Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition
Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition
复制标题
放射组学、肿瘤体积和血液生物标志物用于早期预测接受免疫检查点抑制治疗的转移性黑色素瘤患者的假性进展
DOI：
10.1158/1078-0432.ccr-20-0020
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发表时间：
2020-08-15
影响因子：
11.5
通讯作者：
Levesque, Mitchell P.
中科院分区：
文献类型：
--
作者：
Basler, Lucas;Gabrys, Hubert S.;Levesque, Mitchell P.
目的：我们评估了预测潜力的正电子发射断层扫描（PET）/CT为基础的放射组学，病变体积，和常规的血液标志物的早期区分pseudoprogression从真正的progression. ExperimentalDesigns：112例转移性黑色素瘤治疗免疫检查点抑制被纳入我们的研究。中位随访时间为22个月。在三个时间点：基线（TP 0）、3个月（TP 1）和6个月（TP 2），通过CT和2[18 F]氟-2脱氧-D-葡萄糖（FDG）-PET成像对716个转移瘤进行单独分割。在病灶个体水平（RECIST 1.1）上定义缓解，并与FDG-PET/CT放射组学特征和血液标志物LDH/S100进行回顾性相关分析。结果：2年（中位数）总生存期，无进展生存期，免疫无进展生存期分别为69%（未达到），24%（6个月），42%（16个月），分别。在3个月时，106个（16%）病变进展，其中30个（5%）在6个月时被确定为假性进展。出现假进展性病变和没有出现真正进展性病变的患者的结局与有反应的患者相似，2年总生存率明显更高，为100%（30个月），而出现真正进展/没有出现真正进展的患者的2年总生存率为15%（10个月）（P = 0.002）。混合进行性/假进行性病变的患者介于53%（25个月）之间。血液预测模型（LDHthornS 100）的AUC = 0.71。较高的LDH/S100值表明假进展的可能性较低。基于体积的模型：AUC = 0.72（TP 1）和AUC = 0.80（TP 0/TP 1之间的Δ体积）。放射组学模型（包括/不包括体积相关特征）：AUC = 0.79/0.78。组合血液/体积模型：AUC = 0.79。组合血液/放射组学模型（包括体积相关特征）：AUC = 0.78。联合血液/放射组学模型（排除体积相关特征）表现最好：AUC = 0.82。结论：基于PET/CT的放射组学，特别是联合血液参数，是早期鉴别假进展的有前景的生物标志物，可能避免增加毒性或延迟治疗转换。
Purpose: We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months.Experimental Design: 112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months ( TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated.Results: Two-year (median) overall survival, progression-free survival, and immune progression-free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression (P = 0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction model (LDHthornS100) achieved an AUC = 0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC = 0.72 (TP1) and AUC = 0.80 (delta-volume between TP0/TP1). Radiomics models (including/ excluding volume-related features): AUC = 0.79/0.78. Combined blood/volume model: AUC = 0.79. Combined blood/radiomics model (including volume-related features): AUC = 0.78. The combined blood/radiomics model (excluding volume-related features) performed best: AUC = 0.82.Conclusions: Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.