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-2-deoxy-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 (LDH+S100) 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.

中文翻译：

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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假性进展的放射组学、肿瘤体积和血液生物标志物。

目的：我们评估了基于正电子发射断层扫描 (PET)/CT 的放射组学、病变体积和常规血液标志物的预测潜力，用于早期区分假性进展与 3 个月时的真实进展。实验设计：我们的研究包括 112 名接受免疫检查点抑制治疗的转移性黑色素瘤患者。中位随访时间为 22 个月。在三个时间点：基线 (TP0)、3 个月 (TP1) 和 6 个月 (TP2)，在 CT 和 2[18F] 氟-2-脱氧-D-葡萄糖 (FDG)-PET 成像上分别分割了 716 个转移灶。反应在病灶个体水平 (RECIST 1.1) 上定义，并与 FDG-PET/CT 影像学特征和血液标志物 LDH/S100 回顾性相关。生成了七个多变量预测模型类。结果：两年（中位）总生存期，无进展生存率和无免疫进展生存率分别为 69%（未达到）、24%（6 个月）和 42%（16 个月）。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。假性进展性病变和没有真正进展性病变的患者与有反应的患者有相似的结果，2 年总生存率为 100%（30 个月），而真正进展/无假性进展的患者的 2 年总生存率为 15%（10 个月）。 P = 0.002）。混合进行性/假性进行性病变的患者介于 53%（25 个月）之间。血液预测模型 (LDH+S100) 的 AUC = 0.71。较高的 LDH/S100 值表明假性进展的可能性较低。基于体积的模型：AUC = 0.72 (TP1) 和 AUC = 0。80（TP0/TP1 之间的增量体积）。放射组学模型（包括/排除与体积相关的特征）：AUC = 0.79/0.78。联合血液/容量模型：AUC = 0.79。组合血液/放射组学模型（包括体积相关特征）：AUC = 0.78。组合的血液/放射组学模型（不包括体积相关特征）表现最佳：AUC = 0.82。结论：基于无创 PET/CT 的放射组学，尤其是结合血液参数，是早期鉴别假性进展的有希望的生物标志物，可能避免增加毒性或延迟治疗转换。组合的血液/放射组学模型（不包括体积相关特征）表现最佳：AUC = 0.82。结论：基于无创 PET/CT 的放射组学，尤其是结合血液参数，是早期鉴别假性进展的有希望的生物标志物，可能避免增加毒性或延迟治疗转换。组合的血液/放射组学模型（不包括体积相关特征）表现最佳：AUC = 0.82。结论：基于无创 PET/CT 的放射组学，尤其是结合血液参数，是早期鉴别假性进展的有希望的生物标志物，可能避免增加毒性或延迟治疗转换。