Patient-reported use of pancreatic enzyme replacement treatment (PERT) in pancreatic cancer in New Zealand and Australia: a cross-sectional survey study.

PURPOSE: This study investigated pancreatic enzyme replacement therapy (PERT) use in people diagnosed with pancreatic cancer in New Zealand (NZ) and Australia (AU). METHODS: A cross-sectional survey study was conducted using a mixed-media campaign to recruit people with pancreatic cancer and collect information about current PERT use. The questionnaire gathered data on participant demographics, awareness of PERT, prescribing practices and efficacy of enzyme replacement. RESULTS: Over 300 people with pancreatic cancer were recruited, 135 from New Zealand and 199 from Australia. Every region, state and territory was represented except for the West Coast (NZ) and the Northern Territory (AU), the lowest populated areas in both countries. In New Zealand, 60% of participants had heard about PERT, compared to 69.3% in Australia. Dosing regimens were inconsistent in both countries, with 18% and 27% of participants being prescribed PERT considered best practice in New Zealand and Australia, respectively. Before PERT commencement, 70% of participants experienced symptoms of malabsorption, with all symptoms improving after therapy was established. The majority of participants were compliant with their medication. CONCLUSION: PERT use in pancreatic cancer in New Zealand and Australia was highly variable and not compliant with international guidelines in which PERT is recommended as standard therapy. Enzyme replacement is effective for improving the symptoms of malabsorption in patients with pancreatic cancer. Clinician education may be needed to help improve the use of PERT in people with pancreatic cancer.

Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Recruitment of participants with pancreatic cancer to a mixed media study for optimal recruitment in an Australasian survey of pancreatic enzyme replacement.

BACKGROUND: Pancreatic cancer is relatively rare and aggressive, with digestion and malabsorption issues often leading to significant weight loss. Recruitment of people with this malignancy into studies can be challenging, and innovative methods need to be explored to improve recruitment rates. AIM: To describe a mixed media methodology and the outcomes used to recruit patients to participate in a binational survey. METHODS: The details of the mixed media method used to identify and recruit people with pancreatic cancer are described. This method was used to investigate pancreatic enzyme replacement therapy use in people with pancreatic cancer across Australia and Aotearoa New Zealand. RESULTS: The mixed media approach was successful in reaching 334 participants from a range of ethnicities and regions. Results showed that social media platforms were notably more efficient and cost-effective than radio and newspaper but required additional expertise, including graphic design and media strategy knowledge. CONCLUSIONS: Social media is an effective and efficient method of recruiting people with pancreatic cancer to a national survey. Studies using media to recruit patients may need to include team members with a range of skills.

Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.

BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

Impact of first-line FOLFIRINOX versus Gemcitabine/Nab-Paclitaxel chemotherapy on survival in advanced pancreatic cancer: Evidence from the prospective international multicentre PURPLE pancreatic cancer registry.

BACKGROUND: First-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. OBJECTIVE: To compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. METHODS: A retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. FINDINGS: From 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). CONCLUSION: There was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC.

Glycolipid-peptide conjugate vaccines elicit CD8+ T-cell responses and prevent breast cancer metastasis.

Objectives: Metastasis is the principal cause of breast cancer mortality. Vaccines targeting breast cancer antigens have yet to demonstrate clinical efficacy, and there remains an unmet need for safe and effective treatment to reduce the risk of metastasis, particularly for people with triple-negative breast cancer (TNBC). Certain glycolipids can act as vaccine adjuvants by specifically stimulating natural killer T (NKT) cells to provide a universal form of T-cell help. Methods: We designed and made a series of conjugate vaccines comprising a prodrug of the NKT cell-activating glycolipid α-galactosylceramide covalently linked to tumor-expressed peptides, and assessed these using E0771- and 4T1-based breast cancer models in vivo. We employed peptides from the model antigen ovalbumin and from clinically relevant breast cancer antigens HER2 and NY-ESO-1. Results: Glycolipid-peptide conjugate vaccines that activate NKT cells led to antigen-presenting cell activation, induced inflammatory cytokines, and, compared with peptide alone or admixed peptide and α-galactosylceramide, specifically enhanced CD8+ T-cell responses against tumor-associated peptides. Primary tumor growth was delayed by vaccination in all tumor models. Using 4T1-based cell lines expressing HER2 or NY-ESO-1, a single administration of the relevant conjugate vaccine prevented tumor colonisation of the lung following intravenous inoculation of tumor cells or spontaneous metastasis from breast, respectively. Conclusion: Glycolipid-peptide conjugate vaccines that activate NKT cells prevent lung metastasis in breast cancer models and warrant investigation as adjuvant therapies for high-risk breast cancer.

Postpartum opportunistic advice in primary care for women who have had gestational diabetes: a qualitative study of health care professionals' views.

BACKGROUND: Women who have had gestational diabetes during pregnancy are at very high risk of developing type 2 diabetes later in life, but their understanding of the risks is often limited. In this study we explored the views of health care professionals regarding offering brief opportunistic advice to women after their pregnancy, during unrelated consultations in primary care, relating to reducing diabetes risk. METHODS: The study took place in three Health Boards in Scotland. We conducted semi-structured one-to-one interviews (either face-to-face or telephone) with two health visitors, three practice nurses, two GPs, two diabetes consultants and two obstetricians. A focus group with five health visitors was also held. A topic guide was followed, covering the feasibility and acceptability of delivering brief opportunistic advice during a routine consultation, the optimal way to identify and recall women with previous gestational diabetes, and the possible content and timing of any such intervention. A thematic approach was used to analyse the qualitative data generated. RESULTS: The interviews/discussion lasted from 15 to 51 min. There was widespread support from all participants for offering opportunistic advice, and general consensus that health visitors would be best placed to do this as part of the Universal Health Visiting Pathway in Scotland. Thematic analysis generated three significant points of discussion: implications for training of health visitors, the need for a systematic approach to identifying women with gestational diabetes, and the optimal timing of delivery. Despite an already demanding schedule of providing advice and education to women, health visitors were confident that they could offer educational advice, provided that they received appropriate training to do so. However, there would need to be a watertight system for identifying women in their care who had had gestational diabetes. In terms of timing, later visits around 6-8 months after delivery were considered most suitable. CONCLUSIONS: There is support from health care professionals, and most pertinently from health visitors, that the frequency of routine visits with women during the Universal Health Visiting Pathway programme in Scotland provides potential opportunities for education around future diabetes risk to women who have had gestational diabetes.