Editorial

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4 pages, 200 KiB

Open AccessEditorial

Animal Models for Radiotherapy Research: All (Animal) Models Are Wrong but Some Are Useful

by Karl T. Butterworth and Jacqueline P. Williams

Cancers 2021, 13(6), 1319; https://doi.org/10.3390/cancers13061319 - 16 Mar 2021

Cited by 6 | Viewed by 1613

Abstract

The distinguished statistician, George E [...] Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

Research

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14 pages, 3201 KiB

Open AccessArticle

Evaluation of a Novel Liquid Fiducial Marker, BioXmark^®, for Small Animal Image-Guided Radiotherapy Applications

by Kathryn H. Brown, Mihaela Ghita, Giuseppe Schettino, Kevin M. Prise and Karl T. Butterworth

Cancers 2020, 12(5), 1276; https://doi.org/10.3390/cancers12051276 - 18 May 2020

Cited by 10 | Viewed by 2691

Abstract

BioXmark^® (Nanovi A/S, Denmark) is a novel fiducial marker based on a liquid, iodine-based and non-metallic formulation. BioXmark^® has been clinically validated and reverse translated to preclinical models to improve cone-beam CT (CBCT) target delineation in small animal image-guided radiotherapy (SAIGRT). [...] Read more.

BioXmark^® (Nanovi A/S, Denmark) is a novel fiducial marker based on a liquid, iodine-based and non-metallic formulation. BioXmark^® has been clinically validated and reverse translated to preclinical models to improve cone-beam CT (CBCT) target delineation in small animal image-guided radiotherapy (SAIGRT). However, in phantom image analysis and in vivo evaluation of radiobiological response after the injection of BioXmark^® are yet to be reported. In phantom measurements were performed to compare CBCT imaging artefacts with solid fiducials and determine optimum imaging parameters for BioXmark^®. In vivo stability of BioXmark^® was assessed over a 5-month period, and the impact of BioXmark^® on in vivo tumour response from single-fraction and fractionated X-ray exposures was investigated in a subcutaneous syngeneic tumour model. BioXmark^® was stable, well tolerated and detectable on CBCT at volumes ≤10 µL. Our data showed imaging artefacts reduced by up to 84% and 89% compared to polymer and gold fiducial markers, respectively. BioXmark^® was shown to have no significant impact on tumour growth in control animals, but changes were observed in irradiated animals injected with BioXmark^® due to alterations in dose calculations induced by the sharp contrast enhancement. BioXmark^® is superior to solid fiducials with reduced imaging artefacts on CBCT. With minimal impact on the tumour growth delay, BioXmark^® can be implemented in SAIGRT to improve target delineation and reduce set-up errors. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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22 pages, 3777 KiB

Open AccessArticle

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury

by Rachel A. Schlaak, Anne Frei, Brian L. Fish, Leanne Harmann, Tracy Gasperetti, Jamie L. Pipke, Yunguang Sun, Hallgeir Rui, Michael J. Flister, Benjamin N. Gantner and Carmen Bergom

Cancers 2020, 12(4), 983; https://doi.org/10.3390/cancers12040983 - 16 Apr 2020

Cited by 6 | Viewed by 2399

Abstract

While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration. [...] Read more.

While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration. We analyzed the functional requirement for these cells in RIHD using a genetic model of T- and B-cell deficiency (interleukin-2 receptor gamma chain knockout (IL2RG^−/−)) and observed a complex role for these cells. Surprisingly, while IL2RG deficiency conferred protection from cardiac hypertrophy, it worsened heart function via echocardiogram three months after a large single RT dose, including increased end-systolic volume (ESV) and reduced ejection fraction (EF) and fractional shortening (FS) (p < 0.05). Fractionated RT, however, did not yield similarly increased injury. Our results indicate that T cells are not uniformly required for RIHD in this model, nor do they account for our previously reported differences in cardiac RT sensitivity between SS and SS.BN3 rats. The increasing use of immunotherapies in conjunction with traditional cancer treatments demands better models to study the interactions between immunity and RT for effective therapy. We present a model that reveals complex roles for adaptive immune cells in cardiac injury that vary depending on clinically relevant factors, including RT dose/fractionation, sex, and genetic background. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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12 pages, 1486 KiB

Open AccessArticle

Tumor Size Matters—Understanding Concomitant Tumor Immunity in the Context of Hypofractionated Radiotherapy with Immunotherapy

by Jean Philippe Nesseler, Mi-Heon Lee, Christine Nguyen, Anusha Kalbasi, James W. Sayre, Tahmineh Romero, Philippe Nickers, William H. McBride and Dörthe Schaue

Cancers 2020, 12(3), 714; https://doi.org/10.3390/cancers12030714 - 18 Mar 2020

Cited by 16 | Viewed by 3220

Abstract

The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent [...] Read more.

The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1. Immune profiles within T1 and T2 tumors and in spleen changed drastically with tumor burden in untreated mice with infiltrating CD4+ content declining, while the proportion of CD4+ Tregs rose. Myeloid cell representation escalated in larger tumors, resulting in major decreases in the lymphoid:myeloid ratios. In general, activation of Tregs and myeloid-derived suppressor cells allow immunogenic tumors to grow, although their relative contributions change with time. The evidence suggests that primary T1 tumors self-regulate their immune content depending on their size and this can influence the lymphoid compartment of T2 tumors, especially with respect to Tregs. Tumor burden is a major confounding factor in immune analysis that has to be taken into consideration in experimental models and in the clinic. hRT caused complete local regression of primary tumors, which was accompanied by heavy infiltration of CD8+ T cells activated to express IFN-γ and PD-1; while certain myeloid populations diminished. In spite of this active infiltrate, primary hRT failed to generate the systemic conditions required to cause abscopal regression of unirradiated microscopic tumors unless PD-1 blockade, which on its own was ineffective, was added to the RT regimen. The combination further increased local and systemically activated CD8+ T cells, but few other changes. This study emphasizes the subtle interplay between the immune system and tumors as they grow and how difficult it is for local RT, which can generate a local immune response that may help with primary tumor regression, to overcome the systemic barriers that are generated so as to effect immune regression of even small abscopal lesions. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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16 pages, 4487 KiB

Open AccessArticle

Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts

by Vui King Vincent-Chong and Mukund Seshadri

Cancers 2020, 12(3), 579; https://doi.org/10.3390/cancers12030579 - 02 Mar 2020

Cited by 8 | Viewed by 4361

Abstract

Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model [...] Read more.

Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD₅₀ for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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23 pages, 5062 KiB

Open AccessArticle

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

by J. Tyson McDonald, Robert Stainforth, Jack Miller, Thomas Cahill, Willian A. da Silveira, Komal S. Rathi, Gary Hardiman, Deanne Taylor, Sylvain V. Costes, Vinita Chauhan, Robert Meller and Afshin Beheshti

Cancers 2020, 12(2), 381; https://doi.org/10.3390/cancers12020381 - 07 Feb 2020

Cited by 20 | Viewed by 5559

Abstract

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation [...] Read more.

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. Methods: We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 to 1.0 Gy for ground studies, as well as samples flown in low Earth orbit (LEO) with total doses of 1.0 mGy to 30 mGy, were utilized. Results: From this analysis, we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. Conclusions: We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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9 pages, 10853 KiB

Open AccessArticle

Non-Invasive Targeted Hepatic Irradiation and SPECT/CT Functional Imaging to Study Radiation-Induced Liver Damage in Small Animal Models

by Rafi Kabarriti, N. Patrik Brodin, Hillary Yaffe, Mark Barahman, Wade R. Koba, Laibin Liu, Patrik Asp, Wolfgang A. Tomé and Chandan Guha

Cancers 2019, 11(11), 1796; https://doi.org/10.3390/cancers11111796 - 15 Nov 2019

Cited by 5 | Viewed by 2778

Abstract

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the [...] Read more.

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers. In the setting of modern-day radiation oncology, a truly translational animal model would require the ability to deliver RT to specific parts of the liver, through non-invasive image guidance methods. To this end, we developed a targeted hepatic irradiation model on the Small Animal Radiation Research Platform (SARRP) using contrast-enhanced cone-beam computed tomography image guidance. Using this model, we showed evidence of the early development of region-specific RILD through functional single photon emission computed tomography (SPECT) imaging. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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Review

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26 pages, 1360 KiB

Open AccessReview

Animal Models in Microbeam Radiation Therapy: A Scoping Review

by Cristian Fernandez-Palomo, Jennifer Fazzari, Verdiana Trappetti, Lloyd Smyth, Heidrun Janka, Jean Laissue and Valentin Djonov

Cancers 2020, 12(3), 527; https://doi.org/10.3390/cancers12030527 - 25 Feb 2020

Cited by 24 | Viewed by 5026

Abstract

Background: Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres. Objective: This scoping [...] Read more.

Background: Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres. Objective: This scoping review was conducted to map the available evidence and provide a comprehensive overview of the similarities, differences, and outcomes of all experiments that have employed animal models in MRT. Methods: We considered articles that employed animal models for the purpose of studying the effects of MRT. We searched in seven databases for published and unpublished literature. Two independent reviewers screened citations for inclusion. Data extraction was done by three reviewers. Results: After screening 5688 citations and 159 full-text papers, 95 articles were included, of which 72 were experimental articles. Here we present the animal models and pre-clinical radiation parameters employed in the existing MRT literature according to their use in cancer treatment, non-neoplastic diseases, or normal tissue studies. Conclusions: The study of MRT is concentrated in brain-related diseases performed mostly in rat models. An appropriate comparison between MRT and conventional radiotherapy (instead of synchrotron broad beam) is needed. Recommendations are provided for future studies involving MRT. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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15 pages, 1655 KiB

Open AccessReview

Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity

by Michael K. Farris, Corbin A. Helis, Ryan T. Hughes, Michael C. LeCompte, Alexander M. Borg, Karina Nieto, Michael T. Munley and Jeffrey S. Willey

Cancers 2020, 12(2), 427; https://doi.org/10.3390/cancers12020427 - 12 Feb 2020

Cited by 5 | Viewed by 2672

Abstract

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of [...] Read more.

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose–response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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14 pages, 1370 KiB

Open AccessFeature PaperReview

Patient Derived Models to Study Head and Neck Cancer Radiation Response

by Pippa F. Cosper, Lindsey Abel, Yong-Syu Lee, Cristina Paz, Saakshi Kaushik, Kwangok P. Nickel, Roxana Alexandridis, Jacob G. Scott, Justine Y. Bruce and Randall J. Kimple

Cancers 2020, 12(2), 419; https://doi.org/10.3390/cancers12020419 - 12 Feb 2020

Cited by 16 | Viewed by 5041

Abstract

Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head [...] Read more.

Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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22 pages, 1285 KiB

Open AccessReview

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

by Rachel A. Schlaak, Gopika SenthilKumar, Marjan Boerma and Carmen Bergom

Cancers 2020, 12(2), 415; https://doi.org/10.3390/cancers12020415 - 11 Feb 2020

Cited by 38 | Viewed by 4995

Abstract

Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic [...] Read more.

Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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13 pages, 1149 KiB

Open AccessReview

Neurocognitive Decline Following Radiotherapy: Mechanisms and Therapeutic Implications

by Simonetta Pazzaglia, Giovanni Briganti, Mariateresa Mancuso and Anna Saran

Cancers 2020, 12(1), 146; https://doi.org/10.3390/cancers12010146 - 08 Jan 2020

Cited by 47 | Viewed by 5650

Abstract

The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at [...] Read more.

The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at treatment, and younger age associates with harsher deficiencies. Radiation has been shown to induce damage in several cell populations of the mouse brain. Indeed, brain exposure causes a dysfunction of the neurogenic niche due to alterations in the neuronal and supporting cell progenitor signaling environment, particularly in the hippocampus—a region of the brain critical to memory and cognition. Consequent deficiencies in rates of generation of new neurons, neural differentiation and apoptotic cell death, lead to neuronal deterioration and lasting repercussions on neurocognitive functions. Besides neural stem cells, mature neural cells and glial cells are recognized IR targets. We will review the current knowledge about radiation-induced damage in stem cells of the brain and discuss potential treatment interventions and therapy methods to prevent and mitigate radiation related cognitive decline. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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16 pages, 2757 KiB

Open AccessReview

Preclinical Models of Craniospinal Irradiation for Medulloblastoma

by Jennifer L. Stripay, Thomas E. Merchant, Martine F. Roussel and Christopher L. Tinkle

Cancers 2020, 12(1), 133; https://doi.org/10.3390/cancers12010133 - 05 Jan 2020

Cited by 5 | Viewed by 5114

Abstract

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the [...] Read more.

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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Other

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12 pages, 2222 KiB

Open AccessBrief Report

Development and Validation of a Clinically Relevant Workflow for MR-Guided Volumetric Arc Therapy in a Rabbit Model of Head and Neck Cancer

by Eftekhar Rajab Bolookat, Harish Malhotra, Laurie J. Rich, Sandra Sexton, Leslie Curtin, Joseph A. Spernyak, Anurag K. Singh and Mukund Seshadri

Cancers 2020, 12(3), 572; https://doi.org/10.3390/cancers12030572 - 01 Mar 2020

Cited by 2 | Viewed by 2212

Abstract

There is increased interest in the use of magnetic resonance imaging (MRI) for guiding radiation therapy (RT) in the clinical setting. In this regard, preclinical studies can play an important role in understanding the added value of MRI in RT planning. In the [...] Read more.

There is increased interest in the use of magnetic resonance imaging (MRI) for guiding radiation therapy (RT) in the clinical setting. In this regard, preclinical studies can play an important role in understanding the added value of MRI in RT planning. In the present study, we developed and validated a clinically relevant integrated workflow for MRI-guided volumetric arc therapy (VMAT) in a VX2 rabbit neck tumor model of HNSCC. In addition to demonstrating safety and feasibility, we examined the therapeutic impact of MR-guided VMAT using a single high dose to obtain proof-of-concept and compared the response to conventional 2D-RT. Contrast-enhanced MRI (CE-MRI) provided excellent soft tissue contrast for accurate tumor segmentation for VMAT. Notably, MRI-guided RT enabled improved tumor targeting ability and minimal dose to organs at risk (OAR) compared to 2D-RT, which resulted in notable morbidity within a few weeks of RT. Our results highlight the value of integrating MRI into the workflow for VMAT for improved delineation of tumor anatomy and optimal treatment planning. The model combined with the multimodal imaging approach can serve as a valuable platform for the conduct of preclinical RT trials. Full article

(This article belongs to the Special Issue Animal Models for Radiotherapy Research)

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