1例KRAS突变的结直肠癌患者术前接受化疗联合免疫治疗的效果报道

doi:10.3969/j.issn.1674-8115.2025.09.018

上海交通大学学报（医学版） ›› 2025, Vol. 45 ›› Issue (9): 1256-1260.doi: 10.3969/j.issn.1674-8115.2025.09.018

• 病例报告 • 上一篇

1例KRAS突变的结直肠癌患者术前接受化疗联合免疫治疗的效果报道

江怡, 黄晨浩, 李祉良, 吴珺玮, 赵任, 张弢()

上海交通大学医学院附属瑞金医院普外科，上海 200025

收稿日期:2025-05-05 接受日期:2025-08-12 出版日期:2025-09-28 发布日期:2025-09-30
通讯作者: 张　弢，副主任医师，博士；电子信箱：woodyhom@yahoo.com。
基金资助:
国家自然科学基金(82202839);上海交通大学医学院“双百人”项目(20240043)

Effect of preoperative chemotherapy combined with immunotherapy in a colorectal cancer patient with KRAS mutation

JIANG Yi, HUANG Chenhao, LI Zhiliang, WU Junwei, ZHAO Ren, ZHANG Tao()

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2025-05-05 Accepted:2025-08-12 Online:2025-09-28 Published:2025-09-30
Contact: ZHANG Tao, E-mail: woodyhom@yahoo.com.
Supported by:
National Natural Science Foundation of China(82202839);“Two-Hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20240043)

摘要/Abstract

摘要：

结直肠癌（colorectal cancer，CRC）作为全球高发恶性肿瘤，其发病率呈持续上升趋势，尤其早发性CRC在年轻人群中的增长引发关注。新辅助治疗作为局部进展期CRC的重要治疗策略，通过降低肿瘤分期、提升手术根治率及改善预后展现出显著潜力。该文报道1例39岁男性乙状结肠腺癌患者，临床分期为cT_4aN_2aM₀（Ⅲ_C期），基因检测提示原癌基因KRAS突变（G13D）、微卫星稳定（microsatellite stability，MSS）型，伴癌胚抗原（carcinoembryonic antigen，CEA）显著升高、淋巴结转移及盆腔可疑种植结节，具有高侵袭性与潜在腹膜转移风险。针对这一传统免疫治疗应答不佳的难治性亚型，给予患者CapeOx方案（卡培他滨+奥沙利铂）序贯联合斯鲁利单抗的新辅助治疗。经6个治疗周期后肿瘤显著缩小，成功行腹腔镜下乙状结肠根治术，术后病理证实无残留（ypT₀N₀）。该病例提示，对于传统免疫治疗耐药的KRAS突变MSS型CRC患者，CapeOx化疗序贯程序性死亡受体1（programmed death-1，PD-1）抑制剂的联合策略可诱导深度病理缓解，为局部晚期患者提供转化治疗机会，但该治疗方案的普适性及长期获益性仍需长期研究及随访。

关键词: 结直肠癌, 新辅助治疗, KRAS突变, 微卫星稳定型

Abstract:

Colorectal cancer (CRC), a highly prevalent malignant tumor worldwide, has shown a continuously increasing incidence, particularly with the rise of early-onset CRC in young populations. Neoadjuvant therapy, as an important strategy for locally advanced CRC, shows significant potential to downstage tumors, improve radical surgical cure rates, and enhance prognosis. In this paper, a 39-year-old male patient with sigmoid colon adenocarcinoma at clinical stage cT_4aN_2aM₀ (stage Ⅲ_C) is reported. Genetic testing revealed a mutation in the oncogene KRAS (G13D) and microsatellite stability (MSS). The patient also had significantly elevated carcinoembryonic antigen (CEA), lymph node metastasis, and suspected pelvic implant nodules, with a high risk of invasiveness and potential peritoneal metastasis. Because he had a refractory subtype of CRC with poor response to traditional immunotherapy, the patient was treated with neoadjuvant therapy, comprising CapeOx regimen (capecitabine+oxaliplatin), followed sequentially by sluzumab; after 6 treatment cycles, the tumor shrank significantly, and laparoscopic radical sigmoid colon resection was successfully performed, with no residual (ypT₀N₀) confirmed by postoperative pathology. This case suggests that for patients with KRAS-mutated MSS CRC resistant to traditional immunotherapy, a combination of CapeOx chemotherapy followed by programmed death-1 (PD-1) inhibitors may induce a deep pathological response and provide translational treatment opportunities for locally advanced patients. However, the universality and long-term benefits of this treatment regimen still require further longitudinal studies and clinical follow-up.

Key words: colorectal cancer (CRC), neoadjuvant therapy, KRAS mutation, microsatellite stability (MSS)

中图分类号:

R735.3

江怡, 黄晨浩, 李祉良, 吴珺玮, 赵任, 张弢. 1例KRAS突变的结直肠癌患者术前接受化疗联合免疫治疗的效果报道[J]. 上海交通大学学报（医学版）, 2025, 45(9): 1256-1260.

JIANG Yi, HUANG Chenhao, LI Zhiliang, WU Junwei, ZHAO Ren, ZHANG Tao. Effect of preoperative chemotherapy combined with immunotherapy in a colorectal cancer patient with KRAS mutation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(9): 1256-1260.

图/表 2

图1 患者新辅助治疗前及3个周期CapeOx方案化疗后的下腹部增强CT图像Note： A‒C. Images before neoadjuvant therapy. D‒F. Images after neoadjuvant therapy. A and D, B and E, and C and F correspond to the same slice, respectively. The nodular shadows (red arrows) and the tumor size (yellow arrows) both reduced after neoadjuvant therapy. Bladder filling condition was different between the two examinations.

Fig 1 Contrast-enhanced lower abdominal CT scans of the patient before neoadjuvant therapy and after 3 cycles of CapeOx chemotherapy

图2 新辅助治疗后手术切除肿瘤组织的病理学检查（H-E染色）Note： A. ×40. B. ×200. The tumor cells were large, irregular in shape, with a high nucleocytoplasmic ratio, strong basophilia, and very few mitotic figures (yellow arrow). More connective tissue was observed between tumor cell clusters arranged in nests (blue arrows). Only a few tumor cells showed punctate necrosis (black arrow).

Fig 2 Pathological examination of surgically resected tumor tissue after neoadjuvant therapy (H-E staining)

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1例KRAS突变的结直肠癌患者术前接受化疗联合免疫治疗的效果报道

Effect of preoperative chemotherapy combined with immunotherapy in a colorectal cancer patient with KRAS mutation

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