Is there a role for [18F]-FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature

Hypoxia is a major cause of radioresistance in head and neck cancer (HNC), resulting in treatment failure and disease recurrence. 18F-fluoromisonidazole ([18F]FMISO) PET has been proposed as a means of localising intratumoural hypoxia in HNC so that radiotherapy can be specifically escalated in hypoxic regions. This concept may be challenging to implement in routine clinical practice however, given that [18F]FMISO PET is costly, time consuming and difficult to access. The aim of this review was to summarise clinical studies involving [18F]FMISO PET and to appraise the evidence for its role in guiding radiotherapy treatment in HNC. A comprehensive literature search was conducted on PubMed and Web of Science databases. Studies investigating [18F]FMISO PET in newly diagnosed HNC patients were considered eligible for review. We found the following important results from our literature review: (1) Studies have demonstrated a correlation between [18F]FMISO PET and other hypoxia biomarkers, although the results are not consistent enough to propose a proxy biomarker of [18F]FMISO PET. (2) [18F]FMISO PET uptake changes during a course of radiotherapy treatment, suggesting that imaging should be repeated during treatment. (3) Tumour recurrences do not always occur within the pretreatment hypoxic volume on [18F]FMISO PET. (4) Dose modification studies using [18F]FMISO PET are in a pilot phase. Our results show that currently there is insufficient evidence to propose [18F]FMISO PET for radiotherapy dose adaptation in HNC in a routine clinical setting. Part of the challenge is that hypoxia is a dynamic phenomenon, and thus areas identified on a single scan may not be representative. At present, it is anticipated that [18F]FMISO PET will remain useful within the research setting only.