Abstract
BackgroundThe added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy.MethodsA systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes.ResultsWe included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable.ConclusionsIn this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.
Highlights
The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear
The pooled weighted median overall survival (OS) in patients who underwent resection was calculated. For studies reporting the latter outcome from time of resection, the median OS time was increased with the estimated duration of neoadjuvant treatment based on the reported median number of cycles plus 1 month as estimated time between the end of chemotherapy and surgery date
In this systematic review and meta-analysis including 512 patients with (B)RPC, no difference in survival could be demonstrated between treatment with neoadjuvant FOLFIRINOX with radiotherapy or neoadjuvant FOLFIRINOX alone
Summary
Pancreatic ductal adenocarcinoma is one of the most aggressive solid tumors.[1]. it is only the 12th most common cancer globally, it is one of the leading causes of cancer-related death in developed countries.[2]. Two patientlevel meta-analyses of observational studies in patients with locally advanced pancreatic cancer (LAPC) and BRPC treated with FOLFIRINOX ± radiotherapy showed promising results.[17,18] Due to limited high-level evidence, current guidelines do not draw final conclusions on whether these multidrug regimens should be combined with radiotherapy.[3,4,5] The role of neoadjuvant radiotherapy in addition to neoadjuvant FOLFIRINOX in patients with (B)RPC remains unclear. Eligible studies reported outcomes for treatment-naıve patients with resectable or borderline resectable pancreatic cancer [(B)RPC] as defined within each study, and who were either treated with neoadjuvant FOLFIRINOX alone (FOLFIRINOX alone group) or with neoadjuvant FOLFIRINOX followed by any type of radiotherapy (FOLFIRINOX with radiotherapy group). Letters to the editor, case reports, conference abstracts, and articles written in language other than English were excluded
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