Department of Radiation Oncology, Gustave Roussy, Villejuif, France.
Université Paris Saclay, Inserm U1030, Radiothérapie Moléculaire et Innovation Thérapeutique, Gustave Roussy, Villejuif, France.
J Immunother Cancer. 2022 Oct;10(10). doi: 10.1136/jitc-2022-004867.
While there is still a significant need to identify potential biomarkers that can predict which patients are most likely to respond to immunotherapy treatments, radiomic approaches have shown promising results. The objectives of this study were to evaluate whether a previously validated radiomics signature of CD8 T-cells could predict progressions at a lesion level and whether the spatial heterogeneity of this radiomics score could be used at a patient level to assess the clinical response and survival of melanoma patients.
Clinical data from patients with advanced melanoma treated in our center with immunotherapy were retrieved. Radiomic features were extracted and the CD8 radiomics signature was applied. A progressive lesion was defined by an increase in lesion size of 20% or more. Dispersion metrics of the radiomics signature were estimated to evaluate the impact of interlesion heterogeneity on patient's response. Fine-tuned cut-offs for predicting overall survival were evaluated after splitting data into training and test sets.
A total of 136 patients were included in this study, with 1120 segmented lesions at baseline, and 1052 lesions at first evaluation. A low CD8 radiomics score at baseline was associated with a significantly higher risk of lesion progression (AUC=0.55, p=0.0091), especially for lesions larger than >1 mL (AUC=0.59 overall, p=0.0035, with AUC=0.75, p=0.002 for subcutaneous lesions, AUC=0.68, p=0.01, for liver lesions and AUC=0.62, p=0.03 for nodes). The least infiltrated lesion according to the radiomics score of CD8 T-cells was positively associated with overall survival (training set HR=0.31, p=0.00062, test set HR=0.28, p=0.016), which remained significant in a multivariate analysis including clinical and biological variables.
These results confirm the predictive value at a lesion level of the biologically inspired CD8 radiomics score in melanoma patients treated with anti-PD1-based immunotherapy and may be interesting to assess the disease spatial heterogeneity to evaluate the patient prognosis with potential clinical implication such as tumor selection for focal ablative therapies.
虽然仍有很大的需求来确定潜在的生物标志物，以预测哪些患者最有可能对免疫治疗产生反应，但放射组学方法已经显示出了有希望的结果。本研究的目的是评估以前验证过的 CD8 细胞放射组学特征是否可以预测病变水平的进展，以及该放射组学评分的空间异质性是否可以用于患者水平，以评估黑色素瘤患者的临床反应和生存。
从在我们中心接受免疫治疗的晚期黑色素瘤患者中检索临床数据。提取放射组学特征，并应用 CD8 放射组学特征。通过增加 20%或更多的病变大小来定义进行性病变。估计放射组学特征的离散度指标，以评估病变间异质性对患者反应的影响。在将数据分为训练集和测试集后，评估预测总生存期的微调截止值。
本研究共纳入 136 例患者，基线时有 1120 个分割病变，第一次评估时有 1052 个病变。基线时低 CD8 放射组学评分与病变进展的风险显著相关（AUC=0.55，p=0.0091），特别是对于大于 >1 毫升的病变（总体 AUC=0.59，p=0.0035，皮下病变 AUC=0.75，p=0.002，肝脏病变 AUC=0.68，p=0.01，淋巴结病变 AUC=0.62，p=0.03）。根据 CD8 T 细胞放射组学评分，最少浸润的病变与总生存期呈正相关（训练集 HR=0.31，p=0.00062，测试集 HR=0.28，p=0.016），在包括临床和生物学变量的多变量分析中仍然具有显著性。
这些结果在接受基于抗 PD1 的免疫治疗的黑色素瘤患者中证实了生物启发的 CD8 放射组学评分在病变水平上的预测价值，并且可能有助于评估疾病的空间异质性，以评估患者的预后，具有潜在的临床意义，例如为局部消融治疗选择肿瘤。
