摘要
目的：探讨可切除局部晚期食管胃结合部腺癌行新辅助化疗（奥沙利铂＋卡培他滨， XELOX方案）的临床疗效。方法： 采用前瞻性研究方法。选取2011年1月至2014年12月汕头大学医学院附属肿瘤医院收治的106例可切除局部晚期食管胃结合部腺癌患者的临床病理资料。采用随机、单盲对照研究，通过随机数字表法将入组患者分为试验组和对照组；试验组采用新辅助化疗（XELOX方案）＋手术治疗＋术后辅助化疗（XELOX方案），对照组采用手术治疗＋术后辅助化疗（XELOX方案）。两组患者由同一组手术医师行全胃切除＋食管空肠Roux-en-Y吻合＋D2淋巴结清扫术。观察指标：（1）治疗情况。（2）术后病理学检查结果。（3）随访和生存情况。采用门诊方式进行随访，了解患者肿瘤复发、转移和生存情况，随访时间截至2017年2月。正态分布的计量资料以±s表示，组间比较采用t检验。非正态分布的计量资料以M（范围）表示，采用非参数检验。计数资料比较采用x2检验。等级资料比较采用非参数检验。采用KaplanMeier法绘制生存曲线和计算生存率，采用Logrank检验比较生存情况。结果：筛选出符合研究条件的患者106例，其中试验组54例，对照组52例。（1）治疗情况：①术前新辅助化疗情况：54例试验组患者术前行新辅助化疗2-4个周期，化疗期间胃肠道反应21例，1-2级粒细胞减少症17例，谷丙转氨酶（ALT）升高8例，3级粒细胞减少症1例，无不良反应7例。54例试验组患者术前新辅助化疗疗效：完全缓解4例，部分缓解27例，疾病稳定20例，疾病进展3例。54例试验组患者术前新辅助化疗反应程度：0级4例，1级13例，2级25例，3级12例。②手术治疗情况：试验组与对照组患者术前癌胚抗原分别为4.71 μg/L （0.20-36.19 μg/L）、14.09 μg/L （0.71-178.20 μg/L） ，两组比较，差异有统计学意义（Z=-1.92，P〈0.05）。两组患者均成功施行全胃切除＋食管空肠Roux-en-Y吻合＋D2淋巴结清扫术。试验组与对照组患者手术时间分别为（210±31）min、（195±26）min，两组比较，差异有统计学意义（t=-2.45，P〈0.05）。试验组患者术中出血量、术中输血、术后肛门首次排气时间、术后首次排便时间、术后首次进食时间、术后并发症、术后住院时间分别为（216±172）mL、6例、（4.3±1.0）d、（4.5±0.8）d、（3.1±0.5）d、11例、（15.0±5.0）d，对照组患者分别为（174±108）mL、4例、（4.2±1.0）d、（4.4±0.8）d、（3.1±0.5）d、15例、（15.0±5.0）d，两组患者上述指标比较，差异均无统计学意义（t=-1.01， χ^2=0.36，t=-0.31，-0.88，-0.36， χ^2=1.03，t=-0.38，P〉0.05）。③术后辅助化疗情况：试验组与对照组患者术后均完成辅助化疗。54例试验组患者发生化疗不良反应粒细胞减少症、ALT升高、胃肠道反应分别为25、5、28例，对照组分别为21、 7、30例，两组患者上述指标比较，差异均无统计学意义（χ^2=0.38，0.47，0.36，P〉0.05）。部分患者合并多种化疗不良反应症状。（2）术后病理学检查结果：试验组患者术后肿瘤最大直径，脉管癌栓，神经浸润，病理学T分期（T0、T2、T3、T4期），病理学TNM分期（0、Ⅰ、Ⅱ、Ⅲ期）分别为（3.6±1.4）cm、5、10、4、10、20、20、4、7、15、28例；对照组分别为（4.5±1.7）cm、24、30、0、2、13、37、0、1、12、39例，两组患者上述指标比较，差异均有统计学意义（t=-2.88， x2=18.14，17.30，Z=14.74，8.13，P〈0.05）。（4）随访和生存情况：试验组54例患者中，52例获得随访，随访时间为4-72个月，中位随访时间为32个月；对照组52例患者中，49例获得随访，随访时间为5-71个月，中位随访时间为36个月。试验组54例患者术后无病生存时间为26个月 （3-72个月），1、3、5年无瘤生存率分别为79.5%，64.7%，61.3%；术后总体生存时间为27个月（5-72个月）， 1、3、5年总体生存率分别为88.3%，69.2%，62.1%。17例患者肿瘤复发，其中腹腔局部复发2例、远处转移15例。对照组52例患者术后无病生存时间为33个月（2-71个月），1、3、5年无瘤生存率分别为89.7%，55.4%，55.4%；术后中位总体生存时间为33个月（5-71个月）， 1、3、5年总体生存率分别为91.8%，72.1%，59.7%。19例患者肿瘤复发，其中腹腔局部复发8例、远处转移11例。两组患者无病生存情况及总体生存情况比较，差异均无统计学意义（χ^2=0.018，0.596，P〉0.05）。两组患者腹腔局部复发患者比较，差异有统计学意义（x2=4.41，P〈0.05）。试验组31例完全缓解和部分缓解患者无瘤生存时间为29个月（8-72个月），总体生存时间为38个月（10-72个月）；23例疾病稳定和疾病进展患者无瘤生存时间为11个月（3-68个月），总体生存时间为18个月（4-68个月），两者无瘤生存时间和总体生存时间比较，差异均有统计学意义（χ^2=5.27，7.72，P〈0.05）。 结论： 采用奥沙利铂＋卡培他滨新辅助化疗方案对可切除局部晚期食管胃结合部腺癌患者安全有效，肿瘤降期明显，术后腹腔局部复发率下降，但患者远期生存无明显获益。
Objective： To investigate the clinical efficacy of neoadjuvant chemotherapy （oxaliplatin ＋ capecitabine, XELOX） for the resectable locally advanced adenocarcinoma of esophagealgastric junction （AEG）. Methods：The prospective study was conducted. The clinicopathological data of 106 locally advanced AEG patients who were admitted to the Cancer Hospital of Shantou University Medical College from January 2011 to December 2014 were collected. All the patients were divided into the treatment group and control group by single blind, randomized, controlled random number table. Patients underwent preoperative neoadjuvant chemotherapy （XELOX） ＋ surgery ＋ postoperative adjuvant chemotherapy （XELOX） in the treatment group and surgery ＋ postoperative adjuvant chemotherapy （XELOX） in the control group. Total gastrectomy ＋ Roux-en-Y esophagojejunostomy ＋ D2 lymphadenectomy were applied to patients by the same team of doctors. Observation indicators： （1） treatment situations; （2） results of postoperative pathological examination; （3） followup and survival situations. Followup using outpatient examination was performed to detect the postoperative tumor recurrence or metastasis and patients′ survival up to February 2017. Measurement data with normal distribution were represented as ±s, and comparisons between groups were evaluated with the t test. Measurement data with skewed distribution were described as M （range） and analyzed by the nonparametric test. Comparisons of count data were analyzed using the chisquare test. The ordinal data were compared using the nonparametric test. Survival rate and curve were respectively calculated and drawn by the KaplanMeier method and survivals were compared using the Longrank method.
Results：One hundred and six patients were screened for eligibility, including 54 in the treatment group and 52 in the control group. （1） Treatment situations： ① preoperative neoadjuvant chemotherapy： 54 in the treatment group received 2-4 cycle neoadjuvant chemotherapy. During the chemotherapy, gastrointestinal reaction, grade 1-2 granulocytopenia, elevated alanine transaminase （ALT） and grade 3 granulocytopenia were detected in 21, 17, 8, 1 patients, and 7 patients had no adverse reaction. The complete response（CR）, partial response （PR）, stable disease （SD） and progressive disease （PD） of neoadjuvant chemotherapy in the treatment group were detected in 4, 27, 20 and 3 patients, respectively. Of 54 patients in the treatment group, 4, 13, 25 and 12 were in grade 0, 1, 2 and 3 of response to preoperative chemotherapy, respectively. ② Surgical situations： preoperative carcinoembryonic antigen （CEA） in the treatment and control groups were respectively 4.71 μg/L （range, 0.20-36.19 μg/L） and 14.09 μg/L （range, 0.71-178.20 μg/L）, with a statistically significant difference between groups （Z=-1.92, P〈0.05）. All patients underwent total gastrectomy ＋ Roux-en-Y esophagojejunostomy ＋ D2 lymphadenectomy. Operation time in the treatment and control groups were respectively （210±31）minutes and （195±26）minutes, with a statistically significant difference between groups （t=-2.45, P〈0.05）. Volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative anal exsufflation, time to defecation, time for initial diet intake, cases with postoperative complications and duration of hospital stay were respectively （216±172）mL, 6, （4.3±1.0）days, （4.5±0.8）days, （3.1±0.5）days, 11, （15.0±5.0）days in the treatment group and （174±108）mL, 4, （4.2±1.0）days, （4.4±0.8）days, （3.1±0.5）days, 15, （15.0±5.0）days, with no statistically significant difference between groups （t=-1.01, χ^2=0.36, t=-0.31, -0.88, -0.36, χ^2=1.03, t=-0.38, P〉0.05）. ③ Postoperative adjuvant chemotherapy： all the patients completed the postoperative adjuvant chemotherapy. The granulocytopenia, elevated ALT and gastrointestinal reaction occurred in 25, 5, 28 patients in the treatment group and 21, 7, 30 patients in the control group, respectively, with no statistically significant difference between groups （x2=0.38, 0.47, 0.36, P〉0.05）. Some of the patients were merged with multiple adverse reactions. （2） Results of postoperative pathological examination： maximum tumor dimension, cases with lymphovascular invasion, perineural invasion, T0, T2, T3, T4 （T stage）, stage 0, Ⅰ, Ⅱ and Ⅲ （TNM stage） were respectively （3.6±1.4）cm, 5, 10, 4, 10, 20, 20, 4, 7, 15, 28 in the treatment group and （4.5±1.7）cm, 24, 30, 0, 2, 13, 37, 0, 1, 12, 39 in the control group, with statistically significant differences between groups （t=-2.88, x2=18.14, 17.30, Z=14.74, 8.13, P〈0.05）. （3） Followup and survival situations： of 54 patients in the treatment group, 52 were followed up for 4-72 months, with a median time of 32 months; of 52 patients in the control group, 49 were followed up for 5-71 months, with a median time of 36 months. The postoperative diseasefree survival time, 1, 3 and 5year tumorfree survival rates, postoperative overall survival time and 1, 3 and 5year overall survival rates were respectively 26 months （range, 3-72 months）, 79.5%, 64.7%, 61.3%, 27 months （range, 5-72 months）, 88.3%, 69.2% and 62.1% in the treatment group. Seventeen patients had tumor recurrence, including 2 with intraperitoneal local recurrence and 15 with distant metastasis. The postoperative diseasefree survival time, 1, 3 and 5year tumorfree survival rates, postoperative overall survival time and 1, 3 and 5year overall survival rates were respectively 33 months （range, 2-71 months）, 89.7%, 55.4%, 55.4%, 33 months （range, 5-71 months）, 91.8%, 72.1% and 59.7% in the control group. Nineteen patients had tumor recurrence, including 8 with intraperitoneal local recurrence and 11 with distant metastasis. There was no statistically significant difference in diseasefree survival and overall survival between groups （χ^2=0.018, 0.596, P〉0.05）. There was a statistically significant difference in cases with local recurrence between groups （χ^2=4.41, P〈0.05） The tumorfree survival time and overall survival time in the treatment group were respectively 29 months （range, 8-72 months）, 38 months （range, 10-72 months） in 31 patients with CR and PR and 11 months （range, 3-68 months）, 18 months （range, 4-68 months） in 23 patients with SD and PD, showing statistically significant differences in tumorfree and overall survival times （χ^2=5.27, 7.72, P〈0.05）. Conclusion：Neoadjuvant chemotherapy with oxaliplatin and capecitabine is safe and effective for patients with the resectable locally advanced AEG, it can also decrease tumor stage and reduce local recurrence, but fail to demonstrate a survival benefit.
作者
林佳锐
庄业忠
王伟峰
李镠洋
翁桢泓
黄棉生
许慕明
Lin Jiarui;Zhuang Yezhong;Wang Weifeag;Li Liuyang;Weng Zhenhong;Huang Miansheng;Xu Muming.(Department of Abdominal Surgery, Cancer Hospital of Shantou University Medical College, Shantou 515000, Guangdong Province, China)
出处
《中华消化外科杂志》
CAS
CSCD
北大核心
2018年第6期619-625,共7页
Chinese Journal of Digestive Surgery
基金
广东省中医药局科研项目（20171177）
关键词
食管胃结合部肿瘤
局部晚期
新辅助化疗
Adenocarcinoma of esophagogastric junction
Locally advanced
Neoadjuvant chemotherapy
