Transfer Learning Approach to Vascular Permeability Changes in Brain Metastasis Post-Whole-Brain Radiotherapy.

The purpose of this study is to further validate the utility of our previously developed CNN in an alternative small animal model of BM through transfer learning. Unlike the glioma model, the BM mouse model develops multifocal intracranial metastases, including both contrast enhancing and non-enhancing lesions on DCE MRI, thus serving as an excellent brain tumor model to study tumor vascular permeability. Here, we conducted transfer learning by transferring the previously trained GBM CNN to DCE MRI datasets of BM mice. The CNN was re-trained to learn about the relationship between BM DCE images and target permeability maps extracted from the Extended Tofts Model (ETM). The transferred network was found to accurately predict BM permeability and presented with excellent spatial correlation with the target ETM PK maps. The CNN model was further tested in another cohort of BM mice treated with WBRT to assess vascular permeability changes induced via radiotherapy. The CNN detected significantly increased permeability parameter Ktrans in WBRT-treated tumors (p < 0.01), which was in good agreement with the target ETM PK maps. In conclusion, the proposed CNN can serve as an efficient and accurate tool for characterizing vascular permeability and treatment responses in small animal brain tumor models.

Post-Irradiation Treatment with a Superoxide Dismutase Mimic, MnTnHex-2-PyP5+, Mitigates Radiation Injury in the Lungs of Non-Human Primates after Whole-Thorax Exposure to Ionizing Radiation.

Radiation injury to the lung is the result of acute and chronic free radical formation, and there are currently few effective means of mitigating such injury. Studies in rodents indicate that superoxide dismutase mimetics may be effective in this regard; however, studies in humans or large animals are lacking. We hypothesized that post-exposure treatment with the lipophilic mitochondrial superoxide dismutase mimetic, MnTnHex-2-PyP5+ (hexyl), would reduce radiation-induced pneumonitis and fibrosis in the lungs of nonhuman primates. Rhesus monkeys (Macaca mulatta) received 10 Gy whole thorax irradiation, 10 Gy + hexyl treatment, sham irradiation, or sham irradiation + hexyl. Hexyl was given twice daily, subcutaneously, at 0.05 mg/kg, for 2 months. Animals were monitored daily, and respiratory rates, pulse oximetry, hematology and serum chemistry panels were performed weekly. Computed tomography scans were performed at 0, 2, and 4 months after irradiation. Supportive fluid therapy, corticosteroids, analgesics, and antibiotics were given as needed. All animals were humanely euthanized 4.5 months after irradiation, and pathologic assessments were made. Multifocal, progressive lung lesions were seen at 2 and 4 months in both irradiated groups. Hexyl treatment delayed the onset of radiation-induced lung lesions, reduced elevations of respiratory rate, and reduced pathologic increases in lung weight. No adverse effects of hexyl treatment were found. These results demonstrate (1) development of a nonhuman primate model of radiation-induced lung injury, (2) a significant mitigating effect of hexyl treatment on lung pathology in this model, and (3) no evidence for toxicity of hexyl at the dose studied.

Gamma Knife radiosurgery for brain metastases from gastrointestinal primary.

INTRODUCTION: In this study, we assessed clinical outcomes of patients with brain metastases from a gastrointestinal (GI) primary cancer and patterns of failure after stereotactic radiosurgery including failure within the radiosurgical volume, distant failure and leptomeningeal failure (LMF). We also assessed other factors associated with the patients' neurologic and extraneuraxial disease that may affect clinical outcomes. METHODS: We reviewed our institutional series of 62 consecutive patients with brain metastases treated with stereotactic radiosurgery, which included 17 patients with oesophageal, 44 patients with colorectal and one patient with anal canal primary. The median marginal dose to the radiosurgery volume was 17 Gy (range 10-24 Gy). Thirteen patients were treated with whole-brain radiotherapy (WBRT) prior to GKS. RESULTS: The median dose delivered to the margin of the tumour was 17 Gy (range: 10-24 Gy). The median largest tumour diameter was 2.7 cm (range: 0.60-6.1 cm). The median overall survival (OS) was 7.1 months with a median follow-up of 6.1 months and a range of 0-31.7 months. Freedom from local failure was 86.5% and 62.2% at 6 and 12 months respectively. Freedom from distant failure was 73.2% and 42.2% at 6 and 12 months, respectively, and 40% of patients died of neurologic death. LMF occurred in seven patients, all of whom had colorectal primaries. Multivariate analysis revealed that craniotomy for resection of brain metastasis (HR = 2.63, P < 0.02), an absence of extracranial disease (HR = 2.28, P < 0.03), and prolonged time to distant brain failure (HR = 2.85, P < 0.01) predicted for improved survival. CONCLUSIONS: Colorectal cancer metastases tend to have a higher rate of leptomeningeal failure than other types of GI cancer metastases. Radiosurgical management of brain metastases from GI primary represents an acceptable management option. Neurologic death remains problematic.

Invited review--neuroimaging response assessment criteria for brain tumors in veterinary patients.

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.