Treatment Of Exocrine Pancreatic Insufficiency Research Articles

Challenges of Managing Type 3c Diabetes in the Context of Pancreatic Resection, Cancer and Trauma.

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic or pancreoprivic diabetes, is a specific type of DM that often develops as a result of diseases affecting the exocrine pancreas, exhibiting an array of hormonal and metabolic characteristics. Several pancreatic exocrine diseases and surgical procedures may cause T3cDM. Diagnosing T3cDM remains difficult as the disease characteristics frequently overlap with clinical presentations of type 1 DM (T1DM) or type 2 DM (T2DM). Managing T3cDM is likewise challenging due to numerous confounding metabolic dysfunctions, including pancreatic endocrine and exocrine insufficiencies and poor nutritional status. Treatment of pancreatic exocrine insufficiency is of paramount importance when managing patients with T3cDM. This review aims to consolidate the latest information on surgical etiologies of T3cDM, focusing on partial pancreatic resections, total pancreatectomy, pancreatic cancer and trauma.

Nutritional status in advanced pancreatic cancer

Background. Exocrine pancreatic insufficiency (EPI) occurs in most patients with advanced pancreatic cancer (PC) and even more often when a tumor is localized in the head of the pancreas. However, insufficient attention is paid to the diagnosis of EPI and assessment of nutritional status, which negatively affects the results of treatment.
 Materials and methods. One hundred fifty eight patients with primary diagnosed locally advanced and metastatic PC were included in the retrospective study. We used the calculation of the odds ratio with 95% CI with an assessment of the p value using the Pearson ÷2 test to compare the incidence of clinical and laboratory parameters of nutritional status with values below the lower limit of normal (LLN) depending on the location of the tumor in the pancreas.
 Results. Fecal elastase test was performed in only 19 (12%) patients. In this group, the incidence of EPI was 73.6%. Pancreatic enzyme replacement therapy in the minimal sufficient dose was prescribed in 17.1% of the general cohort. The level of hemoglobin, erythrocytes and albumin below the LLN was found in patients with the tumor in the pancreatic head, respectively, 2.742 (95% CI 1.27–5.92), 3.788 (95% CI 1.554–9.232) and 9.767 (95% CI 1.255–76.027) times more often than in patients with cancer in the body-tail of the pancreas. In patients with the tumor in the pancreatic head, the lower levels of hemoglobin (median 125 g/l vs 132 g/l, respectively), erythrocytes (4.19 mil/μl vs 4.51 mil/μl), total protein (69.6 g/l vs 71.5 g/l), and albumin (40.1 g/l vs 42 g/l), as well as the values of nutritional indices: prognostic nutritional index, nutritional risk index, hemoglobin, albumin, lymphocyte and platelet ratio index, and prognostic immune nutritional index were observed.
 Conclusion. Diagnosis and treatment of EPI remains inadequately attended. The values of nutritional status parameters in patients with PC in the head are lower than in patients with a tumor in the body-tail of the pancreas, which reflects the contribution of EPI.

Exocrine pancreatic insufficiency and fat malabsorption related to pancreatectomy and other gastrointestinal surgery: A narrative review.

Surgical resection is the mainstay of treatment for patients with tumors of the pancreas. There are a number of well-recognized complications that account for the significant morbidity associated with the operation, including exocrine pancreatic insufficiency (EPI). Patients with pancreatic cancer commonly have evidence of EPI prior to surgery, and this is exacerbated by an operation, the extent of the insult being dependent on the indication for surgery and the operation performed. There are accumulating data to demonstrate that treatment of EPI with pancreatic enzyme replacement (PERT) enhances clinical outcomes after surgery by reducing critical complications; this in turn may enhance oncological outcomes. Data would indicate that quality of life (QoL) is also improved after surgery when enzymes are prescribed. To date, many surgeons and clinicians have not appreciated the need for PERT or the benefits it may bring to their patients; therefore, education of clinicians remains a significant opportunity. In turn, patient education about consumption of the correct dose of enzymes at the appropriate time is key to an optimal outcome. In addition, because of the complex nature of the regulation of pancreatic exocrine function, there is evidence to support the presence of EPI following operations performed on other gastrointestinal (GI) organs, including the esophagus, stomach, and small intestine. The aim of this review is to document the existing published evidence in relation to EPI and its treatment with PERT following GI surgery.

Fat malabsorption in pancreatic cancer: Pathophysiology and management.

Exocrine pancreatic insufficiency (EPI) is common in pancreatic ductal adenocarcinoma (PDAC) and may lead to significant nutrition compromise. In the setting of cancer cachexia and gastrointestinal toxicities of cancer treatments, untreated (or undertreated) EPI exacerbates weight loss, sarcopenia, micronutrient deficiencies, and malnutrition. Together, these complications contribute to poor tolerance of oncologic therapies and negatively impact survival. Treatment of EPI in PDAC involves the addition of pancreatic enzyme replacement therapy, with titration to improve gastrointestinal symptoms. Medical nutrition therapies may also be applicable and may include fat-soluble vitamin replacement, medium-chain triglycerides, and, in some cases, enteral nutrition. Optimizing nutrition status is an important adjunct treatment approach to improve quality of life and may also improve overall survival.

How a significant increase in survival in pancreatic cancer is achieved. The role of nutritional status and supportive care: A review

Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.

Real-World Patient Experience With Pancreatic Enzyme Replacement Therapy in the Treatment of Exocrine Pancreatic Insufficiency.

This study aimed to provide patients insights on the management of exocrine pancreatic insufficiency (EPI) with pancreatic enzyme replacement therapy (PERT). A survey of 75 members of Inspire's Pancreatitis or Pancreatic Cancer Support communities was conducted. Eligibility included having EPI secondary to chronic pancreatitis, pancreatic cancer, pancreatic surgery, or acute pancreatitis, and current/past PERT experience. Patients were 73% female, 57% aged 50 to 69 years, and 85% White, with PERT prescribed by a gastroenterologist/pancreatologist for 64%. Only approximately half of respondents agreed that their healthcare provider provided detailed information about EPI (54%) or how PERT works to treat EPI (56%). Most respondents (83%) reported searching for information about EPI, 56% were taking PERT solely before or after eating, 36% reported taking suboptimal PERT doses, and 39% reported no follow-up. In addition, 24% decreased their PERT dosage without consulting their physician, and 21% reported purposely skipping PERT. This study reveals potential barriers to effective treatment of EPI with PERT, including lack of patient education, mainly how and when to take PERT, gaps in appropriate dosing, and lack of patient follow-up. Continued focus on patient and provider education is essential to address these gaps and optimize the treatment of EPI.

Fat-soluble vitamin deficiency and exocrine pancreatic insufficiency among adults with chronic pancreatitis: Is routine monitoring necessary for all patients?

Chronic pancreatitis (CP) is often associated with exocrine pancreatic insufficiency (EPI), which may increase risk for fat-soluble vitamin depletion. Although vitamin D deficiency is widespread among the general population, vitamins A, E, and K deficiencies may more uniquely present in patients with CP. Yet, it is unclear whether fat-soluble vitamin status should be routinely monitored in all patients with CP or limited to those with EPI. The purpose of this review is to describe the laboratory status of vitamins A, E, and K in adult patients with CP and their association with exocrine pancreatic function. Five primary, observational studies met the inclusion criteria for qualitative synthesis. Biochemical deficiencies in fat-soluble vitamins were observed across trials but results varied with respect to whether EPI increased risk. Challenges related to the diagnosis and treatment of EPI along with potential confounders may contribute to the heterogeneity among study results. Although more studies are needed to determine the influence of pancreatic enzyme replacement therapy on fat-soluble vitamin status as well as effective vitamin repletion strategies, clinicians should consider periodically screening for deficiencies in all patients with CP regardless of EPI to avoid associated health effects of vitamin depletion.

S6 Treatment of Exocrine Pancreatic Insufficiency in Patients with Chronic/Recurrent Acute Pancreatitis Improves Treatment Satisfaction and Decreases Healthcare Utilization: Interim Findings from the PACT-CP Registry

S6 Treatment of Exocrine Pancreatic Insufficiency in Patients with Chronic/Recurrent Acute Pancreatitis Improves Treatment Satisfaction and Decreases Healthcare Utilization: Interim Findings from the PACT-CP Registry

S17 Pancrelipase for the Treatment of Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis: Rationale and Methodology of a Prospective, Observational, Multicenter, Cohort Study

S17 Pancrelipase for the Treatment of Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis: Rationale and Methodology of a Prospective, Observational, Multicenter, Cohort Study

A Systematic Review of Exocrine Pancreatic Insufficiency Prevalence and Treatment in Type 1 and Type 2 Diabetes.

Type 1 diabetes and type 2 diabetes have high rates of associated exocrine pancreatic insufficiency (EPI). This review evaluated the current evidence on prevalence and treatment of EPI in type 1 and type 2 diabetes and compared general population prevalence rates of EPI and prevalence of other common gastrointestinal conditions such as celiac disease and gastroparesis based on within-diabetes rates of common gastrointestinal (GI) conditions. Prevalence of EPI in type 1 diabetes ranges from 14% to 77.5% (median 33%), while EPI in type 2 diabetes ranges from 16.8% to 49.2% (median 29%), and where type of diabetes is not specified in studies, ranges from 5.4% to 77%. In studies with control groups of the general population, prevalence of EPI overall in those without diabetes ranged from 4.4% to 18%, median 13%, which is comparable with other estimated general population prevalence rates of EPI (10%-20%). Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes (both type 1 and type 2) who present with gastrointestinal symptoms, such as steatorrhea or changes in stool, bloating, and/or abdominal pain, should be screened for EPI. Both diabetes specialists and gastroenterologists and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms.

1304-P: Exocrine Pancreatic Insufficiency (EPI) Likely Overlooked in Diabetes as Common Cause of Gastrointestinal-Related Symptoms

Background: Exocrine Pancreatic Insufficiency (EPI/PEI) occurs when the pancreas no longer makes enough enzymes to support digestion. Awareness among diabetes care providers does not match the likely rates of prevalence and contributes to underscreening and underdiagnosis of EPI among people with diabetes. Methods: A systematic review of EPI was performed. Resulting articles were analyzed for whether the articles were on diabetes or other co-conditions. Articles on EPI and diabetes were analyzed for type of diabetes, prevalence of EPI reported in diabetes, and publication name. A subsequent literature review of prevalence studies of gastrointestinal conditions in people with diabetes was also performed and data was analyzed to estimate prevalence and compare rates of gastroparesis, celiac, and EPI among people with diabetes. Results: The systematic review of EPI found 644 articles, of which only 40 were focused on EPI and diabetes (12 Type 1, 7 Type 2, 20 both T1/T2 or all types; 1 neonatal). They represent 9.6% of the EPI co-condition literature (n=418) and were published in 29 journals, of which only 9 were diabetes journals. Most were studies on prevalence or diagnosis; whereas one recent article demonstrates a method for evaluating improved glycemic variability following treatment for EPI. The literature review on other GI conditions in people with diabetes found prevalence of 1.3% for gastroparesis, with differing estimates in Type 1 (up to 5% for those who sought care) and Type 2 (1%), and 5% for celiac in Type 1. Prevalence reported for EPI in people with diabetes is higher: estimates vary from 20-50%. Conclusion: Gastroparesis and celiac are often top of mind for diabetes providers, yet EPI/PEI is ~10 times more common among people with diabetes. Healthcare providers who see people with diabetes should increase the screening of fecal elastase (FEL-1) for people with diabetes who mention gastrointestinal symptoms. Disclosure D.M.Lewis: None.

Pancreatic exocrine insufficiency in diabetes mellitus

Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT).

Recent Advances in Pancreatic Ductal Adenocarcinoma: Strategies to Optimise the Perioperative Nutritional Status in Pancreatoduodenectomy Patients.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy for which the mainstay of treatment is surgical resection, followed by adjuvant chemotherapy. Patients with PDAC are disproportionately affected by malnutrition, which increases the rate of perioperative morbidity and mortality, as well as reducing the chance of completing adjuvant chemotherapy. This review presents the current evidence for pre-, intra-, and post-operative strategies to improve the nutritional status of PDAC patients. Such preoperative strategies include accurate assessment of nutritional status, diagnosis and appropriate treatment of pancreatic exocrine insufficiency, and prehabilitation. Postoperative interventions include accurate monitoring of nutritional intake and proactive use of supplementary feeding methods, as required. There is early evidence to suggest that perioperative supplementation with immunonutrition and probiotics may be beneficial, but further study and understanding of the underlying mechanism of action are required.

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

Pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC) is well documented, but there is no consensus regarding optimal screening. 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. 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. 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. 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.

Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients.

Current and Future Therapeutic Approaches of Exocrine Pancreatic Insufficiency in Children with Cystic Fibrosis in the Era of Personalized Medicine

This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.

Kreon® (Creon®) vs. Lipancrea®: In Vitro Comparison of Two Encapsulated Pancreatin Preparations.

Kreon® (Creon®) and Lipancrea® are pancreatic enzyme supplements indicated in the treatment of exocrine pancreatic insufficiency. In order to determine their interchangeability, an in vitro comparison of their physical properties and enzymatic activity was carried out. Capsule fill weight and particle size were also determined in order to establish their physical properties. Amylase, lipase and protease activities, lipase release at different pHs and the dissolution time of pellets were assessed for enzymatic analysis. The length range of Kreon® and Lipancrea® pellets was 1.1-2.2 mm and 1.5-2.8 mm, respectively. Protease activity was below the label claim for Lipancrea® and above for Kreon® presentations. Lipase and amylase activity were equal to or higher than the label claim in both preparations. In dissolution experiments simulating the stomach passage, significant release of lipase activity was observed for Lipancrea® (% actual activity: 41% for Lipancrea® 8000; 21% for Lipancrea® 16000) after 60 min at pH 5.0. No release of lipase activity was observed for Kreon® at that particular pH. Enzyme release for Lipancrea® at pH 6.0 was generally slower than for Kreon® and seemed to be influenced by the preceding incubation at lower pH. More than 85% of Kreon® and Lipancrea® dissolved in a pH 6.0 phosphate buffer within 20 min. Despite the similarities of the enzyme content on the respective labels, Kreon® and Lipancrea® differ in pellet size, enzymatic activity and release. This may impact their therapeutic efficacy and, therefore, may limit their interchangeability.

Is endocrine and exocrine function improved following duodenal preserving pancreatic head resection over whipple for chronic pancreatitis?

The aim of our study was to evaluate the rates of treatment for post-operative exocrine pancreatic insufficiency (EPI) and diabetes mellites (DM) between Duodenal Preserving Pancreatic Head Resections (DPPHR) and Pancreaticoduodenectomy (PD) from a prospectively maintained database of patients with chronic pancreatitis. 104 patients were identified for inclusion, 62 of whom underwent DPPHR and 42 underwent PD. Study endpoints included changes in treatment for EPI and DM. In the DPPHR group, the vast majority (n=55) received a Frey procedure, with a small minority of patients undergoing a Beger procedure (n=4) or Berne modification (n=3). Patients in the DPPHR group had a lower rate of new persistent treatment for EPI post-operatively compared to patients who underwent PD (28.0% vs. 76.5%, p=0.002). There was no difference in the rate of new onset DM, with low rates of new insulin dependent diabetics in both groups. Both groups had equal efficacy in terms of pain control, with 67.7% of the DPPHR group and 61.9% of the PD group remaining opioid free at long-term follow-up (p=0.539). In patients with head-predominant chronic pancreatitis, DPPHR was associated with reduced rates of new EPI treatment and similar endocrine function compared with PD.

Exocrine and Endocrine Insufficiency in Autoimmune Pancreatitis: A Matter of Treatment or Time?

Background: Autoimmune pancreatitis (AIP) is a specific form of chronic pancreatitis with a high relapse rate after treatment. AIP patients are burdened with an increased risk of long-term sequelae such as exocrine and endocrine insufficiency. Our objective was to investigate if pharmacological treatment affects both endocrine and exocrine pancreatic function in patients with AIP. Methods: We included 59 patients with definite AIP in the final analysis. Screening for diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI) was performed at the time of AIP diagnosis and during follow-up. Results: There were 40 (67.8%) males and 19 (32.2%) females; median age at diagnosis was 65 years. Median follow-up after the diagnosis of AIP was 62 months. PEI prevalence at diagnosis was 72.7% and was 63.5% at follow-up. The cumulative incidence of DM was 17.9%, with a prevalence of DM at diagnosis of 32.8%. No strong association was found between pharmacological treatment and occurrence of PEI and DM. Univariate analysis identified potential risk factors for PEI (other organ involvement and biliary stenting) and for DM (overweight, blue-collar profession, smoking, weight loss or obstructive jaundice as presenting symptoms, imaging showing diffuse pancreatic enlargement, smoking). In a multivariate analysis, only obstructive jaundice was identified as a risk factor for DM both at diagnosis and during follow-up. Conclusions: Our results suggest that the prevalence of endocrine and exocrine insufficiency in AIP is high at diagnosis with an additional risk of PEI and DM during follow-up despite pharmacological treatment.

P-91 Quality of life (QoL)-based end-points for patients with advanced pancreatic ductal adenocarcinoma (aPDAC): Results from the PanDA prospective observational study

Adequate design of clinical trials using QoL-based primary-end points to assess benefit derived from supportive interventions such as exercise, nutrition or complementary therapies is challenging in PDAC due to a lack of available data describing baseline QoL and changes over time for this patient population. PanDA was a prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with aPDAC (NCT03616431). QoL data using the EORTC QlQ-C30 and QLQ-PAN26 questionnaires were collected for the follow-up cohort at baseline (BSL), week6 (W6) and month3 (M3). This post-hoc analysis included patients with aPDAC and explored the mean and standard deviation (SD) of the Physical Functioning Scale (PhFS) at BSL, W6, M3) and mean (SD) intra-patient changes over time (W6-BSL and M3-BSL). Subgroup analysis by stage (locally-advanced vs metastatic) was also performed. Percentage of patients evaluable at each time point was reported. Descriptive statistical analysis was performed (Stata v.17). Of 37 patients recruited into the follow-up cohort, 32 met eligibility criteria for this post hoc analysis. Thirty (93.8%), 17 (53.1%; all had paired BSL data) and 13 (40.6%; all had paired BSL data) patients were evaluable with PhFS data available at BSL, W6 and M3, respectively. PhFS (mean (SD); number of observations) did not vary over time when all patients were analysed together (BSL: 76.17(26.46);30) (W6: 79.18(12.74);17) (M3: 74.46(16.76);13). Intra-patient mean changes at W6 (-6.59(15.13);17) or M3 (-5.46(24.82);13). Subgroup analysis identified that changes in W6 were more marked in patients with metastatic disease (-12.14(15.54);7) compared to locally advanced (-2.70(14.32);10). Changes on PhFS over time were likely impacted by selection bias. Intra-patient mean changes at W6 or M3 seemed more reliable to be utilised as primary-end point and sample size calculation in future clinical trials. Subgroup analysis identified that changes in W6 were more marked in patients with metastatic Intra-patient changes rather than pooled results may be more reliable when designing clinical trials with QoL-based primary end-points in aPDAC. W6 assessment may be most informative, as waiting until M3 may compromise the power of the study due to significant drop out.