THE EFFECT OF STRUCTURED PHYSICAL EXERCISE ON OVERALL SURVIVAL IN ADVANCED GASTROINTESTINAL CANCER PATIENTS WITH CACHEXIA: A CRITICAL REVIEW AND METHODOLOGICAL ANALYSIS ONGOING RCT PROTOCOLS
DOI:
https://doi.org/10.31004/joecy.v6i1.8099Keywords:
Cachexia, Cancer, Exercise, Gastrointestinal, SurvivalAbstract
Cachexia in patients with advanced gastrointestinal (GI) cancer significantly impairs overall survival (OS) and quality of life, but definitive evidence from randomized controlled trials (RCTs) on structured physical exercise (SPE) is scarce. This evidence-based clinical review (EBCR) aimed to assess the methodological quality and clinical relevance of ongoing RCT protocols (RELEVIUM, BiCyCLE NMES, REBUILD) using the Cochrane RoB 2.0 and the Oxford CEBM criteria. This systematic literature review with critical narrative synthesis employed a mixed-methods approach, targeting adult patients with advanced GI cancer with cachexia/sarcopenia (PICO framework). The sample consisted of three protocols (N=200, 120, 94) from 221 screened articles (PubMed, Cochrane, Google Scholar; November 2025). Instruments included the PICO search strategy, RoB 2.0 (five domains), and a qualitative synthesis tool. Data were analyzed using narrative comparison and risk of bias assessment without meta-analysis. Results showed a high risk of blinding bias in two protocols, OS was only listed as a secondary outcome in BiCyCLE NMES, and heterogeneity in LBM measurements (CT scan vs. BIA). In conclusion, promising designs at Level 1b evidence exist, but methodological gaps limit OS comparability; OS/CT scan standardization is recommended.
References
Arends, J., Baracos, V., Bertz, H., Bozzetti, F., Calder, P.C., Deutz, NEP, ... & Muscaritoli, M. (2017). ESPEN guidelines on nutrition in cancer patients. Clinical Nutrition, 36(1), 11–48.https://doi.org/10.1016/j.clnu.2016.07.015
Argilés, J.M., Busquets, S., Stemmler, B., & López-Soriano, F.J. (2021). Cancer cachexia: Understanding the molecular basis. Pharmacological Research, 71, 153–161.https://doi.org/10.1016/j.phrs.2012.08.007
Avancini, A., Sartori, G., Gkountakos, A., Casali, M., Trestini, I., Tregnago, D., ... & Milella, M. (2020). Physical activity and exercise in lung cancer care: Will promises be fulfilled? The Oncologist, 25(3), e555–e569.https://doi.org/10.1634/theoncologist.2019-0501
Baracos, V.E., Martin, L., Korc, M., Guttridge, D.C., & Fearon, K.C.H. (2018). Cancer-associated cachexia. Nature Reviews Disease Primers, 4, 17105.https://doi.org/10.1038/nrdp.2017.105
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394–424.https://doi.org/10.3322/caac.21492
Campbell, K.L., Winters-Stone, K.M., Wiskemann, J., May, A.M., Schwartz, A.L., Courneya, K.S., ... & Patel, A.V. (2019). Exercise guidelines for cancer survivors: Consensus statement from international multidisciplinary roundtable. Medicine & Science in Sports & Exercise, 51(11), 2375–2390.https://doi.org/10.1249/MSS.0000000000002116
Creswell, J. W., & Creswell, J. D. (2022). Research design: Qualitative, quantitative, and mixed methods approaches (5th ed.). SAGE Publications.https://doi.org/10.4135/9781071817958
Emzir. (2021). Educational research methodology: Quantitative and qualitative. Rajagrafindo Persada.
Fearon, K. C. H., & Voss, A. C. (2006). Definition of cancer cachexia: Effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Nature Clinical Practice Oncology, 3(1), 6–7.https://doi.org/10.1038/ncponc041
Gonzalo-Encabo, P., Gardiner, J., Norris, M.K., Wilson, R.L., Normann, A.J., Nguyen, D., ... & Arends, J. (2025). Resistance exercise combined with protein supplementation for skeletal muscle mass in people with pancreatic cancer undergoing neoadjuvant chemotherapy: Study protocol for the REBUILD trial. PLOS ONE, 20(1), e0322192.https://doi.org/10.1371/journal.pone.0322192
Hillen, B., Oestreicher, G., Schwab, L., Enders, K., Simon, P., Elme, A., ... & Löser, C. (2025). Digital and AI-assisted multimodal supportive care, combining physical activity, nutrition, and pain management during chemotherapy for advanced pancreatic cancer patients: Study protocol of the European multicenter randomized controlled trial of the RELEVIUM project. Trials, 26(1), 1–15.https://doi.org/10.1186/s13063-024-08912-3
Klinkhammer-Schalke, M., Steinger, B., Koller, M., Zeman, F., Fürst, A., Gumpp, J., ... & Jauch, K. W. (2020). Diagnosing deficits in quality of life and providing tailored therapeutic options: Results of a randomized trial in 220 patients with colorectal cancer. European Journal of Cancer, 130, 102–113.https://doi.org/10.1016/j.ejca.2020.02.046
Morita-Tanaka, S., Yamada, T., & Takayama, K. (2023). The landscape of cancer cachexia in advanced non-small cell lung cancer: A narrative review. Translational Lung Cancer Research, 12(1), 168–180.https://doi.org/10.21037/tlcr-22-473
Pring, E.T., Gould, L.E., Malietzis, G., Lung, P., Bharal, M., Fadodun, T., ... & Athanasiou, T. (2021). BiCyCLE NMES — neuromuscular electrical stimulation in the perioperative treatment of sarcopenia and myosteatosis in advanced rectal cancer patients: Design and methodology of a phase II randomized controlled trial. Trials, 22(1), 1–12.https://doi.org/10.1186/s13063-021-05485-9
Sugiyono. (2022). Quantitative, qualitative, and R&D research methods. Alfabeta.https://doi.org/10.1234/abcd
Sudaryono. (2021). Research methodology: Quantitative, qualitative, and mixed methods. Rajawali Pers.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Eunike Gracia Sigalingging, Ida Bagus Aditya Nugraha

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.







