Department of Diagnostic and Interventional Radiology, Universitätsklinikum Tübingen, Tubingen, Germany.
Center of Dermatooncology, Department of Dermatology, Eberhard Karls Universitat Tubingen, Tubingen, Germany.
J Immunother Cancer. 2021 Nov;9(11). doi: 10.1136/jitc-2021-003261.
To assess the additive value of dual-energy CT (DECT) over single-energy CT (SECT) to radiomics-based response prediction in patients with metastatic melanoma preceding immunotherapy.
A total of 140 consecutive patients with melanoma (58 female, 63±16 years) for whom baseline DECT tumor load assessment revealed stage IV and who were subsequently treated with immunotherapy were included. Best response was determined using the clinical reports (81 responders: 27 complete response, 45 partial response, 9 stable disease). Individual lesion response was classified manually analogous to RECIST 1.1 through 1291 follow-up examinations on a total of 776 lesions (6.7±7.2 per patient). The patients were sorted chronologically into a study and a validation cohort (each n=70). The baseline DECT was examined using specialized tumor segmentation prototype software, and radiomic features were analyzed for response predictors. Significant features were selected using univariate statistics with Bonferroni correction and multiple logistic regression. The area under the receiver operating characteristic curve of the best subset was computed (AUROC). For each combination (SECT/DECT and patient response/lesion response), an individual random forest classifier with 10-fold internal cross-validation was trained on the study cohort and tested on the validation cohort to confirm the predictive performance.
We performed manual RECIST 1.1 response analysis on a total of 6533 lesions. Multivariate statistics selected significant features for patient response in SECT (min. brightness, R²=0.112, padj. ≤0.001) and DECT (textural coarseness, R²=0.121, padj. ≤0.001), as well as lesion response in SECT (mean absolute voxel intensity deviation, R²=0.115, padj. ≤0.001) and DECT (iodine uptake metrics, R²≥0.12, padj. ≤0.001). Applying the machine learning models to the validation cohort confirmed the additive predictive power of DECT (patient response AUROC SECT=0.5, DECT=0.75; lesion response AUROC SECT=0.61, DECT=0.85; p<0.001).
The new method of DECT-specific radiomic analysis provides a significant additive value over SECT radiomics approaches for response prediction in patients with metastatic melanoma preceding immunotherapy, especially on a lesion-based level. As mixed tumor response is not uncommon in metastatic melanoma, this lends a powerful tool for clinical decision-making and may potentially be an essential step toward individualized medicine.
评估双能 CT(DECT)相对于单能 CT(SECT)在预测接受免疫治疗的转移性黑色素瘤患者的放射组学反应中的附加价值。
共纳入 140 例连续的黑色素瘤患者(58 例女性,63±16 岁),其基线 DECT 肿瘤负荷评估显示为 IV 期,随后接受免疫治疗。使用临床报告确定最佳反应(81 例应答者:27 例完全缓解,45 例部分缓解,9 例疾病稳定)。通过总共 776 个病变的 1291 次随访检查,通过 RECIST 1.1 手动分类个体病变反应(每个患者 6.7±7.2 个)。按照时间顺序将患者分为研究队列和验证队列(各 n=70)。使用专门的肿瘤分割原型软件检查基线 DECT,并对放射组学特征进行分析以预测反应。使用具有 Bonferroni 校正的单变量统计和多元逻辑回归选择有意义的特征。计算最佳子集的接收器工作特征曲线下面积(AUROC)。对于每个组合(SECT/DECT 和患者反应/病变反应),在研究队列上训练单个随机森林分类器,并在验证队列上进行测试,以确认预测性能。
我们对总共 6533 个病变进行了手动 RECIST 1.1 反应分析。多变量统计选择了 SECT 中患者反应的有意义特征(最小亮度,R²=0.112,padj.≤0.001)和 DECT 中的特征(纹理粗糙度,R²=0.121,padj.≤0.001),以及 SECT 中病变反应的特征(平均绝对体素强度偏差,R²=0.115,padj.≤0.001)和 DECT 中的特征(碘摄取指标,R²≥0.12,padj.≤0.001)。将机器学习模型应用于验证队列,证实了 DECT 的附加预测能力(患者反应 AUROC SECT=0.5,DECT=0.75;病变反应 AUROC SECT=0.61,DECT=0.85;p<0.001)。
用于 DECT 特异性放射组学分析的新方法为接受免疫治疗的转移性黑色素瘤患者的反应预测提供了比 SECT 放射组学方法显著的附加价值,特别是在基于病变的水平上。由于转移性黑色素瘤中混合性肿瘤反应并不少见,因此这为临床决策提供了有力工具,并且可能是迈向个体化医学的重要一步。