Prospective Observational Study of Prevalence, Assessment and Treatment of Pancreatic Exocrine Insufficiency in Patients with Inoperable Pancreatic Malignancy (PANcreatic Cancer Dietary Assessment-PanDA).

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.

Vitamin D Receptor Expression Is Significantly Decreased in Bone Metastases Compared to Matched Primary Breast Cancer Tumours.

There is ample evidence today that vitamin D signalling via the vitamin D receptor (VDR) plays a pivotal role in cancer growth and metastasis. The aim of this study was to analyse VDR expression of primary breast cancer and corresponding bone metastases tissue samples. Collectively, 15 sample pairs and 11 samples of patients that did not develop metastases were analysed histologically for VDR expression (n = 41). Overall, VDR expression was significantly lower in bone metastases compared to primary tumour samples (p < .0001). Downregulation of the VDR in breast cancer cells may define a critical turning point in oncogenesis that accelerates cancer cell dissemination and metastases.

Pancreatic Enzyme Replacement Therapy for Patients Diagnosed With Pancreaticobiliary Cancer: Validation of an Algorithm for Dose Escalation and Management.

OBJECTIVE: An algorithm was designed aiming to provide consistency of pancreatic enzyme replacement therapy (PERT) dosing/titration across healthcare professionals in pancreaticobiliary cancers (PBCs). This prospective observational study aimed to validate this algorithm. METHODS: Consecutive patients with inoperable or postoperative PBC with pancreatic exocrine insufficiency (PEI) symptoms, not taking PERT, or taking below the algorithm "starting dose," were eligible. A dietitian or clinical nurse specialist reviewed patients for up to 3 weeks, titrating PERT as per the algorithm. Feasibility of algorithm deliverability was assessed by the percentage of patients with successful completion (primary objective). RESULTS: Twenty-five patients were eligible (N = 25): at baseline, 22 took PERT (100% on suboptimal doses, 54.5% taking incorrectly) and 3 initiated PERT because of PEI symptoms. Algorithm completion (20 of 25, 80%) confirming deliverability by dietitians (11 of 12, 92%) and clinical nurse specialists (9 of 13, 69%). Symptom resolution occurred in 8 of 19 (42%), 3 of 7 (43%), and 1 of 3 (33%) patients at first, second, and third reviews, respectively; advice compliance was between 63% and 86%. CONCLUSIONS: This algorithm provides a structured method to titrate PERT. At diagnosis, all patients with PBC should be assessed for PEI and adequate PERT initiated. Regular reviews are required for timely symptom resolution and adequate escalation, facilitating differential diagnosis if refractory symptoms exist.

Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol.

INTRODUCTION: Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy. METHODS AND ANALYSIS: This prospective observational study will be carried out in patients with pancreatic malignancy (including adenocarcinoma and neuroendocrine neoplasms). Consecutive patients with inoperable pancreatic malignancy referred for consideration of first-line chemotherapy will be considered for eligibility. The study comprises three cohorts: demographic cohort (primary objective to prospectively investigate the prevalence of PEI in patients with inoperable pancreatic malignancy); sample size 50, diagnostic cohort (primary objective to design and evaluate an optimal diagnostic panel to detect PEI in patients with inoperable pancreatic malignancy); sample size 25 and follow-up cohort (primary objective to prospectively evaluate the proposed PEI diagnostic panel in a cohort of patients with inoperable pancreatic malignancy); sample size 50. The following is a summary of the protocol and methodology. ETHICS AND DISSEMINATION: Full ethical approval has been granted by the North West Greater Manchester East Research and Ethics Committee, reference: 17/NW/0597. This manuscript reflects the latest protocol V.8 approved 21 April 2020. Findings will be disseminated by presentation at national/international conferences, publication in peer-review journals and distribution via patient advocate groups. TRIAL REGISTRATION NUMBER: 194255, NCT0361643.

Impact on prognosis of early weight loss during palliative chemotherapy in patients diagnosed with advanced pancreatic cancer.

AIM: Weight loss at diagnosis is common in pancreatic cancer (PC) and can adversely affect overall survival (OS). Little is known about the impact of weight loss occurring during palliative treatment. This study aimed to investigate if early weight loss during chemotherapy for inoperable PC affects OS. METHOD: This retrospective study included patients newly-diagnosed with inoperable PC. Consecutive patients initiating first-line palliative chemotherapy between Jan'15 - Jan'19 with data on percentage weight loss at week 4 of treatment (%WLWeek4) were eligible. %WLWeek4 was dichotomised using 5% cut-off. OS was measured from chemotherapy initiation. Survival analysis was performed using Cox regression. RESULTS: Eligible patients (n = 255); 59.2% with head/neck PC; 52.6% metastatic; received triplet (32.2%), doublet (42.7%) or single-agent (25.1%) palliative chemotherapy. Median %WLWeek4 was -2.05% (95% confidence interval (CI) -2.58 to -1.56); %WLWeek4 was ≥5% in 23.1% patients. Patients on triplet chemotherapy were more likely to develop %WLWeek4 of ≥5% [35.4% (triplet) vs. 19.3% (doublet) vs 14.1% (monotherapy); multivariable Odds Ratio (triplet vs monotherapy) =3.25; 95% CI 1.40-7.56; p-value 0.006]. Median OS was 9.7 months (95% CI 8.54-10.41). Multivariable Cox regression demonstrated shorter OS if %WLWeek4 ≥5% (median OS 7.4 months (95% CI 6.27-10.01) vs. 9.9 months (95% CI 9.20-12.05); HR 2.37 (95% CI 1.64-3.42), P < 0.001); this was independent from other factors (stage, age, number of chemotherapy drugs, ECOG-PS), including response to therapy (supporting that %WLWeek4 impacted on OS regardless of response to therapy). CONCLUSION: In advanced PC treated with palliative chemotherapy, a %WLWeek4 ≥5% was more prevalent in patients undergoing triplet chemotherapy, and was associated with shorter OS, regardless of response/progression to therapy. Early identification and intervention of weight loss seems to be key to improve patient outcomes.

Early recognition of anorexia through patient-generated assessment predicts survival in patients with oesophagogastric cancer.

Cancer cachexia is common in patients with oesophagogastric cancer (OG) and is linked to overall survival (OS). One of the key components of cachexia is anorexia; it is not known whether anorexia impacts on OS and there is no method of routine screening in current practice. Diagnosis relies on patients describing the symptoms, clinicians diagnosing anorexia and acting upon it. Patients with oesophageal/gastroesophageal junction or gastric cancer were assessed using the Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). FAACT A/CS includes 12 questions validated previously to diagnose anorexia in patients with cancer. Of the 182 patients included, 69% scored ≤37/48 and were considered to be anorexic; FAACT A/CS was a better predictor of OS in metastatic patients than body mass index or weight loss in the six months prior to cancer diagnosis. The median OS of patients with FAACT A/CS scores of >37 was longer than patients with scores of ≤37 (19.3 months vs 6.7 months, Hazard Ratio [HR] 2.9, 95% Confidence Interval [CI] 1.4-6.0, p<0.0001). Patients with performance status (PS) 0-2 and FAACT A/CS >37 had substantially longer OS than those with PS 0-2 and FAACT A/CS ≤37 (18.7 months vs 7.9 months, HR 2.5 (95% CI 1.2-5.1, P<0.0001). The FAACT A/CS questionnaire allows clinicians to identify patients with anorexia who may benefit from early nutrition interventions. Importantly, this is the first study to show the association between anorexia and survival in patients with metastatic OG cancers. This will form the basis of future interventional studies to improve patient outcomes.