Treatment of locally advanced pancreatic cancer
Authors:   , Brada Lilly Janne Hilkka 
Published: February 2025

This thesis aimed to evaluate the nationwide clinical practice and oncologic outcomes in the treatment of LAPC.

2. This chapter provides an overview of the clinical practice of treatment of LAPC patients. Median overall survival was 10 months. The majority of patients start with chemotherapy (77%). In the Netherlands FOLFIRINOX is the first choice of chemotherapy (77%), with a median overall survival of 14 months. A resection was performed in 13% of patients after FOLFIRINOX with a median overall survival of 23 months. This study showed that there is no standard treatment for patients diagnosed with LAPC after first line chemotherapy.

3. This chapter reports that LAPC patients aged 75 years and older are less likely to be treated with chemotherapy, compared to younger patients. Elderly patients who were treated with chemotherapy reported a comparable overall survival to the younger patient groups. The results of this study suggest that chemotherapy should probably be considered more often in elderly patients.

4. A multicenter prospective cohort study researching the safety and effectiveness in patients with LAPC was performed. Unfortunately, the study was terminated early. This chapter provides the outcomes of the study combined with LAPC patients treated with nab-paclitaxel plus gemcitabine in the forgoing time period. Disease control rate was 71% after 2 cycles and median overall survival was 8 months. In the majority of patients (75%) an adverse event occurred, there was no treatment-related mortality. Nab-paclitaxel plus gemcitabine seems to be safe and effective, even in patients with a relatively worse performance score.

5. It is unclear which specific patients benefit from FOLFIRINOX and might undergo a resection after treatment. In this chapter, two nomograms were developed to predict overall survival and the possibility for a resection in patients with LAPC who can start treatment with FOLFIRINOX. These nomograms could be a helpful tool to support the decision-making process and patient counseling.

6. It is difficult to distinguish the exact benefit of resection from the benefit of FOLFIRINOX. Patients with LAPC undergoing resection after FOLFIRINOX were matched to patients treated with FOLFIRNOX only. Matching was based on predictors for overall survival. The median overall survival was 24 months in resected patients versus 15 months in non-resected patients. After propensity score matching the overall survival remained 24 vs 15 months for the resected and non-resected patients, respectively. These findings suggest that resection in LAPC patients is associated with an improved overall survival.

7. In this chapter the short- and long-term outcomes of resected LAPC patients are compared to the outcomes in (borderline) resectable pancreatic cancer patients, to put the outcomes in perspective. LAPC patients had an overall better clinical performance. Pancreas-specific complications, ninety-day mortality, disease free interval, and overall survival were comparable. This chapter suggests that resection in carefully selected LAPC patients is safe and probably effective.

8. It is of interest which patients after resection of LAPC develop early recurrence. because they probably have little benefit from surgery. This chapter predicted the optimal cut-off point for early recurrence and factors associated with it. It was established that early recurrence occurs in the first 6 months after resection.

9. This chapter describes the results of the multicenter international randomized controlled PELICAN trial. Patients with LAPC are randomized to continuation of chemotherapy or to intra-operative RFA followed by chemotherapy. In the PELICAN trial overall survival (OS) was 12.1 months in the RFA plus chemotherapy group and 11.6 months in the chemotherapy only group. Progression free survival (PFS) was 5.8. months vs 6.9 months. This trial showed no survival benefit of patients with LAPC treated with RFA complementary to chemotherapy compared to chemotherapy alone.