Long-term remission and survival in dogs with high-grade, B cell lymphoma treated with chemotherapy with or without sequential low-dose rate half-body irradiation.

BACKGROUND: Standard of care for dogs with high-grade lymphoma, multiagent chemotherapy, achieves good initial responses but long-term remissions are infrequent; previous studies using half-body irradiation suggest improved long-term outcomes. HYPOTHESIS: The addition of low-dose rate half-body irradiation would improve outcomes in dogs with B-cell lymphoma. ANIMALS: Client-owned dogs with stage III or higher, substage a, B-cell lymphoma that achieved complete remission after 4 doses of multiagent chemotherapy. METHODS: A case-controlled design comparing 2-year remission and survival rates between dogs treated with CHOP-based chemotherapy and those treated with chemotherapy and sequential low-dose rate half-body irradiation. RESULTS: Thirty-eight dogs were enrolled with 18 included in final analysis, 9 prospectively-enrolled dogs and 9 case-matched historical controls. The irradiation cohort's 2-year disease-free rate was 56% whereas median duration exceeded the 730-day study period compared with 0% and 261 days in the chemotherapy only group. Remission duration significantly differed between cohorts (P < .01), hazard ratio 0.218 (95% CI: 0.06-0.77). The irradiation cohort's 2-year survival rate was 78% with median overall survival duration exceeding the 730 day study period compared with 11% and 286 days in the chemotherapy only group. Overall survival time significantly differed between cohorts (P < .02), hazard ratio 0.173 (95% CI: 0.03-0.839). CONCLUSIONS AND CLINICAL IMPORTANCE: The improved long-term outcome achieved by dogs administered sequential low-dose rate half-body irradiation in this study is similar to previous observational studies. Where long-term remission is sought in dogs with B-cell lymphoma low-dose rate half-body irradiation could be considered in addition to standard chemotherapy.

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

Accuracy of Dose Calculation for Hemibody Treatments at Extended Distance Using a Commercial Treatment Planning System.

PURPOSE: The objective of this study was to assess the accuracy of monitor units (MUs) calculation for extended distance hemibody (HB) treatments in Pinnacle, a commercial treatment planning system. The agreement between planning and delivery of low-dose radiation therapy (LD-RT) was assessed with direct comparison to expected doses and tabulated total body irradiation (TBI) calculations. Studies over the past decades indicate that LD-RT has strong potential to be an effective treatment modality for cancer patients with minimal toxicities. This physics-based study aims to provide sufficient conclusions required for prospective clinical studies involving HB irradiation regimes. Specifically, this study may provide reassurance of MU calculation in the Pinnacle system for an upcoming trial regarding nontargeted LD-RT for recurrent prostate cancer. METHODS: Water phantom: A plan was created in Pinnacle to deliver 100 cGy to a water phantom with an ion chamber mount. A percent depth dose was obtained. Electrometer readings were recorded with each irradiation of 400 MUs at varying ion chamber depths at extended distance. A percent depth dose was created from tabulated data. Anthropomorphic phantom: A parallel opposed pair plan was created in Pinnacle to deliver 150 cGy over 10 fractions to the umbilicus of the phantom at 4 m extended source-to-surface distance. The MUs required to deliver 150 cGy, as per Pinnacle were delivered to the phantom using 6 MV photons. Thermoluminescent dosimeters (TLD), used to measure exposure using light-emitting crystals, were placed along six reference locations (lung, mid-T-spine, abdomen, mid-pelvis, thigh, and mid-abdomen) on the phantom. TLD measurements were then compared with the Pinnacle-derived ROI mean doses. For experiment 2, TBI calculation factors were used to determine the required MUs to deliver 150 cGy to the prescription (Rx) point. The calculated MUs were delivered, and TLD readings were recorded to compare the level of agreement of using TBI calculations for HB treatments. RESULTS: Water phantom: Pinnacle did not accurately estimate dmax at extended distance; however, it did accurately estimate the dose past dmax. Anthropomorphic phantom: A 10% variation to expected dose was deemed significant. Both Pinnacle and TBI calculations were accurate methods of planning HB LD-RT treatment, with insignificant difference. Pinnacle's overall average variation across ROIs was borderline significant at 12.1%. CONCLUSION: At extended source-to-surface distance, Pinnacle inaccurately estimated the entrance dose and dmax. Anthropomorphic phantom studies indicated borderline significant variation, as per the implemented 10% limit. TBI calculations presented similar conclusions. For purposes of HB LD-RT, a borderline 10% variation will have insignificant impact to the patient's ability to tolerate treatment. Trial-eligible prostate cancer patients are currently being treated for HB LD-RT at the Juravinski Cancer Centre.

Efficacy and safety of 3D-conformal half body irradiation in patients with multiple bone metastases.

Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3 Gy fractions, bid, ≥ 6 h apart, on 2 consecutive days (total dose: 12 Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs. Acute and late toxicity was scored based on RTOG and EORTC-RTOG scales, respectively. Pain was evaluated using the Pain-Drug scores and the Visual Analog Scale (VAS). One hundred and eighty patients were eligible for inclusion in this retrospective analysis. Grade 3 and 4 acute toxicity rates were 1.1% and 0.0%, respectively. Mean VAS before and after HBI was 5.3 versus 2.7, respectively (p: 0.0001). Based on VAS, 37.5% of patients showed complete pain relief (VAS: 0) while 38.1% had partial response (≥ 2-point VAS reduction). Overall, Pain and Drug Score reduction was observed in 76.3% and 50.4% of patients, respectively. 1-, 2-, and 3-year pain progression free survival was 77.0%, 63.4%, and 52.7%, respectively. Thirty patients (16.7%) underwent RT retreatment on the same site with median 15.9 months interval (range 2-126 months). HBI delivered with 3D-CRT technique is safe and effective. It provides long lasting pain control in patients with multiple BMs with negligible rates of relevant toxicity.

Efeitos do fenômeno da irradiação do método de facilitação neuromuscular proprioceptiva no acidente vascular encefálico sobre o membro inferior: estudo preliminar / Effects of the irradiation phenomena of the Proprioceptive Neuromuscular Facilitation method on the cerebrovascular accident on the lower limb: preliminary study

Introdução: A irradiação pelo método de Facilitação Neuromuscular Proprioceptiva (FNP) não se restringe somente a ativação da musculatura agonista, mas aos músculos homólogos e contralaterais. Objetivo: avaliar o efeito da irradiação sobre a ativação muscular do membro inferior parético, equilíbrio e marcha de indivíduos na fase subaguda pós-AVE. Métodos: cinco indivíduos, avaliados antes e após a intervenção de 12 sessões, incluindo o padrão extensor da diagonal primitiva (D2) de membro superior bilateralmente, em várias posições, por meio da eletromiografia, da escala Fulg-Meyer (FM) e Índice do Andar Dinâmico (IAM). Resultados: As avaliações da FM e do IAM não apresentaram diferenças significativas. A anova fatorial revelou que as variáveis independentes tarefa (p=,00000), músculo (p=,0016) e avaliação (p=,01882) mostraram diferença significativa entre as avaliações. Conclusão: A irradiação do método FNP não promoveu mudanças significativas no equilíbrio e na marcha, mas mostrou ser eficaz na ativação dos músculos do membro inferior nestes pacientes hemiparéticos em recuperação.

Introduction: The method by irradiation of Proprioceptive Neuromuscular Facilitation (PNF) is not only restricted to agonist activation of muscles, but the counterparts and contralateral muscles. Objective: To evaluate the effect of irradiation in the activation of paretic muscles of lower limb, on balance and gait of individuals in post-stroke subacute phase. Methods: five subjects, evaluated before and after 12 sessions of intervention based on extensor pattern of the bilateral upper limb in various positions, through electromyography, Fulg-Meyer (FM) and Dynamic Gait Index (DGI). Results: The evaluations of FM and DGI did not present significant differences. The anova factorial revealed that the independent variables task (p =, 00000), muscle (p =, 0016) and evaluation (p =, 01882) showed significant difference. Conclusion: Irradiation of the FNP method did not promote significant changes in balance and gait, but was shown to be effective in the activation of the lower limb muscles in these hemiparetic patients in recovery.

A novel Hemi-Body Irradiation technique using electron beams (HBIe-).

PURPOSE: Certain radiation responsive skin diseases may develop symptoms on the upper or the lower half of the body. The concept of a novel Hemi-Body Electron Irradiation (HBIe-) technique, described in this work, provides a low cost, LINAC based, intermediate treatment option in between extremely localized and Total Skin irradiation techniques. MATERIALS AND METHODS: The HBIe- technique, developed in our department, incorporates a custom crafted treatment chamber equipped with adjustable Pb shielding and a single electron beam in extended Source-Skin Distance (SSD) setup. The patient is positioned in 'Stanford' technique positions. The geometrical setup provides both optimal dose homogeneity and dose deposition up to a depth of 2 cm. To confirm this, the following characteristics were measured and evaluated: a) percentage depth dose (PDD) on the treatment plane produced by a single electron beam at perpendicular incidence for six fields at 'Stanford' angles, b) 2D profile of the entrance dose on the treatment plane produced by a single field and c) the total surface dose on an anthropomorphic phantom delivered by all 6 fields. RESULTS: The resulting homogeneity of the surface dose in the treatment plane for an average patient was 5-6%, while surface dose homogeneity on the anthropomorphic phantom was 7% for both the upper and the lower HBIe- variants. The total PDD exhibits an almost linear decrease to a practical range of 2 g/cm2. CONCLUSION: In conclusion, HBIe- was proven effective in delivering the prescribed dose to the target area, while protecting the healthy skin.

Gene expression signature for early prediction of late occurring pancytopenia in irradiated baboons.

Based on gene expression changes measured in the peripheral blood within the first 2 days after irradiation, we predicted a pancytopenia in a baboon model. Eighteen baboons were irradiated with 2.5 or 5 Gy. According to changes in blood cell counts, the surviving baboons (n = 17) exhibited a hematological acute radiation syndrome (HARS) either with or without a pancytopenia. We used a two stage study design where stage I was a whole genome screen (microarrays) for mRNA combined with a qRT-PCR platform for simultaneous detection of 667 miRNAs using a part of the samples. Candidate mRNAs and miRNAs differentially upregulated or downregulated (>2-fold, p < 0.05) during the first 2 days after irradiation were chosen for validation in stage II using the remaining samples and using throughout more sensitive qRT-PCR. We detected about twice as many upregulated (mean 2128) than downregulated genes (mean 789) in baboons developing an HARS either with or without a pancytopenia. From 51 candidate mRNAs altogether, 11 mRNAs were validated using qRT-PCR. These mRNAs showed only significant differences between HARS groups and H0, but not between HARS groups with and without pancytopenia. Six miRNA species (e.g., miR-574-3p, p = 0.009, ROC = 0.94) revealed significant gene expression differences between HARS groups with and without pancytopenia and are known to sensitize irradiated cells. Hence, in particular, the newly identified miRNA species for prediction of pancytopenia will support the medical management decision making.

Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol.

REASONS FOR PERFORMING STUDY: Laminitis is a painful disease for which adequate pain management remains a challenging and largely unmet medical need. OBJECTIVES: To investigate plasma concentrations, analgesic and physiological effects of 2 doses of tramadol in horses with chronic laminitis. STUDY DESIGN: Nonrandomised trial. METHODS: Four horses with naturally occurring chronic laminitis received 5 mg/kg bwt and then 10 mg/kg bwt tramadol orally every 12 h for one week with a one-week washout between. Noninvasive arterial blood pressure, heart and respiratory rates, intestinal sounds and forelimb off-loading frequency were evaluated before and during treatments. Plasma tramadol and metabolite (M1 and M2) concentrations were measured on predetermined days and times after the morning dosing. RESULTS: Forelimb off-loading frequency decreased significantly with 10 mg/kg bwt (40%, P = 0.02) but not with 5 mg/kg bwt (9%, P = 0.4). Physiological variables did not change significantly with either treatment. For 5 and 10 mg/kg bwt treatments, respectively, individual maximum plasma concentrations (µg/l) ranged from 329 to 728 and 628 to 1330 (tramadol), 12-24 and 32-80 (M1), and 90-157 and 239-362 (M2). Respective median area under the concentration vs. time curves (h µg/l) were 727 and 1426, 33 and 88, 303 and 1003. CONCLUSIONS: Twice daily oral tramadol at 10 mg/kg bwt may produce analgesic plasma levels in horses with chronic laminitis.

The extent of irradiation-induced long-term visceral organ damage depends on cranial/brain exposure.

In case of high-dose radiation exposure, mechanisms controlling late visceral organ damage are still not completely understood and may involve the central nervous system. To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection. Although hind limbs- and head-protected irradiated rats exhibited similar hematopoietic and spleen reconstitution, a late body weight loss was observed in hind limbs-protected rats only. Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected. Plasma measurements of inflammation biomarkers (haptoglobin and the chemokine CXCL1) suggest that the attenuated organ damage in hind limbs-protected rats may be in part related to reduced acute and chronic inflammation. Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.

Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration.

The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high-performance liquid chromatography with a 0.005 µg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double-peak phenomenon was observed, and the first (Cmax1 ) and second (Cmax2) peaks were 1.99 ± 0.43 µg/mL at 2.0 h and 2.27 ± 0.38 µg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 µg/mL) was also observed, and initial concentration of 45.76 µg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half-life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady-state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.

Half-body irradiation with tomotherapy for pain palliation in metastatic breast cancer.

CONTEXT: Half-body irradiation (HBI) is the fastest and most effective tool against uncontrolled pain from widespread bone metastases but is somewhat toxic. OBJECTIVES: To assess the feasibility of lower HBI with helical tomotherapy in patients with metastatic breast cancer in terms of acute toxicity and delay in chemotherapy administration. METHODS: Thirteen breast cancer patients with multiple painful bone metastases to the lower half of the body were enrolled in this prospective trial. Eight patients were receiving chemotherapy. Target volume included all bones from the L3-L4 interface to the femoral shafts. Radiation consisted of 8 Gy in one fraction, delivered with helical tomotherapy. Patients were premedicated only with oral steroids. Pain intensity was scored using the Numeric Rating Scale from 0 to 10. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 3.0. Quality of life was scored with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, before and 21 days after the radiation course. This trial was approved by the local review board. RESULTS: Median follow-up was at seven months (range 2-12 months). All but two patients had pain relief in the radiated field. Six patients stopped their analgesic drug consumption. Toxicity was acceptable: two Grade 3 hematologic toxicities were registered (anemia and leukopenia). Grade 1-2 toxicities were hematologic = 13, fever = 3, nausea = 2, and diarrhea = 1. Three of the eight patients had a delay in chemotherapy administration because of leukopenia or anemia. Twelve patients answered to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and an improved quality of life was documented in eight cases. CONCLUSION: Lower HBI delivered with helical tomotherapy resulted in a well-tolerated regimen, without significant delay in chemotherapy schedule.

Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice.

Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.

There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4(+) T cells, CD8(+) T cells, Treg cells, B cells, NK cells, NK1.1(+) T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.

Prevention and treatment of vitamin D deficiency in Dutch psychogeriatric nursing home residents by weekly half-body UVB exposure after showering: a pilot study.

BACKGROUND: in older people, induction of cutaneous vitamin D production by ultraviolet B (UVB) exposure may be preferable to oral supplementation: it cannot cause toxic levels, it helps to prevent polypharmacy and, moreover, there are indications that UVB exposure has beneficial effects on health and well being by mechanisms other than the vitamin D pathway alone. OBJECTIVE: the aim of this pilot study is to investigate whether weekly, half-body, UVB irradiation after showering can increase serum 25-hydroxyvitamin D (25(OH)D) to sufficient levels, in a Dutch psychogeriatric nursing home population. METHOD: subjects were eight psychogeriatric nursing home patients, mean age: 79 ± 8. Exclusion criteria were going outdoors into the sun more than once a week, the presence of actinic or cancer skin lesions and known resistance to body contact. The intervention consisted of weekly half-body UVB irradiation, after showering, over 8 weeks, with 0.5 minimal erythemal dose (MED). Main outcome measures were change in fasting serum levels of 25(OH)D and parathyroid hormone (PTH) at 0, 2, 4 and 8 weeks. RESULTS: at baseline, mean serum 25(OH)D was 28.5 nmol/l. Mean serum 25(OH)D levels increased to 46.5 nmol/l. Median serum PTH levels decreased by 20% after 8 weeks of treatment. CONCLUSION: an 8 week course of weekly, frontal half-body irradiation with UVB, at 0.5 MED, leads to an significant increase in 25(OH)D serum levels, but this period is too short to reach vitamin D sufficiency.

Initial evaluation of safety of wide-field irradiation in the treatment of hematopoietic neoplasia in the cat.

Localized radiation therapy is well tolerated in cats with confined tumors; however, the use of wide-field radiation therapy to treat disseminated neoplasia has not been evaluated systematically in this species. Wide-field external beam radiation therapy, which we define as irradiation of cranial or caudal halves of the body either individually or sequentially, was undertaken as an experimental option to treat cats with either chemotherapy-refractory or naive hematopoietic neoplasia considered to have a poor prognosis. Fifteen cats with hematopoietic malignancies received wide-field external beam radiation therapy between 2003 and 2006. Cats received 8 Gy delivered in 4 Gy fractions with 60Co photons. Treatment-related toxicity was scored according to criteria established by the Veterinary Cooperative Oncology Group. Animals without preexisting abnormalities on hemograms exhibited no or mild (Grade 1 or 2) hematopoietic toxicity. Although most cats (14 of 15) had preexisting gastrointestinal (GI) signs, these signs were stable (29%) or improved (42%) following irradiation. Worsening GI signs following irradiation occurred transiently in two cats and in association with progressive disease in two others. No pulmonary, renal, hepatic, or dermatologic toxicities were detected. In summary, wide-field external beam radiation therapy can be administered safely to, and may provide therapeutic benefit for, cats with disseminated hematopoietic neoplasia.

Clinical tolerance in large field radiotherapy--the knowledge gained over the last ten years.

Malignant disorders are still far from being successfully managed in spite of the apparent progress achieved by surgical treatment, high energy radiotherapy (RT) and chemotherapy (CHT). They keep being the second most frequent cause of lethal outcomes both in Bulgaria and in most countries of the world. One of the promising approaches to increasing the efficaciousness of treatment is development and use of methods that are in full accord with the modern requirements of a complex therapy. Over the last fifty years, large field radiation techniques, applied as systemic therapy in oncology, have been investigated and established. These techniques show the transition in oncology to using actively various variants of large field radiotherapy (LFR), the "heavy artillery" of oncoradiologic practice, as an alternative or adjunct therapy to chemotherapy (CHT). In the present paper we review the current knowledge in the field and present the clinical experience accumulated over the last ten years with respect to clinical tolerance in the major large-field radiotherapy techniques--total body irradiation, half body irradiation, whole abdominal irradiation, total and partial lymphoid irradiation. Described in detail are the contemporary knowledge about clinical and hematologic tolerance in total body irradiation as part of the myelo- and nonmyeloablative conditioning regimens as well as in half body irradiation as a systemic therapy in oncology. We also present the amassed experience in clinical tolerance in partial body irradiation in the form of whole abdominal and total or partial lymphoid irradiation. Another point worth noting based again on the experience gained over the last ten years is that for LFR we need to develop a radiotherapy technique that is designed carefully to achieve an optimal therapeutic effect that should include the disease control, good clinical tolerance and reduction of post-radiotherapy sequelae.

Densities of glutamatergic and GABAergic presynaptic terminals are altered in experimental cortical dysplasia.

PURPOSE: Cortical dysplasia (CD) is a major cause of epilepsy in children and adults, but underlying mechanisms of epileptogenesis in this disorder are poorly understood. We have utilized the irradiated rat model to study an injury-based form of diffuse CD in rats. Prior studies in this model have shown reduced numbers of γ-aminobutyric acid (GABA)ergic interneurons and reduced inhibitory synaptic currents in pyramidal cells in CD. We analyzed the number of excitatory and inhibitory presynaptic terminals in the neocortex of irradiated rats to better characterize altered connectivity in experimental CD. METHODS: Antibodies to vesicular glutamate transporter 1 (VGLUT1), vesicular glutamate transporter 2 (VGLUT2), vesicular GABA transporter (VGAT), and parvalbumin (PV) were used to quantify glutamatergic and GABAergic presynaptic terminals in control and dysplastic cortex. RESULTS: We found that the density of VGLUT1 terminals was increased in CD in comparison to layers IV, V, and VI in control cortex. VGLUT2 terminals were increased in CD compared to layers IV and VI. VGAT terminals were reduced in CD compared to layers II/III, IV, and V in controls as were PV-immunoreactive somata and terminals. DISCUSSION: These findings suggest an overall increase in excitatory synaptic connectivity and decrease in inhibitory synaptic connectivity in CD in irradiated rat. We propose that these changes contribute to hyperexcitability in these animals and may contribute to epileptogenicity in some forms of human CD.

Comparison of serum iohexol clearance and plasma creatinine clearance in clinically normal horses.

Objective-To determine whether a limited sampling time method based on serum iohexol clearance (Cl(iohexol)) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Cl(creatinine)). Animals-10 clinically normal adult horses. Procedures-A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cl(iohexol) and plasma Cl(creatinine) was compared with limits of agreement plots. Results-Values obtained for plasma Cl(creatinine) ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cl(iohexol) was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods. Conclusions and Clinical Relevance-Use of serum Cl(iohexol) yielded estimates of GFR in clinically normal adult horses similar to those for plasma Cl(creatinine). This study was the first step in the evaluation of the use of serum Cl(iohexol) for estimating GFR in adult horses.

Hemithoracic radiotherapy after extrapleural pneumonectomy for malignant pleural mesothelioma: a dosimetric comparison of two well-described techniques.

INTRODUCTION: Extrapleural pneumonectomy (EPP) with adjuvant radiotherapy may be used to treat malignant pleural mesothelioma. Radiation pneumonitis, felt to be related to contralateral lung radiation dose, may affect patient mortality in this setting. Two standard therapeutic approaches currently used to deliver adjuvant radiotherapy were compared in this study: intensity modulation radiation treatment (IMRT) with a planned dose of 45 Gray (Gy) and a modified electron-photon technique delivering 54 Gy. METHODS: Treatment plans of 10 mesothelioma patients who underwent EPP and hemithoracic IMRT to a total dose of 45 Gy were analyzed. Plans using a combination of opposed anterior posterior radiation fields and electron supplementation (electron-photon technique [EPT]) to a total dose of 54 Gy were then generated and compared with IMRT plans. RESULTS: Dosimetric comparison revealed a significant reduction in contralateral lung dose with EPT versus IMRT, even with increased prescription dose used with EPT plans. Median heart and contralateral kidney doses were also significantly reduced with EPT versus IMRT. Dose coverage of planning target volume and doses to spinal cord, liver, and ipsilateral kidney were similar with use of the two techniques. CONCLUSIONS: Our data suggest that hemithoracic radiotherapy delivered after EPP using EPT may minimize dose to contralateral lung and other structures when compared with IMRT, without compromise of planning target volume coverage.

Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.