Page 22 - Read Online

Page 6 of 8 Dankbaar et al. J Cancer Metastasis Treat 2021;7:56 https://dx.doi.org/10.20517/2394-4722.2021.112

enhanced sequences. All these features could be used to improve automatic detection algorithms for ENE.
In addition, the information from imaging could be combined with genomic and epigenetic markers. It has
[42]
for example been shown that high-risk TP53 mutations are associated with ENE . Moreover, advances in
next generation sequencing and multi-platform genomic and epigenetic characterization of solid tumors
may result in an individualized determination of treatment response and prognosis in patients with HNSCC
in the future [43-45] .

DISCUSSION
As of the introduction of TNM8 in 2017, head and neck surgeons, pathologists, and radiologists are trying
to implement the new ENE criteria in daily practice. As described above, there is a large variation in the
reported diagnostic performance of both CT and MRI for the detection of ENE. This variation is most likely
caused by significant variations in the histological and radiological diagnostic criteria. The histological
criteria are not mentioned in the majority of the studies. Furthermore, in most studies that mentioned
histological criteria, no difference was made between macroscopic invasion and microscopic ENE in the
analysis. With standardized histological criteria and identification of clinically relevant ENE on histology,
radiological criteria can be improved. Accurately defining the radiological criteria of clinically relevant ENE
and testing the reproducibility of these criteria will improve the applicability in clinical practice and thereby
aid treatment decision making. It is likely that automated detection algorithms with the incorporation of
MRI radiomics will also benefit from these efforts. We expect refinements of the ENE criteria in the
upcoming TNM9. In addition, genomic and epigenetic features are expected to play an increasingly
important role in future determination of response and prognosis of patients with HNSCC.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data interpretation
and manuscript drafting: Dankbaar JW, Pameijer FA

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.

REFERENCES
1. Coatesworth AP, Tsikoudas A, MacLennan K. The cause of death in patients with head and neck squamous cell carcinoma. J Laryngol
Otol 2002;116:269-71. DOI PubMed
2. Leemans CR, Tiwari R, Nauta JPJ, Van der Waal I, Snow GB. Regional lymph node involvement and its significance in the
development of distant metastases in head and neck carcinoma. Cancer 1993;71:452-6. DOI PubMed