Physical Functioning in Resectable Cancer of the Pancreas – Protocol for A Systematic Review

Study reporting and registration

This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocol (PRISMA-P) guidelines¹⁸. The completed PRISMA-P checklist is included as extended data. The systematic review is registered on PROSPERO (PROSPERO registration number: CRD420251020095).

Eligibility criteria

The eligibility criteria for this systematic review will be derived from the PICO Framework (Population, Intervention, Comparison, Outcome) (Table 1)¹⁹.

Population. Studies that include adult patients (≥ 18 years old) with a histological confirmed diagnosis of pancreatic cancer will be included.

Intervention. Studies must include patients who were scheduled for/ or having completed surgical resection for pancreatic cancer. Studies where participants receive neoadjuvant/adjuvant chemotherapy/ chemoradiotherapy in addition to surgery will also be included.

Outcome. Only studies which include an objective measure of physical function will be included. Specifically, under the Functional Ability Framework developed by Rikli and Jones²⁰ this review will include objective measures which assess physical functioning in terms of physical parameters (e.g. cardiorespiratory fitness and muscle strength), function (e.g. ones ability to engage in functional activities such as walking), and ability to achieve activity goals (e.g. one’s ability to engaged in physical activity for daily living). Examples of physical functioning measures identified in our previous review¹³ which may fall under each of these categories are presented in Table 2.

Study type. This review will include randomised controlled trials and non-randomised controlled trials of interventions which include patients scheduled for or/ having completed surgical resection for pancreatic cancer and include an objective measurement of physical function as an endpoint. It will also include cohort studies which measure physical function objectively. The exclusion criteria will be (i) where physical function is only measured by subjective means e.g. questionnaire, (ii) article unavailable in English, (iii) systematic reviews, meta-analysis, case studies, letter to the editor, conference proceeding (iv) abstracts not available in full text, and (v) grey literature. No limitations will be placed on publication date or geographic location.

Information sources and search strategy

The databases EMBASE, Medline OVID, CINAHL, Cochrane Library and Web of Science will be searched. The search strategy was initially devised by subject librarian (DM) for our original review¹³ in 2019 and subsequently revised in conjunction with subject librarian (NL) in advance of this new review to focus solely on resectable cancer of the pancreas (Extended Data). The search strategy will include terms relating to pancreatic cancer resection and physical functioning.

Study records

Data management. Following completion of the final search, references will be downloaded into EndNote 21 Desktop Reference management software and then imported into the Covidence Systematic Review Management System. Removal of duplicates is automated within the Covidence system.

Data collection. Titles and abstracts screening will be completed by two independent reviewers, irrelevant articles will be excluded, and any conflicts that occur will be resolved by a third reviewer through the Covidence system. Full texts of remaining articles will be similarly assessed by two independent reviewers and conflicts resolved by a third reviewer.

Data extraction. Data extraction will also be performed in duplicate independently by two reviewers and data extracted will be compared for accuracy any discrepancies will be resolved using a data extraction spreadsheet in Microsoft Excel. The authors plan to extract the following data: author, year of publication, patient characteristics (age, gender, and treatment types), physical function results, and details of any exercise interventions. Where further information or clarity is required on a particular study, LON will contact corresponding authors via email to seek further data.

Risk of bias assessment. Risk of bias will be assessed in duplicate and any disagreements will be resolved by consensus. The Quality in Prognostic Studies (QUIPS)²¹ tool will determine the risk of bias on included prognostic studies. For interventional studies, the RoB 2 (A revised Cochrane risk-of-bias tool for randomised trials)²² and ROBINS-I tool (Risk of Bias in Non-Randomised Studies of Interventions)²³ will be applied. Each of these measures categorise risk of bias as low, moderate, or high serious. Valid studies are considered to have low risk of bias, moderate risk studies may be susceptible to bias, whereas those categorised as high/serious bias may have significant bias which may invalidate study results²⁴.

Data analysis and synthesis. Data will be synthesized narratively according to the Synthesis Without Meta-Analysis (SWiM) guidelines²⁵. If the nature of the data permits a meta-analysis will be conducted using Review Manager (RevMan). A random effects model will be applied in consideration of the likely heterogeneity amongst studies. Statistical heterogeneity will be assessed using the I² statistic, with values exceeding 50% indicating substantial heterogeneity.

Certainty of the evidence assessment (GRADE). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)²⁶ approach will be used to assess the certainty of the evidence. Two reviewers will use the GRADEpro GT tool to consider the certainty of the evidence in consideration of: study limitations, unexplained heterogeneity of inconsistency, imprecision, indirectness and publication bias. Disagreements in rating will be resolved in consultation with a third reviewer.

Potential limitations

Due to the absence of translation resources, it will not be possible to include papers not available in English. Only peer reviewed published research will be included in this review, potentially yielding a risk of publication bias.

Tracked and dated amendments

Any updates to this protocol will be documented and presented in a table in the subsequent manuscript detailing the results of the systematic review.

Dissemination

The findings of this systematic review will be published in a peer-reviewed journal upon completion and presented at appropriate national and international conferences in the field of cancer rehabilitation.