Prompt gamma and neutron detection in BNCT utilizing a CdTe detector.

In this work, a novel sensor technology based on CdTe detectors was tested for prompt gamma and neutron detection using boronated targets in (epi)thermal neutron beam at FiR1 research reactor in Espoo, Finland. Dedicated neutron filter structures were omitted to enable simultaneous measurement of both gamma and neutron radiation at low reactor power (2.5 kW). Spectra were collected and analyzed in four different setups in order to study the feasibility of the detector to measure 478 keV prompt gamma photons released from the neutron capture reaction of boron-10. The detector proved to have the required sensitivity to detect and separate the signals from both boron neutron and cadmium neutron capture reactions, which makes it a promising candidate for monitoring the spatial and temporal development of in vivo boron distribution in boron neutron capture therapy.

Characterization of a double-sided silicon strip detector autoradiography system.

PURPOSE: The most commonly used technology currently used for autoradiography is storage phosphor screens, which has many benefits such as a large field of view but lacks particle-counting detection of the time and energy of each detected radionuclide decay. A number of alternative designs, using either solid state or scintillator detectors, have been developed to address these issues. The aim of this study is to characterize the imaging performance of one such instrument, a double-sided silicon strip detector (DSSD) system for digital autoradiography. A novel aspect of this work is that the instrument, in contrast to previous prototype systems using the same detector type, provides the ability for user accessible imaging with higher throughput. Studies were performed to compare its spatial resolution to that of storage phosphor screens and test the implementation of multiradionuclide ex vivo imaging in a mouse preclinical animal study. METHODS: Detector background counts were determined by measuring a nonradioactive sample slide for 52 h. Energy spectra and detection efficiency were measured for seven commonly used radionuclides under representative conditions for tissue imaging. System dead time was measured by imaging (18)F samples of at least 5 kBq and studying the changes in count rate over time. A line source of (58)Co was manufactured by irradiating a 10 µm nickel wire with fast neutrons in a research reactor. Samples of this wire were imaged in both the DSSD and storage phosphor screen systems and the full width at half maximum (FWHM) measured for the line profiles. Multiradionuclide imaging was employed in a two animal study to examine the intratumoral distribution of a (125)I-labeled monoclonal antibody and a (131)I-labeled engineered fragment (diabody) injected in the same mouse, both targeting carcinoembryonic antigen. RESULTS: Detector background was 1.81 × 10(-6) counts per second per 50 × 50 µm pixel. Energy spectra and detection efficiency were successfully measured for seven radionuclides. The system dead time was measured to be 59 µs, and FWHM for a (58)Co line source was 154 ± 14 µm for the DSSD system and 343 ± 15 µm for the storage phosphor system. Separation of the contributions from (125)I and (131)I was performed on autoradiography images of tumor sections. CONCLUSIONS: This study has shown that a DSSD system can be beneficially applied for digital autoradiography with simultaneous multiradionuclide imaging capability. The system has a low background signal, ability to image both low and high activity samples, and a good energy resolution.

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.

Accuracy of the electron transport in mcnp5 and its suitability for ionization chamber response simulations: A comparison with the egsnrc and penelope codes.

PURPOSE: In this work, accuracy of the mcnp5 code in the electron transport calculations and its suitability for ionization chamber (IC) response simulations in photon beams are studied in comparison to egsnrc and penelope codes. METHODS: The electron transport is studied by comparing the depth dose distributions in a water phantom subdivided into thin layers using incident energies (0.05, 0.1, 1, and 10 MeV) for the broad parallel electron beams. The IC response simulations are studied in water phantom in three dosimetric gas materials (air, argon, and methane based tissue equivalent gas) for photon beams ((60)Co source, 6 MV linear medical accelerator, and mono-energetic 2 MeV photon source). Two optional electron transport models of mcnp5 are evaluated: the ITS-based electron energy indexing (mcnp5(ITS)) and the new detailed electron energy-loss straggling logic (mcnp5(new)). The electron substep length (ESTEP parameter) dependency in mcnp5 is investigated as well. RESULTS: For the electron beam studies, large discrepancies (>3%) are observed between the MCNP5 dose distributions and the reference codes at 1 MeV and lower energies. The discrepancy is especially notable for 0.1 and 0.05 MeV electron beams. The boundary crossing artifacts, which are well known for the mcnp5(ITS), are observed for the mcnp5(new) only at 0.1 and 0.05 MeV beam energies. If the excessive boundary crossing is eliminated by using single scoring cells, the mcnp5(ITS) provides dose distributions that agree better with the reference codes than mcnp5(new). The mcnp5 dose estimates for the gas cavity agree within 1% with the reference codes, if the mcnp5(ITS) is applied or electron substep length is set adequately for the gas in the cavity using the mcnp5(new). The mcnp5(new) results are found highly dependent on the chosen electron substep length and might lead up to 15% underestimation of the absorbed dose. CONCLUSIONS: Since the mcnp5 electron transport calculations are not accurate at all energies and in every medium by general clinical standards, caution is needed, if mcnp5 is used with the current electron transport models for dosimetric applications.

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.

Validation of dose planning calculations for boron neutron capture therapy using cylindrical and anthropomorphic phantoms.

In this paper, the accuracy of dose planning calculations for boron neutron capture therapy (BNCT) of brain and head and neck cancer was studied at the FiR 1 epithermal neutron beam. A cylindrical water phantom and an anthropomorphic head phantom were applied with two beam aperture-to-surface distances (ASD). The calculations using the simulation environment for radiation application (SERA) treatment planning system were compared to neutron activation measurements with Au and Mn foils, photon dose measurements with an ionization chamber and the reference simulations with the MCNP5 code. Photon dose calculations using SERA differ from the ionization chamber measurements by 2-13% (disagreement increased along the depth in the phantom), but are in agreement with the MCNP5 calculations within 2%. The (55)Mn(n,gamma) and (197)Au(n,gamma) reaction rates calculated using SERA agree within 10% and 8%, respectively, with the measurements and within 5% with the MCNP5 calculations at depths >0.5 cm from the phantom surface. The (55)Mn(n,gamma) reaction rate represents the nitrogen and boron depth dose within 1%. Discrepancy in the SERA fast neutron dose calculation (of up to 37%) is corrected if the biased fast neutron dose calculation option is not applied. Reduced voxel cell size (6 cm from the phantom surface. Increasing discrepancy along the phantom depth is expected to be caused by the inaccurately determined effective point of the ionization chamber.

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

PURPOSE: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. METHODS AND MATERIALS: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. RESULTS: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). CONCLUSIONS: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy.

Radiation sensitive polymer gels are among the most promising three-dimensional dose verification tools developed to date. Polymer gel dosimeter known by the acronym MAGIC has been tested for evaluation of its use in boron neutron capture (BNCT) dosimetry. We irradiated a large (diameter 10 cm, length 20 cm) cylindrical gel phantom in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. Gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator to compare dose response in the two different types of beams. Irradiated gel phantoms were imaged using MRI to determine their relaxation rate R2 maps. The measured and normalized dose distribution in the epithermal neutron beam was compared to the dose distribution calculated by computer simulation. The results support the feasibility MAGIC gel in BNCT dosimetry.

A toolkit for epithermal neutron beam characterisation in BNCT.

Methods for dosimetry of epithermal neutron beams used in boron neutron capture therapy (BNCT) have been developed and utilised within the Finnish BNCT project as well as within a European project for a code of practise for the dosimetry of BNCT. One outcome has been a travelling toolkit for BNCT dosimetry. It consists of activation detectors and ionisation chambers. The free-beam neutron spectrum is measured with a set of activation foils of different isotopes irradiated both in a Cd-capsule and without it. Neutron flux (thermal and epithermal) distribution in phantoms is measured using activation of Mn and Au foils, and Cu wire. Ionisation chamber (IC) measurements are performed both in-free-beam and in-phantom for determination of the neutron and gamma dose components. This toolkit has also been used at other BNCT facilities in Europe, the USA, Argentina and Japan.

A dosimetric study on the use of bolus materials for treatment of superficial tumors with BNCT.

For treatment of superficially located tumors, such as head and neck cancers that invade the skin, the tumor dose may remain low on the skin when such tumors are treated with epithermal neutrons in boron neutron capture therapy (BNCT). The goal of this study was to examine the effects of bolus material for BNCT of superficial tumors, to verify the calculated (55)Mn(n, gamma) and the (197)Au(n, gamma) activation reaction rates and the neutron and the gamma doses in a phantom irradiated with a bolus, to measure the neutron activation of the bolus materials after irradiation, and according to depth dose distribution, to estimate when it is advantageous to use a bolus in BNCT. The present data show that both paraffin and water gel can be used as a bolus material for BNCT. However, we recommend paraffin for clinical use, since it is durable and can be easily shaped. A 5 mm paraffin bolus increases the surface dose approximately 50%, and its use may be advantageous for treatment of superficial tumors where the planning target volume (PTV) reaches to 6 cm or less in tissue depth.

Undifferentiated sinonasal carcinoma may respond to single-fraction boron neutron capture therapy.

A large, rapidly progressing, unresectable undifferentiated sinonasal head and neck carcinoma regressed rapidly following single fraction boron neutron capture therapy (BNCT). The main toxicity consisted of mucositis lasting for a few days. The quality of life improved and was excellent until tumour recurrence 6 months after the date of BNCT.

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine.

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50-60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25-29 Gy (W), and the average whole brain dose 2-3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.

Dose planning with comparison to in vivo dosimetry for epithermal neutron irradiation of the dog brain.

Boron neutron capture therapy (BNCT) is an experimental type of radiotherapy, presently being used to treat glioblastoma and melanoma. To improve patient safety and to determine the radiobiological characteristics of the epithermal neutron beam of Finnish BNCT facility (FiR 1) dose-response studies were carried on the brain of dogs before starting the clinical trials. A dose planning procedure was developed and uncertainties of the epithermal neutron-induced doses were estimated. The accuracy of the method of computing physical doses was assessed by comparing with in vivo dosimetry. Individual radiation dose plans were computed using magnetic resonance images of the heads of 15 Beagle dogs and the computational model of the FiR 1 epithermal neutron beam. For in vivo dosimetry, the thermal neutron fluences were measured using Mn activation foils and the gamma-ray doses with MCP-7s type thermoluminescent detectors placed both on the skin surface of the head and in the oral cavity. The degree of uncertainty of the reference doses at the thermal neutron maximum was estimated using a dose-planning program. The estimated uncertainty (+/-1 standard deviation) in the total physical reference dose was +/-8.9%. The calculated and the measured dose values agreed within the uncertainties at the point of beam entry. The conclusion is that the dose delivery to the tissue can be verified in a practical and reliable fashion by placing an activation dosimeter and a TL detector at the beam entry point on the skin surface with homogeneous tissues below. However, the point doses cannot be calculated correctly in the inhomogeneous area near air cavities of the head model with this type of dose-planning program. This calls for attention in dose planning in human clinical trials in the corresponding areas.