Electronic brachytherapy used for the successful treatment of three different types of equine tumours

Bradley, William; Schilpp, D.; Khatibzadeh, Sarah M.

doi:10.1111/eve.12420

Cited by 18 publications

(5 citation statements)

References 9 publications

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“…Most of the tumors show a slow growth pattern over years, however, more than 60% become malignant and cause clinical problems due to enlargement und widespread metastases [ 29 – 31 ]. Treatment options reported with varying outcomes include systemic and local approaches, such as immunotherapy [ 32 – 34 ], cimetidine application [ 35 , 36 ], radiation [ 37 ], surgery [ 38 , 39 ], and chemotherapy with cisplatin alone [ 40 , 41 ] or in combination with electrochemotherapy [ 42 , 43 ]. Although effective in many cases, surgical excision can be challenging due to the unfavorable localization of the tumors and the intratumoral injection of the mutagenic and carcinogenic cisplatin is linked to strict safety rules [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

et al. 2020

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Equine sarcoid (ES) is the most prevalent skin tumor in equids worldwide. Additionally, aging grey horses frequently suffer from equine malignant melanoma (EMM). Current local therapies targeting these skin tumors remain challenging. Therefore, more feasible topical treatment options should be considered. In order to develop a topical therapy against ES and EMM, betulinyl-bis-sulfamate and NVX-207, derivatives of the naturally occurring betulin and betulinic acid, respectively, were evaluated for their antiproliferative (crystal violet staining assay), cytotoxic (MTS assay) and apoptotic (AnnexinV staining, cell cycle investigations) effects on primary ES cells, EMM cells and equine dermal fibroblasts in vitro. The more potent derivative was assessed for its in vitro penetration and permeation on isolated equine skin within 30 min and 24 h using Franz-type diffusion cells and HPLC analysis. Betulinyl-bis-sulfamate and NVX-207 inhibited the proliferation and metabolism in ES cells, EMM cells and fibroblasts significantly (p < 0.001) in a time- and dose-dependent manner. NVX-207 had superior anticancer effects compared to betulinyl-bis-sulfamate. Both compounds led to the externalization of phosphatidylserines on the cell membrane and DNA fragmentation, demonstrating that the effective mode of action was apoptosis. After 48 h of treatment with NVX-207, the number of necrotic cells was less than 2% in all cell types. Detected amounts of NVX-207 in the different skin layers exceeded the half-maximal inhibitory concentrations calculated by far. Even though data obtained in vitro are auspicious, the results are not unconditionally applicable to the clinical situation. Consequently, in vivo studies are required to address the antitumoral effects of topically applied NVX-207 in ES and EMM patients.

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Section: Introductionmentioning

confidence: 99%

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

et al. 2020

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“…Electronic brachytherapy systems with low KeV Xrays (@1) is currently pursued on equine patients in several hospitals worldwide for convenient and effective treatments. nIORT® has a much higher (@16) RBE than the above mentioned practice, therefore nIORT® application might be much more successful for the equine treatments 49,50 . The design of the 100 kV-10mA DD-CNG equipped a typical IORT applicator and its shielding structure is currently under development.…”

Section: Discussionmentioning

confidence: 94%

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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“…Particularly because there is no established gold-standard treatment for equine melanoma, comparative study protocols should be considered for prospective studies. The phytochemical therapy introduced here and other described treatment modalities including surgery [ 62 , 63 ], radiation [ 64 , 65 ], (electro)chemotherapy [ 66 , 67 , 68 ] or immunotherapy [ 39 , 50 , 69 , 70 ] could be investigated. Moreover, approaches combining the aforementioned therapies with BA or NVX-207 as an adjunctive topical treatment could be the subject of further research.…”

Section: Discussionmentioning

confidence: 99%

Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses

Weber

Delarocque

Feige

et al. 2021

Animals

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The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.

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Electronic brachytherapy used for the successful treatment of three different types of equine tumours

Cited by 18 publications

References 9 publications

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer

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

Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses

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