@article{strasberg_rossmeisl_kelsey_yoshikawa_gieger_nolan_2024, title={A prospective evaluation of succinct prednisone tapering after brain tumor irradiation in dogs}, volume={8}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.17163}, abstractNote={To ameliorate anticipated or ongoing neurological deficits, dogs undergoing brain tumor irradiation often are prescribed lengthy courses of prednisone PO during and after radiotherapy (RT). This practice can contribute to unwanted corticosteroid-associated morbidity and may be unnecessary.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Strasberg, Jason R. and Rossmeisl, John H. and Kelsey, Krista L. and Yoshikawa, Hiroto and Gieger, Tracy L. and Nolan, Michael W.}, year={2024}, month={Aug} }
 @article{gieger_magestro_walz_yoshikawa_nolan_2024, title={Outcomes of Stereotactic Radiation Therapy Versus Fractionated Radiation Therapy in 44 Dogs With Pituitary Masses: A Multi-Institutional Retrospective Study (2016-2022)}, volume={6}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12991}, abstractNote={ABSTRACT Although canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full‐course fractionated radiation therapy (FRT). A multi‐institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50–54 Gy in 19–20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty‐four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375–840 days). Young age at the time of treatment was significant for survival ( p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614–892 days) and 445 days for dogs ≥9 years of age (95% CI, 183–707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gieger, Tracy L. and Magestro, Leanne and Walz, Jillian and Yoshikawa, Hiroto and Nolan, Michael W.}, year={2024}, month={Jun} }
 @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

OBJECTIVE
To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST).


ANIMALS
129 dogs.


PROCEDURES
In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome.


RESULTS
After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462).


CLINICAL RELEVANCE
This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.
}, 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{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

OBJECTIVE
To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS).


ANIMALS
14 client-owned cats.


PROCEDURES
Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time.


RESULTS
Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status.


CLINICAL RELEVANCE
The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.
}, 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{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={AbstractBackgroundLittle is known regarding the comparative efficacy of various irradiation strategies used to treat intranasal carcinomas (INC) in cats.ObjectivesInvestigate outcomes and prognostic factors associated with survival for cats with INC.AnimalsForty‐two cats with INC that underwent radiotherapy (RT).MethodsSingle‐arm retrospective study. Medical record review for cats with INC that underwent RT at 1 of 7 veterinary RT facilities. Irradiation protocols categorized as: definitive‐intent fractionated RT (FRT), definitive‐intent stereotactic RT (SRT), and palliative‐intent RT (PRT). Median overall survival time (OST) and disease progression‐free survival (PFS; documented by advanced transverse imaging, or recurrence of symptoms) were calculated. Associations between tumor stage, RT protocol/intent, and adjunctive treatment usage and outcome were calculated.ResultsCats underwent SRT (N = 18), FRT (N = 8), and PRT (N = 16). In multivariate modeling, cats received definitive‐intent treatment (DRT; FRT/SRT) had significantly longer median PFS (504 days, [95% confidence interval (CI): 428–580 days] vs PRT 198 days [95% CI: 62–334 days]; p = 0.006) and median OST [721 days (95% CI: 527–915 days) vs 284 days (95% CI: 0–570 days); p = 0.001]). Cats that underwent second DRT course at time of recurrence lived significantly longer than cats that received 1 RT course (either DRT or PRT [median OST 824 days (95% CI: 237–1410 days) vs 434 days (95% CI: 277–591 days); p = .028]).ConclusionIn cats with INC, DRT is associated with prolonged OST and PFS as compared to PRT. If tumor progression occurs, a second course of DRT should be considered.}, 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{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{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={AbstractNasal tumor size can change during radiation therapy (RT). The amount of peritumoral fluid (eg, mucohemorrhagic effusions) can also fluctuate. How often this occurs and the magnitude of change are unknown. Likewise, there are no data which describe dosimetric effects of these changing volumes during a course of RT in veterinary medicine. This study addresses that gap in knowledge. Using pet dogs with nasal tumors, three CT image sets were created. Different Hounsfield units were applied to the gross tumor volume (GTV) of each image set: unchanged, –1000 (AIR), –1000 (to the portion of the GTV that actually underwent volume reduction during clinical RT; REAL). Two plans were created: 18‐fraction three‐dimensional conformal RT (3DCRT) and three‐fraction intensity‐modulated stereotactic RT (IM‐SRT). For nearby normal tissues and GTV, near‐maximum doses (D2% and D5%) and volumes receiving clinically significant doses were recorded. To verify “AIR” results, thermoluminescent dosimeters recorded dose in cadavers that were irradiated using both 3DCRT and IM‐SRT plans. “AIR” scenario had ≤1.5 Gray (Gy) increases in D2% and ≤3.2 cc increases of volume. “REAL” scenario had ≤0.97 Gy increases in D5% and ≤0.55 cc increases of volume at clinically relevant doses. Both were statistical significant. Results suggest that near‐complete resolution of GTV warrants plan revision.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Yoshikawa, Hiroto and Nolan, Michael W.}, year={2019}, month={Sep}, pages={594–604} }
 @article{yoshikawa_sunada_hirakawa_fujimori_elmegerhi_leary_kato_2019, title={Radiobiological Characterization of Canine Malignant Melanoma Cell Lines with Different Types of Ionizing Radiation and Efficacy Evaluation with Cytotoxic Agents}, volume={20}, ISSN={["1422-0067"]}, DOI={10.3390/ijms20040841}, abstractNote={Canine malignant melanoma (CMM) is a locally and systemically aggressive cancer that shares many biological and clinical characteristics with human mucosal melanoma. Hypofractionated radiation protocols have been used to treat CMM but little is known about its radiation biology. This pilot study is designed to investigate response of CMM cell lines to various ionizing radiations and cytotoxic agents to better understand this canine cancer. Four CMM cell lines were evaluated by clonogenic survival assay under aerobic and hypoxic conditions and parameters such as alpha beta (α/β) ratio, oxygen enhancement ratio (OER), and relative biological effectiveness (RBE) were calculated after 137Cs, 6 megavoltage (MV) photon, or carbon ion irradiation. Six cytotoxic agents (cisplatin, camptothecin, mitomycin C, bleomycin, methtyl methanesulfonate and etoposide) were also assessed for their efficacy. Under aerobic condition with 6 MV photon, the α/β ratio of the four cell lines ranged from 0.3 to >100, indicating a wide variation of cellular sensitivity. The ratio increased under hypoxic condition compared to aerobic condition and this was more dramatic in 137Cs and 6 MV photon treatments. OER of carbon was lower than 137Cs at D10 in 3 of the 4 cell lines. The RBE values generally increased with the increase of LET. Different cell lines showed sensitivity/resistance to different cytotoxic agents. This study revealed that CMM has a wide range of radiosensitivity and that hypoxia can reduce it, indicating that widely used hypofractionated protocols may not be optimal for all CMM patients. Several cytotoxic agents that have never been clinically assessed can improve treatment outcome.}, number={4}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Yoshikawa, Hiroto and Sunada, Shigeaki and Hirakawa, Hirokazu and Fujimori, Akira and Elmegerhi, Suad and Leary, Del and Kato, Takamitsu A.}, year={2019}, month={Feb} }
 @article{sweet_nolan_yoshikawa_gieger_2019, title={Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases}, ISSN={1476-5810 1476-5829}, url={http://dx.doi.org/10.1111/vco.12481}, DOI={10.1111/vco.12481}, abstractNote={AbstractRadiotherapy is often considered in the management of canine multilobular osteochondrosarcoma (MLO), but its efficacy against bulky MLO tumours is poorly described. This retrospective case series describes the clinical outcomes of pet dogs with MLO treated with a stereotactic radiation therapy (SRT) prescription of 30 Gy in three consecutive daily 10 Gy fractions. Dogs with an imaging (via computed tomography [CT] scan) and/or pathologic diagnosis of MLO were included. Patient demographics, tumour characteristics, radiation plan dosimetry, toxicity and outcome data were obtained retrospectively from the records. The median progression‐free survival time (MPFST) and median overall survival time (MST) were calculated using a LOGLOG test. Eight dogs were included. None had evidence of metastasis at the time of SRT. Clinical signs associated with the MLO included a mass noted by owner, stertor, vestibular signs, exophthalmos and abnormal mentation. Of the five dogs that had CT scans performed 3 to 9 months after SRT, tumour volume decreased by 26% to 87% in four dogs and increased by 32% in one dog. Late radiation toxicity was documented in three dogs (VRTOG Grade 1 skin and/or ocular, n = 2; Grade 3 central nervous system, n = 1). Confirmed local disease progression (n = 3; two were treated with a second course of SRT) and suspected pulmonary metastasis (n = 2) occurred 90 to 315 days after SRT. The MPFST was 223 days (interquartile range [IQR]: 144.5‐276.5 days). The MST was 329 days (IQR: 241.5‐408 days). This protocol was well‐tolerated, but the duration of response was short‐lived.}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Sweet, Katherine A. and Nolan, Michael W. and Yoshikawa, Hiroto and Gieger, Tracy L.}, year={2019}, month={Jun} }
 @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_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={{"Label"=>"PURPOSE/OBJECTIVES", "NlmCategory"=>"OBJECTIVE"} 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. {"Label"=>"METHODS AND MATERIALS", "NlmCategory"=>"METHODS"} 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. {"Label"=>"RESULTS", "NlmCategory"=>"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. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"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{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{yoshikawa_maranon_battaglia_ehrhart_charles_bailey_larue_2014, title={Predicting clinical outcome in feline oral squamous cell carcinoma: tumour initiating cells, telomeres and telomerase}, volume={14}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12117}, DOI={10.1111/vco.12117}, abstractNote={AbstractFeline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi‐1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi‐1 expression, supporting the predictive value of Bmi‐1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi‐1, Ki67 and EGFR. Taken together, our results imply that Bmi‐1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition – in combination with SRT – would be expected to have beneficial treatment outcome.}, number={4}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Yoshikawa, H. and Maranon, D. G. and Battaglia, C. L. R. and Ehrhart, E. J. and Charles, J. B. and Bailey, S. M. and LaRue, S. M.}, year={2014}, month={Sep}, pages={371–383} }
 @article{randall_yoshikawa_kraft_larue_2013, title={A Translational Feline Model of Oral Squamous Cell Carcinoma for Evaluating Tumor Volume Delineation With PET/CT}, volume={3}, ISSN={1879-8500}, url={http://dx.doi.org/10.1016/j.prro.2013.01.099}, DOI={10.1016/j.prro.2013.01.099}, abstractNote={Oral squamous cell carcinoma (SCC) is a locally invasive naturally occurring tumor in cats that responds poorly to radiation therapy. Most cats succumb to failure from local recurrence within 6 months. Feline SCC has comparable histological characteristics, higher pretreatment epidermal growth factor (EGRF) and microvascular density (MDV) values that are associated with a worsened prognosis, similar to human oral SCC. Unlike rodent models, spontaneous tumors in cats are heterogeneous and often hypoxic. The tumors are large enough to obtain adequate biopsy material, and the cats can be imaged and treated with the same modalities as cancer patients. Positron emission tomography- computed tomography (PET/CT) with 18F-fluoro-2-deoxy-D-glucose detects areas with higher glucose metabolism. The goal of the current study was to evaluate the role of 18F-FDG PET for feline radiation therapy patients with oral SCC, as a model of tumor delineation for human disease.}, number={2}, journal={Practical Radiation Oncology}, publisher={Elsevier BV}, author={Randall, E. and Yoshikawa, H. and Kraft, S. and LaRue, S.}, year={2013}, month={Apr}, pages={S29} }
 @article{yoshikawa_ehrhart_charles_custis_larue_2013, title={Assessment of predictive molecular variables in feline oral squamous cell carcinoma treated with stereotactic radiation therapy}, volume={14}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12050}, DOI={10.1111/vco.12050}, abstractNote={AbstractThis study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression‐free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO2). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment‐related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers.}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Yoshikawa, H. and Ehrhart, E. J. and Charles, J. B. and Custis, J. T. and LaRue, S. M.}, year={2013}, month={Jul}, pages={39–57} }
 @article{yoshikawa_randall_kraft_larue_2013, title={Comparison between 2-18f-fluoro-2-deoxy-d-glucose positron emission tomography and contrast-enhanced computed tomography for measuring gross tumor volume in cats with oral squamous cell carcinoma}, volume={54}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/vru.12016}, DOI={10.1111/vru.12016}, abstractNote={Feline oral squamous cell carcinoma is one of the most refractory feline malignancies. Most patients succumb due to failure in local tumor control. 2‐18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (18F‐FDG PET) is increasingly being used for veterinary oncology staging as it highlights areas with higher glucose metabolism. The goal of the current prospective study was to compare gross tumor volume measurements using 18F‐FDG PET vs. those using computed tomography (CT) for stereotactic radiation therapy planning in cats with oral squamous cell carcinoma. Twelve cats with confirmed oral squamous cell carcinoma underwent pretreatment 18F‐FDG PET/CT. Gross tumor volumes based on contrast‐enhanced CT and 18F‐FDG PET were measured and compared among cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary squamous cell carcinoma group (n = 8, P = 0.002) and for the total number of patients (n = 12, P = 0.006), but not in the lingual/laryngeal group (n = 4, P = 0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high‐18F‐FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group (P = 0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that 18F‐FDG PET warrants further investigation as a supplemental imaging modality in cats with oral squamous cell carcinoma because it detected regions of possible primary tumor that were not detected on CT images.}, number={3}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Yoshikawa, Hiroto and Randall, Elissa K. and Kraft, Susan L. and LaRue, Susan M.}, year={2013}, month={Feb}, pages={307–313} }
 @article{randall_kraft_yoshikawa_larue_2013, title={Evaluation of 18F-FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma}, volume={14}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12047}, DOI={10.1111/vco.12047}, abstractNote={Abstract18F‐fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG‐PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy‐proven oral SCC were imaged with whole body 18FDG‐PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG‐PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9–24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG‐PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG‐PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Randall, E. K. and Kraft, S. L. and Yoshikawa, H. and LaRue, S. M.}, year={2013}, month={Jun}, pages={28–38} }
 @article{harmon_yoshikawa_custis_larue_2013, title={Evaluation of canine prostate intrafractional motion using serial cone beam computed tomography imaging}, volume={54}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/j.1740-8261.2012.01986.x}, DOI={10.1111/j.1740-8261.2012.01986.x}, abstractNote={This study used kilovoltage (kV) cone beam computed tomography (CBCT) imaging to characterize canine intrafractional prostate motion during hypofractionated stereotactic radiotherapy treatment. Serial CBCT images taken just prior to initiating treatment, and at several times during the treatment session, were acquired throughout the course of treatment for canine patients. All patients were immobilized in dorsal recumbency while using an air‐inflated rectal balloon. For each treatment session, rigid registration of intrafraction CBCT images with the interfraction CBCT used for setup verification was performed. Contours of the prostate and urethra were drawn on each CBCT image set and the center of mass for each structure was evaluated as a function of time. A total of seven canine patients was included in the study, resulting in 41 CBCT images collected during a total of 12 treatment sessions. Over 70% of our data were collected for CBCTs taken between 20 and 51 min after final patient setup was complete. The mean intrafraction movement in a single direction for the prostate and urethra was ≤0.14 mm and ≤0.22 mm, respectively. The maximum intrafraction movement for the prostate and urethra was ≤ 1.60 mm and ≤ 2.00 mm, respectively. The maximum variability in intrafraction movement for the prostate and urethra, as defined by two standard deviations, was ≤1.40 mm and ≤1.50 mm, respectively. Minimal intrafraction variability using appropriate patient positioning and rectal balloon, combined with kV CBCT image‐guided radiation therapy tools to account for interfraction changes, permit accurate and precise targeting of structures of interest.}, number={1}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Harmon, Joseph, Jr. and Yoshikawa, Hiroto and Custis, James and LaRue, Susan}, year={2013}, month={Jan}, pages={93–98} }
 @article{yoshikawa_ehrhart_charles_thamm_larue_2012, title={Immunohistochemical characterization of feline oral squamous cell carcinoma}, volume={73}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.73.11.1801}, DOI={10.2460/ajvr.73.11.1801}, abstractNote={Abstract
Objective—To evaluate the expression of Ki67 and epidermal growth factor receptor (EGFR), mitotic index (MI), and microvascular density (MVD) in feline oral squamous cell carcinoma (SCC) via immunohistochemical staining on archival tumor tissues and to seek a correlation between these markers and clinical variables.
Sample—22 archived tumor samples of feline oral SCC.
Procedures—Immunohistochemical staining for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time.
Results—The 22 tumors had wide variation in Ki67 expression, MI, MVD, and EGFR expression. Tongue SCC had higher MVD than did mandibular and maxillary SCC. Tumor expression of EGFR was inversely proportional to survival time.
Conclusions and Clinical Relevance—Results suggested that EGFR expression might be a valuable prognostic factor for treatment outcome in feline oral SCC. It also identified higher angiogenesis in tongue SCC, compared with mandibular and maxillary SCC, which may account for a different clinical outcome. Further prospective characterization of feline oral SCC may provide a better understanding of the underlying molecular factors that drive its behavior and offer the possibility for future patient-specific treatment plans.}, number={11}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Yoshikawa, Hiroto and Ehrhart, E. J. and Charles, Joseph B. and Thamm, Douglas H. and LaRue, Susan M.}, year={2012}, month={Nov}, pages={1801–1806} }
 @article{yoshikawa_harmon_custis_larue_2012, title={Repeatability of a planning target volume expansion protocol for radiation therapy of regional lymph nodes in canine and feline patients with head tumors}, volume={53}, ISSN={1058-8183}, url={http://dx.doi.org/10.1111/j.1740-8261.2012.01972.x}, DOI={10.1111/j.1740-8261.2012.01972.x}, abstractNote={For canine and feline patients with head tumors, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study was to assess the repeatability of a planning target volume (PTV) expansion protocol for these LNs. Two CT image sets from 44 dogs and 37 cats that underwent radiation therapy for head tumors were compared to determine LN repositioning accuracy and precision; planning‐CT (for radiation therapy planning) and cone‐beam CT (at the time of actual treatment sessions). Eleven percent of dogs and 65% of cats received treatment to their LNs. In dogs, the mandibular LNs were positioned more caudally (P = 0.0002) and the right mandibular and right retropharyngeal LNs were positioned more to the left side of the patient (P = 0.00015 and P = 0.003, respectively). In cats, left mandibular LN was positioned higher (toward roof) than the planning‐CT (P = 0.028). In conclusion, when the patient immobilization devices and bony anatomy matching are used to align the primary head target and these LNs are treated simultaneously, an asymmetrical PTV expansion that ranges 4–9 mm (dogs) and 2–4 mm (cats), depending on the directions of couch movement, should be used to include the LNs within the PTV at least 95% of the time.}, number={6}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Yoshikawa, Hiroto and Harmon, Joseph F. and Custis, James T. and LaRue, Susan M.}, year={2012}, month={Sep}, pages={667–672} }
 @article{yoshikawa_mayer_2009, title={External beam radiation therapy for canine intracranial meningioma}, volume={50}, number={1}, journal={The Canadian Veterinary Journal / La Revue veterinaire canadienne}, author={Yoshikawa, H. and Mayer, M.N.}, year={2009}, month={Jan}, pages={97–100} }
 @article{mayer_yoshikawa_sidhu_2009, title={Impact of tissue inhomogeneity on dose distribution in the canine carpal and tarsal regions for cobalt and 6MV photons}, volume={50}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.2009.01543.x}, DOI={10.1111/j.1740-8261.2009.01543.x}, abstractNote={We quantified the effect of tissue inhomogeneity on dose distribution in a canine distal extremity resulting from treatment with cobalt photons and photons from a 6 MV accelerator. Monitor units for a typical distal extremity treatment were calculated by two methods, using equally weighted, parallel‐opposed fields. The first method was a computed tomography (CT)‐based, computerized treatment plan, calculated without inhomogeneity correction. The second method was a manual point dose calculation to the isocenter. A computerized planning system was then used to assess the dose distribution achieved by these two methods when tissue inhomogeneity was taken into account. For cobalt photons, the median percentage of the planning target volume (PTV) that received <95% of the prescribed dose was 4.5% for the CT‐based treatment plan, and 26.2% for the manually calculated plan. For 6 MV photons, the median percentage of the PTV that received <95% of the prescribed dose was <1% for both planning methods. The PTV dose achieved without using inhomogeneity correction for cobalt photons results in potentially significant under dosing of portions of the PTV.}, number={3}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Mayer, Monique N. and Yoshikawa, Hiroto and Sidhu, Narinder}, year={2009}, month={May}, pages={319–322} }
 @article{mayer_yoshikawa_moriarity_sidhu_2009, title={Use of a petroleum-based bolus for photon radiation therapy of distal extremities in dogs}, volume={50}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.2009.01523.x}, DOI={10.1111/j.1740-8261.2009.01523.x}, abstractNote={While skin sparing is an advantage of megavoltage beams, in certain clinical situations the planning target volume includes the skin surface and a skin sparing effect is not desirable. A tissue equivalent material, termed build up bolus, is used in these situations to provide adequate absorbed dose at the surface of the skin. However, an irregular patient contour can lead to air gaps between the build up bolus and the skin surface, which may result in variability in radiation dose across the target volume. The shape of the canine distal hind extremity is irregular, and commercially available bolus materials do not conform well to this region. The purpose of this study was to assess the dose homogeneity achieved using a petroleum‐based bolus material, in combination with a commercially available sheet bolus, for radiation treatment of the canine tarsus. Repeated setups were performed to mimic daily treatment setups in the clinic setting, and computed tomographic scans were performed after each setup. Dose distribution achieved with a cobalt therapy machine and a 6 MV linear accelerator was assessed using three‐dimensional treatment planning software. The dose to the clinical target volume fell within 95% and 107% of the prescribed dose for both treatment machines, which is considered clinically acceptable by the authors. This petroleum‐based bolus is equivalent to water in its photon attenuation, conforms well to an irregular patient contour, and retains its shape after positioning. Applications to other anatomical sites could be considered.}, number={2}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Mayer, Monique N. and Yoshikawa, Hiroto and Moriarity, Leo and Sidhu, Narinder}, year={2009}, month={Mar}, pages={235–238} }
 @article{yoshikawa_nakamoto_ozawa_dickinson_2008, title={A Dog with Osteosarcoma which Metastasized to the Eye Months before Metastasis to Other Organs}, volume={70}, ISSN={0916-7250 1347-7439}, url={http://dx.doi.org/10.1292/jvms.70.825}, DOI={10.1292/jvms.70.825}, abstractNote={A 9-year-old male Shih Tzu with osteosarcoma had a forelimb amputation and underwent chemotherapy. During chemotherapy, the right eye was enucleated due to refractory glaucoma, and was diagnosed as anterior uveal malignant melanoma. The dog lived for 4 months after the enucleation without treatment. After the dog died, the mass in the eye was re-evaluated immunohistochemically, and it was diagnosed as metastasis of appendicular osteosarcoma. Metastasis of appendicular osteosarcoma to the anterior chamber is quite rare, and the clinical course which showed clinically detectable metastases to the eye before systemic multi-organ metastases was quite unique.}, number={8}, journal={Journal of Veterinary Medical Science}, publisher={Japanese Society of Veterinary Science}, author={Yoshikawa, Hiroto and Nakamoto, Yuya and Ozawa, Tsuyoshi and Dickinson, Ryan M.}, year={2008}, pages={825–828} }
 @article{yoshikawa_mayer_linn_dickinson_carr_2008, title={A dog with squamous cell carcinoma in the middle ear}, volume={49}, number={9}, journal={The Canadian veterinary journal / La Revue veterinaire canadienne}, author={Yoshikawa, H. and Mayer, M.N. and Linn, K.A. and Dickinson, R.M. and Carr, A.P.}, year={2008}, month={Sep}, pages={877–879} }
 @article{mayer_grier_yoshikawa_ringwood_2008, title={Complications associated with the use of vascular access ports in dogs receiving external beam radiation therapy}, volume={233}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.233.1.96}, DOI={10.2460/javma.233.1.96}, abstractNote={Abstract
Objective—To assess the perioperative and postoperative complications associated with use of vascular access ports (VAPs) in the jugular and lateral saphenous veins of dogs requiring frequent anesthetic episodes for radiation therapy.
Design—Cohort study.
Animals—40 dogs referred to a veterinary teaching hospital.
Procedures—VAPs were used in 23 dogs, and intravenous catheters inserted in a peripheral vein were used in 17 dogs. The frequency of perioperative and postoperative complications associated with VAP use and the frequency of infection associated with intravenous catheter use were recorded. Results of bacterial culture of VAP tips and amount of time required for VAP placement and removal and for anesthetic induction were also recorded.
Results—VAP-associated perioperative complications included malposition of the catheter tip in 4 of 23 (17.4%) dogs. The VAP-associated postoperative complications included seroma formation in 7 (30.4%) dogs, breakage of port-anchoring sutures in 3 (13.0%) dogs, suspected fatal catheter-related septicemia in 1 (4.3%) dog, and temporary partial withdrawal occlusion in 18 of 255 (7.1%) anesthetic episodes.
Conclusions and Clinical Relevance—Placement of VAPs provided ready access in dogs receiving radiation therapy. Most complications were minor and self-limiting; however, a low risk of serious complications existed. Use of fluoroscopy to assess position of the catheter tip is recommended to decrease the risk of malposition. Immediate removal of a VAP is recommended when clinical signs of infection develop. Removal of a VAP at the completion of radiation therapy should be performed unless the benefit of continued vascular access outweighs the risks.}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Mayer, Monique N. and Grier, Candace K. and Yoshikawa, Hiroto and Ringwood, P. Brendon}, year={2008}, month={Jul}, pages={96–103} }
 @article{yoshikawa_watanabe_ozawa_2008, title={Odontoclastic Resorptive Lesions in a Dog}, volume={70}, ISSN={0916-7250 1347-7439}, url={http://dx.doi.org/10.1292/jvms.70.103}, DOI={10.1292/jvms.70.103}, abstractNote={We found odontoclastic resorptive lesions on premolars and molars in a 4- year-old miniature dachshund. The teeth had been extracted because the dentin was resorbed. In some teeth, the roots had been replaced by hard tissue, and so we amputated the crowns and curetted roots and alveolar bone. Histopathological examination revealed that the dentin was resorbed by odontoclasts and was replaced with bony tissue. Ten months later we found resorptive lesions in other teeth, and we treated them along with the first treatment. At the time of writing, since this is the first report of a dog with the same lesion in other teeth after the first treatment, we hope to establish better treatment and prevention methods.}, number={1}, journal={Journal of Veterinary Medical Science}, publisher={Japanese Society of Veterinary Science}, author={Yoshikawa, Hiroto and Watanabe, Kazuhiro and Ozawa, Tsuyoshi}, year={2008}, pages={103–105} }