title: Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: final analysis of a phase I/II trial.
abstract: OBJECTIVE
  To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy.
  
  
  METHODS
  In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT.
  
  
  RESULTS
  Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%).
  
  
  CONCLUSIONS
  Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Kankaanranta
authors.forename: Tiina
authors.initials: T
authors.lastname: Seppälä
authors.forename: Hanna
authors.initials: H
authors.lastname: Koivunoro
authors.forename: Kauko
authors.initials: K
authors.lastname: Saarilahti
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
authors.forename: Juhani
authors.initials: J
authors.lastname: Collan
authors.forename: Eero
authors.initials: E
authors.lastname: Salli
authors.forename: Mika
authors.initials: M
authors.lastname: Kortesniemi
authors.forename: Jouni
authors.initials: J
authors.lastname: Uusi-Simola
authors.forename: Petteri
authors.initials: P
authors.lastname: Välimäki
authors.forename: Antti
authors.initials: A
authors.lastname: Mäkitie
authors.forename: Marko
authors.initials: M
authors.lastname: Seppänen
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
authors.forename: Hannu
authors.initials: H
authors.lastname: Revitzer
authors.forename: Mauri
authors.initials: M
authors.lastname: Kouri
authors.forename: Petri
authors.initials: P
authors.lastname: Kotiluoto
authors.forename: Tom
authors.initials: T
authors.lastname: Seren
authors.forename: Iiro
authors.initials: I
authors.lastname: Auterinen
authors.forename: Sauli
authors.initials: S
authors.lastname: Savolainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
mesh_terms: D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods*; D003528:Carcinoma, Adenoid Cystic / Q000401:mortality / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy*; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005221:Fatigue / Q000209:etiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000209:etiology; D052016:Mucositis / Q000209:etiology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy*; D010025:Osteoradionecrosis / Q000209:etiology; D010146:Pain / Q000209:etiology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000532:radiotherapy*; D014987:Xerostomia / Q000209:etiology
chemical_list: C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine