Target Definition by C11-Methionine-PET for the Radiotherapy of Brain Metastases

doi:10.1016/j.ijrobp.2008.08.056

International Journal of Radiation OncologyBiologyPhysics

Volume 74, Issue 3, 1 July 2009, Pages 714-722

https://doi.org/10.1016/j.ijrobp.2008.08.056 Get rights and content

Purpose

To evaluate the ability of 11C-methionine positron emission tomography (MET-PET) to delineate target volumes for brain metastases and to investigate to what extent tumor growth is presented by magnetic resonance imaging (MRI) and MET-PET.

Materials and Methods

Three observers undertook target definition in 19 patients with 95 brain metastases by MRI and MET-PET images. MRI gross target volume (GTV) (GTV-MRI) was defined as the contrast-enhanced area on gadolinium-enhanced T1-weighted MRI. MET-PET GTV (GTV-PET) was defined as the area of an accumulation of MET-PET apparently higher than that of normal tissue on MET-PET images. The size of occupation ratio was determined using the following equation: SOR (%) of MET are within × mm margin outside GTV-MRI = the volume of the GTV-PET within × mm outside the GTV-MRI/the volume of the GTV-PET.

Results

For GTV-MRI volumes of ≤0.5 mL, the sensitivity of tumor detection by MET-PET was 43%. For GTV-MRI volume of >0.5 mL, GTV-PET volumes were larger than GTV-MRI volumes and a significant correlation was found between these variables by linear regression. For all tumor sizes and tumor characteristics, a 2-mm margin outside the GTV-MRI significantly improved the coverage of the GTV-PET.

Conclusions

Although there were some limitations in our study associated with spatial resolution, blurring effect, and image registrations with PET images, MET-PET was supposed to have a potential as a promising tool for the precise delineation of target volumes in radiotherapy planning for brain metastases.

Introduction

Brain metastasis is the most common neurologic complication of cancer and occurs in 30% of cancer patients (1). Stereotactic radiotherapy (SRT), radiosurgery (SRS), and intensity-modulated radiotherapy of brain metastases involve the administration of high doses of radiation to a limited target volume to eradicate tumor cells and preserve surrounding normal tissue. For this therapy to succeed, the first premise is that tumor extensions must be correctly defined. The accurate definition of gross target volume (GTV) is crucial, but there is no consensus about the definition or necessity of a GTV of brain metastases. Many centers define GTV as the contrast-enhancing tumor only 2, 3, and some add a margin of 1–2 mm based on the belief that this caters for the possibility of tumor cells beyond a contrast-enhancing lesion 4, 5, 6. Recently Brigitta et al.(7) reported that infiltrative growth has an impact on defining the clinical target volume for SRS of brain metastases, and concluded that a margin of ∼1 mm should be added to the visible lesion.

Noninvasive imaging techniques are a central component of treatment planning in radiation oncology, and the information gained from different imaging modalities is usually complementary in nature. In this regard, combining morphologic (computed tomography [CT], magnetic resonance imaging [MRI]), and functional data (positron emission tomography [PET]) enormously improve the possibilities of interpreting three-dimensional brain data for treatment planning in radiotherapy. PET has been used now for 2 decades to assess cerebral metabolism in patients with gliomas 8, 9. However, 18F-fluoro-deoxy-2-glucose is compromised for brain tumors because most metastases occur at the gray-white junction, and it is often impossible to separate a small hypermetabolic focus of a metastatic tumor with little surrounding edema from normal cortical glucose utilization. 11C-methionine PET (MET-PET) (10) plays an important role in improving diagnostic procedures. Later studies have suggested that MET-PET indeed improves accuracy vs. 18F-fluoro-deoxy-2-glucose-PET for the differential diagnosis of recurrent brain tumors (11). Furthermore, it has been suggested that MET-PET may outline more precisely the true extent of viable tumor tissue than MRI, whereas MRI has the capability to better delineate the total extent of associated pathologic changes, such as edema, in the adjacent brain (12). However, no published study has quantified tumor extension from brain metastasis by MET-PET and MRI and compared these two imaging modalities. We undertook the present study to quantify the merits of MET-PET vs. MRI for the delineation of brain metastasis extensions and to demonstrate its implications for treatment planning. We compared the MRI and MET-PET for radiotherapy treatment planning for brain metastases and investigated and quantified extent of brain metastasis growth and compared the merits of MRI and MET-PET in this context.

Section snippets

Patients

During the 12-month period between January 2006 and December 2006, 19 newly diagnosed consecutive brain metastasis patients (Table 1) underwent SRS or SRT treatment planning at our department. CT, gadolinium-enhanced T1-weighted MRI, and MET-PET were separately performed within 1 week in the 19 patients (14 men and 5 women; age range, 54–82 years; mean, 68 years) with a total of 95 brain metastases (40 lung, 32 breast, 10 bladder, 7 renal, and 6 colorectal carcinomas) (Table 2) for SRS or SRT

Results

Patient characteristics are given in Table 1. The largest diagnostic groups were lung cancer (non–small-cell lung cancer [NSCLC]). 42% of metastases (n = 40) were from NSCLC, and 34% (n = 32) were from breast cancer (breast ca). Metastases from other different pathologies were grouped together as “Other” for statistical evaluation (Table 2).

Sensitivities of tumor detection by MET-PET are shown in Table 3. When the GTV-MRI volumes were ≤0.5 mL, the sensitivity of tumor detection by MET-PET was

Discussion

The results of this study demonstrate that MET-PET has a substantial impact on the visualization of tumor extensions from brain metastases. The integration of MET-PET into radiooncologic treatment planning provides encouraging results, because MET-PET is highly sensitive in the context of brain tumor tissue. In the present study, the biologic target volume using MET-PET helped to describe tumor morphology (GTV) with greater accuracy than that achievable using traditional radiologic modalities

Conclusion

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Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 1
2019, Critical Reviews in Oncology/Hematology
Citation Excerpt :
Matsuo et al. evaluated the differences, in terms of the extent of tumor growth, between 11C-MET-PET and MRI demonstrated that in the setting of GTV-MRI, GTV-PET volumes were 0.5 mL larger than MRI volumes. Interestingly, for all tumor sizes and characteristics, a 2-mm margin outside the GTV-MRI significantly improved the coverage of the GTV-PET (Matsuo et al., 2009). Re-irradiation is an important issue in modern brain RT for primary and secondary cancer.
Functional and molecular imaging, including positron emission tomography with computed tomography imaging (PET/CT) is increasing for radiotherapy (RT) definition of the target volume. This expert review summarizes existing data of functional imaging modalities and RT management, in terms of target volume delineation, for the following anatomical districts: brain (for primary and secondary tumors), head/neck and lung.
A collection of available published data was made, by PubMed a search. Only original articles were carefully and critically revised.
For primary and secondary brain tumors, amino acid PET radiotracers could be useful to identify microscopic residual areas and to differ between recurrence and treatment-related alterations in case of re-irradiation. As for head and neck neoplasms may benefit from precise PET/CT-based target delineation, due to the major capability to identify high-risk RT areas. In primary and secondary lung cancer, PET/CT could be useful both to delimit a tumor and collapsed lungs and as a predictive parameter of treatment response.
Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Nevertheless, several uncertainties remain on the standard method to properly assess the target volume definition including PET information for primary and secondary brain tumors.
Positron Emission Tomography
2016, Handbook of Clinical Neurology
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The authors concluded that tumor volumes defined by MRI and MET PET differ substantially, suggesting that MET PET may significantly improve the definition of target volumes in patients with brain metastases. Using MET PET/CT imaging, the biologic characterization of tissue can be combined with an accurate presentation of the anatomy (Matsuo et al., 2009). Additionally, the use of MET and CHO in PET imaging of brain metastases has been correlated to histopathology findings from stereotactic biopsy.
Positron emission tomography (PET) is a minimally invasive imaging procedure with a wide range of clinical and research applications. PET allows for the three-dimensional mapping of administered positron-emitting radiopharmaceuticals such as ¹⁸F-fluorodeoxyglucose (for imaging glucose metabolism). PET enables the study of biologic function in both health and disease, in contrast to magnetic resonance imaging (MRI) and computed tomography (CT), that are more suited to study a body's morphologic changes, although functional MRI can also be used to study certain brain functions by measuring blood flow changes during task performance. This chapter first provides an overview of the basic physics principles and instrumentation behind PET methodology, with an introduction to the merits of merging functional PET imaging with anatomic CT or MRI imaging. We then focus on clinical neurologic disorders, and reference research on relevant PET radiopharmaceuticals when applicable. We then provide an overview of PET scan interpretation and findings in several specific neurologic disorders such as dementias, epilepsy, movement disorders, infection, cerebrovascular disorders, and brain tumors.
PET/MRI and PET/CT in lung lesions and thoracic malignancies
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Preliminary data from Huellner et al30 recommend the use of respiratory-gated periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) sequences in whole-body PET/MRI with better results than that with whole-body PET/CT for staging and restaging of patients with cancer. A diagnostic gap of 18F-FDG-PET/CT examinations are brain metastases, as the physiologically high background in the brain leads to a detection rate of FDG-PET of only 24% for brain metastases as compared with 88% in MRI.44,45 Therefore, an additional MRI of the brain is mandatory for therapeutic planning in patients with metastasized lung cancer46 (Fig. 10).
More than one decade ago, introduction of integrated PET/CT scanners changed oncologic imaging and oncologic patient management profoundly. With these systems, the metabolic information acquired by PET can be anatomically localized even to small structures such as small primary tumors, lymph nodes, and soft tissue masses owing to the high-resolution multidetector CT scanners. This has made PET/CT a most reliable method for tumor detection, characterization, staging, and response monitoring. The importance of an integrated functional and morphologic approach to better understand the biology of oncologic disease and to improve therapy planning is underlined by the increasing number of PET/CT systems worldwide, leading to an increasing number of scientific publications in the field. The paradigmatic indication of integrated PET/CT is staging of patients with lung cancer, as PET/CT allows for precise pretherapeutic staging and also posttreatment restaging according to the TNM criteria. The growing numbers of targeted therapy strategies in the fields of surgery, chemotherapy, and radiation therapy, which are adapted to dedicated tumor stages, require the exact classifications of each patient’s tumor stage. In this context, whole-body examinations using integrated ¹⁸F-FDG-PET/CT have been shown to reduce the side effects of futile invasive procedures and reduce additional costly staging procedures. In this review article, the diagnostic and therapeutic effects of PET/CT examinations are highlighted and compared with some competitive techniques such as scintigraphy, MRI, and, where possible, integrated PET/MRI.
Clinical value of [<sup>11</sup>C]methionine PET for stereotactic radiation therapy with intensity modulated radiation therapy to metastatic brain tumors
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Along the same line, the relationship between pathology and metabolism found in stereotactic biopsy and the increased knowledge about MET-PET in brain tumor strengthen the valuable link between MET uptake and histology. Matsuo et al (13) demonstrated that there was severe discrepancy between PET- and MRI-defined target volumes in their report of metastatic brain tumors, and those findings suggested that MET-PET might significantly improve the definition of target volumes in patients with brain metastases (13). Based on those recent PET studies, MET-PET images were imported in the planning software for the SRT-IMRT dosimetry as the supplemental information in this preliminary study, and the final target volume was defined and drawn on the stereotactic MR image, taking into account the respective contributions of MET-PET and MRI (Fig. 1).
This study investigated the clinical impact of ¹¹C-labeled methionine-positron emission tomography (MET-PET) for stereotactic radiation therapy with intensity modulated radiation therapy (SRT-IMRT) in metastatic brain tumors.
Forty-two metastatic brain tumors were examined. All tumors were treated with SRT-IMRT using a helical tomotherapy system. Gross tumor volume (GTV) was defined and drawn on the stereotactic magnetic resonance (MR) image, taking into account the respective contributions of MR imaging and MET-PET. Planning target volume (PTV) encompassed the GTV-PET plus a 2-mm margin. SRT-IMRT was performed, keeping the dose for PTV at 25-35 Gy in 5 fractions. The ratio of the mean value of MET uptake to the contralateral normal brain (L/N ratio) was plotted for the PTV prior to SRT-IMRT, at 3 months following SRT-IMRT, and at 6 months following SRT-IMRT. Tumor characteristic changes of MET uptake before and after SRT-IMRT were evaluated quantitatively, comparing them with MRI examination.
Mean ± SD L/N ratios were 1.95 ± 0.83, 1.18 ± 0.21, and 1.12 ± 0.25 in the pre-SRT-IMRT group, in the 3 months post-SRT-IMRT group, and in the 6 months post-SRT-IMRT group, respectively. Differences in the mean L/N ratio between the pre-SRT-IMRT group and the 3-month post-SRT-IMRT group and between the pre-SRT-IMRT group and the 6 month post-SRT-IMRT group were statistically significant, irrespective of MRI examination.
We showed examples of metastatic lesions demonstrating significant decreases in MET uptake following SRT-IMRT. MET-PET seems to have a potential role in providing additional information, although MRI remains the gold standard for diagnosis and follow-up after SRT-IMRT. The present study is a preliminary approach, but to more clearly define the impact of PET-based radiosurgical assessment, further experimental and clinical analyses are required.
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Not all CNS tumor types may require imaging with CMET for more accurate tumor volume definition. In patients with brain metastases undergoing planning for stereotactic radiosurgery, the differences between volumes defined by contrast enhancement on MR imaging and CMET-PET could be accounted for by a simple 2-mm expansion on the MR imaging–defined volume that would cover more than 95% of a CMET-defined tumor volume.49 The ability to image cellular proliferation in vivo has the potential to be a valuable tool in the study, diagnosis, and treatment of tumors of the CNS.
Image fusion in nuclear medicine: From concepts to clinical application
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: Parts of this article were presented at 49th Annual Meeting of American Society for Therapeutic Radiation Oncology (ASTRO), October 28–November 1, 2007, Los Angeles, CA.

: Conflicts of interest: none

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Clinical InvestigationTarget Definition by C11-Methionine-PET for the Radiotherapy of Brain Metastases

Purpose

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Conclusion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Nucl Instrum Meth Phys Res A

Int J Radiat Oncol Biol Phys

Management of brain metastasis

Rev Neurol

Stereotactic radiosurgery for the treatment of brain metastases

Cancer

Long-term follow-up for brain metastases treated by percutaneous single high-dose radiation

Cancer

Traitement premier des metastases cerebrales par irradiation en condition stereotaxique. [First treatment for brain metastases by stereotactic radiosurgery]

Bull Cancer

Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastasis

J Clin Oncol

A pathology-based substrate for target definition in radiosurgery of brain metastases

Int J Radiat Oncol Biol Phys

Glucose utilization of cerebral gliomas measured by [18F]fluorodeoxyglucose and positron emission tomography

Neurology

Clinical Investigation
Target Definition by C11-Methionine-PET for the Radiotherapy of Brain Metastases