Abstract:
Background: Several non-randomized studies have investigated gemcitabine-based neo-adjuvant treatments followed by surgery in BR-PDAC. We aimed to explore the effectiveness of this treatment on overall survival (OS) in resected patients.
Methods: A computerized search of PubMed, Embase, Ovid Medline and Cochrane Library was carried out to retrieve all articles published on neoadjuvant treatment for BR-PDAC from the time of database inception to 31 March 2017. The primary outcome was OS. Secondary outcomes were disease-free survival (DFS), chemotherapy toxicity and R0 resection. Primary and secondary outcomes were calculated using the individual participant data (IPD). Patients were staged as BR-PDAC according to the NCCN preoperative radiological criteria (version 2.2016).
Findings: Median OS in the seven included studies ranged between 22.9-41.2 and 9.3-15.4 months in resected and nonresected patients, respectively (Table). Four centers provided IDP of 170 (68%) patients treated with gemcitabine-based regimens; 121 (71%) patients also received pre-operative radiation. Pooled median patient level OS were 27.2 (95% CI 23-31.3) and 20.4 (95% CI 12.7-28) months in the resected and non-resected group (p=0.03) (Figure). DFS after resection was 17.9 (95% 14.3-21.5) months. The different gemcitabine based protocols did not show any significantly OS differences. Eighty-two (48.2%) patients experienced Grade III-IV adverse events. Resection and R0 resection rates were 62% (105 patients) and 88% (92 patients), respectively. Interpretation: Gemcitabine-based neoadjuvant therapy followed by surgery is an effective option in BR-PDAC. Median OS in both resected and non-resected patients appears longer than with upfront surgery. RCTs should further investigate treatment sequencing and specific elements of neoadjuvant therapy regimens.
