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SURGERY WITH CURATIVE INTENT IN OLIGOMETASTATIC PANCREATIC CANCER TO THE LIVER IN THE ERA OF FOLFIRINOX: A SYSTEMATIC REVIEW AND META-ANALYSIS
Ottavia De Simoni*1, Marco Scarpa2, Marco Tonello1, Pierluigi Pilati1, Francesca Tolin1, Ylenia Spolverato2, Mario Gruppo1
1Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; 2University Hospital of Padua, Padua, Italy

BACKGROUND
Although chemotherapy is considered the standard of care for patients with metastatic pancreatic cancer (mPDAC), the improved survival achieved using new polychemotherapy regimens have suggested a potential role for conversion surgery following favorable response to initial chemotherapy (IC).
The purpose of this systematic review is to summarize the available evidences on the role of surgical resection with curative intent following chemotherapy in mPDAC, focusing on oligometastatic disease of the liver (lmPDAC).
MATERIALS AND METHODS
A systematic review was performed by searching 5 public databases for potentially relevant studies.
Eligible studies were those reporting on patients with lmPDAC undergoing surgery with curative intent after favorable response to IC We excluded case series with fewer than ten patients, insufficient descriptions of survival and IC data and downstaging criteria. Series reporting palliative surgery were also excluded.
Studies were included if they addressed surgical treatment of oligometastatic pancreatic cancer after IC. The main outcome measures was median overall survival (OS). Quality assessment was performed.
RESULTS
Nine observational retrospective studies were included and five of these focused on surgery for lmPDAC after IC. A total of 472 patients with mPDAC were analysed. The most common IC regimen was FOLFIRINOX (N 87, 58,7%). Interval between last IC and surgery varied from a median of 2 to 12 months. Both pancreatoduodenectomy (PD) and distal pancreatectomy (DP) were well represented (PD 182, 38,5%; DP 156, 33%). In all studies the main metastatic site was liver (N 315 patients). Surgery on liver metastases was heterogeneous, with a predominance of atypical resections (N 153 procedures).
Data about downstaging criteria, inclusion criteria for surgery, IC regimens and outcomes of patients with lmPDAC who underwent surgery after IC are reported in Table 1. Median OS varied from a median of 23 to 56 months after conversion surgery.
Only three studies reported survival comparison among patients treated with IC+surgery vs IC alone. Quality assessment is reported in Table 2: statistical heterogeneity resulted to be significantly high among these studies (I2: 80%, p<0.007) and different dataset could not be pooled. Nevertheless, reported OS seemed to be longer in patients with lmPDAC who underwent IC + surgery, compared to CT alone.
CONCLUSIONS
Despite wide heterogeneity of chemotherapy regimens, different downstaging criteria and potential selection biases, selected patients with oligometastatic lmPDAC could undergo conversion surgery after IC, with significantly higher survivals rates and acceptable morbidity rates compared to patients treated with chemotherapy alone. Future trials are needed for definition of univocal criteria of downstaging, oligometastatic definition and indications for surgery.

Table 1. Data about downstaging criteria, inclusion criteria for surgery, IC regimens and outcomes of five series of patients with lmPDAC who underwent surgery after IC

Table 2. Quality assessment of three studies reporting median overall survival of patients undergone CT plus surgery vs CT only.


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