Definitive-intent uniform megavoltage fractioned radiotherapy protocol for presumed canine intracranial gliomas: retrospective analysis of survival and prognostic factors in 38 cases (2013-2019).
ABSTRACT: BACKGROUND:Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5?weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT's impact on the dogs' clinical signs and Qol were evaluated by the owners. RESULTS:The disease-specific MST was 698?days (95% CI: 598-1135). Survival at 1 and 2?years were respectively 74.2?±?7.4% and 49.0?±?9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed. CONCLUSIONS:RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life's quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
Project description:Background: The high incidence of recurrence and unpredictable clinical outcome for paediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. Gain of chromosome 1q has been reported as a frequent aberration and correlate of adverse outcome in ependymoma. We therefore evaluated a prognostic role for 1q25 gain across three age-defined European clinical trial cohorts of paediatric intracranial ependymoma. Methods: The frequency of 1q gain in paediatric ependymoma was assessed across 51 tumours (42 primary, 9 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was evaluated by interphase FISH (iFISH) across 189 primary intracranial ependymomas from children treated on the CCLG/SIOP CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT group, n = 64). Results were correlated with clinical, histological and survival data. Findings: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (3/9, 33 %). Gain of 1q25 was the strongest independent predictor of tumour progression in both CNS9204 (HR 3·36, p = 0·0009) and BBSFOP (HR 4·10, p = 0·0009) trial cohorts. In contrast, 1q25 gain was not prognostic for the older CNS9904/RT only group (PFS: p = 0·37, OS: p = 0·95). Clinical variables implicated in adverse outcome amongst cohorts included incomplete tumour resection and posterior fossa location. Interpretation: This is the first study to prospectively identify then validate a prognostic genomic marker for childhood ependymoma across independent prospective trial groups. 1q25 gain predicts progression in primary chemotherapy cohorts but not those treated by post-operative radiotherapy. We propose 1q25 gain is incorporated as an adverse marker into future European chemotherapeutic clinical trial design. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from flash frozen tumour specimens and patient-matched peripheral blood Copy number analysis of Affymetrix 500K SNP arrays was performed for DNA from 51 ependymomas and 40 constitutional DNA samples. Analysing broad genomic aberrations in 51 paediatric ependymomas, looking particularly at 1q gain.
Project description:BACKGROUND:Dermatological conditions are common in English bulldogs (EBs). HYPOTHESIS/OBJECTIVES:This cross-sectional study describes the dermatological health status of a group of EBs and compares the results with owner perceptions and its possible impact on quality of life (QoL). Computed tomographic (CT) findings of the ear canals were compared between EBs and mesaticephalic dogs. ANIMALS:Twenty-seven EBs participating in a health study in Finland. METHODS AND MATERIALS:A QoL questionnaire was completed for EBs with owner-reported clinical signs referable to the skin or ear. Clinical evaluation included recording the Canine Atopic Dermatitis Extent and Severity Index, the Otitis Index Score, false paw pad grading and the presence of interdigital furunculosis. These were summed to form a total clinical score (TCS). The cross-sectional surface areas of the horizontal ear canals were measured from CT images and compared with respective images of 14 mesaticephalic dogs collected from a patient database. RESULTS:All 27 EBs had abnormal findings on dermatological examination, but 37% of the owners had not recognized skin or ear signs. The median QoL score was 5.0 (range 0-12) and correlated with TCS (correlation coefficient = 0.507, P < 0.05). English bulldogs had narrower horizontal ear canals than mesaticephalic dogs (P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE:All EBs had abnormal dermatological findings that were unnoticed or considered to be of minor significance to the QoL by most owners. Narrow ear canals were common, possibly related to the brachycephalic conformation of the breed.
Project description:Effective treatments are needed for idiopathic chronic rhinitis in dogs, but assessment of efficacy requires a practical, quantifiable method for assessing severity of disease.To develop and perform initial validity and reliability testing of an owner-completed questionnaire for assessing clinical signs and dog and owner quality of life (QOL) in canine chronic rhinitis.Twenty-two dogs with histopathologically confirmed chronic rhinitis and 72 healthy dogs.In this prospective study, an online questionnaire was created based on literature review and feedback from veterinarians, veterinary internists with respiratory expertise, and owners of dogs with rhinitis. Owners of affected dogs completed the questionnaire twice, 1 week apart, to test reliability. Healthy dogs were assessed once. Data were analyzed using the Rasch Rating Scale Model, and results were interpreted using Messick's framework for evaluating construct validity evidence.Initial item generation resulted in 5 domains: nasal signs, paranasal signs, global rhinitis severity, and dog's and owner's QOL. A 25-item questionnaire was developed using 5-point Likert-type scales. No respondent found the questionnaire difficult to complete. Strong psychometric evidence was available to support the substantive, generalizability, content, and structural aspects of construct validity. Statistical differences were found between responses for affected and control dogs for all but 2 items. These items were eliminated, resulting in the 23-item Severity of Nasal Inflammatory Disease (SNIFLD) questionnaire.The SNIFLD questionnaire provides a mechanism for repeated assessments of disease severity in dogs with chronic rhinitis.
Project description:Hypercortisolism is caused by a cortisol-secreting adrenocortical tumour (ACT) in approximately 15%-20% of cases in dogs. Little is known about which molecular markers are associated with malignant behaviour of canine ACTs. The objective of this study was to identify molecular markers of prognosis, which could be useful to refine prognostic prediction and to identify potential treatment targets. Cortisol-secreting ACTs were included from 40 dogs, of which follow-up information was available. The ACTs were classified as low risk of recurrence tumours (LRT; n = 14) or moderate-high risk of recurrence tumours (MHRT; n = 26), based on the novel histopathological Utrecht score. Normal adrenals (NAs) were included from 11 healthy dogs as reference material. The mRNA expression of 14 candidate genes was analysed in the 40 ACTs and in 11 NAs with quantitative RT-PCR. The genes' expression levels were statistically compared between NAs, LRTs and MHRTs. Univariate and multivariate analyses were performed to determine the association of the genes' expression levels with survival. Seven genes were differentially expressed between NAs and ACTs, of which pituitary tumour-transforming gene-1 (PTTG1) and topoisomerase II alpha (TOP2A) were also differentially expressed between LRTs and MHRTs. In survival analyses, high expression levels of Steroidogenic factor-1 (SF-1), PTTG1 and TOP2A were significantly associated with poor survival. In conclusion, we have identified several genes that are part of the molecular signature of malignancy in canine ACTs. These findings can be used to refine prognostic prediction, but also offer insights for future studies on druggable targets.
Project description:Intracranial Ewing sarcoma (EwS) is rare and publications on primary or metastatic intracranial EwS are minimal. The aim of this study was to describe incidence, clinical behavior, treatment, and factors associated with outcome in patients with primary intracranial EwS or patients with a primary extracranial EwS and cerebral metastases at diagnosis. We reviewed all patients with primary or with metastatic intracranial EwS at diagnosis registered in the International Clinical Trial Euro-E.W.I.N.G.99 (EE99). In total, 17 of 1435 patients (1.2%) presented with primary intracranial EwS; 3 of them had metastatic disease. Four patients (0.3%) with primary extracranial EwS presented with intracranial metastatic lesions. The 3-year event-free survival (EFS) was 64% and overall survival (OS) was 70% in patients with a primary intracranial EwS. Local control in patients with primary intracranial EwS consisted of surgery (6%), radiotherapy (RT) (18%), or both modalities (76%). Univariate analysis showed that patients < 15 years of age had significantly better outcome (EFS: 72%; OS: 76%) compared to those aged above 15 years (EFS: 13%; OS: 25%). In conclusion, primary intracranial EwS and extracranial EwS with cerebral metastases at diagnosis is rare, yet survival is comparable with local and metastatic EwS elsewhere in the body. Age and stage of disease are important prognostic factors. Besides chemotherapeutic treatment, local control with surgical resection combined with RT is recommended whenever feasible.
Project description:BACKGROUND: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). METHODS: Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). RESULTS: The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. CONCLUSIONS: Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases.
Project description:To guide early stage breast cancer patients to choose between breast conserving surgery (BCS) and mastectomy (MST) considering the predicted cosmetic result and quality of life (QoL).A decision model was built to compare QoL after BCS and MST. Treatment could result in BCS with good cosmesis, BCS with poor cosmesis, MST only, and MST with breast reconstruction. QoL for these treatment outcomes were obtained from a previous study and the literature and translated into EuroQoL-5D derived utilities. Chance of good cosmesis after BCS was predicted based on tumor location and tumor/breast volume ratio. The decision model determined whether the expected QoL was superior after BCS or MST based on chance of good cosmesis.The mean utility for the treatments such as BCS with good cosmesis, BCS with poor cosmesis, MST only, and MST with breast reconstruction were 0.908, 0.843, 0.859, and 0.876, respectively. BCS resulted in superior QoL compared to MST in patients with a chance of good cosmesis above 36%. This 36% threshold is reached in case the tumor is located in the upper lateral, lower lateral, upper medial, lower medial, and central quadrant of the breast with a tumor/breast volume ratio below 21.6, 4.1, 15.1, 3.2, and 14.7, respectively.BCS results in superior QoL in patients with tumors in the upper breast quadrants or centrally and a tumor/breast volume ratio below 15. MST results in superior QoL in patients with tumors in the lower breast quadrants and a tumor/breast volume ratio above 4.
Project description:The pathomechanism of Angiostrongylus vasorum infection-associated bleeding diathesis in dogs is not fully understood.To describe rotational thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum and to compare ROTEM parameters between infected dogs with and without clinical signs of bleeding.A total of 21 dogs presented between 2013 and 2016.Dogs with A. vasorum infection and ROTEM evaluation were retrospectively identified. Thrombocyte counts, ROTEM parameters, clinical signs of bleeding, therapy, and survival to discharge were retrospectively retrieved from patient records and compared between dogs with and without clinical signs of bleeding.Evaluation by ROTEM showed hyperfibrinolysis in 8 of 12 (67%; 95% CI, 40-86%) dogs with and 1 of 9 (11%; 95% CI, 2-44%) dogs without clinical signs of bleeding (P = .016). Hyperfibrinolysis was associated with severe hypofibrinogenemia in 6 of 10 (60%; 95% CI, 31-83%) of the cases. Hyperfibrinolysis decreased or resolved after treatment with 10-80 mg/kg tranexamic acid. Fresh frozen plasma (range, 14-60 mL/kg) normalized follow-up fibrinogen function ROTEM (FIBTEM) maximal clot firmness in 6 of 8 dogs (75%; 95% CI, 41-93%). Survival to discharge was 67% (14/21 dogs; 95% CI, 46-83%) and was not different between dogs with and without clinical signs of bleeding (P = .379).Hyperfibrinolysis and hypofibrinogenemia were identified as an important pathomechanism in angiostrongylosis-associated bleeding in dogs. Hyperfibrinolysis and hypofibrinogenemia were normalized by treatment with tranexamic acid and plasma transfusions, respectively.
Project description:BACKGROUND: Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance. RESULTS: A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers. CONCLUSIONS: Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.
Project description:Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals.To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT.Eight dogs with presumptive PNST.This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy.Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy.This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.