Boron neutron capture therapy (BNCT) in Finland: technological and physical prospects after 20 years of experiences.

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to treat patients with certain malignant tumours. To date, over 300 treatments have been carried out at the Finnish BNCT facility in various on-going and past clinical trials. In this technical review, we discuss our research work in the field of medical physics to form the groundwork for the Finnish BNCT patient treatments, as well as the possibilities to further develop and optimize the method in the future. Accordingly, the following aspects are described: neutron sources, beam dosimetry, treatment planning, boron imaging and determination, and finally the possibilities to detect the efficacy and effects of BNCT on patients.

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

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.

L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: a Phase I study.

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.

Differences between Finnish and European reference values for pulmonary diffusing capacity.

OBJECTIVES: To compare European (ECSC) and Finnish reference values for single-breath diffusing capacity for carbon monoxide (DL(CO)). STUDY DESIGN: Finnish reference values for DL(CO), specific diffusing capacity (DL(CO)/VA) and total lung capacity (TLC) were compared with ECSC reference values calculated for different age, height and weight groups. In addition, 10 healthy subjects performed the test with both the Finnish method (inhaled volume 90% of vital capacity, VC) and the ECSC method (inhaled volume 100% of VC). METHODS: Percentual differences between the ECSC and Finnish reference values for DL(CO), TLC and DL(CO)/VA were calculated. The results of measurements of DL(CO) and TLC by using inhaled volume of 100% of VC and 90% of VC in 10 healthy subjects were compared. RESULTS: The Finnish DL(CO) reference value for men was 3-12% and for women 8-20% smaller than the ECSC reference value. TLC calculated according to Finnish equations was 2-14% greater than that based on ECSC equations. The ECSC reference value for DL(CO)/VA was about 20% greater than the Finnish reference value in men and 30% greater than that in women. The 10 healthy subjects had significantly higher DL(CO) when measured according to the ECSC method as compared with the Finnish one (p < 0.004). CONCLUSIONS: The Finnish reference values for DL(CO) were about 10% smaller, but TLC 10% and DL(CO)/VA 20-30% greater than ECSC reference values in subjects of the same age, height, weight and gender. The difference in DL(CO) is explained by the different inhaled lung volumes used in the two methods, the difference in lung volumes probably arising from ethnic differences in thoracic cavity.