Role of 11-C-methionine positron emission tomography for the delineation of the tumor volume in pharyngo-laryngeal squamous cell carcinoma: comparison with FDG-PET and CT

doi:10.1016/j.radonc.2004.02.013

Radiotherapy and Oncology

Volume 71, Issue 3, June 2004, Pages 267-273

https://doi.org/10.1016/j.radonc.2004.02.013 Get rights and content

Abstract

Background and purpose

Although computed tomography (CT) remains the imaging modality of reference in head and neck squamous cell carcinoma (HNSCC) for the three-dimensional (3D) conformal radiotherapy, its poor soft tissue contrast can hamper precisely delineate the tumor volume. Besides anatomical imaging, 2-[18F] fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) has been shown to enhance the accuracy of the tumor delineation but l-methyl [11C]-methionine-positron emission tomography (MET-PET) has never been tested for this purpose. This study was undertaken to determine the potential added value of MET-PET for the delineation of gross target volume (GTV) in HNSCC, as compared to CT and FDG-PET.

Patients and methods

Twenty-three patients (10 oropharynx, 8 larynx and 5 hypopharynx) presenting with stage II–IV HNSCC were prospectively enrolled. They were treated by primary radiotherapy or by total laryngectomy. Images (CT, FDG-PET and MET-PET) were acquired with a thermoplastic mask and after coregistration, tumor volumes were delineated on CT and using an adaptative threshold-based automatic method on FDG- and MET-PET. Absolute volumes as well as the mismatch between modalities were compared.

Results

For oropharyngeal lesions, FDG volumes were significantly smaller (19.43 ml±21.36) than CT (29.04 ml±30.97) (P=0.013). On the other hand, MET volumes (24.36 ml±20.59) were not different from CT volumes. Similar results were found for laryngeal and hypopharyngeal tumors, with volume of 24.93 ml±19.02 for CT, 21.84 ml±15.32 for MET-PET and 14.49 ml±11.3 for FDG-PET (P=0.003). Large mismatches were observed between modalities, in particular between CT and PET.

Conclusions

Our study confirms that the use of FDG-PET may result in a significant reduction of GTV's as compared to CT. On the contrary, MET-PET does not have any additional value since MET volumes are not different from CT volumes, probably because of the high uptake of MET by the normal mucosa and salivary glands surrounding the tumor.

Introduction

An accurate three-dimensional (3D) delineation of target volumes in radiotherapy appears to be more and more important since the introduction of 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) in clinical routine. Indeed, these techniques allow for precisely sculpting the radiation dose to target volumes. The intrinsic characteristics of computed tomography scanner (CT), i.e. the information on the electronic density mapping used for dose calculation and its accurate anatomical definition without geometric distortion, make this imaging modality the reference in treatment planning. Nevertheless, large variations in tumor volume delineation have been shown in lung cancers [3] and in laryngeal tumors [8] because of the lack of soft tissues contrast of CT. Moreover, for oral cavity and oropharyngeal tumors, the presence of teeth filling may complicate the image interpretation.

In complement to the anatomic imaging procedures, functional imaging techniques, particularly 2-[18F] fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET), are being evaluated as a tool for radiotherapy treatment planning. The underlying assumption for the use of FDG for tumor imaging is the increased glucose metabolism of cancer compared to normal tissue [15]. The potential role of FDG-PET in radiation treatment planning for head and neck cancers has only been evaluated in a recent study led by Daisne et al. [5]. This study showed that gross target volumes (GTV's) were smaller when volumes were drawn on FDG-PET, compared to CT and MRI in head and neck squamous cell carcinoma (HNSCC) [5].

Besides FDG, l-methyl [11C]-methionine (MET) PET has also been used for characterization of HNSCC. The uptake of MET has been shown to reflect amino acid increased transport, transmethylation rate and protein synthesis within malignant tissues [15]. Sensitivity and specificity of MET-PET for HNSCC staging are similar to FDG [10]. A relationship between MET uptake and cell proliferation of HNSCC has been shown in vitro and in vivo [12], [13], [14], suggesting that MET could be more specific than FDG for measuring tumor aggressiveness. In addition, the early response to chemotherapy could be successfully assessed by MET in hypopharyngeal tumors, allowing for adapting the treatment scheme [4].

It progressively appears that metabolic imaging could interestingly complement CT and MRI to enhance the accuracy of tumor volume delineation in the context of conformal radiation therapy. PET-MET and FDG imaging could allow for targeting the tumor tissue with the highest metabolic activity, i.e. the viable part of the tumor deserving maximal treatment. The use of functional imaging could reduce both the risk of geographical misses as well as the dose delivered to the normal surrounding tissue. As a consequence, higher doses could be delivered to the tumor itself, aiming at increasing the probability of tumor local control. However, the head and neck region is a complex region and PET imaging suffers from the lack of anatomical landmarks. Moreover, physiological FDG and MET uptake by the normal structures such as salivary glands, or by non-tumor tissues such as acute inflammation (especially during radiotherapy), can hamper the accuracy of tumor volume delineation. Therefore, metabolic imaging must be carefully assessed before it is routinely introduced as a new GTV determination tool. In this study, we evaluated MET-PET as an imaging method for GTV's delineation of head and neck squamous-cell carcinomas, and compared it to FDG-PET and CT.

Section snippets

Patient selection

Twenty-three patients with a primary stage II–IV HNSCC were prospectively enrolled between February 2000 and July 2002. Ten patients had an oropharyngeal tumor—with 1 patient having a double site, 8 had a laryngeal tumor and 5 had a hypopharyngeal tumor. Nineteen patients were treated in the framework of organ preservation protocols using either accelerated radiotherapy or concomitant chemo-radiation schedules. The 4 remaining patients who all presented an extensive T4 laryngeal tumor were

Oropharyngeal tumors (n=11) (Table 1)

The median CT volume was similar to the median MET volume, but both were larger than the median FDG volume. The difference between CT and FDG was statistically significant (P=0.013). Only one FDG tumor volume was found larger than the CT volume (patient no 6). Median MET volume was larger than median FDG volume, and this was statistically significant (P=0.003). For the patient no 6, the FDG and MET volumes were similar. Detailed data are shown in Table 1.

The volume mismatch of CT over MET and

Discussion

The results of our study show that MET and FDG are not equivalent in determining the tumor volumes of HNSCC. Although the use of FDG-PET can reduce the tumor volumes by 40% as compared to CT, MET-PET volumes are not statistically different from the CT volumes. Moreover, MET-PET volumes are significantly larger than FDG-PET volumes.

The S/B ratio methodology used for obtaining the PET volumes was previously validated by both an experimental sphere's model [7] and a clinical study [5]. In the

Acknowledgments

This publication was supported by Grant 7.4538.02 from the Fond National de Recherche Scientifique (FNRS).

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Role of 11-C-methionine positron emission tomography for the delineation of the tumor volume in pharyngo-laryngeal squamous cell carcinoma: comparison with FDG-PET and CT

Abstract

Background and purpose

Patients and methods

Results

Conclusions

Introduction

Section snippets

Patient selection

Oropharyngeal tumors (n=11) (Table 1)

Discussion

Acknowledgments

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Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

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Radiology

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Radiology

Observer variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion

Int J Radiat Oncol Biol Phys