A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

Background: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking.

Uncertainty estimation using a 3D probabilistic U-Net for segmentation with small radiotherapy clinical trial datasets.

Background And Objectives: Bio-medical image segmentation models typically attempt to predict one segmentation that resembles a ground-truth structure as closely as possible. However, as medical images are not perfect representations of anatomy, obtaining this ground truth is not possible. A surrogate commonly used is to have multiple expert observers define the same structure for a dataset.

Partially Ablative Body Radiotherapy (PABR): A novel approach for palliative radiotherapy of locally advanced bulky unresectable sarcomas.

Background: Locally advanced, bulky, unresectable sarcomas cause significant tumour mass effects, leading to burdensome symptoms. We have developed a novel Partially Ablative Body Radiotherapy (PABR) technique that delivers a high, ablative dose to the tumour core and a low, palliative dose to its periphery aiming to increase overall tumour response without significantly increasing treatment toxicity.

Aim: This study aims to report the safety and oncologic outcomes of PABR in patients with bulky, unresectable sarcomas.

Selection of motion management in liver stereotactic body radiotherapy and its impact on treatment time.

Background And Purpose: Reduction of respiratory tumour motion is important in liver stereotactic body radiation therapy (SBRT) to reduce side effects and improve tumour control probability. We have assessed the distribution of use of voluntary exhale breath hold (EBH), abdominal compression (AC), free breathing gating (gating) and free breathing (FB), and the impact of these on treatment time.

Materials And Methods: We assessed all patients treated in a single institution with liver SBRT between September 2017 and September 2021.

Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice.

Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity.

Atlantoaxial instability secondary to osteomyelitis managed surgically by atlantoaxial instrumentation: A case report and systematic review.

Cat scratch disease (CSD), caused by , may atypically present with vertebral osteomyelitis. Antibiotic regimens are tailored to presentation, which is markedly variable and not well defined for any atypical disease. In cases of spinal instability, the use of antibiotics alone may not be sufficient.

Impact of Medical Operability and Total Metastatic Ablation on Outcomes After SABR for Oligometastases.

Purpose: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites.

Methods And Materials: Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database.

Long-term Patterns of Failure and the Value of Blood Prognostic Markers in Anal Cancers Treated With Intensity-Modulated Radiation Therapy.

Background: To analyze the long-term outcomes and prognostic value of hematological parameters in anal cancer patients receiving intensity-modulated radiation therapy (IMRT).

Materials: Hospital records of consecutive patients with anal squamous cell carcinoma who received curative-intent IMRT according to a standardized contouring protocol between 2010 and 2020 were reviewed. Locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method.

Complete ophthalmoplegia secondary to idiopathic intracranial hypertension managed successfully with dural sinus stenting: A case and systematic review.

Idiopathic Intracranial Hypertension (IIH) typically occurs in obese (BMI >30 kg/m) females of childbearing age in the absence of any apparent intracranial space-occupying lesion. Patients typically present with headache, nausea, vomiting, tinnitus, and blurry vision secondary to increased intracranial pressure, with more severe cases involving cranial neuropathies and ophthalmological manifestations. Complete ophthalmoplegia is a rare event in IIH.

AGITG MASTERPLAN: a randomised phase II study of modified FOLFIRINOX alone or in combination with stereotactic body radiotherapy for patients with high-risk and locally advanced pancreatic cancer.

Background: Among patients with non-metastatic pancreatic cancer, 80% have high-risk, borderline resectable or locally advanced cancer, with a 5-year overall survival of 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in these patients.

Methods And Design: MASTERPLAN is a multi-centre randomised phase II trial of 120 patients with histologically confirmed potentially operable pancreatic cancer (POPC) or inoperable pancreatic cancer (IPC).

A novel mechanism of enhanced transcription activity and fidelity for influenza A viral RNA-dependent RNA polymerase.

During RNA elongation, the influenza A viral (IAV) RNA-dependent RNA polymerase (RdRp) residues in the active site interact with the triphosphate moiety of nucleoside triphosphate (NTP) for catalysis. The molecular mechanisms by which they control the rate and fidelity of NTP incorporation remain elusive. Here, we demonstrated through enzymology, virology and computational approaches that the R239 and K235 in the PB1 subunit of RdRp are critical to controlling the activity and fidelity of transcription.

Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients.

Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (i.v.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

Background: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR.

Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi-institutional patterns of practice review.

Introduction: Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.

Characterising the immune microenvironment in liposarcoma, its impact on prognosis and the impact of radiotherapy.

Background And Objectives: Limited literature exists examining the immune microenvironment in liposarcoma, particularly with regard to the impact of radiotherapy. A major problem is the lack of scoring system for the tumour-infiltrating lymphocytes (TILs) in sarcoma. This study aims to describe the immune environment pre- and postradiotherapy and identify the optimal immune infiltrate scoring system for sarcoma.

Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases.

Purpose: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease.

Methods And Materials: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study.

Results of phase II trial of intensified neoadjuvant treatment with interdigitating radiotherapy and chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid in patients with locally advanced rectal cancer (PROARCT trial).

Background And Purpose: The chemotherapy exposure during chemoradiotherapy for rectal cancer is adequate for radiosensitization but suboptimal for treatment of distant micrometastasis. This study aimed to determine tolerability, dose intensity, response, and toxicity of a novel intensified neoadjuvant treatment approach.

Materials And Methods: Eligible patients were MRI-staged T3-4NxM0 rectal adenocarcinoma.

A six-plex droplet digital RT-PCR assay for seasonal influenza virus typing, subtyping, and lineage determination.

Background: There are two influenza A subtypes (H1 and H3) and two influenza B lineages (Victoria and Yamagata) that currently co-circulate in humans. In this study, we report the development of a six-plex droplet digital RT-PCR (ddRT-PCR) assay that can detect HA and M segments of influenza A (H1, H3, and M) and influenza B (Yamagata HA, Victoria HA, and M) viruses in a single reaction mixture. It can simultaneously detect six different nucleic acid targets in a ddRT-PCR platform.

Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic Stereotactic Body Radiation Therapy (SBRT).

Purpose: Nonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required.

Methods And Materials: Specialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018.

The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers.

Purpose: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia.

Participants: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach.

A clinical trial with protracted infusion 5-fluorouracil and mitomycin C for localized squamous cell carcinoma of the anus.

Purpose: Mitomycin C (MMC) plus standard 5-fluorouracil (FU) infusion in weeks 1 and 5 often contributes to radiotherapy interruptions and possibly less-than-ideal outcomes in anal cancer. This study was to evaluate alternative strategies for chemotherapy delivery that might be less toxic or more efficacious, and outcomes of patient-initiated treatment interruption for severe acute toxicity.

Materials And Methods: This was a prospective, nonrandomized study for patients with T1-4N0-3M0 anal squamous carcinoma.

Platination of cysteine by an epidermal growth factor receptor kinase-targeted hybrid agent.

Hybrid molecules have been developed which are comprised of a tyrosine kinase-targeted, quinazoline-based scaffold and a flexibly linked dia(m)minechloridoPt(ii) moiety. The target compounds maintain high affinity and selectivity for ErbB family kinase proteins and one of the derivatives induces platinum adducts with a pharmacologically important cysteine residue.