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Meta-Analysis
. 2019 Sep;101(7):453-462.
doi: 10.1308/rcsann.2019.0060. Epub 2019 Jul 15.

Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: a systematic review and meta-analysis

K Rangarajan  1 , P H Pucher  1   2 , T Armstrong  1 , A Bateman  3 , Zzr Hamady  1
Affiliations
Meta-Analysis

Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: a systematic review and meta-analysis

K Rangarajan et al. Ann R Coll Surg Engl. 2019 Sep.

Abstract

Background: Pancreatic ductal adenocarcinoma remains a disease with a poor prognosis despite advances in surgery and systemic therapies. Neoadjuvant therapy strategies are a promising alternative to adjuvant chemotherapy. However, their role remains controversial. This meta-analysis aims to clarify the benefits of neoadjuvant therapy in resectable pancreatic ductal adenocarcinoma.

Methods: Eligible studies were identified from MEDLINE, Embase, Web of Science and the Cochrane Library. Studies comparing neoadjuvant therapy with a surgery first approach (with or without adjuvant therapy) in resectable pancreatic ductal adenocarcinoma were included. The primary outcome assessed was overall survival. A random-effects meta-analysis was performed, together with pooling of unadjusted Kaplan-Meier curve data.

Results: A total of 533 studies were identified that analysed the effect of neoadjuvant therapy in pancreatic ductal adenocarcinoma. Twenty-seven studies were included in the final data synthesis. Meta-analysis suggested beneficial effects of neoadjuvant therapy with prolonged survival compared with a surgery-first approach, (hazard ratio 0.72, 95% confidence interval 0.69-0.76). In addition, R0 resection rates were significantly higher in patients receiving neoadjuvant therapy (relative risk 0.51, 95% confidence interval 0.47-0.55). Individual patient data analysis suggested that overall survival was better for patients receiving neoadjuvant therapy (P = 0.008).

Conclusions: Current evidence suggests that neoadjuvant chemotherapy has a beneficial effect on overall survival in resectable pancreatic ductal adenocarcinoma in comparison with upfront surgery and adjuvant therapy. Further trials are needed to address the need for practice change.

Keywords: Cancer; Neoadjuvant; Pancreas; Surgery.

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Figures

Figure 1
Figure 1
PRISMA flowchart of search strategy and results.
Figure 2
Figure 2
Forest plot of survival rates following neoadjuvant chemotherapy compared with surgery first (top) and adjuvant compared with no adjuvant therapy (bottom).
Figure 3
Figure 3
Forest plot of negative (R0) resection margins for patients receiving neoadjuvant chemotherapy compared with surgery first (CI, confidence interval; RR, relative risk).
Figure 4
Figure 4
Forest plot of morbidity rates for neoadjuvant chemotherapy compared with surgery first.
Figure 5
Figure 5
Funnel plot of hazard ratios for overall survival comparing neoadjuvant chemotherapy with surgery first (HR, hazard ration; SE, standard error).
Figure 6
Figure 6
Kaplan–Meier survival curve for overall survival for neoadjuvant chemotherapy and surgery first for patients with pancreatic ductal adenocarcinoma with number at risk values (P = 0.008).
See this image and copyright information in PMC

References

    1. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993; (1): 68–733. - PubMed
    1. Neoptolemos JP, Stocken DD, Friess H et al. . A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; (12): 1,200–1,210. - PubMed
    1. Neoptolemos JP, Palmer DH, Ghaneh P et al. . Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet 2017; (10073): 1,011–1,024. - PubMed
    1. Edeline J, Bonnetain F, Phelip JM et al. . Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol 2017; (4 Suppl): 225. - PubMed
    1. Aloia TA, Aloia TE, Lee JE et al. . Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg 2007; (3): 347–355. - PubMed

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