Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study

Abstract

Purpose: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.

Methods and materials: (18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans.

Results: The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing.

Conclusion: It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

Conflict of interest statement

Conflict of interest: none.

Figures

Fig. 1

Example of multimodality image registration of (Top Left) computed tomography (CT), (Top Right) fluorodeoxyglucose (FDG), (Bottom Left) fluorine-18–labeled fluoromisonidazole (18F-FMISO), and (Bottom Right) fused FDG-18F-FMISO. Three enlarged images (indicated by arrows) of FDG, 18F-FMISO, and fused FDG-18F-FMISO also shown.

Fig. 2

Example of delineation of gross tumor volume (GTV) and corresponding hypoxic GTV (GTVh) by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and fluorine-18–labeled fluoromisonidazole (18F-FMISO) PET/CT image fusion. (a) CT axial slice, (b) FDG-PET axial scan, and (c)18F-FMISO PET axial slice.

Fig. 3

Example of fluorine-18–labeled fluoromisonidazole (18F-FMISO) positron emission tomography (PET)–guided intensity-modulated radiotherapy (IMRT) plan for locoregionally advanced supraglottic carcinoma. (a) Axial comparison of original clinical plan (a-1) and 18F-FMISO PET–guided IMRT plan (a-2). (b) Sagittal view of 18F-FMISO PET–guided IMRT plan. (c) Coronal view of 18F-FMISO PET–guided IMRT plan.

Fig. 4

Second example of fluorine-18–labeled fluoromisonidazole (18F-FMISO) positron emission tomography (PET)–guided intensity-modulated radiotherapy (IMRT) plan for locoregionally advanced oropharyngeal carcinoma. (a) Axial comparison of original clinical plan (a-1) and 18F-FMISO PET–guided IMRT plan (a-2). (b) Sagittal view of 18F-FMISO PET–guided IMRT plan. (c) Coronal view of 18F-FMISO PET–guided IMRT plan. (d) Dose–volume histogram of 18F-FMISO PET–guided IMRT plan.

Fig. 5

Example of case in which hypoxic gross tumor volume (GTVh) escalated to 105 Gy within 33 fractions. (a) Axial, (b) coronal, (c) sagittal views, and (d) dose–volume histogram.

Fig. 6

Example of case in which hypoxic gross tumor volume (GTVh) escalated to 100 Gy, while preserving normal tissue constraints. (a) Axial. (b) Coronal views.