PATHOLOGIC COMPLETE RESPONSE FOLLOWING PREOPERATIVE CHEMORADIATION VS CHEMOTHERAPY FOR PANCREATIC DUCTAL ADENOCARCINOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.
Quoc Riccardo Bao*1, Marco Ventin3, Lorenzo Dell'Atti1, Marzia Tripepi2, Isabella Frigerio2, Marco Scarpa1, Gaya Spolverato1
1Universita degli Studi di Padova, Padova, Veneto, Italy; 2Ospedale P Pederzoli Casa di Cura Privata SpA, Peschiera del Garda, Veneto, Italy; 3Massachusetts General Hospital, Boston, MA
Background. The rate of pathologic complete response (pCR) following neadjuvant treatment for pancreatic ductal adenocarcinoma (PDAC) seems to be increased since the introduction of new multiagent regimens and actually ranges between 2% and 16% in PDAC. However, the role of chemoradiation (CRT) in terms of pathologic response, resecability, and survival benefit is still debated. The aim of this study was to compare the rates of pCR in patients with PDAC receiving neoadjuvant chemotherapy (ChT) or CRT, and secondarly, to compare if the rate of R0 resection and overall survival (OS).
Methods. This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022341466). A systematic review was conducted on MEDLINE/PubMed and Embase public archives for studies published between 2012 and 2022. All studies reporting clinical outcomes of patients with PDAC following neoadjuvant therapy were considered eligible for inclusion in this systematic review and meta-analysis. Studies were included with no distinction regarding to the clinical stage (resectable, borderline-resectable or locally-advanced) or pancreatic location of the primary tumor. Only studies reporting separately the outcomes after pancreatectomy after any type ChT or CRT were included. A meta-analysis comparing the rate of pCR, R0 resection rate, and 3-year OS following ChT vs CRT in patients undergoing pancreatectomy for PDAC was performed. The heterogeneity of the studies was assessed using the I2 statistic.
Results. The literature search identified 4003 potentially relevant studies, 19 studies eligible for full-text assessment, and 5 studies, published between 2016 and 2022, were included in the systematic review and in the meta-analysis. Of them, 2 were retrospective single-center studies, 2 were retrospective multi-center studies, and one was a prospective Phase II multi-center RCT. Overall, 433 patients and 770 in ChT and CRT group respectively were included in the meta-analysis. Among patients assigned to ChT the most frequent regimen was FOLFIRINOX (80%); among those who underwent CRT the most common regimen was FOLFIRINOX+RT (49.2%). A statistically significant increased rate of pCR and R0 resections among resected patients were found in CRT patients (OR 3.38, 95% CI 1.51-7.57, p=0.003, and OR 1.52, 95% CI 1.14-2.02, p=0.004, respectively), whereas 3-year OS was not different in the two groups (OR 1.08, 95% CI 0.77-1.52, p=0.64), even if CRT was used more often in patients with a locally advanced PDAC (56.8% Vs 32.6%, p<0.0001) .
Conclusions. The use of CRT may have positive impact on pathologic response and R0 resection rate, whereas a benefit in survival was not reported, probably due to the risk of micrometastasis and distant metastasis that may impact on survival of locally advanced PDAC patients.
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