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. 2019 Jul 10;14(1):120.
doi: 10.1186/s13014-019-1330-0.

Network meta-analysis comparing neoadjuvant chemoradiation, neoadjuvant chemotherapy and upfront surgery in patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma

Qiancheng Hu  1 , Dan Wang  2 , Ye Chen  1 , Xiaofen Li  1 , Peng Cao  1 , Dan Cao  3
Affiliations

Network meta-analysis comparing neoadjuvant chemoradiation, neoadjuvant chemotherapy and upfront surgery in patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma

Qiancheng Hu et al. Radiat Oncol. .

Abstract

Purpose: Neoadjuvant chemoradiation or chemotherapy has improved the treatment efficacy of patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma (PDAC). Due to the optimal regimen remains inconclusive, we aimed to compare these treatments in terms of margin negative (R0) resection rate and overall survival (OS) with Bayesian analysis.

Patients and methods: We reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiation, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology and ClinicalTrials.gov database from 2009 to 2018 to estimate relative odds ratios (ORs) for margin negative (R0) resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.

Results: A total of 14 literatures with 1056 patients were enrolled in this Bayesian analysis. In the pairwise meta-analysis from limited head-to-head studies, compared with neoadjuvant chemotherapy, neoadjuvant chemoradiation showed superior OS significantly (HR 0.8, 95% CI 0.60-0.99, p < 0.001) and there was no significant difference in R0 resection rate (OR 1.02, 95%CI 0.45-2.33, I2 = 34.6%). However, in the network meta-analysis from all enrolled clinical trials, neoadjuvant chemoradiation showed significantly higher R0 resection rate over upfront surgery (HR 0.15, 95% CrI 0.02-0.56), whereas neoadjuvant chemotherapy did not provide better efficacy in R0 resection over upfront surgery (HR 0.42, 95% CrI 0.02-4.41). For R0 resection rate, neoadjuvant chemoradiation has the highest probability of ranking one compared with neoadjuvant chemotherapy or upfront surgery (79% vs 21% vs 0%). For OS, neoadjuvant chemotherapy has the highest probability of ranking one compared with neoadjuvant chemoradiation or upfront surgery (98% vs 0% vs 2%). Neoadjuvant chemotherapy was associated with higher rates of postoperative complications (rank worst: 84%), followed by neoadjuvant chemoradiotherapy (13%) and upfront surgery (3%).

Conclusions: Different neoadjuvant treatment was selected based on various purposes, whether increasing R0 resection rate or not. Future clinical trials comparing neoadjuvant chemoradiation with neoadjuvant chemotherapy are warranted to confirm our results.

Keywords: Bayesian analysis; Neoadjuvant therapy; Network meta-analysis; Pancreatic ductal adenocarcinoma.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Literature search and selection
Fig. 2
Fig. 2
a Comparison of R0 resection rate according to pairwise meta-analysis. b Comparison of overall survival according to pairwise meta-analysis
Fig. 3
Fig. 3
a Pooled odds ratios for R0 resection rate. (Red represents statistical significance). b Pooled hazard ratios for overall survival. (Red represents statistical significance)
Fig. 4
Fig. 4
Ranking of treatments in terms of R0 resection and overall survival
Fig. 5
Fig. 5
Ranking of treatments in terms of postoperative complications
See this image and copyright information in PMC

References

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