Combined Effect of Sarcopenia and Systemic Inflammation on Survival in Patients with Advanced Stage Cancer Treated with Immunotherapy.
Biomarkers
Immunotherapy
Inflammation
Risk stratification
Sarcopenia
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
01
10
2019
accepted:
31
10
2019
entrez:
13
3
2020
pubmed:
13
3
2020
medline:
22
6
2021
Statut:
ppublish
Résumé
Sarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy. We performed a retrospective review of 90 patients enrolled on immunotherapy-based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias-adjusted log-rank test. A four-level risk stratification was used to create low-risk (PLR <242 and nonsarcopenic), intermediate-risk (PLR <242 and sarcopenic), high-risk (PLR ≥242 and nonsarcopenic), and very-high-risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival. Most patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high-risk, high-risk, and intermediate-risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65-27.01; p < .001; HR, 5.32; CI, 1.96-14.43; p = .001; and HR, 4.01; CI, 1.66-9.68; p = .002, respectively) and progression-free survival (HR, 12.29; CI, 5.15-29.32; p < .001; HR, 3.51; CI, 1.37-9.02; p = .009; and HR, 2.14; CI, 1.12-4.10; p = .022, respectively) compared with low-risk patients. Baseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy-treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents. Sarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk-stratification system that combined sarcopenia and platelet-to-lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression-free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk-stratify patients who are beginning treatment with immunotherapy.
Sections du résumé
BACKGROUND
Sarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy.
METHODS
We performed a retrospective review of 90 patients enrolled on immunotherapy-based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias-adjusted log-rank test. A four-level risk stratification was used to create low-risk (PLR <242 and nonsarcopenic), intermediate-risk (PLR <242 and sarcopenic), high-risk (PLR ≥242 and nonsarcopenic), and very-high-risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival.
RESULTS
Most patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high-risk, high-risk, and intermediate-risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65-27.01; p < .001; HR, 5.32; CI, 1.96-14.43; p = .001; and HR, 4.01; CI, 1.66-9.68; p = .002, respectively) and progression-free survival (HR, 12.29; CI, 5.15-29.32; p < .001; HR, 3.51; CI, 1.37-9.02; p = .009; and HR, 2.14; CI, 1.12-4.10; p = .022, respectively) compared with low-risk patients.
CONCLUSION
Baseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy-treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents.
IMPLICATIONS FOR PRACTICE
Sarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk-stratification system that combined sarcopenia and platelet-to-lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression-free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk-stratify patients who are beginning treatment with immunotherapy.
Identifiants
pubmed: 32162807
doi: 10.1634/theoncologist.2019-0751
pmc: PMC7066707
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e528-e535Subventions
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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