Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy)

OBJECTIVE To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS 14 client-owned cats. PROCEDURES Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

Clinical Values and Markers of Radiation-Induced Liver Disease for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Stereotactic Body Radiotherapy

BackgroundInformation about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients.MethodsIn our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up.ResultsMedian overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p < 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p < 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p < 0.05).ConclusionsThe development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients.

Machine Learning and Radiomic Features to Predict Overall Survival Time for Glioblastoma Patients

Glioblastoma is an aggressive brain tumor with a low survival rate. Understanding tumor behavior by predicting prognosis outcomes is a crucial factor in deciding a proper treatment plan. In this paper, an automatic overall survival time prediction system (OST) for glioblastoma patients is developed on the basis of radiomic features and machine learning (ML). This system is designed to predict prognosis outcomes by classifying a glioblastoma patient into one of three survival groups: short-term, mid-term, and long-term. To develop the prediction system, a medical dataset based on imaging information from magnetic resonance imaging (MRI) and non-imaging information is used. A novel radiomic feature extraction method is proposed and developed on the basis of volumetric and location information of brain tumor subregions extracted from MRI scans. This method is based on calculating the volumetric features from two brain sub-volumes obtained from the whole brain volume in MRI images using brain sectional planes (sagittal, coronal, and horizontal). Many experiments are conducted on the basis of various ML methods and combinations of feature extraction methods to develop the best OST system. In addition, the feature fusions of both radiomic and non-imaging features are examined to improve the accuracy of the prediction system. The best performance was achieved by the neural network and feature fusions.

Identification of the Upregulation of MRPL13 as a Novel Prognostic Marker Associated with Overall Survival Time and Immunotherapy Response in Breast Cancer

Mitochondrial ribosomal protein (MRPL) genes have been reported to participate in many cellular processes, such as cell proliferation, apoptosis, and cell cycle. Meanwhile, the occurrence rate of breast cancer (BRCA) in China steadily increased. Exploring the prognostic value of MRPL genes in BRCA could provide novel biomarkers for BRCA. In this study, to identify prognosis-related genes in breast cancer, the P value and the hazard ratio (HR) of all genes are analyzed with TCGA database. We revealed higher expression level of CEL, PGK1, WNT3A, USP41, LINC02037, PCMT1, LRP11, MCTS1, TCP1, TMEM31, STK4-AS1, STXBP5, LOC100287036, SLC16A2, MRPL13, DERL1, and TARS was correlated to shorter OS time in BRCA. However, higher expression level of JCHAIN, KLRB1, and TNFRSF14 was correlated to longer OS time in BRCA. The further analysis demonstrated MRPL13 was overexpressed in BRCA. Subtype analysis showed that MRPL13 was overexpressed in luminal, HER2-positive BRCA, and TNBC samples and was highest in TNBC samples. Moreover, we revealed higher expression of MRPL13 was significantly correlated to shorter OS time and higher TMB levels in BRCA. Pan-cancer analysis further revealed the prognostic value of MRPL13 in human cancers. MRPL13 expression was significantly increased in multiple human cancers, such as bladder cancer, colon cancer, liver cancer, and prostate cancer. Pan-cancer TMB and overall survival time showed dysregulation of MRPL13 is significantly related to the OS and TMB levels in various cancers. These results further proved that MRPL13 may be a pan-cancer biomarker for predicting prognosis and the response to immunotherapy.

Toceranib phosphate (Palladia) for the treatment of canine exocrine pancreatic adenocarcinoma

Background Canine pancreatic carcinoma is a rare, aggressive tumour that is often diagnosed late in the course of disease. Effective treatment strategies have been elusive, and overall survival time is short. In humans, treatment with tyrosine kinase inhibitors alone, or in combination with IV gemcitabine, have been moderately effective. As canine and human pancreatic carcinomas share many clinical aspects, strategies that mimic human treatment regimens may confer a better outcome in canine patients. The aim of this study was to assess the role of the veterinary tyrosine kinase inhibitor, toceranib phosphate, in the treatment of cytologically or histologically confirmed canine pancreatic carcinomas. Results Retrospectively, medical records of dogs with confirmed pancreatic carcinoma treated with toceranib were reviewed. Eight dogs were identified that fit the inclusion criteria. Toceranib was well-tolerated by all patients. Six were treated in the gross disease setting. Four had image-based evaluation of clinical benefit (complete response, partial response, or stable disease of > 10 weeks). Of those patients, 1 achieved a partial response, 2 stable disease, and 1 had progressive disease, for an overall clinical benefit rate of 75 %. An additional dog had clinically stable disease that was not confirmed via imaging. The toceranib-specific median overall survival time was 89.5 days (range: 14–506 days). Conclusions Although limited in patient number, this small study suggests that toceranib may have biologic activity in dogs with pancreatic carcinoma. Larger, prospective studies are needed to confirm these preliminary results and define the use of toceranib in the microscopic disease setting.

Maintenance treatment in relapsed canine lymphoma after a short L-CHOP protocol

Objective A number of different rescue protocols for relapsed canine multicentric large-cell lymphoma have been described. The aim of this pilot study was to evaluate the efficacy of a maintenance treatment in dogs that experienced a second complete remission after a short L-CHOP-rescue protocol. Material and methods Included in the study were dogs experiencing the first lymphoma relapse during a treatment-free period which were treated with a short L-CHOP protocol, achieved a complete remission and were afterwards treated with a continuous maintenance phase (MP) protocol. The L-CHOP protocol consisted of weekly treatments, with at least 3 additional treatments following complete remission. Thereafter the MP protocol with 2-week treatment intervals was conducted. It consisted of alternating oral home administration of different alkylating agents and one intravenously administered cytotoxic agent of a different mechanism of action. The dogs were presented either every 4 or 6 weeks for intravenous treatment and at this time a complete blood count was performed. The durations of the first remission, disease-free interval and overall survival time were evaluated. Results A total of 20 dogs were included in the study. A median of 7 weekly applications were given before the treatment was switched to the MP protocol. During MP, 14 dogs were treated intravenously every 6 weeks and 6 dogs every 4 weeks. Haematological adverse events were mainly mild. During the L-CHOP-protocol, one septic event occurred, and 2 dogs were hospitalized due to gastrointestinal adverse events. No patient required hospitalization during the MP. Fifteen dogs completed at least one cycle in the MP and a median of 8.5 chemotherapeutic treatments were administered. The median disease-free interval was 264 days and the median overall survival time was 737 days. Conclusion and clinical relevance The protocol was generally well tolerated. Since 5 patients showed disease progression during the first cycle of the MP, dogs should ideally be evaluated for minimal residual disease before being switched to the MP. The case number in the presented study was low and the treatment relatively heterogeneous. Therefore, more dogs have to be treated with the proposed protocol before general recommendations can be made.

Treatment of Canine Oral Melanoma with Adjuvant Chemotherapy and Immunotherapy

Background: Melanoma is the most frequent cancer in the canine oral cavity. It shows an aggressive behavior, characterized by rapid and invasive growth and high metastatic potential. Metastasis is seen in more than 80% of dogs at time of death. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poor prognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to the disease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanoma and treated with adjuvant chemotherapy and immunotherapy. Materials, Methods & Results:A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocytic melanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oral malignant melanoma. Tumor size (T1: < 2 cm; T2: 2 - 4 cm; T3: > 4 cm), regional metastasis (N0: no metastasis; N1: metastasis) and presence of distant metastasis (M0: no metastasis; M1: metastasis) are evaluated. Then, cases were divided into 4 stages: I (T1 N0 M0), II (T2 N0 M0), III (T3 N0-1 M0, Tx N1 M0) and IV (Tx Nx M1). Diagnoses were confirmed with histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were divided into 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted to surgery associated with adjuvant chemotherapy with four 21-day cycles of carboplatin (300 mg/m2) and immunotherapy with six 7-day cycles of interferon-α (3 x 106 IU/m2) were included in group 2 (G2). Twenty dogs diagnosed with oral melanoma were evaluated: 3 were included in G1 and 17 in G2. Considering clinical staging of the dogs: 7 stage II, 12 stage III and only 1 stage IV. There was no stage I patients. In poorly differentiated neoplasias, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Patient follow-up was obtained through the evaluation of patient records and telephone interviews with owners. The overall survival time (OS) was defined by the period (in days) between the date of surgical excision and the death caused by the disease. Median overall survival time was 86 days for animals in G1 and 894 days for animals in G2 (P = 0.01). Discussion: Carboplatin was considered an appropriate cytostatic drug to treat microscopic disease in oral melanoma. INF-α was chosen for immunotherapy in this study because it promotes immune system stimulation associated with an indirect antiproliferative effect on neoplastic cells. The association of INF-α and carboplatin resulted in a significant increase in overall survival, when compared to the literature, suggesting that association of chemotherapy and immunomodulation is an important strategy in the treatment of canine oral melanoma. Controlled prospective randomized trials are necessary to confirm the benefits of chemotherapy and immunotherapy association to treat canine oral melanoma. Adjuvant therapy with chemotherapy and immunotherapy was considered effective to increase overall survival and maintained quality of life of dogs diagnosed with oral melanoma.

Contribution of intraoperative stimulation mapping to glioblastoma surgery within or adjacent to descending motor pathways: survival analysis and functional outcome comparison between two series in a single institution

Purpose Extensive resection probably confers a modest survival advantage in patients with glioblastoma. Studies have revealed the positive effects of intraoperative stimulation mapping (ISM) on the extent of resection, but no consensus for contribution of intraoperative stimulation mapping is reached. Methods This retrospective study enrolled two groups of patients who underwent surgery for motor-eloquent glioblastoma: the non-ISM group of 57 patients (surgery in 2008–2013) and ISM group of 13 patients (surgery in 2014–2015). The two groups and subgroups based on resection extent and postoperative additional neurological deficit were compared using Kaplan–Meier analysis and the log-rank test. Results Gross or near total resection (≥ 90% resection quality) was significantly more common in the ISM group than the non-ISM group (76.9% versus 24.6%; p = 0.001). The extent of resection was also significantly greater (90.5% ± 15.6% versus 64.6% ± 29.2%; p = 0.002). The neurological outcome in the ISM group was thus superior, but the two differences were not significant. The median progression-free survival time was significantly longer in the ISM group (22.0 ± 5.1 months vs 8.0 ± 1.0 months; p = 0.037) but a significant difference was not indicated in median overall survival time (22.0 ± 8.4 months vs 16.0 ± 2.2 months; p = 0.167). Conclusion ISM was discovered to lead to higher quality of resection and delayed recurrence. The neurological outcome and median overall survival time in the ISM group was thus superior, but the two differences were not significant. Trial registration number (for clinical trials) Nil