Liu Wenzhi, Liu Lili, Wang Ruoyu, Gong Guanyu, Ding Xinjia, Yang Bin, Bao Yun, Wang Zhiqiang, Zhang Bo, Zhao Dewei, Wu Fei, Ding Yan
The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Oncol. 2019 Feb 7;9:55. doi: 10.3389/fonc.2019.00055. eCollection 2019.
Primary appendiceal adenocarcinoma with peritoneal pseudomyxoma (PPM) has a high recurrence rate and refractory to medical interventions such as repetitive debulking surgery and systemic chemotherapy. Genome-based targeted therapy for such cases has not been well-documented. Here we present a 63-years-old women, who was diagnosed with recurrent mucinous adenocarcinoma of the appendix with local invasions and peritoneal carcinomatosis, was refractory to systemic chemotherapy after surgery. We used a regime developed using whole exome sequencing. Somatic mutations in the genes encoding VEGFR2, FGFR1, FGFR2, FGFR3, and KRAS were identified in the patient's tumor tissue. The patient was then treated with bevacizumab plus oxaliplatin. After 4 months of treatment, pelvic CT showed dramatic reduction of pseudomyoma and a decline of CA199 level from 5436.7 to 1121.4 U/ml. Continual treatment with bevacizumab-capecitabine remained effective and the patient's CA199 level further decreased to 401.26 U/ml according to the follow-up examination on Aug 15th, 2018. Results from this study show the evidence of gene mutations involving VEGF signal activation in the recurrence of appendiceal adenocarcinoma. Our results also suggest the association of these mutations with the effectiveness of anti-VEGF treatment using bevacizumab. Therefore, the screening of gene mutations involved in VEGF signaling and targeted therapy with anti-VEGF drugs may provide a new option to manage refractory/recurrent advanced-stage appendiceal adenocarcinoma.
原发性阑尾腺癌伴腹膜假黏液瘤（PPM）复发率高，对重复减瘤手术和全身化疗等医学干预措施难治。基于基因组的此类病例靶向治疗尚无充分文献记载。在此，我们报告一名63岁女性，她被诊断为复发性阑尾黏液腺癌伴局部侵犯和腹膜转移，术后对全身化疗难治。我们使用了通过全外显子测序开发的方案。在患者肿瘤组织中鉴定出编码VEGFR2、FGFR1、FGFR2、FGFR3和KRAS的基因中的体细胞突变。然后该患者接受贝伐单抗加奥沙利铂治疗。治疗4个月后，盆腔CT显示假黏液瘤显著缩小，CA199水平从5436.7降至1121.4 U/ml。继续使用贝伐单抗 - 卡培他滨治疗仍然有效，根据2018年8月15日的随访检查，患者的CA199水平进一步降至401.26 U/ml。本研究结果显示了阑尾腺癌复发中涉及VEGF信号激活的基因突变证据。我们的结果还表明这些突变与使用贝伐单抗的抗VEGF治疗效果相关。因此，筛查涉及VEGF信号传导的基因突变并用抗VEGF药物进行靶向治疗可能为治疗难治性/复发性晚期阑尾腺癌提供新的选择。
