Kersting Josephine, Ranft Andreas, Bhadri Vivek, Brichard Bénédicte, Collaud Stéphane, Cyprová Sona, Eich Hans, Ek Torben, Gelderblom Hans, Hardes Jendrik, Haveman Lianne, Hartmann Wolfgang, Hauser Peter, Heesen Philip, Jürgens Heribert, Kanerva Jukka, Kühne Thomas, Raciborska Anna, Rascon Jelena, Rechl Victor, Streitbürger Arne, Timmermann Beate, Uhlenbruch Yasmine, Dirksen Uta
Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
German Cancer Consortium, Partnersite Essen, Essen, Germany.
Adv Radiat Oncol. 2023 Jun 14;8(4):101269. doi: 10.1016/j.adro.2023.101269. eCollection 2023 Jul-Aug.
Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS.
The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response.
S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 ( = .42) and in the RT group 52.9%, 62.5%, and 70.3% ( = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, = .96; histologic response, = .07; tumor volume, = .50; dose, = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, = .15; age, = .08; sex, = .40).
In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.
放射治疗（RT）是尤因肉瘤（EwS）治疗的一个组成部分。2008年尤因肉瘤治疗方案推荐的放疗剂量为45至54 Gy。然而，一些患者接受了其他剂量的放疗。我们分析了不同放疗剂量对EwS患者无事件生存期（EFS）和总生存期（OS）的影响。
2008年尤因肉瘤数据库纳入了528例接受放疗的非转移性EwS患者。推荐的多模式治疗包括多药化疗以及由手术（手术与放疗组）和/或放疗（放疗组）组成的局部治疗。采用单变量和多变量Cox回归模型分析EFS和OS，模型纳入了年龄、性别、肿瘤体积、手术切缘和组织学反应等已知预后因素。
332例患者（62.9%）接受了手术与放疗，145例患者（27.5%）接受了根治性放疗。57.8%的患者接受标准剂量≤53 Gy（d1），35.5%的患者接受高剂量54至58 Gy（d2），6.6%的患者接受非常高剂量≥59 Gy（d3）。在放疗组中，11.7%的患者放疗剂量为d1，44.1%的患者为d2，44.1%的患者为d3。手术与放疗组中，d1组的三年EFS为76.6%，d2组为73.7%，d3组为68.2%（P = 0.42）；放疗组中，相应的三年EFS分别为52.9%、62.5%和70.3%（P = 0.63）。多变量Cox回归显示，手术与放疗组中年龄≥15岁（风险比[HR]，2.68；95%置信区间[CI]，1.63 - 4.38）和切缘不根治（HR，1.76；95% CI，1.05 - 2.93）为独立因素（性别，P = 0.96；组织学反应，P = 0.07；肿瘤体积，P = 0.50；剂量，P = 0.10），放疗组中肿瘤体积大（HR，2.20；95% CI，1.21 - 4.0）为独立因素（剂量，P = 0.15；年龄，P = 0.08；性别，P = 0.40）。
在联合局部治疗模式组中，较高放疗剂量的治疗对EFS有影响，而根治性放疗时较高剂量的放疗与OS增加相关。发现了剂量选择偏倚的指征。即将开展的试验将以随机方式评估不同放疗剂量的价值，以控制潜在的选择偏倚。
