ArticleThe value of positron emission tomography for monitoring response to radiotherapy in head and neck cancer
Introduction
Radiotherapy is one of the cornerstones in the treatment of head and neck cancer. The goal of radiotherapy is to obtain tumor eradication while sparing normal tissue as much as possible. The probability to cure a patient by radiotherapy is determined by characteristics of the tumor (e.g., site, size, grade of differentiation, stage of disease, tumor oxygenation, and intrinsic radiosensitivity) and patient (e.g., weight loss, performance status, and comorbidity), but also by treatment-related factors, such as radiation dose and fractionation.
It would be of great value if the ultimate response to radiotherapy could be predicted, ideally prior to or early during treatment, to allow treatment modifications. Measurement of response in head and neck cancer has traditionally been performed using clinical, histologic and/or radiologic evaluation. Changes in tumor size and appearance, measurable with physical examination or anatomical imaging techniques (e.g., computed tomography [CT] and magnetic resonance imaging [MRI]), occur late during the course of radiotherapy, usually not before completion. In anatomical imaging, all voxels (volume elements) with a particular value represent a structural property of the tissue (e.g., attenuation characteristics, proton density), while with functional imaging the values represent a biochemical property. In contrast to changes in morphology, functional changes are anticipated earlier during treatment. Positron emission tomography (PET) is a quantitative functional imaging modality that provides the possibility to measure a wide range of tissue-specific parameters such as metabolism, receptor density, cell proliferation, and uptake of therapeutic agents with high sensitivity. Owing to its limited anatomical depiction, PET cannot replace other diagnostic procedures, but it does contribute valuable complementary diagnostic information.1 The advantage of PET compared with conventional techniques is the potential for early response monitoring, during and in the first weeks after completion of radiotherapy. In addition, it might be used for the prediction of response before the start of treatment.
Section snippets
FDG-PET
Central to PET is the use of tracers, which are labeled with positron-emitting isotopes. The most commonly used tracer in oncology is 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analog of glucose, which is transported into the cell and subsequently phosphorylated to FDG-6-PO4.
Before treatment
High intensity of FDG is strongly correlated with the proportion of cells in the S + G2/M-phase of the cell cycle (S = synthesis, G = gap, M = mitosis/proliferation),19 but a correlation between pretreatment accumulation and response to radiotherapy is far from clear. Small but statistically significant differences in proliferative fraction did not produce detectable differences in deoxyglucose incorporation, although a significant correlation was found between the S-phase fraction and deoxyglucose
Monitoring response using other PET tracers
Inflammation, which may be present in large amounts in the irradiated area, can also result in increased FDG uptake, thereby complicating interpretation of tumor response. Therefore, FDG might not be the ideal tracer to monitor response to radiotherapy. Beyond FDG, other specific characteristics can be imaged using PET, for instance, hypoxia. Hypoxia may be a cure-limiting factor in radiotherapy in HNSCC,78 because cells under anaerobic conditions are less sensitive to radiation. In 2000,
Discussion
High FDG uptake is strongly correlated with the proportion of cells in the proliferative phase of the cell cycle,19 but a correlation between accumulation and response to radiotherapy is far from clear. The fact that higher FDG uptake is associated with greater cell viability14., 15. and a higher propensity for cells to divide17., 20. may explain the poorer survival of patients with tumors with high FDG uptake.27., 67., 68., 69., 70., 71. Prospective studies are needed in large groups of
References (100)
- et al.
Thoracic nodal staging with PET imaging with 18FDG in patients with bronchogenic carcinoma
Chest
(1995) - et al.
Deoxyglucose uptake by a head and neck squamous carcinoma: influence of changes in proliferative fraction
Int. J. Radiat. Oncol. Biol. Phys.
(2000) - et al.
Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer
Eur. J. Cancer
(2000) - et al.
Clinical utility of FDG-PET in detecting head and neck tumors. A comparison of diagnostic methods and modalities
Clin. Positron Imaging
(2000) - et al.
Reproducibility of common semi-quantitative parameters for evaluating lung cancer glucose metabolism with positron emission tomography using 2-deoxy-2-[18f]fluoro-D-glucose
Mol. Imaging Biol.
(2002) - et al.
Optimizing imaging time for improved performance in oncology PET studies
Mol. Imaging Biol.
(2002) - et al.
Quantitative assessment of tumor metabolism using FDG-PET imaging
Nucl. Med. Biol.
(2000) - et al.
Positron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy
Int. J. Radiat. Oncol. Biol. Phys.
(1993) - et al.
Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck
Radiother. Oncol.
(1996) - et al.
A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy
Radiother. Oncol.
(2000)