1. Boron Neutron Capture Therapy (BNCT) in the Management of Recurrent Laryngeal Cancer 
ICNCT-16, , Helsinki, Finland
Haapaniemi A¹, Kankaanranta L², Saat R3, Koivunoro H², Saarilahti K², Mäkitie A¹, Atula T¹, Joensuu H²  
Departments of ¹Otorhinolaryngology – Head and Neck Surgery, ²Oncology and 3Radiology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

2. Laryngeal cancer 157 000 new cases/year (Globocan 2012)
Surgery -> oncological treatment
Recurrence/persistense after treatment 27 % (Finland )
Treatment of recurrence
Salvage surgery (total laryngectomy)
Reirradiation
How to preserve the larynx?

3. Rationale for BNCT Short range radiation effect -> local therapy
Appears safe in previously irradiated patients
Pictures:

4. BNCT for recurrent laryngeal SCC
Safety?
Efficacy?
Preservation of functional larynx?

5. Patients Review of patient data 2005-2012, n=9, all with SCC
Age: years
Sex: 1 female, 8 male

6. Primary tumor Primary tumour: Previous RT or CRT
7 glottic, 1 supraglottic, 1 subglottic
T1-T3, N0-2, M0-1
Previous RT or CRT
Median radiation dose 66 Gy ( Gy )
Median time from last RT 17 mo (1-151 mo)

7. Status before BNCT 6 recurrent, 3 persistent Reason for BNCT
8 local, rT2-4a
1 regional, N2b
Reason for BNCT
Inoperable, n=2
Refusal of total laryngectomy / functional reasons, n=7

8. Treatment at FiR 1 Number of sessions L-BPA-F 400mg/kg over 2h
Average tumor dose 29 Gy (W) (range, Gy)
Average blood boron concentration at neutron irradiation 18 μg/g (range, μg/g)

9. Response assessment
Toxicity : National Cancer Institute Common Terminology Criteria for Adverse Events (CTC) version 3.0.
Response : Clinical assessment + Radiological assessment (RECIST v. 1.1, 2009)
One patient died 1 month after BNCT (pneumonia)

10. Toxicity Early toxicity Late toxicity
Grade III, n=5 (62.5%)
stomatitis, mucositis, dysphagia, oral cavity pain and fatigue
Late toxicity
Grade III, n=3 (37.5%)
stomatitis and mucositis
No gr IV-V toxicity, nor soft tissue or osteoradionecrosis was observed

11. Results Response rate 78% Initial responses (3 months post BNCT)
CR, n=2
PR, n=5
PD, n=1
One patient died of pneumonia 1 mo after BNCT
T3N2M1, persistense after CRT
No response assessment, clinical signs of response

12. 2 patiens (CR) with no progression, 1 is alive
Time to progression 6.6 months
2 patients (PR) refused total laryngectomy, died of progression
3 patients (PR) underwent laryngectomy, 1 is alive
1 patient (PR) died with pulmonary metastasis

13. Median OS 13 months after BNCT
1 year OS 56%, 2 year OS 22%
2 patients alive and disease-free 27 and 55 months after BNCT

14. Laryngectomy after BNCT
3 patients
2 patients with fistula
1 patient with normal healing
Fistula rate comparable to that reported in the literature after CRT

15. Glottic rT2, CR response duration 55+ months (ongoing)
Copyright Riste Saat

16. Supraglottic rT3, PR response duration 7.4 mo
6 weeks after BNCT
Before BNCT
Copyright Aaro Haapaniemi

17. Glottic rT2, PR response duration 5.8 mo
Before BNCT
4 months after BNCT
Copyright Aaro Haapaniemi

18. rN2b, PR response duration 8.3 mo
Copyright Leena Kankaanranta

19. Conclusions BNCT appears to be safe in recurrent LSCC
No severe side-effects
High initial response rate (78%)
Modest cure rate with BNCT alone (1 patient)
Future considerations:
Patient selection
Treatment intensification