Abstract
The purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and 18F-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (F D), SUVmax (F SUVmax) were statistically assessed. F D ≥ 1 and F ADC ≥ 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC ≥ 1 in both post-treatment scans and F D ≥ 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD40l, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.
Highlights
The prognosis of patients with disseminated melanoma has been poor, with an approximately 10% 5-year survival[4,5]
Our results show the potential of magnetic resonance imaging (MRI) measuring apparent diffusion coefficient (ADC) and intra voxel incoherent motion (IVIM)-parameters to assess tumor response to immunotherapies as exemplified in this study on local immunomodulatory AdCD40L-gene therapy in patients with refractory metastatic MM
This is the first report on Diffusion-weighted - magnetic resonance imaging (DW-MRI) for tumor response evaluation in MM patients treated with immunomodulation
Summary
The prognosis of patients with disseminated melanoma has been poor, with an approximately 10% 5-year survival[4,5]. Response to immunotherapy is still mainly based on assessment of computed tomography (CT) and magnetic resonance imaging (MRI) according to RECIST 1.114 benefits of immunotherapy may not require significant reduction in tumor size[15] and functional methods have been applied. In 1999, the European Organization for Research and Treatment of Cancer (EORTC) proposed the first PET-based response criteria to assess therapy response in solid tumors[21,22]. Diffusion-weighted - magnetic resonance imaging (DW-MRI) is routinely included in MRI examination protocols for tumor diagnosis, to differ benign from malignant lesions, to detect recurrent disease, and to assess treatment response[27,28]. FDG-PET/CT is established in the clinical praxis to assess immunotherapy responses in Hodgkin lymphoma and Head&Neck and lung cancer, almost having replaced CT35 the role of DW-MRI in this regard is not yet established
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