Clinical investigation
Brain
Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET

Accepted for oral presentation at the 2005 American Society for Therapeutic Radiology and Oncology (ASTRO) 47th Annual Meeting, Denver, Colorado, October 16–20, 2005.
https://doi.org/10.1016/j.ijrobp.2005.12.006Get rights and content

Purpose: To evaluate the influence of 68-Ga-labeled DOTA (0)-D-Phe (1)-Tyr (3)-Octreotide positron emission tomography ([68Ga]-DOTATOC-PET) for target definition for fractionated stereotactic radiotherapy (FSRT) as a complementary modality to computed tomography (CT) and magnetic resonance imaging (MRI). Because meningiomas show a high expression of somatostatin receptor subtype 2, somatostatin analogs such as DOTATOC offer the possibility of receptor-targeted imaging.

Patients and Methods: Twenty-six patients received stereotactic CT, MRI, and [68Ga]-DOTATOC-PET as part of their treatment planning. Histology was: World Health Organization (WHO) Grade 1 61.5%, WHO Grade 2 7.7%, WHO Grade 3 3.9%, and undetermined 26.9%. Six patients received radiotherapy as primary treatment, 2 after subtotal resection; 17 patients were treated for recurrent disease. Dynamic PET scans were acquired before radiotherapy over 60 min after intravenous injection of 156 ± 29 MBq [68Ga]-DOTATOC. These PET images were imported in the planning software for FSRT. Planning target volume (PTV)-I outlined on CT and contrast-enhanced MRI was compared with PTV-II outlined on PET. PTV-III was defined with CT, MRI, and PET and was actually used for radiotherapy treatment.

Results: PTV-III was smaller than PTV-I in 9 patients, the same size in 7 patients, and larger in 10 patients. Median PTV-I was 49.6 cc, median PTV-III was 57.2 cc. In all patients [68Ga]-DOTATOC-PET delivered additional information concerning tumor extension. PTV-III was significantly modified based on DOTATOC-PET data in 19 patients. In 1 patient no tumor was exactly identified on CT/MRI but was visible on PET.

Conclusion: These data demonstrate that [68Ga]-DOTATOC-PET improves target definition for FSRT in patients with intracranial meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI resulted in significant alterations in target definition in 73%.

Introduction

Meningiomas are the most common nonglial primary brain tumors, accounting for approximately 14–20% of all brain tumors in adults (1, 2). More than 90% of intracranial meningiomas are histopathologically benign and typically slow-growing. Surgical resection is the preferred treatment, whenever total removal can be accomplished with acceptable morbidity rates, with long-term control rates of 33% to 60% (3, 4, 5). Postoperative radiation therapy improves long-term local control and prevents tumor regrowth, especially after incomplete removal in several cases (6, 7, 8, 9, 10). For target volume definition in radiation therapy, morphologic imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI) are usually used. However, these imaging methods have their limitations for target delineation in infiltrative lesions and postoperative conditions. As reported in the literature, meningiomas show expression of a variety of receptors such as progesterone, androgen, platelet-derived growth factor, epidermal growth factor, prolactine, dopamine as well as somatostatin-receptors (11, 12). Meningiomas show high expression of the somatostatin-receptor subtype 2 (SSTR2). A somatostatin analog DOTA (0)-D-Phe (1)-Tyr (3)-Octreotide (DOTATOC) has been developed based on modifications of octreotide, which is commercially available for somatostatin receptor scintigraphy (13). DOTATOC that is labeled with the positron-emitting generator radionuclide 68Ga (t½ = 68 min) can be used for the visualization of these tumors for stereotactic treatment planning. [68Ga]-DOTATOC is of special value for scintigraphic evaluation of patients with SSTR-positive lesions for its increased spatial resolution and the ability to quantify biodistribution. In contrast to 18F-fluorodeoxy-glucose (FDG), [68Ga]-DOTATOC shows very high meningioma to background ratios (14).

These findings justify the investigation of the feasibility of positron emission tomography (PET) as an additional method for target volume definition and to integrate DOTATOC-PET images for stereotactic radiation therapy to improve targeting. [68Ga]-DOTATOC-PET is of special value for scintigraphic evaluation of patients with SSTR-positive lesions showing an increased spatial resolution and the ability to quantify biodistribution. In contrast to, e.g., 18F-FDG, [68Ga]-DOTATOC showed very high meningioma to background ratio. Furthermore, [68Ga]-DOTATOC has been shown to provide additional information regarding the extension of meningiomas located at the skull base next to osseous structures (14).

The aim of the present study was to evaluate the influence of [68Ga]-DOTATOC-PET for target volume definition in patients with intracranial meningiomas as a complementary imaging modality to CT and MRI.

Section snippets

Patients and methods

Twenty-six patients with intracranial meningiomas received stereotactic CT, MRI, and additional [68Ga]-DOTATOC-PET as part of their image acquisition for fractionated stereotactic radiotherapy (FSRT) treatment planning. Median age at treatment was 49.4 years (range, 21.4–73.9 years). The male/female ratio was 4:22, the median Karnofsky performance score was 90%. Tumor distribution was: World Health Organization (WHO) Grade 1 in 61.5%, WHO Grade 2 in 7.7%, WHO Grade 3 in 3.9%. In 7 of 26

Target volume definition by correlation of CT and MRI

The PTV-I included the macroscopic tumor visible on CT and T1-weighted MRI contrast-enhanced scans with a safety margin of 1–2 mm to the normal brain tissue, 3 mm to adjacent osseous structures, and 5 mm along the dura. Median PTV-I was 49.6 cc (range, 2.2–240 cc). In 1 patient with an optic nerve sheath meningioma no tumor could be exactly defined, neither on CT nor on MRI. In another patient with prior total resection of the meningioma according to the surgical report, no differentiation

Discussion

This is the first report of the use of DOTATOC-PET to provide valuable information in addition to CT and MRI for target volume definition of FSRT in patients with intracranial meningioma. We have proved in 26 consecutive patients that an additional DOTATOC-PET scan significantly positively influences target volume coverage and allows sparing of adjacent normal tissue.

Several studies exist for target volume definition of radiotherapy in patients with non–small-cell lung cancer, colorectal

Conclusion

Radiation targeting with fused [68Ga]-DOTATOC-PET, CT, and MRI resulted in significant alterations in target volume definition in 19 of 26 patients (73%). These data demonstrate that [68Ga]-DOTATOC-PET improves target volume definition for FSRT in patients with intracranial meningiomas. It could be easily integrated in the radiotherapy planning process. A differentiation between tumor and pituitary gland in lesions next to the cavernous sinus is not possible. Long-term follow-up is necessary to

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    This study was supported in part by Deutsche Forschungsgemeinschaft (grants HA2901/3-1 and 3-2).

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