Yousefirizi Fereshteh, Gowdy Claire, Klyuzhin Ivan S, Sabouri Maziar, Tonseth Petter, Hayden Anna R, Wilson Donald, Sehn Laurie H, Scott David W, Steidl Christian, Savage Kerry J, Uribe Carlos F, Rahmim Arman
Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada.
BC Children's Hospital, Vancouver, BC V6H 3N1, Canada.
Cancers (Basel). 2024 Mar 8;16(6):1090. doi: 10.3390/cancers16061090.
Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients.
Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE).
To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (-value> 0.05).
This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [F]FDG PET-CT scans.
准确的预后预测对于在癌症治疗中做出明智的临床决策至关重要。在本研究中,我们评估了化疗后利用放射组学特征随时间的变化(Δ放射组学:绝对值和相对值)来预测原发性纵隔大B细胞淋巴瘤(PMBCL)患者复发/进展及进展时间(TTP)的可行性。
鉴于2011年之前缺乏标准分期PET扫描,在我们的回顾性研究中,103例PMBCL患者中只有31例有治疗前和治疗结束时(EoT)的扫描。因此,我们的放射组学分析聚焦于这31例在R-CHOP化疗前后接受[F]FDG PET-CT扫描的患者。对其扫描进行专家手动病变分割以进行Δ放射组学分析,另外还有19例EoT扫描,共50例分割扫描用于单时间点分析。计算放射组学特征(PET和CT上的),以及最大和平均标准化摄取值(SUVmax和SUVmean)、总代谢肿瘤体积(TMTV)、肿瘤播散(Dmax)、总病变糖酵解(TLG)和累积标准化摄取值-体积直方图曲线下面积(AUC-CSH)。我们还应用了基于径向平均强度(RIM)变化的纵向分析。为了预测复发/进展,我们利用个体系数近似风险估计(ICARE)和机器学习(ML)技术(K近邻(KNN)、线性判别分析(LDA)和随机森林(RF)),包括在特征选择的相关性分析后进行顺序特征选择(SFS)。对于TTP,使用ICARE和CoxNet方法。在所有模型中,我们在使用合成少数过采样技术(SMOTE)平衡数据集后,使用嵌套交叉验证(CV)(10个外折和5次重复,以及5个内折和20次重复)。
为了利用基线(分期)和EoT扫描之间的Δ放射组学预测复发/进展,在准确性和F1分数方面表现最佳(F1分数是精确率和召回率的调和平均值,其中精确率是真阳性与真阳性和假阳性之和的比值,召回率是真阳性与真阳性和假阴性之和的比值)的是ICARE(准确性 = 0.81 ± 0.15,F1 = 0.77 ± 0.18)、RF(准确性 = 0.89 ± 0.04,F1 = 0.87 ± 0.04)和LDA(准确性 = 0.89 ± 0.03,F1 = 0.89 ± 0.03),与仅使用EoT放射组学特征所达到的预测能力相比更高。对于我们分析的第二类,TTP预测,表现最佳的是CoxNet(LASSO特征选择),使用基线 + Δ特征(同时包含基线和Δ特征)时c指数 = 0.67 ± 0.06。通过Δ放射组学得到的TTP结果与使用从EoT扫描中提取的放射组学特征进行TTP分析(使用CoxNet(SFS)时c指数 = 0.68 ± 0.09)相当。当使用EoT扫描时,Deauville评分(DS)对TTP的表现为n = 50时c指数 = 0.66 ± 0.09,n = 31例时c指数 = 0.67 ± 0.03,与来自EoT扫描或基线 + Δ特征的放射组学特征相比无显著差异(p值> 0.05)。
这项工作证明了Δ放射组学的潜力以及使用EoT扫描从PMBCL [F]FDG PET-CT扫描预测进展和TTP的重要性。