Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: Final analysis of a phase I/II trial

Leena Kankaanranta, Tiina Seppälä, Hanna Koivunoro, Kauko Saarilahti, Timo Atula, Juhani Collan, Eero Salli, Mika Kortesniemi, Jouni Uusi-Simola, Petteri Välimäki, Antti Mäkitie, Marko Seppänen, Heikki Minn, Hannu Revitzer, Mauri Kouri, Petri Kotiluoto, Tom Seren, Iiro Auterinen, Sauli Savolainen, Heikki Joensuu (Corresponding Author)

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Abstract

Purpose: 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 and Materials: 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.

Original languageEnglish
Pages (from-to)e67-e75
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume82
Issue number1
DOIs
Publication statusPublished - 1 Jan 2012
MoE publication typeA1 Journal article-refereed

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Boron Neutron Capture Therapy
Head and Neck Neoplasms
therapy
boron
cancer
neutrons
grade
Therapeutics
tumors
Photons
progressions
Disease-Free Survival
Osteoradionecrosis
Carcinoma
Recurrence
Xerostomia
Neoplasms
Mucositis
terminology
Boron

Keywords

  • Boron neutron capture therapy
  • Boronophenylalanine
  • Head-and-neck cancer
  • Radiotherapy

Cite this

Kankaanranta, Leena ; Seppälä, Tiina ; Koivunoro, Hanna ; Saarilahti, Kauko ; Atula, Timo ; Collan, Juhani ; Salli, Eero ; Kortesniemi, Mika ; Uusi-Simola, Jouni ; Välimäki, Petteri ; Mäkitie, Antti ; Seppänen, Marko ; Minn, Heikki ; Revitzer, Hannu ; Kouri, Mauri ; Kotiluoto, Petri ; Seren, Tom ; Auterinen, Iiro ; Savolainen, Sauli ; Joensuu, Heikki. / Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer : Final analysis of a phase I/II trial. In: International Journal of Radiation Oncology Biology Physics. 2012 ; Vol. 82, No. 1. pp. e67-e75.
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title = "Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: Final analysis of a phase I/II trial",
abstract = "Purpose: 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 and Materials: 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.",
keywords = "Boron neutron capture therapy, Boronophenylalanine, Head-and-neck cancer, Radiotherapy",
author = "Leena Kankaanranta and Tiina Sepp{\"a}l{\"a} and Hanna Koivunoro and Kauko Saarilahti and Timo Atula and Juhani Collan and Eero Salli and Mika Kortesniemi and Jouni Uusi-Simola and Petteri V{\"a}lim{\"a}ki and Antti M{\"a}kitie and Marko Sepp{\"a}nen and Heikki Minn and Hannu Revitzer and Mauri Kouri and Petri Kotiluoto and Tom Seren and Iiro Auterinen and Sauli Savolainen and Heikki Joensuu",
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Kankaanranta, L, Seppälä, T, Koivunoro, H, Saarilahti, K, Atula, T, Collan, J, Salli, E, Kortesniemi, M, Uusi-Simola, J, Välimäki, P, Mäkitie, A, Seppänen, M, Minn, H, Revitzer, H, Kouri, M, Kotiluoto, P, Seren, T, Auterinen, I, Savolainen, S & Joensuu, H 2012, 'Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: Final analysis of a phase I/II trial', International Journal of Radiation Oncology Biology Physics, vol. 82, no. 1, pp. e67-e75. https://doi.org/10.1016/j.ijrobp.2010.09.057

Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer : Final analysis of a phase I/II trial. / Kankaanranta, Leena; Seppälä, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Välimäki, Petteri; Mäkitie, Antti; Seppänen, Marko; Minn, Heikki; Revitzer, Hannu; Kouri, Mauri; Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro; Savolainen, Sauli; Joensuu, Heikki (Corresponding Author).

In: International Journal of Radiation Oncology Biology Physics, Vol. 82, No. 1, 01.01.2012, p. e67-e75.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer

T2 - Final analysis of a phase I/II trial

AU - Kankaanranta, Leena

AU - Seppälä, Tiina

AU - Koivunoro, Hanna

AU - Saarilahti, Kauko

AU - Atula, Timo

AU - Collan, Juhani

AU - Salli, Eero

AU - Kortesniemi, Mika

AU - Uusi-Simola, Jouni

AU - Välimäki, Petteri

AU - Mäkitie, Antti

AU - Seppänen, Marko

AU - Minn, Heikki

AU - Revitzer, Hannu

AU - Kouri, Mauri

AU - Kotiluoto, Petri

AU - Seren, Tom

AU - Auterinen, Iiro

AU - Savolainen, Sauli

AU - Joensuu, Heikki

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Purpose: 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 and Materials: 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.

AB - Purpose: 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 and Materials: 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.

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KW - Boronophenylalanine

KW - Head-and-neck cancer

KW - Radiotherapy

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