BNCT
Ave. tumor volume;
52.2 (+/-45.3) mL
Tumor volume (% of control)
Each dot は何を示す？
Days after BNCT 11 11

12. Case 17 : Anaplastic meningioma
Pre-BNCT
This is case 17, anaplastic meningioma.
The upper is pre-BNCT and the lower shows 10 M after BNCT.
White arrows show the good tumor control.
１０M after
BNCT 12

13. Case 7: anaplastic meningioma with sarcomatous transform
Prior to BNCT
７M after BNCT
This is case 7, sarcoma transformed from anaplastic meninigioma.
This is pre-BNCT and this is 7 month after BNCT.
Red arrows show the drastic effects of BNCT.
But we lost the case by sysltemic metastasis in lung and lever.
７M after BNCT
Left :Chest XP
Rt.: abd CT
Systemic metastasis
to lung and lever 13

14. Case 8: Rhabdoid meningioma
3 wks prior to
BNCT
1 M after
BNCT
2 M after
BNCT
4 M after
BNCT
This is case 8 rhabdoid meninigioma.
These are Pre BNCT, 1 M after BNCT, 2 M after BNCT
These changes are pseudoprogression.
White arrow shows equivocal CE. Simultaneously cytology showed malignant cells in CSF.
We lost the case by CSF dissemination.
CSF
dissemination
Pseudoprogression
(enlargement on contrasted MRI) 14

15. Case 14: Atypical meningioma
Pre-BNCT
This is case 14 atypical meningioma.
These are PRE BNCT and 6M after BNCT.
Irradiated massed responded well, however, you can see the new lesion out of field of neutron irradiaion.
６M after
BNCT
Recurrence at the Out-of-the field of BNCT 15

16. 2014 Survival analysis (Kaplan-Meyer) Median survival 59.6 months
Osaka Medical College, Neurosurgery
Survival analysis (Kaplan-Meyer)
Median survival 59.6 months
(95%CI: 42.8 – 113.4) (after diagnosis)
<2-y 100, 3-y 79.2, 5-y 48.6>
Median survival 24.6 months
(95%CI: 12.9 – 44.0) (after BNCT)
<1-y 78.5, 2-y 45.8>
after BNCT
after diagnosis
Survival rate
Months after BNCT / diagnosis (m)

17. 2014 Osaka Medical College, Neurosurgery
Case
Age/Sex
PET
(T/N)
Depth
(mm)
　Longivity (M)
from
diag BNCT
Remarks 1
Papillary 29 F
5.0 39
44.2
22.4
metastasis 2
Anaplastic 48
2.8 59
43.2
14.1 3 60 - 49
32.4
12.9
Gastric Ca meta 4 67 M 70
70.7
13.1
Local 5 77
4.5
45.7
24.6
senility 6
Atypical 72
2.0 69
64.3
6.4 RN 7
Sarcoma 57
2.7 92
113.4
8.6 8
Rabdoid 26
3.1 66
30.4
7.3
dissemination 9 62
4.4
36.8
9.4 10 56
3.9 74
47.5
44.0
alive 11 38 68
28.3
12.4 12
3.5 54
56.8
55.6 13 65
3.6 64
59.6
40.4 14 75
4.0
12.3
16.1 15 79
3.7
12.8
8.3 16 45
69.1
15.0 17
22.1
15.6
Out of field 18 50 52
68.6
10.7 19 63 76
10.4 20 41
3.0
30.1 21
anaplastic
6.3
33.3
2.5 22
4.7
30.7
15.7 23
17.6
15.3 24
atypical 33
24.1
10.5 25
2.4 34 35
16.0 85
23.6
11.7 27 46
25.8
8.8 28
17.7
10.3 40
27.9 30
2.9
2.2 31
4.3
193.8
1.0
We lost one case by local tumor progression.
4 cases by systemic metastasis, 3 cases by CSF disseminarion and 1 case by recurrence at out of field irradiaation.
Local; Local recurrence, RN; radiation necrosis 17

18. 45F, anaplastic meningioma, WHO G3 (two-field irradiation)
700mglkg (200mg/kg/h x mg/kg/h x 3)
　　Malignant meningioma 　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　
Irrad
30+31 m
BPA (pre)
33.6
Ave.1, 2
34, 39
skin
6.0
brain
12.2
Optic N
>7.0
Tumor
70.0
4.0cm
51.0
11/ 8/2012
BNCT
T/N=4.7

19. 45F, anaplastic meningioma, WHO G3 (two-field irradiation)
700mglkg (200mg/kg/h x mg/kg/h x 3)
　　Malignant meningioma 　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　
Irrad
30+31 m
BPA (pre)
33.6
Ave.1, 2
34, 39
skin
6.0
brain
12.2
Optic N
>7.0
Tumor
70.0
4.0cm
51.0
11/ 5/2012
12/20/2012
11/ 8/2012
BNCT
Marked decrease in BPA uptake within 2months after BNCT
T/N=4.7

20. 2014 Conclusion Malignant meningioma is good candidate for BNCT.
Osaka Medical College, Neurosurgery
Conclusion
Malignant meningioma is good candidate for BNCT.
BNCT can reduce the tumor size and control MM locally, but not for systemic metastasis or recurrence from Out-of the field region.
Major causes of death are
Systemic metastasis
CSF dissemination
Recurrence at out of field of BNCT

21. Thank you Clinical results of Boron neutron capture therapy
for the patients with malignant meningioma
S. Kawabata1, S-I. Miyatake1, G. Futamura1, R. Hiramatsu1, Y. Matsushita1, M. Furuse1, Y. Tamura1, T. Kuroiwa1,
H. Tanaka2, Y. Sakurai2, S-I. Masunaga2, M. Suzuki2, K. Ono2
1Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan 2 Department of Radiation Life Science and Radiation Medical Science, Kyoto University Research Reactor Institute, Kumatori, Osaka, Japan