Susan Larue - Academia.edu (original) (raw)

Papers by Susan Larue

Research paper thumbnail of Combining radiation therapy with other treatment modalities

Seminars in Veterinary Medicine and Surgery, Sep 1, 1995

Combining treatment modalities is indicated when single modality treatment does not result in ade... more Combining treatment modalities is indicated when single modality treatment does not result in adequate tumor control, or if the cosmetic or functional outcome of single modality treatment is less than desirable. The combination of surgery and radiation has proven useful in the treatment of both human and veterinary patients. Surgery can be used to remove large, bulky tumors whereas radiation therapy eliminates the subclinical disease adjacent to the tumor mass that invades important normal tissue structures. If properly combined, the result should be better tumor control combined with a better functional and cosmetic outcome. Radiation therapy can be administered preoperatively, postoperatively, and intraoperatively, depending on a variety of factors. Radiation therapy combined with hyperthermia has a strong scientific rationale. Hyperthermia is particularly effective against some cells, such as those in late S-phase, that are resistant to radiation therapy. Nutrient-deprived cells and cells with low pH are also very sensitive to hyperthermia, and these may reflect areas in a tumor where hypoxia may be present. Therapeutic gain has been shown in randomized clinical trials combining radiation therapy and hyperthermia in tumor bearing dogs. However, the disadvantage of hyperthermia for both human and veterinary tumors remains the inability to adequately maintain uniform temperatures to the tumors. Chemotherapy is an important adjuvant to radiation therapy for the control of distant tumor spread. The scientific rationale for combining chemotherapy with radiation therapy for local control is less clear, and is complex because of a variety of factors.

Research paper thumbnail of Tumor physiology and cell kinetics

Seminars in veterinary medicine and surgery (small animal)

ABSTRACT

Research paper thumbnail of Soft tissue sarcomas in dogs

The Canadian veterinary journal. La revue vétérinaire canadienne, 2005

Research paper thumbnail of Canine and Feline Nasal and Paranasal Sinus Tumors

Veterinary Clinics of North America: Small Animal Practice, 1992

Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that ori... more Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that originate on the nasal planum are common in the cat but are not discussed in this article. The prevalence of tumors of the nasal and paranasal sinuses ranges between 0.3 to 2.4% of tumors surveyed in the dog and 4.2% of all tumors diagnosed in one study in the cat. 2-4 • 12 • 16 • 17 In the dog, tumors of the nasal and paranasal sinuses are generally seen in older animals (median, 10 years), with various sex and breed distributions reported. 3 • 12 • 16 • 17 Affected cats are generally older males with a mean age of 8 to 10 years. 4 • 6 Although the most common cause of unilateral epistaxis, facial deformity, and epiphora in the aged dog and cat is a malignant nasal or paranasal tumor, other differentials must be considered. 22 Definitive diagnosis is based on the signalment, history, physical examination findings, radiographs, and histologic evidence of malignant neoplasia. Radiation therapy, with or without surgery, has been considered to be the most effective treatment. This article reviews the clinical features and optimum methods for diagnosing nasal tumors in the dog and cat. Therapeutic strategies are also discussed.

Research paper thumbnail of Hyperthermic treatment of malignant diseases: current status and a view toward the future

Seminars in oncology, 1997

New studies in hyperthermia at the basic science, engineering, and clinical level have stimulated... more New studies in hyperthermia at the basic science, engineering, and clinical level have stimulated renewed enthusiasm for re-investigating its potential as an anticancer therapy. This article reviews the salient features of these recent results and points out areas for additional investigation. Highlighting these new results is the publication of several positive phase III trials for thermoradiotherapy compared to radiotherapy alone. Important highlights are the encouraging results using magnetic resonance imaging for noninvasive thermometry. If this technology is successfully implemented with real time power control it will revolutionize the clinical application of hyperthermia.

Research paper thumbnail of Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction

International journal of radiation oncology, biology, physics, Jan 15, 2015

Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopatholog... more 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 corr...

Research paper thumbnail of Lung Resection Using Surgical Staples in Dogs and Cats

Veterinary Surgery, 1987

Thirty seven dogs and cats were subjected to lobectomy, partial lobectomy, or pneumonectomy using... more Thirty seven dogs and cats were subjected to lobectomy, partial lobectomy, or pneumonectomy using stapling equipment. The most common indication was neoplasia. No operative, perioperative, or long-term deaths could be attributed to the use of staples; complications were minimal. Staple resection was believed to be safe, fast, and efficient for removal of various segments of canine and feline lung.

Research paper thumbnail of Evaluation of 18F-FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma

Veterinary and Comparative Oncology, 2013

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/... more 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy-proven oral SCC were imaged with whole body 18FDG-PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG-PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9-24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG-PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG-PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.

Research paper thumbnail of Intraoperative radiation (IORT) injury to sciatic nerve in a large animal model

Radiotherapy and Oncology, 1994

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intra... more Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). To assess IORT injury to peripheral nerve, three groups of five beagle dogs received doses of 12, 20 or 28 Gy to the surgically exposed and isolated right sciatic nerve in the mid-femoral region using 6 MeV electrons. The left sciatic nerve of each dog served as its own control. As a surgical control five dogs received surgical exposure of the nerve only. Monthly neurologic exams, electromyogram and nerve conduction studies were performed following treatment for 12 months. After that dogs were euthanatized and histologic studies of nerves were done to define the degree of axon and myelin loss as well as presence of fibrosis and vascular lesions for different doses of IORT. Results showed that the threshold dose most likely related to expression of severe radiation damage to the nerve in this model is between 20 and 25 Gy. Radiation injury to peripheral nerve appears to be the result of direct radiation effects on Schwann cells and nerve vasculature and secondary effects resulting from damage to regional muscle and vasculature. A theoretical mechanism of radiation injury to peripheral nerve is proposed.

Research paper thumbnail of Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids

Nutrition Research, 2011

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammator... more Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E₂, thromboxane B₂, leukotriene B₄, and 11-dehydro thromboxane B₂), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P < .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy.

Research paper thumbnail of Amputation and Cisplatin for Treatment of Canine Osteosarcoma

Journal of Veterinary Internal Medicine, 1991

Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventee... more Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two dogs received postoperative doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1,282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma.

Research paper thumbnail of Outcomes of Pituitary Tumor Irradiation in Cats

Journal of Veterinary Internal Medicine, 2006

Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors ... more Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors in cats is limited. Radiation therapy is effective in controlling the clinical signs associated with pituitary tumors in cats, with a low incidence of adverse effects. Eight cats were irradiated at Colorado State University between 1991 and 2002 for spontaneous pituitary tumors. A retrospective review of records was made to assess tumor control and incidence of radiation-induced adverse effects. Pituitary carcinoma was diagnosed in 2 cats and pituitary adenoma in 6 cats. Total radiation dosage ranged from 4,500 to 5,400 cGy administered Monday through Friday in 270 or 300 cGy fractions. Acute effects were limited to epilation and mild otitis externa. Focal brain necrosis adjacent to regrowth of a pituitary carcinoma and a second tumor in the radiation field were reported as possible late effects. Median survival, regardless of cause of death of the 8 cats, was 17.4 months (range, 8.4 to 63.1 months). Median survival could not be determined if cats were censored for non-tumor-related causes of death. Six cats were alive at 1 year, and 3 cats were alive at 2 years after treatment. Tumor recurrence was seen in 1 cat with a pituitary carcinoma. Neurologic signs improved within 2 months in all 5 cats that presented with abnormal neurologic signs. Clinical signs caused by a concurrent endocrine disorder began to improve within 1-5 months in the 7 cats with hyperadrenocorticism or acromegaly. Radiation therapy is an effective primary treatment modality for cats presenting with neurologic signs associated with a pituitary mass and can improve clinical signs associated with concurrent hyperadrenocorticism or acromegaly in cats with no neurologic abnormalities.

Research paper thumbnail of Effects of intraoperative irradiation and intraoperative hyperthermia on canine sciatic nerve: Neurologic and electrophysiologic study

International Journal of Radiation Oncology*Biology*Physics, 1996

Pupuse: Late radiation lqjnry to perIpberal nerve may be the limitjng factor in the cWcai applica... more Pupuse: Late radiation lqjnry to perIpberal nerve may be the limitjng factor in the cWcai applicat$on of intraoperative radiation therapy (IORT). The combhation of IORT with intraoperatlve hyperWn& (IOHT) ~specificconcentsregardingtbeeffectsoncertainnormaltiarmessuchas~~e~nwve,which~t be included in the treatment iield. The objective of this study was to compare the effect of IORT alone to the effect of IORT comW with IOIIT on peripheral nerve in normal beagle dogs. Methods and Materialsz Young adult beagle dogs were randomized into five groups of three to five dogs each toreceiveIORTdosesof16,2O,24,2S,or32Gyto5anofsmgicaUyexposedrightsciaticnerveusing6MeV el~~amlsixgroupsoffourtofivedogseachreceivedIORTdasesof0,12,16,~,~,or28Gy~ with 44°C of IOHT for 60 min. IOHT was performed using a water circ&t& hyperthermia devlcewlth~ multi&umel thermometq system on the surgically exposed sciatic nerve. Nem-olo@c and eJe&rqhyslo@ic. xammahs were done before and monthly after treatment for 24 months. ElectrophysioIog& studies haduded &ctromyographIc (EMG) e xambmtions of motor tictioh as well as motor nerve conduction velnc&s studies Results Two years after treatment, the effective dose for 50% compIiadion (ED& for limb paresis in dogs exposed to IORT only was 22 Gy. The EDs for paresis in dogs exposed to IORT combii with IOEIT weds 15 Gy. Tbe thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more promhx& changes suchasEMGabnormalities,decreaseinconductionvelocityandamplitudeoftheactionpdential,andcomplete amduction bIo& in dw that received the combiin of IORT and IOHT. The latency to development of pedpbed neuropathies was shorter for dogs exposed to the combined treatment. Conclusion: The lHobebility of developing peripheral nem-opathies in a large anhnal model was higher for. ORT combmed with IOHT, than for IORT alone. The dose req&ed to produce the same level of h&e mdiation &my to the sciatic nerve was reduced by a factor of 1.5 (TER) if IORT was combined with 44°C of IOHT for 60 min. Intraoperatlve irrsdiation, Intraoperatlve hyperthermia, Peripheral nerve.

Research paper thumbnail of A phase i hyperthermia- induced interleukin- 12 gene- therapy trial in a spontaneously arising feline soft tissue sarcoma model

International Journal of Radiation Oncology*Biology*Physics, 2004

Research paper thumbnail of 1050 Influence of volume on intraoperatively irradiated canine ureters

International Journal of Radiation Oncology*Biology*Physics, 1995

Purpose/Objective: lntraopcrative radiation therap', tlOkT) is used to deliver high single doses ... more Purpose/Objective: lntraopcrative radiation therap', tlOkT) is used to deliver high single doses of radiation to the tumor bed following surgical removal of various abdominal malignancies The ad,,antage or [ORT is the ability to remove sensitive normal tissues from the treamlent field and limit the volume of normal tissue irradiated. The purpose of this study was to determine dose-volume relationships for retruperitoneal tissues.

Research paper thumbnail of Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct

International Journal of Hyperthermia, 2006

Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic ... more Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under control of a heat shock promoter. This approach limits systemic toxicity by restricting IL-12 delivery locally to the tumour. The kinetics of the downstream cytokines interferon-gamma (IFN-gamma) and interferon inducible protein-10 (IP-10) and other molecules affecting angiogenesis, vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were also studied. 4T1 tumours were grown in Balb/C mice and the AdhspmIL-12 construct was injected intra-tumourally. The tumours were heated after 24 h using a water bath. At various time points post-heating the tumours were collected and quantitatively assessed for cytokine production and vascularity. A significant reduction was seen in the tumour vasculature of the treated group vs. the control group mice. Systemic effects of IL-12 were limited to generalized immunostimulation. No hepatoxicity was noted. This study suggests that IL-12 can be effectively delivered using a gene-based approach with a heat shock promoter. This results in quantitatively measurable anti-angiogenesis and general immunostimulation. The complex inter-play of other pro- and anti-angiogenic factors (IFN-gamma, IP-10, VEGF and PAI-1) was also studied.

Research paper thumbnail of Using units of CEM 43°C T90, local hyperthermia thermal dose can be delivered as prescribed

International Journal of Hyperthermia, 2000

... DE THRALL{*, GL ROSNER{, C. AZUMA{, SM LARUE}, BC CASE{, T. SAMULSKI{ and MW DEWHIRST{ {Colle... more ... DE THRALL{*, GL ROSNER{, C. AZUMA{, SM LARUE}, BC CASE{, T. SAMULSKI{ and MW DEWHIRST{ {College ... possible. It was also desirable to have similar numbers of hyperthermia treatments in each ther-mal dose group. ...

Research paper thumbnail of Induction of theHuman Heat Shock Promoter HSP70Bby Nutritional Stress: Implications for Cancer Gene Therapy

Cancer Investigation, 2008

We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (I... more We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (IL-12) gene under control of the heat-inducible promoter HSP70B. This construct, AdhspfIL12, was used in a phase I trial in feline soft tissue sarcomas. During the course of our experiments, we noted that IL-12 was being produced in the transfected Crandell Feline Kidney (CrFK) cells under certain conditions even in the absence of hyperthermia. This observation was further explored to identify the cause of this unintended HSP70B induction. We used real-time PCR as a sensitive method to quantitatively detect the presence of even small amounts of IL-12 mRNA. This served as a surrogate indicator of HSP70B induction. Various conditions were tested to induce the heat shock promoter, including nutritional deprivation, radiation and changes in pH. Nutritional stresses, specifically the absence of glucose and glutamine, could induce the heat shock promoter, thus, resulting in production of the downstream gene product. Other factors known to trigger the heat shock response, pH change, and reactive oxygen species production were also studied but were not found to contribute to heat shock promoter induction in our setting. The human heat shock promoter (HSP70B) is reported to be an efficient and tightly regulated promoter. We discovered, using sensitive real-time PCR techniques, that it can also be induced in response to cellular nutrient stresses. The pros and cons of this phenomenon and its implications for cancer gene therapy are discussed.

Research paper thumbnail of Comparison of adaptive radiotherapy techniques for the treatment of bladder cancer

The British Journal of Radiology, 2013

Objective: Day-today anatomical variations complicate bladder cancer radiotherapy treatment. This... more Objective: Day-today anatomical variations complicate bladder cancer radiotherapy treatment. This work quantifies the impact on target coverage and irradiated normal tissue volume for different adaptive strategies. Methods: 20 patients were retrospectively planned using different three-dimensional conformal radiotherapy treatment strategies for whole-bladder carcinoma: (i) ''conventional'' treatment used isotropic expansion of the clinical target volume (CTV) by 15 mm to the planning target volume (PTV) for daily treatment; (ii) ''plan of the day'' used daily volumetric on-treatment imaging [cone beam CT (CBCT)] to select from four available plans with varying superior PTV margins; (iii) ''composite'' strategies used ontreatment CBCTs from Fractions 1-3 to inform a composite CTV and adapted PTV (5and 10-mm margins for composite 1 and composite 2, respectively) for subsequent treatment. Target coverage was evaluated from available CBCTs (the first three fractions then the minimum weekly thereafter), and the reduction in the irradiated volume (i.e. within the 95% isodose) was quantified. Results: Plan of the day improved target coverage (i.e. all of the bladder within the 95% isodose throughout the treatment) relative to conventional treatment (p50.10), while no such benefit was observed with composite 2. Target coverage was reduced with composite 1 relative to conventional treatment. The mean irradiated volume was reduced by 17.2%, 35.0% and 14.6% relative to conventional treatment, for plan of the day, composite 1 and composite 2, respectively (p,0.01 in all cases). No parameters predictive of large changes in bladder volume later in the treatment were identified. Conclusions: Adaptive techniques can maintain or improve target coverage while allowing for reduced irradiated volume and possibly reduced toxicity. The plan-of-theday technique appeared to provide the optimal balance between target coverage and normal tissue sparing. Advances in knowledge: This study suggests that plan-of-the-day techniques will provide optimal outcomes for adaptive bladder radiotherapy.

Research paper thumbnail of Use of Radiation and a Slow-Release Cisplatin Formulation for Treatment of Canine Nasal Tumors

Veterinary Radiology <html_ent glyph="@amp;" ascii="&amp;"/> Ultrasound, 2004

The purpose of this study was to evaluate the combined use of radiation and a slow-release cispla... more The purpose of this study was to evaluate the combined use of radiation and a slow-release cisplatin chemotherapy formulation for treatment of malignant nasal tumors in dogs. In this retrospective analysis, 51 dogs were evaluated with respect to treatment toxicity, tumor type, stage of disease, cribriform plate involvement, and overall survival. In general, treatment was well tolerated. Mean and median survival as assessed by the Kaplan-Meier product limit method was 570 and 474 days, respectively. No other factors, including tumor type, stage of disease, or cribriform plate invasion had a significant impact on survival. In conclusion, a combination of slow release cisplatin chemotherapy and radiation for the treatment of canine nasal tumors is well tolerated. Results of this analysis warrant further study to elucidate possible other beneficial radiation potentiating drugs and dosing schedules.

Research paper thumbnail of Combining radiation therapy with other treatment modalities

Seminars in Veterinary Medicine and Surgery, Sep 1, 1995

Combining treatment modalities is indicated when single modality treatment does not result in ade... more Combining treatment modalities is indicated when single modality treatment does not result in adequate tumor control, or if the cosmetic or functional outcome of single modality treatment is less than desirable. The combination of surgery and radiation has proven useful in the treatment of both human and veterinary patients. Surgery can be used to remove large, bulky tumors whereas radiation therapy eliminates the subclinical disease adjacent to the tumor mass that invades important normal tissue structures. If properly combined, the result should be better tumor control combined with a better functional and cosmetic outcome. Radiation therapy can be administered preoperatively, postoperatively, and intraoperatively, depending on a variety of factors. Radiation therapy combined with hyperthermia has a strong scientific rationale. Hyperthermia is particularly effective against some cells, such as those in late S-phase, that are resistant to radiation therapy. Nutrient-deprived cells and cells with low pH are also very sensitive to hyperthermia, and these may reflect areas in a tumor where hypoxia may be present. Therapeutic gain has been shown in randomized clinical trials combining radiation therapy and hyperthermia in tumor bearing dogs. However, the disadvantage of hyperthermia for both human and veterinary tumors remains the inability to adequately maintain uniform temperatures to the tumors. Chemotherapy is an important adjuvant to radiation therapy for the control of distant tumor spread. The scientific rationale for combining chemotherapy with radiation therapy for local control is less clear, and is complex because of a variety of factors.

Research paper thumbnail of Tumor physiology and cell kinetics

Seminars in veterinary medicine and surgery (small animal)

ABSTRACT

Research paper thumbnail of Soft tissue sarcomas in dogs

The Canadian veterinary journal. La revue vétérinaire canadienne, 2005

Research paper thumbnail of Canine and Feline Nasal and Paranasal Sinus Tumors

Veterinary Clinics of North America: Small Animal Practice, 1992

Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that ori... more Tumors involving the nasal cavity and nearby sinuses are rare in the dog and cat. Tumors that originate on the nasal planum are common in the cat but are not discussed in this article. The prevalence of tumors of the nasal and paranasal sinuses ranges between 0.3 to 2.4% of tumors surveyed in the dog and 4.2% of all tumors diagnosed in one study in the cat. 2-4 • 12 • 16 • 17 In the dog, tumors of the nasal and paranasal sinuses are generally seen in older animals (median, 10 years), with various sex and breed distributions reported. 3 • 12 • 16 • 17 Affected cats are generally older males with a mean age of 8 to 10 years. 4 • 6 Although the most common cause of unilateral epistaxis, facial deformity, and epiphora in the aged dog and cat is a malignant nasal or paranasal tumor, other differentials must be considered. 22 Definitive diagnosis is based on the signalment, history, physical examination findings, radiographs, and histologic evidence of malignant neoplasia. Radiation therapy, with or without surgery, has been considered to be the most effective treatment. This article reviews the clinical features and optimum methods for diagnosing nasal tumors in the dog and cat. Therapeutic strategies are also discussed.

Research paper thumbnail of Hyperthermic treatment of malignant diseases: current status and a view toward the future

Seminars in oncology, 1997

New studies in hyperthermia at the basic science, engineering, and clinical level have stimulated... more New studies in hyperthermia at the basic science, engineering, and clinical level have stimulated renewed enthusiasm for re-investigating its potential as an anticancer therapy. This article reviews the salient features of these recent results and points out areas for additional investigation. Highlighting these new results is the publication of several positive phase III trials for thermoradiotherapy compared to radiotherapy alone. Important highlights are the encouraging results using magnetic resonance imaging for noninvasive thermometry. If this technology is successfully implemented with real time power control it will revolutionize the clinical application of hyperthermia.

Research paper thumbnail of Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction

International journal of radiation oncology, biology, physics, Jan 15, 2015

Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopatholog... more 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 corr...

Research paper thumbnail of Lung Resection Using Surgical Staples in Dogs and Cats

Veterinary Surgery, 1987

Thirty seven dogs and cats were subjected to lobectomy, partial lobectomy, or pneumonectomy using... more Thirty seven dogs and cats were subjected to lobectomy, partial lobectomy, or pneumonectomy using stapling equipment. The most common indication was neoplasia. No operative, perioperative, or long-term deaths could be attributed to the use of staples; complications were minimal. Staple resection was believed to be safe, fast, and efficient for removal of various segments of canine and feline lung.

Research paper thumbnail of Evaluation of 18F-FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma

Veterinary and Comparative Oncology, 2013

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/... more 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy-proven oral SCC were imaged with whole body 18FDG-PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG-PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9-24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG-PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG-PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.

Research paper thumbnail of Intraoperative radiation (IORT) injury to sciatic nerve in a large animal model

Radiotherapy and Oncology, 1994

Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intra... more Peripheral nerve appears to be a dose-limiting normal tissue in the clinical application of intraoperative radiation therapy (IORT). To assess IORT injury to peripheral nerve, three groups of five beagle dogs received doses of 12, 20 or 28 Gy to the surgically exposed and isolated right sciatic nerve in the mid-femoral region using 6 MeV electrons. The left sciatic nerve of each dog served as its own control. As a surgical control five dogs received surgical exposure of the nerve only. Monthly neurologic exams, electromyogram and nerve conduction studies were performed following treatment for 12 months. After that dogs were euthanatized and histologic studies of nerves were done to define the degree of axon and myelin loss as well as presence of fibrosis and vascular lesions for different doses of IORT. Results showed that the threshold dose most likely related to expression of severe radiation damage to the nerve in this model is between 20 and 25 Gy. Radiation injury to peripheral nerve appears to be the result of direct radiation effects on Schwann cells and nerve vasculature and secondary effects resulting from damage to regional muscle and vasculature. A theoretical mechanism of radiation injury to peripheral nerve is proposed.

Research paper thumbnail of Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids

Nutrition Research, 2011

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammator... more Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E₂, thromboxane B₂, leukotriene B₄, and 11-dehydro thromboxane B₂), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy.

Research paper thumbnail of Amputation and Cisplatin for Treatment of Canine Osteosarcoma

Journal of Veterinary Internal Medicine, 1991

Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventee... more Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two dogs received postoperative doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1,282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma.

Research paper thumbnail of Outcomes of Pituitary Tumor Irradiation in Cats

Journal of Veterinary Internal Medicine, 2006

Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors ... more Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors in cats is limited. Radiation therapy is effective in controlling the clinical signs associated with pituitary tumors in cats, with a low incidence of adverse effects. Eight cats were irradiated at Colorado State University between 1991 and 2002 for spontaneous pituitary tumors. A retrospective review of records was made to assess tumor control and incidence of radiation-induced adverse effects. Pituitary carcinoma was diagnosed in 2 cats and pituitary adenoma in 6 cats. Total radiation dosage ranged from 4,500 to 5,400 cGy administered Monday through Friday in 270 or 300 cGy fractions. Acute effects were limited to epilation and mild otitis externa. Focal brain necrosis adjacent to regrowth of a pituitary carcinoma and a second tumor in the radiation field were reported as possible late effects. Median survival, regardless of cause of death of the 8 cats, was 17.4 months (range, 8.4 to 63.1 months). Median survival could not be determined if cats were censored for non-tumor-related causes of death. Six cats were alive at 1 year, and 3 cats were alive at 2 years after treatment. Tumor recurrence was seen in 1 cat with a pituitary carcinoma. Neurologic signs improved within 2 months in all 5 cats that presented with abnormal neurologic signs. Clinical signs caused by a concurrent endocrine disorder began to improve within 1-5 months in the 7 cats with hyperadrenocorticism or acromegaly. Radiation therapy is an effective primary treatment modality for cats presenting with neurologic signs associated with a pituitary mass and can improve clinical signs associated with concurrent hyperadrenocorticism or acromegaly in cats with no neurologic abnormalities.

Research paper thumbnail of Effects of intraoperative irradiation and intraoperative hyperthermia on canine sciatic nerve: Neurologic and electrophysiologic study

International Journal of Radiation Oncology*Biology*Physics, 1996

Pupuse: Late radiation lqjnry to perIpberal nerve may be the limitjng factor in the cWcai applica... more Pupuse: Late radiation lqjnry to perIpberal nerve may be the limitjng factor in the cWcai applicat$on of intraoperative radiation therapy (IORT). The combhation of IORT with intraoperatlve hyperWn& (IOHT) ~specificconcentsregardingtbeeffectsoncertainnormaltiarmessuchas~~e~nwve,which~t be included in the treatment iield. The objective of this study was to compare the effect of IORT alone to the effect of IORT comW with IOIIT on peripheral nerve in normal beagle dogs. Methods and Materialsz Young adult beagle dogs were randomized into five groups of three to five dogs each toreceiveIORTdosesof16,2O,24,2S,or32Gyto5anofsmgicaUyexposedrightsciaticnerveusing6MeV el~~amlsixgroupsoffourtofivedogseachreceivedIORTdasesof0,12,16,~,~,or28Gy~ with 44°C of IOHT for 60 min. IOHT was performed using a water circ&t& hyperthermia devlcewlth~ multi&umel thermometq system on the surgically exposed sciatic nerve. Nem-olo@c and eJe&rqhyslo@ic. xammahs were done before and monthly after treatment for 24 months. ElectrophysioIog& studies haduded &ctromyographIc (EMG) e xambmtions of motor tictioh as well as motor nerve conduction velnc&s studies Results Two years after treatment, the effective dose for 50% compIiadion (ED& for limb paresis in dogs exposed to IORT only was 22 Gy. The EDs for paresis in dogs exposed to IORT combii with IOEIT weds 15 Gy. Tbe thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more promhx& changes suchasEMGabnormalities,decreaseinconductionvelocityandamplitudeoftheactionpdential,andcomplete amduction bIo& in dw that received the combiin of IORT and IOHT. The latency to development of pedpbed neuropathies was shorter for dogs exposed to the combined treatment. Conclusion: The lHobebility of developing peripheral nem-opathies in a large anhnal model was higher for. ORT combmed with IOHT, than for IORT alone. The dose req&ed to produce the same level of h&e mdiation &my to the sciatic nerve was reduced by a factor of 1.5 (TER) if IORT was combined with 44°C of IOHT for 60 min. Intraoperatlve irrsdiation, Intraoperatlve hyperthermia, Peripheral nerve.

Research paper thumbnail of A phase i hyperthermia- induced interleukin- 12 gene- therapy trial in a spontaneously arising feline soft tissue sarcoma model

International Journal of Radiation Oncology*Biology*Physics, 2004

Research paper thumbnail of 1050 Influence of volume on intraoperatively irradiated canine ureters

International Journal of Radiation Oncology*Biology*Physics, 1995

Purpose/Objective: lntraopcrative radiation therap', tlOkT) is used to deliver high single doses ... more Purpose/Objective: lntraopcrative radiation therap', tlOkT) is used to deliver high single doses of radiation to the tumor bed following surgical removal of various abdominal malignancies The ad,,antage or [ORT is the ability to remove sensitive normal tissues from the treamlent field and limit the volume of normal tissue irradiated. The purpose of this study was to determine dose-volume relationships for retruperitoneal tissues.

Research paper thumbnail of Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct

International Journal of Hyperthermia, 2006

Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic ... more Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under control of a heat shock promoter. This approach limits systemic toxicity by restricting IL-12 delivery locally to the tumour. The kinetics of the downstream cytokines interferon-gamma (IFN-gamma) and interferon inducible protein-10 (IP-10) and other molecules affecting angiogenesis, vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were also studied. 4T1 tumours were grown in Balb/C mice and the AdhspmIL-12 construct was injected intra-tumourally. The tumours were heated after 24 h using a water bath. At various time points post-heating the tumours were collected and quantitatively assessed for cytokine production and vascularity. A significant reduction was seen in the tumour vasculature of the treated group vs. the control group mice. Systemic effects of IL-12 were limited to generalized immunostimulation. No hepatoxicity was noted. This study suggests that IL-12 can be effectively delivered using a gene-based approach with a heat shock promoter. This results in quantitatively measurable anti-angiogenesis and general immunostimulation. The complex inter-play of other pro- and anti-angiogenic factors (IFN-gamma, IP-10, VEGF and PAI-1) was also studied.

Research paper thumbnail of Using units of CEM 43°C T90, local hyperthermia thermal dose can be delivered as prescribed

International Journal of Hyperthermia, 2000

... DE THRALL{*, GL ROSNER{, C. AZUMA{, SM LARUE}, BC CASE{, T. SAMULSKI{ and MW DEWHIRST{ {Colle... more ... DE THRALL{*, GL ROSNER{, C. AZUMA{, SM LARUE}, BC CASE{, T. SAMULSKI{ and MW DEWHIRST{ {College ... possible. It was also desirable to have similar numbers of hyperthermia treatments in each ther-mal dose group. ...

Research paper thumbnail of Induction of theHuman Heat Shock Promoter HSP70Bby Nutritional Stress: Implications for Cancer Gene Therapy

Cancer Investigation, 2008

We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (I... more We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (IL-12) gene under control of the heat-inducible promoter HSP70B. This construct, AdhspfIL12, was used in a phase I trial in feline soft tissue sarcomas. During the course of our experiments, we noted that IL-12 was being produced in the transfected Crandell Feline Kidney (CrFK) cells under certain conditions even in the absence of hyperthermia. This observation was further explored to identify the cause of this unintended HSP70B induction. We used real-time PCR as a sensitive method to quantitatively detect the presence of even small amounts of IL-12 mRNA. This served as a surrogate indicator of HSP70B induction. Various conditions were tested to induce the heat shock promoter, including nutritional deprivation, radiation and changes in pH. Nutritional stresses, specifically the absence of glucose and glutamine, could induce the heat shock promoter, thus, resulting in production of the downstream gene product. Other factors known to trigger the heat shock response, pH change, and reactive oxygen species production were also studied but were not found to contribute to heat shock promoter induction in our setting. The human heat shock promoter (HSP70B) is reported to be an efficient and tightly regulated promoter. We discovered, using sensitive real-time PCR techniques, that it can also be induced in response to cellular nutrient stresses. The pros and cons of this phenomenon and its implications for cancer gene therapy are discussed.

Research paper thumbnail of Comparison of adaptive radiotherapy techniques for the treatment of bladder cancer

The British Journal of Radiology, 2013

Objective: Day-today anatomical variations complicate bladder cancer radiotherapy treatment. This... more Objective: Day-today anatomical variations complicate bladder cancer radiotherapy treatment. This work quantifies the impact on target coverage and irradiated normal tissue volume for different adaptive strategies. Methods: 20 patients were retrospectively planned using different three-dimensional conformal radiotherapy treatment strategies for whole-bladder carcinoma: (i) ''conventional'' treatment used isotropic expansion of the clinical target volume (CTV) by 15 mm to the planning target volume (PTV) for daily treatment; (ii) ''plan of the day'' used daily volumetric on-treatment imaging [cone beam CT (CBCT)] to select from four available plans with varying superior PTV margins; (iii) ''composite'' strategies used ontreatment CBCTs from Fractions 1-3 to inform a composite CTV and adapted PTV (5and 10-mm margins for composite 1 and composite 2, respectively) for subsequent treatment. Target coverage was evaluated from available CBCTs (the first three fractions then the minimum weekly thereafter), and the reduction in the irradiated volume (i.e. within the 95% isodose) was quantified. Results: Plan of the day improved target coverage (i.e. all of the bladder within the 95% isodose throughout the treatment) relative to conventional treatment (p50.10), while no such benefit was observed with composite 2. Target coverage was reduced with composite 1 relative to conventional treatment. The mean irradiated volume was reduced by 17.2%, 35.0% and 14.6% relative to conventional treatment, for plan of the day, composite 1 and composite 2, respectively (p,0.01 in all cases). No parameters predictive of large changes in bladder volume later in the treatment were identified. Conclusions: Adaptive techniques can maintain or improve target coverage while allowing for reduced irradiated volume and possibly reduced toxicity. The plan-of-theday technique appeared to provide the optimal balance between target coverage and normal tissue sparing. Advances in knowledge: This study suggests that plan-of-the-day techniques will provide optimal outcomes for adaptive bladder radiotherapy.

Research paper thumbnail of Use of Radiation and a Slow-Release Cisplatin Formulation for Treatment of Canine Nasal Tumors

Veterinary Radiology <html_ent glyph="@amp;" ascii="&amp;"/> Ultrasound, 2004

The purpose of this study was to evaluate the combined use of radiation and a slow-release cispla... more The purpose of this study was to evaluate the combined use of radiation and a slow-release cisplatin chemotherapy formulation for treatment of malignant nasal tumors in dogs. In this retrospective analysis, 51 dogs were evaluated with respect to treatment toxicity, tumor type, stage of disease, cribriform plate involvement, and overall survival. In general, treatment was well tolerated. Mean and median survival as assessed by the Kaplan-Meier product limit method was 570 and 474 days, respectively. No other factors, including tumor type, stage of disease, or cribriform plate invasion had a significant impact on survival. In conclusion, a combination of slow release cisplatin chemotherapy and radiation for the treatment of canine nasal tumors is well tolerated. Results of this analysis warrant further study to elucidate possible other beneficial radiation potentiating drugs and dosing schedules.