Belinda Lee

Introduction: The prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor with 2-year recurrence rates around 80% despite curative-intent surgery. This study evaluated factors associated with early recurrence in a contemporary, multi-center, Australasian population. A better understanding of patients at risk of early recurrence (ER) could improve selection of operative candidates. Methods: De-identified data were extracted from 23 hospitals participating in the PURPLE pancreatic cancer registry between 2016 and 2024. Clinicopathological features, treatment, recurrence patterns, and survival were examined. ER was defined as cancer recurrence within 12 months of surgery. Results: Of 3041 patients identified, 539 completed curative intent surgery. At a median follow-up of 21.8 months, 74% of resected cases had recurred. The median recurrence free survival was 14.3 months. ER occurred in 41% of patients and was associated with advanced age ( P = 0.04), worse performance status ( P < 0.01), T3–T4 stage ( P = 0.01), CA19-9 > 300 U/ml ( P < 0.01), involvement of more than two lymph nodes ( P < 0.01), lymphovascular invasion ( P = 0.01), and no neoadjuvant and/or adjuvant treatment ( P < 0.01). There was a significant association between the primary tumor location and recurrence site ( P = 0.046). The median OS of those with isolated lung (31.4 months) and locoregional (29.2 months) recurrences was longer than those with liver (21.3 months) or peritoneal (20.7 months) recurrences ( P = 0.01). The use of neoadjuvant and adjuvant therapy was associated with lower ER rates ( P < 0.01). Conclusion: A high proportion of resected PDAC patients experienced ER. Multiple pathological factors can predict ER. Primary tumor location was associated with site of recurrence. Neoadjuvant and adjuvant therapy significantly reduced ER and increased OS.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality with poor survival outcomes. Resection is the sole definitive management; however, most PDACs are diagnosed with unresectable disease including metastatic, locally advanced (LAPC) or borderline resectable (BRPC). Recently, neoadjuvant therapy has demonstrated potential in downstaging these tumours for resection. This literature review explores current and novel approaches in the management of BRPC and LAPC. Methods: A systematic search of Medline, Embase, Cochrane Central and Emcare databases was conducted on 7 April 2025. Inclusion criteria were primary articles that explored current and novel therapies that led to downstaging of BRPC and LAPC to resection, as well as resection outcomes and oncological outcomes associated with this. Articles that explored other pancreatic cancer subtypes or either resectable or metastatic disease were excluded. All meta-analyses were performed using a random-effects model based on the inverse variance method. Results: A total of 88 studies involving 8585 patients were included in the review, predominately from retrospective studies (57%, n = 50). Neoadjuvant regimens incorporating chemotherapy or radiotherapy, whether sequential or concurrent, demonstrated the highest proportions of R0 resections with N0 status. Overall, most modalities showed evidence of survival benefit following resection compared to non-operative management, with pooled differences demonstrated for chemotherapy alone (HR 0.33, 95% CI 0.25–0.44) and sequential chemotherapy and radiotherapy (HR 0.49, 95% CI 0.25–0.95). However, no significant differences between these modalities were demonstrated. Other modality-specific conclusions regarding survival benefit could not be elucidated. Conclusions: The rising incidence and global mortality from PDAC underscore the significance of identifying approaches to optimise the management of BRPC and LAPC. This review emphasises the importance of neoadjuvant therapy, both current and novel with surgical resection, which may warrant further investigation in future clinical trials. However, it is important to acknowledge the clinical heterogeneity of current data, which may introduce bias. Nevertheless, these findings can help to inform guidelines on the management of BRPC and LAPC.

Background: Pancreatic cancer is often diagnosed at an advanced stage with poor survival. Risk assessment tools have been developed to aid early diagnosis of pancreatic cancer in primary care settings (QCancer ^® , electronic Risk Assessment Tool [eRAT], and the Queensland Institute of Medical Research [QIMR] Berghofer Pancreatic Cancer Decision Support Tool [QPaC Tool]) but have not been validated in the Australian setting. Aim: To estimate and compare the performance of these tools for identifying patients with undiagnosed pancreatic cancer using Australian primary care data. Design and setting: A cohort study was conducted using linked primary care and cancer registry data from Victoria, Australia. Method: Patients presenting to primary care with signs and/or symptoms included in the tools (recorded in the primary care ‘reason for encounter’) were included. Diagnostic accuracy statistics for each tool (and their individual signs and symptoms) were compared. Results: Patients with pancreatic cancer were more likely ( P ® was 0.8% (95% CI = 0.54 to 1.15). Conclusion: When applied to Australian primary care data, none of the tools were strongly predictive of pancreatic cancer. New diagnostic models incorporating additional data could potentially improve their predictive performance.

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.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterised by late diagnosis and poor prognosis. Despite advancements, current diagnostic and prognostic strategies remain limited. Liquid biopsy techniques, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), circulating tumour exosomes, and proteomics, offer potential solutions to improve PDAC diagnosis, prognostication, and management. A systematic search of Ovid MEDLINE identified studies published between 2019 and 2024, focusing on liquid biopsy biomarkers for PDAC. A total of 49 articles were included. ctDNA research shows some promise in diagnosing and prognosticating PDAC, especially through detecting mutant KRAS in minimal residual disease assays. CTC analyses had low sensitivity for early-stage PDAC and inconsistent prognostic results across subpopulations. Exosomal studies revealed diverse biomarkers with some diagnostic and prognostic potential. Proteomics, although relatively novel, has demonstrated superior accuracy in PDAC diagnosis, including early detection, and notable prognostic capacity. Proteomics combined with CA19-9 analysis has shown the most promising results to date. An update on multi-cancer early detection testing, given its significance for population screening, is also briefly discussed. Liquid biopsy techniques offer promising avenues for improving PDAC diagnosis, prognostication, and management. In particular, proteomics shows considerable potential, yet further research is needed to validate existing findings and comprehensively explore the proteome using an unbiased approach.

Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.