Imaging and liquid biopsy in the prediction and evaluation of response to PRRT in neuroendocrine tumors: implications for patient management

Abstract

Purpose The aim of this narrative review is to give an overview on current and emerging imaging methods and liquid biopsy for prediction and evaluation of response to PRRT. Current limitations and new perspectives, including artificial intelligence, are discussed. Methods A literature review of PubMed/Medline was performed with representative keywords. The search included articles published online through August 31, 2020. All searches were restricted to English language manuscripts. Results Peptide radio receptor therapy (PRRT) is a prospectively evaluated and approved therapy option in neuroendocrine tumors (NETs). Different ligands targeting the somatostatin receptor (SSTR) are used as theranostic pairs for imaging NET and for PRRT. Response assessment in prospective trials often relies on the morphological RECIST 1.1 criteria, based on lesion size in CT or MRI. The role of SSTR-PET and quantitative uptake parameters and volumetric data is still not defined. Monoanalyte tumor marker chromogranin A has a limited value for response assessment after PRRT. New emerging liquid biopsy techniques are offering prediction of response to PRRT and prognostic value. Conclusions New response criteria for NET patients undergoing PRRT will comprise multiparametric hybrid imaging and blood-based multianalyte markers. This represents tumor biology and heterogeneity.

Liquid Biopsy in Pre-Metastatic Niche: From Molecular Mechanism to Clinical Application

“…Single-cell sequencing has increased the understanding of the molecular pathways involved in triggering cancer progression (141). Molecular imaging, especially when combined with liquid biopsy for screening, promises early disease localization because biochemical changes precede anatomical changes (142). The methylation patterns informed by cfDNA sequencing can be used for epigenetic variation assessment, with potential value for early detection of fatal malignancies (143).…”

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

“…Notably, PFS and OS were comparable in patients with objective response and SD. Nonetheless, response assessment after PRRT solely based on tumor shrinkage may not be sufficient, given the fact that changes in tumor perfusion and tumor necrosis are not considered [ 38 ]. Furthermore, the nadir of the tumor shrinkage occurs late after treatment, from several months to even several years [ 39 ].…”

“…Response criteria for PET imaging of NETs are highly desirable. The difficulty with molecular imaging of the SSTR is based on the fact that a quantitative decrease in ligand uptake on PET imaging after PRRT can be caused by a therapeutic effect but also by disease progression, perfusion changes or dedifferentiation [ 38 ]. SSTR PET imaging is useful to document progression through the appearance of new lesions.…”

“…At present, the role of circulating biomarkers (Chromogranin A (CgA), Neuron Specific Enolase (NSE), 5-Hydroxyindole-3-Acetic Acid (5-HIAA)) in response assessment after PRRT is limited, due to low sensitivity and specificity [ 42 ]. New techniques involving liquid biopsies are being studied [ 38 ].…”

“…Another way of PRRT optimization can be achieved by pretreatment patient stratification. This strategy is gaining popularity over the last few years, given the fact that 15–30% of the patients show progression during PRRT and 10–20% of patients progress within the year after termination of PRRT [ 38 , 47 , 53 , 64 , 152 ]. Several predictors have been investigated in this setting, which include molecular or imaging markers of response.…”