Skeletal Muscle Index Changes on Locoregional Treatment Application After FOLFIRINOX and Survival in Pancreatic Cancer

Background: Patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) require complex management strategies. This study evaluated the prognostic significance of the perichemotherapy skeletal muscle index (SMI) and carbohydrate antigen 19-9 (CA 19-9) in patients with BRPC or LAPC treated with FOLFIRINOX.

Methods: We retrospectively evaluated 227 patients with BR or LAPC who received at least four cycles of chemotherapy between 2015 and 2020. We analysed chemotherapy response, changes in SMI (ΔSMI, %) on computed tomography (CT) and CA19-9 to determine their impact on progression-free survival (PFS) and overall survival (OS). After the early application of loco-regional treatments (LRT) within 3 months after completing four cycles of chemotherapy, the outcomes were compared between ΔSMI and CA19-9 subgroups.

Results: Among 227 patients (median age, 60 years; 124 [54.6%] male) with 97 BR and 130 LAPC, 50.7% showed partial response (PR) to chemotherapy, 44.5% showed stable disease and 4.8% showed progressive disease (PD). Post-chemotherapy CA19-9 levels were normalized in 41.0% of patients. The high and low ΔSMI groups (based on the gender-specific cut-off of -8.6% for males and -2.9% for females) comprised 114 (50.2%) and 113 (49.8%) patients, respectively. The high ΔSMI group had poorer survival rates than the low ΔSMI group in both PFS (HR = 1.32, p = 0.05) and OS (HR = 1.74, p = 0.001). Multivariable analysis showed that ΔSMI (high vs. low; PFS, HR = 1.39, p = 0.03; OS, HR = 1.82, p < 0.001) and post-chemotherapy response (PD vs. PR/SD; PFS, HR = 18.69, p < 0.001; OS, HR = 6.19, p < 0.001) were independently associated with both PFS and OS. Additionally, the post-chemotherapy CA19-9 (≥ 37 vs. < 37; HR = 1.48, p = 0.01) was an independent predictor for PFS. Early application of LRT after chemotherapy significantly improved PFS and OS in both ΔSMI groups (all p < 0.05). However, it was not beneficial in the group with high ΔSMI and post-chemotherapy CA19-9 ≥ 37 (PFS, p = 0.39 and OS, p = 0.33).

Conclusions: Progressive sarcopenic deterioration after four cycles of chemotherapy was associated with poor survival outcomes in patients with BR or LAPC after FOLFIRINOX. We also investigated the optimal clinical setting for the early application LRTs using the ΔSMI and post-chemotherapy CA 19-9.