三维适形放疗和三维适形放疗联合化疗治疗食管癌
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摘要
背景与目的：食管癌的常规放射治疗疗效仍然较差。三维适形放射治疗(3D-CRT)改善了靶区剂量分布并减少了正常组织照射,是放射治疗技术上的一大进步。常规放疗技术联合同步化疗已被证实有效,人们有理由期望3D-CRT同步联合化疗能够进一步改善食管癌患者的远期生存。本研究旨在比较单用3D-CRT和3D-CRT联合同期化疗治疗食管癌的疗效,包括局部控制、远处转移、长期生存和晚期并发症情况。
方法：回顾性分析351例经病理确诊,接受3D-CRT治疗的食管癌患者临床资料。其中同期放化疗93例,单纯放疗258例。比较两种方法对食管癌病人的治疗效果。
3D-CRT的大体肿瘤靶区(GTV)包括胸部CT在纵隔窗显示出来的食管原发肿瘤,以及在纤维食管镜所见到而在计算机断层扫描(computed tomography,CT)图像上未显示的病灶。局部区域转移的淋巴结,也包含在GTV内。临床靶区(CTV)为GTV宽度外扩5-10mm,食管纵轴上下外扩20mm,不作区域淋巴结预防性照射。计划靶区(PTV)为CTV外扩5-10mm。利用射野方向观(BEV)和多维平面重建工具使射束包括PTV,并尽量减少正常组织的照射剂量。PTV的中心点给予处方剂量,不做不均匀性校正。胸段病变多数病例采用3野照射,包括1个前野和2个后斜野；颈段病变多采用1个前野和2个水平或前斜野加楔形板。通过分析剂量体积直方图(DVH)进行计划的优化,考虑正常组织的剂量限制。放射治疗采用6MV光子线直线加速器,包括多叶准直器(MLC)或铅挡块。总放疗剂量40-76Gy,中位剂量66Gy,常规分割。同期放化疗组的病人放疗期间接受同期化疗2个周期,放疗结束后辅助化疗2个周期,顺铂(75 mg/m2)第一天和5-氟尿嘧啶(500 mg/m2)第一天到第四天的静脉滴注
统计：采用SPSS13.0统计软件包。用Kaplan-Meier法计算总生存率、无病生存率、疾病相关生存率、无复发生存率和无转移生存率。单因素分析采用Kaplan-Meier方法,有统计学意义者纳入Cox回归模型进行多因素分析。所有病例开始放疗的第1天作为起始随访时间。
结果：中位随访时间18.5个月。1、2、3年总生存率同期放化疗组分别为77.7%、55.4%、44.4%；单纯放疗组分别为68.4%、41.4%、32.7%(X2=5.777,P=0.016),差异有统计学意义。1、2、3年无病生存率同期放化疗组分别为51.1%、35.6%、28.0%；单纯放汕头大学医学院硕士学位论文三维适形放疗和三维适形放疗联合化疗治疗食管癌中文摘要疗组分别为48.4%、30.5%、25.0%(X2=0.808,P=0.369),差异没有统计学意义。1、2、3年疾病相关生存率同期放化疗组分别为79.8%、58.1%、46.5%；单纯放疗组分别为70.6%、44.4%、36.0%(X2=4.445,P=0.035),差异有统计学意义。1、2、3年无复发生存率同期放化疗组分别为66.9%、48.3%、41.3%,单纯放疗组分别为56.7%、36.9%、29.9%(X2=4.043,P=0.044),差异有统计学意义。两组无转移生存率的差异无统计学意义。两组病人晚期并发症发生率的差异无统计学意义。
单因素分析显示性别、病灶部位和同期化疗是影响预后的重要因素。多因素分析显示女性、病灶位于颈段、胸上段和同期化疗是有利的独立预后因素。女性、病灶位于颈段或胸上段和同期放化疗者有着较好的预后。
结论：
1.三维适形放射治疗联合同期化疗治疗食管癌比单纯三维适形放疗疗效有明显提高。同期放化疗显著提高总生存率、疾病相关生存率和无复发生存率。
2.单因素和多因素分析均显示女性、病灶位于颈段或胸上段和同期化疗是食管癌放射治疗的有利预后因素。女性患者、病灶位于颈段或胸上段和接受同期放化疗者有较好的预后。
Background and Objectives:Although treatment options for esophageal carcinoma have been improved during the past decades, the overall prognosis remains poor irrespective of the therapeutic modality applied. With respect to radiotherapy, the need for improved clinical outcome in esophageal carcinoma has led to further efforts in radiation delivery and performance. Three-dimensional (3D) conformal radiation therapy is one of the most commonly accepted radiotherapy techniques at presence, for its precise and reliable dose distribution in target and normal tissue. Given the proved efficacy of concurrent chemoradiotherapy using conventional radiation technique, the question arouse in how far the survival is improved in 3D-comformal radiation planning era. This research aims to evaluate the-treatment outcomes of 3D-conformal radiation therapy concomitant with chemotherapy versus 3D-conformal radiotherapy alone in patients with esophageal carcinoma, including local control, distant metastases, long-term survival and late complications.
Methods:A retrospective analysis was conducted to the clinical data of 351 patients pathologically confirmed with esophageal carcinoma.93 cases received concurrent chemoradiotherapy, and 258 received radiotherapy alone.
The gross tumor volume (GTV) consisted of the primary esophageal gross tumor shown on mediastinal window of chest computed tomography(CT). In addition, the regions of tumor described on esophagoscopy but not seen on CT were also included.Regional lymph nodes≥10 mm in maximal diameter were considered positive and included in the GTV. For the planning target volume (PTV), a 1.0-1.5cm margin was placed around GTV, and 3.0cm superior and inferior of GTV (at the long axis of esophagus) to encompass potential submucosal invasion. The beam's eye view (BEV) and multiplanar reconstruction facilities were used to fully encompass the PTV and to minimize dose to normal tissues. The dose was prescribed to the center of PTV with no correction of inhomogeneity. Most of the cases used a three-field approach with one anterior and a pair of posterior oblique portals for lesions in the thorax, and most of the cases used a anterior and two horizontal portals or two anterior oblique portals with wedges for lesions in the neck. Optimization of the plan was based on dose-volume histogram (DVH) analyses and constraints for normal structures. Radiotherapy was delivered using 6 MV photons with multileaf collimator (MLC) or cerrobend blocks. Radiation dose ranged from 40 to 76Gy (median 66Gy) with conventional fractionation. The patients who underwent chemoradiotherapy received two cycles of concurrent and two cycles of adjuvant combination of cisplatin (75mg/m2) and 5-fluorouracil(500mg/m2) by 4-day infusion. The radiotherapy alone group received the same radiation therapy schedule without chemotherapy.
Statistic:Kaplan-Meier method was used to analyze the survival and log-rank test was used to evaluate the difference between the groups. Cox regression model was used to analyze the prognostic factor. The first day of irradiation was taken as the initial date to begin observation for all events
Results:The median follow-up time was 18.5 months. The 1,2,3-year overall survival rates in patients with concurrent chemoradiotherapy and with radiotherapy alone were 77.7%, 55.4%,44.4%; and 68.4%,41.4%,32.7%, respectively (χ2=5.777, P=0.016). The 1,2,3-year disease-specific survival rates were 79.8%,58.1%,46.5% in chemoradiotherapy group while 70.6%,44.4% and 36.0% in radiation alone group, respectively(χ2= 4.445, P=0.035). The overall survival rates and disease-specific survival rates had been improved significantly in chemoradiotherapy group compared with radiotherapy alone group. Recurrence-free survival (RFS) rates were also in favour of concomitant chemoradiotherapy group(χ2=4.043, P=0.044). The incidence of late complications did not increase significantly in the patients who received concurrent chemotherapy. By univariate and multivariate analyses, female gender, primary tumor location and concurrent chemotherapy were independent factors predictive of better survival.
Conclusion:3D-comformal radiation therapy is an accepted reference standard approach for non-operative esophageal cancer. The concomitant addition of cisplatin and 5-Fu has a statistically significant positive impact on overall and disease-specific survival rates. This combined treatment modality appears to offer therapeutic benefit without increasing late complications.
方法：回顾性分析351例经病理确诊,接受3D-CRT治疗的食管癌患者临床资料。其中同期放化疗93例,单纯放疗258例。比较两种方法对食管癌病人的治疗效果。
3D-CRT的大体肿瘤靶区(GTV)包括胸部CT在纵隔窗显示出来的食管原发肿瘤,以及在纤维食管镜所见到而在计算机断层扫描(computed tomography,CT)图像上未显示的病灶。局部区域转移的淋巴结,也包含在GTV内。临床靶区(CTV)为GTV宽度外扩5-10mm,食管纵轴上下外扩20mm,不作区域淋巴结预防性照射。计划靶区(PTV)为CTV外扩5-10mm。利用射野方向观(BEV)和多维平面重建工具使射束包括PTV,并尽量减少正常组织的照射剂量。PTV的中心点给予处方剂量,不做不均匀性校正。胸段病变多数病例采用3野照射,包括1个前野和2个后斜野；颈段病变多采用1个前野和2个水平或前斜野加楔形板。通过分析剂量体积直方图(DVH)进行计划的优化,考虑正常组织的剂量限制。放射治疗采用6MV光子线直线加速器,包括多叶准直器(MLC)或铅挡块。总放疗剂量40-76Gy,中位剂量66Gy,常规分割。同期放化疗组的病人放疗期间接受同期化疗2个周期,放疗结束后辅助化疗2个周期,顺铂(75 mg/m2)第一天和5-氟尿嘧啶(500 mg/m2)第一天到第四天的静脉滴注
统计：采用SPSS13.0统计软件包。用Kaplan-Meier法计算总生存率、无病生存率、疾病相关生存率、无复发生存率和无转移生存率。单因素分析采用Kaplan-Meier方法,有统计学意义者纳入Cox回归模型进行多因素分析。所有病例开始放疗的第1天作为起始随访时间。
结果：中位随访时间18.5个月。1、2、3年总生存率同期放化疗组分别为77.7%、55.4%、44.4%；单纯放疗组分别为68.4%、41.4%、32.7%(X2=5.777,P=0.016),差异有统计学意义。1、2、3年无病生存率同期放化疗组分别为51.1%、35.6%、28.0%；单纯放汕头大学医学院硕士学位论文三维适形放疗和三维适形放疗联合化疗治疗食管癌中文摘要疗组分别为48.4%、30.5%、25.0%(X2=0.808,P=0.369),差异没有统计学意义。1、2、3年疾病相关生存率同期放化疗组分别为79.8%、58.1%、46.5%；单纯放疗组分别为70.6%、44.4%、36.0%(X2=4.445,P=0.035),差异有统计学意义。1、2、3年无复发生存率同期放化疗组分别为66.9%、48.3%、41.3%,单纯放疗组分别为56.7%、36.9%、29.9%(X2=4.043,P=0.044),差异有统计学意义。两组无转移生存率的差异无统计学意义。两组病人晚期并发症发生率的差异无统计学意义。
单因素分析显示性别、病灶部位和同期化疗是影响预后的重要因素。多因素分析显示女性、病灶位于颈段、胸上段和同期化疗是有利的独立预后因素。女性、病灶位于颈段或胸上段和同期放化疗者有着较好的预后。
结论：
1.三维适形放射治疗联合同期化疗治疗食管癌比单纯三维适形放疗疗效有明显提高。同期放化疗显著提高总生存率、疾病相关生存率和无复发生存率。
2.单因素和多因素分析均显示女性、病灶位于颈段或胸上段和同期化疗是食管癌放射治疗的有利预后因素。女性患者、病灶位于颈段或胸上段和接受同期放化疗者有较好的预后。
Background and Objectives:Although treatment options for esophageal carcinoma have been improved during the past decades, the overall prognosis remains poor irrespective of the therapeutic modality applied. With respect to radiotherapy, the need for improved clinical outcome in esophageal carcinoma has led to further efforts in radiation delivery and performance. Three-dimensional (3D) conformal radiation therapy is one of the most commonly accepted radiotherapy techniques at presence, for its precise and reliable dose distribution in target and normal tissue. Given the proved efficacy of concurrent chemoradiotherapy using conventional radiation technique, the question arouse in how far the survival is improved in 3D-comformal radiation planning era. This research aims to evaluate the-treatment outcomes of 3D-conformal radiation therapy concomitant with chemotherapy versus 3D-conformal radiotherapy alone in patients with esophageal carcinoma, including local control, distant metastases, long-term survival and late complications.
Methods:A retrospective analysis was conducted to the clinical data of 351 patients pathologically confirmed with esophageal carcinoma.93 cases received concurrent chemoradiotherapy, and 258 received radiotherapy alone.
The gross tumor volume (GTV) consisted of the primary esophageal gross tumor shown on mediastinal window of chest computed tomography(CT). In addition, the regions of tumor described on esophagoscopy but not seen on CT were also included.Regional lymph nodes≥10 mm in maximal diameter were considered positive and included in the GTV. For the planning target volume (PTV), a 1.0-1.5cm margin was placed around GTV, and 3.0cm superior and inferior of GTV (at the long axis of esophagus) to encompass potential submucosal invasion. The beam's eye view (BEV) and multiplanar reconstruction facilities were used to fully encompass the PTV and to minimize dose to normal tissues. The dose was prescribed to the center of PTV with no correction of inhomogeneity. Most of the cases used a three-field approach with one anterior and a pair of posterior oblique portals for lesions in the thorax, and most of the cases used a anterior and two horizontal portals or two anterior oblique portals with wedges for lesions in the neck. Optimization of the plan was based on dose-volume histogram (DVH) analyses and constraints for normal structures. Radiotherapy was delivered using 6 MV photons with multileaf collimator (MLC) or cerrobend blocks. Radiation dose ranged from 40 to 76Gy (median 66Gy) with conventional fractionation. The patients who underwent chemoradiotherapy received two cycles of concurrent and two cycles of adjuvant combination of cisplatin (75mg/m2) and 5-fluorouracil(500mg/m2) by 4-day infusion. The radiotherapy alone group received the same radiation therapy schedule without chemotherapy.
Statistic:Kaplan-Meier method was used to analyze the survival and log-rank test was used to evaluate the difference between the groups. Cox regression model was used to analyze the prognostic factor. The first day of irradiation was taken as the initial date to begin observation for all events
Results:The median follow-up time was 18.5 months. The 1,2,3-year overall survival rates in patients with concurrent chemoradiotherapy and with radiotherapy alone were 77.7%, 55.4%,44.4%; and 68.4%,41.4%,32.7%, respectively (χ2=5.777, P=0.016). The 1,2,3-year disease-specific survival rates were 79.8%,58.1%,46.5% in chemoradiotherapy group while 70.6%,44.4% and 36.0% in radiation alone group, respectively(χ2= 4.445, P=0.035). The overall survival rates and disease-specific survival rates had been improved significantly in chemoradiotherapy group compared with radiotherapy alone group. Recurrence-free survival (RFS) rates were also in favour of concomitant chemoradiotherapy group(χ2=4.043, P=0.044). The incidence of late complications did not increase significantly in the patients who received concurrent chemotherapy. By univariate and multivariate analyses, female gender, primary tumor location and concurrent chemotherapy were independent factors predictive of better survival.
Conclusion:3D-comformal radiation therapy is an accepted reference standard approach for non-operative esophageal cancer. The concomitant addition of cisplatin and 5-Fu has a statistically significant positive impact on overall and disease-specific survival rates. This combined treatment modality appears to offer therapeutic benefit without increasing late complications.
引文
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