L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: A phase i study

Leena Kankaanranta, Tiina Seppälä, Hanna Koivunoro, Petteri Välimäki, Annette Beule, Juhani Collan, Mika Kortesniemi, Jouni Uusi-Simola, Petri Kotiluoto, Iiro Auterinen, Tom Sern, Anders Paetau, Kauko Saarilahti, Sauli Savolainen, Heikki Joensuu

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Abstract

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of l-boronophenylalanine-fructose (l-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of l-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated l-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of l-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

Original languageEnglish
Pages (from-to)369-376
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume80
Issue number2
DOIs
Publication statusPublished - 1 Jun 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

Boron Neutron Capture Therapy
Glioma
radiation therapy
therapy
boron
Radiotherapy
neutrons
Fructose
dosage
surgery
National Cancer Institute (U.S.)
Astrocytoma
Neutrons
neutron irradiation
Glioblastoma
toxicity
planning
grade
safety
cancer

Keywords

  • Anaplastic astrocytoma
  • Boron neutron capture therapy
  • Boronophenylalanine
  • Brain tumor
  • Glioblastoma

Cite this

Kankaanranta, Leena ; Seppälä, Tiina ; Koivunoro, Hanna ; Välimäki, Petteri ; Beule, Annette ; Collan, Juhani ; Kortesniemi, Mika ; Uusi-Simola, Jouni ; Kotiluoto, Petri ; Auterinen, Iiro ; Sern, Tom ; Paetau, Anders ; Saarilahti, Kauko ; Savolainen, Sauli ; Joensuu, Heikki. / L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy : A phase i study. In: International Journal of Radiation Oncology Biology Physics. 2011 ; Vol. 80, No. 2. pp. 369-376.
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title = "L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: A phase i study",
abstract = "Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of l-boronophenylalanine-fructose (l-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of l-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated l-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of l-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.",
keywords = "Anaplastic astrocytoma, Boron neutron capture therapy, Boronophenylalanine, Brain tumor, Glioblastoma",
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Kankaanranta, L, Seppälä, T, Koivunoro, H, Välimäki, P, Beule, A, Collan, J, Kortesniemi, M, Uusi-Simola, J, Kotiluoto, P, Auterinen, I, Sern, T, Paetau, A, Saarilahti, K, Savolainen, S & Joensuu, H 2011, 'L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: A phase i study', International Journal of Radiation Oncology Biology Physics, vol. 80, no. 2, pp. 369-376. https://doi.org/10.1016/j.ijrobp.2010.02.031, https://doi.org/10.1016/j.ijrobp.2010.02.031

L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy : A phase i study. / Kankaanranta, Leena; Seppälä, Tiina; Koivunoro, Hanna; Välimäki, Petteri; Beule, Annette; Collan, Juhani; Kortesniemi, Mika; Uusi-Simola, Jouni; Kotiluoto, Petri; Auterinen, Iiro; Sern, Tom; Paetau, Anders; Saarilahti, Kauko; Savolainen, Sauli; Joensuu, Heikki.

In: International Journal of Radiation Oncology Biology Physics, Vol. 80, No. 2, 01.06.2011, p. 369-376.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy

T2 - A phase i study

AU - Kankaanranta, Leena

AU - Seppälä, Tiina

AU - Koivunoro, Hanna

AU - Välimäki, Petteri

AU - Beule, Annette

AU - Collan, Juhani

AU - Kortesniemi, Mika

AU - Uusi-Simola, Jouni

AU - Kotiluoto, Petri

AU - Auterinen, Iiro

AU - Sern, Tom

AU - Paetau, Anders

AU - Saarilahti, Kauko

AU - Savolainen, Sauli

AU - Joensuu, Heikki

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of l-boronophenylalanine-fructose (l-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of l-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated l-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of l-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

AB - Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of l-boronophenylalanine-fructose (l-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of l-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated l-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of l-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

KW - Anaplastic astrocytoma

KW - Boron neutron capture therapy

KW - Boronophenylalanine

KW - Brain tumor

KW - Glioblastoma

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U2 - 10.1016/j.ijrobp.2010.02.031

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