Metastatic Disease Burden

The presence of distant metastases, most commonly in the bone and bone marrow, is one of the most significant predictors of outcome for patients with neuroblastoma. The methods for detecting metastases have evolved significantly over the past two decades and moving forward continued advances in methods for measuring minimal residual disease in the blood and bone marrow and the use of cell-free tumor DNA-based technologies will allow more sensitive detection of metastatic disease at diagnosis, during treatment, and at the time of recurrence. In this chapter, we review the standard clinical methods used to detect metastatic disease at diagnosis and to determine the response to treatment. These include imaging and bone marrow histology-based assays. We will also present the data to support the potential integration of minimal residual disease (MRD) assays that detect neuroblastoma-specific transcripts in blood and bone marrow. Finally, we will review recent discoveries that are enabling the detection of neuroblastoma circulating tumor DNA (ctDNA) in patients. Ultimately, more sensitive and specific assays to detect disease burden at diagnosis, during therapy, and at recurrence may be integrated into clinical trials. These newer methods should complement or potentially reduce the need for invasive tests and some imaging scans in order to monitor disease response to novel therapies.