Hypoxia with 18F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (18F-FETNIM PET/CT) in locoregionally advanced head and neck cancer: Hypoxia changes during chemoradiotherapy and impact on clinical outcome

Abstract

Hypoxia is a well-recognized biological characteristic to therapy resistance and negative prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). This study aims to investigate the changes of hypoxia measured by F-fluoroerythronitroimidazole (FETNIM) uptake on integrated positron emission tomography and computed tomography (PET/CT) during chemoradiotherapy and its prognostic value of clinical outcome in locoregionally advanced HNSCC.Thirty-two patients with locoregionally advanced HNSCC who received definitive treatment with concurrent chemoradiotherapy underwent FETNIM PET/CT scans before and after 5 weeks of treatment. The intensity of hypoxia using the maximum standardized uptake value (SUVmax) was evaluated both on primary lesion and metastatic lymph node (MLN). The pre-SUVmax and mid-SUVmax were defined as SUVmax on pre- and mid-FETNIM PET/CT. The local control (LC), regional control (RC), distant metastatic-free survival (DMFS), and overall survival (OS) were collected in patient follow-ups.Mid-SUVmax decreased significantly both in the primary tumor (t = 8.083, P < .001) and MLN (t = 6.808, P < .001) compared to pre-SUVmax. With a median follow-up of 54 months, the 5-year LC, RC, DMFS, and OS rates were 55%, 66.7%, 64.7%, and 55%, respectively, for all of the patients. On univariate analysis, patients with high pre-SUVmax in primary tumor had significantly worse LC (56.3% vs 87.5%, P = .046) and OS (43.8% vs 87.5%, P = .023) than other patients. Patients with high mid-SUVmax had significantly worse DMFS (50% vs 84.6%, P = .049) and OS (33.3% vs 73.1%, P = .028) than other patients. The tumor grade and mid-SUVmax were the significant predictors of OS on multivariate analysis.In this study, hypoxia in tumor significantly decreased during chemoradiotherapy. The persistent hypoxia predicted poor OS. The data provided evidence that FETNIM PET/CT could be used dynamically for selecting appropriate patients and optimal timing of hypoxia-adapted therapeutic regimens.

Figure 1

A patient with hypopharyneal cancer. (A) Pre-FDG /CT: primary tumor (red arrow), lymph node metastasis (blue arrow). (B) Pre-¹⁸F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (FETNIM PET/CT): highly focally increased and visually detectable uptake in primary tumor (red arrow), but FETNIM uptake in lymph node metastasis similar to that of background (blue arrow). (C) Mid-FETNIM PET/CT: FETNIM uptake in primary tumor similar to that of background (red arrow), remain undetectable in lymph node metastasis (blue arrow).

Figure 2

Another patient with hypopharyneal cancer. (A) Pre-¹⁸F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (FETNIM PET/CT): highly increased and visually detectable uptake in a lymph node metastasis (red arrow), contrarily, FETNIM uptake in primary tumor similar to that of background (blue arrow). (B) Mid-FETNIM PET/CT: persistent FETNIM uptake in the lymph node metastasis (red arrow), remain undetectable in primary tumor (blue arrow).

Figure 3

The receiver operator characteristic curves of SUVmax for predicting survival.

Figure 4

Changes of fluoroerythronitroimidazole uptake before and mid-treatment on primary lesions (A) and lymph nodes (B).

Figure 5

Survival identified by SUVmax. (A) Pre-SUVmax for local control. (B) Pre-SUVmax for overall survival (OS). (C) Mid-SUVmax for distant metastatic-free survival. (D) Mid-SUVmax for OS.