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)

BNCT using BPA

made it possible to cure

skin malignant melanoma

without severe skin damage.

89

Skin Mm 32 　 　

H & N tumor 55

Mm 12

non-Mm 43

Other 2 　 　

Case distribution of BNCT（ 1987～ 2013）

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 )

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)

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)

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)

Tumor distance from skin surface (cm)

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)

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

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%

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%

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

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

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

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

Irradiation time ：　 42 minutes

Tumor doses ＝ 23-35Gy-eq

Mucosal doses ＝ 13Gy-eq

JRR-4

3 months after BNCT 11 months after BNCT

CR for 8 years

Prior to BNCT

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

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

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

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

T/N=5.2

59 years old （ Female ）　 Malignant melanoma 　（ before BNCT ）

37Gy-eq≦Tumor dose

8 m. later 11 m. 13 m. 18 m.

Dose distribution in Tumor （ Gy-eq )

Before BNCT 18 m. later

Before BNCT 18 m. later

18 months after BNCT

2013.12.2 　（ 2.5 y after BNCT )

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

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.

Thank you for your attention.

Seto Inland Sea, OKAYAMA, Japan.