Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology

Nolan, Michael W.; Kent, Michael S.; Boss, Mary Keara

doi:10.3389/fonc.2019.01291

Cited by 17 publications

(22 citation statements)

References 97 publications

(84 reference statements)

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“…We have previously shown in vitro that the FLASH effect depends on oxygen concentration ( 27 ). Due to the similarities between the tumors of companion animals and humans, also in terms of oxygen profiles ( 19 ), canine cancer patients provide an opportunity for further studying the oxygen dependence in a clinically relevant setting.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, companion animal cancer patients provide an opportunity for performing cross-disciplinary research that has the potential to benefit human and veterinary cancer patients alike. In a recent review article by Nolan et al, the authors describe previous translational studies, where canine cancer patients have been used to model normal tissue response, tumor oxygenation and DNA damage response, and to optimize irradiation parameters for human radiotherapy ( 19 ). Companion animal cancer patients are usually treated with radiotherapy over a period 2-4 weeks, typically 16-20 fractions with a fractional dose of 2.5-4 Gy ( 19 ), requiring multiple anesthesia sessions which may be stressful for the patient.…”

Section: Introductionmentioning

confidence: 99%

“…In a recent review article by Nolan et al, the authors describe previous translational studies, where canine cancer patients have been used to model normal tissue response, tumor oxygenation and DNA damage response, and to optimize irradiation parameters for human radiotherapy ( 19 ). Companion animal cancer patients are usually treated with radiotherapy over a period 2-4 weeks, typically 16-20 fractions with a fractional dose of 2.5-4 Gy ( 19 ), requiring multiple anesthesia sessions which may be stressful for the patient. In contrast, FLASH-RT is delivered in a single or a few fraction(s), making this modality practical and attractive for companion animal radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Konradsson

Arendt

Jensen³

et al. 2021

Front. Oncol.

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FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Konradsson

Arendt

Jensen³

et al. 2021

Front. Oncol.

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“…DNA repair mechanisms are highly conserved between mammalian species, and that there is high homology between key DNA damage response genes in humans and dogs. 10,28 Numerous studies in dogs have modeled normal tissue radiation response and those studies have helped optimize human oncology care, however, no large studies of canine models have been used in space radiation studies of normal tissue effects.…”

Section: What Exactly Is the Operational Space Radiation Environment?mentioning

confidence: 99%

Everything you wanted to know about space radiation but were afraid to ask

Chancellor

Nowadly

Williams

et al. 2021

Journal of Environmental Science and Health, Part C

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The space radiation environment is a complex combination of fast-moving ions derived from all atomic species found in the periodic table. The energy spectrum of each ion species varies widely but is prominently in the range of 400-600 MeV/n. The large dynamic range in ion energy is difficult to simulate in ground-based radiobiology experiments. Most ground-based irradiations with mono-energetic beams of a single one ion species are delivered at comparatively high dose rates. In some cases, sequences of such beams are delivered with various ion species and energies to crudely approximate the complex space radiation environment. This approximation may cause profound experimental bias in processes such as biologic repair of radiation damage, which are known to have strong temporal dependencies. It is possible that this experimental bias leads to an over-prediction of risks of radiation effects that have not been observed in the astronaut cohort. None of the primary health risks presumably attributed to space radiation exposure, such as radiation carcinogenesis, cardiovascular disease, cognitive deficits, etc., have been observed in astronaut or cosmonaut crews. This fundamentally and profoundly limits our understanding of the effects of GCR on humans and limits the development of effective radiation countermeasures.

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“…Owing to the extension of the lifespan of companion animals, the number of elderly dogs and cats have been increasing, and many dogs and cats are newly diagnosed with cancer every year [ 26 , 27 ]. Radiation therapy, which is one of the three major treatments for cancer, has been increasingly used in veterinary hospitals as an alternative for treating cancer in dogs and cats [ 24 , 26 ]. To achieve the most effective radiation therapy, it is important to balance between the toxicity between normal and cancer cells.…”

mentioning

confidence: 99%

Inhibition of Crandell-Rees Feline Kidney cell proliferation by X-ray-induced senescence

Koike

Yutoku

Koike

2021

The Journal of Veterinary Medical Science

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Radioresistance and radiotoxicity have been reported following cancer treatments in felines. Optimizing radiation doses to induce cytotoxic effects to only cancer cells and not normal cells is critical in achieving effective radiation therapy; however, the mechanisms of radiation resistance, radiotoxicity, and DNA damage response (DDR) in feline cells have not yet been elucidated. A DNA double-strand break (DSB) is the most toxic type of DNA damage induced by X-rays and heavy ion beams used in treating cancers. Crandell-Rees Feline Kidney (CRFK) cells is one of the most widely used cat cells in life science research. Here, we report that DSB-triggered senescence induced by X-rays is important in inhibiting the proliferation of CRFK cells. We demonstrated through cell proliferation assay that X-rays at doses 2 Gy and 10 Gy are toxic to CRFK cells that irradiating CRFK cells inhibits their proliferation. In X-irradiated CRFK cells, a dose-dependent increase in DSB-triggered senescence was detected according to morphological changes and using senescence-associated β galactosidase staining assay. Moreover, our data indicated that in CRFK cells, the major DDR pathway, which involves the phosphorylation of H2AX at Ser139, was normally activated by ATM kinases. Our findings are useful in the understanding of X-rays-induced cellular senescence and in elucidating biological effects of radiation, e.g. , toxicity, in feline cells. Furthermore, our findings suggest that the CRFK cell line is an excellent matrix for elucidating radioresistance and radiotoxicity in cat cells.

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Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology

Cited by 17 publications

References 97 publications

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients

Everything you wanted to know about space radiation but were afraid to ask

Inhibition of Crandell-Rees Feline Kidney cell proliferation by X-ray-induced senescence

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