Background and Objectives: A high systemic immune-inflammation index (SIII) at diagnosis of various cancers, including pancreatic cancer, is associated with poor prognosis. The impact of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) chemotherapy or stereotactic body radiotherapy on this index is unknown. In addition, the prognostic value of changes in the SIII during treatment is unclear. In this retrospective analysis, we aimed to find answers regarding patients with advanced pancreatic cancer. Methods: Patients with advanced pancreatic cancer treated with FOLFIRINOX chemotherapy alone or with FOLFIRINOX chemotherapy followed by stereotactic body radiotherapy between 2015 and 2021 in 2 tertiary referral centers were included. Baseline characteristics, laboratory values at 3 time points during treatment, and survival outcomes were collected. The patient-specific evolutions of SIII and their association with mortality were assessed with joint models for longitudinal and time-to-event data. Results: Data of 141 patients were analyzed. At a median follow-up time of 23.0 months (95% CI: 14.6–31.3), 97 (69%) patients had died. Median overall survival was 13.2 months (95% CI: 11.0–15.5). During treatment with FOLFIRINOX, the log (SIII) was reduced by −0.588 (95% CI: −0.0978, −0.197; P = 0.003). One unit increase in log (SIII) increased the hazard ratio of dying by 1.604 (95% CI: 1.068–2.409; P = 0.023). Conclusions: In addition to carbohydrate antigen 19-9, the SIII is a reliable biomarker in patients with advanced pancreatic cancer.

Background: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. Methods: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. Results: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16−CD11b+HLA−DR^low myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. Conclusions: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.

Background/Objectives: Stereotactic body radiotherapy (SBRT) aims to prolong overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) with vascular contact without progression of disease after (m)FOLFIRINOX. The primary objective of this study was to determine the potential value of SBRT. Methods: This nationwide, retrospective cohort study included patients with PDAC without progression of disease after at least four cycles of (m)FOLFIRINOX. The study comprised two cohorts, the SBRT and the No SBRT group. A landmark analysis excluded patients with a follow-up or OS time less than 12 months to minimize immortal time bias in the SBRT group. The primary outcome was OS from diagnosis. Secondary outcomes were the histopathological characteristics after resection. Results: Overall, 331 patients were included, of whom 231 were in the landmark analysis. In the overall cohort, the median OS was 20.7 months in the SBRT group versus 15.7 months in the No SBRT group (p = 0.004). In the landmark analysis, the median OS was 23.2 months in the SBRT group compared to 22.3 months in the No SBRT group (p = 0.554). These results indicate the presence of immortal time bias in the overall cohort in favor of the SBRT group. In the subgroup after resection, ypT0-2 (95% versus 76.5% [p = 0.026]), ypN0 (75% versus 37.3% [p < 0.004]), and absence of perineural invasion (50% versus 68.6% [p = 0.015]) were more prevalent in the SBRT group. Conclusions: In a landmark analysis, including only patients who survived at least 12 months after diagnosis, we found no difference in median OS between (m)FOLFIRINOX-only and (m)FOLFIRINOX with consecutive SBRT.