Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Johns Hopkins Biostatistics Center, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2024 Feb 1;118(2):474-484. doi: 10.1016/j.ijrobp.2023.09.007. Epub 2023 Oct 3.
To determine the association between consolidative radiation (RT) and survival in children, adolescents, and young adults with metastatic sarcoma.
Eligibility criteria included patients aged ≤39 years with newly diagnosed metastatic bone or soft tissue sarcoma who completed local control of the primary tumor without disease progression. Consolidative RT was defined as RT to all known sites of metastatic disease. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The least absolute shrinkage and selection operator Cox provided adjusted estimates. To account for immortal time bias, consolidative RT was used as a time-varying covariate in a time dependent Cox model. Distant failure was estimated using the Fine-Gray model.
Patients (n = 85) had a median age at diagnosis of 14.8 years. Most common histology was Ewing Sarcoma (45.9%) followed by rhabdomyosarcoma (40.0%). Receipt of consolidative RT was associated with Ewing Sarcoma (P < .001) and local control modality as those who underwent local control with surgery and RT compared with surgery alone were more likely to be treated with consolidative RT (P = .034). Consolidative RT was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.17-0.98; P = .045) and improved PFS (HR, 0.37; 95% CI, 0.16-0.88; P = .024) after adjusting for confounding variables and immortal time bias. Patients treated with consolidative RT also experienced a lower risk of distant failure (HR, 0.33; 95% CI, 0.17-0.64; P = .001). In an independent data set of patients with metachronous progression (n = 36), consolidative RT remained independently associated with improved OS.
Consolidative RT was independently associated with improved OS and PFS and decreased risk of distant failure in child, adolescent, and young adult patients with metastatic sarcoma. Future work should evaluate biomarkers to optimize patient selection, timing, and dose for consolidative RT.
确定巩固性放疗(RT)与转移性肉瘤儿童、青少年和年轻成人患者生存之间的关系。
纳入标准为年龄≤39 岁、新诊断为转移性骨或软组织肉瘤、完成原发性肿瘤局部控制且无疾病进展的患者。巩固性 RT 定义为对所有已知转移性疾病部位进行 RT。采用 Kaplan-Meier 法估计总生存(OS)和无进展生存(PFS)。最小绝对收缩和选择算子 Cox 提供调整后的估计。为了考虑到不朽时间偏差,将巩固性 RT 作为时变协变量纳入时依 Cox 模型。远处失败使用 Fine-Gray 模型进行估计。
患者(n=85)诊断时的中位年龄为 14.8 岁。最常见的组织学类型是尤文肉瘤(45.9%),其次是横纹肌肉瘤(40.0%)。接受巩固性 RT 与尤文肉瘤(P<0.001)和局部控制方式相关,与仅接受手术相比,接受手术和 RT 局部控制的患者更有可能接受巩固性 RT(P=0.034)。在调整混杂因素和不朽时间偏差后,巩固性 RT 与 OS 改善独立相关(风险比 [HR],0.41;95%CI,0.17-0.98;P=0.045)和 PFS 改善(HR,0.37;95%CI,0.16-0.88;P=0.024)。接受巩固性 RT 的患者远处失败的风险也较低(HR,0.33;95%CI,0.17-0.64;P=0.001)。在具有异时性进展的患者的独立数据集(n=36)中,巩固性 RT 仍与 OS 改善独立相关。
巩固性 RT 与转移性肉瘤儿童、青少年和年轻成人患者的 OS 和 PFS 改善以及远处失败风险降低独立相关。未来的工作应评估生物标志物,以优化患者选择、巩固性 RT 的时机和剂量。