Radioclinomics for prediction of treatment response to immune checkpoint therapy and molecular targeted therapies in patients with metastatic malignant melanoma.

在过去的十年中，转移性恶性黑色素瘤患者的全身治疗已经发生了根本性的改善，包括免疫检查点抑制疗法（immune checkpoint inhibition therapy，简称iciti）和分子靶向治疗（molecular targeted therapies，简称MTT）。免疫检查点抑制疗法（immune checkpoint inhibition therapy，简称“免疫检查点抑制疗法”）是癌症治疗的新范式之一，它可以显著改善实体瘤患者的总生存期和无进展生存期。主要针对PD-1或PD-L1的抗体，在肿瘤学，特别是在恶性黑色素瘤的治疗方面取得了重要的临床进展。然而，在大多数情况下，只有20%的患者从抗pd -1/PD-L1抗体单药治疗中表现出持久的获益，而80%的患者没有获益。与之相比，分子靶向治疗用于braf突变患者，使50-60%的患者获得治疗益处。虽然与传统治疗相比，恶性黑色素瘤的治疗已经提升到更高的成功水平，但治疗反应的评估仍然局限于基于大小的RECIST评估，无法评估早期治疗反应或反应预测，从而无法早期和充分区分反应者和无反应者。关于临床和组织生物标志物在恶性黑色素瘤患者中的预测潜力的初步阳性报告的潜在翻译，尚未对基于成像的恶性黑色素瘤转移的生物标志物进行研究。放射组学已被证明有潜力与新的成像生物标志物补充现有的诊断工作，以改善癌症的检测、诊断、预后预测和治疗反应。基于CT和MR成像的放射基因组学的一些早期研究已经证明了它的诊断和预测潜力，可以提高对肿瘤生物学的理解，以及诊断和治疗监测的新方法。该项目旨在确定基于CT成像和临床参数的预后和预测性生物标志物，用于免疫检查点抑制剂和分子靶向治疗转移性黑色素瘤患者。因此，与目前的RECIST 1.1标准相比，计划评估定量放射临床分析的潜力，以改进反应评估并准确预测对ict和MTT的治疗反应。总的目标是引入新的生物标志物，用于预测和评估转移性黑色素瘤患者的反应。这些体内放射临床标志物有可能改善患者分层，使其进入更精确的初始诊断和治疗途径，并在临床环境中改善个性化医疗，从而改善治疗监测。

Over the past decade systemic treatment of patients with metastatic malignant melanoma has undergone essential improvements, in terms of new medicinal treatment options including immune checkpoint inhibition therapy (ICIT) and molecular targeted therapies (MTT). One of the new paradigms of cancer treatment, by means of immune checkpoint inhibition therapy (ICIT), has revealed a significant improvement in overall survival and progression-free survival of patients with solid tumors . ICIT, mainly antibodies targeting PD-1 or PD-L1, has led to important clinical advances in oncology, in particular regarding the treatment of malignant melanoma. Nevertheless, in most entities only 20 % of patients exhibit durable benefit from monotherapy with anti-PD-1/PD-L1 antibodies, while 80 % of patients fail to benefit. In comparison to ICIT molecular targeted therapies are administered to patients with BRAF-mutations, enabling treatment benefits in 50-60% of the patients. While treatment of malignant melanoma has been elevated to superior success levels when compared to conventional treatment, assessment of therapy response is still restricted to size-based RECIST assessment, failing to assess early treatment response or response prediction to enable early and sufficient differentiation between responders and non-responders. A potential translation of initial positive reports on the predictive potential of clinical and tissue biomarkers in patients with malignant melanoma has yet to be investigated regarding imaging-based biomarkers on metastases of malignant melanoma. Radiomics has been shown to bear the potential to complement current diagnostic workup with new imaging biomarkers for improved cancer detection, diagnosis, prediction of prognosis and treatment response. A number of early investigations on radiogenomics based on CT and MR imaging have demonstrated its diagnostic and predictive potential for improved understanding of tumor biology as well as new approaches toward diagnosis and treatment monitoring. This project aims to identify prognostic and predictive biomarkers based on CT imaging and clinical parameters for treatment with immune checkpoint inhibitors and molecular targeted therapies in metastatic melanoma patients. Hereby, it is planned to evaluate the potential of quantitative radioclinical analyses to improve response assessment and accurately predict treatment response to ICIT and MTT compared to current RECIST 1.1 criteria. The overall aim is to introduce novel biomarkers for response prediction and assessment of metastatic melanoma patients treated with ICIT and MTT. These in vivo radioclinomic markers bear the potential to improve patient stratification into more precise initial diagnostic and therapeutic pathways and enable improved treatment monitoring, in terms of improved personalized medicine in clinical settings.