子宫颈癌新辅助化疗采用流式细胞测定指导放射治疗最佳时机的探讨

Flow cytometry in determining the optimal radiotheraphy time of neoadjuvant chemotherapy for cervical cancer

目的采用流式细胞技术检测新辅助化学治疗（简称化疗）子宫颈癌后不同时间肿瘤细胞周期分布状态,探讨放射治疗的最佳时机。方法选择2013年1月至2014年5月贵阳医学院附属肿瘤医院Ⅱb期-Ⅲb期病理明确诊断为宫颈癌患者90例,中位年龄51岁。治疗方案为新辅助化疗＋同步放化疗。新辅助化疗为TP方案（紫杉醇＋顺铂或紫杉醇＋洛铂化疗）2周期;同步化疗采用顺铂或洛铂单药;放射治疗采用盆腔调强放射治疗（IMRT）及三维适形近距离治疗。分别收集治疗前、2周期化疗后、同期放化疗前5 d、开始同期放化疗、开始同期放化疗期间每5 d取材1次、同期放化疗结束、同期放化疗结束后10 d、同期放化疗结束后30 d时DNA倍体分析。DNA倍体分析采用BD FACSCantoⅡ流式细胞仪分析。结果 2周期新辅助化疗后处于高S期细胞所占比率与新辅助化疗前相比较明显升高,分别为42.0%和60.3%（P=0.028）,差异有统计学意义（P〈0.05）。2周期新辅助化疗后10-15 d处于高S期细胞所占比率渐下降,与新辅助化疗前相接近（P=0.119）,差异无统计学意义。放射治疗至30.6 Gy时S期细胞所占比率与新辅助化疗前相比较略有下降,放射治疗结束后处于高S期细胞所占比率进一步下降,明显低于新辅助化疗前（P=0.009）。结论子宫颈癌新辅助化疗后肿瘤细胞再分布的存在提示放射治疗最好在新辅助化疗后10-15 d开始。通过DNA倍体分析了解细胞周期,有助于指导放射治疗时间,从而增加放射治疗疗效。

Objective To investigate the optimal time of radiation therapy by using flow cytometry in detecting distribution of tumor cell cycle at different time after neoadjuvant chemotherapy for patients with cervical cancer. Methods From January2013 to May 2014, 90 patients with Ⅱb- Ⅲb cervical cancer diagnosed by pathology were enrolled, the median age was 51 years old, and the treatment methods were neoadjuvant chemotherapy ＋ concurrent radiotherapy and chemotherapy. Neoadjuvant chemotherapy used TP method（paclitaxel ＋ cisplatin or paclitaxel ＋ chemotherapy with lobaplatin） for 2 cycles, concurrent chemotherapy was cisplatin and lobaplatin monotherapy; radiotherapy was pelvic intensity-modulated radiation therapy（IMRT）and three dimensional conformal brachytherapy. The treatment data was collected and carried out DNA ploidy analyze before treatment, after 2 cycles of chemotherapy, before 5 days of concurrent radiotherapy and chemotherapy, at the beginning concurrent chemoradiotherapy, after radiotherapy and chemotherapy treatment, after 10 days of radiotherapy and 30 days of chemotherapy, and data was also extracted once on every 5 days during concurrent chemoradiotherapy. DNA ploidy analyze was carried out by BD FACSCanto Ⅱ flow cytometry. Results High S-phase cell rate after 2 cycles of neoadjuvant chemotherapy increased significantly compared with that of before neoadjuvant chemotherapy, which were 42.0 % and 60.3 %（P = 0.028）, the difference was statistically significant（P〈0.05）. High S-phase cell rate at 10- 15 days after 2 cycles neoadjuvant chemotherapy decreased gradually and approached the data with neoadjuvant chemotherapy, and the difference was no statistically significant（P = 0.119）. High S-phase cell rate of neoadjuvant chemotherapy of radiation therapy at 30.6 Gy was slight decreased compared with that of before neoadjuvant chemotherapy. High S-phase cell rates after radiotherapy declined further, and became significantly lower than that of before neoadjuvant chemotherapy（P = 0.009）. Conclusion It is demonstrated that tumor cell distributions after neoadjuvant chemotherapy for cervical cancer shows the treatment optimal time 10-15 days after neoadjuvant chemotherapy. The DNA ploidy analysis in cell cycle is helpful to determine the radiation treatment time, which may increase efficacy of radiation therapy.