调强放疗和三维适形放疗及普通放疗在局部进展期中低位直肠癌患者中的应用比较

Comparison of the application among intensity-modulated radiotherapy,3D-conformal radiotherapy and conventional radiotherapy for locally advanced middle-low rectal cancer

目的探讨调强放疗、三维适形放疗及普通放疗在局部进展期中低位直肠癌患者中的应用比较。方法2015年1月至2016年12月期间,昆明医科大学第三附属医院结直肠外科对临床分期为cT3N+M0或cT4N0/+M0局部进展期中低位直肠癌患者予以术前同期放化疗,将其中资料完整的93例纳入本回顾性队列研究,根据放疗方式的不同将患者分为调强放疗组(17例)、三维适形放疗组(28例)和普通放疗组(48例)。普通放疗频率及剂量为:1次/d,5次/周,共5周,单次剂量为2.0Gy,总剂量为50Gy。三维适形及调强放疗频率及剂量均为:1次/d,5次/周,共计23~28次,单次剂量为1.8~2.0Gy,总剂量为45.0~50.4Gy;化疗方案均使用卡培他滨片,按照825mg/m2剂量,每天2次,每周5d,放疗时同期服用。比较上述3组患者治疗效果、放化疗不良反应及治疗前后免疫功能的变化情况。结果3组患者基本资料的比较,差异无统计学意义(均P>0.05)。调强放疗组和三维适形放疗组患者接受永久造口的比率分别为29.4%(5/17)和32.1%(9/28),均低于普通放疗组患者(58.3%,28/48),差异有统计学意义(χ2=7.982,P=0.030),但调强放疗组与三维适形放疗组患者接受永久性造口比率差异无统计学意义(χ^2=0.037,P=0.848)。全组患者病理完全缓解(pCR)为23.7%(22/93),三维适形放疗组患者病理完全缓解(pCR)率为39.3%(11/28),高于普通放疗组和调强放疗组[分别为12.5%(6/48)和29.4%(5/17)],差异有统计学意义(χ^2=7.407,P=0.025),但普通放疗组患者与调强放疗组患者pCR率之间的差异无统计学意义(χ^2=2.554,P=0.110)。3组患者均未出现3级以上不良反应,骨髓抑制和肝肾功能相关标志物的不良反应情况、消化道反应以及放射性皮炎发生率的差异均无统计学意义(均P>0.05)。接受同期放化疗治疗后,调强放疗组和普通放疗组患者CD3+/CD4+细胞比率均较治疗前下降[两组分别为(31.1±10.9)比(23.1±9.3),(33.6±7.2)比(27.4±10.7)],CD3+/CD8+细胞比率上调[两组分别为(24.8±10.9)比(36.1±15.2),(24.0±8.3)比(30.9±14.4)],差异均具有统计学意义(均P<0.05),但三维适形放疗组患者治疗前后指标的差异无统计学意义(P>0.05)。治疗后,调强放疗组患者CD4+/CD8+细胞比率下降[(1.6±1.0)比(0.8±0.6),t=3.838,P=0.003],但普通放疗组和三维适形放疗组患者治疗前后CD4+/CD8+细胞比率的差异无统计学意义(均P>0.05)。结论调强放疗和三维适形放疗能够显著减少患者获得永久性造口比率,三维适形放疗方案能使患者获得更高的pCR率,而调强放疗较三维适形放疗方案在患者近期疗效中并未表现明显优势,反而使患者出现显著免疫功能抑制状态。因此,建议三维适形放疗方案可作为局部进展期中低位直肠癌患者、尤其伴随免疫功能抑制患者的最佳术前治疗策略。

Objective To compare the application among intensity-modulated radiotherapy (IMRT), three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (CRT) for locally advanced middle-low rectal cancer.Methods From January 2015 to December 2016, 93 locally advanced middle-low rectal cancer patients with clinical stage cT3N+M0 or cT4N0/+M0 who underwent preoperative concurrent chemoradiotherapy at Department of Colorectal Surgery, the Third Affiliated Hospital of Kunming Medical University and had complete data were enrolled in this retrospective cohort study. Patients were divided into IMRT group (17 cases), 3D-CRT group (28 cases) and CRT group (48 cases) according to different radiotherapy methods. The frequency and dose of CRT were 1 time/d, 5 times/week, for a total of 5 weeks, with a single dose of 2.0 Gy, the total dose was 50 Gy. Frequency and dose of 3D-CRT and IMRT were 1 time/d, 5 times/week, for a total of 23 to 28 times, with a single dose of 1.8 to 2.0 Gy, and a total dose of 45.0 to 50.4 Gy. The chemotherapy regimen was performed with capecitabine tablets at a dose of 825 mg/m^2 twice a day for 5 days every week, at the same time during radiotherapy. The efficacy, chemotherapy adverse reactions and immune function of the three groups were compared. Results There was no significant difference in the baseline data among the three groups (all P>0.05). The proportion of patients receiving permanent ostomy in the IMRT group and the 3D-CRT group was 29.4%(5/17) and 32.1%(9/28) respectively, which was lower than 58.3%(28/48) in CRT group, and the difference was statistically significant (χ^2=7.982, P=0.030), while this proportion was not significantly different between IMRT and 3D-CRT group (χ^2=0.037, P=0.848). The pathologic complete response (pCR) rate was 23.7%(22/93) in the whole study, and the pCR rate was 39.3%(11/28) in the 3D-CRT group, which was higher than that of CRT group and IMRT group [12.5%(6/48) and 29.4%(5/17)], and the difference was statistically significant (χ^2=7.407, P=0.025), while there was no significant difference in pCR rate between CRT group and IMRT group (χ^2=2.554, P=0.110). There was no adverse reaction of grade 3 or above in all three groups. No significant difference in the incidence of bone marrow suppression, abnormal liver and kidney function markers, digestive tract reaction or radiation dermatitis was found (all P>0.05). After receiving concurrent chemoradiotherapy, the proportion of CD3/CD4 cells in the IMRT group and the CRT group decreased compared with that before treatment (23.1±9.3 vs. 31.1±10.9, 27.4±10.7 vs. 33.6±7.2, respectively);the proportion of CD3/CD8 cells was up-regulated (36.1±15.2 vs. 24.8±10.9, 30.9±14.4 vs. 24.0±8.3, respectively), and the differences were statistically significant (both P<0.05), while the above indexes before and after treatment were not significantly different in the 3D-CRT group (all P>0.05). After treatment, the proportion of CD4/CD8 cells in IMRT group decreased (0.8±0.6 vs. 1.6±1.0, t=3.838, P=0.003), while this proportion was not significantly different in CRT group and 3D-CRT group (all P>0.05). Conclusions IMRT and 3D-CRT can reduce the rate of permanent stoma. 3D-CRT can increase pCR rate. No obvious advantage is shown in IMRT as compared with 3D-CRT in the short-term efficacy. On the contrary, an immunosuppressive status may occur. Therefore, 3D-CRT is recommended as the best preoperative treatment strategy for patients with locally advanced middle-low rectal cancer, especially for those with immunosuppression status.