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 16 th International Congress on Neutron Capture Therapy (2014)

2. BNCT using BPA made it possible to cure skin malignant melanoma without severe skin damage.

3. 89 Skin Mm32 H & N tumor55 Mm12 non-Mm43 Other2 Case distribution of BNCT （ 1987 ～ 2013 ）

4. CaseNCT-no.AgeSexi-StageBNCT site Primary/Meta at BNCT site Previous Tx Tumor size （ cm ） Tumor distance from skin surface (cm) 1NCT-3355 Ｍ T2N0M0Nasal cavityPrimaryOp + Chemsuperficial3 2NCT-3874 Ｆ T2N0M0Nasal cavityMetaOp + chemsuperficial4 3NCT-3966MT1N2bM0NeckMetaOp2.5 * 3.03 4NCT-4074MT1N0M0Nasal cavityPrimary ＿ superficial2.5 5NCT-4271 Ｆ T4N0M0Nasal cavityPrimaryOp + Chem3.0 * 2.55 6NCT-4364MT2N0M0Nasal cavityPrimaryOp + Chem1.5 * 0.56 7NCT-4469MT4N0M0Nasal cavityPrimaryOp + Chem4.0 * 5.08 8NCT-4774 Ｆ T1N0M0Nasal cavityPrimaryOp + Chemsuperficial2 9NCT-5369MT1N0M0Nasal cavityPrimaryOp + Chem1.0 * 1.53.5 10NCT-5572MTxN2aM0NeckPrimary ＿ 2.0 * 2.03 11NCT-6859 Ｆ T1N0M0NeckMetaOp + Chem10.0 * 8.06 12NCT-7937MT1N0M0NeckMetaChem21.0 * 18.010 Head & Neck Melanoma cases ( 2005 - 2013 )

5. CaseNCT-no.AgeSexi-StageBNCT site Primary/Meta at BNCT site Previous Tx Tumor size （ cm ） Tumor distance from skin surface (cm) 1NCT-3355 Ｍ T2N0M0Nasal cavityPrimaryOp + Chemsuperficial3 2NCT-3874 Ｆ T2N0M0Nasal cavityMetaOp + chemsuperficial4 3NCT-3966MT1N2bM0NeckMetaOp2.5 * 3.03 4NCT-4074MT1N0M0Nasal cavityPrimary ＿ superficial2.5 5NCT-4271 Ｆ T4N0M0Nasal cavityPrimaryOp + Chem3.0 * 2.55 6NCT-4364MT2N0M0Nasal cavityPrimaryOp + Chem1.5 * 0.56 7NCT-4469MT4N0M0Nasal cavityPrimaryOp + Chem4.0 * 5.08 8NCT-4774 Ｆ T1N0M0Nasal cavityPrimaryOp + Chemsuperficial2 9NCT-5369MT1N0M0Nasal cavityPrimaryOp + Chem1.0 * 1.53.5 10NCT-5572MTxN2aM0NeckPrimary ＿ 2.0 * 2.03 11NCT-6859 Ｆ T1N0M0NeckMetaOp + Chem10.0 * 8.06 12NCT-7937MT1N0M0NeckMetaChem21.0 * 18.010 Head & Neck Melanoma cases (2005-2013)

6. CaseNCT-no.AgeSexi-StageBNCT site Primary/Meta at BNCT site Previous Tx Tumor size （ cm ） Tumor distance from skin surface (cm) 1NCT-3355 Ｍ T2N0M0Nasal cavityPrimaryOp + Chemsuperficial3 2NCT-3874 Ｆ T2N0M0Nasal cavityMetaOp + chemsuperficial4 3NCT-3966MT1N2bM0NeckMetaOp2.5 * 3.03 4NCT-4074MT1N0M0Nasal cavityPrimary ＿ superficial2.5 5NCT-4271 Ｆ T4N0M0Nasal cavityPrimaryOp + Chem3.0 * 2.55 6NCT-4364MT2N0M0Nasal cavityPrimaryOp + Chem1.5 * 0.56 7NCT-4469MT4N0M0Nasal cavityPrimaryOp + Chem4.0 * 5.08 8NCT-4774 Ｆ T1N0M0Nasal cavityPrimaryOp + Chemsuperficial2 9NCT-5369MT1N0M0Nasal cavityPrimaryOp + Chem1.0 * 1.53.5 10NCT-5572MTxN2aM0NeckPrimary ＿ 2.0 * 2.03 11NCT-6859 Ｆ T1N0M0NeckMetaOp + Chem10.0 * 8.06 12NCT-7937MT1N0M0NeckMetaChem21.0 * 18.010 Head & Neck Melanoma cases (2005-2013)

7. CaseNCT-no.AgeSexi-StageBNCT site Primary/Meta at BNCT site Previous Tx Tumor size （ cm ） Tumor distance from skin surface (cm) 1NCT-3355 Ｍ T2N0M0Nasal cavityPrimaryOp + Chemsuperficial3 2NCT-3874 Ｆ T2N0M0Nasal cavityMetaOp + chemsuperficial4 3NCT-3966MT1N2bM0NeckMetaOp2.5 * 3.03 4NCT-4074MT1N0M0Nasal cavityPrimary ＿ superficial2.5 5NCT-4271 Ｆ T4N0M0Nasal cavityPrimaryOp + Chem3.0 * 2.55 6NCT-4364MT2N0M0Nasal cavityPrimaryOp + Chem1.5 * 0.56 7NCT-4469MT4N0M0Nasal cavityPrimaryOp + Chem4.0 * 5.08 8NCT-4774 Ｆ T1N0M0Nasal cavityPrimaryOp + Chemsuperficial2 9NCT-5369MT1N0M0Nasal cavityPrimaryOp + Chem1.0 * 1.53.5 10NCT-5572MTxN2aM0NeckPrimary ＿ 2.0 * 2.03 11NCT-6859 Ｆ T1N0M0NeckMetaOp + Chem10.0 * 8.06 12NCT-7937MT1N0M0NeckMetaChem21.0 * 18.010 Head & Neck Melanoma cases (2005-2013)

8. Tumor distance from skin surface (cm)

9. CaseNCT-no.AgeSexi-StageBNCT site Primary/Meta at BNCT site Previous Tx Tumor size （ cm ） Tumor distance from skin surface (cm) 1NCT-3355 Ｍ T2N0M0Nasal cavityPrimaryOp + Chemsuperficial3 2NCT-3874 Ｆ T2N0M0Nasal cavityMetaOp + chemsuperficial4 3NCT-3966MT1N2bM0NeckMetaOp2.5 * 3.03 4NCT-4074MT1N0M0Nasal cavityPrimary ＿ superficial2.5 5NCT-4271 Ｆ T4N0M0Nasal cavityPrimaryOp + Chem3.0 * 2.55 6NCT-4364MT2N0M0Nasal cavityPrimaryOp + Chem1.5 * 0.56 7NCT-4469MT4N0M0Nasal cavityPrimaryOp + Chem4.0 * 5.08 8NCT-4774 Ｆ T1N0M0Nasal cavityPrimaryOp + Chemsuperficial2 9NCT-5369MT1N0M0Nasal cavityPrimaryOp + Chem1.0 * 1.53.5 10NCT-5572MTxN2aM0NeckPrimary ＿ 2.0 * 2.03 11NCT-6859 Ｆ T1N0M0NeckMetaOp + Chem10.0 * 8.06 12NCT-7937MT1N0M0NeckMetaChem21.0 * 18.010 Head & Neck Melanoma cases (2005-2013)

10. CaseBoron (blood)BPA-PET T/N （Ｂ） Tumor size （ cm ） Tumor dose (Min.) (Gy-eq) Skin dose (Max.) (Gy-eq) Local responsealive / death 125ppm ＿ 3Superficial2311.9CRalive 2 32 ｐｐｍ＿ 3Superficial26.211CRdeath 3 32 ｐｐｍ ○3 ≦ 5cm 28.18.2CRdeath 425ppm ＿ 3Superficial25.213.4PRdeath 5 24 ｐｐｍ ○3 ≦ 5cm 1915CRdeath 625ppm○2.7 ≦ 5cm 21.115.8PDdeath 7 27 ｐｐｍ ○3.7 ≦ 5cm 23.39.8PDdeath 827ppm ＿ 3Superficial29.69.5CRdeath 9 29 ｐｐｍ ○2.5 ≦ 5cm 27.216.6CRdeath 10 24 ｐｐｍ ○3.1 ≦ 5cm 23.419PRdeath 11 32 ｐｐｍ ○5 5cm ≦ 372.9CRalive 1225ppm○6.9 5cm ≦ 24.53.8PDdeath

11. Overall survival rate （ n=12) ( years ) 5-year : 25%

12. Local relapse - free survival rate (n=12) ( years ) 5-year : 54%

13. ( years ) ≧ 25Gy-eq (6) ≦ 25Gy-eq (6) Local relapse - free survival rate according to min. tumor dose

14. Tumor distance from skin surface 10 cm 5 cm Minimum tumor dose ( Gy-eq ) Non-CRCR

15. Tumor depth from skin surface 10 cm 5 cm Minimum tumor dose ( Gy-eq ) Non-CRCR

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

17. Irradiation time ： 42 minutes Tumor doses ＝ 23-35Gy-eq Mucosal doses ＝ 13Gy-eq JRR-4

18. 3 months after BNCT 11 months after BNCT CR for 8 years Prior to BNCT

19. Tumor depth from skin surface 10 cm 5 cm Minimum tumor dose ( Gy-eq ) Non-CRCR

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

21. Tumor depth from skin surface 10 cm 5 cm Minimum tumor dose ( Gy-eq ) Non-CRCR

22. Salvage BNCT--- 59Yo. Female Local LN recurrent malignant melanoma after operation (TxN1bM0, Stage Ⅲ B, amelanotic melanoma) melanoma(?) resection LN recurrence resection recurrence rapid growth NCT-68

23. T/N=5.2 59 years old （ Female ） Malignant melanoma （ before BNCT ） 37Gy-eq ≦ Tumor dose

24. 8 m. later11 m.13 m.18 m.

25. Dose distribution in Tumor （ Gy-eq )

26. Before BNCT 18 m. later

27. Before BNCT18 m. later

28. 18 months after BNCT

29. 2013.12.2 （ 2.5 y after BNCT )

30. Tumor depth from skin surface 10 cm 5 cm Minimum tumor dose ( Gy-eq ) Non-CRCR

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.

32. Thank you for your attention. Seto Inland Sea, OKAYAMA, Japan.