Prognostic Evaluation of Fluor 18 Labelled FLUROMISONIDAZOLE (18F-FMISO) Positon Emission Tomography-Computed Tomography (PET-CT) in Head and Neck Squamous Cell Carcinomas
Hypoxia is one of the major worst prognostic factors of clinical outcome in cancer. It is
actually admitted that hypoxia is heterogeneous, variable within different tumour types and
that it varies spatially and temporally in a tumor. Hypoxia induce proteomic and gene
expression changes that lead to increase angiogenesis, invasion and metastases. So, the
hypoxic fraction in solid tumours reduces their sensitivity to conventional treatment
modalities, modulating therapeutic response to ionizing radiation or certain
chemotherapeutic agents. This is particularly important in head and neck cancers (HNC).
Hypoxic cells in solid tumours could influence local failure following radiotherapy and has
been associated with malignant progression, loco regional spread and distant metastases and
represents an increasing probability of recurrence.
Thus, the non-invasive determination and monitoring of the oxygenation status could be of
tumours is of importance to predict patient outcome and eventually modify therapeutic
strategies in those tumours. Today, the oxygenation status of individual tumours is not
assessed routinely. Numerous different approaches have been proposed to identify hypoxia in
tumours. Eppendorf oxygen electrode measurements (pO2 histography) may be considered as a
'gold standard' for hypoxia in human malignancies. However, it is an invasive method being
confined to superficial, well accessible tumours and requires many measures. PET using
[18F]Fluoro-deoxyglucose (18F-FDG), allows non-invasive imaging of glucose metabolism and
takes a growing place in cancer staging, But 18F-FDG can't assess correctly the oxygenation
status of tumours. PET with appropriate radiotracers enables non-invasive assessment of
presence and distribution of hypoxia in tumours. Nitroimidazoles are a class of electron
affinic molecules that were shown to accumulate in hypoxic cells in vitro and in vivo.
[18F]-FMISO is the most frequently used tracer ; its intracellular retention is dependent on
oxygen tension. Consequently, [18F]-FMISO has been used as a non-invasive technique for
detection of hypoxia in humans. Different authors have demonstrated that it is suitable to
localize and quantify hypoxia. Thus, [18F]-FMISO PET has been studied to evaluate prognosis
and predict treatment response. However, some investigators report an unclear correlation
between Eppendorf measurements and standardized uptake values (SUV). This observation may be
explained by the structural complexity of hypoxic tumour tissues. Nevertheless, there is a
need of standardized procedures to acquire and quantify [18F]-FMISO uptake. Today, the use
of this tracer is very limited in clinic and the academic studies have included small
populations of patients and suffer of the heterogeneity of technical procedures.
The aim of this study is to determine the optimal acquisition protocol and image
reconstruction to describe [18F]-FMISO uptake in HNC, then, to validate [18F]-FMISO-PET as a
predictive marker of response to treatment.
Intervention Model: Single Group Assignment, Masking: Single Blind (Investigator), Primary Purpose: Health Services Research
Correlation between a hypoxic volume determined by [18F]-FMISO PET-CT and a treatment response two years after radical treatment.
Inclusion (Day 0) and after two years
CLERMONT-GALLERANDE Henri, MCU-PH
University Hospital, Bordeaux
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)