@article{meneses_gidcumb_marcus_gonzalez_lai_mishra_lascelles_nolan_2023, title={Acute radiotherapy-associated oral pain may promote tumor growth at distant sites}, volume={13}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2023.1029108}, abstractNote={IntroductionPatients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.}, journal={FRONTIERS IN ONCOLOGY}, author={Meneses, Constanza S. and Gidcumb, Emily M. and Marcus, Karen L. and Gonzalez, Yarines and Lai, Yen Hao and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2023}, month={May} } @article{woelfel_mariani_nolan_keenihan_topulos_early_munana_musulin_olby_2023, title={Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes}, volume={4}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16703}, DOI={10.1111/jvim.16703}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Woelfel, Christian W. and Mariani, Christopher L. and Nolan, Michael W. and Keenihan, Erin K. and Topulos, Sophia P. and Early, Peter J. and Munana, Karen R. and Musulin, Sarah E. and Olby, Natasha J.}, year={2023}, month={Apr} } @article{baja_kelsey_ruslander_gieger_nolan_2022, title={A retrospective study of 101 dogs with oral melanoma treated with a weekly or biweekly 6 Gy x 6 radiotherapy protocol}, volume={4}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12815}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Baja, Alexie J. and Kelsey, Krista L. and Ruslander, David M. and Gieger, Tracy L. and Nolan, Michael W.}, year={2022}, month={Apr} } @article{watson-skaggs_gieger_yoshikawa_nolan_2022, title={Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy)}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.08.0122}, abstractNote={Abstract}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Watson-Skaggs, Maegan L. and Gieger, Tracy L. and Yoshikawa, Hiroto and Nolan, Michael W.}, year={2022}, month={Jan}, pages={64–71} } @article{nolan_uzan_green_lana_lascelles_2022, title={Intensity of perioperative analgesia but not pre-treatment pain is predictive of survival in dogs undergoing amputation plus chemotherapy for extremity osteosarcoma}, volume={3}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12808}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Nolan, Michael W. and Uzan, Olivia C. and Green, Noah A. and Lana, Susan E. and Lascelles, B. Duncan X.}, year={2022}, month={Mar} } @article{gieger_haney_nolan_2022, title={Re-irradiation of canine non-lymphomatous nasal tumours using stereotactic radiation therapy (10 Gy x 3) for both courses: Assessment of outcome and toxicity in 11 dogs}, volume={2}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12801}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gieger, Tracy L. and Haney, Siobhan M. and Nolan, Michael W.}, year={2022}, month={Feb} } @article{nolan_berman_watson-skaggs_quinn_marcus_russell_yoshikawa_olby_gieger_2022, title={Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.03.0141}, abstractNote={Abstract}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Nolan, Michael W. and Berman, Alyssa R. and Watson-Skaggs, Maegan L. and Quinn, Claire N. and Marcus, Karen L. and Russell, Katharine and Yoshikawa, Hiroto and Olby, Natasha J. and Gieger, Tracy L.}, year={2022}, month={Sep}, pages={1496–1506} } @article{lai_lascelles_nolan_2021, title={Behavioral phenotyping of cancer pain in domesticated cats with naturally occurring squamous cell carcinoma of the tongue: initial validation studies provide evidence for regional and widespread algoplasticity}, volume={9}, ISSN={["2167-8359"]}, DOI={10.7717/peerj.11984}, abstractNote={Feline oral squamous cell carcinoma (FOSCC) is a common and naturally occurring condition that recapitulates many features of human head and neck cancer (HNC). In both species, there is need for improved strategies to reduce pain caused by HNC and its treatment. Research to benefit both species could be conducted using pet cats as a comparative model, but this prospect is limited by lack of validated methods for quantifying FOSCC-associated pain. A prospective non-randomized pilot study was performed for initial validation of: (1) a pet owner administered quality of life questionnaire and visual assessment scoring tool (FORQ/CLIENT); (2) a clinician assessment questionnaire (UFEPS/VET); (3) electronic von Frey testing [EVF]; and (4) Cochet-Bonnet (COBO) aesthesiometry. To assess intra-rater reliability, discriminatory ability, and responsiveness of each assay, 6 cats with sublingual SCC and 16 healthy control cats were enrolled. The intra-rater reliability was moderate-to-good for the clinical metrology instruments and EVF (intraclass correlation coefficient [ICC] ≥ 0.68), but poor for COBO (ICC = 0.21). FORQ/CLIENT scores were higher (worse quality of life) in FOSCC cats vs healthy controls. The internal reliability of FORQ/CLIENT scoring was high (Cronbach α = 0.92); sensitivity and specificity were excellent (100% when using cut-offs determined using receiver operating characteristic [ROC] curves). For the FORQ/CLIENT, there was strong and inverse correlation between scores from the questions and visual assessment (r =  − 0.77, r2 = 0.6, P < 0.0001). For the UFEPS/VET, Cronbach’s α was 0.74 (high reliability). Sensitivity and specificity were 100% and 94%, respectively, when using a cut-off score (3.5) based on ROC curves (Youden index of 0.94). Total UFEPS/VET scores were positively correlated with FORQ/CLIENT scores (r2 = 0.72, P < 0.0001). Sensitivity of EVF and COBO ranged from 83 to 100% and specificity ranged from 56 to 94%. Cats with cancer were more sensitive around the face (lower response thresholds) and on the cornea (longer filament lengths) than control animals (P < 0.03). Reduced pressure response thresholds were also observed at a distant site (P = 0.0002) in cancer cats. After giving buprenorphine, EVF pressure response thresholds increased (P = 0.04) near the mandible of cats with OSCC; the length of filament required to elicit a response in the COBO assay also improved (shortened; P = 0.017). Based on these preliminary assessments, the assays described herein had reasonable inter-rater reliability, and they were able to both discriminate between cats with and without oral cancer, and respond in a predictable manner to analgesic therapy. In cats with tongue cancer, there was evidence for regional peripheral sensitization, and widespread somatosensory sensitization. These results provide a basis for multi-dimensional assessments of pain and sensitivity in cats with oral SCC.}, journal={PEERJ}, author={Lai, Yen-Hao Erik and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Aug} } @article{price_lai_marcus_robertson_lascelles_nolan_2021, title={Early radiation-induced oral pain signaling responses are reduced with pentoxifylline treatment}, volume={62}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12943}, abstractNote={Abstract}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Price, Mikayla L. and Lai, Yen-Hao Erik and Marcus, Karen L. and Robertson, James B. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Mar}, pages={255–263} } @article{lai_baumer_meneses_roback_robertson_mishra_lascelles_nolan_2021, title={Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels}, volume={196}, ISSN={["1938-5404"]}, DOI={10.1667/RADE-21-000103.1}, abstractNote={Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Female CD-1 mice received single high-dose (27 Gy) tongue irradiation, or sham irradiation. Animals were euthanized either before overt glossitis developed (days 1 and 5 postirradiation), when glossitis was severe (day 11), or after mice had recovered (days 21 and 45). Tongue irradiation caused upregulation of the Trpv1 gene in trigeminal ganglia (TG) neurons. Other TRP genes (Trpv2, Trpv4, Trpa1, Trpm8) and Gfrα3 (which acts upstream of several TRP channels) were also upregulated in TGs and/or tongue tissue, in response to radiation. Ex vivo calcium imaging experiments demonstrated that the proportions of TG neurons responding to histamine (an activator of TRPV1, TRPV4 and TRPA1), TNF-α (an activator of TRPV1, TRPV2 and TRPV4), and capsaicin (a TRPV1 agonist), were increased as early as one day after tongue irradiation; these changes persisted for at least 21 days. In a subsequent experiment, we found that genetic deletion of TRPV1 mitigated weight loss (a surrogate marker of pain severity) in mice with severe glossitis. The results intimate that various TRP channels, and TRPV1 in particular, should be explored as analgesic targets for patients experiencing pain after oral irradiation.}, number={4}, journal={RADIATION RESEARCH}, author={Lai, Yen and Baumer, Wolfgang and Meneses, Constanza and Roback, Donald M. and Robertson, James B. and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Oct}, pages={331–344} } @article{lai_morhard_ramanujam_nolan_2021, title={Minimally invasive ethyl cellulose ethanol ablation in domesticated cats with naturally occurring head and neck cancers: Six cats}, volume={19}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12687}, abstractNote={Abstract}, number={3}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Lai, Yen-Hao Erik and Morhard, Robert and Ramanujam, Nirmala and Nolan, Michael W.}, year={2021}, month={Sep}, pages={492–500} } @article{yoshikawa_gieger_saba_fredrickson_kubicek_haney_ruslander_kelsey_mcentee_nolan_2021, title={Retrospective evaluation of intranasal carcinomas in cats treated with external-beam radiotherapy: 42 cases}, volume={35}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16098}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Yoshikawa, Hiroto and Gieger, Tracy L. and Saba, Corey F. and Fredrickson, Kirsha and Kubicek, Lyndsay and Haney, Siobhan and Ruslander, David and Kelsey, Krista L. and McEntee, Margaret C. and Nolan, Michael W.}, year={2021}, month={Mar}, pages={1018–1030} } @article{hunt_choudhury_nukala_nolan_ahmad_ashcraft_koontz_2021, title={Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer}, volume={24}, ISSN={["1476-5608"]}, DOI={10.1038/s41391-020-0247-x}, abstractNote={{"Label"=>"BACKGROUND"} Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. {"Label"=>"METHODS"} A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. {"Label"=>"RESULTS"} Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. {"Label"=>"CONCLUSION"} ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.}, number={1}, journal={PROSTATE CANCER AND PROSTATIC DISEASES}, author={Hunt, Anastasia A. and Choudhury, Kingshuk Roy and Nukala, Varun and Nolan, Michael W. and Ahmad, Alina and Ashcraft, Kathleen A. and Koontz, Bridget F.}, year={2021}, month={Mar}, pages={128–134} } @article{gieger_seiler_nolan_2021, title={Treatment of feline gastrointestinal intermediate- or large-cell lymphoma with lomustine chemotherapy and 8 Gy abdominal cavity radiation therapy}, volume={23}, ISSN={["1532-2750"]}, DOI={10.1177/1098612X20959602}, abstractNote={Objectives The goal of this study was to document the outcomes and toxicity of a novel multimodality treatment protocol for feline gastrointestinal intermediate- or large-cell lymphoma (FGL) in which cats were treated at 21-day intervals. }, number={6}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Gieger, Tracy L. and Seiler, Gabriela S. and Nolan, Michael W.}, year={2021}, month={Jun}, pages={469–476} } @article{clerc-renaud_gieger_larue_nolan_2021, title={Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study}, volume={35}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16078}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Clerc-Renaud, Benoit and Gieger, Tracy L. and LaRue, Susan M. and Nolan, Michael W.}, year={2021}, month={Mar}, pages={1052–1061} } @article{gieger_nolan_2021, title={Treatment outcomes and target delineation utilizingCTandMRIin 13 dogs treated with a uniform stereotactic radiation therapy protocol (16 Gy single fraction) for pituitary masses: (2014-2017)}, volume={19}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12627}, abstractNote={Abstract}, number={1}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gieger, Tracy L. and Nolan, Michael W.}, year={2021}, month={Mar}, pages={17–24} } @article{rickard_yoshikawa_palmer_liu_dewhirst_nolan_zhang_2020, title={Cherenkov emissions for studying tumor changes during radiation therapy: An exploratory study in domesticated dogs with naturally-occurring cancer}, volume={15}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0238106}, abstractNote={Purpose Real-time monitoring of physiological changes of tumor tissue during radiation therapy (RT) could improve therapeutic efficacy and predict therapeutic outcomes. Cherenkov radiation is a normal byproduct of radiation deposited in tissue. Previous studies in rat tumors have confirmed a correlation between Cherenkov emission spectra and optical measurements of blood-oxygen saturation based on the tissue absorption coefficients. The purpose of this study is to determine if it is feasible to image Cherenkov emissions during radiation therapy in larger human-sized tumors of pet dogs with cancer. We also wished to validate the prior work in rats, to determine if Cherenkov emissions have the potential to act an indicator of blood-oxygen saturation or water-content changes in the tumor tissue–both of which have been correlated with patient prognosis. Methods A DoseOptics camera, built to image the low-intensity emission of Cherenkov radiation, was used to measure Cherenkov intensities in a cohort of cancer-bearing pet dogs during clinical irradiation. Tumor type and location varied, as did the radiation fractionation scheme and beam arrangement, each planned according to institutional standard-of-care. Unmodulated radiation was delivered using multiple 6 MV X-ray beams from a clinical linear accelerator. Each dog was treated with a minimum of 16 Gy total, in ≥3 fractions. Each fraction was split into at least three subfractions per gantry angle. During each subfraction, Cherenkov emissions were imaged. Results We documented significant intra-subfraction differences between the Cherenkov intensities for normal tissue, whole-tumor tissue, tissue at the edge of the tumor and tissue at the center of the tumor (p<0.05). Additionally, intra-subfraction changes suggest that Cherenkov emissions may have captured fluctuating absorption properties within the tumor. Conclusion Here we demonstrate that it is possible to obtain Cherenkov emissions from canine cancers within a fraction of radiotherapy. The entire optical spectrum was obtained which includes the window for imaging changes in water and hemoglobin saturation. This lends credence to the goal of using this method during radiotherapy in human patients and client-owned pets.}, number={8}, journal={PLOS ONE}, author={Rickard, Ashlyn G. and Yoshikawa, Hiroto and Palmer, Gregory M. and Liu, Harrison Q. and Dewhirst, Mark W. and Nolan, Michael W. and Zhang, Xiaofeng}, year={2020}, month={Aug} } @article{crownshaw_mcentee_nolan_gieger_2020, title={Evaluation of variables associated with outcomes in 41 dogs with incompletely excised high-grade soft tissue sarcomas treated with definitive-intent radiation therapy with or without chemotherapy}, volume={256}, ISSN={["1943-569X"]}, DOI={10.2460/javma.256.7.783}, abstractNote={Abstract}, number={7}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Crownshaw, Abigail H. and McEntee, Margaret C. and Nolan, Michael W. and Gieger, Tracy L.}, year={2020}, month={Apr}, pages={783–791} } @article{elliott_linder_nolan_2020, title={Feasibility study evaluating arrhythmogenesis and cardiac damage after heart-base irradiation in mice: A brief communication}, volume={6}, ISSN={["2053-1095"]}, DOI={10.1002/vms3.303}, abstractNote={Abstract}, number={4}, journal={VETERINARY MEDICINE AND SCIENCE}, author={Elliott, James and Linder, Keith and Nolan, Michael W.}, year={2020}, month={Nov}, pages={1009–1016} } @article{nolan_green_divito_lascelles_haney_2020, title={Impact of radiation dose and pre-treatment pain levels on survival in dogs undergoing radiotherapy with or without chemotherapy for presumed extremity osteosarcoma}, volume={18}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12576}, abstractNote={Abstract}, number={4}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Nolan, Michael W. and Green, Noah A. and DiVito, Elizabeth M. and Lascelles, B. Duncan X. and Haney, Siobhan M.}, year={2020}, month={Dec}, pages={538–547} } @article{baja_lewbart_luff_nolan_2020, title={Unexpected but transient tumour enlargement preceded complete regression and long-term control after irradiation of squamous cell carcinoma in a red-eared slider (Trachemys scripta elegans)}, volume={8}, ISSN={["2052-6121"]}, DOI={10.1136/vetreccr-2019-001039}, abstractNote={A red‐eared slider with a chronic non‐healing ulcerative shell lesion was diagnosed with cutaneous squamous cell carcinoma (SCC). The animal underwent surgical debulking and adjuvant hypofractionated radiation therapy. The lesion initially responded, with near‐complete tumour regression, but then began growing again just a few months after finishing radiotherapy. Then, after several months with no additional tumour‐directed therapy, the lesion again regressed. Five years post‐irradiation and with no further treatment, the turtle now remains tumour‐free. This unusual pattern of disease regression, followed by transient growth and then long‐term local tumour control, suggests either a spontaneous remission or a pseudoprogression‐like phenomenon. Careful clinical follow‐up and reporting of future cases will aid in determining whether this pseudoprogression‐like event was random, versus being a common component of the chelonian response to irradiation of cutaneous SCC.}, number={2}, journal={VETERINARY RECORD CASE REPORTS}, author={Baja, Alexie J. and Lewbart, Gregory A. and Luff, Jennifer A. and Nolan, Michael W.}, year={2020}, month={Jun} } @article{yoshikawa_nolan_2019, title={Changes in target volume during irradiation of canine intranasal tumors can significantly impact radiation dosimetry}, volume={60}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12782}, abstractNote={Abstract}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Yoshikawa, Hiroto and Nolan, Michael W.}, year={2019}, month={Sep}, pages={594–604} } @misc{nolan_kent_boss_2019, title={Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology}, volume={9}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2019.01291}, abstractNote={It is estimated that more than 6 million pet dogs are diagnosed with cancer annually in the USA. Both primary care and specialist veterinarians are frequently called upon to provide clinical care that improves the quality and/or quantity of life for affected animals. Because these cancers develop spontaneously in animals that often share the same environment as their owners, have intact immune systems and are of similar size to humans, and because the diagnostic tests and treatments for these cancers are similar to those used for management of human cancers, canine cancer provides an opportunity for research that simultaneously helps improve both canine and human health care. This is especially true in the field of radiation oncology, for which there is a rich and continually evolving history of learning from the careful study of pet dogs undergoing various forms of radiotherapy. The purpose of this review article is to inform readers of the potential utility and limitations of using dogs in that manner; the peer-reviewed literature will be critically reviewed, and current research efforts will be discussed. The article concludes with a look toward promising future directions and applications of this pet dog “model.”}, journal={FRONTIERS IN ONCOLOGY}, author={Nolan, Michael W. and Kent, Michael S. and Boss, Mary-Keara}, year={2019}, month={Nov} } @article{gieger_nolan_roback_suter_2019, title={Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias}, volume={60}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12776}, abstractNote={Abstract}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Gieger, Tracy L. and Nolan, Michael W. and Roback, Donald M. and Suter, Steven E.}, year={2019}, month={Sep}, pages={586–593} } @article{magestro_cahoon_gieger_nolan_2019, title={Radiotherapy isocenters verified by matching to bony landmarks of the canine and feline head differ when localized using volumetric versus planar imaging}, volume={17}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12522}, abstractNote={Abstract}, number={4}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Magestro, Leanne M. and Cahoon, Joyce Y. and Gieger, Tracy L. and Nolan, Michael W.}, year={2019}, month={Dec}, pages={562–569} } @article{nolan_balogh_waltman_2019, title={Teaching Tip: Virtual Oncology Clinic}, volume={46}, ISSN={["1943-7218"]}, DOI={10.3138/jvme.0817-107r}, abstractNote={ Due to limitations in traditional approaches to didactic and clinical learning, professional veterinary medical students face challenges in developing skills and competencies related to clinical practice. The Veterinary Information Network’s (VIN) Virtual Clinic (VVC) aims to support learning by using gaming techniques to simulate clinical case management in a low-risk setting. The VVC lets students explore medical scenarios inside a virtual hospital. The purpose of this article is to describe the development and implementation of a learning approach that blends classroom instructor-directed learning with online simulation-based learning, using the VVC. We share challenges and successes of this approach. The case vignettes in the specific example described herein are for canine multicentric lymphoma. However, the lessons learned through the implementation of this oncology clinic module are expected to apply to a wide range of clinical disciplines. }, number={3}, journal={JOURNAL OF VETERINARY MEDICAL EDUCATION}, author={Nolan, Michael W. and Balogh, Marton and Waltman, Suzanne Shelly}, year={2019}, pages={367–371} } @article{nolan_gieger_2019, title={Update in Veterinary Radiation Oncology Focus on Stereotactic Radiation Therapy}, volume={49}, ISSN={["1878-1306"]}, DOI={10.1016/j.cvsm.2019.05.001}, abstractNote={Stereotactic radiotherapy (SRT) involves the precise delivery of highly conformal, dose-intense radiation to well-demarcated tumors. Special equipment and expertise are needed, and a unique biological mechanism distinguishes SRT from other forms of external beam radiotherapy. Families find the convenient schedules and minimal acute toxicity of SRT appealing. Common indications in veterinary oncology include nasal, brain, and bone tumors. Many other solid tumors can also be treated, including spinal, oral, lung, heart-base, liver, adrenal, and prostatic malignancies. Accessibility of SRT is improving, and new data are constantly emerging to define parameters for appropriate case selection, radiation dose prescription, and long-term follow-up."}, number={5}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Nolan, Michael W. and Gieger, Tracy L.}, year={2019}, month={Sep}, pages={933-+} } @article{adams_nolan_ivanisevic_2018, title={Ga Ion-Enhanced and Particle Shape-Dependent Generation of Reactive Oxygen Species in X-ray-Irradiated Composites}, volume={3}, ISSN={["2470-1343"]}, DOI={10.1021/acsomega.8b00524}, abstractNote={The reported results test the effects of the collective behavior hypothesized to contribute to the production of more reactive oxygen species (ROS) in vitro and result in an enhanced radiosensitization. The role of particle shape in composites with gallium oxyhydroxide (GaOOH) particles and Matrigel is studied. Particles of two different shapes are embedded into the gel to understand only the materials effect on the generation of ROS rather than cell penetrating variations. The paper reports materials characterization by scanning electron microscopy and X-ray diffraction. The stability of the particles within the composite is assessed by quantification of leached metal using inductively coupled plasma mass spectrometry. The amount of ROS in each construct under variable radiation conditions is quantified in the presence and absence of PC12 cells seeded on top of the composites. The viability of cells is also recorded under different in vitro conditions. The collective materials characterization and the results from the bioassays are used to explain the role of anisotropy on the radiosensitization of nanostructures containing Ga. The presence of Ga ions in composites can have a radiosensitizing effect, and the amount of the available Ga3+ determines the magnitude of the radiosensitization. The shape of the particles determines the stability in aqueous solutions and release of Ga3+ that triggers ROS production. The concentration and shape of Ga-containing materials can be combined to generate an additive effect by increasing the amount of available free metal ions in solution. The studies with GaOOH containing composites enable one to explore the role of key parameters that lead to an increased efficiency of radiation treatments.}, number={5}, journal={ACS OMEGA}, author={Adams, W. T. and Nolan, Michael W. and Ivanisevic, Albena}, year={2018}, month={May}, pages={5252–5259} } @article{gieger_nolan_2018, title={Linac-based stereotactic radiation therapy for canine non-lymphomatous nasal tumours: 29 cases (2013-2016)}, volume={16}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12334}, abstractNote={Twenty‐nine dogs were treated with linac‐based stereotactic radiation therapy (SRT) for non‐lymphomatous nasal tumours. Only dogs with a follow‐up time >365 days were included in this retrospective analysis. No dogs had evidence of distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3 daily 10 Gy fractions was delivered using intensity‐modulation, cone‐beam CT‐based image guidance and a robotic treatment couch. Clinical signs improved in all cases. Nineteen dogs had CT scans 3‐4 months post‐SRT and all had partial or complete tumour response. Minimal acute toxicities were detected. Clinically significant late toxicities included oronasal or nasocutaneous fistulas (N = 3) and biopsy‐confirmed fungal rhinitis with no evidence of tumour progression (N = 2). The median progression‐free survival (PFS) was 354 days, with 49% and 39% progression‐free at 1 and 2 years post‐SRT, respectively. The median survival time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post‐SRT, respectively. Neither the clinical parameters evaluated (modified Adams’ stage, histopathology, presence of intracranial extension of the tumour) nor dosimetric data were predictive for PFS or ST. This SRT protocol appears to be well tolerated, and PFI and ST are comparable or superior to those reported in other definitive‐intent radiotherapy protocols.}, number={1}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gieger, T. L. and Nolan, M. W.}, year={2018}, month={Mar}, pages={E68–E75} } @article{kelsey_gieger_nolan_2018, title={Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs}, volume={59}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12636}, abstractNote={Abstract}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kelsey, Krista L. and Gieger, Tracy L. and Nolan, Michael W.}, year={2018}, pages={632–638} } @article{magestro_gieger_nolan_2018, title={Stereotactic body radiation therapy for heart-base tumors in six dogs}, volume={20}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2018.04.001}, abstractNote={Heart-base tumors are increasingly treated with radiotherapy, yet safety and efficacy are incompletely understood. This case series describes outcomes after stereotactic body radiation therapy (SBRT) for presumed chemodectoma. Six pet dogs. A retrospective study was performed, including dogs with a clinical diagnosis of chemodectoma and treatment with three-fraction SBRT (30 Gy total). Heart-base tumors, presumed or confirmed to be chemodectomas, were diagnosed via histopathology or imaging. Treatment was delivered with intensity modulation and cone-beam computed tomography–based image guidance, using a linear accelerator and robotic couchtop. Intrafraction respiratory motion was managed with either neuromuscular blockade and breath-holding (n = 3) or high-frequency jet ventilation (n = 3); mean total anesthesia times for each technique were 165 and 91 min per fraction, respectively. Four tumors were assessed after SBRT; tumor volume decreased by 30–76%. Possible treatment-related complications included cough, tachyarrhythmias, and congestive heart failure. Two dogs experienced sudden death 150 and 294 days after SBRT. Three dogs are alive 408–751 days after SBRT, and one dog died of unrelated disease 1,228 days after SBRT. This SBRT protocol resulted in rapid tumor volume reduction, and jet ventilation effectively reduced treatment delivery times. However, cardiac arrhythmias (presumably tumor or treatment associated) and sudden death were common after SBRT. Therefore, SBRT is a potentially useful treatment but may not be appropriate for dogs with incidentally diagnosed, slowly growing tumors, which are not causing cardiovascular disturbances. Longer follow-up and larger case numbers are needed to more completely define safety and impact of treatment on long-term survivability.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Magestro, L. M. and Gieger, T. L. and Nolan, M. W.}, year={2018}, month={Jun}, pages={186–197} } @misc{nolan_dobson_2018, title={The future of radiotherapy in small animals - should the fractions be coarse or fine?}, volume={59}, ISSN={["1748-5827"]}, DOI={10.1111/jsap.12871}, abstractNote={Radiation therapy has been used to treat animal cancers for more than 100 years. Clinical experiences and experimental results have been widely published and provide a basis for the recognition of radiation therapy as an integral component of multimodal cancer management in veterinary oncology. As the expectations of pet owners and the demand for treatment of companion animals with cancer have increased, veterinary oncology itself has undergone dramatic advances in the past several decades both in terms of improved diagnostics and treatments, including increased accessibility of radiation therapy. Synchronous with development of the specialism of veterinary radiation oncology, confusion and controversy have arisen with regard to distinguishing between different types of radiotherapy and methods of treatment delivery. Importantly, the confusion extends beyond semantics, and includes opinionated debate about defining which forms of therapy (if any at all) are optimal for a given patient. This exemplifies how, despite marks of maturity including age and a robust publication history, the field of veterinary radiation oncology is in some ways still in its infancy. The purpose of this article is to review the evidence base for daily (fine) fractionation versus weekly (coarse) hypofractionation in veterinary oncology, using selected tumour types as examples.}, number={9}, journal={JOURNAL OF SMALL ANIMAL PRACTICE}, author={Nolan, M. W. and Dobson, J. M.}, year={2018}, month={Sep}, pages={521–530} } @article{swift_mcgrath_nolan_young_reese_rao_randall_leary_larue_2017, title={Clinical and imaging findings, treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi-center study}, volume={58}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12535}, abstractNote={Abstract}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Swift, Katie E. and McGrath, Stephanie and Nolan, Michael W. and Young, Martin and Reese, Michael and Rao, Sangeeta and Randall, Elissa and Leary, Del and LaRue, Susan}, year={2017}, pages={679–689} } @article{berg_pearce_rohrbaugh_jiang_nolan_ivanisevic_2017, title={Gallium containing composites as a tunable material to understand neuronal behavior under variable stiffness and radiation conditions}, volume={71}, ISSN={["1873-0191"]}, DOI={10.1016/j.msec.2016.10.022}, abstractNote={We report a composite biomaterial containing nanostructured GaOOH and Matrigel™ that can be modulated with respect to its stiffness and radiosensitization properties. A variety of concentrations of GaOOH were added to the composite to alter the mechanical properties of the material as well as to tune the radiosensitizing properties to the composite. PC-12 cells were used to study the combined effects of different stimuli on cell behavior. NGF was given to the cells to record their morphology as well as viability. An increase in the substrate stiffness caused an increase in neurite outgrowth but a decrease in cell viability. In addition, increasing the radiation dose decreased neurite outgrowth but increased cell viability when radiosensitizing particles were present. A subtractive effect between radiosensitizing and mechanical stimuli was observed when PC-12 cells were grown on the GaOOH containing composite.}, journal={MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS}, author={Berg, Nora G. and Pearce, Brady L. and Rohrbaugh, Nathaniel and Jiang, Lin and Nolan, Michael W. and Ivanisevic, Albena}, year={2017}, month={Feb}, pages={317–321} } @article{gieger_nolan_2017, title={Management of Radiation Side Effects to the Skin}, volume={47}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/J.CVSM.2017.06.004}, DOI={10.1016/J.CVSM.2017.06.004}, abstractNote={Radiation therapy (RT) is an essential component for management of many cancers. Veterinary health care professionals must counsel owners about the potential side effects of RT, the anticipated management plan, and associated costs. For most veterinary patients treated with RT, acute radiation side effects are mild; however, careful radiation treatment planning and appropriate management of acute side effects are essential to try to prevent chronic sequelae and the need for ongoing wound care. This article reviews acute and late side effects to the skin and their management.}, number={6}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Gieger, Tracy and Nolan, Michael}, year={2017}, month={Nov}, pages={1165–1180} } @article{nolan_long_marcus_sarmadi_roback_fukuyama_baeumer_lascelles_2017, title={Nocifensive Behaviors in Mice with Radiation-Induced Oral Mucositis}, volume={187}, ISSN={["1938-5404"]}, url={https://dx.doi.org/10.1667/rr14669.1}, DOI={10.1667/rr14669.1}, abstractNote={Oral mucositis can result in significant dysphagia, and is the most common dose-limiting acute toxicity in head and neck cancer patients receiving chemoradiotherapy. There is a critical need to determine the cellular and molecular mechanisms that underlie radiotherapy-associated discomfort in patients with mucositis. The objective was to induce oral mucositis in mice, using a clinical linear accelerator, and to quantify resultant discomfort, and characterize peripheral sensitization. A clinical linear accelerator was used to deliver ionizing radiation to the oral cavity of mice. Mucositis severity scoring, and various behavioral assays were performed to quantify bouts of orofacial wiping and scratching, bite force, gnawing behavior and burrowing activity. Calcium imaging was performed on neurons of the trigeminal ganglia. Glossitis was induced with a single fraction of at least 27 Gy. Body weight decreased and subsequently returned to baseline, in concert with development and resolution of mucositis, which was worst at day 10 and 11 postirradiation, however was resolved within another 10 days. Neither bite force, nor gnawing behavior were measurably affected. However, burrowing activity was decreased, and both facial wiping and scratching were increased while mice had visible mucositis lesions. Sensory nerves of irradiated mice were more responsive to histamine, tumor necrosis factor alpha and capsaicin. Radiation-induced glossitis is associated with hyper-reactivity of sensory neurons in the trigeminal ganglia of mice, and is accompanied by several behaviors indicative of both itch and pain. These data validate an appropriate model for cancer treatment related discomfort in humans.}, number={3}, journal={RADIATION RESEARCH}, publisher={BioOne}, author={Nolan, Michael W. and Long, C. Tyler and Marcus, Karen L. and Sarmadi, Shayan and Roback, Donald M. and Fukuyama, Tomoki and Baeumer, Wolfgang and Lascelles, B. Duncan X.}, year={2017}, month={Mar}, pages={397–403} } @article{nolan_gieger_karakashian_nikolova-karakashian_posner_roback_rivera_chang_2017, title={Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model}, volume={16}, ISSN={1533-0346 1533-0338}, url={http://dx.doi.org/10.1177/1533034617690980}, DOI={10.1177/1533034617690980}, abstractNote={ GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID ( P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy. }, number={3}, journal={Technology in Cancer Research & Treatment}, publisher={SAGE Publications}, author={Nolan, Michael W. and Gieger, Tracy L. and Karakashian, Alexander A. and Nikolova-Karakashian, Mariana N. and Posner, Lysa P. and Roback, Donald M. and Rivera, Judith N. and Chang, Sha}, year={2017}, month={Feb}, pages={357–365} } @article{nolan_arkans_lavine_defrancesco_myers_griffith_posner_keene_tou_gieger_et al._2017, title={Pilot study to determine the feasibility of radiation therapy for dogs with right atrial masses and hemorrhagic pericardial effusion}, volume={19}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2016.12.001}, DOI={10.1016/j.jvc.2016.12.001}, abstractNote={To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs.Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial.A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined.No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days.In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Nolan, M.W. and Arkans, M.M. and LaVine, D. and DeFrancesco, Teresa and Myers, J.A. and Griffith, E.H. and Posner, L.P. and Keene, B.W. and Tou, S.P. and Gieger, Tracy and et al.}, year={2017}, month={Apr}, pages={132–143} } @article{gieger_nettifee-osborne_hallman_johannes_clarke_nolan_williams_2017, title={The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma}, volume={81}, number={3}, journal={Canadian Journal of Veterinary Research}, author={Gieger, T. L. and Nettifee-Osborne, J. and Hallman, B. and Johannes, C. and Clarke, D. and Nolan, M. W. and Williams, L. E.}, year={2017}, pages={199–205} } @article{adamson_mein_meng_gunasingha_yoon_miles_walder_fathi_beyer_spector_et al._2017, title={Utilizing a diagnostic kV imaging system for x-ray psoralen activated cancer therapy (X-PACT)}, volume={3}, number={3}, journal={Biomedical Physics & Engineering Express}, author={Adamson, J. and Mein, S. and Meng, B. and Gunasingha, R. and Yoon, S. W. and Miles, D. and Walder, H. and Fathi, Z. and Beyer, W. and Spector, N. and et al.}, year={2017} } @article{berg_pearce_snyder_rohrbaugh_nolan_adhikari_khan_ivanisevic_2016, title={Interfaces with Tunable Mechanical and Radiosensitizing Properties}, volume={8}, ISSN={["1944-8252"]}, DOI={10.1021/acsami.5b11639}, abstractNote={We report the fabrication of a composite containing nanostructured GaOOH and Matrigel with tunable radiosensitizing and stiffness properties. Composite characterization was done with microscopy and rheology. The utility of the interface was tested in vitro using fibroblasts. Cell viability and reactive oxygen species assays quantified the effects of radiation dosages and GaOOH concentrations. Fibroblasts' viability decreased with increasing concentration of GaOOH and composite stiffness. During ionizing radiation experiments the presence of the scintillating GaOOH triggered a different cellular response. Reactive oxygen species data demonstrated that one can reduce the amount of radiation needed to modulate the behavior of cells on interfaces with different stiffness containing a radiosensitizing material.}, number={34}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Berg, Nora G. and Pearce, Brady L. and Snyder, Patrick J. and Rohrbaugh, Nathaniel and Nolan, Michael W. and Adhikari, Prajesh and Khan, Saad A. and Ivanisevic, Albena}, year={2016}, month={Aug}, pages={21956–21961} } @article{yoshikawa_nolan_lewis_larue_2016, title={Retrospective evaluation of interfractional ureteral movement in dogs undergoing radiation therapy to elucidate appropriate setup margins}, volume={57}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/vru.12309}, DOI={10.1111/vru.12309}, abstractNote={Radiation‐induced ureteral damage can result in serious complications (i.e., hydronephrosis). Also, ureters can be included in planning target volume (PTV) such as ureteral invasion of urinary bladder carcinoma. Therefore, knowing the interfractional movement of the ureters is critical for creation of appropriate planning organs at risk (pOAR) and PTV. This retrospective and descriptive study of 17 dogs with genitourinary carcinomas that underwent intensity‐modulated, image‐guided radiation therapy (IM‐IGRT) was conducted to describe the movement and calculate suggested pOAR/PTV expansions at three locations (at the levels of third lumbar vertebra, immediately cranial to vesicoureteral junction [VUJ], and midway between those two) and from two perspectives: during a course of (1) IM‐IGRT, where position verification is performed using soft tissue registration when the dogs underwent clinical IM‐IGRT; (2) radiation therapy whereby position verification is performed using planar radiography with a corresponding bony registration. This registration was performed by fusing the radiation planning computed tomography (CT) and cone‐beam CTs using bony landmarks. With soft tissue registration, findings supported the use of larger pOAR expansion (0.7–1.8 cm) for the mid region of the ureters compared to the areas near VUJ (0.7–1.1 cm). With bony registration, findings supported the use of larger pOAR/PTV expansions (1.6–1.7 cm) for dorsal direction bilaterally at areas near VUJ compared to those with soft tissue registration (0.9–1.0 cm). The results of this study should help radiation oncologists use appropriate ureter expansions for specific patient orientations and positioning verification methods.}, number={2}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Yoshikawa, Hiroto and Nolan, Michael W. and Lewis, Dustin W. and Larue, Susan M.}, year={2016}, month={Mar}, pages={170–179} } @article{griffin_nolan_selmic_randall_custis_larue_2016, title={Stereotactic radiation therapy for treatment of canine intracranial meningiomas}, volume={14}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12129}, abstractNote={Abstract}, number={4}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Griffin, L. R. and Nolan, M. W. and Selmic, L. E. and Randall, E. and Custis, J. and LaRue, S.}, year={2016}, month={Dec}, pages={E158–E170} } @article{yoshikawa_roback_larue_nolan_2015, title={Dosimetric consequences of using contrast-enhanced computed tomographic images for intensity-modulated stereotactic body radiotherapy planning}, volume={56}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/vru.12281}, DOI={10.1111/vru.12281}, abstractNote={Potential benefits of planning radiation therapy on a contrast‐enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity‐modulated stereotactic body radiotherapy (IM‐SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross‐sectional study. All IM‐SBRT plans were constructed on a pre‐ or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM‐SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre‐ and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM‐SBRT for tumors near “reservoirs” for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM‐SBRT treatment planning.}, number={6}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Yoshikawa, Hiroto and Roback, Donald M. and Larue, Susan M. and Nolan, Michael W.}, year={2015}, month={Aug}, pages={687–695} } @article{nolan_gieger_vaden_2015, title={Management of transitional cell carcinoma of the urinary bladder in dogs: Important challenges to consider}, volume={205}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2015.03.022}, abstractNote={Interventional radiology (IR) involves the use of contemporary imaging modalities to gain access to different structures in order to deliver materials for therapeutic purposes. Veterinarians have been expanding the use of these minimally invasive techniques in animals with a variety of conditions involving all of the major body systems. Interventional oncology (IO) is a growing subspecialty of IR in human medicine used (1) to restore patency to malignant obstructions through endoluminal stenting, (2) to provide dose escalations to tumors without increasing systemic chemotherapy toxicities via superselective transarterial chemotherapy delivery, (3) to stop hemorrhage or reduce blood flow to tumors via transarterial embolization or chemoembolization, and (4) to provide therapies for those cancers with no safe or effective alternative options.This review provides a brief introduction to a few of the techniques currently available to veterinarians for cancer treatment. For each technique, the concept for improved palliation, patient quality of life, or tumor control is presented, followed by the most current veterinary clinical information available. Although promising, more studies will be necessary to determine if veterinary IO will provide the same benefits as has already been demonstrated in oncology care in humans.}, number={2}, journal={VETERINARY JOURNAL}, author={Nolan, Michael W. and Gieger, Tracy L. and Vaden, Shelly L.}, year={2015}, month={Aug}, pages={126–127} } @article{arkans_gieger_nolan_2015, title={Misadministration of radiation therapy in veterinary medicine: a case report and literature review}, volume={15}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12161}, DOI={10.1111/vco.12161}, abstractNote={Abstract}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Arkans, M. M. and Gieger, T. L. and Nolan, M. W.}, year={2015}, month={Jul}, pages={237–246} } @article{nolan_marolf_ehrhart_rao_kraft_engel_yoshikawa_golden_wasserman_larue_2015, title={Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction}, volume={91}, ISSN={0360-3016}, url={http://dx.doi.org/10.1016/j.ijrobp.2014.12.025}, DOI={10.1016/j.ijrobp.2014.12.025}, abstractNote={

Purpose/Objectives

Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation.

Methods and Materials

Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes.

Results

SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT.

Conclusions

This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.}, number={4}, journal={International Journal of Radiation Oncology*Biology*Physics}, publisher={Elsevier BV}, author={Nolan, Michael W. and Marolf, Angela J. and Ehrhart, E.J. and Rao, Sangeeta and Kraft, Susan L. and Engel, Stephanie and Yoshikawa, Hiroto and Golden, Anne E. and Wasserman, Todd H. and LaRue, Susan M.}, year={2015}, month={Mar}, pages={796–806} } @article{berg_nolan_paskova_ivanisevic_2014, title={Surface Characterization of Gallium Nitride Modified with Peptides before and after Exposure to Ionizing Radiation in Solution}, volume={30}, ISSN={0743-7463 1520-5827}, url={http://dx.doi.org/10.1021/la5040245}, DOI={10.1021/la5040245}, abstractNote={An aqueous surface modification of gallium nitride was employed to attach biomolecules to the surface. The modification was a simple two-step process using a single linker molecule and mild temperatures. The presence of the peptide on the surface was confirmed with X-ray photoelectron spectroscopy. Subsequently, the samples were placed in water baths and exposed to ionizing radiation to examine the effects of the radiation on the material in an environment similar to the body. Surface analysis confirmed degradation of the surface of GaN after radiation exposure in water; however, the peptide molecules successfully remained on the surface following exposure to ionizing radiation. We hypothesize that during radiation exposure of the samples, the radiolysis of water produces peroxide and other reactive species on the sample surface. Peroxide exposure promotes the formation of a more stable layer of gallium oxyhydroxide which passivates the surface better than other oxide species.}, number={51}, journal={Langmuir}, publisher={American Chemical Society (ACS)}, author={Berg, Nora G. and Nolan, Michael W. and Paskova, Tania and Ivanisevic, Albena}, year={2014}, month={Dec}, pages={15477–15485} } @article{nolan_randall_larue_lunn_stewart_kraft_2013, title={Accuracy of CT and MRI for contouring the feline optic apparatus for radiation therapy planning}, volume={54}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/vru.12070}, DOI={10.1111/vru.12070}, abstractNote={Consistency and accuracy in normal tissue contouring in radiotherapy planning is important for comparison of dosimetry and toxicity data between studies. The purpose of this study was to determine whether magnetic resonance imaging (MRI) improves the accuracy of optic apparatus contouring as compared with computed tomography (CT) in both normal and acromegalic cats, and to construct a reference contour of the feline optic apparatus. Both CT and MRI were performed on cadavers of four healthy cats, as well as on five radiotherapy patients with feline acromegaly. Contours of the optic apparatus were drawn for each imaging study. The volume, center of mass, and the degree of concordance and mismatch were determined for each, and compared with a reference standard. Precontrast CT was found to overestimate volume as compared with MRI in acromegalic cats; no other statistically significant differences were identified in the volume, concordance index or mismatch index values of normal or acromegalic cats. Contours derived from T2‐wieghted MRI were subjectively considered to best match the reference standard. The caudal margin of the optic chiasm and the optic tracts were difficult to confidently contour regardless of which imaging modality and/or sequence was used. In conclusion, findings from the current study supported the use of a combination of CT and MR images and a priori knowledge of the shape of the optic apparatus to guide accurate contouring, especially where image contrast is not sufficient to clearly delineate the margins. Guidelines for feline optic apparatus contouring developed in this study can be used for future studies.}, number={5}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Nolan, Michael W. and Randall, Elissa K. and LaRue, Susan M. and Lunn, Katharine F. and Stewart, Jeff and Kraft, Susan L.}, year={2013}, month={Jun}, pages={560–566} } @article{nolan_griffin_custis_larue_2013, title={Stereotactic body radiation therapy for treatment of injection-site sarcomas in cats: 11 cases (2008–2012)}, volume={243}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.243.4.526}, DOI={10.2460/javma.243.4.526}, abstractNote={Abstract}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Nolan, Michael W. and Griffin, Lynn R. and Custis, James T. and LaRue, Susan M.}, year={2013}, month={Aug}, pages={526–531} } @article{nolan_kogan_griffin_custis_harmon_biller_larue_2012, title={Intensity-Modulated and Image-Guided Radiation Therapy for Treatment of Genitourinary Carcinomas in Dogs}, volume={26}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/j.1939-1676.2012.00946.x}, DOI={10.1111/j.1939-1676.2012.00946.x}, abstractNote={BackgroundExternal beam radiation therapy can be used to treat pelvic tumors in dogs, but its utility is limited by lack of efficacy data and associated late complications.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Nolan, M.W. and Kogan, L. and Griffin, L.R. and Custis, J.T. and Harmon, J.F. and Biller, B.J. and LaRue, S.M.}, year={2012}, month={May}, pages={987–995} } @article{nolan_roberts_zimmerman_smith_2010, title={Pathology in Practice}, volume={236}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.236.6.631}, DOI={10.2460/javma.236.6.631}, abstractNote={A 7-month-old 25-g (0.055-lb) male calico Oranda goldfish (Carassius auratus) was evaluated because of a rapidly enlarging mass that affected the oral cavity and left operculum.Associated clinical signs included left opercular flaring, progressive gill pallor, left-sided exophthalmia, and suppressed appetite.The fish had been acquired from a retail vendor 1 month earlier; it appeared thin but otherwise outwardly healthy prior to development of these signs a week before the evaluation.The goldfish had been housed in a tank with a sexually mature female fancy goldfish; the fish had}, number={6}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Nolan, Michael W. and Roberts, Helen E. and Zimmerman, Kurt L. and Smith, Stephen A.}, year={2010}, month={Mar}, pages={631–633} } @article{chandra_nolan_malarkey_2009, title={Chemical Carcinogenesis of the Gastrointestinal Tract in Rodents: An Overview with Emphasis on NTP Carcinogenesis Bioassays}, volume={38}, ISSN={0192-6233 1533-1601}, url={http://dx.doi.org/10.1177/0192623309356452}, DOI={10.1177/0192623309356452}, abstractNote={Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasms of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at least 26 chemicals inducing tumors in both species. Glandular stomach tumors are rare, and the few reported are usually neuroendocrine tumors (carcinoids) originating from the enterochromaffin-like (ECL) cells. Of 290 carcinogenic agents identified by the NTP, 19 (7%) caused intestinal neoplasia, 14 in the rat and 5 in the mouse. Neoplasms occurred in both males and females, exclusively in the small intestine (SI) of the mouse and in the LI or both SI and LI in the rat. Enteric carcinogens (NTP) frequently induced neoplasms at other alimentary sites (oral cavity, esophagus, and stomach). In conclusion, the most common induced GIT tumors are squamous neoplasms of the forestomach, glandular neoplasms of the stomach are rare, and rats appear more prone to developing LI (colorectal) cancer compared to mice.}, number={1}, journal={Toxicologic Pathology}, publisher={SAGE Publications}, author={Chandra, Sundeep A. and Nolan, Michael W. and Malarkey, David E.}, year={2009}, month={Dec}, pages={188–197} } @article{nolan_smith_2007, title={Amphibian Resources on the Internet}, volume={48}, ISSN={1084-2020}, url={http://dx.doi.org/10.1093/ilar.48.3.290}, DOI={10.1093/ilar.48.3.290}, abstractNote={The use of amphibians in classrooms and research laboratories has increased, along with a corresponding increase in the amount of information about these animals on the Internet. This review is intended to aid both novices and experts in the search of such information. The bibliography of Internet resources is organized by discipline and includes general and selected species information, taxonomy, natural history, anatomy and histology, physiology, ontogeny, genetics, conservation, toxicology, medicine and surgery, sources (for animals, housing, and research tools), listservs, databases, associations, educational sources, and husbandry. For each web site, descriptive titles, web addresses, and a brief review are provided. Note that the authors of this review cannot assure the accuracy of content in these web resources.}, number={3}, journal={ILAR Journal}, publisher={Oxford University Press (OUP)}, author={Nolan, M. W. and Smith, S. A.}, year={2007}, month={Jan}, pages={290–296} } @article{nolan_smith_jones_2007, title={Pharmacokinetics of oxytetracycline in the American horseshoe crab, Limulus polyphemus}, volume={30}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2007.00891.x}, DOI={10.1111/j.1365-2885.2007.00891.x}, abstractNote={The American horseshoe crab, Limulus polyphemus, is regularly cultured and maintained in research laboratories and public aquaria. Rising concerns over the health of these captive animals makes the diagnosis and treatment of pathological conditions in L. polyphemus essential. This study investigated the kinetics of oxytetracyline following either intravascular or oral dosing. Oxytetracylcine is a broad‐spectrum antibiotic used in the treatment of various bacterial diseases of aquatic animals. A noncompartmental model was developed to describe the pharmacokinetics of oxytetracycline (OTC) in the horseshoe crab. The following parameters were determined for a single intravascular bolus of 25 mg/kg OTC: AUC = 9524.60 μg·h/mL, MRT = 443.65 h, Clb = 0.044 mL/min/kg, Vd(ss) = 1.164 L/kg, t1/2 = 128.3 h, Cmax = 55.90 μg/mL, Cave = 27.39 μg/mL. Following a single oral bolus of 25 mg/kg, these parameters were calculated: AUC = 5861.81 μg·h/mL, MRT = 395.89 h, Clb = 0.071 mL/min/kg, Vd(ss) = 1.688 L/kg, t1/2 = 210.0 h, Cmax = 7.83 μg/mL, Cave = 2.89 μg/mL, F = 61.56%.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Nolan, M. W. and Smith, S. A. and Jones, D.}, year={2007}, month={Oct}, pages={451–455} }