Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

Abstract

BackgroundOsteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator.MethodsThe therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison.ResultsThe results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy.ConclusionsThe possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery.

Thermal Neutron Relative Biological Effectiveness Factors for Boron Neutron Capture Therapy from In Vitro Irradiations

“…The geometry of the experimental arrangement was accurately simulated, calculating the dose by means of the kerma factor that depends on the nitrogen content of each cell line. Corrections due to charged particle disequilibrium effects, which are important, as shown by Bortolussi et al [ 21 ], were included in the dose estimations. More details can be found in Ref.…”

Dose assessment with MCNP5/X code for boron neutron capture therapy of pancreas cancer

“…In clin i cal stud ies [24][25][26], con sid er ing rel a tive bi o log i cal ef fec tive ness (RBE), the au thors re ported that the op ti mal BNCT pa ram e ters and char ac ter is tics of the pa tient's can cer, which is the C/H ra tio (C is a can cer dose, H is healthy or gan or tis sue dose) ³3, depend ing on the type of can cers.…”

Extending neutron autoradiography technique for boron concentration measurements in hard tissues

“…Recently, in vitro and in vivo osteosarcoma models have been used to assess boron uptake on the UMR-106 osteosarcoma cell line (Ferrari et al 2009, Postuma et al 2016, and to determine the 10 B distribution in normal and tumor tissue sections (Bortolussi et al 2017). Essentially, two nuclear techniques were employed for this purpose: alpha spectrometry (Bortolussi and Altieri 2013) and neutron autoradiography (Portu et al 2015).…”