新辅助化疗对腹腔镜局部进展期胃癌D2根治术安全性及预后的影响

Effect of neoadjuvant chemotherapy on the safety of laparoscopic D2 radical resection and prognosis of patients with locally advanced gastric cancer

  • 摘要:
    目的 探讨新辅助化疗对腹腔镜局部进展期胃癌D2根治术安全性及预后的影响。
    方法 采用倾向评分匹配及回顾性队列研究方法。收集2016年12月至2021年12月空军军医大学第二附属医院收治的351例行腹腔镜局部进展期胃癌D2根治术患者的临床病理资料;男256例,女95例;年龄为(58±9)岁。351例患者中,124例行新辅助化疗,设为新辅助化疗组;227例行术后辅助化疗,设为辅助化疗组。观察指标:(1)倾向评分匹配情况及匹配后两组患者一般资料比较。(2)新辅助化疗效果评估。(3)术中及术后情况。(4)术后组织病理学检查情况。(5)随访情况。倾向评分匹配按1∶1最近邻匹配法匹配。正态分布的计量资料以x±s表示,组间比较采用t检验;偏态分布的计量资料以M(范围)或MQ1,Q3)表示,组间比较采用秩和检验。计数资料以绝对数表示,组间比较采用χ²检验。采用Kaplan⁃Meier法绘制生存曲线,Log‑Rank检验进行生存分析。
    结果 (1)倾向评分匹配情况及匹配后两组患者一般资料比较。351例患者中,154例配对成功,新辅助化疗组和辅助化疗组各77例。倾向评分匹配后消除性别、年龄、术前体质量指数、临床T分期、临床N分期因素混杂偏倚,具有可比性。(2)新辅助化疗效果评估。77例新辅助化疗组患者中,完全缓解0例、部分缓解26例、疾病稳定46例、疾病进展5例。客观缓解率为33.8%(26/77),疾病控制率为93.5%(72/77)。新辅助化疗敏感患者中,男15例,女11例;新辅助化疗不敏感患者中,男46例,女5例;两者性别比较,差异有统计学意义(χ²=11.05,P<0.05)。(3)术中及术后情况。新辅助化疗组患者手术时间、术中出血量、术中输血、术后首次肛门排气时间、术后首次进食流质食物时间、术后住院时间、发生术后短期并发症、住院费用分别为(308±71)min、100(20~600)mL、5例、3.0(2.0~10.0)d、4.0(2.0~12.0)d、9.0(4.0~31.0)d、7例、7.96(7.37,8.58)万元;辅助化疗组患者上述指标分别为(296±67)min、100(20~500)mL、4例、3.5(1.0~14.0)d、4.0(2.0~15.0)d、8.0(5.0~45.0)d、11例、8.18(7.52,9.19)万元;两组患者上述指标比较,差异均无统计学意义(t=1.13,Z=-0.37,χ²=0.12,Z=-1.26、-0.33、-0.70,χ²=1.01,Z=-1.04,P>0.05)。(4)术后组织病理学检查情况。154例患者均达到R0切除。新辅助化疗组患者病理学T分期(T1期、T2期、T3期、T4期),病理学N分期(N0期、N1期、N2期、N3期),阳性淋巴结数目,人类表皮生长因子受体2(阴性、阳性)分别为3、7、5、62例,27、19、19、12例,1(0~28)枚,59、18例;辅助化疗组患者上述指标分别为0、0、2、75例,17、15、21、24例,3(0~31)枚,44、33例;两组患者上述指标比较,差异均有统计学意义(Z=-3.39、-2.55、-3.12,χ²=6.60,P<0.05)。(5)随访情况。154例患者中,143例获得随访,随访时间为37(5~69)个月。新辅助化疗组和辅助化疗组患者3年总生存率、3年无病生存率分别为72.1%、70.0%和74.8%、76.6%;两组患者上述指标比较,差异均无统计学意义(χ²=0.14,0.60,P>0.05)。
    结论 与术后辅助化疗比较,新辅助化疗不增加行腹腔镜胃癌D2根治术的局部进展期患者手术风险,可以使肿瘤降期,但未能展现改善生存的优势。

     

    Abstract:
    Objective To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D2 radical resection and prognosis of patients with locally advanced gastric cancer.
    Methods The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow‑up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M(Q1,Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan‑Meier method was used to draw survival curves, and the Log‑Rank test was used for survival analysis.
    Results (1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them (χ²=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20‒600)mL, 5, 3.0(range, 2.0‒10.0)days, 4.0(range, 2.0‒12.0)days, 9.0(range, 4.0‒31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20‒500)mL, 4, 3.5(range, 1.0‒14.0)days, 4.0(range, 2.0‒15.0)days, 8.0(range, 5.0‒45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups (t=1.13, Z=‒0.37, χ²=0.12, Z=‒1.26, ‒0.33, ‒0.70, χ²=1.01, Z=‒1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0‒28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0‒31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups (Z=‒3.39, ‒2.55, ‒3.12, χ²=6.60, P<0.05). (5) Follow‑up. Of the 154 patients, 143 patients were followed up for 37(range, 5‒69)months. The 3‑year overall survival rate and 3‑year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups (χ²=0.14, 0.60, P>0.05).
    Conclusions Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.

     

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