David R Fogelman1, J Morris2, L Xiao2, M Hassan3, S Vadhan4, M Overman3, S Javle3, R Shroff3, G Varadhachary3, R Wolff3, L Vence5, A Maitra6, C Cleeland7, X S Wang7. 1. Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. dfogelman@mdanderson.org. 2. Department of Biostatistics, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. 3. Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. 4. Department of Sarcoma Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. 5. Department of Immunology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. 6. Department of Pathology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. 7. Department of Symptom Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Abstract
BACKGROUND: Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients. METHODS: Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy. RESULTS: Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker. CONCLUSIONS: Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.
BACKGROUND:Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancerpatients. METHODS:Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy. RESULTS: Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker. CONCLUSIONS:Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.
Entities:
Keywords:
Cachexia; Cytokine; Inflammation; Pancreatic cancer
Authors: Barbra S Miller; Kathleen M Ignatoski; Stephanie Daignault; Ceit Lindland; Megan Doherty; Paul G Gauger; Gary D Hammer; Stewart C Wang; Gerard M Doherty Journal: World J Surg Date: 2012-07 Impact factor: 3.352
Authors: Thomas Pausch; Werner Hartwig; Ulf Hinz; Thomas Swolana; Bogota D Bundy; Thilo Hackert; Lars Grenacher; Markus W Büchler; Jens Werner Journal: Surgery Date: 2012-07-06 Impact factor: 3.982
Authors: Katie M Di Sebastiano; Lin Yang; Kevin Zbuk; Raimond K Wong; Tom Chow; David Koff; Gerald R Moran; Marina Mourtzakis Journal: Br J Nutr Date: 2012-07-04 Impact factor: 3.718
Authors: Herbert I Hurwitz; Nikhil Uppal; Stephanie A Wagner; Johanna C Bendell; J Thaddeus Beck; Seaborn M Wade; John J Nemunaitis; Philip J Stella; J Marc Pipas; Zev A Wainberg; Robert Manges; William M Garrett; Deborah S Hunter; Jason Clark; Lance Leopold; Victor Sandor; Richard S Levy Journal: J Clin Oncol Date: 2015-09-08 Impact factor: 44.544
Authors: Kenneth Fearon; Florian Strasser; Stefan D Anker; Ingvar Bosaeus; Eduardo Bruera; Robin L Fainsinger; Aminah Jatoi; Charles Loprinzi; Neil MacDonald; Giovanni Mantovani; Mellar Davis; Maurizio Muscaritoli; Faith Ottery; Lukas Radbruch; Paula Ravasco; Declan Walsh; Andrew Wilcock; Stein Kaasa; Vickie E Baracos Journal: Lancet Oncol Date: 2011-02-04 Impact factor: 41.316
Authors: Sophie Cousin; A Hollebecque; S Koscielny; O Mir; A Varga; V E Baracos; J C Soria; S Antoun Journal: Invest New Drugs Date: 2013-12-17 Impact factor: 3.850
Authors: P Cresta Morgado; M Daud; M Carballido; G Méndez; S Iseas; V Lobbe; G De Simone; A Navigante Journal: Support Care Cancer Date: 2018-08-18 Impact factor: 3.603
Authors: Barry J Laird; Donald McMillan; Richard J E Skipworth; Marie T Fallon; D Robert Paval; Iain McNeish; Iain J Gallagher Journal: Inflammation Date: 2021-04-27 Impact factor: 4.092