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Meta-Analysis
. 2020 Mar 4;15(3):e0230060.
doi: 10.1371/journal.pone.0230060. eCollection 2020.

The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies

Pedro Luiz Serrano Usón Junior  1   2 , Fernanda D'Avila Sampaio Tolentino  1 , Vanessa Montes Santos  1 , Edna Terezinha Rother  1 , Fernando Cotait Maluf  1   3
Affiliations
Meta-Analysis

The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies

Pedro Luiz Serrano Usón Junior et al. PLoS One. .

Abstract

The real impact of specific sites of metastasis on prognosis of metastatic pancreatic cancer (MPC) is unknown. To evaluate the association of specific metastatic sites and survival outcomes in MPC a systematic literature review was performed including prospective randomized trials of systemic treatments in metastatic pancreatic cancer indexed in PubMed, Embase and Web of Science. Data regarding systemic treatment regimens, progression free survival and overall survival were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Of 1,052 abstracts, 7 randomized trials were considered eligible with a combined sample size of 2,975 MPC patients. Combining the studies with meta-analysis, we could see that patients with liver metastasis had a HR for death of 1.53 with 95% CI of 1.15 to 2.02 (p-value 0.003) and HR for risk of progression of 1.96 with 95% CI of 1.28 to 2.99 (p-value 0.002), without significant heterogeneity. Having two or more sites of metastasis comparing to one site did not have impact on overall survival; RR of 1.05 with 95% CI 0.91 to 1.23 (p-value 0.493). In conclusion, liver metastasis confers worse outcomes among patients with MPC. Apparently, multiple metastatic sites do not present worse prognosis when compared with only one organ involved, therefore, demonstrating the severity of this disease. Prospective studies evaluating other treatments are necessary to address the impact of local treatments in liver metastasis in MPC.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow Diagram of the included studies.
Fig 2
Fig 2. Summary of risk of bias in the randomized controlled trials included.
Fig 3
Fig 3. Forest Plot for risk of death and liver metastasis based on hazard ratios (N = 2633).
Overall the presence of hepatic metastasis increases the risk of death around 50% (HR1,53 CI 95% [1,15; 2,02] (p 0,003).
Fig 4
Fig 4. Funnel plot for HR of OS and liver metastasis.
Funnel plot shows the absence of studies with a greater number of patients than the mean analyzed.
Fig 5
Fig 5. Forest plot for relative risk of death with three or more sites of metastasis compared to one site.
The forest plot based on number of events, shows absence of statistical significance of the sites of metastasis in relative risk of death.
See this image and copyright information in PMC

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