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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 16 th International Congress on Neutron Capture Therapy (2014)
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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.

Jan 12, 2016

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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.

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: 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.

BNCT using BPA

made it possible to cure

skin malignant melanoma

without severe skin damage.

Page 3: 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.

89

Skin Mm 32    

H & N tumor 55

Mm 12

non-Mm 43

Other 2    

Case distribution of BNCT( 1987~ 2013)

Page 4: 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.

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: 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.

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: 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.

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: 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.

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: 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.

Tumor distance from skin surface (cm)

Page 9: 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.

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: 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.

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: 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.

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: 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.

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: 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.

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: 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.

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: 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.

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: 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.

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: 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.

Irradiation time :  42 minutes

Tumor doses = 23-35Gy-eq

Mucosal doses = 13Gy-eq

JRR-4

Page 18: 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.

3 months after BNCT 11 months after BNCT

CR for 8 years

Prior to BNCT

Page 19: 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.

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: 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.

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: 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.

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: 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.

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: 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.

T/N=5.2

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

37Gy-eq≦Tumor dose

Page 24: 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.

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

Page 25: 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.

Dose distribution in Tumor ( Gy-eq )

Page 26: 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.

Before BNCT 18 m. later

Page 27: 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.

Before BNCT 18 m. later

Page 28: 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.

18 months after BNCT

Page 29: 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.

2013.12.2  ( 2.5 y after BNCT )

Page 30: 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.

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: 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.

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: 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.

Thank you for your attention.

Seto Inland Sea, OKAYAMA, Japan.