Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Eur J Cancer. 2023 May;185:167-177. doi: 10.1016/j.ejca.2023.02.017. Epub 2023 Feb 24.
Predicting checkpoint inhibitors treatment outcomes in melanoma is a relevant task, due to the unpredictable and potentially fatal toxicity and high costs for society. However, accurate biomarkers for treatment outcomes are lacking. Radiomics are a technique to quantitatively capture tumour characteristics on readily available computed tomography (CT) imaging. The purpose of this study was to investigate the added value of radiomics for predicting clinical benefit from checkpoint inhibitors in melanoma in a large, multicenter cohort.
Patients who received first-line anti-PD1±anti-CTLA4 treatment for advanced cutaneous melanoma were retrospectively identified from nine participating hospitals. For every patient, up to five representative lesions were segmented on baseline CT, and radiomics features were extracted. A machine learning pipeline was trained on the radiomics features to predict clinical benefit, defined as stable disease for more than 6 months or response per RECIST 1.1 criteria. This approach was evaluated using a leave-one-centre-out cross validation and compared to a model based on previously discovered clinical predictors. Lastly, a combination model was built on the radiomics and clinical model.
A total of 620 patients were included, of which 59.2% experienced clinical benefit. The radiomics model achieved an area under the receiver operator characteristic curve (AUROC) of 0.607 [95% CI, 0.562-0.652], lower than that of the clinical model (AUROC=0.646 [95% CI, 0.600-0.692]). The combination model yielded no improvement over the clinical model in terms of discrimination (AUROC=0.636 [95% CI, 0.592-0.680]) or calibration. The output of the radiomics model was significantly correlated with three out of five input variables of the clinical model (p < 0.001).
The radiomics model achieved a moderate predictive value of clinical benefit, which was statistically significant. However, a radiomics approach was unable to add value to a simpler clinical model, most likely due to the overlap in predictive information learned by both models. Future research should focus on the application of deep learning, spectral CT-derived radiomics, and a multimodal approach for accurately predicting benefit to checkpoint inhibitor treatment in advanced melanoma.
由于预测免疫检查点抑制剂治疗黑色素瘤的结果具有不可预测性和潜在致命毒性,且对社会的成本高昂,因此这是一项重要的任务。然而,目前缺乏准确的治疗结果生物标志物。放射组学是一种从易于获得的计算机断层扫描(CT)图像中定量捕获肿瘤特征的技术。本研究的目的是在一个大型多中心队列中,研究放射组学对预测黑色素瘤患者接受免疫检查点抑制剂治疗的临床获益的附加价值。
从九家参与医院回顾性确定接受一线抗 PD1±抗 CTLA4 治疗的晚期皮肤黑色素瘤患者。对每位患者,在基线 CT 上最多对五个代表性病变进行分割,并提取放射组学特征。使用机器学习管道对放射组学特征进行训练,以预测临床获益,定义为疾病稳定超过 6 个月或根据 RECIST 1.1 标准的反应。通过留一中心交叉验证评估该方法,并与基于先前发现的临床预测因子的模型进行比较。最后,在放射组学和临床模型的基础上构建联合模型。
共纳入 620 例患者,其中 59.2%患者经历了临床获益。放射组学模型的受试者工作特征曲线下面积(AUROC)为 0.607 [95%置信区间,0.562-0.652],低于临床模型的 AUROC(0.646 [95%置信区间,0.600-0.692])。联合模型在判别力(AUROC=0.636 [95%置信区间,0.592-0.680])或校准方面均未优于临床模型。放射组学模型的输出与临床模型的五个输入变量中的三个显著相关(p<0.001)。
放射组学模型对临床获益的预测具有中等的预测价值,且具有统计学意义。然而,放射组学方法无法为更简单的临床模型增加价值,这可能主要是由于两个模型学到的预测信息存在重叠。未来的研究应集中于深度学习、光谱 CT 衍生的放射组学和多模态方法的应用,以准确预测晚期黑色素瘤对免疫检查点抑制剂治疗的获益。