Spyridon Tsiouris

Glioma recurrence versus radiation necrosis: accuracy of current imaging modalities

Treatment for brain gliomas is a combined approach of surgery, radiation therapy and chemotherapy. Nevertheless, high-grade gliomas usually recur despite treatment. Ionizing radiation therapy to the central nervous system may cause post-radiation damage. Differentiation between post-irradiation necrosis and recurrent glioma on the basis of clinical signs and symptomatology has not been possible. Computed tomography (CT) and magnetic resonance imaging (MRI) suffer from significant limitations when applied to differentiate recurrent brain tumor from radiation necrosis. We reviewed the contribution of recent MRI techniques, single-photon emission CT and positron emission tomography to discriminate necrosis for glioma recurrence. We concluded that despite the progress being made, further research is needed to establish reliable imaging modalities that distinguish between true tumour progression and treatment-related necrosis.

Evaluation of meningioma aggressiveness by 99mTc-Tetrofosmin SPECT

OBJECTIVES Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase -- as determined by DNA flow cytometry -- are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. PATIENTS AND METHODS Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by (99m)Tc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. RESULTS Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r=0.733, P=0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. CONCLUSION These results imply that (99m)Tc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity.

Evaluation of glioma proliferation by 99mTc-Tetrofosmin

The proliferation potential of gliomas is an indicator of their aggressiveness with significant implications in patient management and prognosis, but its assessment requires tissue sampling.1 We evaluated the relationship between glioma proliferation (as expressed by the Ki-67 index) and the uptake of the tumor-seeking radiotracer technetium-99m Tetrofosmin (99mTc-TF). Fourteen patients with a space-occupying lesion suspicious for glioma on structural brain imaging were prospectively enrolled. Scintitomographic (SPECT) imaging was performed and within a week the lesion was removed surgically; Ki-67 was assessed in the excised specimens by MIB-1 immunostaining. Three patients were excluded from the study because their lesions were proven metastatic. In the 11 patients eligible for analysis (7 males, 4 females; mean age 49.5 ± 7.5 years), the diagnosis was glioblastoma multiforme (6 cases), anaplastic astrocytoma (1), anaplastic oligodendroglioma (2), low-grade oligodendroglioma (1), and low-grade astrocytoma (1). We found a significant positive linear correlation between 99mTc-TF uptake and Ki-67 expression (r = 0.95, p = 0.001 [Spearman rank analysis]; Fig. 1 – 3). No significant correlation was observed between tracer uptake and tumor grade (r = 0.27, p = 0.420). The preliminary results of this pilot study, although deriving from a limited patient sample, propose that this tracer may hold a potential role as a noninvasive marker of glioma proliferative activity. Figure 1 T1-weighted, gadolinium-enchanced MRI (A) in a low-grade oligodendroglioma of the left frontal lobe. Faint 99mTc-Tetrofosmin uptake (B, arrow) correlated with Ki-67 approx. 2% (C; MIB-1 ×100). Figure 3 Correlation between 99mTc-Tetrofosmin uptake (expressed as lesion-to-normal [L/N] uptake ratio) and cellular proliferation rate (MIB-1) in the studied gliomas.

Correlation of glioma proliferation assessed by flow cytometry with 99mTc-Tetrofosmin SPECT uptake

OBJECTIVES Brain single-photon emission computed tomography (SPECT) has been proposed as a potentially useful modality for the metabolic assessment of various brain tumors. MATERIAL AND METHODS In a 10-patient prospective pilot study we evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with glioma proliferative activity assessed by flow cytometric analysis. (99m)Tc-TF brain SPECT was performed shortly before surgical tumor excision. RESULTS Eight patients were diagnosed with glioblastoma multiform and 2 with anaplastic astrocytoma. All tumors were aneuploid. We found a significant positive linear correlation between (99m)Tc-TF uptake and percentage of tumor cells on the S-phase of the cell cycle (r=0.92, P=0.001). CONCLUSION Initial evidence suggests that (99m)Tc-TF could provide a non-invasive indicator of glioma proliferative activity.

Percutaneous radiofrequency thermal ablation in the management of lung tumors: presentation of clinical experience on a series of 35 patients.

PURPOSE To present our results in a series of 35 patients with malignant pulmonary lesions, who underwent radiofrequency thermal ablation (RFA) during a period of 18 months. MATERIALS AND METHODS In our institution, 55 RFA sessions under computed tomography (CT) guidance were performed on 48 pulmonary malignant lesions (23 inoperable primary and 25 metastatic) in 35 patients. RESULTS Total necrosis was noted in 19 primary (82.6%) and in 19 metastatic lesions (76%). In four primary (17.4%) and in six metastatic lesions (14%), partial necrosis was achieved, and a second RFA session was performed. The 6-month spiral CT follow-up demonstrated recurrence in seven lesions (14.5%) (four primary and three metastatic), which were treated with an additional RFA session. Two of the patients who underwent the procedure died of disseminated disease after one year, accounting for a 1-year survival rate of 94.2%. Mean survival was 14.48 +/- 3.3 months. CONCLUSION RFA is an effective method for treating unresectable lung carcinoma and lung metastases.

Influence of glioma's multidrug resistance phenotype on (99m)Tc-tetrofosmin uptake.

PurposeMultidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer. Several chemotherapeutic and radiopharmaceutical agents are substrates of the pumps encoded by the MDR genes, and therefore, their accumulation is prevented. We evaluated in vivo whether [99mTc]tetrofosmin (99mTc-TF) uptake is influenced by the MDR profile of gliomas.ProceduresEighteen patients with histologically confirmed glioma were included in the study. Brain single-photon emission computed tomography by 99mTc-TF was performed within a week prior to surgical excision, and the expression of MRP5 was assessed by immunohistochemistry. Radiotracer accumulation was assessed by a semiquantitative method, calculating the lesion-to-normal uptake ratio.ResultsUsing Spearmans ρ analysis, we found no correlation between tracer uptake expressed as lesion-to-normal and MRP5 expression. There was a significant correlation between glioma aggressiveness as assessed by Ki-67/MIB-1 and MRP5 expression.ConclusionThe present data suggest that 99mTc-TF uptake is not influenced by gliomas MDR phenotype. Thus, 99mTc-TF constitutes a suitable radiotracer for imaging gliomas.

Assessment of glioma proliferation using imaging modalities

The assessment of glioma proliferation rate is important to predict tumor behavior, response to therapy and prognosis. Various methods, largely involving immunohistological markers in tissue samples, have been proposed to this aim; however, they all require tissue removal through a biopsy or during a surgical procedure. Consequently, non-invasive imaging modalities that could reliably assess the proliferative potential of intracranial space-occupying lesions in vivo would be of obvious significance. In the present study we review the contribution of MRI, positron emission tomography and single-photon emission CT for the assessment of the proliferative potential of gliomas.

Comparison of diffusion tensor, dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma

INTRODUCTION Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis. METHODS A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, (99m)Tc-Tetrofosmin brain SPECT. RESULTS Both (99m)Tc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between (99m)Tc-Tetrofosmin uptake ratio and rCBV (P=0.003). CONCLUSIONS Dynamic susceptibility contrast MRI and brain SPECT with (99m)Tc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.

Correlation of diffusion tensor, dynamic susceptibility contrast MRI and 99mTc-Tetrofosmin brain SPECT with tumour grade and Ki-67 immunohistochemistry in glioma

OBJECTIVE Assessment of the grade and type of glioma is of paramount importance for prognosis. Tumour proliferative potentials may provide additional information on the behaviour of the tumour, its response to treatment and prognosis. The purpose of this study was to investigate the correlation between diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography (SPECT), and the tumour grade and Ki-67 labelling index in newly diagnosed gliomas. METHODS Study was made of patients with suspected glioma on brain MRI between December 2010 and January 2012, by DTI, DSC MRI and (99m)Tc-Tetrofosmin brain SPECT. The proliferative activity of each tumour was measured by deriving the Ki-67 proliferation index from immunohistochemical staining of tumour specimens. RESULTS Glioma was newly diagnosed in 25 patients (17 men, 8 women, aged 19-79 years, median 55 years). The Ki-67 index ranged from 1% to 80% (mean 19.4%). On evaluation of the relationship between the (99m)Tc-Tetrofosmin tumour uptake by gliomas was found to be significantly correlated with cellular proliferation (rho=0.924, p<0.0001). Regarding DTI, significant negative correlation was demonstrated between the apparent diffusion coefficient (ADC) ratio and the Ki-67 index (rho=-0.545, p=0.0087). Significant correlation was also observed between the fractional anisotropy (FA) ratio and the Ki-67 index (rho=0.489, p=0.02). Strong correlation was found between relative cerebral blood volume (rCBV) and Ki-67 index (rho=0.853, p<0.0001), and between the (99m)Tc-Tetrofosmin lesion-to-normal (L/N) uptake ratio and rCBV (rho=0.808, p ≤ 0.0001). Significant negative correlation was demonstrated between the (99m)Tc-Tetrofosmin L/N ratio and ADC ratio (rho=-0.513, p=0.014). These imaging techniques were able to distinguish between low-grade and high-grade gliomas. CONCLUSIONS Findings on DSC MRI and brain SPECT with (99m)Tc-Tetrofosmin metrics were more closely correlated with glioma cellular proliferation.

The value of 99mTc-tetrofosmin brain SPECT in predicting survival in patients with glioblastoma multiforme.

99mTc-tetrofosmin brain SPECT has been reported as a useful tool for the evaluation of glioma proliferation. In the present study, we set out to investigate the prognostic value of 99mTc-tetrofosmin brain SPECT in patients with glioblastoma multiforme. Methods: We prospectively studied 18 patients (13 men, 5 women; mean age ± SD, 60.8 ± 7.79 y) who were operated on for glioblastoma multiforme. All patients underwent preoperative 99mTc-tetrofosmin brain SPECT, and surgical excision was performed within a week after SPECT. All patients received postoperative radiotherapy and chemotherapy. Results: By calculating the lesion-to-normal (L/N) 99mTc-tetrofosmin uptake ratio, we found that patients with an L/N ratio of more than 4.7 had significantly worse survival than did patients with an L/N ratio of 4.7 or less. Furthermore, patients with a Karnofsky Performance Score more than 90 had a significantly better survival rate. Although patients with near-total tumor resection who were younger than 60 y survived longer, the difference did not reach statistical significance. In the multivariate analysis, 99mTc-tetrofosmin uptake and Karnofsky Performance Score were identified as factors with independent prognostic power. Conclusion: 99mTc-tetrofosmin brain SPECT may be an independent prognostic factor in patients with glioblastoma multiforme. Further larger studies are needed to verify these results.