Impact of 18F-FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin.

OBJECTIVES: 18F-FDG PET/CT is increasingly performed in patients with differen-tiated thyroid cancer. The aim of this study was to assess the clinical impact of 18F-FDG PET/CT on the management of patients with differentiated thyroid carcinoma who had elevated serum thyroglobulin (Tg) and negative 131I whole body scan (WBS). METHODS: 67 patients with differentiated thyroid carcinoma were included in this study. The findings of 18F-FDG PET/CT imaging were compared with histo-pathology, follow up imaging, or clinical follow-up results. The diagnostic accuracy of 18F-FDG PET/CT was evaluated for the entire patient group and for those patients with stimulated serum thyroglobulin levels of less than 5, 5-10, and more than 10 pmol/L as well as for local recurrences and metastases sites. The impact of 18F-FDG PET/CT on therapeutic management was also evaluated. RESULTS: 30/67 patients had positive findings on 18F-FDG PET/CT; 28 were true-positive and 2 were false-positive. 18F-FDG PET/CT results were true-negative in 36 patients and false-negative in 1 patient. The overall sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were, 96.5%, 94.5%, 95.5%, 93.3%, and 97.2% respectively. Positive 18F-FDG PET/CT findings were directly correlated with stimulated serum thyroglobulin levels, 7.1% had Tg between 5-10, and 92.9% had Tg greater than 10 pmol/L. 18F-FDG PET/CT had a high or moderate impact on treatment management in 28 (41.8%) of patients. CONCLUSION: 18F-FDG PET/CT is able to improve diagnostic accuracy and have management impact in a therapeutically relevant way in patients with differentiated thyroid carcinoma who present with rising thyroglobulin level, negative 131I WBS, and clinical suspicion of recurrent disease.

Predicting primary treatment failure using interim FDG-PET scanning in diffuse large B-cell lymphoma.

Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, ΔSUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET.

OBJECTIVES: The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). METHODS: Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. RESULTS: The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). CONCLUSION: There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology.

FDG PET/CT in the liver: lesions mimicking malignancies.

PURPOSE: 18F-fluorodeoxyglucose (FDG) PET/CT is invaluable in managing liver lesions, in particular in the evaluation of suspected liver metastases. It is both sensitive and specific in detecting liver metastases from a wide range of primary cancers, and may change clinical management, most commonly by detecting additional lesions and decreasing the number of futile surgeries. However, some benign lesions may also show increased metabolic activity which can lead to false positive PET findings. We describe some of these lesions and their imaging characteristics that may help in differentiating them from malignant metastases. METHODS: e reviewed all whole body FDG PET/CT studies performed over a 5-year period in our institution, and identified those with focal liver lesions showing increased FDG uptake for which histological results were available. RESULTS: majority of lesions showing increased metabolic activity were due to malignant disease, such as metastases or primary liver tumours. However, we also found increased FDG uptake in non-neoplastic lesions such as Cryptococcosis, abscesses, and secondary inflammation from cholecystitis. Increased metabolic activity was also seen in some benign neoplasms such as hepatic adenomas and hemangioendotheliomas. CONCLUSION: DG PET/CT is currently the most sensitive non-invasive imaging modality for the detection of hepatic metastases, particularly from the gastrointestinal tract. False positive results are rare, and have been described mainly in abscesses. However, other lesions can also show increased metabolic activity, and failure to differentiate these from metastases may result in inappropriate treatment.

Long-term survival of 42 patients with resected N2 non-small-cell lung cancer: the impact of 2-(18)F-fluoro-2-deoxy-D-glucose positron emission tomogram mediastinal staging.

OBJECTIVE: Prognostic information known preoperatively allows stratification of patients to surgery; induction therapy and surgery; or definitive chemoradiotherapy and may prevent a futile thoracotomy. Attention has focussed on the standard uptake value (SUV) of the primary tumour but less has been described regarding the 18F-fluoro-2-deoxy-D-glucose (18F-FDG) avidity of mediastinal nodes. We aimed, in a group of surgically resected cN0-1 but pN2 tumours, to compare the survival of patients with and without 18F-FDG avid mediastinal nodes. METHODS: Retrospective review of a surgical database identified cN0-1 non-small-cell lung cancer (NSCLC) patients with pN2 disease after resection. Survival of non-FDG avid N2 versus FDG avid N2 groups was compared after stratification according to variables found on univariate analysis to affect survival. RESULTS: From January 1993 to December 2006, 42 patients were identified; 27 (64%) had non-FDG avid N2 disease. Five-year and median survival were better in the non-FDG avid N2 disease group, 25% versus 0% and 30 (16-44) versus 13 (10-16) months, respectively (p=0.02). After 1998, the difference in survival was 41% versus 0% and 35 (14-56) versus 12 (16-18) months, respectively (p=0.02). CONCLUSIONS: After resection, patients with non-FDG avid N2 disease have better survival than patients with FDG avid N2 disease. Exploratory thoracotomy alone (after frozen section analysis) cannot be advocated in patients with non-FDG avid N2 disease as survival after resection appears at least equivalent to alternate therapeutic approaches in this group. This assertion may be tempered if right pneumonectomy is required or R0 resection is unachievable. Mediastinal nodal avidity may improve stratification in future studies of long-term survival in NSCLC.

Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies.

UNLABELLED: PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed primary brain tumors for the presence of hypoxia, as indicated by the uptake of 18F-fluoromisonidazole (18F-FMISO) and to examine the relationship of hypoxia to the uptake of 18F-FDG and molecular markers of hypoxia. METHODS: Seventeen patients with suspected primary glioma were enrolled prospectively in this study. Sixteen patients had histology, with 2 having metastatic disease. All patients had PET studies with 18F-FMISO and 18F-FDG and MRI studies. Immunohistochemistry was undertaken with tumor markers of angiogenesis and hypoxia. Patients were monitored for disease progression and statistical analysis of data was performed. RESULTS: Of the 14 patients with histology, 8 died with a median time of 16 mo (range, 2-30 mo) until death. Of those who died, 7 had positive and 1 had negative 18F-FMISO uptake. 18F-FMISO uptake was observed in all high-grade gliomas but not in low-grade gliomas. A significant relationship was found between 18F-FDG or 18F-FMISO uptake and expression of VEGF-R1 and Ki67 expression. Other immunohistochemical markers demonstrated a trend toward increased uptake but none was significant. CONCLUSION: 18F-FMISO PET provides a noninvasive assessment of hypoxia in glioma and was prognostic for treatment outcomes in the majority of patients. 18F-FMISO PET may have a role not only in directing patients toward targeted hypoxic therapies but also in monitoring response to such therapies.

Assessment of the role of FDG PET in the diagnosis and management of children with refractory epilepsy.

PURPOSE: We performed a retrospective analysis of the results of FDG PET scans in children with refractory epilepsy referred to our centre over an 8-year period, with a view to ascertaining the impact of FDG PET on subsequent patient management. METHODS: A questionnaire was used to assess the impact of FDG PET scan on diagnosis, management and clinical decision-making processes for epilepsy surgery from the managing clinician's perspective. FDG PET scan results were also compared with MRI, EEG and SPECT results and coded according to whether the FDG PET scan provided independent information and localisation of epileptogenic regions. RESULTS: A total of 118 eligible patients under the age of 14 years were identified, with questionnaires being completed on 113 evaluable patients (96%). The pre-PET management plan consisted of consideration for surgery in 92 patients (81%) and medical therapy for the remaining 21 patients (19%). Managing physicians rated FDG PET as providing information additional to that obtained with other investigations regarding epileptogenic sites in 88 patients (77%). FDG PET had either a minor or a major impact on clinical management in 58 patients (51%), principally with regard to surgical candidacy. CONCLUSION: FDG PET has a definite role in the assessment of paediatric patients with refractory epilepsy who are being considered for surgery. In the future, analysis of FDG PET data in specific subpopulations of children with refractory epilepsy may lead to novel insights regarding aetiology.

Impact of 2-deoxy-2[F-18]fluoro-D-glucose Positron Emission Tomography on the management of patients with advanced melanoma.

OBJECTIVES: Accurate staging of patients with melanoma is vital to guide appropriate treatment. 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) has been reported to be a sensitive and specific technique for the staging of advanced melanoma, however, few studies provide information regarding its impact on patient management. METHODS: We retrospectively reviewed the FDG-PET scan results of 92 patients with melanoma who had 126 scans performed over a six-year period. These patients were seen at the specialist melanoma clinic at our Institution, and 84 patients (92%) had stage III or IV disease. FDG-PET scan results were correlated with computed tomography (CT) scans and other imaging when available, and with clinical follow-up of a minimum of three to six months. The impact of FDG-PET scans on patient management was also assessed. RESULTS: On a lesion-by-lesion analysis, FDG-PET had a sensitivity of 92%, a specificity of 88%, and an accuracy of 91%. FDG-PET correctly affected the clinical decision-making process in 40 of 126 patient studies (32%), particularly assisting in the selection of patients for surgery. CONCLUSION: FDG-PET has an important role in guiding the management of patients with advanced melanoma, particularly when surgery is contemplated.

Positron emission tomography with selected mediastinoscopy compared to routine mediastinoscopy offers cost and clinical outcome benefits for pre-operative staging of non-small cell lung cancer.

PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is an important staging procedure in patients with non-small cell lung cancer (NSCLC). We aimed to demonstrate, through a decision tree model and the incorporation of real costs of each component, that routine FDG-PET imaging as a prelude to curative surgery will reduce requirements for routine mediastinoscopy and overall hospital costs. METHODS: A decision tree model comparing routine whole-body FDG-PET imaging to routine staging mediastinoscopy was used, with baseline variables of sensitivity, specificity and prevalence of non-operable and metastatic disease obtained from institutional data and a literature review. Costings for hospital admissions for mediastinoscopy and thoracotomy of actual patients with NSCLC were determined. The overall and average cost of managing patients was then calculated over a range of FDG-PET costs to derive projected cost savings to the community. RESULTS: The prevalence of histologically proven mediastinal involvement in patients with NSCLC presenting for surgical assessment at our institution is 20%, and the prevalence of distant metastatic disease is 6%. Based on literature review, the pooled sensitivity and specificity of FDG-PET for detection of mediastinal spread are 84% and 89% respectively, and for mediastinoscopy, 81% and 100%. The average cost of mediastinoscopy for NSCLC in our institution is 4,160 AUD, while that of thoracotomy is 15,642 AUD. The cost of an FDG-PET scan is estimated to be 1,500 AUD. Using these figures and the decision tree model, the average cost saving is 2,128 AUDper patient. CONCLUSION: Routine FDG-PET scanning with selective mediastinoscopy will save 2,128 AUD per patient and will potentially reduce inappropriate surgery. These cost savings remain robust over a wide range of disease prevalence and FDG-PET costs.

Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography.

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans.

Evaluation of 18 F-fluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer.

OBJECTIVE: To prospectively evaluate the use of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in the initial staging of squamous cell head and neck carcinoma. SUMMARY BACKGROUND DATA: The status of cervical lymph nodes is an important prognostic factor and determinant of management approach in squamous cell head and neck cancer. METHODS: FDG-PET findings were compared with those of computed tomography (CT) before removal of the primary tumor and/or neck dissection. Histopathologic analysis was used as the gold standard for assessment of the sensitivity and specificity of these modalities. RESULTS: FDG-PET correctly identified the primary tumor in 35 of 40 patients in whom the site of the primary was known clinically and still present (sensitivity 88%). None of four unknown primaries were detected. Tumors not detected by FDG-PET were generally superficial, with depths of less than 4 mm. CT correctly identified 18 of the 35 primary tumors (sensitivity 51%). Eleven of 17 CT false-negative tumors were detected by FDG-PET. The sensitivity and specificity for the presence of metastatic neck disease on FDG-PET were 82% and 100%, respectively; those for CT were 81% and 81%, respectively. FDG-PET was true positive for metastatic neck disease in two of the three CT false-negative patients. CONCLUSIONS: FDG-PET shows promise in the initial staging of head and neck cancer and provides additional accuracy to a conventional staging process using CT.

Positron emission tomography and epilepsy.

PURPOSE: This review examines the current role of positron emission tomography (PET) in the investigation and management of patients with epilepsy. PROCEDURES: A literature review utilizing MEDLINE(R) and other sources was undertaken. For the comparison of the accuracy of PET with magnetic resonance imaging (MRI) for seizure focus localization, only publications since 1994 were examined. Individual patient data was tabulated to provide figures for seizure focus localization rates for different types of focal epilepsy and the prognostic value of PET findings for epilepsy surgery outcome. RESULTS: The majority of PET studies used 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The epileptogenic sites typically show reduced FDG uptake (hypometabolism). In patients with intractable temporal lobe epilepsy (TLE), unilateral temporal lobe hypometabolism (UTH) corresponding to the seizure focus was seen in 86% of patients. In the same population, MRI demonstrated relevant abnormalities in 76%. UTH contralateral to the seizure focus was rarely seen (3%). Following temporal lobectomy, 86% of patients with ipsilateral UTH had a good outcome. When MRI was normal, UTH predicted a good outcome in 82%. Fifty percent with bitemporal hypometabolism had independent bilateral foci, and in those who proceeded to surgery only 50% had a good result. In extratemporal epilepsy, hypometabolism relevant to the focus was seen in 67% but, as in TLE, it was often more extensive than pathological abnormality. Recently evidence of a role for 11C-Flumazenil has emerged with reduced binding in the primary epileptogenic site. 11C-Flumazenil abnormalities appear more restricted to abnormal cortex and may be a better guide to the extent of resection required for surgical success. CONCLUSIONS: FDG-PET has a key role in the evaluation of patients with intractable partial epilepsy, particularly when surgery is a treatment option. Development and application of more specific biochemical probes may further improve the clinical value of PET for the understanding and treatment of epilepsy.