Canterbury District Health Board

X-ray photon-counting computed tomography (PCCT) for extremity allows multi-energy high-resolution (HR) imaging but its radiation dose can be further improved. Despite the great potential of deep learning techniques, their application in HR volumetric PCCT reconstruction has been challenged by the large memory burden, training data scarcity, and domain gap issues. In this paper, we propose a deep learning-based approach for PCCT image reconstruction at halved dose and doubled speed validated in a New Zealand clinical trial. Specifically, we design a patch-based volumetric refinement network to alleviate the GPU memory limitation, train network with synthetic data, and use model-based iterative refinement to bridge the gap between synthetic and clinical data. Our results in a reader study of 8 patients from the clinical trial demonstrate a great potential to cut the radiation dose to half that of the clinical PCCT standard without compromising image quality and diagnostic value.

TPS7084 Background: Autologous chimeric antigen receptor (CAR) T-cells directed against CD19 are a standard of care for relapsed or refractory (r/r) large B-cell lymphoma (LBCL). CAR T-cells incorporating a CD28 costimulatory domain are among the most effective CAR T-cell therapies for LBCL, but are associated with high rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In a phase I dose escalation and expansion study (ENABLE-1, NCT04049513), a new ‘third-generation’ CAR T-cell incorporating a TLR2 co-stimulatory domain alongside CD28 (WZTL-002) demonstrated low rates of CRS and ICANS and promising efficacy. a recommended phase 2 dose (RP2D) of 0.5 – 1.0×10 6 CAR + cells/kg was selected following dose escalation, and outpatient management and automated closed-system WZTL-002 manufacture were implemented within a dose expansion cohort. ENABLE-2 (ClinicalTrials.gov NCT06486051) is a multicentre phase 2 that aims to assess the efficacy and safety of WZTL-002 in patients with r/r LBCL. Methods: Eligible participants are age 18 – 75 years with relapsed or refractory LBCL (either de novo or transformed from follicular or marginal zone lymphoma) following 1 or 2 prior lines of therapy, have assessable disease and satisfactory organ function. Leukapheresis is conducted to obtain autologous T-cells, which are transduced ex vivo to express a third-generation CD19-directed CAR incorporating CD28, TLR2 and CD3zeta stimulatory domains (1928T2z). Bridging therapy is permitted pending WZTL-002 manufacture and product release. Lymphodepletion comprises intravenous fludarabine (30mg/m 2 ) and cyclophosphamide (500mg/m 2 ) daily for 3 days. Two days later a single dose of WZTL-002 is administered at 0.5 – 1.0×10 6 CAR + cells/kg (capped at 10 8 CAR + cells). Participants undergo daily outpatient assessments for toxicities including CRS and ICANS for the first 11 days after WZTL-002 administration, and at days 14 and 28. Disease response is assessed by PET/CT scans at day 28, 3 months and 6 months, and duration of response by CT scan at months 12 and 24. The co-primary endpoints are complete response rate (Lugano criteria) and ICANS rate (any grade) 3 months after WZTL-002 administration. Secondary outcomes include safety (with CRS, ICANS and cytopenias as adverse events of special interest), and progression-free, event-free and overall survival. The first participant was enrolled on 13 August 2024. Clinical trial information: NCT06486051 .

The management of hepatopancreatobiliary (HPB) cancers has progressed due to advances in systemic therapies, imaging, and surgical techniques. While there have been outcome improvements in selected HPB cancer patients, decision-making for radical resections in advanced disease is still contentious. Discussions should extend beyond technical feasibility to include patient comorbidities, ECOG status, frailty, the likelihood of an R0 resection, complication risks, quality of life, and meaningful survival benefit. Although there is potential for cure, at a time of increasing pressure on healthcare resources, it is timely to focus on this contentious issue. Radical operations for advanced cancers carry significant perioperative risks. Complications such as infections and prolonged recovery periods, or the psychological burden in the event of a failed surgical intervention can be considerable, particularly when the expected benefits – such as improved survival or palliation – are not realized. Many surgical outcome assessments focus on technical success and oncological metrics while neglecting patient-reported outcomes, including pain, mobility, and emotional well-being. Even in the era of genomics, immunotherapy, and personalized medicine, Dr. Blake Cady's principles of surgical oncology are relevant.1 Dr. Cady emphasized that 'biology is king', meaning tumour characteristics ultimately dictate outcomes, irrespective of surgical skill. He reinforced the importance of restraint in surgical decision-making, particularly in advanced malignancies. This principle supports multidisciplinary care, where surgical intervention is integrated with systemic therapies to optimize outcomes. However, decision-making within multidisciplinary teams (MDTs) is complex and can be variable. To add confusion, many patients continue to regard surgery as the best option, even when evidence suggests limited benefit.2 Even within an MDT setting, it is not always clear why and who makes the final decision to pursue surgery. While standard surgical approaches such as sub-segmental or anatomical liver resections, and both proximal and distal pancreatectomy have become safer compared with the past and are well established for conditions such as localized carcinomas, unifocal NETs, and dysplastic lesions, the issues raised in this perspective pertain to radical HPB resections involving either major vascular reconstructions, multi-visceral resections, or extended lymphadenectomy, where the oncological benefit is uncertain despite the increased surgical risk. Radical surgery is sometimes advocated for the potential palliative benefits in advanced HPB cancers; however, it is important to weigh these against the risks of complications, prolonged recovery, and possible functional decline, especially when modern palliative care offers effective symptom management with fewer risks. Ensuring that treatment decisions are guided by robust MDT discussions and shared decision-making can help prevent overtreatment, allowing patients to make informed choices that prioritize quality of life and align with their personal values. Because many MDT meetings are composed primarily of interventional specialists, there would be value in integrating palliative care physicians into these discussions or alternatively seeking a dedicated high-risk clinic consultation (including an anaesthetic perspective) to provide more balanced guidance.3 The ability to identify when the proposed operation might be futile for the patient is now also possible with AI using large clinical datasets.4 A broader input ensures that patients fully understand both the surgical and non-surgical options, leading to a more unbiased assessment of the true risks and benefits before proceeding with radical interventions. The debate over radical resections centres on the increased risk to patients and inconsistent outcomes, often driven by individual surgeon preferences rather than robust data.5, 6 A good example of a novel surgical procedure being implemented without enough prior evaluation of the efficacy and safety profile is the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS). Initially celebrated for improving resectability rates compared to two-stage hepatectomy, ALPPS was subsequently found to be associated with significant complications, including an 8.3% mortality rate in a Scandinavian multicentre randomized controlled trial.7 This illustrates the need for thorough validation before adopting such techniques and underscores concerns about informed patient consent. Radical surgical approaches extend beyond patient risk – they also have major financial and resource implications. Prolonged hospital stays, increased resource utilization, and higher readmission rates place a strain on hospital budgets and staffing. While some patients achieve survival or palliation benefits, many others experience significant complications or marginal gains. Cost-benefit analyses should be incorporated into surgical evaluations, with a focus on both the economic impact and workforce sustainability. Arguably, this should also extend to another expensive component of cancer care – pharmaceutical costs. Recent NHS data highlights the opportunity cost with population health losses elsewhere in the system due to the high cost and limited effectiveness of certain cancer drugs.8 Although cost considerations are important, economic factors alone should not justify radical surgery when the likelihood of meaningful benefit is low; instead, treatment decisions should be based on robust evidence, objective surgical outcomes data, and open discussions that realistically assess the potential for cure and quality of life impact. While HPB cancers have traditionally been considered chemo-resistant, advances in molecular profiling, targeted therapies, and immunotherapy have redefined treatment strategies, enabling better patient selection and improving systemic therapy efficacy; as a result, upfront radical surgery, particularly for advanced tumours, is no longer always appropriate. Instead, treatment decisions should be guided by tumour biology, likely response to systemic therapy, and multidisciplinary evaluation. For example, FOLFIRINOX and gemcitabine-nab-paclitaxel (Abraxane) have improved resectability rates in borderline resectable pancreatic cancer. However, in the broader HPB cancer context, the role of neoadjuvant therapies is still unclear, highlighting the need for caution when combining novel systemic treatments with radical approaches.9 Personalized medicine promises more precise treatment through molecular diagnostics and genetic profiling, and this may identify those who would benefit most from radical surgery. However, as of 2025, the implementation of this is limited due to cost, infrastructure, and technical barriers.10 Another major issue in HPB cancer surgery is the lack of consistent protocols for determining resectability, leading to variations in patient management.11 Recent findings, such as those by Badgery et al., reveal significant interobserver variability among surgeons and radiologists when assessing borderline resectable pancreatic cancer, even when reviewing the same imaging data.12 A centralized approach to preoperative assessment, including central registries and quality-control frameworks, could track radical and neoadjuvant interventions, providing real-time evaluations to align clinical and research efforts with evidence-based practice. While some patients with aggressive malignancies such as glioblastoma (GBM) may be offered cytoreductive operations with an inevitable R1 margin, in contrast, HPB cancer resections are only beneficial when an R0 margin is achieved, as R1 or R2 margins are consistently associated with poor survival and minimal palliative gain. Therefore, decision-making in HPB cancer should be guided by a realistic likelihood of achieving R0 and the potential benefit over non-surgical alternatives. Unquestionably, there is a need to address the variability in radical surgical decision-making and outcomes in Australia and New Zealand.5 A good start might be to establish a prospective, compulsory database tracking all decision making and outcomes after radical resections. Ideally, this would also include outcomes of those who were not offered resection. The Australian & Aotearoa New Zealand, Hepatic, Pancreatic & Biliary Association (AANZHPBA) is well placed to commence this process by first defining 'standard' versus 'radical' operations and then developing evidence-based guidelines for HPB cancers. Subsequently, a robust registry could be established to improve clinical accountability and support healthcare systems in managing radical cancer operations. Drawing on the model of the Australia and New Zealand Liver and Intestinal Transplant Registry (ANZLITR) – which has demonstrated excellent outcomes, even for cancer patients – such a registry could justify the cost by enabling evidence-based decision-making.13 However, unlike liver transplantation, which benefits from a nationally funded program, liver resections occur at a far greater volume and lack centralized funding support. For such an initiative to succeed, participation would need to be mandatory across institutions and there would have to be collaboration between surgical and non-surgical medical communities, healthcare funders, and policymakers. Adopting a governance and funding model like the liver transplantation program could ensure the feasibility and sustainability of a national registry, allowing for improved standardization and data-driven insights. Given that the transformation of the management of cancers such as melanoma, GIST, and breast cancer has been driven primarily by advances in molecular research rather than increasingly radical surgical techniques, there is also a need for greater engagement of HPB surgeons in translational science and biomarker-driven treatment approaches. Establishing a national registry that, ideally, would also be linked to a tumour bank for non-standard HPB resections which would facilitate real-time evaluation of outcomes, ensuring that surgical innovation is aligned with evidence-based practice and multidisciplinary collaboration. Radical resections in HPB cancers highlight the tension between surgical innovation and evidence-based care. However, decision-making should be guided by tumor biology and validated evidence. The principles of surgical oncology remain relevant today, reminding clinicians to temper technical ambition with scientific rigor. Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians.

Fear avoidance behaviour is associated with slow recovery from mild traumatic brain injury (mTBI). This study is a preliminary evaluation of graded exposure therapy (GET), which directly targets fear avoidance behaviour, for reducing post-concussion symptoms (PCS) and disability following mTBI. In a historical comparison design, we compared two groups from independent randomized trials. The GET + UC group (N = 34) received GET (delivered over 16 videoconference sessions) in addition to usual care (UC). The historical comparison group (N = 71) received UC only. PCS severity (Rivermead Post Concussion Symptoms Questionnaire; RPQ) and disability (World Health Organization Disability Assessment Schedule; WHODAS 2.0 12-item) were measured at clinic intake (M = 2.7, SD = 1.1 months after injury) and again at M = 4.9 (SD = 1.1) months after injury. Between-group differences were estimated using linear mixed effects regression, with a sensitivity analysis controlling for injury-to-assessment intervals. The estimated average change on the RPQ was -14.3 in the GET + UC group and -5.3 in the UC group. The estimated average change on the WHODAS was -5.3 in the GET + UC group and -3.2 in the UC group. Between-group differences post-treatment were -5.3 on the RPQ and -1.5 on the WHODAS. Treatment effects were larger in sensitivity analyses. Findings suggest that a randomized controlled trial is warranted.