术前多基因联合检测指导化疗对进展期神经母细胞瘤儿童手术切除率及预后的影响

目的 探索术前多基因联合对进展期神经母细胞瘤(NB)患儿手术切除率及预后的影响.方法 收集2013年1月至2015年l月本院收治的采取手术治疗的进展期(Ⅲ、Ⅳ期) NB 患儿 46例,均经病理确诊.根据INSS 分期及COG危险度分层,本组病例Ⅲ期 19 例 (41.3%) ,Ⅳ期 27 例 (58.7%) ,中危15例(32.6%),高危31例(67.4%).46例患儿均行术前新辅助化疗及手术治疗.依据术前是否行多基因联合检测分为多基因联合检测化疗组和常规化疗组.多基因联合检测组患儿,根据药敏结果参考选择化疗方案,如常规方案中有一种药物敏感,则可选择该方案进行化疗.如常规方案中无敏感药物或化疗两个疗程后评估提示化疗效果欠佳,则根据药敏结果选用包含至少一个敏感药物的化疗方案.结果 3例ERCC阴性中危患者最初使用方案无铂类药物,肿瘤缩小不满意,后根据药敏检测更换包含铂类药物方案后肿瘤缩小明显,均在更换方案后2~3个疗程行手术,其余4例中危患儿均提示TOPOIIα高表达,选用了OPEC方案及卡铂+足叶乙甙/阿霉素轮换.高危患儿中5例TOPOI阴性患儿最初均使用CT方案,第二或三个疗程时根据药敏结果换用OPEC方案.其余患儿检测结果提示对铂类、足叶乙甙或蒽环类其中之一敏感,使用OPEC方案化疗.多基因联合检测组术前化疗3~6个疗程,平均 4.6个疗程,常规化疗组术前化疗4~8个疗程,平均 5.6个疗程.多基因联合检测组患儿肿瘤瘤体缩减率明显高于常规化疗组.两组患儿手术切除率差异无统计学意义.本资料所有患儿均获得随访,随访时间14~30个月,平均21个月,总体生存率为60.9%,中危组患儿2年生存率为80%,高危组期患儿2年生存率51.6%.多基因联合检测化疗组2年生存率为中危85.7%,高危53.8%,总生存率为65%,常规化疗组2年生存率为中危75%,高危50%,总生存率为57.7%.两组相比差异无统计学意义.结论 进展期神经母细胞瘤患儿联合检测ERCC1、TOPOI 和TOPOIIα表达指导个体化化疗,有效率有所提高,化疗不良反应减少,改善了患儿生活质量.

Impact of combined detection of multiple genes on resection rate and prognosis of advanced neuroblastoma in children

Objective To explore the impact of combined detection of ERCC1 (excision repair cross complementing gene-1) and TOPOI (topoisomerase I) and TOPOIIα(topoisomerase IIα) on resection rate and prognosis of advanced neuroblastoma in children.Methods Forty-six children with advanced neuroblastoma were recruited between January 2013 and January 2015.According to the international neuroblastoma staging system and COG risk stratification, 19 cases (41.3%) were classified as stage III and 27 cases (58.7%) as stage IV.And 15 cases (32.6%) were classified as intermediate risk and 31 cases (67.4%) as high risk.All underwent neoadjuvant chemotherapy and surgery.They were divided into two groups based on whether a detection of multiple genes was performed.In gene detection group, chemotherapeutic regimens were selected according to the results of drug susceptibility.Routine regimens with at least sensitive one drug were selected.If no sensitive drugs were included or the effect of chemotherapy remained poor after two courses of chemotherapy, other regimens containing at least one sensitive drug were selected.Results Among 20 cases of gene detection, platinum-free regimen was initially used for 3 intermediate-risk ERCC (-) patients, tumor shrinkage was not satisfied, replacement regimen containing platinum drugs were used according to the results of drug susceptibility, the effects were significant and surgery was performed after 2 to 3 courses after regimen replacement.The gene testing results showed a high expression of TOPOIIα in the remaining 4 intermediate-risk patients among high-risk patients, CT regimen was used initially in 5 TOPOI (-) patients and switched to OPEC regimen in the second or third cycle according to the results of gene detection.OPEC regimen was selected in the remaining high-risk patients as the results of gene detection suggested that at least one drug was sensitive among platinum, etoposide and anthracycline.The mean time of preoperative chemotherapy was 4.6 (3-6) courses for gene detection group while the number was 5.6 (4-8) for control group.The rate of tumor reduction was statistically superior in gene detection group to that in control group.The resection rate was statistically insignificant for both groups.Follow-ups were conducted for all cases.The overall survival rate was 60.9%.And the 2-year survival rates of intermediate and high-risk patients were 80% and 53.8% respectively.In gene detection group, the 2-year survival rate was 85.7% for intermediate-risk patients and 53.8% for high-risk ones while the survival rate was 75% for intermediate-risk patients and 50% for high-risk ones in control group respectively.And the inter-group differences were statistically insignificant.Conclusions Combined detection of gene expression of ERCC1, TOPOI and TOPOIIαmay guide individualized chemotherapy in advanced neuroblastoma patients so as to improve the response rate, reduce adverse reactions and boost the quality-of-life.