Boron Neutron Capture Therapy (BNCT) in the Management of Recurrent

Laryngeal Cancer

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

ICNCT-16, 14.-19.6.2014, 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

1. Safety?2. Efficacy?3. 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: – 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– 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

– 1, n=6– 2, n=3

• 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– 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

ResultsResponse 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, CRresponse duration 55+ months (ongoing)

Copyright Riste Saat

Before BNCT6 weeks after BNCT

Supraglottic rT3, PRresponse duration 7.4 mo

Copyright Aaro Haapaniemi

Glottic rT2, PRresponse duration 5.8 mo

Before BNCT 4 months after BNCT

Copyright Aaro Haapaniemi

Copyright Leena Kankaanranta

rN2b, PRresponse duration 8.3 mo

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