基于分子靶标检测的58例难治或复发恶性实体肿瘤患儿个体化治疗

Individualized therapy for 58 children with refractory or relapsed malignant solid tumors based on the target detection of chemosensitivity

目的探讨基于分子靶标检测的个体化治疗在提高难治或复发恶性实体肿瘤患儿预后中的临床应用价值。方法收集2012年9月1日至2019年3月31日在上海交通大学医学院附属新华医院诊治的恶性实体肿瘤患儿的临床信息,采用免疫组织化学染色、实时荧光定量PCR、二代测序的方法,检测并分析常用抗肿瘤药物的分子靶标。比较个体化治疗组与舒缓治疗组患儿的肿瘤缓解率及生存率。结果172例患儿接受分子靶标检测,其中13例标本采集于首次化疗前,159例标本采集于新辅助化疗后。结果显示,除甲氨蝶呤外的常用化疗药物均存在天然耐药,蒽环类药物在化疗后耐药率从41.9%上升至78.3%(P<0.05)。29例初发且难治患儿中,个体化治疗组的中位生存时间[(6.0±4.6)个月]及预期2年生存率[(39.2±22.6)%]均大于舒缓治疗组的[(1.5±1.4)个月,0](均P<0.05)。29例复发患儿中,个体化治疗组的中位生存时间[(6.0±2.3)个月]大于舒缓治疗组的[(1.0±0.5)个月](P<0.05),但预期2年生存率2组间差异无统计学意义(P=0.292)。结论可尝试扩展甲氨蝶呤在儿童恶性实体肿瘤治疗中的应用范围。基于分子靶标检测的个体化治疗可提高难治性恶性实体肿瘤患儿的总体生存率,而复发患儿的再治疗方案有待进一步探讨。

Objective To investigate the clinical value of individualized therapy based on the molecular target detection to improve the prognosis of children with refractory or relapsed malignant solid tumor.Methods The clinical data of children who were diagnosed with malignant solid tumors between September 1st 2012 and March 31th 2019 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled.The chemosensitivity of commonly used antitumor drugs was investigated and analyzed by detecting the target gene or protein with immunohistochemistry,real time fluorescence quantitative polymerase chain reaction and next generation sequencing.The tumor response rates and survival rates of patients with refractory or relapsed malignant solid tumors in individualized therapy group were compared with that in palliative therapy group.Results The chemosensitivity of commonly used antitumor drugs was investigated in 172 patients.When other tissues were collected after neoadjuvant chemotherapy in 159 cases,the tumor tissues were collected before primary chemotherapy in 13 cases.The results of chemosensitivity in whole patients suggested the natural resistance of tumor cells to commonly used antitumor drugs except Methotrexate.The resis-tance rate of anthracyclines increased from 41.9%to 78.3%after chemotherapy(P<0.05).Both the median survival time[(6.0±4.6)months]and the expected 2-year survival rate[(39.2±22.6)%]of individualized therapy group were higher than the median survival time[(1.5±1.4)months]and the expected 2-year survival rate(0)of palliative therapy group in 29 children developing primary and refractory disease(all P<0.05).The median survival time[(6.0±2.3)months]of the individualized therapy group was higher than that[(1.0±0.5)months]of palliative therapy group in 29 children suffering from relapsed disease(P<0.05).However,there was no significant diffe-rence of expected 2-year survival rate between the 2 groups(P=0.292).Conclusions An attempt may be made to expand the application scope of Methotrexate in therapy of children suffering from malignant solid tumors.Individualized therapy based on the target detection of chemosensitivity can increase the overall survival rate of patients with refractory malignant solid tumors.However,treatment methods for children with recurrence disease still need further researches.