Page 1
Clinical results of BNCT
for Head and Neck melanoma
J. Hiratsuka, N.Kamitani, N.Morita T.Aihara, A.Maruhashi * and K.Ono *
Kawasaki Medical School*Research Reactor Institute, Kyoto University
16th International Congress on Neutron Capture Therapy (2014)
Page 2
BNCT using BPA
made it possible to cure
skin malignant melanoma
without severe skin damage.
Page 3
89
Skin Mm 32
H & N tumor 55
Mm 12
non-Mm 43
Other 2
Case distribution of BNCT( 1987~ 2013)
Page 4
Case NCT-no. Age Sex i-Stage BNCT site Primary/Meta at BNCT site Previous Tx
Tumor size
( cm )
Tumor distance from skin surface
(cm)
1 NCT-33 55 M T2N0M0 Nasal cavity Primary Op + Chem superficial 3
2 NCT-38 74 F T2N0M0 Nasal cavity Meta Op + chem superficial 4
3 NCT-39 66 M T1N2bM0 Neck Meta Op 2.5 * 3.0 3
4 NCT-40 74 M T1N0M0 Nasal cavity Primary _ superficial 2.5
5 NCT-42 71 F T4N0M0 Nasal cavity Primary Op + Chem 3.0 * 2.5 5
6 NCT-43 64 M T2N0M0 Nasal cavity Primary Op + Chem 1.5 * 0.5 6
7 NCT-44 69 M T4N0M0 Nasal cavity Primary Op + Chem 4.0 * 5.0 8
8 NCT-47 74 F T1N0M0 Nasal cavity Primary Op + Chem superficial 2
9 NCT-53 69 M T1N0M0 Nasal cavity Primary Op + Chem 1.0 * 1.5 3.5
10 NCT-55 72 M TxN2aM0 Neck Primary _ 2.0 * 2.0 3
11 NCT-68 59 F T1N0M0 Neck Meta Op + Chem 10.0 * 8.0 6
12 NCT-79 37 M T1N0M0 Neck Meta Chem 21.0 * 18.0 10
Head & Neck Melanoma cases ( 2005 - 2013 )
Page 5
Case NCT-no. Age Sex i-Stage BNCT site Primary/Meta at BNCT site Previous Tx
Tumor size
( cm )
Tumor distance from skin surface
(cm)
1 NCT-33 55 M T2N0M0 Nasal cavity Primary Op + Chem superficial 3
2 NCT-38 74 F T2N0M0 Nasal cavity Meta Op + chem superficial 4
3 NCT-39 66 M T1N2bM0 Neck Meta Op 2.5 * 3.0 3
4 NCT-40 74 M T1N0M0 Nasal cavity Primary _ superficial 2.5
5 NCT-42 71 F T4N0M0 Nasal cavity Primary Op + Chem 3.0 * 2.5 5
6 NCT-43 64 M T2N0M0 Nasal cavity Primary Op + Chem 1.5 * 0.5 6
7 NCT-44 69 M T4N0M0 Nasal cavity Primary Op + Chem 4.0 * 5.0 8
8 NCT-47 74 F T1N0M0 Nasal cavity Primary Op + Chem superficial 2
9 NCT-53 69 M T1N0M0 Nasal cavity Primary Op + Chem 1.0 * 1.5 3.5
10 NCT-55 72 M TxN2aM0 Neck Primary _ 2.0 * 2.0 3
11 NCT-68 59 F T1N0M0 Neck Meta Op + Chem 10.0 * 8.0 6
12 NCT-79 37 M T1N0M0 Neck Meta Chem 21.0 * 18.0 10
Head & Neck Melanoma cases (2005-2013)
Page 6
Case NCT-no. Age Sex i-Stage BNCT sitePrimary/Meta
at BNCT site
Previous TxTumor size
( cm )
Tumor distance from skin surface
(cm)
1 NCT-33 55 M T2N0M0 Nasal cavity Primary Op + Chem superficial 3
2 NCT-38 74 F T2N0M0 Nasal cavity Meta Op + chem superficial 4
3 NCT-39 66 M T1N2bM0 Neck Meta Op 2.5 * 3.0 3
4 NCT-40 74 M T1N0M0 Nasal cavity Primary _ superficial 2.5
5 NCT-42 71 F T4N0M0 Nasal cavity Primary Op + Chem 3.0 * 2.5 5
6 NCT-43 64 M T2N0M0 Nasal cavity Primary Op + Chem 1.5 * 0.5 6
7 NCT-44 69 M T4N0M0 Nasal cavity Primary Op + Chem 4.0 * 5.0 8
8 NCT-47 74 F T1N0M0 Nasal cavity Primary Op + Chem superficial 2
9 NCT-53 69 M T1N0M0 Nasal cavity Primary Op + Chem 1.0 * 1.5 3.5
10 NCT-55 72 M TxN2aM0 Neck Primary _ 2.0 * 2.0 3
11 NCT-68 59 F T1N0M0 Neck Meta Op + Chem 10.0 * 8.0 6
12 NCT-79 37 M T1N0M0 Neck Meta Chem 21.0 * 18.0 10
Head & Neck Melanoma cases (2005-2013)
Page 7
Case NCT-no. Age Sex i-Stage BNCT site Primary/Meta at BNCT site Previous Tx
Tumor size
( cm )
Tumor distance from skin surface
(cm)
1 NCT-33 55 M T2N0M0 Nasal cavity Primary Op + Chem superficial 3
2 NCT-38 74 F T2N0M0 Nasal cavity Meta Op + chem superficial 4
3 NCT-39 66 M T1N2bM0 Neck Meta Op 2.5 * 3.0 3
4 NCT-40 74 M T1N0M0 Nasal cavity Primary _ superficial 2.5
5 NCT-42 71 F T4N0M0 Nasal cavity Primary Op + Chem 3.0 * 2.5 5
6 NCT-43 64 M T2N0M0 Nasal cavity Primary Op + Chem 1.5 * 0.5 6
7 NCT-44 69 M T4N0M0 Nasal cavity Primary Op + Chem 4.0 * 5.0 8
8 NCT-47 74 F T1N0M0 Nasal cavity Primary Op + Chem superficial 2
9 NCT-53 69 M T1N0M0 Nasal cavity Primary Op + Chem 1.0 * 1.5 3.5
10 NCT-55 72 M TxN2aM0 Neck Primary _ 2.0 * 2.0 3
11 NCT-68 59 F T1N0M0 Neck Meta Op + Chem 10.0 * 8.0 6
12 NCT-79 37 M T1N0M0 Neck Meta Chem 21.0 * 18.0 10
Head & Neck Melanoma cases (2005-2013)
Page 8
Tumor distance from skin surface (cm)
Page 9
Case NCT-no. Age Sex i-Stage BNCT sitePrimary/Meta at BNCT
sitePrevious Tx
Tumor size
( cm )
Tumor distance from skin surface
(cm)
1 NCT-33 55 M T2N0M0 Nasal cavity Primary Op + Chem superficial 3
2 NCT-38 74 F T2N0M0 Nasal cavity Meta Op + chem superficial 4
3 NCT-39 66 M T1N2bM0 Neck Meta Op 2.5 * 3.0 3
4 NCT-40 74 M T1N0M0 Nasal cavity Primary _ superficial 2.5
5 NCT-42 71 F T4N0M0 Nasal cavity Primary Op + Chem 3.0 * 2.5 5
6 NCT-43 64 M T2N0M0 Nasal cavity Primary Op + Chem 1.5 * 0.5 6
7 NCT-44 69 M T4N0M0 Nasal cavity Primary Op + Chem 4.0 * 5.0 8
8 NCT-47 74 F T1N0M0 Nasal cavity Primary Op + Chem superficial 2
9 NCT-53 69 M T1N0M0 Nasal cavity Primary Op + Chem 1.0 * 1.5 3.5
10 NCT-55 72 M TxN2aM0 Neck Primary _ 2.0 * 2.0 3
11 NCT-68 59 F T1N0M0 Neck Meta Op + Chem 10.0 * 8.0 6
12 NCT-79 37 M T1N0M0 Neck Meta Chem 21.0 * 18.0 10
Head & Neck Melanoma cases (2005-2013)
Page 10
CaseBoron
(blood)BPA-PET T/N (B)
Tumor size ( cm )
Tumor dose (Min.) (Gy-eq)
Skin dose
(Max.)
(Gy-eq)
Local response
alive / death
1 25ppm _ 3 Superficial 23 11.9 CR alive
2 32ppm _ 3 Superficial 26.2 11 CR death
3 32ppm ○ 3 ≦ 5cm 28.1 8.2 CR death
4 25ppm _ 3 Superficial 25.2 13.4 PR death
5 24ppm ○ 3 ≦ 5cm 19 15 CR death
6 25ppm ○ 2.7 ≦ 5cm 21.1 15.8 PD death
7 27ppm ○ 3.7 ≦ 5cm 23.3 9.8 PD death
8 27ppm _ 3 Superficial 29.6 9.5 CR death
9 29ppm ○ 2.5 ≦ 5cm 27.2 16.6 CR death
10 24ppm ○ 3.1 ≦ 5cm 23.4 19 PR death
11 32ppm ○ 5 5cm ≦ 37 2.9 CR alive
12 25ppm ○ 6.9 5cm ≦ 24.5 3.8 PD death
Page 11
Survival Plot
0 1 2 3 4 5 6 7 8 9Time
0.0
0.2
0.4
0.6
0.8
1.0
Overall survival rate ( n=12)
( years )
5-year : 25%
Page 12
Survival Plot
0 1 2 3 4 5 6 7 8 9Time
0.0
0.2
0.4
0.6
0.8
1.0
Local relapse - free survival rate (n=12)
( years )
5-year : 54%
Page 13
Survival Plot
0 1 2 3 4 5 6 7 8 9Time
0.0
0.2
0.4
0.6
0.8
1.0
lh
DOSE
( years )
≧25Gy-eq (6)
≦25Gy-eq (6)
Local relapse - free survival rate according to min. tumor dose
Page 14
18 20 22 24 26 28 30 32 34 36 38
Tum
or d
istan
ce fr
om s
kin
surf
ace
10 cm
5 cm
Minimum tumor dose ( Gy-eq )
Non-CR CR
Page 15
18 20 22 24 26 28 30 32 34 36 38
Tum
or d
epth
from
ski
n su
rfac
e
10 cm
5 cm
Minimum tumor dose ( Gy-eq )
Non-CR CR
Page 16
Relapse findings
• 55 years old ( male )
• Malignant melanoma of the nasal cavity
• Relapse occurred 3 months after resection and chemotherapy • The T/N ratio was 3.0.
• October 2005: BNCT
Salvage BNCT --- NCT-33
septum
Page 17
Irradiation time : 42 minutes
Tumor doses = 23-35Gy-eq
Mucosal doses = 13Gy-eq
JRR-4
Page 18
3 months after BNCT 11 months after BNCT
CR for 8 years
Prior to BNCT
Page 19
18 20 22 24 26 28 30 32 34 36 38
Tum
or d
epth
from
ski
n su
rfac
e
10 cm
5 cm
Minimum tumor dose ( Gy-eq )
Non-CR CR
Page 20
Pre-BNCT
2 m later
NCT-44
Local response : PD
Dead of Mm 1 year later
3 m later5 m later
T/B=3.7
23.3Gy-eq≦Tumor dose
Page 21
18 20 22 24 26 28 30 32 34 36 38
Tum
or d
epth
from
ski
n su
rfac
e
10 cm
5 cm
Minimum tumor dose ( Gy-eq )
Non-CR CR
Page 22
Salvage BNCT--- 59Yo. Female
Local LN recurrent malignant melanoma after operation
(TxN1bM0, Stage BⅢ , amelanotic melanoma)
melanoma(?) resection LN recurrence resection recurrence rapid growth
NCT-68
Page 23
T/N=5.2
59 years old ( Female ) Malignant melanoma ( before BNCT )
37Gy-eq≦Tumor dose
Page 24
8 m. later 11 m. 13 m. 18 m.
Page 25
Dose distribution in Tumor ( Gy-eq )
Page 26
Before BNCT 18 m. later
Page 27
Before BNCT 18 m. later
Page 28
18 months after BNCT
Page 29
2013.12.2 ( 2.5 y after BNCT )
Page 30
18 20 22 24 26 28 30 32 34 36 38
Tum
or d
epth
from
ski
n su
rfac
e
10 cm
5 cm
Minimum tumor dose ( Gy-eq )
Non-CR CR
Page 31
Summary
We presented the latest clinical results of 12 patients with H & N melanoma treated by BNCT.
Almost all patients have been dead of local failure and distant metastases. In spite of continuous CR, some patients have been dead of systemic metastases.
Patients irradiated more than 25Gy-eq as minimum tumor dose tended to show good response ---- no statistically significant difference!
There is a strong possibility to achieve CR, if melanoma is irradiated more than 25Gy-eq and the tumor distance is less than 5cm.
Page 32
Thank you for your attention.
Seto Inland Sea, OKAYAMA, Japan.