Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance

Abstract

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.

A radiomics model to predict γδ T‐cell abundance and overall survival in head and neck squamous cell carcinoma

“…Radiomics provides high‐dimensional quantitative information that might have been overlooked or unrecognized with the naked eye to aid diagnosis based on imaging features, refers to “digital biopsy.” Furthermore, a radiomics prediction model can provide clinical treatment guidance before surgery. A recent study built a radiomics model to track the evolutionary route of nasopharyngeal carcinoma metastasis and further predict survival 48 . Wang et al 49 .…”

“…Many investigators are committed to building a radiomics model to predict intratumoral immune cells precisely and generalizability. 21,48 Notably, this is the first report to assess γδ T-cell abundance using radiomics. Thus, the radiomics model is becoming a popular research direction for predicting prognosis and treatment efficacy.…”

“…A recent study built a radiomics model to track the evolutionary route of nasopharyngeal carcinoma metastasis and further predict survival. 48 Wang et al 49 established a radiomics model based on CT to predict the CD8+ T cell abundance status in HNSCC, with the AUC of 0.786. Another radiomic analysis was performed to identify HPV status and yielded sufficient performance in patients with HNSCC.…”

Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

“…The spatiotemporal genetic heterogeneity of solid tumors has been associated with a dismal prognosis due to decreased therapy response and higher rates of tumor recurrence [ 95 , 96 ]. This also applies to patients with HNSCCs, even in the setting of a favorable HPV+ tumor status [ 33 , 97 , 98 , 99 ].…”

“…Patients with hematogenous metastasis exhibited upregulations of PD-L1 and PD-L2, suggesting that immune checkpoint inhibition may be a viable treatment option for this group. In contrast, patients with lymphatic metastasis showed a better response to chemotherapy in combination with locoregional radiotherapy [ 99 ].…”