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Abstract：
OBJECTIVE: To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S).
METHODS: Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection).
RESULTS: A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051).
CONCLUSIONS: Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.
METHODS: Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection).
RESULTS: A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051).
CONCLUSIONS: Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.
摘要：
目的：评估接受新辅助放化疗（N-RCT）后手术（S）的食管癌（EC）患者的肺剂量学因素与术中和术后死亡率之间的关系。
方法：纳入标准为：年龄<85岁，诊断时没有远处转移，没有诱导化疗，适形放疗,总剂量≤50.4Gy，和可用剂量体积直方图(DVH)数据。一百三十五名患者符合我们的纳入标准。中位年龄为62岁。N-RCT包括36-50.4Gy（中位数45Gy），每分1.8-2Gy。伴随化疗包括113例患者的5-氟尿嘧啶（5-FU）和顺铂，15例患者的顺铂和紫杉烷衍生物。七名患者接受了单一细胞毒性剂。在130例患者中进行了腹胸外科手术，在5例患者中进行了跨期切除术。从全肺DVH产生以下剂量学参数：平均剂量，V5、V10、V15、V20、V30、V40、V45和V50。主要终点是术中和术后死亡率（从N-RCT开始到手术切除后60天）。
结果：共观察到10例术后死亡（7％）：手术干预后30天内3例（2％）和30至60天内7例（5％）；手术期间无患者死亡。在单变量分析中，体重减轻（诊断前6个月≥10%，风险比：1.60，95CI：0.856-2.992，p=0.043），东部肿瘤协作组-绩效状态(ECOG2vs.1，风险比：1.931，95CI：0.898-4.150，p=0.018）和术后肺部加非肺部并发症（风险比：2.533，95CI：0.978-6.563，p=0.004）与术后死亡率显着相关。术后死亡率与照射的肺体积之间没有显着关联。肺V45是唯一与术后肺部和非肺部并发症发生率显着相关的变量（实验（B）：1.285，95CI1.029-1.606，p=0.027），但没有术后肺部并发症（Exp（B）：1.249，95CI0.999-1.561，p=0.051）。
结论：在接受中等剂量（36-50.4Gy）常规分割适形放疗联合广泛使用的放射增敏剂治疗的患者中，肺放射量与术后死亡率无相关性。术后死亡率与更大的体重减轻显着相关，不良的表现状况和术后并发症的发展，但与治疗相关的因素无关。由于观察到与术后并发症的风险相关，因此限制接受较高辐射剂量的肺体积似乎是谨慎的。
方法：纳入标准为：年龄<85岁，诊断时没有远处转移，没有诱导化疗，适形放疗,总剂量≤50.4Gy，和可用剂量体积直方图(DVH)数据。一百三十五名患者符合我们的纳入标准。中位年龄为62岁。N-RCT包括36-50.4Gy（中位数45Gy），每分1.8-2Gy。伴随化疗包括113例患者的5-氟尿嘧啶（5-FU）和顺铂，15例患者的顺铂和紫杉烷衍生物。七名患者接受了单一细胞毒性剂。在130例患者中进行了腹胸外科手术，在5例患者中进行了跨期切除术。从全肺DVH产生以下剂量学参数：平均剂量，V5、V10、V15、V20、V30、V40、V45和V50。主要终点是术中和术后死亡率（从N-RCT开始到手术切除后60天）。
结果：共观察到10例术后死亡（7％）：手术干预后30天内3例（2％）和30至60天内7例（5％）；手术期间无患者死亡。在单变量分析中，体重减轻（诊断前6个月≥10%，风险比：1.60，95CI：0.856-2.992，p=0.043），东部肿瘤协作组-绩效状态(ECOG2vs.1，风险比：1.931，95CI：0.898-4.150，p=0.018）和术后肺部加非肺部并发症（风险比：2.533，95CI：0.978-6.563，p=0.004）与术后死亡率显着相关。术后死亡率与照射的肺体积之间没有显着关联。肺V45是唯一与术后肺部和非肺部并发症发生率显着相关的变量（实验（B）：1.285，95CI1.029-1.606，p=0.027），但没有术后肺部并发症（Exp（B）：1.249，95CI0.999-1.561，p=0.051）。
结论：在接受中等剂量（36-50.4Gy）常规分割适形放疗联合广泛使用的放射增敏剂治疗的患者中，肺放射量与术后死亡率无相关性。术后死亡率与更大的体重减轻显着相关，不良的表现状况和术后并发症的发展，但与治疗相关的因素无关。由于观察到与术后并发症的风险相关，因此限制接受较高辐射剂量的肺体积似乎是谨慎的。
