Page 14 - Demo

Chapter 112contact with the superior mesenteric artery, celiac trunk, or common hepatic artery (9) (https://dpcg.nl). This stage is referred to as locally advanced pancreatic cancer (LAPC). Patients diagnosed with either LAPC (unresectable, without distant metastasis) or metastatic pancreatic cancer are typically not considered candidates for curative treatment. Instead, palliative chemotherapy is recommended to enhance survival and alleviate cancer-related symptoms. However, for patients with LAPC, the option of resection may be reconsidered following chemotherapy based on their response to treatment. In a non-randomized study around 12% of patients with LAPC underwent surgical resection after treatment with FOLFIRINOX (10). For patients with LAPC or metastatic disease, FOLFIRINOX and nab-paclitaxel plus gemcitabine are currently widely used regimes. In the Netherlands the preferred first-line treatment for fit patients is FOLFIRINOX, as stated in the recently updated version of the Dutch pancreatic cancer guideline (https://richtlijnendatabase.nl/richtlijn/pancreascarcinoom). FOLRIFINOX resulted in an improvement in response rate (RR), progression free survival (PFS) and OS compared to gemcitabine monotherapy (median OS of 11.1 vs. 6.8 months) for patients with metastatic PDAC (11). Gemcitabine in combination with nabpaclitaxel showed an improved RR, OS and PFS compared to gemcitabine monotherapy (median OS of 8.5 vs. 6.7 months) (12). For patients with a known germline BRCA1/2 mutation olaparib maintenance therapy can be considered although no significant OS benefit was observed in a recent update of the POLO trial (13). The optimal second-line systemic therapy approach for patients in a good clinical condition after first-line FOLFIRINOX failure is not known. An OS of 11.5 and 12.4months from diagnosis was reported for gemcitabine based secondline therapy after FOLFIRINOX resistance in a retrospective cohort study (14). Liposomal irinotecan and 5-FU/leucovorin is approved for use in patients with metastatic PDAC previously treated with gemcitabine-based therapy. This approval is based on the observed improvement in median OS compared to treatment with 5-FU/ leucovorin alone in the final OS analysis of the global phase 3 NAPOLI-1 trial (OS 6.2 vs 4.2 months; hazard ratio [HR] 0.75) (15). In a previous Dutch NCR cohort the median OS was 11.2 months for patients who were treated with all types of systemic second-line therapy (16). Best supportive care is considered for patients in a moderate condition.Part one of this thesis describes two studies exploring therapeutic interventions in patients with pancreatic cancer. In chapter 2 we focus on patients with LAPC.