Tumour tissue as a source for molecular profiling and for in vivo models has limitations (e.g., difficult access, limited availability, single time point, potential heterogeneity between primary and metastatic sites). Conversely, liquid biopsies provide an easily accessible approach, enabling timely and longitudinal interrogation of the tumour molecular makeup, with increased ability to capture spatial and temporal intra-tumour heterogeneity compared to tumour tissue. Blood-borne biomarker assays (e.g., circulating tumour cells (CTCs), circulating free/tumour DNA (cf/ctDNA)) pose unique opportunities for aiding in the molecular characterisation and phenotypic subtyping of neuroendocrine neoplasms and will be discussed in this article.

Phase 3 trials have established standard first-line (1L) and 2L systemic therapy options for patients with advanced biliary cancer (ABC). However, a standard 3L treatment remains undefined. Clinical practice and outcomes for 3L systemic therapy in patients with ABC were therefore evaluated from three academic centres. Included patients were identified using institutional registries; demographics, staging, treatment history, and clinical outcomes were collected. Kaplan–Meier methods were used to assess progression-free survival (PFS) and overall survival (OS). Ninety-seven patients, treated between 2006 and 2022, were included; 61.9% had intrahepatic cholangiocarcinoma. At the time of analysis, there had been 91 deaths. Median PFS from initiating 3L palliative systemic therapy (mPFS3) was 3.1 months (95%CI 2.0–4.1), while mOS3 was 6.4 months (95%CI 5.5–7.3); mOS1 was 26.9 months (95%CI 23.6–30.2). Among patients with a therapy-targeted molecular aberration (10.3%; n = 10; all received in 3L), mOS3 was significantly improved versus all other included patients (12.5 vs. 5.9 months; p = 0.02). No differences in OS1 were demonstrated between anatomical subtypes. Fourth-line systemic therapy was received by 19.6% of patients (n = 19). This international multicentre analysis documents systemic therapy use in this select patient group, and provides a benchmark of outcomes for future trial design.

Introduction: Pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC) is well documented, but there is no consensus regarding optimal screening. Methods and analysis: Patients diagnosed with aPC referred for palliative therapy were prospectively recruited. A full dietetic assessment (including Mid-Upper Arm Circumference (MUAC), handgrip and stair-climb test), nutritional blood panel, faecal elastase (FE-1) and ¹³C-mixed triglyceride breath tests were performed. Primary objective: prevalence of dietitian-assessed PEI (demographic cohort (De-ch)); design (diagnostic cohort (Di-ch)) and validation (follow-up cohort (Fol-ch)) of a PEI screening tool. Logistic and Cox regressions were used for statistical analysis. Results: Between 1 July 2018 and 30 October 2020, 112 patients were recruited (50 (De-ch), 25 (Di-ch) and 37 (Fol-ch)). Prevalence of PEI (De-ch) was 64.0% (flatus (84.0%), weight loss (84.0%), abdominal discomfort (50.0%) and steatorrhea (48.0%)). The derived PEI screening panel (Di-ch) included FE-1 (normal/missing (0 points); low (1 point)) and MUAC (normal/missing (>percentile 25) (0 points); low (2 points)) and identified patients at high-risk (2–3 total points) of PEI [vs. low-medium risk (0–1 total points)]. When patients from the De-ch and Di-ch were analysed together, those classified by the screening panel as “high-risk” had shorter overall survival (multivariable Hazard Ratio (mHR) 1.86 (95% CI 1.03–3.36); p-value 0.040). The screening panel was tested in the Fol-ch; 78.4% patients classified as “high-risk”, of whom 89.6% had dietitian-confirmed PEI. The panel was feasible for use in clinical practice (64.8% patients completed all assessments), with high acceptability (87.5% would repeat it). Most patients (91.3%) recommended dietetic input for all patients with aPC. Conclusions: PEI is present in most patients with aPC; early dietetic input provides a holistic nutritional overview, including, but not limited to, PEI. This proposed screening panel may help to prioritise those at higher risk of PEI, requiring urgent dietitian input. Its prognostic role needs further validation.

Background: Neuroendocrine tumours (NETs) are a rare and heterogeneous group of neoplasms that mainly originate from the gastroenteropancreatic tract (GEP-NETs). The vast majority of NETs tend to overexpress somatostatin receptors (SSTRs), which can be targeted by somatostatin analogues (SSAs). ⁶⁸Gallium DOTA SSTR peptide positron emission tracer computed tomography (⁶⁸Ga PET-CT) has emerged as superior to other imaging modalities in identifying SSTRs. This study aimed to assess whether patients with GEP- NETs treated with SSAs have similar outcomes irrespective of tracer uptake intensity on ⁶⁸Ga PET-CT. Methods: Patient cases undergoing ⁶⁸Ga PET-CT imaging between November 2015 and September 2020 at The Christie NHS Foundation Trust, with diagnosis of histologically-confirmed advanced GEP-NETs receiving SSAs, were reviewed retrospectively. Kaplan-Meier and Cox regression were utilised to analyse progression free (PFS) and overall survival (OS). Results: Of 644 patients imaged with ⁶⁸Ga PET-CT, 132 met inclusion criteria. The median age of patients was 62 years; ECOG performance status 0: 62 (47%), 1: 56 (42%), 2: 13 (10%); primary sites: ileum: 54 (41%), pancreas: 26 (20%), cancer of unknown primary: 20 (15%), Grade (G)1: 63 (47%), G2: 56 (42%), G3: 3 (2%), unknown: 11 (8%); ⁶⁸Ga PET-CT tracer uptake increased: 124 (94%), no increased tracer uptake: 8 (6%). 66 patients (50%) progressed, and 99 (74%) were alive at analysis. Median PFS on SSAs was 20.82 months (95% confidence interval (CI) 12.2–30.03) for patients with increased tracer uptake (n=63) and 8.26 months (95% CI 4.55-not available (NA)) for patients with no increased tracer uptake (n=3) (Hazard Ratio (HR): 4.19 (95% CI 1.238–14.28), P=0.022). Median OS from commencement of SSA was: 99.51 months (95% CI 95.96 – NA) for patients with increased tracer uptake and 47.67 months for patients with no increased tracer uptake (95% CI 13.41 – NA) (HR 2.93 (95% CI 1.011–8.49), P=0.048). Conclusions: ⁶⁸Ga PET-CT scans are an accurate tool for diagnosis and localisation of NETs. Median PFS and OS appears to be greater in patients receiving SSAs with increased uptake on the ⁶⁸Ga PET-CT. However, further evaluation in larger cohorts is needed to definitively assess clinical benefit of SSAs in the ⁶⁸Ga PET-CT negative cohort.