Abstract
BackgroundNasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong. We aim to utilise liquid biopsies for serial monitoring of disseminated NPC in patients to compare with PET-CT imaging in detection of minimal residual disease.MethodProspective serial monitoring of liquid biopsies was performed for 21 metastatic patients. Circulating tumour cell (CTC) enrichment and characterisation was performed using a sized-based microfluidics CTC chip, enumerating by immunofluorescence staining, and using target-capture sequencing to determine blood mutation load. PET-CT scans were used to monitor NPC patients throughout their treatment according to EORTC guidelines.ResultsThe longitudinal molecular analysis of CTCs by enumeration or NGS mutational profiling findings provide supplementary information to the plasma EBV assay for disease progression for good responders. Strikingly, post-treatment CTC findings detected positive findings in 75% (6/8) of metastatic NPC patients showing complete response by imaging, thereby demonstrating more sensitive CTC detection of minimal residual disease. Positive baseline, post-treatment CTC, and longitudinal change of CTCs significantly associated with poorer progression-free survival by the Kaplan–Meier analysis.ConclusionsWe show the potential usefulness of application of serial analysis in metastatic NPC of liquid biopsy CTCs, as a novel more sensitive biomarker for minimal residual disease, when compared with imaging.
Highlights
Nasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong
We demonstrate the feasibility of utilising liquid biopsies for Circulating tumour cell (CTC) enumeration and NGS analysis to obtain the blood mutation load and comparative plasma EBV assay for monitoring the efficacy of chemotherapeutic treatment in NPC patients having distant metastasis
The EBV plasma status collected at the middle and end of treatment was a good independent predictive biomarker for treatment response representative of the tumour bulk and significantly associated with progressionfree survival (PFS) in metastatic NPC patients
Summary
Nasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong. We aim to utilise liquid biopsies for serial monitoring of disseminated NPC in patients to compare with PET-CT imaging in detection of minimal residual disease. Post-treatment CTC findings detected positive findings in 75% (6/8) of metastatic NPC patients showing complete response by imaging, thereby demonstrating more sensitive CTC detection of minimal residual disease. CONCLUSIONS: We show the potential usefulness of application of serial analysis in metastatic NPC of liquid biopsy CTCs, as a novel more sensitive biomarker for minimal residual disease, when compared with imaging. Because of its innocuous symptoms, the tumour often progresses to advanced stages prior to diagnosis. This greatly reduces survival and the quality of life. In Hong Kong young males less than 44 years of age, NPC is the top cancer in terms of incidence. Earlier diagnosis and better predictive markers for metastatic tumours are important in the quest to improve patient survival. the survival for NPC patients with recurrent or primary metastatic disease is dismal, with a median overall survival of 20 months.
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