Project Details
Projekt
Radioclinomics for prediction of treatment response to immune checkpoint therapy and molecular targeted therapies in patients with metastatic malignant melanoma.
Applicant
Professorin Dr. Lale Umutlu
Subject Area
Nuclear Medicine, Radiotherapy, Radiobiology
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 428212161
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.
DFG Programme
Priority Programmes
