Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer
Abstract Background By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5‐fluorouracil, leucovorin, irinotecan...
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doaj-9f89d638b69540c7a93b551592c5638c2020-11-25T00:14:20ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092018-08-019467368410.1002/jcsm.12307Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancerJoshua K. Kays0Safi Shahda1Melissa Stanley2Teresa M. Bell3Bert H. O'Neill4Marc D. Kohli5Marion E. Couch6Leonidas G. Koniaris7Teresa A. Zimmers8Department of Surgery Indiana University School of Medicine Indianapolis IN USADepartment of Hematology/Oncology Indiana University School of Medicine Indianapolis IN USADepartment of Hematology/Oncology Indiana University School of Medicine Indianapolis IN USADepartment of Surgery Indiana University School of Medicine Indianapolis IN USADepartment of Hematology/Oncology Indiana University School of Medicine Indianapolis IN USADepartment of Radiology University of California San Francisco School of Medicine San Francisco CA USADepartment of Otolaryngology–Head and Neck Surgery Indiana University School of Medicine Indianapolis IN USADepartment of Surgery Indiana University School of Medicine Indianapolis IN USADepartment of Surgery Indiana University School of Medicine Indianapolis IN USAAbstract Background By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin therapy. Methods We performed a retrospective review of 53 patients with advanced PDAC on 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement by computed tomography (CT), trend, univariate, and multivariate analysis were performed. Results Among all patients, three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle and Fat Wasting (MFW), while 17% had Fat‐Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (P = 0.02). FW (HR = 5.2; 95% confidence interval = 1.5–17.3) and MFW (HR = 1.8; 95% confidence interval = 1.1–2.9) were associated with an increased risk of mortality compared with NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumours were also associated with decreased OMS. On multivariate analysis, cachexia phenotype and chemotherapy response were independently associated with survival. Notably, CT‐based body composition analysis detected tissue loss of >5% in 81% of patients, while the traditional definition of >5% body weight loss identified 56.6%. Conclusions Distinct cachexia phenotypes were observed in this homogeneous population of patients with equivalent stage, diagnosis, and first‐line treatment. This suggests cellular, molecular, or genetic heterogeneity of host or tumour. Survival among patients with FW was as poor as for MFW, indicating adipose tissue plays a crucial role in cachexia and PDAC mortality. Adipose tissue should be studied for its mechanistic contributions to cachexia.https://doi.org/10.1002/jcsm.12307CachexiaPancreatic cancerSarcopeniaFOLFIRINOXMuscle wasting |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joshua K. Kays Safi Shahda Melissa Stanley Teresa M. Bell Bert H. O'Neill Marc D. Kohli Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers |
spellingShingle |
Joshua K. Kays Safi Shahda Melissa Stanley Teresa M. Bell Bert H. O'Neill Marc D. Kohli Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer Journal of Cachexia, Sarcopenia and Muscle Cachexia Pancreatic cancer Sarcopenia FOLFIRINOX Muscle wasting |
author_facet |
Joshua K. Kays Safi Shahda Melissa Stanley Teresa M. Bell Bert H. O'Neill Marc D. Kohli Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers |
author_sort |
Joshua K. Kays |
title |
Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer |
title_short |
Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer |
title_full |
Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer |
title_fullStr |
Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer |
title_full_unstemmed |
Three cachexia phenotypes and the impact of fat‐only loss on survival in FOLFIRINOX therapy for pancreatic cancer |
title_sort |
three cachexia phenotypes and the impact of fat‐only loss on survival in folfirinox therapy for pancreatic cancer |
publisher |
Wiley |
series |
Journal of Cachexia, Sarcopenia and Muscle |
issn |
2190-5991 2190-6009 |
publishDate |
2018-08-01 |
description |
Abstract Background By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin therapy. Methods We performed a retrospective review of 53 patients with advanced PDAC on 5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement by computed tomography (CT), trend, univariate, and multivariate analysis were performed. Results Among all patients, three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle and Fat Wasting (MFW), while 17% had Fat‐Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (P = 0.02). FW (HR = 5.2; 95% confidence interval = 1.5–17.3) and MFW (HR = 1.8; 95% confidence interval = 1.1–2.9) were associated with an increased risk of mortality compared with NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumours were also associated with decreased OMS. On multivariate analysis, cachexia phenotype and chemotherapy response were independently associated with survival. Notably, CT‐based body composition analysis detected tissue loss of >5% in 81% of patients, while the traditional definition of >5% body weight loss identified 56.6%. Conclusions Distinct cachexia phenotypes were observed in this homogeneous population of patients with equivalent stage, diagnosis, and first‐line treatment. This suggests cellular, molecular, or genetic heterogeneity of host or tumour. Survival among patients with FW was as poor as for MFW, indicating adipose tissue plays a crucial role in cachexia and PDAC mortality. Adipose tissue should be studied for its mechanistic contributions to cachexia. |
topic |
Cachexia Pancreatic cancer Sarcopenia FOLFIRINOX Muscle wasting |
url |
https://doi.org/10.1002/jcsm.12307 |
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