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S M LaRue

Publications and source records attributed to S M LaRue.

At least 19 recordsLinked to original sources
PubMed2001

Treatment with a combination of doxorubicin, surgery, and radiation versus surgery and radiation alone for cats with vaccine-associated sarcomas: 25 cases (1995-2000).

OBJECTIVE: To compare use of doxorubicin, surgery, and radiation versus surgery and radiation alone for treatment of cats with vaccine-associated sarcoma. DESIGN: Retrospective study. ANIMALS: 25 cats with vaccine-associated sarcomas. PROCEDURE: Time to first recurrence and survival time were compared between the 2 treatment groups. The number of surgeries (1 or > 1) were compared with respect to time to first recurrence and survival time. RESULTS: Median time to first recurrence was 661 days for the group that received doxorubicin, surgery, and radiation. Median time to first recurrence has not yet been attained for the group treated with surgery and radiation alone. Median survival time was 674 days for the group treated with doxorubicin, surgery, and radiation and 842 days for the group treated with surgery and radiation alone. For time to first recurrence and survival time, significant differences were not detected between cats that had 1 surgery and those that had > 1 surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Significant differences between the 2 treatment groups were not detected. The efficacy of doxorubicin in the treatment of vaccine-associated sarcomas is uncertain.

Animals↗
PubMed1998

Principles of adjunctive radiation therapy.

Radiation therapy is becoming increasingly available to the practicing veterinarian. It is important that veterinarians be familiar with mechanisms and biologic effects of radiation used as a therapeutic modality in the treatment of cancer. It is also important that the veterinarian understand oncologic decision making and indications for various modalities including radiation therapy, surgery, and chemotherapy. Surgery and radiation therapy can be particularly complementary in combined therapy to achieve a functional and cosmetic result. This review introduces basic radiation therapy concepts, particularly regarding combination of radiation and surgery in the treatment of cancer in animals.

Animals↗
PubMed1998

Effects of volume irradiated on the function of the canine ureter.

This study was designed to investigate the influence of the volume irradiated on the probability of ureteral complications and to provide data for volume modeling. One hundred thirty-four purpose-bred beagle dogs received single intraoperative doses of 6 MeV electrons ranging from 12 to 54 Gy to three lengths of ureter: 2, 4 or 8 cm. The response was evaluated by excretory urography. The ED50 was 21.9 Gy (95% CI 13.3-30 Gy) for 8 cm 3 years after treatment. The estimated ED50's were greater than 43 Gy for 4 cm and 85 Gy for 2 cm. Reducing the length of ureter irradiated from 8 cm to 4 cm increased the ED50 for ureteral dilation by at least a factor of 2, while reduction from 8 cm to 2 cm increased the ED50 by at least a factor of 4. The ED50 for renal injury secondary to stenosis was 30.5 Gy (95% CI 17.2-232 Gy) when an 8-cm field was irradiated. There was a significant effect of volume irradiated on the frequency of ureteral stenosis. Reducing the length of ureter included in the treatment field should allow delivery of higher doses to tumors without increased complications.

Animals↗
PubMed1995

Tumor physiology and cell kinetics.

The abnormal physiological state of tumors has traditionally been thought to be a source of treatment resistance and altered metastatic phenotype. However, the recent recognition that this altered physiological state is unique to solid cancers gives some hope that tumor selective therapeutic strategies could be developed that will specifically target these cells. Investigations into the development of drugs that specifically target acidotic and hypoxic cells could represent a significantly selective adjuvant therapy to be used in combination with more traditional forms of treatment. Newer forms of targeted therapy will rely on delivery of directed antibodies, growth factor receptor ligands, or gene therapy, delivered via immune cells or viruses. Unfortunately, physiological barriers exist in tumors that will impede the success of such strategies no matter how specific they are. Methods to ameliorate high interstitial pressures and defects in adhesion molecule function are needed to circumvent these barriers. Current methods of evaluating tumor cell kinetics provide data quickly, so this information could impact treatment decisions. Kinetic parameters are proving to be useful tools in selecting patient subpopulations that may respond better to altered treatment regimens. Studies in spontaneous rodent and xenografted human tumors have shown that the number of clonogens per tumor and their intrinsic sensitivity to radiation are major determinants of radiation tumor control dose.

Animals↗
PubMed1995

Radiation therapy of thoracic and abdominal tumors.

Until recently, radiotherapy of thoracic and abdominal tumors in animals has been limited. However, the availability of computerized tomography and other imaging techniques to aid in determining the extent of tumor, an increase in knowledge of dose tolerance of regional organs, the availability of isocentrically mounted megavoltage machines, and the willingness of patients to pursue more aggressive treatment is making radiation therapy of tumors in these regions far more common. Tumor remission has been reported after radiation therapy of thymomas. Radiation therapy has been used to treat mediastinal lymphoma refractory to chemotherapy, and may be beneficial as part of the initial treatment regimen for this disease. Chemodectomas are responsive to radiation therapy in human patients, and favorable response has also been reported in dogs. Although primary lung tumors in dogs are rare, in some cases radiation therapy could be a useful primary or adjunctive therapy. Lung is the dose-limiting organ in the thorax. Bladder and urethral tumors in dogs have been treated using intraoperative and external-beam radiation therapy combined with chemotherapy. These tumors are difficult to control locally with surgery alone, although the optimal method of combining treatment modalities has not been established. Local control of malignant perianal tumors is also difficult to achieve with surgery alone, and radiation therapy should be used. Intraoperative radiation therapy combined with external-beam radiation therapy has been used for the management of metastatic carcinoma to the sublumbar lymph nodes. Tolerance of retroperitoneal tissues may be decreased by disease or surgical manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1995

Combining radiation therapy with other treatment modalities.

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.

Animals↗
PubMed1995

Palliative radiation therapy.

Animal owners may be reluctant to have pets with incurable cancer subjected to euthanasia. Palliative radiation therapy may provide significant relief of pain in such pets. Palliative irradiation is comprised of a few radiation treatments, frequently given over a short time and using larger than normal fractional doses. Animals tolerate palliative irradiation well, and recent reports attest to the usefulness of palliative radiation to relieve discomfort associated with both skeletal and extraskeletal tumors. Although there is more to learn regarding the response of canine and feline tumors to palliative irradiation, it is a proven modality for relief of pain in many incurable cancer patients.

Animals↗
PubMed1995

Normal tissue tolerance and management of radiation injury.

The objective of effective cancer therapy includes preservation of normal tissue function and reducing injury as much as possible. Acutely responding tissues such as skin and mucous membranes generally show a reaction during the course of radiation therapy. Normally those reactions heal rapidly after radiation therapy is completed. The short-term injury is justified if a reasonable probability of local tumor control is expected with an increase in survival of several months. Late effects are more challenging to manage and, therefore, the probability of occurrence is reduced by the methods of irradiation. If the tumor is located such that eyes or salivary glands are included in the field, the late effects include keratoconjunctivitis sicca and, less frequently, xerostomia. Those responses require continual observation and care by the animal owner. A goal in radiation therapy is to keep the incidence of serious complications such as bone or soft-tissue necrosis below 5%. The incidence of complications of radiation therapy that have serious impact on quality of life or quality as a companion animal is probably much less than 5%.

Animals↗
PubMed1994

Impact of heterogeneity in the predictive value of kinetic parameters in canine osteosarcoma.

Intratumoral heterogeneity has been identified as a potential problem in the efficacy of predictive assays. Canine osteosarcoma is an extremely heterogeneous solid tumor that has been shown to be an excellent model for the human disease. Intratumoral heterogeneity of kinetic parameters and the effect of heterogeneity on predicting outcome of treatment (time until metastasis) were studied in dogs with naturally occurring osteosarcoma. Dogs were treated with amputation or tumor excision and limb-sparing followed by chemotherapy with cisplatin. Kinetic parameters evaluated included v, duration of DNA synthesis (Ts), and potential doubling time (Tpot), determined using in vivo labeling with bromodeoxyuridine and flow cytometry. In 30 tumors, multiple samples were obtained and evaluated. There was significantly more variation between tumors from different dogs than intratumoral variation of v, Ts, and Tpo. Variations in v, Ts, and Tpot within a tumor were associated with both sample location and tumor subpopulation. Time to metastasis was determined in 51 dogs with tumors sampled for kinetics. Multiple samples were available from 25 of these tumors. Cox proportional hazard analysis was performed using either the fastest or slowest Tpot from each sample. The fastest available Tpots were highly significant (P < 0.001) for prediction of outcome. The slowest available Tpots were also significant predictors, although the statistical strength was compromised (P = 0.024). Obtaining at least two samples in large tumors known to be heterogeneous is recommended to improve the predictive ability of Tpot. v is a more limited predictor but can useful when Tpot is not available. In canine osteosarcoma, an extremely heterogeneous tumor, kinetic parameters were shown to be predictors of outcome.

Animals↗
PubMed1994

Histologically low-grade, yet biologically high-grade, fibrosarcomas of the mandible and maxilla in dogs: 25 cases (1982-1991).

Medical records of 25 dogs with histologically low-grade fibrous masses of the maxilla and mandible were reviewed. Most of the dogs had extensive clinical histories and had had previous biopsies of the affected regions, from which specimens were often interpreted as benign fibrous connective tissue. The most common breed represented was Golden Retriever (13/25 dogs, 52%). Skull radiographs were evaluated for 22 dogs, and 16 dogs (72%) had evidence of bone lysis. At admission, none of the dogs had radiographic evidence of pulmonary metastasis. On subsequent examinations and necropsy, prevalence of pulmonary metastasis was 12% (3/25 dogs) and of regional lymph node metastasis, 20% (5/25 dogs). Histologic appearance of all specimens was similar and was characterized by proliferation of fibrous connective tissue, with moderate to low cellularity, that aggressively infiltrated adjacent normal tissue. Treatment modalities varied considerably. Surgical excision in combination with radiation therapy, surgery alone, radiation therapy alone, and radiation therapy used adjunctly with localized hyperthermia prolonged survival times in some dogs. The clinical signs, tumor behavior, and histologic characteristics of these lesions were distinctive from those in previously described oral fibrosarcomas in dogs. Comparatively, these tumors most closely resembled aggressive fibromatoses in human beings in regard to clinical signs, local invasive behavior, and histologic appearance, but differed in the prevalence of metastasis.

Animals↗
PubMed1994

Intraoperative radiation (IORT) injury to sciatic nerve in a large animal model.

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.

Animals↗
PubMed1994

[Radiotherapy in small animal medicine: fundamentals, indications and significance].

This article describes the general principles of radiation therapy, reviews the indications for this treatment modality and discusses the response of tumors and normal tissue to radiation. Radiation modalities and treatment protocols currently available in Switzerland are presented. Treatments of spontaneous tumors in animals contribute to the development of radiation therapy in human medicine at the same time.

Animals↗
PubMed1992

Canine and feline nasal and paranasal sinus tumors.

Tumors involving the nasal cavity and nearby sinuses are relatively rare in the dog and cat. 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, differentials must be considered. In each case, a definitive diagnosis is made on the basis of the signalment, history, physical examination findings, radiographs, and histologic evidence of malignant neoplasia. Although many treatment options exist, radiation therapy, with or without surgery, has been considered to be most effective.

Animals↗
PubMed1992

Bromodeoxyuridine labeling and DNA content of pulmonary arterial medial cells from hypoxia-exposed and nonexposed healthy calves.

Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo DNA synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total DNA content in medial cells from control (pulmonary arterial pressure = 32 +/- 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 +/- 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P < 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia-exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of DNA content by flow cytometry indicated a decrease (P < 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and DNA content of cells from the pulmonary arteries of hypoxia-exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of DNA synthesis and subsequent cell division.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Percent tumor necrosis as a predictor of treatment response in canine osteosarcoma.

The percent tumor necrosis was determined in 200 dogs with spontaneously occurring osteosarcoma. One hundred dogs had no treatment before amputation or death. One hundred other dogs were treated with either radiation therapy alone (n = 23), intraarterial (IA) cisplatin alone (n = 16), intravenous (IV) cisplatin alone (n = 6), radiation therapy plus IA cisplatin (n = 47), or radiation therapy plus IV cisplatin (n = 8). Eighty-nine of these 100 dogs had their tumors resected 3 weeks after the end of therapy (6 weeks after the initiation of therapy) and replaced with a cortical bone allograft. Dogs with preoperative treatment were evaluated for local tumor control and time to metastasis. The mean percent tumor necrosis in untreated osteosarcoma was 26.8%. The mean percent tumor necrosis for dogs receiving radiation only, IA cisplatin only, and IV cisplatin only was 81.6%, 49.1% and 23.8%, respectively. The mean percent tumor necrosis for dogs receiving radiation therapy plus IA cisplatin or radiation therapy plus IV cisplatin was 83.7% and 78.2%, respectively. There was no significant difference between percent tumor necrosis in untreated osteosarcoma compared with those receiving IV cisplatin, but there was a significant increase in percent tumor necrosis with all other treatments. A mathematic model for the effect of cisplatin and radiation dose was developed using multiple regression analysis. The radiation dose calculated to cause at least 80% tumor necrosis was 42.2 Gy (95% confidence interval [CI], 38.0 to 47.6 Gy) when radiation was given alone and 28.1 Gy (95% CI, 21.3 to 36.6 Gy) when radiation was combined with IA cisplatin. Areas of viable tumor tended to be most frequent adjacent to the articular cartilage and in the joint capsule. Percent tumor necrosis was strongly predictive for local tumor control; 28 of 32 dogs with greater than 80% tumor necrosis had local control, and only eight of 29 dogs with less than 79% tumor necrosis had local control (P = 0.0047). There was no correlation between percent tumor necrosis and time to metastasis.

Animals↗
PubMed1991

Intraoperative radiotherapy with localized radioprotection: diminished duodenal toxicity with intraluminal WR2721.

The radiosensitive duodenum must be treated during IORT of human pancreatic head tumors, leading to an approximately 25% incidence of late bleeding. This study aimed to decrease the toxicity by administering WR2721 directly into the duodenal lumen. Duodenal toxicity in the canine was evaluated after intraoperative radiotherapy (IORT) with and without the intraluminal radioprotector WR2721. Eight adult dogs were divided into two groups. All underwent IORT using a 5.7 cm cone that covered the duodenum and pancreas. 30.0 Gy IORT was given with 6 MeV electrons. Cholecystojejunostomy and gastrojejunostomy were performed. Four dogs served as IORT only controls; one was unevaluable. Four dogs received WR2721, intraluminally at 720 mg/m2, in 16-18 ml Ringer's. Atraumatic clamps were placed on proximal and distal duodenum, without vascular compromise. WR2721 was injected into the duodenal lumen 30 minutes prior to IORT. Immediate postoperative recovery of the dogs receiving WR2721 was faster than controls. Necropsies were performed at 6 months. Grossly increased adhesions were noted in controls. Histopathologically, mucosal atrophy was greater in control dogs. Duodenal ulceration was noted in all controls, but in only one of four WR2721 dogs. Masson's trichrome and Verhoff Van Gieson stains demonstrated increased perivascular fibrosis, intimal proliferation, and fibrinoid medial necrosis of vessels in all controls, and one WR2721 dog. The other three WR2721 dogs had only mild perivascular fibrosis. Radioprotection, evaluated by the presence or absence of pancreatic atrophy, appeared to stop just beyond the bowel wall. In summary, WR2721 provided duodenal radioprotection in most dogs. The intraluminal administration of WR2721 allows decreased systemic side effects, and may eliminate tumor absorption. The study indicates that the intraluminal use of radioprotectors has broad potential application.

Amifostine↗
PubMed1990

Comparison of DNA aneuploidy of primary and metastatic spontaneous canine osteosarcomas.

Spontaneous canine osteosarcomas were analyzed for DNA aneuploidy and percentage of S phase cells using flow cytometry. Forty-eight dogs were studied in which both a primary tumor and subsequent metastases were available. The DNA index distributions for the primary tumors and the metastases were quite similar. However, when individual primary tumors and metastases derived from them were compared, many of the cases had different ploidy values. The tumor cells were also analyzed for percentage of S phase. The diploid metastases had less than 17% S phase cells, whereas the aneuploid metastases had up to 40% S phase cells. There was a direct correlation between the DNA index and the percentage of S phase in the metastases.

Aneuploidy↗