Clinical study
Differentiation of tumor recurrence from radiation necrosis in high-grade gliomas using 201Tl-SPECT

https://doi.org/10.1016/j.jocn.2007.12.008Get rights and content

Abstract

MRI is routinely performed to detect recurrence in patients with primary brain tumors, but it may not differentiate recurrent tumor from radiation-induced necrosis reliably. Thallium-201 single-photon emission computed tomography (201Tl-SPECT) might be useful in distinguishing between these two clinical entities. In a retrospective study 201Tl-SPECT studies with corresponding MRI studies in 19 patients with clinical or radiological suspicion of high-grade tumor recurrence were reviewed. The diagnostic accuracies of both modalities were based on the subsequent histology or clinical course where biopsy was not performed. Post-scan histology was available in nine patients (43%) who underwent re-resection. The SPECT result determined management in six patients (29%). Post-SPECT survival was significantly better in patients with negative 201Tl-SPECT studies compared to patients with positive studies (median survival 15 + vs. 6 months) (p = 0.04, log-rank test). The sensitivity and specificity of 201Tl-SPECT in diagnosing tumor recurrence were 83% and 100%, respectively. 201Tl-SPECT can accurately differentiate tumor recurrence from radiation necrosis in patients with high-grade gliomas and abnormal MRI findings post irradiation. This is reflected in a significantly longer post-scan survival time in patients with a negative 201Tl-SPECT result.

Introduction

Management of high-grade gliomas remains one of the greatest challenges in oncology, requiring a multidisciplinary approach, which consists of cytoreductive surgery, radiation therapy and chemotherapy. Nonetheless, these tumors recur almost invariably, with a median survival of 14.6 months in patients with glioblastoma multiforme treated with concurrent radiotherapy and temozolomide followed by 6 months of adjuvant temozolomide.1

Serial MRI is routinely performed in these patients after primary treatment to detect tumor recurrence. However, conventional contrast-enhanced CT scans or MRI cannot reliably distinguish radiation necrosis from recurrent tumor. Both entities can cause extensive edema and blood–brain barrier disruption that result in mass effect and abnormal contrast enhancement.[2], [3] Radiation-induced necrosis often occurs within 2 years after radiation therapy, the same time frame during which tumor recurrence is most frequent.4

Differentiation between tumor progression and radiation necrosis carries obvious prognostic and therapeutic implications. To overcome this problem, several functional and physiological imaging techniques, such as MR spectroscopy (MRS), perfusion-weighted MRI, positron emission tomography (PET), and thallium-201 single-photon emission computed tomography (201Tl-SPECT) have been examined for clinical use.[5], [6], [7], [8], [9], [10], [11], [12] Radiothallium (201Tl) is a monovalent cationic radioisotope with biological properties similar to potassium.13 Experimental evidence suggests that the ionic movement of thallium and potassium are related to active transport through an adenosine triphosphate (ATP) cell membrane pump, and that 201Tl uptake is related to cell growth rates.14 Previous studies showed substantial 201Tl uptake in brain tumors with little uptake in normal brain.[15], [16] In the mid-1980s, noting the disparity between clinical status and CT scan results in patients with gliomas, Kaplan et al. found 201Tl to be superior to CT scans, gallium-67 citrate and technetium-99m gluceptate in identifying viable tumors.11 Subsequently, other studies suggest that 201Tl-SPECT may be a useful method to differentiate between tumor recurrence and radiation necrosis.[12], [17], [18], [19], [20]

We use 201Tl-SPECT in our centre to clarify equivocal MRI findings in patients with post-irradiated brain tumors. Although previous studies have examined the accuracy of 201Tl-SPECT in differentiating radiation necrosis from recurrent tumor, its impact on clinical decision making has not been explored. The aim of this study was to establish the value of 201Tl-SPECT in differentiating radiation necrosis from recurrent tumor, and its influence on therapeutic decision making in a cohort of patients with post-irradiated high-grade gliomas and abnormal MRI findings.

Section snippets

Patients

We identified 19 consecutive patients with primary brain tumors who underwent 201Tl-SPECT at the Royal Melbourne Hospital between March 2004 and May 2007. Two patients had two 201Tl-SPECTs during this time. Therefore, a total of 21 SPECT scans from 19 patients were included in this retrospective analysis. MRIs were performed as routine follow-up evaluation of treated brain tumors, or when there was clinical suspicion of disease recurrence. In all patients, 201Tl-SPECT was prompted either by an

Demographics

Patient characteristics and treatment history of the 19 patients in this study are shown in Table 1. Median age for all patients was 51 (range, 25–78 years), with three patients above 70 years. All patients had histologically confirmed high-grade gliomas. Seven patients had glioblastoma multiforme, seven had anaplastic astrocytoma, and five had anaplastic oligoastrocytoma. Most patients (89%) had undergone either a complete or partial resection of their gliomas, while the remaining two patients

Discussion

Ionizing radiation applied to the central nervous system can result in a localized area of necrosis in the brain. The most common MRI characteristics of radiation necrosis consist of an enhancing mass with a central area of necrosis, which mimics tumor recurrence. The incidence of pure radiation necrosis was 14% in a series of 148 patients with treated malignant gliomas, with another 11% of patients with a mixture of predominantly radiation necrosis intermingled with limited residual and/or

Acknowledgement

The result of this study was presented at the Glioma 2007 Meeting, Sydney, Australia.

References (38)

  • F. Benard et al.

    Imaging gliomas with positron emission tomography and single-photon emission computed tomography

    Sem Nuc Med

    (2003)
  • T.Z. Wong et al.

    Positron emission tomography imaging of brain tumors

    Neuroimaging Clin N Am

    (2002)
  • Z. Keidar et al.

    SPECT/CT in tumour imaging: technical aspects and clinical applications

    Semin Nucl Med

    (2003)
  • R. Stupp et al.

    Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma

    N Engl J Med

    (2005)
  • S. Cha

    Perfusion imaging of brain tumors

    Top Magn Reson Imaging.

    (2004)
  • P.A. Hein et al.

    Diffusion-weighted imaging in the follow-up of treated high-grade gliomas: tumor recurrence versus radiation injury

    AJNR

    (2004)
  • P.E. Valk et al.

    Radiation injury of the brain

    AJR

    (1991)
  • J.P. Rock et al.

    Associations among magnetic resonance spectroscopy, apparent diffusion coefficients, and image-guided histopathology with special attention to radiation necrosis

    Neurosurgery

    (2004)
  • H.P. Schlemmer et al.

    Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy

    Neuroradiology

    (2002)
  • M. Lemort et al.

    Progress in magnetic resonance imaging of brain tumors

    Curr Opin Oncol

    (2007)
  • S. Cha

    Update on brain tumor imaging: from anatomy to physiology

    AJNR Am J Neuroradiol

    (2006)
  • P.E. Ricci et al.

    Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography?

    AJNR Am J Neuroradiol

    (1998)
  • D.D. Langleben et al.

    PET in differentiation of recurrent brain tumor from radiation injury

    J Nucl Med.

    (2000)
  • W.D. Kaplan et al.

    Thallium-201 brain tumor imaging: A comparative study with pathologic correlation

    J Nucl Med

    (1987)
  • Y. Yamamoto et al.

    99mTc-MIBI and 201Tl SPET in the detection of recurrent brain tumours after radiation therapy

    Nucl Med Commun.

    (2002)
  • K.T. Kim et al.

    Thallium-201 SPECT Imaging of brain tumors: methods and results

    J Nucl Med

    (1990)
  • D. Ancri et al.

    Diagnosis of cerebral lesions by thallium-201

    Radiol

    (1978)
  • D. Sun et al.

    Clinical application of 201Tl SPECT imaging of brain tumors

    J Nucl Med

    (2000)
  • R.B. Schwartz et al.

    Radiation necrosis vs high-grade recurrent glioma: differentiation by using dual-isotope SPECT with 201Tl and 99mTc-HMPAO [abstract]

    AJNR Am J Neuroradiol

    (1991)
  • Cited by (41)

    • Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma

      2015, Clinical Radiology
      Citation Excerpt :

      SPECT is a 3D nuclear medicine technique. Thallium-201 (201Tl) has been shown to be useful in differentiating pseudoprogression from true progression with a sensitivity from 84% to 100% and a specificity from 50% to 100%.89–92 Yamamoto et al.92 found a potential for cut-offs to be applied.

    View all citing articles on Scopus
    View full text