Pilot study of F¹⁸-Fluorodeoxyglucose Positron Emission Tomography/computerised tomography in Wilms’ tumour: Correlation with conventional imaging, pathology and immunohistochemistry

Abstract

Wilms’ tumour is the second most common paediatric solid tumour. Prognosis is good although higher stage disease carries significant mortality and treatment related morbidity. In the UK, risk stratification is based on histological response to pre-operative chemotherapy. F¹⁸-Fluorodeoxyglucose Positron Emission Tomography (F¹⁸FDG-PET) is an emerging functional imaging technique in paediatric oncology. Little is known about the relationship between F¹⁸FDG-PET images and the disease process of Wilms’ tumour. We performed F¹⁸FDG-PET/CT scans in seven children with Wilms’ tumour after induction chemotherapy, immediately before surgery. The standard uptake values (SUV) of F¹⁸FDG-PET/CT images were related to conventional imaging and histopathological findings. In total seven children were studied. F¹⁸FDG-PET/CT was consistently safely performed. All tumours showed F¹⁸FDG activity. Four tumours had activity with SUV/bw max >5 g/ml. Histological examination of these active areas revealed viable anaplastic Wilms’ tumour. Furthermore, in these four tumours GLUT-1 and Ki67 immunostaining was strongly positive. Three further tumours demonstrated lower uptake (SUV/bw max <5 g/ml), which represented areas of microscopic foci of residual viable tumour mixed with post chemotherapy change. Metastatic disease was F¹⁸FDG avid in two of four children with stage four diseases. In conclusion, following chemotherapy, active Wilms’ tumour is F¹⁸FDG avid and higher SUV was seen in histologically high risk disease.

Introduction

Wilms’ tumour (nephroblastoma) is the second most common solid tumour of childhood. There is 94% overall survival in stage I tumours and 75% in stage IV disease (United Kingdom Wilms’ Tumour 2 study).¹ Recommended imaging at diagnosis typically relies on conventional cross sectional anatomical imaging using ultrasound, CT and MRI, which provide little functional information about the tumour.

Treatment in Europe consists of pre and post-operative chemotherapy. Prior to surgery, ultrasound or CT reassessment of the tumour is required. This imaging provides information about change in tumour size and can potentially identify features such as tumour necrosis. However, although change in tumour size is important for surgical management it correlates poorly with histological features,² which may be of prognostic significance. Functional information about the presence of active disease within the primary tumour or residual metastases remains elusive.

¹⁸F-Fluorodeoxyglucose Positron Emission Tomography (¹⁸F-FDG-PET) detects metabolic activity of malignant cells and reflects increased activity as increased avidity.3, 4, 5 There is limited access to PET scanners and the procedure itself is long and complex making the acquisition of ¹⁸F-FDG-PET images in children problematic. Urinary tract scanning is additionally complicated by the renal excretion of ¹⁸F-FDG, resulting in visualisation of collecting systems and bladder, which may obscure underlying disease. The addition of fused CT images in the new generation of PET/CT scanners has helped to resolve some of these issues; the CT component not only shortens scan acquisition time, as the scan is used for attenuation correction, but also allows accurate anatomical location of areas of ¹⁸F-FDG uptake.

Shulkin et al. have looked at the role of ¹⁸F-FDG-PET scanning in three cases of Wilms’ tumour⁶ and suggested it to be FDG avid. We have performed a series of PET/CT studies to investigate the technique’s potential in children with Wilms’ tumour. We hypothesised that ¹⁸F-FDG-PET/CT, if positive, would provide additional functional information to conventional imaging post induction chemotherapy and immediately prior to surgery, in Wilms’ tumour. Such information could aid clinical decisions related to treatment response and local therapy (e.g. pulmonary radiotherapy, resection of lung metastases and nephron sparing surgery for bilateral Wilms’ tumour). To investigate this we compared the ¹⁸F-FDG-PET/CT with CT or US scan and tumour pathology. Misch et al.⁷ have demonstrated an increased standard uptake values (SUV) in one case of anaplastic Wilms’ tumour when compared with eight cases with intermediate histology when assessing the role of ¹⁸F-FDG-PET in 12 cases of Wilms’ tumour. We hypothesised that the standard uptake value on ¹⁸F-FDG-PET/CT would relate to tumour pathology. If this were the case, ¹⁸F-FDG-PET/CT might be able to highlight active tumour. A further objective was to determine whether immunohistochemical staining for GLUT-1 (a marker of increased glucose uptake) and Ki67 (an indicator of cellular proliferation, known to correlate with ¹⁸F-FDG uptake in several tumour types) corresponded not only to tumour histological type but also to SUV on ¹⁸F-FDG-PET/CT. These data would further confirm the association between ¹⁸F-FDG positivity and Wilms’ tumour allowing the integration of this tool into clinical practice.