Boron Neutron Capture Therapy (BNCT) in the Management of Recurrent Laryngeal Cancer  ICNCT-16, 14.-19.6.2014, 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

Laryngeal cancer 157 000 new cases/year (Globocan 2012) Surgery -> oncological treatment Recurrence/persistense after treatment 27 % (Finland 2001-2005) Treatment of recurrence Salvage surgery (total laryngectomy) Reirradiation How to preserve the larynx?

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

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

Patients Review of patient data 2005-2012, n=9, all with SCC Age: 51-81 years Sex: 1 female, 8 male

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 (37.8-72 Gy ) Median time from last RT 17 mo (1-151 mo)

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

Treatment at FiR 1 Number of sessions L-BPA-F 400mg/kg over 2h Average tumor dose 29 Gy (W) (range, 22-38 Gy) Average blood boron concentration at neutron irradiation 18 μg/g (range, 13-22 μg/g)

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)

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

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

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

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

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

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

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

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

rN2b, PR response duration 8.3 mo Copyright Leena Kankaanranta

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