@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_gieger_2024, title={Update in Veterinary Radiation Oncology Focus on Stereotactic Radiation Therapy}, volume={54}, ISSN={["1878-1306"]}, DOI={10.1016/j.cvsm.2023.12.009}, 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={3}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Nolan, Michael W. and Gieger, Tracy L.}, year={2024}, month={May}, pages={559–575} }
 @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.MethodsMice underwent single fraction tongue irradiation (27 Gy, or 0 Gy “sham” control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics.ResultsTongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once).DiscussionThis research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.}, 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={AbstractBackgroundPituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs.ObjectivesTo document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy.AnimalsTwenty‐six client‐owned dogs with acute onset of neurological dysfunction.MethodsRetrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports.ResultsCommon presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1‐weighted hypo‐ to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7‐641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41‐1719 days).Conclusions and Clinical ImportanceDogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.}, 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={AbstractOne radiotherapy (RT) protocol used for canine oral melanoma (OM) gives 36 Gy total, in six weekly or biweekly fractions (6 Gy × 6). This retrospective study characterizes oncologic outcomes for a relatively large group of dogs treated with this protocol and determines whether radiation dose intensity (weekly vs. biweekly) affected either progression‐free or overall survival (PFS and OS). Dogs were included if 6 Gy × 6 was used to treat grossly evident OM, or if RT was used postoperatively in the subclinical disease setting. Kaplan–Meier statistics and Cox regression modelling were used to determine the predictive or prognostic value of mitotic count, bony lysis, World Health Organization (WHO) stage (I, II, III, or IV), using systemic anti‐cancer therapies, tumour burden at the time of RT (macroscopic vs. subclinical), radiation dose intensity (weekly vs. biweekly), and treatment planning type (manual vs. computerized). The median PFS and OS times for all dogs (n = 101) were 171 and 232 days, respectively. On univariate analysis PFS and OS were significantly longer (p = <.05) with subclinical tumour burden, WHO stages I or II, and weekly irradiation. On multivariable analysis, only tumour stage remained significant; therefore, cases were grouped by WHO stage (I/II vs. III/IV). With low WHO stage (I/II), PFS and OS were longer when irradiating subclinical disease (PFS: risk ratio = 0.449, p = .032; OS: risk ratio = 0.422, p = .022); this was not true for high WHO stage (III/IV). When accounting for other factors, radiation dose intensity had no measurable impact on survival in either staging group.}, 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

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{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={AbstractThe purpose of this bi‐institutional retrospective study was to determine whether, in dogs treated with limb amputation and adjunctive chemotherapy for osteosarcoma, oncologic outcomes are impacted by either: (1) baseline cancer pain severity, or (2) the approaches used for perioperative pain management. Data were extracted from the medical records of 284 dogs that underwent both limb amputation and chemotherapy (carboplatin and/or doxorubicin) between 1997 and 2017 for localized (non‐metastatic) osteosarcoma of the appendicular skeleton. Kaplan–Meier survival curves and Cox proportional hazard (PH) models were used to determine the impact that retrospectively scored baseline pain levels (high vs. low) and various analgesic and local anaesthetic treatments had on both metastasis‐free survival and all‐cause mortality. For the entire population, the median disease free interval and median overall survival times were 253 and 284 days, respectively. Baseline pain was rated as “low” in 84 dogs, and “high” in 190 dogs; pain severity had no detectable effect on either metastasis‐free survival or all‐cause mortality. When accounting for the potential influences of known prognostic factors, dogs treated with what was characterized as a high‐intensity perioperative analgesic plan (including both a non‐steroidal anti‐inflammatory drug [NSAID] and a bupivacaine‐eluting soaker catheter placed at the amputation site) had a higher probability of survival than dogs treated with a low‐intensity perioperative analgesic plan (neither an NSAID, nor a soaker catheter); the median overall survival times were 252 and 378 days, respectively (hazard ratio: 2.922; p = .020).}, 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={AbstractNo uniformly beneficial treatments exist for dogs with non‐lymphomatous nasal tumours (NLNT) that relapse after radiotherapy (RT). Reirradiation may prolong survival and improve quality of life. In this retrospective study, we describe outcomes for 11 dogs that had CT‐confirmed locoregional progression of NLNT after an initial course of stereotactic RT (SRT#1; 10 Gy × 3) and were then re‐treated with the same type of protocol (SRT#2, also 10 Gy × 3). The median time between SRT #1 and SRT #2 was 243 days (95% CI: 78–385 days). Ten dogs (91%) had a clinical benefit after SRT#1; five dogs (45%) had clinical benefit after SRT#2. Adverse events after SRT#2 included nasocutaneous or oronasal fistula formation (N = 3 at 180, 270, and 468 days), seizures (N = 2 at 78 and 330 days), bacterial or fungal rhinitis (N = 2 at 240 and 385 days), and facial swelling (N = 1 at 90 days). All 11 dogs have died, due to disease progression, presumed radiotoxicity, or declining quality of life; in most cases, it was difficult to discern between these conditions. The median overall survival time (OST) from SRT#1 was 745 days (95% CI: 360–1132). The median overall survival time (OST) from SRT #2 was 448 days (95% CI: 112–626). For these dogs, survival was prolonged, but adverse events after SRT#2 were common (8/11; 73%). Therefore, before consenting to re‐irradiation with this protocol, pet owners should be counselled about survivorship challenges, including risk for severe toxicities, and persistence of clinical signs.}, 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

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{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{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={AbstractIt is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose‐ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single‐arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti‐inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/− 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species.}, 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={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{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={AbstractBackgroundLocoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti‐inflammatory drugs (NSAIDs).ObjectivesTo characterize event‐free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions).AnimalsFifty‐one client‐owned dogs treated between 2008 and 2017.MethodsDogs were retrospectively categorized into treatment groups: (a) first‐line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first‐line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment‐induced toxicoses, event‐free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment‐related factors on survival was assessed using Cox proportional hazards modeling.ResultsMedian EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self‐limiting.Conclusions and Clinical ImportanceMild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.}, 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{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{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={AbstractRadiation‐induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF‐α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation‐induced mucositis (RIM) and radiation‐associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF‐α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross‐sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real‐time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF‐α, its receptor, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF‐α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF‐α’s receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF‐α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.}, 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{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

OBJECTIVE
To evaluate potential prognostic indicators for local recurrence, distant metastasis, and survival time in dogs with incompletely excised high-grade soft tissue sarcomas (HGSTSs), as defined by a mitotic index ≥ 9, that underwent definitive-intent radiation treatment (RT; ≥ 48 Gy total dose) with or without adjuvant chemotherapy.


ANIMALS
41 client-owned dogs with HGSTSs treated with surgical resection followed by definitive-intent RT between January 1, 2000, and December 31, 2016.


PROCEDURES
Medical records were reviewed retrospectively, and data were collected. The Kaplan-Meier method was used to evaluate the overall survival time (OST) of dogs and time to progression (TTP) of disease, starting from the first day of RT. The Cox proportional hazards model was used to analyze the impact of results for several variables on OST and TTP.


RESULTS
The median OST was 981 days, with 1-, 3-, and 5-year survival rates of 85%, 43%, and 18%, respectively. The median TTP was not reached; however, the mean TTP was 1,581 days. Ten of the 41 (24%) dogs developed metastasis, and 8 (20%) developed local recurrence. Sixteen of the 41 dogs received chemotherapy. The hazard of disease progression over the study period increased as the mitotic index (hazard ratio [HR], 1.115) or duration of RT (HR, 1.427) increased. The hazard of death over the study period increased as the RT duration (HR, 1.372) or surgical scar length (HR, 1.272) increased.


CONCLUSIONS AND CLINICAL RELEVANCE
Although adjuvant chemotherapy was not associated with improved survival time in dogs of the present study, results indicated that improved OST and TTP could be achieved through strict adherence to the prescribed irradiation schedule and avoidance of unnecessary prolongation of the course of RT.
}, 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={AbstractRadiation‐induced heart disease (RIHD) is a potential cause of morbidity and mortality in dogs undergoing thoracic irradiation. Arrhythmias and sudden death have been documented in dogs undergoing stereotactic body radiation therapy for heart base tumours. A study was proposed to interrogate the effect of different stereotactic‐like radiation prescriptions on RIHD development, including arrhythmogenesis and classical histological endpoints in a mouse model. A pilot study was performed initially. The heart base of CD1 (n = 3) and C57Bl/6J (n = 3) female mice were irradiated (12 Gy × 3, daily) with a clinical linear accelerator. No significant adverse effects were noted and each mouse survived the entire subsequent 3‐month observation period. At various time points, no arrhythmias were identified on ECG analysis. Cardiac histology (haematoxylin and eosin, and picrosirius red staining) was performed at 3 months. In a single CD1 mouse and two C57BI/6J mice, multifocal, minimal, peri‐vascular lymphoplasmacytic inflammation was noted within the irradiated proximal heart. In one mouse of each strain, a small, single focus of fibrinoid vascular necrosis was observed. Overall, there was no significant myocardial necrosis, atrophy or inflammation. Picrosirius red staining revealed no evidence of fibrosis in any mouse. Dosimetric verification indicated that the irradiation was successful and delivered as planned, with an average predicted‐to‐measured dose‐difference within 5%. While this study did not demonstrate significant arrhythmogenesis, certain modifications of the experimental mouse irradiation procedures are discussed which may enable more translationally relevant modelling of the canine cardiac response to SBRT‐like irradiation.}, 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={AbstractThe purpose of this bi‐institutional retrospective study was to determine whether survival for dogs with extremity osteosarcoma (OS) is improved through the use of stereotactic radiotherapy (SRT; a single fraction of 25 Gy, or 36 Gy total given in three consecutive daily fractions) plus chemotherapy, vs lower dose conventionally planned and delivered hypofractionated radiotherapy (CHRT; 14‐20 Gy total in 1‐2 consecutive daily fractions) plus chemotherapy. We also sought to determine whether baseline pain severity influences oncologic outcomes following radiotherapy for canine extremity OS. The medical records of 82 dogs undergoing radiotherapy for confirmed or presumed OS were reviewed. In dogs receiving combinations of both chemotherapy and radiotherapy, survival was significantly longer with SRT vs CHRT (median overall survival time: 350 vs 147 days; P = .031). In a univariate analysis, dogs with pulmonary metastases and high pain at the time of irradiation had short overall survival times; use of high radiation doses and chemotherapy were associated with improved survival. Separate multivariable models were built to assess the predictive nature of various factors that might influence event‐free or overall survival in dogs treated with radiotherapy, with or without chemotherapy; for dogs treated with both chemotherapy and radiotherapy, overall survival times were significantly longer when baseline pain scores were ‘low’ (vs ‘high’; hazard ratio: 0.258; P = .030), radiation doses were high (hazard ratio: 0.943; P = .034). Neither pain nor radiation dose were associated with survival in dogs treated with radiotherapy, without chemotherapy.}, 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{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. Methods This was a prospective, single-arm study. Twelve client-owned cats with cytologically diagnosed FGL were treated with a combination of abdominal cavity radiation therapy (RT; 8 Gy total dose administered in two 4 Gy fractions, 21 days apart), lomustine chemotherapy (approximately 40 mg/m2, administered orally at 21-day intervals for four treatments), prednisolone (5 mg PO q24h) and cobalamin (250 µg/week SC). Results Three cats were euthanized prior to the second treatment and it was difficult to discern treatment-associated toxicity from progressive disease. Four of the remaining cats developed cytopenias, resulting in 7–14-day lomustine treatment delays and/or dose reductions. Six cats had a partial response to treatment and three had stable disease based on ultrasound at day 21 (50% overall response rate). Three of these six cats completed the study and lived >240 days; one died of refractory diabetes mellitus with no clinical evidence of FGL, and the other two died as a result of FGL. The median overall survival time was 101 days (95% confidence interval [CI] 9–240). The median progression-free survival time was 77 days (95% CI 8–212). Necropsies were performed in eight cats, which revealed multifocal lymphoma throughout the gastrointestinal tract and other organs. Conclusions and relevance Oncological outcomes reported herein are comparable to those achieved with multiagent injectable chemotherapy (eg, CHOP). Treatment was seemingly well tolerated in most cats and was relatively cost-effective. It is therefore plausible that improved disease control may be achievable through continued optimization and intensification of the combinatorial chemoradiotherapy protocol. }, 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{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={AbstractCanine pituitary tumours are increasingly treated with stereotactic radiotherapy (SRT). Here, we report clinical outcomes in dogs treated with single‐fraction SRT; we also explore technical aspects of SRT treatment planning. A single‐institution retrospective study was performed, including any dog with a pituitary mass (PM) that was treated using a standardized single‐fraction (16 Gy) SRT protocol between 2014 and 2017. Via medical records review, 13 cases were identified. Nine dogs neurologically improved after SRT. Four dogs experienced MRI‐documented tumour volume reduction. Nine dogs experienced neurologic decline in 1.5 to 18 months after SRT and were euthanized. The median overall survival time was 357 days, with 15% alive 18 months after SRT. To better understand whether SRT target delineation is predictably altered by use of magnetic resonance imaging (MRI) in addition to computed tomography (CT), two radiation oncologists (RO) retrospectively re‐evaluated all imaging studies used for SRT planning in these 13 cases. Gross tumour volume (GTV) was contoured on co‐registered CT and MRIs for each case. In seven cases, CT alone was deemed inadequate for GTV contouring by at least one RO. T1 post‐contrast MRI was considered the ideal image for GTV contouring in 11 cases. Contouring on MRI yielded larger GTV than CT for 11 cases. Inter‐observer variability existed in each case and was greater for MRI. In summary, use of co‐registered CT and MRI images is generally considered advantageous for PM delineation when using SRT. Notably, survival times reported herein are shorter than what has previously been reported for PM treated with finely fractionated full‐course RT protocols.}, number={1}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gieger, Tracy L. and Nolan, Michael W.}, year={2021}, month={Mar}, pages={17–24} }
 @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={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} }
 @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={AbstractA total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall‐mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source‐to‐axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.}, 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={AbstractThe “gold standard” for verification of patient positioning before linear accelerator‐based stereotactic radiation therapy is kilovoltage cone‐beam computed tomography (kV‐CBCT), which is not uniformly available or utilized; planar imaging is sometimes used instead. The primary aim of this study was to determine if the position of the bony skull, when used as a surrogate for isocenter verification, is different when orthogonal megavoltage (MV) portal or kilovoltage (kV/kV) radiographs are used for image guidance, rather than kV‐CBCT. A secondary aim was to determine the influence of intra‐observer variability, body size and skull conformation on positioning, as determined using these three imaging modalities. Dogs and cats receiving radiotherapy of the head were recruited for this prospective analytical study. Planar (MV portal and kV/kV images) and volumetric (kV‐CBCT) images were acquired before treatment, and manually coregistered with reference images. Differences in skull position when matched based on MV portal, kV/kV images and kV‐CBCT were compared. A total of 65 subjects and 148 unique datasets were evaluated. The Wilcoxon rank‐sum test was used to evaluate effects of transitioning between imaging modalities. When comparing magnitude of shifts in MV to kV‐CBCT, MV to kV/kV and kV/kV to kV‐CBCT, there were statistically significant differences. Results were not measurably impacted by body size, skull conformation or interobserver differences. Based on shift magnitude and direction, an isotropic setup margin of at least 1 mm should be incorporated within the planning target volume when MV or kV planar imaging is used for position verification.}, 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{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={AbstractThe aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow‐up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20–24 Gy to the central portion of the tumor. Thirty‐two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment‐associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross‐sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330–708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.}, 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={AbstractThe clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow‐up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44–424 days and mean 95% CI for stereotactic radiation therapy dogs was 260–518 days).}, 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_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{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_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={AbstractRecent technical advancements in radiation therapy have allowed for improved targeting of tumours and sparing nearby normal tissues, while simultaneously decreasing the risk for medical errors by incorporating additional safety checks into electronic medical record keeping systems. The benefits of these new technologies, however, depends on their proper integration and use in the oncology clinic. Despite the advancement of technology for treatment delivery and medical record keeping, misadministration errors have a significant impact on patient care in veterinary oncology. The first part of this manuscript describes a medical incident that occurred at an academic veterinary referral hospital, in a dog receiving a combination of stereotactic radiation therapy and full‐course intensity‐modulated, image‐guided radiation therapy. The second part of the report is a literature review, which explores misadministration errors and novel challenges which arise with the implementation of advancing technologies in veterinary radiation oncology.}, 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. 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. 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. 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. 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{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={AbstractThe objective of this study is to determine the rate of toxicity, median survival time (MST) and prognostic factors in dogs with presumed intracranial meningiomas that were treated with stereotactic radiation therapy (SRT). Patient demographics, neurological history, details of SRT plans and response to treatment (including toxicity and survival times) were examined for potential prognostic factors. Overall MST (MST) due to death for any cause was 561 days. There was a mild to moderate exacerbation of neurological symptoms 3‐16 weeks following SRT treatments in 11/30 (36.7%) of dogs. This presumed adverse event was treated with corticosteroids, and improvement was seen in most of these dogs.  Death within 6 months of treatment as a result of worsening neurologic signs was seen in 4/30 (13.3%) of dogs. Volume of normal brain that received full dose at a prescription of 8Gy × 3 fractions was predictive of death due to neurological problems within this 6‐month period.}, 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{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
Objective—To evaluate outcomes of stereotactic body radiation therapy (SBRT) in cats with injection-site sarcomas (ISS) via assessment of local responses and recurrences, survival times, and complications.
Design—Retrospective case series.
Animals—11 cats with ISS.
Procedures—Medical records of cats that were treated with SBRT for ISS between June 2008 and July 2012 were reviewed; information on patient demographics (age, sex, and breed), oncological histories (including prior treatment and histologic grade), details of SBRT plans (tumor volume, treatment field sizes, and prescription), response to treatment (including toxicoses), progression-free intervals, and survival times were extracted.
Results—Acute radiation-associated toxicoses were infrequent and limited to mild, self-limiting dermatitis and colitis in 2 and 1 of the 11 cats, respectively. No late radiation-associated toxicoses were observed. The objective response rate was 8 of 11 cats; these patients either had a partial or complete response as determined on the basis of CT or physical examination findings. The median progression-free interval was 242 days, and the median overall survival time was 301 days; median follow-up time of censored subjects was 173 days.
Conclusions and Clinical Relevance—SBRT was completed in 3 to 5 days and was well tolerated when used to treat cats with ISS. Measurable tumor responses were achieved in most cats in this study. Stereotactic body radiation therapy provided a means for palliation of ISS; further investigation is required to determine whether SBRT is a valid treatment option for downstaging disease prior to definitive surgery.}, 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.Hypothesis/ObjectivesThe objective of this study was to assess local tumor control, overall survival, and toxicosis after intensity‐modulated and image‐guided radiation therapy (IM/IGRT) for treatment of genitourinary carcinomas (CGUC) in dogs.Animals21 client‐owned dogs.MethodsA retrospective study was performed. Medical records of dogs for which there was intent to treat with a course of definitive‐intent IM/IGRT for CGUC between 2008 and 2011 were reviewed. Descriptive and actuarial statistics comprised the data analysis.ResultsPrimary tumors were located in the prostate (10), urinary bladder (9), or urethra (2). The total radiation dose ranged from 54–58 Gy, delivered in 20 daily fractions. Grade 1 and 2 acute gastrointestinal toxicoses developed in 33 and 5% of dogs, respectively. Grade 1 and 2 acute genitourinary and grade 1 acute integumentary toxicoses were documented in 5, 5, and 20% of dogs, respectively. Four dogs experienced late grade 3 gastrointestinal or genitourinary toxicosis. The subjective response rate was 60%. The median event‐free survival was 317 days; the overall median survival time was 654 days. Neither local tumor control nor overall survival was statistically dependent upon location of the primary tumor.Conclusions and Clinical ImportanceIM/IGRT is generally well‐tolerated and provides an effective option for locoregional control of CGUC. As compared with previous reports in the veterinary literature, inclusion of IM/IGRT in multimodal treatment protocols for CGUC can result in superior survival times; controlled prospective evaluation is warranted.}, 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} }