1. T. Aihara 1, 2, N. Morita 2, N. Kamitani 3, H. Kumada 1, K. Oonishi 1, M. Suzuki 4, J. Hiratsuka 3, H. Sakurai 1. 1 Proton Medical Research Centre, University of Tsukuba, Tsukuba, Japan 2 Departments of Otolaryngology Head and Neck Surgery, and 3 Radiation Oncology, Kawasaki Medical School, Kurashiki, Japan 4 Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Osaka, Japan A simple strategy to decrease the incidence of fatal carotid blowout syndrome after BNCT for head and neck cancers

2. Purpose Carotid blowout syndrome (CBS) is a life- threatening complication of BNCT for head and neck cancers Determination of the risk factors for CBS is important for the safe use of BNCT This study reviews cases of CBS after BNCT at our institution

3. Indications for BNCT Recurrent Head and Neck Cancer (HNC) or newly diagnosed T3/T4 HNC Maximum depth of tumor within 5-cm from the skin surface T/N ratio of more than 2.5 Consent to perform BNCT from the patient and their family Approval for BNCT by Medical Ethics Committee

4. Treatment procedure Intravenous administration of BPA(500mg/kg) as a BPA-Fructose complex in solution Attachment of TLDs and gold wires to the skin surface involved in the irradiation field Fixation of the patient on the treatment table Neutron flux measurement using gold wire 10 minutes after the start of irradiation Blood sampling at the finish of the BPA infusion, and just before and after irradiation Dose prediction based on the measured blood boron concentration and neutron flux Tumor dose ≧ 20 Gy-Eq Normal skin dose ≦ 15 Gy-Eq Determination of neutron irradiation period

5. Patient characteristics October 2003 - December 2011 Patients33 male21 female12 Age31-83(median:67) Rec/New Recurrence24 (after irradiation:23) New9 Pathology SCC11 MM10 Other12 Radiation field Neck18 (carotid lesion:11) Other15 T/N2.5-5(median:2.7)

6. Patient characteristics October 2003 - December 2011 Patients33 male21 female12 Age31-83(median:67) Rec/New Recurrence24 (after irradiation:23) New9 Pathology SCC11 MM10 Other12 Radiation field Neck18 (carotid lesion:11) Other15 T/N2.5-5(median:2.7)

7. Criteria of involvement grade (IG) High grade >2/3 Low grade ≤ 1/3 Middle grade ≤ 2/3 No involvement

8. Results (n=18) IG Skin defect RT(+)CBS Time to CBS onset Not involved 7 (+)33 (-)43 Low4 (+)11 (-)31 Middle4 (+)11Yes 2 months (-)32 High3 (+)11Yes 3 months (-)22 IG : involvement grade RT : Radiotherapy CBS : carotid blowout syndrome

9. Results (n=18) IG Skin defect RT(+)CBS Time to CBS onset Not involved 7 (+)33 (-)43 Low4 (+)11 (-)31 Middle4 (+)11Yes 2 months (-)32 High3 (+)11Yes 3 months (-)22 IG : involvement grade RT : Radiotherapy CBS : carotid blowout syndrome

10. A case of CBS Case No.6 before irradiation28 days later

11. Discussion Incidence rates of CBS after radiotherapy Newly diagnosed cancer: 2-5% [LingYan Zheng. et al. 2013] Recurrent cancer: 10-20% [Cengiz M. et al. 2011] Incidence rates of CBS after BNCT 4.8% [M, Suzuki. et al. 2013]. CBS developed in two patients after BNCT These two patients had: 1) Skin defects due to tumor invasion. 2) Recurrence close to the carotid artery after irradiation

12. Discussion Incidence rates of CBS after radiotherapy Newly diagnosed cancer: 2-5% [LingYan Zheng. et al. 2013] Recurrent cancer: 10-20% [Cengiz M. et al. 2011] Incidence rates of CBS after BNCT 4.8% [M, Suzuki. et al. 2013] CBS developed in two patients after BNCT These two patients had: 1) Skin defects due to tumor invasion 2) Recurrence close to the carotid artery after irradiation

13. Conclusion Two of 18 patients bled from the carotid artery after BNCT These two patients had skin defects from tumor invasion and recurrence close to the carotid artery after irradiation This protocol for BNCT in recurrent and advanced head and neck cancer may decrease the incidence of fatal CBS