Data Sheet 4_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，以极低的5年生存率为显著特征。尽管免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）在多种实体瘤中已证实具有疗效，但在胰腺导管腺癌的治疗中，尤其是错配修复蛋白完整型（mismatch repair–proficient, pMMR）病例，其应用受到肿瘤微环境（tumor microenvironment, TME）免疫抑制特性的限制。因此，目前亟需针对pMMR型局部晚期胰腺癌的更有效治疗策略。
病例介绍：我们报告1例65岁女性患者，经诊断为局部晚期胰腺癌（cT4N1M0，Ⅲ期），病理证实为胰腺导管腺癌，错配修复蛋白完整型，程序性死亡配体1（programmed death-ligand 1, PD-L1）联合阳性评分（combined positive score, CPS）高达30。初始肿瘤标志物显著升高（CA19-9：62228.8 U/L；癌胚抗原（carcinoembryonic antigen, CEA）：100 ng/mL）。患者接受了一种名为BRICS方案的新型多模式治疗，该方案缩写源自双歧杆菌补充治疗（Bifidobacterium supplementation）、低分割放疗（hypofractionated Radiotherapy）、免疫治疗（PD-1抑制剂）、低剂量化疗（low-dose Chemotherapy）及立体定向治疗（Stereotactic approach）。该方案可根据个体疾病特征进行个性化调整。本病例中，具体治疗方案为：立体定向体部放疗（SBRT）24 Gy/3次分割 → 每21天给予特瑞普利单抗240 mg + 白蛋白结合型紫杉醇200→100 mg + 安罗替尼12 mg，第1~14天给药，同时持续服用双歧杆菌三联活菌片。治疗后影像学检查提示完全缓解（complete response, CR），治疗后5个月肿瘤标志物仍维持正常水平。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，整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联合治疗方案，可在无需手术的前提下，使错配修复蛋白完整型局部晚期胰腺癌且PD-L1高表达的患者获得完全缓解。上述结果挑战了“错配修复蛋白完整型状态必然预示免疫治疗耐药”的主流学术观点。研究结果表明，在程序性死亡配体1联合阳性评分较高的错配修复蛋白完整型胰腺癌患者中，多模式治疗策略可重塑肿瘤微环境并克服免疫抵抗，为该类患者指明了颇具前景的治疗方向。