Victorian Comprehensive Cancer Centre

Penile cancer is a rare malignancy, with an Australian incidence of 0.6 in 100 000 men, with a wide range of clinical presentations, from localised, curable tumours to aggressive forms with high morbidity and mortality. Epidemiological data and management guidelines for penile cancer in Australia are limited. The Australian Penile Cancer Clinical Registry (APCCR) aims to address this gap through a centralised database studying local risk factors, treatment effectiveness, and outcomes. The APCCR is a national, multicentre, prospective clinical quality registry. The primary objective is to map demographic and tumour characteristics, human papillomavirus infection rates, long-term surgical and non-surgical (radiotherapy and chemotherapy) interventions in penile cancer. Secondary objectives include elucidating disparities and interdisciplinary gaps in care and identifying areas for further studies. The registry aims to capture adult men with penile cancer in, utilising retrospective data collection and a prospective cohort design. Retrospective data are extracted from existing medical records, and prospective data are collected at enrolled sites. The registry is built in Research Electronic Data Capture (REDCap) and hosted on BioGrid Australia servers, enabling standardised data collection. Registration with the Australian Register of Clinical Registries is pending approval. The pilot phase of the APCCR is currently operational, with ongoing site recruitment. Five sites in Victoria and New South Wales are currently enrolled in the registry. The APCCR Steering Committee determined reporting and data protocols to ensure accurate data collection. The dataset was developed to comprise relevant clinical metrics on penile cancer diagnosis, disease, intervention, and surveillance. The APCCR is a robust platform for furthering the understanding of penile cancer diagnostic and treatment practices in Australia, aiming to further research and clinical practice changes. This will drive further collaboration and improvements in outcomes for Australian men affected by penile cancer, particularly with ongoing national expansion and improved longitudinal data.

To critically appraise the Radius, Exophytic/endophytic, Nearness of tumor to collecting system or sinus, Anterior/posterior, Location relative to polar lines (R.E.N.A.L.), Preoperative Aspects and Dimensions Used for an Anatomical classification (PADUA), and Radius, Position, iNvasion of sinus (RPN) nephrometry systems with respect to their classification of tumor complexity for surgical planning in robot-assisted partial nephrectomy (RAPN) and to compare their statistical validity, methodological rigor, and predictive performance. A structured synthesis of published evidence identified large multicenter series, prospective cohorts, and meta-analyses from 2009 to 2025 that evaluated the predictive accuracy, methodological design, and clinical relevance of these systems. Key evaluation domains included statistical validation, anatomical parameter selection, and correlation with surgeon-perceived difficulty in RAPN. Both the R.E.N.A.L. and PADUA scores were developed using empirically selected parameters and have historically been validated based on their correlation with perioperative outcomes. However, evidence in the literature now shows that such correlations are inconsistent and often clinically irrelevant in RAPN. In contrast, the RPN score was developed using a statistically modeled approach, reflecting the real-world surgical difficulty of RAPN as perceived by experienced robotic surgeons. Current evidence does not support the continued use of R.E.N.A.L. and PADUA scores as validated tools in RAPN. The RPN score, with its statistically validated, anatomy-based methodology and alignment with surgical difficulty, represents a scientifically superior and clinically practical alternative for standardizing tumor complexity in RAPN.

IntroductionThe commercial determinants of health (CDoH) are a rapidly growing field of research and global health priority. Despite being disproportionately affected, Indigenous Peoples’ voices and perspectives are conspicuously absent from CDoH research and policy. This article outlines the protocol for Addressing Commercial Health determinants: Indigenous Empowerment and Voices for Equity (ACHIEVE), an Aboriginal and Torres Strait Islander-led project in Australia.Methods and analysisACHIEVE integrates four research streams, using a novel combination of methods. The first three streams will (i) conceptualise the CDoH using Indigenous yarning methodology, (ii) evaluate the effectiveness and cost-effectiveness of policies to reduce exposure to harmful marketing and (iii) assess the impacts of specific commercial entities on Aboriginal and Torres Strait Islander health using case studies. The final stream will consolidate findings from streams 1–3 and work with Aboriginal Community Controlled Health Organisations (ACCHOs) to co-create strategies for addressing the commercial determinants of Aboriginal and Torres Strait Islander health.Ethics and disseminationEthical approval for streams 1–3 has been granted by Deakin University Human Research Ethics Committee. ACHIEVE is guided by a governance model that prioritises Indigenous data sovereignty, community and ACCHO partnerships, capacity building and knowledge translation. Findings will be shared with participants, ACCHOs and policymakers to maximise research impact.

Pineal parenchymal tumors (PPTs) are uncommon in general and rare in the adult population. Currently, the optimal treatment for PPT of intermediate differentiation (PPTID) in older patients is unknown. Stereotactic radiosurgery (SRS) has been used as both primary and adjuvant therapy, with single or fractionated doses using Gamma Knife (Elekta, Stockholm, Sweden) or CyberKnife (Accuray Inc., Madison, WI). This article presents the case of a 77-year-old woman with a biopsy-confirmed PPTID. She was treated with single fraction VMAT (volumetric modulated arc therapy)-based SRS on a Varian TrueBeam Edge linac (Varian Medical Systems, Palo Alto, CA) using multiple non-coplanar arcs. Contouring and treatment planning were performed on contrast-enhanced MRI and CT images. Accurate patient set-up and immobilization were achieved with an open-faced thermoplastic mask, real-time motion management using an optical surface monitoring system, and kV CBCT prior to each arc. The patient has shown excellent response for tumor size with frequent follow-up up to 84 months, but 25 months later developed double-vision and headaches with MRI revealing decreasing tumor size but enhancement and FLAIR changes in the adjacent brain parenchyma suggestive of radiation necrosis. These changes stabilized as of 32 months of follow-up, and then started to decrease by 35 months.

BackgroundPost cholecystectomy pain is a common clinical problem. Investigation and management of patients with recurrent episodes of biliary pain and normal imaging is challenging. Low phospholipid associated cholelithiasis (LPAC) is a recently described syndrome that often presents with difficult to manage episodes of post cholecystectomy pain. Ursodeoxycholic acid (UDCA) treatment of LPAC is supported by animal studies and case series but has not been assessed in a randomised trial.MethodsThis protocol presents the design and rationale for an investigator-initiated, prospective, randomised, placebo-controlled, double-blind, Phase 3 crossover trial: Ursodeoxycholic acid in LPAC treating Recurrent Abdominal Pain (ULTRA Pain). The study population consists of 24 patients with difficult to manage post cholecystectomy pain diagnosed with LPAC with no or minimal changes on liver ultrasound imaging. Participants will be recruited through the gastroenterology clinic at Royal Melbourne Hospital and randomly assigned to receive UDCA 10 mg/kg daily for 1 year followed by a matched placebo, or vice versa, separated by an effective 6-week washout period. The primary endpoint is the number of patient reported episodes of biliary pain. Secondary outcomes include the number of episodes of biliary pain with associated transiently elevated liver function tests (LFTs), and episodes of biliary pain in those with the diagnosis of LPAC confirmed by ultrasound, the Recurrent Abdominal Pain Intensity and Disability (RAPID) score, and the score of several questionnaires measuring quality of life. An independent monitor has been appointed to oversee safety of participants. An intention-to-treat analysis will be performed in accordance with CONSORT guidelines. Regression methods appropriate to the type of primary or secondary outcome, such as linear regression for continuous outcome or Poisson or negative binomial regression if found to be skewed, or binary logistic regression for binary outcomes will be employed. Alpha or level of statistical significance will be set to p <0.05 and 95% confidence intervals will be reported throughout.DiscussionThis trial will provide level 1 evidence on the efficacy of UDCA in treating LPAC presenting with post cholecystectomy pain.Trial RegistrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000450819).

Abstract Despite advances in therapy, specific subtypes Acute Myeloid Leukaemia (AML) remains largely incurable. The first-in-class RNA Polymerase I (Pol I) inhibitor, CX-5461, has demonstrated promising activity in both haematological malignancies and solid tumours by selectively inhibiting ribosome biogenesis to induce nucleolar stress, a critical vulnerability in rapidly proliferating cancer cells. CX-5461 has undergone clinical trials for the treatment of both solid and haematological malignancies, and 2nd generation Pol I inhibitor PMR-116 has also entered clinical trials, underscoring the translational potential of drugs that target RNA Polymerase I. To enhance the therapeutic efficacy of Pol I inhibition and prevent the emergence of resistance, we conducted a cell line-based unbiased screen of FDA-approved drugs to identify compounds that might synergise with CX-5461. This screen revealed that the pan-CDK inhibitors Dinaciclib and Flavopiridol enhance nucleolar stress pathway (NSP) activation and are strong candidates for combinatorial therapy with CX-5461. Further analysis showed that the combination of CX-5461 and Dinaciclib acts synergistically across a genetically diverse panel of human AML cell lines. This synergy is dependent on an intact NSP, with both agents independently stabilising p53, but with distinct phenotypic outcomes: Dinaciclib induces rapid apoptosis, whereas CX-5461 primarily enforces cell cycle arrest. This functional complementarity results in efficient tumour cell clearance and likely accounts for the delayed onset of therapy resistance. Importantly, combination treatment with CX-5461 and Dinaciclib significantly improved survival in murine models of AML and reduced colony formation in primary human AML samples. Together these findings provide preclinical evidence for a novel combination treatment strategy that leverages nucleolar stress and cell cycle control to enhance treatment outcomes in AML, paving the way for clinical translation of Pol I-CDK co-targeting therapies.

Abstract Background Tumour genetic profiling has the potential to significantly improve cancer care by informing targeted treatments and improving patient outcomes. As use increases worldwide, greater attention should be paid to consumer experiences, need and priorities. This study is consumer-led and aims to inform an equitable and ethical roll out of future services by exploring consumer: 1) awareness of tumour genetic profiling, 2) experiences with tumour genetic profiling, and 3) priorities for improving access to and delivery of tumour genetic profiling within Victoria, Australia. Methods A consumer reference group was formed and supported by experienced researchers and professional staff of a comprehensive cancer centre alliance to develop and conduct the research study. A cross-sectional survey was conducted between January and May 2024, capturing demographic and disease characteristics, along with questions relating to each aim. Both quantitative and qualitative data were collected. Eligible participants were patients diagnosed with cancer whose treatment teams were based in Victoria, Australia, or caregivers of such patients. Results Of the 181 respondents (n = 36 carers, n = 145 patients), 23% (n = 44) reported that they (or the person they cared for) had undergone tumour genetic profiling. The majority reported a positive impact, including increased knowledge/understanding (n = 30, 68%) and personalised treatment options (n = 23, 52%), with very low decisional regret (mean: 3/100). However, 14% reported no understanding of the results at all, and confusion was reported as a drawback of testing. A higher level of shared decision making was associated with better understanding of results (p = 0.04). The primary barriers to uptake were lack of awareness (n = 88, 83%) and lack of perceived benefit from the treatment team (n = 19, 18%). Key strategies for improvement identified by participants included government-subsidised testing and improved patient and clinician education. Conclusions This study highlights gaps in consumer awareness and access to tumour genetic profiling, as well as the benefits of shared decision making. Overall, consumer-led insights emphasise the need for equitable funding, education, and systemic improvements. These findings can inform policies and practices aimed at delivering person-centred cancer care in Victoria and beyond. Future longitudinal research is needed to comprehensively explore these associations and track progress.

Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach. A systematic search was conducted in Medline OVID, Embase and Web of Science databases following PRISMA guidelines (CRD42022310127). Original research published in peer-reviewed journals between January 2017-Decmeber 2021 were selected. Eligible studies included patients with any cancer and evaluated any potential risk factor for any grade/type of irAE. Study design, sample size, and method for analysing association between irAE and risk factors were compared. A total of 293 eligible studies containing 305,879 patients receiving ICI reported irAE in 58,291 patients (19.1 %). There were 221 retrospective, 55 prospective studies, and 17 systematic reviews/meta-analyses. Eighteen studies evaluated the predictive validity of models. Proposed risk factors were grouped based on common themes and underlying aetiology: 1) patient, 2) laboratory, 3) medical history, 4) cancer-related, 5) clinical score, 6) medications, and 7) imaging features. Opposing associations were reported between advancing age and irAE risk. This systematic review provides a comprehensive overview of evidence on irAE risk factors across a large patient population. Studies were heterogeneous resulting from variations in design, sample size and analysis method, and lack generalisability due to statistically underpowered evidence. We propose an approach to categorise potential irAE risk factors to support ongoing collaborative research.