International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationTarget Definition by C11-Methionine-PET for the Radiotherapy of 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
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 RT planning for brain metastases.
References (27)
- et al.
A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis
Int J Radiat Oncol Biol Phys
(1994) - et al.
A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis
Int J Radiat Oncol Biol Phys
(1994) - et al.
Radiosurgery for brain metastasis (Impact of CTV on local control)
Radiother Oncol
(2003) - et al.
l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: Impact on results of carbon ion radiotherapy
Int J Radiat Oncol Biol Phys
(2008) - et al.
Under-sampling in PET scanners as a source of blurring
Nucl Instrum Meth Phys Res A
(2005) - et al.
Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: First clinical experience
Int J Radiat Oncol Biol Phys
(2003) Management of brain metastasis
Rev Neurol
(1992)- et al.
Stereotactic radiosurgery for the treatment of brain metastases
Cancer
(1997) - et al.
Long-term follow-up for brain metastases treated by percutaneous single high-dose radiation
Cancer
(1993) - et al.
Traitement premier des metastases cerebrales par irradiation en condition stereotaxique. [First treatment for brain metastases by stereotactic radiosurgery]
Bull Cancer
(1999)
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
Cited by (30)
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/HematologyCitation 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.
Positron Emission Tomography
2016, Handbook of Clinical NeurologyCitation Excerpt :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.
PET/MRI and PET/CT in lung lesions and thoracic malignancies
2015, Seminars in Nuclear MedicineCitation Excerpt :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).
Clinical value of [<sup>11</sup>C]methionine PET for stereotactic radiation therapy with intensity modulated radiation therapy to metastatic brain tumors
2012, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :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).
Principles and application of PET in brain tumors
2011, PET ClinicsCitation Excerpt :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
2010, Medecine Nucleaire
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