Clinical Radiobiology of Fast Neutron Therapy: What Was Learnt?

Jones, Bleddyn

doi:10.3389/fonc.2020.01537

Cited by 21 publications

(10 citation statements)

References 56 publications

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“…The difficulties and limitations of the EBRT with fast neutrons 17,18,19 are mostly avoided by the IORT modality. The MCNP analyses demonstrated that the DD-CNG can deliver equivalent dose rates ~2 Gy (RBE)/min thanks to the high neutron flux (@10 8 cm -2 s -1 ), high-LET (~ 40 KeV/ µm as average) and high RBE (@16) of the 2.45 MeV neutrons (vs. 1 for electrons and X-rays).…”

Section: Discussionmentioning

confidence: 99%

“…2. the difficulties and limitations of the irradiation with fast neutrons 17,18,19 are overcome by the IORT modality; 3. some additional advantages could be obtained, in comparison with standard EBRT and IORT techniques with X-rays and electrons. The main reasons of these potential benefits rely on: (i) the almost spatial isotropic irradiation field of the neutron beam, suitable also for irregular surfaces and acting as a sort of ionizing radiation "foam" filling the surgical cavity and allowing to kill potential quiescent cancer cells (QCCs); (ii) the dose peak released at the tissues surface and (iii) its strong decrease in few centimetres in tissues depth (because of the high LET), sparing the neighbouring organs at risk (OARs).…”

Section: Introductionmentioning

confidence: 99%

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A Compact Neutron Generator for the Niort® Treatment of Severe Solid Cancers

Martellini

2023

MRAJ

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In the last four years, TheranostiCentre S.r.l., Berkion Technology LLC and ENEA have patented and fabricated a first prototype of a Compact Neutron Generator (CNG) currently under testing in the ENEA laboratories. Besides the usual applications in the field of materials irradiation, this CNG - producing neutrons of 2.45 MeV energy by using the DD fusion reaction - was conceived for the neutron irradiation of the solid cancer’s tumour bed by means of the Intra-Operative Radiotherapy (IORT) technique, the so-called neutron-IORT (nIORT®). The CNG is self-shielded and light-weight (~120 kg) making possible its remote handling by a robotic arm. Accurate Monte Carlo simulations, modelling the CNG and the “open wound” biological tissues near its irradiation window, demonstrated that the apparatus - operated at 100 kV-10 mA - supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~2 Gy (RBE)/min. Hence, it can administer very high dose levels in limited treatment times. This article briefly summarizes the main findings of this collaborative research study, the clinical rationales underpinning the nIORT® idea and the potential performances of the CNG for the treatment of solid cancer pathologies. Indeed, the CNG can be installed in an operating room dedicated to nIORT® treatments, without posing any environmental and safety issues. Monte Carlo simulations have been carried out by envisioning the CNG equipped with an IORT applicator, that is an applicator pipe with a tuneable diameter to be inserted in the surgical cavity. By foreseeing the clinical endpoints of the standard IORT protocols, the irradiation performances for potential nIORT® treatments - obtained with an applicator pipe of 6 cm diameter - are here reported for different regimes: from 10 up to 75 Gy (RBE), that can be administered in a single session of about 4 to 30 minutes. Besides the dose peak in the centre of the tumour bed, the almost isotropic neutrons emission allows to irradiate the surroundings side-walls of the tumour bed – usually filled by potential quiescent cancer cells (QCCs) – and therefore reducing the chances of local recurrences by improving the local control of the tumour. The rapid decrease in tissues depth of the dose profile (in few centimetres) will spare the neighbouring organs at risk from harmful radiations. Thus, the CNG apparatus developed for nIORT® applications can potentially improve the resectability rate of a given neoadjuvant cancer treatment and, generally, could satisfy all five R’s criteria of radiotherapy. Furthermore, in comparing with the current IORT techniques with electrons or low-keV X-rays, the nIORT® exploiting a high-flux neutrons beam of 2.45 MeV energy could lead to some significant clinical advantages due to its larger Linear Energy Transfer (LET, ~ 40 keV/m as average) and significantly higher Relative Biological Effectiveness (RBE 16) than all other forms of ionizing radiation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Compact Neutron Generator for the Niort® Treatment of Severe Solid Cancers

Martellini

2023

MRAJ

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“…Despite the allegation of high toxicity of FNT [91,92] (based on largely outdated sets of clinical evidence in terms of irradiation regimens and equipment used for neutron beam generation), FNT holds great promise for the treatment of various radioresistant tumors with critically limited therapeutic options [93]. Contemporary studies continue to accumulate essential radiobiological data on high-LET therapy involving proton and C-ion irradiation applicable to FNT of similar parameters (eg, Bragg peak, ionization density) [94,95].…”

Section: Prospectsmentioning

confidence: 99%

Fast and Furious: Fast Neutron Therapy in Cancer Treatment

Гордон

Гулидов

Fatkhudinov

et al. 2022

International Journal of Particle Therapy

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Fast neutron therapy has been used for decades. In conjunction with recent advances in photonic techniques, fast neutrons are no longer of much oncologic interest, which is not unequivocally positive, given their undoubted therapeutic value. This mini-review recalls the history of medical research on fast neutrons, considers their physical and radiobiological properties alongside their benefits for cancer treatment, and discusses their place in modern radiation oncology.

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“…Humans are exposed to neutron radiation in a variety of scenarios including space travel (Benton et al 2001, Koshiishi et al 2007, nuclear incidents (Shuryak et al 2020), and radiotherapy procedures such as fast neutron therapy (Jones 2020), neutron capture therapy (Sauerwein et al 2012), and high-energy (8 MeV) radiotherapy (Howell et al 2006, Maglieri et al 2015. Cancer patients treated with high-energy radiotherapy are exposed to a (relatively) low absorbed dose of various types of non-therapeutic 'secondary' radiation, including a polyenergetic spectrum of neutrons that are generated by interactions of the high-energy primary radiation with matter.…”

Section: Introductionmentioning

confidence: 99%

A study of indirect action’s impact on simulated neutron-induced DNA damage

Manalad

Montgomery²,

Kildea³

2023

Phys. Med. Biol.

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Objective: The risk of radiobiological stochastic effects associated with neutrons is strongly energy dependent. Recent Monte Carlo studies simulating neutron-irradiated nuclear DNA have demonstrated that this energy dependence is correlated with the relative biological effectiveness (RBE) of neutrons to inflict DNA damage clusters that contain difficult-to-repair double-strand breaks. However, these previous investigations were either limited to modeling direct radiation action or considered the effects of both direct and indirect action together without distinguishing between the two. In this study, we aimed to quantify the influence of indirect action in neutron irradiation scenarios and acquire novel estimations of the energy-dependent neutron RBE for inducing DNA damage clusters due to both direct and indirect action.Approach: We explored the role of indirect action in neutron-induced DNA damage by integrating a validated indirect action model into our existing simulation pipeline. Using this pipeline, we performed track-structure simulations of monoenergetic neutron irradiations (1 eV to 10 MeV) in a nuclear DNA model and analyzed the resulting simple and clustered DNA lesions. We repeated the irradiation simulations for 250 keV X-rays that acted as our reference radiation.Main results: Including indirect action significantly increased the occurrence of DNA lesions. We found that indirect action tends to amplify the damage due to direct action by inducing DNA lesions in the vicinity of directly-induced lesions, resulting in additional and larger damage clusters. Our neutron RBE results are qualitatively similar to but lower in magnitude than the established radiation protection factors and the results of previous similar investigations, due to the greater relative impact of indirect action in photon-induced damage than in neutron-induced damage.Significance: Although our model for neutron-induced DNA damage has some important limitations, our findings suggest that the energy-dependent risk of neutron-induced stochastic effects may not be completely modeled alone by the relative potential of neutrons to inflict clustered lesions via direct and indirect action in DNA damage.

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Clinical Radiobiology of Fast Neutron Therapy: What Was Learnt?

Cited by 21 publications

References 56 publications

A Compact Neutron Generator for the Niort® Treatment of Severe Solid Cancers

A Compact Neutron Generator for the Niort® Treatment of Severe Solid Cancers

Fast and Furious: Fast Neutron Therapy in Cancer Treatment

A study of indirect action’s impact on simulated neutron-induced DNA damage

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