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

    Research output: Contribution to journalArticleScientificpeer-review

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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",
    author = "Leena Kankaanranta and Tiina Sepp{\"a}l{\"a} and Hanna Koivunoro and Petteri V{\"a}lim{\"a}ki and Annette Beule and Juhani Collan and Mika Kortesniemi and Jouni Uusi-Simola and Petri Kotiluoto and Iiro Auterinen and Tom Sern and Anders Paetau and Kauko Saarilahti and Sauli Savolainen and Heikki Joensuu",
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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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