Review
Performance of SPECT in the differential diagnosis of glioma recurrence from radiation necrosis

https://doi.org/10.1016/j.jocn.2014.06.102Get rights and content

Abstract

Radiation necrosis (RN) may be a confounder in the diagnosis of glioma recurrence. Several functional imaging techniques, including single photon emission computed tomography (SPECT) and positron emission tomography (PET), have been used to differentiate RN from glioma recurrence. However, to our knowledge the efficacy of SPECT has not been evaluated quantitatively. This meta-analysis evaluated the diagnostic ability of SPECT in differentiating glioma recurrence from RN. PubMed and EMBASE were systematically searched for studies published up to 1 March 2014 that evaluated SPECT in the differential diagnosis of glioma recurrence from RN. The data from eligible studies were evaluated by heterogeneity and threshold effect tests, and the sensitivity, specificity, and areas under the summary receiver-operating characteristic curve (SROC) were calculated. Twenty-eight studies in 24 articles, which included 893 patients (1163 scans) with suspected glioma recurrence after radiotherapy, met all inclusion and exclusion criteria, and were included in the meta-analysis. Their pooled sensitivity and specificity were 0.89 (95% confidence interval [CI]: 0.87, 0.91) and 0.88 (95% CI: 0.84, 0.91), respectively, and the area under the SROC was 0.9403. This meta-analysis showed that SPECT had good diagnostic performance for differentiating glioma recurrence from RN.

Introduction

Gliomas account for approximately 30% of primary brain tumors in the Chinese population [1] and approximately 32% in the USA [2]. Despite progress in surgery, radiotherapy, and chemotherapy, gliomas frequently recur and survival remains poor [3]. Radiation necrosis (RN), a chronic radiotherapy-related reaction with features including disruption of the blood–brain barrier, regional edema and mass effect [4] may confound the diagnosis of glioma recurrence.

RN may be asymptomatic or symptomatic, with increased intracranial pressure and/or focal neurological symptoms. The symptoms of glioma recurrence may be identical to those of RN, indicating that symptoms alone cannot be used for diagnosis. Moreover, RN occurs within 2 years after radiotherapy in most patients, the same time period in which malignant glioma recurrence most frequently occurs [4]. In addition, conventional morphologic imaging modalities, including CT scan and MRI, cannot reliably differentiate between RN and glioma recurrence [4], [5], [6]. This is because RN may occur at or near the original tumor site and the two types of lesions show similar enhancement by contrast agent, growth over time, surrounding edema, and exertion of mass effect [7]. It is clinically important, however, to differentiate between these two entities. Surgery and anti-cancer therapy are not indicated in patients with RN, and their prognosis may be excellent. In contrast, tumor recurrence requires aggressive management and is accompanied by poorer patient outcomes.

Several functional imaging techniques, including single photon emission computed tomography (SPECT), positron emission tomography (PET), and some advanced MRI techniques (diffusion-weighted imaging, perfusion MRI, and magnetic resonance spectroscopy) have been used to differentiate RN from glioma recurrence. These functional imaging methods can provide information about metabolism, regional blood flow, chemical composition, and absorption, with differences in these features used to differentiate between RN and recurrence. For nuclear medicine imaging, PET is increasingly utilized for the postoperative follow-up of patients with brain tumors. However, SPECT is also useful nowadays, due to its low cost, wide availability, and the easy interpretation of results [4]. SPECT has been reported to provide results equal [8], [9] or superior [10], [11] to PET. However, the efficacy of SPECT with various types of radiotracers to distinguish between RN and glioma recurrence has not been evaluated quantitatively to our knowledge. This meta-analysis therefore evaluated the diagnostic accuracy of SPECT using various tracers in patients with glioma who have undergone radiotherapy.

Section snippets

Search strategy

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria [12]. The PubMed and EMBASE databases were searched comprehensively to identify relevant articles published until 1 March 2014. The search algorithm was based on a combination of the terms as follows: (a) “Single photon emission computed tomography” or “single photon emission tomography” or “SPECT” or “SPET”; and (b) glioma or brain neoplasm; and (c) recurrence. Additionally,

Study selection and characteristics

The study selection process is shown in Figure 1. Of the 26 articles deemed eligible for inclusion [9], [10], [11], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], two pairs of articles (Schwartz et al. [21] and Carvalho et al. [22], and Barai et al. [31] and Barai et al. [33]) had overlapping data; thus, only the articles with the most data, that is, those of Carvalho et al. [22] and Barai et al. [33],

Discussion

This systematic review and meta-analysis suggests that SPECT has excellent overall accuracy for differentiating glioma recurrence from RN among patients suspected of recurrence following conventional morphologic imaging modalities such as CT scan and MRI. The AUC under the SROC for the overall analysis and for all subgroups were over 0.9, indicating that SPECT had high diagnostic accuracy, irrespective of glioma grade, reference standard, radiotracer, image analysis method, and study design.

The

Conclusion

This meta-analysis provides evidence that SPECT has good diagnostic performance in differentiating glioma recurrence from RN, independent of glioma grade, reference standard, radiotracer used, image analysis method, and study design. Despite the limitations described above, the wide availability, simple operation, ease of interpretation and relatively low cost of SPECT may make it feasible for reaching a diagnosis in patients with inconclusive results from conventional morphologic imaging. Our

Conflicts of Interest/Disclosures

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

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