Calvary Mater Newcastle Hospital

Heparin remains a foundational parenteral anticoagulant across both acute and chronic care settings. This narrative review summarizes clinical indications and dosing of unfractionated (UFH) and low-molecular-weight heparin (LMWH). It also details laboratory monitoring using activated partial thromboplastin (APTT), anti-factor Xa (anti-Xa), activated clotting time (ACT) and viscoelastic testing (VET), including common pitfalls and interferences. We provide considerations for specific populations as well as complications including heparin resistance, heparin-induced thrombocytopenia (HIT) and heparin reversal strategies. Future research directions include harmonization of therapeutic ranges, mitigation of assay interference and prospective evaluation on monitoring, particular in extracorporeal membrane oxygenation (ECMO), pregnancy and cardiac surgical settings.

The world's population is aging rapidly and older adults carry a disproportionate cancer burden. Despite this, older patients remain underrepresented in clinical research. As a result, the evidence base informing guideline development remains limited. Existing guidelines vary in methodological quality and applicability. We aimed to evaluate the quality and clinical applicability of established geriatric oncology guidelines using the Appraisal of Guidelines Research and Evaluation, version II (AGREE II) instrument. A systematic search was conducted across PubMed, Embase, and the Cochrane Library, in addition to official oncology society websites (ASCO, NCCN, SoFOG, Japanese Geriatric Oncology Group). The search covered publications from January 2000 to May 2025 and was limited to English and to guidelines that specifically address cancer care in older adults and provide documented methodologies. Two reviewers independently appraised each guideline using the AGREE II tool across six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. A total of 807 records were identified,out of which only 6 guidelines met the eligibility criteria. The AGREE II assessment revealed significant variability in guideline quality. Most guidelines scored high in clarity of presentation and scope and purpose, but showed moderate to low scores in stakeholder involvement and applicability. The recent ASCO guidelines demonstrated higher overall methodological rigor, whereas others lacked comprehensive documentation of evidence synthesis and user applicability. While several geriatric oncology guidelines demonstrate acceptable quality, inconsistencies remain, particularly in stakeholder engagement and practical implementation. Enhanced methodological rigor and inclusive development processes are essential for future guideline improvement and effective translation into geriatric oncology practice.

Automated contour quality assurance (QA) has the potential to reduce resource and cost requirements for clinical trial QA. While several studies have developed such models, few have been translated for use in prospective real-world trials. This study aimed to implement a contour QA tool using a previously developed model and evaluate its performance during deployment within the TROG 18.01 NINJA prostate cancer trial. A software tool was developed using an existing prostate clinical target volume (CTV) QA model and integrated into the trial QA workflow. A pilot study was conducted over an 18-month period, during which 56 CTVs were assessed. Reports generated by the tool flagged cases for review and were provided to radiation oncologists to support QA processes. All five protocol-violating CTVs were correctly identified during deployment, yielding a sensitivity of 1.0. However, a higher-than-expected false positive rate resulted in an accuracy of 0.46 and specificity of 0.41. Retrospective analysis showed that many cases submitted deviated from the model's training distribution, primarily due to inconsistencies in MRI acquisition and variation in submitted CTV definitions. Incorporating out-of-distribution detection based on histogram correlation and model uncertainty improved accuracy to 0.69 for in-distribution cases. Radiation oncologists reported time savings of up to 60min per case. However, preparation of data remained time intensive for QA coordinators, highlighting the need for further workflow automation. These findings support the feasibility of automated contour QA in multicentre trials and offer guidance for future implementation at scale.

Hormone receptor-positive (HR+), human epithelial growth factor receptor 2 (HER2) overexpressed breast cancer (BC) represents the more aggressive subtype of HR + BC, typically associated with poor clinical outcomes. Despite significant advancements in the treatment of estrogen receptor-positive (ER+)/HER2 + BC, resistance to endocrine therapy (ET) poses a continued challenge. Imlunestrant is a next-generation, oral, brain-penetrant, pure antagonistic ER degrader designed to deliver continuous ER target inhibition. It has shown favorable clinical benefit, safety, and pharmacokinetics (PK) when used as monotherapy or with targeted therapy in patients with ER+/HER2- advanced BC (ABC). Here, we present the safety and efficacy of imlunestrant with HER2 targeted therapy in patients with ER+/HER2 + ABC of the EMBER trial. Patients were randomized to imlunestrant (400 mg RP2D) + trastuzumab (group A) versus imlunestrant + trastuzumab ± abemaciclib [(150 mg twice daily) group B] or received maintenance treatment with imlunestrant + trastuzumab + pertuzumab until progression or discontinuation at standard doses (group C). In the randomized allocation, eligible patients with locally advanced or metastastic disease had received ≥ 2 prior HER2-directed regimens in the metastatic setting, and no prior treatment with CDK4/6 inhibitors or fulvestrant. The maintenance cohort (group C) was added later to include patients without disease progression after first-line induction taxane-based chemotherapy (any duration), trastuzumab, and pertuzumab. Endpoints included safety, PK, antitumor activity, and tumor biomarker assessments. In total, 45 patients with ER+/HER2 + ABC were treated (group A, n = 18; group B, n = 21; group C, n = 6). Adverse events were consistent with the known safety profiles of the partner drugs. Imlunestrant PK was consistent with previously reported data. For groups A, B, and C, the objective response rates (ORRs) were 7%, 25%, and 33%, respectively, while the clinical benefit rates (CBRs) were 44%, 48%, and 100%. In group C, the duration of response ranged between 5.13 and 9.46 months. In groups A and B, baseline plasma ctDNA sample sequencing identified prevalent alterations in ERBB2 amplification (57%), CCND1 amplification (22%), and mutations in TP53 (49%), PIK3CA (30%), ESR1 (24%), and GATA3 (14%). Imlunestrant in combination with trastuzumab ± abemaciclib or pertuzumab presented a safety profile that was consistent with those of the partnered drugs. No new safety findings were observed. Furthermore, imlunestrant in combination with the partnered drugs demonstrated preliminary antitumor activity in patients with ER+/HER2 + ABC. ClinicalTrials.gov identifier NCT04188548 (Registered 18 November 2019).

BackgroundPrior to the development of the IMRT and VMAT treatment techniques the quality assurance (QA) paradigm was one of routine linac QA supplemented by plan specific independent Monitor Unit checks and manual checks of data transfer. With the introduction of IMRT/VMAT treatment techniques the paradigm changed to include a patient specific measurement (PSQA) to ensure acceptable plan deliverability.PurposeTo inform upon whether QA procedures have improved to the point that measurement‐based PSQA is feasibly no longer required.MethodsThe current status and future trajectory of QA procedures is assessed via a review of the literature pertaining to each of the three sub‐systems of deliverability, namely, treatment planning system (TPS) calculation accuracy, linac delivery performance, and data transfer between treatment planning system and linac.ResultsThe literature pertaining to 3D TPS dosimetry check systems used to assure TPS calculation accuracy is highly positive about such systems ability to provide at least equivalent level testing as measurement based PSQA with regards TPS calculation accuracy. The literature suggests that linac QA procedures have evolved since the advent of IMRT and methodology has been published for assessing the linac in its dynamic state used to deliver IMRT/VMAT. Data transfer QA has also evolved since the advent of IMRT and tests and procedures are now recommended in best practice guidance for both comprehensive data transfer QA programs and pre‐treatment checking and chart rounds. Additionally, the uptake of log file‐based QA methods provides a useful means of testing control point data transfer integrity.ConclusionsContemporary sub‐system deliverability QA has evolved to the point where measurement based PSQA is not necessarily required.

<title>Abstract</title> <bold>Background:</bold> To systematically review and meta-analyse the prognostic value of quantitative mid-treatment imaging biomarkers for predicting locoregional tumour control in patients undergoing definitive radiotherapy for mucosal head and neck squamous cell carcinoma. <bold>Main body:</bold> A systematic literature search (2005–2023) was conducted in PubMed, EMBASE, Scopus, and Cochrane databases according to a pre-registered PROSPERO protocol. Studies evaluating quantitative imaging features derived from CT, MRI, or PET during radiotherapy were included. Imaging features were grouped as baseline, absolute mid-treatment, or relative mid-treatment (delta) parameters. A random-effects meta-analysis was performed on studies reporting receiver operating characteristic (ROC)-based area under the curve (AUC) values. Forty-one studies encompassing 1654 patients were included. Seventeen studies (n = 612 patients) reported sufficient data for meta-analysis. The pooled AUC for relative mid-treatment parameters was 0.796 (95% CI: 0.762–0.831), demonstrating higher predictive performance than absolute mid-treatment parameters (AUC 0.686; 95% CI: 0.628–0.745). Baseline parameters showed moderate predictive ability (AUC 0.736; 95% CI: 0.688–0.785), and while numerically lower than relative mid-treatment parameters, this difference did not reach statistical significance. Diffusion-weighted MRI (ΔADCmean) and FDG-PET (ΔMTV, ΔTLG) emerged as the most consistently predictive modalities. Relative measures offer practical advantages, including internal self-normalisation and improved reproducibility across imaging platforms. <bold>Conclusions:</bold> Relative mid-treatment imaging biomarkers demonstrate superior predictive performance compared to baseline and absolute measures, supporting their potential role in adaptive radiotherapy strategies. Further prospective multi-centre studies with standardised imaging protocols and external validation are essential for clinical translation.

Adjuvant chemotherapy in stage III colon cancer provides uncertain benefit at the individual level. Circulating tumor DNA (ctDNA) may help refine risk-adjusted treatment selection. In this multicenter, randomized, phase 2/3 trial, patients with stage III colon cancer underwent ctDNA testing 5-6 weeks after surgery and were assigned (1:1) to ctDNA-guided or standard management. In the ctDNA-guided arm, patients negative for ctDNA received de-escalated therapy, whereas ctDNA-positive patients received escalated therapy. Clinicians prespecified the standard regimen. Primary endpoints were 3-year recurrence-free survival (RFS) for ctDNA-negative patients and 2-year RFS for ctDNA-positive patients. Secondary endpoints included treatment-related hospitalization and ctDNA clearance. Among 968 evaluable patients, 702 (72.5%) were ctDNA negative. With a median follow-up of 47 months, ctDNA-negative patients experienced significantly fewer recurrences than ctDNA-positive patients (3-year RFS 87% versus 49%; P < 0.001). In ctDNA-negative patients, de-escalation reduced oxaliplatin use (34.8% versus 88.6%) and hospitalizations (8.5% versus 13.2%) but yielded slightly lower RFS than standard management (85.3% versus 88.1%), not meeting the non-inferiority margin. In ctDNA-positive patients, higher ctDNA burden correlated with recurrence risk (3-year RFS 77% to 23% across quartiles; P < 0.001). Escalated therapy did not improve outcomes over standard management (2-year RFS 51% versus 61%). There was no unexpected toxicity. Persistent ctDNA after treatment predicted markedly worse prognosis (3-year RFS 14% versus 79%). ctDNA is validated as a strong prognostic classifier. ctDNA-guided de-escalation reduced oxaliplatin exposure and adverse events with outcomes approaching standard of care, whereas exploratory chemotherapy intensification conferred no RFS benefit, suggesting a need for novel strategies in ctDNA-positive disease.Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617001566325 .