BackgroundPatients 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.MethodsWe 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.ResultsAmong 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).ConclusionsProgressive 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.

中文翻译：

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FOLFIRINOX 后局部治疗应用和胰腺癌生存率的骨骼肌指数变化


背景临界可切除 （BR） 或局部晚期胰腺癌 （LAPC） 患者需要复杂的管理策略。本研究评估了围化疗期骨骼肌指数 （SMI） 和碳水化合物抗原 19-9 （CA 19-9） 在接受 FOLFIRINOX 治疗的 BRPC 或 LAPC 患者中的预后意义。方法我们回顾性评估了 2015 年至 2020 年间至少接受 4 个化疗周期的 227 例 BR 或 LAPC 患者。我们分析了化疗反应、计算机断层扫描 （CT） 和 CA19-9 上 SMI （ΔSMI， %） 的变化，以确定它们对无进展生存期 （PFS） 和总生存期 （OS） 的影响。在完成 4 个化疗周期后 3 个月内早期应用局部区域治疗 （LRT） 后，比较 ΔSMI 和 CA19-9 亚组之间的结局。结果在 227 例 BR 和 130 例 LAPC 患者 （中位年龄 60 岁;124 [54.6%] 男性） 中，50.7% 对化疗部分缓解 （PR），44.5% 表现为疾病稳定，4.8% 表现为疾病进展 （PD）。化疗后 CA19-9 水平在 41.0% 的患者中恢复正常。高和低 ΔSMI 组 （基于男性 -8.6% 和女性 -2.9% 的性别特异性临界值）分别包括 114 名 （50.2%） 和 113 名 （49.8%） 患者。高 ΔSMI 组在 PFS （HR = 1.32，p = 0.05） 和 OS （HR = 1.74，p = 0.001） 方面的生存率均差于低 ΔSMI 组。多变量分析显示，ΔSMI（高与低;PFS，HR = 1.39，p = 0.03;OS，HR = 1.82，p < 0.001）和化疗后反应（PD 与 PR/SD;PFS，HR = 18.69，p < 0.001;OS，HR = 6.19，p < 0.001）与 PFS 和 OS 独立相关。此外，化疗后 CA19-9 （≥ 37 vs. < 37;HR = 1.48，p = 0。01） 是 PFS 的独立预测因子。化疗后早期应用 LRT 可显著改善两组 ΔSMI 组的 PFS 和 OS （均 p < 0.05）。然而，在高 ΔSMI 和化疗后 CA19-9 ≥ 37 的组中没有益处 （PFS，p = 0.39 和 OS，p = 0.33）。结论 4 个化疗周期后进行性肌肉减少症恶化与 FOLFIRINOX 后 BR 或 LAPC 患者生存结局不良相关。我们还研究了使用 ΔSMI 和化疗后 CA 19-9 的早期应用 LRT 的最佳临床环境。