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系统治疗在新的药物治疗选择方面有了实质性的改进，包括免疫检查点抑制治疗(ICIT)和分子靶向治疗(MTT)。免疫检查点抑制疗法(ICIT)是癌症治疗的新范式之一，它显著改善了实体瘤患者的总体生存和无进展生存。ICIT，主要是针对PD-1或PD-L1的抗体，在肿瘤学方面取得了重要的临床进展，特别是在恶性黑色素瘤的治疗方面。然而，在大多数实体中，只有20%的患者显示出持续受益于抗PD-1/PD-L1抗体的单一治疗，而80%的患者未能受益。与ICIT相比，分子靶向治疗适用于BRAF突变患者，使50%-60%的患者受益。虽然与常规治疗相比，恶性黑色素瘤的治疗已经提升到了更高的成功水平，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，从而能够早期和充分区分有效和无反应的患者。关于恶性黑色素瘤患者临床和组织生物标记物预测潜力的初步阳性报道的潜在翻译尚未就恶性黑色素瘤转移的基于成像的生物标记物进行调查。放射组学已被证明具有用新的成像生物标记物来补充当前诊断工作的潜力，以改善癌症的检测、诊断、预后预测和治疗反应。许多基于CT和MR成像的放射基因组学早期研究已经证明了它在提高对肿瘤生物学的理解以及诊断和治疗监测的新方法方面的诊断和预测潜力。该项目旨在根据CT成像和临床参数确定预后和预测性生物标记物，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，计划评估定量放射临床分析的潜力，以改进反应评估，并与当前的RECIST 1.1标准相比准确地预测对ICIT和MTT的治疗反应。总体目标是引入新的生物标志物，用于预测和评估接受ICIT和四甲基偶氮唑盐治疗的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，进入更精确的初始诊断和治疗途径，并在临床环境中改进个性化药物方面的治疗监测。

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.