FPC is a putative genetically heterogeneous syndrome defined as kindreds with multiple blood relatives with pancreatic adenocarcioma (PDAC). It has been hypothesized that germline mutations in DNA repair genes contribute to FPC, resulting in variable outcomes and response. We evaluated survival in FPC patients (pts) with resectable and unresectable PDAC.
Pts were identified from the Ontario Pancreatic Cancer Study database, recruited from January 1998-July 2016. All pts were seen by genetic services. FPC pts were age and stage matched with cases without a family history of PDAC and who tested germline BRCA mutation negative (non-FPC). Stage was classified as early operable (I/II) or late inoperable (III/IV). Pts were matched within 5 years of the treatment period. Only those who had either received surgery or at least 1 cycle of chemotherapy were included. The Kaplan-Meier method was used to assess survival.
144 pts were evaluated, 72 in each cohort. In the FPC group, 65 pts had at least 1 FDR with PDAC and 7 pts, at least 2 relatives (1st-3rd degree) with PDAC. Median age was 66 years; there were more females in the FPC group (54% vs 49%). 33 pts (46%) in each group had early stage disease and received surgery. Adjuvant therapy was given in 70% and 73% of the FPC and non-FPC cohorts respectively. 1 FPC pt, received adjuvant gemcitabine/erlotinib. 6 non-FPC pts received FOLFIRINOX, 3 as neo-adjuvant and 3 as adjuvant treatment. Of those with late stage disease, (n = 39 each), combination chemotherapy was given in 23 (59%) and 28 (72%) pts in FPC vs non-FPC groups respectively. The median overall survival (OS) was 16 months (mths) in the FPC group vs 13mths in the non-FPC group (p = 0.46). Stratifying by stage, in FPC vs non-FPC pts, median OS in early disease was 31 vs 27 mths (p = 0.73) and in late disease 13 vs 9 mths (p = 0.12). Platinum was used in 18 (46%) FPC and 17 (44%) non-FPC pts with late disease. Platinum regimens improved median OS overall compared to no platinum (12mths vs 9mths, p = 0.04) but was not associated with FPC status.
FPC is poorly understood but trends towards a better prognosis and response to therapy. The use of platinum based chemotherapy in these pts could be considered; however further research is warranted.
Clinical trial identification
Legal entity responsible for the study
All authors have declared no conflicts of interest.