A radiation therapy platform to enable upright cone beam computed tomography and future upright treatment on existing photon therapy machines.

Background: The conventional lying down position for radiation therapy can be challenging for patients due to pain, swallowing or breathing issues. To provide an alternative upright treatment position for these patients, we have developed a portable rotating radiation therapy platform which integrates with conventional photon treatment machines. The device enables cone-beam computed tomography (CBCT) imaging of patients in an upright position, and the future delivery of therapeutic radiation.

Porcine-human glioma xenograft model. Immunosuppression and model reproducibility.

Background: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

Aim: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme.

Methods And Results: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups.

Alpelisib Monotherapy for PI3K-Altered, Pretreated Advanced Breast Cancer: A Phase II Study.

Unlabelled: There is limited knowledge on the benefit of the α-subunit-specific PI3K inhibitor alpelisib in later lines of therapy for advanced estrogen receptor-positive (ER+) HER2- and triple-negative breast cancer (TNBC). We conducted a phase II multicohort study of alpelisib monotherapy in patients with advanced PI3K pathway mutant ER+HER2- and TNBC. In the intention-to-treat ER+ cohort, the overall response rate was 30% and the clinical benefit rate was 36%.

Detection of subclinical hemorrhage using electrical impedance: a porcine study.

Analyze the performance of electrical impedance tomography (EIT) in an innovative porcine model of subclinical hemorrhage and investigate associations between EIT and hemodynamic trends.. Twenty-five swine were bled at slow rates to create an extended period of subclinical hemorrhage during which the animal's heart rate (HR) and blood pressure (BP) remained stable from before hemodynamic deterioration, where stable was defined as <15% decrease in BP and <20% increase in HRi.

The value of clinical breast examination in a breast cancer surveillance program for women with germline BRCA1 or BRCA2 mutations.

Objective: To assess the sensitivity and specificity of clinical breast examination for detecting breast cancer in asymptomatic women with predisposing germline mutations enrolled in a cancer risk management program that includes radiologic screening.

Design, Setting: Retrospective, longitudinal cohort study of women with BRCA1/2 mutations who attended the Breast and Ovarian Cancer Risk Management Clinic at the Peter MacCallum Cancer Centre, a tertiary referral centre in Melbourne, during 1 September 2001 - 31 December 2019.

Participants: Consecutive women with BRCA1/2 mutations who did not have personal histories of cancer and had not undergone bilateral risk-reducing mastectomy, and who had visited the clinic at least twice during the study period.

Epinephrine plus chest compressions is superior to epinephrine alone in a hypoxia-induced porcine model of pseudo-pulseless electrical activity.

Aim: Pseudo-pulseless electrical activity (pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG with no clinically detectable pulses. The role of standard external chest compressions (CPR) and its associated intrinsic hemodynamics remains unclear in the setting of pseudo-PEA. We undertook an experimental trial to compare epinephrine alone versus epinephrine with CPR in the treatment of pseudo-PEA.

The Relationship of Ultrasound Measurements of Muscle Deformation With Torque and Electromyography During Isometric Contractions of the Cervical Extensor Muscles.

Objectives: Speckle tracking analysis (STA) of ultrasound (US) images quantifies the longitudinal deformation of a region of muscle tissue to provide a mechanical measure of muscle activity. As the validity and reliability of this method has not yet been adequately assessed, the aim of this study was to determine the validity and reliability of STA in the dorsal neck muscles during isometric neck extension contractions.

Methods: Twenty volunteers performed 3 repetitions of isometric neck extension in a dynamometer at 10%, 20%, 40%, 60%, and 80% of maximal voluntary torque while US and surface electromyography (EMG) data were recorded.

Intravenous calcium as a pressor in a swine model of hypoxic pseudo-pulseless electrical mechanical activity-a preliminary report.

Background: Pseudo-pulseless electrical activity (pseudo-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Pseudo-PEA may constitute up to 40% of reported cases of cardiac arrest. Resuscitation from pseudo-PEA is often associated with hypotension refractory to catecholamine pressors.

Experimentally Observed Cherenkov Light Generation in the Eye During Radiation Therapy.

Purpose: Patients have reported sensations of seeing light flashes during radiation therapy, even with their eyes closed. These observations have been attributed to either direct excitation of retinal pigments or generation of Cherenkov light inside the eye. Both in vivo human and ex vivo animal eye imaging was used to confirm light intensity and spectra to determine its origin and overall observability.

Ultrasound imaging of dorsal neck muscles with speckle tracking analyses - the relationship between muscle deformation and force.

The development of methods of non-invasive measurement of neck muscle function remains a priority in the clinical sciences. In this study, dorsal neck muscle deformation vs time curves (deformation area) were evaluated against incremental force, recorded from non-invasive real-time ultrasound measurement. The results revealed subject-specific moderate to strong linear or non-linear relationships between deformation and force.

Quantitative evaluation of the in vivo biocompatibility and performance of freeze-cast tissue scaffolds.

Quantitative methods are little used for the in vivo assessment of tissue scaffolds to evaluate biocompatibility. To complement current histological techniques, we introduce as a measure of biocompatibility a straightforward, geometric analysis for the quantitative assessment of encapsulation thickness, cross-sectional area, and biomaterial shape. Advantages of this new technique are that it enables, on the one hand, a more complete and objective comparison of scaffolds with differing compositions, architectures, and mechanical properties, and, on the other, a more objective approach to their selection for a given application.

A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2-Positive Metastatic Breast Cancer.

Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated "on-target" lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D).

Design, Manufacture, and Testing of a Tissue Scaffold for Permanent Female Sterilization by Tubal Occlusion.

Current FDA-approved permanent female sterilization procedures are invasive and/or require the implantation of non-biodegradable materials. These techniques pose risks and complications, such as device migration, fracture, and tubal perforation. We propose a safe, non-invasive biodegradable tissue scaffold to effectively occlude the Fallopian tubes within 30 days of implantation.

Treatment of Canine Oral Melanoma with Nanotechnology-Based Immunotherapy and Radiation.

The presence and benefit of a radiation therapy-associated immune reaction is of great interest as the overall interest in cancer immunotherapy expands. The pathological assessment of irradiated tumors rarely demonstrates consistent immune or inflammatory response. More recent information, primarily associated with the "abscopal effect", suggests a subtle radiation-based systemic immune response may be more common and have more therapeutic potential than previously believed.

Hypo-fractionated Radiation, Magnetic Nanoparticle Hyperthermia and a Viral Immunotherapy Treatment of Spontaneous Canine Cancer.

It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia.

Surveillance in Germline TP53 Mutation Carriers Utilizing Whole-Body Magnetic Resonance Imaging.

This prospective study of surveillance strategies uses a whole-body screening program, including whole-body magnetic resonance imaging, in carriers of germline mutations in

Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism.

Cerebral tissue oxygenation (oxygen tension, pO) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO simultaneously at four sites in a rabbit model of ischemic stroke induced by embolic clot. The pO values in healthy brain were not significantly different among the four sites measured over a period of 4 weeks.

Endoscopy after esophagectomy: Safety demonstrated in a porcine model.

Background: Endoscopy is useful in assessing conduit ischemia and anastomotic leaks after esophagectomy but poses a theoretical threat of anastomotic disruption. We used a porcine model to evaluate the safety of endoscopy after esophagectomy.

Methods: We performed esophagectomies in 10 live pigs and performed endoscopy with progressive air insufflation and continuous intraluminal pressure monitoring.

Crizotinib Associated Renal Cysts [CARCs]: incidence and patterns of evolution.

Background: Novel therapeutic agents recently introduced for the treatment of cancer have several unusual side effects. An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib. Many of these lesions undergo spontaneous resolution despite developing complex features on imaging.

Preliminary Assessment of a Hysteroscopic Fallopian Tube Heat and Biomaterial Technology for Permanent Female Sterilization.

Recent failures in hysteroscopic female sterilization procedures have brought into question the implantation of non-resorbable metal devices into the fallopian tubes due to long-term risks such as migration, fragmentation, and tubal perforation. The goal of this study is to assess whether a porous, biodegradable implant can be deposited into the fallopian tube lumen with or without a local mild heat treatment to generate a safe and permanent fallopian tube occlusion/sterilization event. The technologies investigated included freeze-cast collagen-based scaffolds and magnetic nanoparticle (MNP) based scaffolds.

Toxicity and Pharmacokinetic Profile for Single-Dose Injection of ABY-029: a Fluorescent Anti-EGFR Synthetic Affibody Molecule for Human Use.

Purpose: ABY-029, a synthetic Affibody peptide, Z03115-Cys, labeled with a near-infrared fluorophore, IRDye® 800CW, targeting epidermal growth factor receptor (EGFR) has been produced under good manufacturing practices for a US Food and Drug Administration-approved first-in-use human study during surgical resection of glioma, as well as other tumors. Here, the pharmacology, phototoxicity, receptor activity, and biodistribution studies of ABY-029 were completed in rats, prior to the intended human use.

Procedures: Male and female Sprague Dawley rats were administered a single intravenous dose of varying concentrations (0, 245, 2449, and 24,490 μg/kg corresponding to 10×, 100×, and 1000× an equivalent human microdose level) of ABY-029 and observed for up to 14 days.