AUTHOR=Giovinazzo Francesco , Soggiu Fiammetta , Jang Jin-Young , Versteijne Eva , van Tienhoven Geertjan , van Eijck Casper H. , Han Youngmin , Choi Seong Ho , Kang Chang Moo , Zalupski Mark , Ahmad Hasham , Yentz Sarah , Helton Scott , Rose J. Bart , Takishita Chie , Nagakawa Yuichi , Abu Hilal Mohammad 

TITLE=Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01112

DOI=10.3389/fonc.2020.01112

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC.</p><p><bold>Patients and Methods:</bold> A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data.</p><p><bold>Results:</bold> Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1–25.2). R0 rates ranged between 81 and 95% (<italic>I</italic><sup>2</sup> = 0%, <italic>p</italic> = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9–31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3–18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4–18.5) in the group of patients who received upfront surgery (<italic>p</italic> &lt; 0.0001). R0 rates ranged between 81 and 95% (<italic>I</italic><sup>2</sup> = 0%, <italic>p</italic> = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3–34.2) vs. 16.2 months (95% CI 7·9–24.5) in the R1 group (<italic>p</italic> = 0·001).</p><p><bold>Conclusions:</bold> The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.</p>