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.
Highlights
Note that αRef/βRef is about two, that is low compared with usual values used for tumour, but in agreement with α/β ratios reported in literature for sarcomas [33]
This work explores the feasibility of Boron Neutron Capture Therapy (BNCT) for osteosarcoma using a neutron beam from a proton accelerator, from the point of view of the dose distribution
Survival curves for photons, neutrons and BNCT were obtained for an osteosarcoma cell line, allowing the derivation of the RBE/Relative Biological Effectiveness/Compound Biological Effectiveness (CBE) factors and of the parameters for the iso-effective dose in osteosarcoma
Summary
Osteosarcoma 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 [1]. The standard treatment of this malignancy consists in preoperative (neo-adjuvant) chemotherapy followed by surgical removal of all detectable disease (including metastases, that are yet present in 80% of patients at diagnosis), and postoperative (adjuvant) chemotherapy [2]. The standard route of neo adjuvant chemotherapy, surgery and adjuvant chemotherapy is effective in approximately 70% of the patients with localized disease, but for patients with metastases, the long term survival rate is lower than 20% [3]. 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. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator
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