Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol

Background: Local progression of intracranial tumors can be the consequence of insufficient radiation dose delivered. Dose increases in the brain must be made carefully so as not to risk debilitating adverse effects such as radiation necrosis. Hypothesis: A new protocol with 10 × 4 Gy + 11% physical dose increase limited to the macroscopic tumor volume results in a clinically better outcome compared to a 10 × 4 Gy protocol. Animals: Fifty-seven client-owned dogs with primary intracranial neoplasia. Methods: Randomized controlled trial. Twenty-eight dogs were assigned to the control protocol (10 × 4 Gy) and 29 to the simultaneous integrated boost (SIB) protocol with 4.45 Gy dose increase. Treatment groups were compared for outcome and signs of toxicity. Results: Mild, transient acute or early-delayed adverse radiation effects were observed in 5 dogs. Severe late adverse effects were not seen. Between the protocols, no significant differences were found for outcome (intention-to-treat analysis): overall time to progression (TTP) was 708 days (95% confidence interval (95% CI) [545,872]), in the control group it was 828 days (95% CI [401,1256]), and in the SIB group 627 days (95% CI [282,973]; P = .07). Median overall survival (OS) was 684 days (95% CI [516,853]), in the control group it was 724 days (95% CI [623,826]), and in the SIB group 557 days (95% CI [95,1020]; P = .47). None of the tested variables was prognostic in terms of outcome. Conclusion and clinical importance: The dose escalation used with an 11% physical dose increase did not result in better outcome

Strahlentherapie zur Behandlung makroskopischer Analbeuteltumoren des Hundes – eine retrospektive Studie

Canine anal gland tumors are locally invasive and early metastasize to the loco-regional pelvic lymph nodes. Radiation therapy is a good method for loco-regional tumor control, especially in inoperable tumors. Since the organs in the pelvic area are sensitive to both acute and late radiation damage (chronic diarrhea, bleeding, strictures or intestinal perforations) and such damage mainly depends on the fraction size, we examined the radiation protocol used in this study with a reduced number of fractions (hypofractionated) regarding effectiveness and side effects. This retrospective study describes 13 dogs with macroscopic anal gland carcinoma that were irradiated with imaging-guided, intensity-modulated radiation therapy with a hypofractionated curative protocol of 12 × 3,8 Gy. Gross pathology was either in the region of the anal gland and/or in the sublumbar lymph nodes. Ten of the 13 dogs had advanced tumor diseases (stage 3a or 3b). The acute radiation reactions were mild to moderate and had been reported for some of the dogs in a previous study. The mean study time was 572 days (range 105–1292 days). Disease progression was observed or suspected in 7/13 dogs during the study period: local or loco-regional progression occurred in 3 dogs (23 %) and distant metastases in 4 dogs (31 %). Median progression-free survival was 480 days (95 %CI, 223–908), median survival was 597 days (95 %CI, 401–908). One year after treatment, 76,9 % (95 %CI, 53,5–100) of the dogs were still alive. The likelihood of tumor progression was lower with increasing age, otherwise none of the examined tumor or patient factors showed a prognostic influence on progression or survival time. No clinically relevant late side effects were observed apart from slight alopecia, pigmentation changes or dry, scaly skin, Medium to long-term tumor control can be expected in dogs with macroscopic anal gland tumors treated with a moderately hypofractionated radiation therapy protocol (12 × 3,8 Gy). During long-term monitoring no serious side effects or side effects requiring treatment were observed

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Reducing margins for abdominopelvic tumors in dogs: impact on dose‐coverage and normal tissue complication probability

Image‐guided, intensity modulated radiation therapy (IG‐IMRT) reduces dose to pelvic organs at risk without losing dose coverage to the planning target volume (PTV) and might permit margin reductions potentially resulting in lower toxicity. Appropriate PTV margins have not been established for IG‐IMRT in abdominopelvic tumours in dogs, and herein we explore if our usual PTV 5 mm margin can be reduced further. Datasets from dogs that underwent IG‐IMRT for non‐genitourinary abdominopelvic neoplasia with 5 mm‐PTV expansion were included in this retrospective virtual study. The clinical target volumes and organs at risk (OAR) colon, rectum, spinal cord were adapted to each co‐registered cone‐beam computed tomography (CBCT) used for positioning. New treatment plans were generated and smaller PTV margins of 3 mm and 4 mm evaluated with respect to adequate dose coverage and normal tissue complication probability (NTCP) of OAR. Ten dogs with a total of 70 CBCTs were included. Doses to the OAR of each CBCT deviated mildly from the originally planned doses. In some plans, insufficient build‐up of the high dose‐area at the body surface was found due to inadequate or missing bolus placement. Overall, the margin reduction to 4 mm or 3 mm did not impair dose coverage and led to significantly lower NTCP in all OAR except for spinal cord delayed myelopathy. However, overall NTCP for spinal cord was very low (<4%). PTV‐margins depend on patient immobilization and treatment technique and accuracy. IG‐IMRT allows treatment with very small margins in the abdominopelvic region, ensuring appropriate target dose coverage, while minimizing NTCP

Retrospective assessment of radiation toxicity from a definitive‐intent, moderately hypofractionated image‐guided intensity‐modulated protocol for anal sac adenocarcinoma in dogs

A recent calculation study predicted acceptable toxicity in pelvic organs at risk for a new definitive-intent, moderately hypofractionated radiation therapy (RT) protocol (12 x 3.8 Gy), when used with image-guided intensity-modulated radiation therapy (IG-IMRT). We hypothesized this protocol to result in clinically acceptable radiation toxicities. Dogs diagnosed with and irradiated for anal sac adenocarcinoma (ASAC) were retrospectively assessed. Eleven dogs were included, six had prior surgery. Before any therapy, staging according to Polton et al. resulted in the following distribution: stage 1 (n = 1), stage 2 (n = 1), stage 3a (n = 6), stage 3b (n = 3). We scored radiation toxicities at the end of therapy, at weeks 1, 3 and every 3 months after RT according to Veterinary Radiation Therapy Oncology Group radiation toxicity criteria. Clinical follow-up was maintained on regular intervals combined with computed tomography (n = 3). Median follow-up time for dogs still alive was 594 days (range: 224-972 days). Within 1 week post treatment, eight dogs (73%) developed grade 2 and four dogs (36%) grade 1 acute toxicity in the perianal region. All acute toxicities resolved or improved to grade 1 within 3 weeks after treatment. Late toxicity, for example, chronic colitis/diarrhoea, ulcerations, strictures or myelopathies was not observed in any patient. Five dogs were euthanized 105, 196, 401, 508 and 908 days after RT and six dogs were still alive, one in spite of progressive disease. The median progression-free survival was 908 days (95%CI: 215; 1602). The previous theoretically described definitive-intent, moderately hypofractionated protocol using IG-IMRT for the treatment of advanced ASAC showed clinically acceptable acute and late toxicities

Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol

Abstract Background Local progression of intracranial tumors can be the consequence of insufficient radiation dose delivered. Dose increases in the brain must be made carefully so as not to risk debilitating adverse effects such as radiation necrosis. Hypothesis A new protocol with 10 × 4 Gy + 11% physical dose increase limited to the macroscopic tumor volume results in a clinically better outcome compared to a 10 × 4 Gy protocol. Animals Fifty‐seven client‐owned dogs with primary intracranial neoplasia. Methods Randomized controlled trial. Twenty‐eight dogs were assigned to the control protocol (10 × 4 Gy) and 29 to the simultaneous integrated boost (SIB) protocol with 4.45 Gy dose increase. Treatment groups were compared for outcome and signs of toxicity. Results Mild, transient acute or early‐delayed adverse radiation effects were observed in 5 dogs. Severe late adverse effects were not seen. Between the protocols, no significant differences were found for outcome (intention‐to‐treat analysis): overall time to progression (TTP) was 708 days (95% confidence interval (95% CI) [545,872]), in the control group it was 828 days (95% CI [401,1256]), and in the SIB group 627 days (95% CI [282,973]; P = .07). Median overall survival (OS) was 684 days (95% CI [516,853]), in the control group it was 724 days (95% CI [623,826]), and in the SIB group 557 days (95% CI [95,1020]; P = .47). None of the tested variables was prognostic in terms of outcome. Conclusion and Clinical Importance The dose escalation used with an 11% physical dose increase did not result in better outcome

Dose‐escalated simultaneously integrated boost radiation protocol fails to result in a survival advantage for sinonasal tumors in dogs

The prognosis for canine sinonasal tumors remains rather poor despite definitive-intent radiotherapy (RT). Theoretical calculations predicted improved outcomes with simultaneously integrated boost (SIB) protocols. With the hypothesis of clinically detectable differences in outcome between groups, our retrospective study evaluated prognostic variables and outcome in dogs treated with regular versus SIB RT. Dogs with sinonasal tumors treated with either a regular (10 × 4.2 Gy) or new SIB protocol (10 × 4.83 Gy to macroscopic tumor) were included. Information regarding signalment, tumor stage, type, clinical signs, radiation toxicity, response, and outcome was collected. Forty-nine dogs were included: 27 treated regularly and 22 treated with SIB RT. A total of 69.4% showed epistaxis, 6.1% showed epileptic seizures, 46.9% showed stage IV tumors, and 6.1% showed lymph node metastases. Early toxicity was mostly mild. Late grade 1 skin toxicity (alopecia/leucotrichia) was seen in 72.1% of dogs, and a possible grade 3 ocular toxicity (blindness) was seen in one dog. Complete/partial resolution of clinical signs was seen in 95.9% of patients as best clinical response and partial remission was seen as best imaging response in 34.7%. The median progression-free survival (PFS) was 274 days (95% CI: 117-383) for regular and 300 days (95% CI: 143-451) for SIB RT, which was not significantly different (P = 0.42). Similarly, the median overall survival (OS) was 348 days (95% CI: 121-500) for regular and 381 days (95% CI: 295-634) for the SIB RT (P = 0.18). Stratified by protocol, the hazard ratio of stage IV versus stage I-III tumors was 2.29 (95% CI: 1.156-4.551, P = 0.02) for OS but not PFS. All dogs showed acceptable toxicity. In contrast to theoretical predictions, however, we could not show a statistically significant better outcome with the new protocol

Canine presumed glial brain tumours treated with radiotherapy: Is there an inferior outcome in tumours contacting the subventricular zone?

Post-treatment outcome in canine glial tumours is described with a broad range of survival times between 2 and 28 months. After surgery or radiation therapy, the tumours may progress locally or spread within the central nervous system. It is unknown if tumour- or patient-specific factors influence prognosis. In humans, glioblastoma involving the subventricular zone has been found to recur distantly, with shortened time to progression and overall survival. We included 32 dogs irradiated for a presumptive primary glial brain tumour in this retrospective cohort study. Tumours were grouped relative to subventricular zone contact and overt ventricular invasion assessing pre-treatment magnetic resonance images. Median time to progression (TTP) for all cases was 534 days (95%CI, 310-758), with a significantly shorter TTP in dogs with lesions at the subventricular zone (median TTP, 260 vs. 687 days; p = .049). Tumours at the subventricular zone progressed more often (p = .001), and more likely as CNS-metastasis (52.9% vs. 13.3%, p = .028). Median overall survival (OS) was 489 days (95%CI, 147-831) and median tumour-specific survival 609 days (95%CI, 382-835). Involvement of the subventricular zone was significantly associated with a shorter tumour-specific survival (median, 306 vs. 719 days; p = .044). Glial tumours contacting the subventricular zone in dogs have a shorter tumour-specific survival and a higher rate of progression and CNS-metastasis. Despite local tumour control, metastasis must be considered and should prompt further treatment approaches

EC87-219 1987 Nebraska Swine Report

This 1987 Nebraska Swine Report was prepared by the staff in Animal Science and cooperating departments for use in the Extension and Teaching programs at the University of Nebraska-Lincoln. Authors from the following areas contributed to this publication: Swine Nutrition, swine diseases, pathology, economics, engineering, swine breeding, meats, agronomy, and diagnostic laboratory. It covers the following areas: breeding, disease control, feeding, nutrition, economics, housing and meats