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Introduction This protocol outlines a mixed methods study evaluating a new Digital Coordination Centre (DCC) at the Royal Melbourne Hospital (RMH), Melbourne, Australia. While coordination centres show potential for impact, evidence on effective implementation in the Australian context remains scarce. This study aims to address this gap.Methods and analysis The evaluation involves a two-stage approach: a process evaluation to clarify DCC design and identify implementation factors, and an initial outcome evaluation to assess short and medium term outcomes. A developmental approach will support continuous improvement, and implementation science theories applied to unpack change processes. Data sources will include interviews, project documentation and observations, with qualitative and quantitative analyses targeting metrics like emergency department boarding and length of stay.Ethics and dissemination This study has been approved by the RMH Human Research Ethics Committee (QA2023089). Findings will be shared through peer-reviewed publications and conference presentations.

Pancreatic neuroendocrine tumors (pan-NETs) represent a highly heterogeneous and complex pathology, with therapeutic management and prognosis influenced by several biological and clinical characteristics. Chemotherapy, including regimens based on capecitabine and temozolomide (CAPTEM) or the combination of streptozotocin and 5-fluorouracil (STZ-5FU), is indicated for rapidly growing, symptomatic, or high-burden disease requiring swift cytoreduction. Historical studies provide scientific evidence for the STZ-5FU regimen, often retrospective and frequently analyzing small series. Despite these limitations, the efficacy of this treatment is well-established, and it is included in all guidelines as a therapeutic option. This systematic review aims to gather scientific evidence on using STZ-based chemotherapy to assess its real impact in managing well-differentiated metastatic or unresectable pan-NETs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Kirsten rat sarcoma viral oncogene homolog (KRAS) somatic mutations occur in 30% to 40% of patients with colorectal cancer (CRC). These were thought to equally affect prognosis and resistance to anti-epidermal growth factor receptor agents; however, recent data show the activity of KRAS-G12C and pan-RAS inhibitors. The effects of uncommon KRAS (uKRAS) variants are largely unexplored. The distribution and pathogenicity of uKRAS mutations and their relationship with patients' clinicopathologic features were assessed. A total of 2427 CRCs were profiled for KRAS using next-generation sequencing (NGS). The study and control groups included patients with uKRAS (<1% frequency in CRC data sets on cBioPortal) and canonical KRAS mutations, respectively. In silico protein structure modifications and prediction analyses were performed by using PyMOL, trRosetta, and PolyPhen-2. uKRAS mutations affected 35 cases (1.5%), with G13C (28.6%), G12R (20%), and V14I (8.6%) being most common. Missense mutations (D33E, G12W, G12F, Q22H, Q61L, and L19F) occurred in nine cases (25.7%). Duplications (G10dup and L52&#95;G60dup) affected two cases. Pathogenicity analyses showed that G12W, Q22R, L56V, and A130I mutations are probably damaging, with scores between 0.928 and 1.000. No differences were seen in clinicopathologic features. uKRAS mutants had lower event-free survival but no difference in overall survival compared with controls. Although these data are hypothesis generating and need further confirmation, they highlight the importance of NGS-based profiling to identify CRC patients with uKRAS mutations as candidates for personalized therapy., (Copyright © 2025 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: In the last years, a dramatic increase in colorectal cancer (CRC) diagnoses in early-onset (EO) patients has been observed. The prognosis of EO-CRC compared to late-onset (LO) patients is still unclear. This meta-analysis aims to clarify whether there is any difference in the prognosis between the two groups., Methods: A systematic review was conducted on EMBASE-Medline, Pubmed and Cochrane Library in March 2024 to identify studies comparing overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR) and distant recurrence (DR) risk outcomes between EO-CRC (<50 years old) and LO-CRC (>50 years old) with at least 50 patients per group and one year of follow-up. The risk of bias was assessed with the ROBINS-E tool. Data from stage prevalence and survival were extracted and meta-analysed. Meta-regression was used to identify impacting effect modifiers. The PROSPERO registration number was CRD42024573264., Results: Twenty-six studies were identified; 1,062,037 patients (13.4% EO-CRC and 86.6% LO-CRC) were included in the stage prevalence and 567,689 in the prognostic meta-analysis. Overall, 60% of the EO-CRC and 49% of the LO-CRC were diagnosed with an advanced stage (III-IV) of disease (RR 1.26, 95%CI 1.19-1.35, I 2 =87%). EO-CRC had a better OS than LO-CRC (HR 0.89, 95%CI 0.81-0.99, I 2 =89%) but equal CSS (HR 0.94, 95%CI 0.83-1.06, I 2 =82%), DFS (HR 1.05 95%CI 0.94-1.16, I 2 =76%), LR (HR 1.41, 95%CI 0.62-3.18, I 2 =49%) and DR (HR 1.51, 95%CI 0.79-2.89) risk. Meta-regression analysis identified a worse DFS in the EO-CRC rectal cancer subgroup (HR 1.14, 95%CI 1.00-1.30, I 2 =0%)., Conclusions: Despite the high heterogeneity of existing studies, EO-CRC patients are diagnosed with significantly more advanced stages than LO-CRC, although this is not reflected in any difference in cancer-related survival. There is an urgent need for increased vigilance in the early detection of CRC in young patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Davide Ciardiello receives travel support from Sanofi, MBS, and Merck KgA; the other authors do not have any conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background : Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with unique biological characteristics and complications, including thromboembolism. This systematic review evaluates the incidence, types, and clinical outcomes of venous thromboembolic events (VTEs) in NEN patients. Methods : A systematic search of PubMed, Scopus, and Embase was conducted to identify studies on TEs in NENs. Eligible studies included case reports, case series, and retrospective cohort studies reporting VTEs, including deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT). Data were extracted on tumor site, functionality, differentiation grade, and VTE type. Results : In total, 33 studies were included, comprising 26 case reports, 2 case series, and 5 retrospective cohort studies. VTE prevalence ranged from 7.5% to 33% across studies. The most common VTEs were DVT, PE, and portal vein thrombosis (PVT). A meta-analysis revealed a pooled VTE prevalence of 11.1% (95% CI: 9.07-13.53%). Pancreatic NENs exhibited the highest thrombotic burden, particularly in poorly differentiated and advanced-stage tumors. Functioning tumors, including glucagonomas and ACTH-secreting NENs, were strongly associated with VTEs, potentially related to their systemic effects on coagulation and inflammation. Conclusions : Venous thromboembolism is a significant complication in NEN patients, especially in advanced or poorly differentiated tumors. Early detection and targeted management are critical for improving outcomes. Further investigations are required to clarify the mechanisms underlying thromboembolism in NENs and to develop optimized prophylactic and therapeutic strategies tailored to this patient population.

Purpose: This paper outlines the consensus of the Italian Association for Neuroendocrine Tumors(Itanet), the Italian Association of Nuclear Medicine (AIMN), the Italian Society of Endocrinology (SIE), and the Italian Association of Medical Oncology (AIOM) on treating neuroendocrine neoplasms (NENs)with radioligand therapy (RLT)., Methods: A list of 10 questions regarding using RLT ingastroenteropancreatic neuroendocrine tumors (GEP-NETs) was addressed after a careful review of theavailable literature. compiling information from the MEDLINE database, augmented with expert opinionsand recommendations, aligns with the latest scientific research and the author's extensive knowledge.The recommendations are evaluated using the GRADE system, showcasing the level of evidence andthe strength of the recommendations., Results and Conclusions: Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines., Competing Interests: Declarations. Conflict of interest: MA received honoraria as consultants from AAA, Novartis and Recordati outside the submitted work, CMG received honoraria as consultants from Novartis and ITM outside the submitted work, MC received honoraria as consultants from AAA, Novartis, Advanz, Harpoon Therapeutics, Merck, Harbour Biomedical outside the submitted work, AF received honoraria as support for research project and scientific organization from Novartis and Ipsen, NF received honoraria as consultants and speakers from Novartis and ITM outside the submitted work, FS received honoraria as consultants and speakers from AAA, outside the submitted work, MM received honoraria as consultants and speakers from AAA, outside the submitted work. The other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this manuscript., (© 2024. The Author(s).)