Zhao Shuliang, Su Yi, Duan Jinghao, Qiu Qingtao, Ge Xingping, Wang Aijie, Yin Yong
School of Medicine, Shandong University, Ji'nan 250012, China.
Department of Radiotherapy, Yantaishan Hospital of Yantai, Yantai 264001, China.
J Bone Oncol. 2019 Oct 4;19:100263. doi: 10.1016/j.jbo.2019.100263. eCollection 2019 Dec.
Osteosarcoma often requires multidisciplinary treatment including surgery, chemotherapy and radiotherapy. However, tumor behavior can vary widely among patients and selection of appropriate therapies in any individual patient remains a critical challenge. Radiomics seeks to quantify complex aspects of tumor images under the assumption that this information is related to tumor biology. This study tested the hypothesis that a radiomic signature extracted from Diffusion-weighted magnetic resonance images (DWI-MRI) can improve prediction of overall survival (OS) compared with clinical factors alone in localised osteosarcoma.
MATERIALS/METHODS: Pre-treatment DWI-MRI were collected from 112 patients (9-67 years of age) with histological-proven osteosarcoma that were treated with curative intent. The entire dataset was divided in two subsets: the training and validation cohorts containing 76 and 24% of the data respectively. Clinical data were extracted from our medical record. Two experienced radiotherapists evaluated DWI-MRIs for quality and segmented the tumor. A total of 103 radiomic features were calculated for each image. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features. Association between the radiomics signature and OS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. The Cox proportional-hazard regression model was also used to analyze the correlation between the prognostic factor and the survival for the clinical (C) model after the univariate analysis. Radiomics (R) model identified radiomics signature, which is the best predictor from the radiomic variable classes based on LASSO regression. Harrell's C-index was used to demonstrate the incremental value of the radiomics signature to the traditional clinical risk factors for the individualized prediction performance.
Cox proportional-hazard regression model shows that: Tumor size, alkaline phosphatase (ALP) status before treatment and number of courses of chemotherapy were proven as the dependent clinical prognostic factors of osteosarcoma's overall survival time. The radiomics signature was significantly associated with OS, independent of clinical risk factors (radiomics signature: HR: 5.11, 95% CI: 2.85, 9.18, < 0.001). Incorporating the radiomics signature into the coalition (C+R) model resulted in better performance ( < .001) for the estimation of OS (C-index: 0.813; 95% CI: 0.75, 0.89) than with the clinical (C) model (C-index: 0.764; 95% CI: 0.69, 0.85), or the single radiomics (R) model (C-index: 0.712; 95% CI: 0.65, 0.78).
This study shows that the radiomics signature extracted from pre-treatment DWI-MRI improve prediction of OS over clinical features alone. Combination of the radiomics signature and the traditional clinical risk factors performed better for individualized OS estimation in patients with osteosarcoma, which might enable a step forward precise medicine. This method may help better select patients most likely to benefit from intensified multimodality diagnosis and therapies. Future studies will focus on multi-center validation of an optimized model.
骨肉瘤通常需要多学科治疗,包括手术、化疗和放疗。然而,患者之间的肿瘤行为差异很大,为个体患者选择合适的治疗方法仍然是一项严峻挑战。放射组学旨在在假设这些信息与肿瘤生物学相关的前提下,对肿瘤图像的复杂特征进行量化。本研究检验了这样一个假设:与仅使用临床因素相比,从扩散加权磁共振成像(DWI-MRI)中提取的放射组学特征能够改善对局限性骨肉瘤总生存期(OS)的预测。
材料/方法:收集了112例经组织学证实的骨肉瘤患者(年龄9 - 67岁)的治疗前DWI-MRI,这些患者接受了根治性治疗。整个数据集被分为两个子集:训练队列和验证队列,分别包含76%和24%的数据。临床数据从我们的病历中提取。两名经验丰富的放射治疗师评估DWI-MRI的质量并对肿瘤进行分割。为每个图像计算了总共103个放射组学特征。应用最小绝对收缩和选择算子(LASSO)回归来选择特征。探讨了放射组学特征与OS之间的关联。通过多变量Cox回归对放射组学特征作为独立生物标志物进行了进一步验证。单变量分析后,Cox比例风险回归模型也用于分析临床(C)模型中预后因素与生存之间的相关性。放射组学(R)模型识别出放射组学特征,这是基于LASSO回归从放射组学变量类别中得出的最佳预测指标。Harrell's C指数用于证明放射组学特征相对于传统临床危险因素在个体预测性能方面的增量价值。
Cox比例风险回归模型显示:肿瘤大小、治疗前碱性磷酸酶(ALP)状态和化疗疗程数被证明是骨肉瘤总生存时间的相关临床预后因素。放射组学特征与OS显著相关,独立于临床危险因素(放射组学特征:HR:5.11, 95% CI:2.85, 9.18, < 0.00 < span=""><>1)。将放射组学特征纳入联合(C + R)模型在估计OS方面(< < span=""><>.001)比临床(C)模型(C指数:0.764;95% CI:0.69, 0.85)或单一放射组学(R)模型(C指数:0.71 < span=""><>2;95% CI:0.65, 0.78)表现更好。
本研究表明,从治疗前DWI-MRI中提取的放射组学特征比仅使用临床特征能更好地预测OS。放射组学特征与传统临床危险因素相结合在骨肉瘤患者个体OS估计方面表现更佳,这可能推动精准医学向前迈进一步。该方法可能有助于更好地选择最有可能从强化多模态诊断和治疗中获益的患者。未来研究将聚焦于优化模型的多中心验证。