title: Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.
abstract: OBJECTIVE
  To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy.
  
  
  METHODS
  In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively.
  
  
  RESULTS
  Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%.
  
  
  CONCLUSIONS
  Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.
authors.affiliation: Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, Taiwan. Electronic address: lwwang@vghtpe.gov.tw.
authors.forename: Ling-Wei
authors.initials: LW
authors.lastname: Wang
authors.affiliation: Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: National Yang-Ming University, Taiwan; Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan.
authors.forename: Ching-Yin
authors.initials: CY
authors.lastname: Ho
authors.affiliation: Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan.
authors.forename: Yen-Wan
authors.initials: YW
authors.lastname: Hsueh Liu
authors.affiliation: Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan; Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan.
authors.forename: Fong-In
authors.initials: FI
authors.lastname: Chou
authors.affiliation: Nuclear Science and Engineering Department, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: Yuan-Hao
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan.
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Liu
authors.affiliation: Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan.
authors.forename: Jinn-Jer
authors.initials: JJ
authors.lastname: Peir
authors.affiliation: Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan.
authors.forename: Shiang-Huei
authors.initials: SH
authors.lastname: Jiang
authors.affiliation: National Yang-Ming University, Taiwan; Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, Taiwan.
authors.forename: Ching-Sheng
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Taoyuan Veterans Hospital, Taiwan.
authors.forename: Ko-Han
authors.initials: KH
authors.lastname: Lin
authors.affiliation: National Yang-Ming University, Taiwan; Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Shyh-Jen
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: National Yang-Ming University, Taiwan; Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan.
authors.forename: Pen-Yuan
authors.initials: PY
authors.lastname: Chu
authors.affiliation: National Yang-Ming University, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Lo
authors.affiliation: National Yang-Ming University, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taiwan.
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
authors.affiliation: Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, Taiwan.
authors.forename: Sang-Hue
authors.initials: SH
authors.lastname: Yen
mesh_terms: D000328:Adult; D000368:Aged; D001896:Boron Compounds / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods*; D002340:Carotid Artery Diseases / Q000209:etiology; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007819:Laryngeal Edema / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy*; D010649:Phenylalanine / Q000627:therapeutic use; D017785:Photons / Q000627:therapeutic use; D011446:Prospective Studies; D013280:Stomatitis / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001896:Boron Compounds; D010649:Phenylalanine