Data Sheet 3_Complete response to BRICS in Locally advanced pancreatic cancer (pMMR, CPS 30): a case report.pdf

BackgroundLocally advanced pancreatic cancer (LAPC) has a dismal prognosis, marked by an exceedingly low 5-year survival rate. While immune checkpoint inhibitors (ICIs) have demonstrated efficacy across various solid tumors, their application in the treatment of pancreatic ductal adenocarcinoma—particularly in mismatch repair–proficient (pMMR) cases—is restricted by the immunosuppressive nature of the tumor microenvironment (TME). Thus, more effective treatment strategies for pMMR LAPC are urgently needed.
Case presentationWe present a 65-year-old female diagnosed with LAPC (cT4N1M0, Stage III), confirmed pathologically as pancreatic ductal adenocarcinoma with pMMR status and a high programmed death-ligand 1 (PD-L1) combined positive score (CPS) of 30. Initial tumor markers were significantly elevated (CA19-9: 62,228.8 U/L; CEA: 100 ng/mL). The patient received a novel multimodal treatment referred to as the BRICS Regimen, an acronym derived from Bifidobacterium supplementation, Radiotherapy (hypofractionated), Immunotherapy (PD-1 inhibitors), Chemotherapy (low-dose), and Stereotactic approach. This protocol can be modified to match the individual disease characteristics. In this case, the treatment comprised SBRT 24 Gy/3 fractions → q21d toripalimab 240 mg + nab-paclitaxel 200→100 mg + anlotinib 12 mg d1–14, with continuous Bifidobacterium triple viable tablets. Imaging following treatment indicated a complete response (CR), and tumor markers remained normal for 5 months post-therapy. The treatment was well tolerated, with no severe adverse events reported.
ConclusionThis report suggests that a combined modality approach—integrating SBRT, chemotherapy, antiangiogenic therapy, ICI, and probiotics—may achieve CR in patients presenting with pMMR LAPC and high PD-L1 expression, even without surgery. These results challenge the prevailing assumption that pMMR status invariably predicts resistance to immunotherapy. These findings suggest that, in pMMR pancreatic cancers with high PD-L1 CPS, multimodal treatment strategies may remodel the tumor microenvironment and overcome immune resistance, highlighting a promising therapeutic direction.

背景 局部晚期胰腺癌（locally advanced pancreatic cancer, LAPC）预后极差，5年生存率极低。尽管免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）在多种实体瘤中已展现出治疗疗效，但由于胰腺导管腺癌（pancreatic ductal adenocarcinoma）的肿瘤微环境（tumor microenvironment, TME）具有免疫抑制特性，其在该病治疗中的应用受到限制，尤其针对错配修复蛋白完整型（mismatch repair-proficient, pMMR）患者。因此，目前亟需针对错配修复蛋白完整型局部晚期胰腺癌的更有效治疗策略。

病例报告 我们报告1例65岁女性局部晚期胰腺癌患者，临床分期为cT4N1M0 Ⅲ期，经病理证实为胰腺导管腺癌，错配修复蛋白完整型，程序性死亡受体配体1（programmed death-ligand 1, PD-L1）联合阳性评分（combined positive score, CPS）为30分，表达水平较高。初始肿瘤标志物水平显著升高：糖类抗原19-9（CA19-9）为62228.8 U/L，癌胚抗原（CEA）为100 ng/mL。患者接受了一种新型多模式治疗方案——BRICS方案，该缩写由双歧杆菌补充治疗（Bifidobacterium supplementation）、大分割放疗（hypofractionated radiotherapy）、免疫治疗（PD-1抑制剂治疗）、低剂量化疗（low-dose chemotherapy）及立体定向治疗（stereotactic approach）的首字母组合而成，该方案可根据患者个体疾病特征进行调整。本病例的具体治疗方案为：立体定向体部放疗（stereotactic body radiation therapy, SBRT）24 Gy/3次，每21天1个周期；特瑞普利单抗240 mg + 白蛋白结合型紫杉醇初始剂量200 mg（后调整为100 mg）+ 安罗替尼12 mg，于第1~14天口服，同时持续服用双歧三联活菌片。治疗后影像学检查提示完全缓解（complete response, CR），且治疗后5个月内肿瘤标志物均维持在正常水平。该治疗耐受性良好，未报告严重不良事件。

结论 本病例报告提示，错配修复蛋白完整型且PD-L1高表达的局部晚期胰腺癌患者，即使未接受手术治疗，联合立体定向体部放疗、化疗、抗血管生成治疗、免疫检查点抑制剂及益生菌的多模式治疗方案，有望实现完全缓解。该结果挑战了“错配修复蛋白完整型会无一例外导致免疫治疗耐药”的主流学术观点。本研究结果表明，对于错配修复蛋白完整型且PD-L1联合阳性评分较高的胰腺癌患者，多模式治疗策略可重塑肿瘤微环境并克服免疫耐药，为该类患者的治疗指明了极具前景的方向。