{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:26:17Z","timestamp":1782365177082,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research"},{"name":"Alberta Cancer Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013\u20132019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (\u2206SMI, \u2206ATI, cm2\/m2) were measured for patients with CT images available both prior to and 12 \u00b1 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox\u2019s proportional hazards models. Tissue changes varied widely (\u2206SMI: \u221217.8 to +7.3 cm2\/m2, \u2206ATI: \u2212106.1 to +37.7 cm2\/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (\u22123.2 cm2\/m2, p &lt; 0.001; \u221212.4 cm2\/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (\u22121.6 cm2\/m2, p = 0.013) and GEM\/NAB with greater adipose loss (\u221211.2 cm2\/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.<\/jats:p>","DOI":"10.3390\/cancers15174368","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T08:45:31Z","timestamp":1693557931000},"page":"4368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Muscle and Adipose Wasting despite Disease Control: Unaddressed Side Effects of Palliative Chemotherapy for Pancreatic Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-4061","authenticated-orcid":false,"given":"Pamela N.","family":"Klassen","sequence":"first","affiliation":[{"name":"Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie","family":"Baracos","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Martin","sequence":"additional","affiliation":[{"name":"Nutrition Services, Alberta Health Services, Edmonton, AB T5J 3E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, Edmonton, AB T6G 2P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera C.","family":"Mazurak","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"ref_1","unstructured":"Canadian Cancer Statistics Advisory Committee (2019). Canadian Cancer Statistics 2019, Canadian Cancer Statistics Advisory Committee."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","article-title":"Increased Survival in Pancreatic Cancer with Nab-Paclitaxel plus Gemcitabine","volume":"369","author":"Ervin","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer","volume":"364","author":"Conroy","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/bjc.1997.17","article-title":"Changes in Nutritional Status Associated with Unresectable Pancreatic Cancer","volume":"75","author":"Wigmore","year":"1997","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1007\/s00520-020-05346-8","article-title":"Incidence and Frequency of Cancer Cachexia during Chemotherapy for Advanced Pancreatic Ductal Adenocarcinoma","volume":"28","author":"Mitsunaga","year":"2020","journal-title":"Support. Care Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11864-019-0691-9","article-title":"Chemotherapy-Induced Sarcopenia","volume":"21","author":"Bozzetti","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1139\/H08-075","article-title":"A Practical and Precise Approach to Quantification of Body Composition in Cancer Patients Using Computed Tomography Images Acquired during Routine Care","volume":"33","author":"Mourtzakis","year":"2008","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.21037\/apm.2018.12.01","article-title":"Cancer Cachexia Is Defined by an Ongoing Loss of Skeletal Muscle Mass","volume":"8","author":"Baracos","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1158\/1055-9965.EPI-19-0370","article-title":"Postdiagnosis Loss of Skeletal Muscle, but Not Adipose Tissue, Is Associated with Shorter Survival of Patients with Advanced Pancreatic Cancer","volume":"28","author":"Babic","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8662","DOI":"10.1007\/s00330-021-07899-6","article-title":"Prognostic Value of Early Changes in CT-Measured Body Composition in Patients Receiving Chemotherapy for Unresectable Pancreatic Cancer","volume":"31","author":"Deniffel","year":"2021","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1152\/japplphysiol.00363.2020","article-title":"Nonuniform Loss of Muscle Strength and Atrophy during Bed Rest: A Systematic Review","volume":"131","author":"Marusic","year":"2021","journal-title":"J. Appl. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.nut.2018.11.014","article-title":"Effects of \u03c9-3 Supplementation on the Nutritional Status, Immune, and Inflammatory Profiles of Gastric Cancer Patients: A Randomized Controlled Trial","volume":"61","author":"Rodrigues","year":"2019","journal-title":"Nutrition"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/jcsm.12562","article-title":"The Association between Changes in Muscle Mass and Quality of Life in Patients with Metastatic Colorectal Cancer","volume":"11","author":"Derksen","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/jcsm.12267","article-title":"Loss of Skeletal Muscle during Systemic Chemotherapy Is Prognostic of Poor Survival in Patients with Foregut Cancer","volume":"9","author":"Daly","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1017\/S0007114520003463","article-title":"The Impact of Sarcopenia and Decrease in Skeletal Muscle Mass in Patients with Advanced Pancreatic Cancer during FOLFIRINOX Therapy","volume":"125","author":"Uemura","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/jcsm.12368","article-title":"The IMPACT Study: Early Loss of Skeletal Muscle Mass in Advanced Pancreatic Cancer Patients","volume":"10","author":"Basile","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3109\/0284186X.2014.953259","article-title":"Changes in Skeletal Muscle Mass during Palliative Chemotherapy in Patients with Advanced Lung Cancer","volume":"54","author":"Stene","year":"2015","journal-title":"Acta Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.3945\/ajcn.113.060228","article-title":"Central Tenet of Cancer Cachexia Therapy: Do Patients with Advanced Cancer Have Exploitable Anabolic Potential?","volume":"98","author":"Prado","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.pan.2020.09.012","article-title":"Impact on Prognosis of Early Weight Loss during Palliative Chemotherapy in Patients Diagnosed with Advanced Pancreatic Cancer","volume":"20","author":"Carnie","year":"2020","journal-title":"Pancreatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4081\/ejtm.2018.7590","article-title":"Chemotherapy-Induced Muscle Wasting: Association with NF-\u039aB and Cancer Cachexia","volume":"28","author":"Damrauer","year":"2018","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/jcsm.12998","article-title":"Sex Specificity of Pancreatic Cancer Cachexia Phenotypes, Mechanisms, and Treatment in Mice and Humans: Role of Activin","volume":"13","author":"Zhong","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106206","DOI":"10.1016\/j.ijsu.2021.106206","article-title":"Skeletal Muscle Wasting during Neoadjuvant Therapy as a Prognosticator in Patients with Esophageal and Esophagogastric Junction Cancer: A Systematic Review and Meta-Analysis","volume":"97","author":"Wang","year":"2022","journal-title":"Int. J. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1038\/s41430-021-00863-z","article-title":"Adequacy of Nutritional Support Using Computed Tomography (CT) in Patients with Head and Neck Cancer (HNC) during Chemo-Radiotherapy (CRT)","volume":"75","author":"Arribas","year":"2021","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Choi, Y., Oh, D.Y., Kim, T.Y., Lee, K.H., Han, S.W., Im, S.A., Kim, T.Y., and Bang, Y.J. (2015). Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139749"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcsm.12307","article-title":"Three Cachexia Phenotypes and the Impact of Fat-Only Loss on Survival in FOLFIRINOX Therapy for Pancreatic Cancer","volume":"9","author":"Kays","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.clnu.2022.03.016","article-title":"Assessing Dynamic Change in Muscle during Treatment of Patients with Cancer: Precision Testing Standards","volume":"41","author":"Arribas","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/oxfordjournals.aje.a009520","article-title":"Epidemiology of Sarcopenia among the Elderly in New Mexico","volume":"147","author":"Baumgartner","year":"1998","journal-title":"Am. J. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/ejcts\/ezy403","article-title":"Statistical Primer: Multivariable Regression Considerations and Pitfalls\u2020","volume":"55","author":"Grant","year":"2019","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-Associated Cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e20190450","DOI":"10.1084\/jem.20190450","article-title":"Tumor-Derived IL-6 and Trans-Signaling among Tumor, Fat, and Muscle Mediate Pancreatic Cancer Cachexia","volume":"218","author":"Rupert","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_31","first-page":"6193765","article-title":"Assessment of Nutritional Status, Digestion and Absorption, and Quality of Life in Patients with Locally Advanced Pancreatic Cancer","volume":"2017","author":"Wierdsma","year":"2017","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41416-021-01301-4","article-title":"Pancreatic Cancer Cachexia: Three Dimensions of a Complex Syndrome","volume":"124","author":"Kordes","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1634\/theoncologist.2018-0266","article-title":"Pancreas Cancer-Associated Weight Loss","volume":"24","author":"Hendifar","year":"2019","journal-title":"Oncologist"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00520-012-1514-8","article-title":"Symptoms in Advanced Pancreatic Cancer Are of Importance for Energy Intake","volume":"21","author":"Bye","year":"2013","journal-title":"Support. Care Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Campelj, D.G., Goodman, C.A., and Rybalka, E. (2021). Chemotherapy-Induced Myopathy: The Dark Side of the Cachexia Sphere. Cancers, 13.","DOI":"10.3390\/cancers13143615"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1017\/S0029665118000186","article-title":"Barriers to Cancer Nutrition Therapy: Excess Catabolism of Muscle and Adipose Tissues Induced by Tumour Products and Chemotherapy","volume":"77","author":"Schiessel","year":"2018","journal-title":"Proc. Nutr. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e22437","DOI":"10.1096\/fj.202200460R","article-title":"Short Duration Treadmill Exercise Improves Physical Function and Skeletal Muscle Mitochondria Protein Expression after Recovery from <scp>FOLFOX<\/Scp> Chemotherapy in Male Mice","volume":"36","author":"Halle","year":"2022","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1152\/japplphysiol.00325.2022","article-title":"5-Fluorouracil Disrupts Skeletal Muscle Immune Cells and Impairs Skeletal Muscle Repair and Remodeling","volume":"133","author":"VanderVeen","year":"2022","journal-title":"J. Appl. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e389942","DOI":"10.1200\/EDBK_389942","article-title":"Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach","volume":"43","author":"Kadakia","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1056\/NEJMoa1809775","article-title":"FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer","volume":"379","author":"Conroy","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Naumann, P., Eberlein, J., Farnia, B., Liermann, J., Hackert, T., Debus, J., and Combs, S.E. (2019). Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation. Cancers, 11.","DOI":"10.3390\/cancers11111655"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Naito, T., Okayama, T., Aoyama, T., Ohashi, T., Masuda, Y., Kimura, M., Shiozaki, H., Murakami, H., Kenmotsu, H., and Taira, T. (2017). Skeletal Muscle Depletion during Chemotherapy Has a Large Impact on Physical Function in Elderly Japanese Patients with Advanced Non-Small-Cell Lung Cancer. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3562-4"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.pan.2019.07.039","article-title":"Characterising the Impact of Body Composition Change during Neoadjuvant Chemotherapy for Pancreatic Cancer","volume":"19","author":"Griffin","year":"2019","journal-title":"Pancreatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s11605-008-0505-z","article-title":"Cachexia Worsens Prognosis in Patients with Resectable Pancreatic Cancer","volume":"12","author":"Bachmann","year":"2008","journal-title":"J. Gastrointest. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1093\/annonc\/mdx271","article-title":"Forcing the Vicious Circle: Sarcopenia Increases Toxicity, Decreases Response to Chemotherapy and Worsens with Chemotherapy","volume":"28","author":"Bozzetti","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1097\/MPA.0000000000000898","article-title":"Predictors of Pancreatic Cancer-Associated Weight Loss and Nutritional Interventions","volume":"46","author":"Nemer","year":"2017","journal-title":"Pancreas"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:44:42Z","timestamp":1760129082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":46,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15174368"],"URL":"https:\/\/doi.org\/10.3390\/cancers15174368","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,1]]}}}