Dataset Information

Sarcopenia's Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

ABSTRACT:

Background

Although sarcopenia has been reported to predict survival in cancer patients, its impact on patients who received immune checkpoint inhibitors (ICIs) has not been thoroughly investigated. This systematic review aimed to assess the long-term oncologic impact of sarcopenia on patients who received ICIs.

Methods

A systematic review of studies indexed in the PubMed, Embase, and Cochrane databases, up to April 1, 2021, was conducted. Studies that reported hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) based on sarcopenia in patients treated with ICIs were included. The inverse variance method was used with a random-effects model for data analysis.

Results

A total of 1284 patients from 14 studies were included. Among the patients who received ICIs, patients with sarcopenia had a significant increase in overall mortality compared to patients without sarcopenia in univariate analyses (HR = 1.66, 95% CI = 1.20-2.29, p = 0.002) and in adjusted HRs (HR = 1.55, 95% CI = 1.15-2.10, p = 0.004). The same results were obtained for PFS by both univariate analysis (HR = 1.75, 95% CI = 1.37-2.23, p < 0.001) and adjusted HRs (HR = 1.63, 95% CI 1.28-2.09, p < 0.001).

Conclusions

Sarcopenia appears to be an effective biomarker for predicting long-term oncologic outcomes in patients receiving ICI therapy and hence plays an important role when making treatment decisions. However, the fundamental role of this association with survival should be further investigated in large cohorts and clinical trials.

SUBMITTER: Lee D

PROVIDER: S-EPMC8622936 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs.MethodsWe systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed.ResultsA total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55-2.34, p <0.00001) and 1.46 (1.20-1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47-2.14, p <0.00001) and 1.73 (1.36-2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28-0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31-0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30-1.12, p = 0.10) and 0.46(0.19-1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis.ConclusionsPatients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.

Project description:IntroductionHyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.MethodsClinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2).ResultsForty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%-15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, P = .01), metastatic sites >2 (OR = 2.38, P <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, P = .02), and liver metastasis (OR = 3.06, P <.0001) indicate higher risk of HPD.ConclusionsThe pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have considerably improved patient outcomes in various cancer types, but their efficacy remains poorly predictable among patients. The intestinal microbiome, whose balance and composition can be significantly altered by antibiotic use, has recently emerged as a factor that may modulate ICI efficacy. The objective of this systematic review and meta-analysis is to investigate the impact of antibiotics on the clinical outcomes of cancer patients treated with ICIs.MethodsPubMed and major oncology conference proceedings were systematically searched to identify all studies reporting associations between antibiotic use and at least one of the following endpoints: Overall Survival (OS), Progression-Free Survival (PFS), Objective Response Rate (ORR) and Progressive Disease (PD) Rate. Pooled Hazard Ratios (HRs) for OS and PFS, and pooled Odds Ratios (ORs) for ORR and PD were calculated. Subgroup analyses on survival outcomes were also performed to investigate the potential differential effect of antibiotics according to cancer types and antibiotic exposure time windows.Results107 articles reporting data for 123 independent cohorts were included, representing a total of 41,663 patients among whom 11,785 (28%) received antibiotics around ICI initiation. The pooled HRs for OS and PFS were respectively of 1.61 [95% Confidence Interval (CI) 1.48-1.76] and 1.45 [95% CI 1.32-1.60], confirming that antibiotic use was significantly associated with shorter survival. This negative association was observed consistently across all cancer types for OS and depending on the cancer type for PFS. The loss of survival was particularly strong when antibiotics were received shortly before or after ICI initiation. The pooled ORs for ORR and PD were respectively of 0.59 [95% CI 0.47-0.76] and 1.86 [95% CI 1.41-2.46], suggesting that antibiotic use was significantly associated with worse treatment-related outcomes.ConclusionAs it is not ethically feasible to conduct interventional, randomized, controlled trials in which antibiotics would be administered to cancer patients treated with ICIs to demonstrate their deleterious impact versus control, prospective observational studies and interventional trials involving microbiome modifiers are crucially needed to uncover the role of microbiome and improve patient outcomes. Such studies will reduce the existing publication bias by allowing analyses on more homogeneous populations, especially in terms of treatments received, which is not possible at this stage given the current state of the field. In the meantime, antibiotic prescription should be cautiously considered in cancer patients receiving ICIs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42019145675.