Introduction: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. Aim: This study explores the efficacy of multisite intratumoral injections in improving a drug’s distribution while minimizing its side effects. Methods and Results: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p< 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p< 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p= 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p= 0.007). Conclusions: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.
引言：局部晚期不可切除胰腺癌（LAPC）预后极差，瘤内治疗获益有限。我们推测肿瘤内致密的基质阻碍了药物扩散。目的：本研究探讨多部位瘤内注射在改善药物分布同时降低其副作用的疗效。方法与结果：在LAPC原位移植瘤小鼠模型中，每周于四个独立位点进行奥沙利铂瘤内注射，较生理盐水组可减少46%的肿瘤生长（p<0.003）。与吉西他滨、白蛋白结合型紫杉醇或其联合方案相比，奥沙利铂对肿瘤微环境影响最为显著，表现为坏死、凋亡、成纤维细胞、炎症及浸润淋巴细胞增加（p<0.008）。当联合静脉FOLFIRINOX（FFX）方案时，多部位瘤内注射奥沙利铂较单部位注射可降低35%的肿瘤重量（p=0.007）。即使将瘤内治疗频率提高10倍，也未观察到额外可见毒性。该联合治疗方案较其他组显著延长生存期（p=0.007）。结论：多部位瘤内治疗联合全身系统治疗有望缩小LAPC肿瘤体积并提高总生存期。
肿瘤(癌症)患者之家