Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results

Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost-effective. However, patients with nodal-positive PET results should not be excluded from biopsy.     

Cost-effectiveness of PET in the management algorithms of lung tumors: comparison of health economic data

Modelling is an accepted, valid and often necessary method for assessing economic effectiveness in terms of cost per life year gained. Comparing an alternative strategy (a) with a baseline strategy (bl), the incremental cost (COSTa-COSTbl) divided by the incremental life expectancy (LEa-LEbl) defines the incremental cost-effectiveness ratio (ICER). Taking watchful waiting as the low-cost baseline strategy for the management of solitary pulmonary nodules, the ICER of positron emission tomography (PET) [3218 euros (EUR) per life year saved (LYS)] was more favourable than that of exploratory surgery (4210 EUR/LYS) or that of transthoracic needle biopsy (6120 EUR/LYS). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy in case of an intermediate pretest probability of malignancy. For management of potentially operable non-small cell lung cancer the use of PET in patients with normalisized mediastinal lymph nodes on CT was most cost-effective (143 EUR/LYS), and the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. Using PET in patients with enlarged lymph nodes on CT, the ICER raised to 36,667 EUR/LYS. When PET or CT were positive for mediastinal lymph nodes, the exclusion from biopsy confirmation led to cost savings that did not justify the expected reduction in life expectancy. Economic data from the USA and Japan also demonstrated the cost-effectiveness of PET-based algorithms for the management of lung tumours.     

Cost-effectiveness of FDG-PET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany

Management of solitary pulmonary nodules (SPNs) of up to 3 cm was modelled on decision analysis comparing "wait and watch", transthoracic needle biopsy (TNB), exploratory surgery and full-ring dedicated positron emission tomography (PET) using fluorine-18 2-fluorodeoxyglucose (FDG). The incremental cost-effectiveness ratios (ICERs) were calculated for the main risk group, a cohort of 62-year-old men, using first "wait and watch" and second exploratory surgery as the baseline strategy. Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.95 and 0.80 for detecting malignancy in SPNs and at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes. The costs quoted correspond to reimbursement in 1999 by the public health provider in Germany. Decision analysis modelling indicates the potential cost-effectiveness of the FDG-PET strategy for management of SPNs. Taking watchful waiting as the low-cost baseline strategy, the ICER of PET [3218 euros (EUR) per life year saved] was more favourable than that of exploratory surgery (4210 EUR/year) or that of TNB (6120 EUR/year). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy. This constellation was described by a negative ICER of -6912 EUR/year. The PET algorithm was cost-effective for risk and non-risk patients. However, the ICER of PET as the preferred strategy was sensitive to a hypothetical deterioration of any PET parameters by more than 0.07. To transfer the diagnostic efficacy from controlled studies to the routine user and to maintain the cost-effectiveness of this technology, obligatory protocols for data acquisitions would need to be defined. If the prevalence of SPNs is estimated at the USA level (52 per 100,000 individuals) and assuming that multiple strategies without PET are the norm, the overall costs of a newly implemented PET algorithm would be limited to far less than one EUR per member of the public health provider in Germany.     

Cost-effectiveness of FDG-PET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany

Management of solitary pulmonary nodules (SPNs) of up to 3 cm was modelled on decision analysis comparing "wait and watch", transthoracic needle biopsy (TNB), exploratory surgery and full-ring dedicated positron emission tomography (PET) using fluorine-18 2-fluorodeoxyglucose (FDG). The incremental cost-effectiveness ratios (ICERs) were calculated for the main risk group, a cohort of 62-year-old men, using first "wait and watch" and second exploratory surgery as the baseline strategy. Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.95 and 0.80 for detecting malignancy in SPNs and at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes. The costs quoted correspond to reimbursement in 1999 by the public health provider in Germany. Decision analysis modelling indicates the potential cost-effectiveness of the FDG-PET strategy for management of SPNs. Taking watchful waiting as the low-cost baseline strategy, the ICER of PET [3218 euros (EUR) per life year saved] was more favourable than that of exploratory surgery (4210 EUR/year) or that of TNB (6120 EUR/year). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy. This constellation was described by a negative ICER of -6912 EUR/year. The PET algorithm was cost-effective for risk and non-risk patients. However, the ICER of PET as the preferred strategy was sensitive to a hypothetical deterioration of any PET parameters by more than 0.07. To transfer the diagnostic efficacy from controlled studies to the routine user and to maintain the cost-effectiveness of this technology, obligatory protocols for data acquisitions would need to be defined. If the prevalence of SPNs is estimated at the USA level (52 per 100,000 individuals) and assuming that multiple strategies without PET are the norm, the overall costs of a newly implemented PET algorithm would be limited to far less than one EUR per member of the public health provider in Germany.     

Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? – From Chinese healthcare system perspective

Objectives

The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China.

Methods

Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis.

Results

Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800 RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B–A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B–A), and decrease of palliative therapy cost could reduce both the ICER and overall cost.

Conclusions

The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making.     

Solitary pulmonary nodules: accuracy and cost-effectiveness of sodium iodide FDG-PET using Australian data

This study uses Australian data to confirm the accuracy of dedicated sodium iodide (NaI) fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in evaluating indeterminate solitary pulmonary nodules (SPNs) and to determine the conditions under which PET could play a cost-effective role in this evaluation. Ninety-two patients from two Australian hospitals in different states underwent FDG-PET for evaluation of an SPN. Observed values for prior probability of malignancy and diagnostic accuracy of PET were applied to previously published decision tree models using published Australian health care costs. The accuracy of FDG-PET was 93% with a sensitivity of 92% and a specificity of 95%. The prior probability of malignancy (0.54), PET sensitivity and PET specificity indicated cost savings per patient of up to EUR 455 (Adollars 774) based on a PET cost of EUR 706 (Adollars 1,200). PET would remain cost-effective for levels of prior probability up to 0.8-0.9 and a PET cost of EUR 736-1,161 (Adollars 1,252-Adollars 1,974). It is concluded that NaI PET is accurate, cost saving and cost-effective for the characterisation of indeterminate pulmonary nodules in Australia. Comparison with previous reports from the United States confirms that FDG-PET can remain cost-effective despite population differences in medical costs, disease prevalence and PET diagnostic performance.     

Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan.

The management of metastatic thyroid carcinoma patients with a negative 131I scan presents considerable problems. Fifty-four athyrotic papillary thyroid carcinoma patients whose 1311 whole-body scans were negative underwent 18F-fluorodeoxyglucose (FDG) PET; the purpose was to determine whether this procedure could localize metastatic sites. We also assessed its usefulness in the management of these patients. METHODS: Whole-body emission scan was performed 60 min after the injection of 370-555 MBq 18F-FDG, and additional regional attenuation-corrected scans were obtained. Metastasis was pathologically confirmed in 12 patients and was confirmed in other patients by overall clinical evaluation of the findings of other imaging studies and of the subsequent clinical course. RESULTS: In 33 patients, tumor had metastasized, whereas 21 patients were in remission. FDG PET revealed metastases in 31 patients (sensitivity 93.9%), whereas thyroglobulin levels were elevated in 18 patients (sensitivity 54.5%). FDG PET was positive in 14 of 15 metastatic cancer patients with normal thyroglobulin levels. In 20 of 21 patients in remission, FDG PET was negative (specificity 95.2%), whereas thyroglobulin levels were normal in 16 patients (specificity 76.1%). The sensitivity and specificity of FDG PET were significantly higher than those of serum thyroglobulin. In patients with negative 1311 scans, FDG PET detected cervical lymph node metastasis in 87.9%, lung metastasis in 27.3%, mediastinal metastasis in 33.3% and bone metastasis in 9.1%. In contrast, among 117 patients with 131I scan-positive functional metastases, 131I scan detected cervical lymph node metastasis in 61.5%, lung metastasis in 56.4%, mediastinal metastasis in 22.2% and bone metastasis in 16.2%. In all 5 patients in whom thyroglobulin was false-negative with negative antithyroglobulin antibody, PET showed increased 18F-FDG uptake in cervical lymph nodes, mediastinal lymph nodes, or both. Among patients with increased 18F-FDG uptake only in the cervical lymph nodes, the nodes were dissected in 11. Metastasis was confirmed in all, even in normal-sized lymph nodes. CONCLUSION: FDG PET scan localized metastatic sites in 131I scan-negative thyroid carcinoma patients with high accuracy. In particular, it was superior to 131I whole-body scan and serum thyroglobulin measurement for detecting metastases to cervical lymph nodes. FDG PET was helpful for determining the surgical management of these patients.     

CT定位经纤维支气管镜纵隔淋巴结针吸活检术的价值

目的 为明确纵隔淋巴结肿大的性质,进行CT定位经纤维支气管镜纵隔淋巴结针吸活检术（CT－guided transbronchial needle aspiration biopsy,CT-TBNA)的研究。方法 根据纵隔淋巴结分区定位标准,对原发性肺癌（54例）伴纵隔淋巴结肿大、恶性淋巴瘤（5例）、纵隔脓肿（3例）、炎性淋巴结肿大（11例）共73例158枚纵隔肿大 淋巴结行CT－TBNA穿刺活检。结果 CT扫描证实穿刺针在全部158枚淋巴结内,其中86％（136／158）的淋巴结抽吸物经病理检查获得了病理组织学和（或）细胞学诊断,未发生严重并发症。结论 CT－TBNA的标准是可靠的,穿刺操作安全有效,对确定纵隔淋巴结肿大性质和肿瘤分期有重要意义。     

Should mediastinoscopy actually be incorporated into the FDG PET strategy for patients with non-small cell lung carcinoma?

BACKGROUND: Incorporating mediastinoscopy (MS) into the PET-based strategy for non-small cell lung carcinoma (NSCLC) patients might be cost-effective because MS can allow unnecessary thoracotomies to be avoided. The objective of our study was to assess the cost-effectiveness of incorporating MS into a PET strategy for NSCLC patients. METHODS: To determine life expectancy (LE), quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER), a decision-tree sensitivity analysis was designed for histopathologically confirmed NSCLC patients with M0 disease, based on the three competing strategies of chest CT only vs. PET + CT vs. PET + CT + MS. A simulation of 1000 NSCLC patients was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, LE, utilities and cost from published data. One-way sensitivity analyses were performed to determine the influences of mediastinal metastasis prevalence on LE, QALY and ICER. RESULTS: The LE and QALY per patient in the CT only strategy, PET + CT strategy and PET + CT + MS strategy were 4.79 and 4.35, 5.33 and 4.93 and 5.68 and 5.33 years, respectively, with a 20% prevalence of mediastinal metastasis. The ICERs were 906.6 yen x 10(3) (7555 US dollars)/QALY/patient at a 20% mediastinal metastasis prevalence, and 2194 yen x 10(3) (18,282 US dollars)/QALY/patient at a 50% prevalence, but exceeded 5280 yen x 10(3) (44,000 US dollars)/QALY/ patient at 80%. CONCLUSIONS: Our study quantitatively showed the CT + PET + MS strategy in place of the PET + CT strategy in managing NSCLC patients to be cost-effective. MS should be incorporated into the PET + CT strategy for NSCLC patients except in those highly suspected of having mediastinal disease on chest CT or PET.     

Targeted lymph node biopsy in mediastinoscopy using 3D FDG-PET/CT movies: a feasibility study

In non-small-cell lung cancer, positive lymph nodes with increased fluorodeoxyglucose (FDG) uptake may be missed by mediastinoscopy. Lack of pathological confirmation may lead to radical, but unnecessary lung surgery. To minimize these false-negative results, the feasibility and potential value of three-dimensional (3D) FDG-PET/computed tomography (CT) movies were investigated to improve targeted lymph node biopsy during mediastinoscopies. PET/CT images were rendered in 3D volumes with multiplanar reconstructions and maximum intensity projections and reviewed in 3D 'fly-through' and 'fly-around' movies. These movies were developed and optimized by the Departments of Surgery and Nuclear Medicine. Twenty-two consecutive patients with non-small-cell lung cancer were included, of whom eight were FDG-PET positive for mediastinal lymph nodes. 3D FDG-PET/CT movies were presented to surgeons before mediastinoscopy. Surgical consequences were investigated, including sensitivity and the negative predictive value of mediastinoscopy. Results were compared with those of a retrospective study in which 3D techniques were not used. During mediastinoscopies, the 3D-PET/CT movies were found to be helpful in the surgical localization of FDG-positive lymph nodes. It led to more confidence in the surgical approach. The sensitivity and negative predictive value were 86 and 94%, respectively. Although not statistically significant, these results were higher compared with those of the retrospective study (75 and 92%, respectively). 3D FDG-PET/CT guidance during mediastinoscopy is feasible. The movies seem to lead to targeted biopsy of lymph nodes. They may reduce false-negative mediastinoscopies and improve staging of lung cancer. 3D FDG-PET/CT can be seen as a promising tool for further implementation of image-guided surgery.     

FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar carcinoma?

While characterization of lung lesions and staging of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is an established clinical procedure, a lower diagnostic accuracy of FDG-PET for diagnosis and staging of so-called bronchioloalveolar carcinoma (BAC) has been reported. Therefore, the accuracy of PET for diagnosing and staging of BAC was investigated. We studied 41 patients eventually found to have adenocarcinoma with a bronchioloalveolar growth pattern who were referred for characterization or staging of lung lesions with whole-body FDG-PET between January 1998 and March 2001: there were 11 males (27%) and 30 females (73%), with a mean age of 66.0+/-10.9 (range =44-84 years). Patients were imaged using ECAT EXACT or HR+ systems. All patients had non-attenuation-corrected scans, while transmission data for attenuation correction were also available for 12 patients (29%). PET correctly identified BAC in 41 of the 46 (89%) lesions and 39 of the 41 patients (95%). By pathology, 25 patients (61%) were found to have unifocal or nodular lesions; this pattern was correctly identified by PET in 20 patients (80%) and by CT in 18 (72%). PET correctly identified 7 (44%) of 16 patients (39%) who had multicentric or diffuse BAC, and CT identified 11 (69%). Of the 35 patients whose lymph node status was verified pathologically, PET was correct in 27 (77%) and CT in 24 (69%). PET missed 67% of the rare tumors that had a pure BAC pattern with no invasive component. It is concluded that the diagnostic performance of whole-body FDG-PET is similar in most patients with lesions with a BAC pattern and in other non-small cell lung cancer types. PET is less accurate in patients with rare BAC tumors that have no invasive component.     

Cost-effectiveness analysis of strategies introducing FDG-PET into the mediastinal staging of non-small-cell lung cancer from the French healthcare system perspective

AIM: To determine the most cost-effective strategy using PET for mediastinal staging of potentially operable non-small-cell lung cancer (NSCLC). METHODS: Four decision strategies based on French NSCLC work-up practices for the selection of potential surgical candidates were compared, comprising CT only, PET for negative CT, PET for all with anatomical CT, and CT and PET for all cases. The medical literature was surveyed to obtain values for all variables of interest. Costs were assessed with reimbursements from the French healthcare insurance for the year 1999. Expected cost and life expectancy were calculated for all possible outcomes of each strategy. Sensitivity analysis was performed to determine the effects of changing variables on the expected cost and life expectancy. RESULTS: Compared with the CT only strategy, CT and PET for all resulted in a relative reduction of 70% of surgery for persons with mediastinal lymph node metastasis. PET for all with anatomical CT was shown to be a cost-effective alternative to the CT only, with life expectancy increased by 0.10 years and expected cost savings of 61 euros. This strategy was more favourable than PET for negative CT. Overall, sensitivity analyses showed the robustness of the results. CONCLUSION: The introduction of thoracic PET for NSCLC staging is potentially cost-effective in France. Further clinical investigation might help to validate this result.     

Improved radiologic staging of lung cancer with 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography and computed tomography registration

PURPOSE: To determine if volumetric nonlinear registration or registration of thoracic computed tomography (CT) and 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) datasets changes the detection of mediastinal and hilar nodal disease in patients undergoing staging for lung cancer and if it has any impact on radiologic lung cancer staging. METHOD: Computer-based image registration was performed on 45 clinical thoracic helical CT and FDG-PET scans of patients with lung cancer who were staged by mediastinoscopy and/or thoracotomy. Thoracic CT, FDG-PET, and registration datasets were each interpreted by 2 readers for the presence of metastatic nodal disease and were staged independently of each other. Results were compared with surgical pathologic findings. RESULTS: One hundred and thirty lymph node stations in the mediastinum and hila were evaluated each on CT, PET, and registration datasets. Sensitivity, specificity, positive predictive value, and negative predictive value, respectively, for detecting metastatic nodal disease for CT were 74%, 78%, 55%, 88%; for PET with CT side by side, 59% to 76%, 77% to 89%, 48% to 68%, and 84% to 91%; and for CT-PET registration, 71% to 76%, 89% to 96%, 70% to 86%, and 90% to 91%. Registration images were significantly more sensitive in detecting nodal disease over PET for 1 reader (P = 0.0156) and were more specific than PET (P = 0.0107 and 0.0017) in identifying the absence of mediastinal disease for both readers. Registration was significantly more accurate for staging when compared with PET for both readers (P = 0.002 and 0.035). CONCLUSION: Registration of CT and FDG-PET datasets significantly improved the specificity of detecting metastatic disease. In addition, registration improved the radiologic staging of lung cancer patients when compared with CT or FDG-PET alone.     

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 ¹⁸F-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 AUD$4,160, while that of thoracotomy is AUD$15,642. The cost of an FDG-PET scan is estimated to be AUD$1,500. Using these figures and the decision tree model, the average cost saving is AUD$2,128 per patient.Conclusion Routine FDG-PET scanning with selective mediastinoscopy will save AUD$2,128 per patient and will potentially reduce inappropriate surgery. These cost savings remain robust over a wide range of disease prevalence and FDG-PET costs.     

FDG-PET for preoperative staging of bladder cancer

Purpose The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication.Methods Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method.Results The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003).Conclusion Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy.     

3'-18F-fluoro-3'-deoxy-L-thymidine: a new tracer for staging metastatic melanoma?

In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F-FLT PET) for staging patients with clinical stage III melanoma was investigated. METHODS: Ten patients with melanoma and metastases to the locoregional draining lymph nodes, clinical stage III-based on physical examination, chest radiography, lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430 MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American Joint Committee on Cancer Staging System, which includes physical examination, spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size and mitotic rate of metastatic lymph nodes and skin metastases were determined. RESULTS: All histopathologic samples and (18)F-FLT PET lesions were categorized over anatomic regions and correlated. All locoregional metastases were correctly visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node metastatic disease was 88%. There were 3 true-negative and 2 false-positive lesions. The detection limit for lymph node metastases appeared to be approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT PET detected a total of 3 additional lesions with therapeutic consequences, without influencing staging. These lesions were initially missed by clinical staging. CONCLUSION: (18)F-FLT PET seems promising for (re)staging purposes in clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET should be compared with (18)F-FDG PET.     

Overexpression of Glut1 in lymphoid follicles correlates with false-positive (18)F-FDG PET results in lung cancer staging.

The evaluation of mediastinal lymph node involvement in non-small cell lung carcinoma (NSCLC) is very important for the selection of surgical candidates. PET using (18)F-FDG has remarkably improved mediastinal staging in NSCLC. However, false (18)F-FDG PET results remain a problem. This study was undertaken to identify histologic and immunohistochemical differences between cases showing false and true results of mediastinal lymph node involvement assessed by (18)F-FDG PET. METHODS: Preoperative (18)F-FDG PET examinations were performed on 62 patients with NSCLC, and mediastinal lymph node sampling was done at thoracotomy or mediastinoscopy. In 111 lymph nodes, the size, glucose transporter 1 (Glut1) expression, grade of follicular hyperplasia, and involved proportion of tumor were examined and compared with the (18)F-FDG PET findings. RESULTS: Lymphoid follicular cells were strongly positive for the expression of Glut1. The grade of follicular hyperplasia in false-positive lymph nodes was higher than that in true-negative nodes (P < 0.001). The Glut1 expression of metastatic tumors was higher in true-positive nodes than that in false-negative nodes (P < 0.001). Metastatic squamous cell carcinomas showed stronger Glut1 expression than adenocarcinomas and no false-negative results on (18)F-FDG PET. On the other hand, metastatic adenocarcinomas exhibited focal and weak Glut1 expression with frequent false-negative results. CONCLUSION: The results of this study indicate that (a). lymphoid follicular hyperplasia with Glut1 overexpression may have a causal relationship with high (18)F-FDG uptake of false-positive nodes and (b). the lower expression of Glut1 in metastatic tumors, such as adenocarcinomas, might be responsible for false-negative lymph nodes.     

FDG-PET for axillary lymph node staging in primary breast cancer

Management of the axilla in patients with operable breast cancer is still one of the most controversial areas in clinical oncology. The best procedure to examine the lymph nodes is still standard axillary lymph node dissection; nevertheless, the morbidity associated with this procedure is well known. Based on these considerations, it is important for progress in the treatment of operable breast cancer that strategies are found that permit a less invasive method of axillary sampling which does not impair the patient's quality of life. The technique of sentinel lymph node (SLN) biopsy has recently been proposed for this purpose, with very important results. SLN has now become routine practice in the surgical management of breast cancer, and in many institutions patients with a negative SLN biopsy are spared axillary dissection, while those with a positive SLN biopsy are submitted to axillary node dissection. The good accuracy of SLN biopsy represents a significant advance in the management of primary breast cancer; however, false negative axillary results can occur in a variable percentage of patients, and the contribution of the SLN procedure to the detection of metastases in the internal mammary and supraclavicular lymph nodes is not clear. Among the recently developed imaging modalities, positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has in particular been applied to the study of lymph node metastases in cancer patients. Several clinical studies have been carried out to evaluate the accuracy of PET in the axillary staging of operable primary breast cancer. These studies have sometimes provided conflicting results, either supporting the possibility of using FDG-PET to select patients who need axillary dissection or questioning whether FDG-PET can accurately assess the axillary status in primary breast cancer. All the limitations and the advantages of FDG-PET are discussed in this paper, by examining the performance of scanner technology and the possible causes of the false negative results. In the experience of the authors, comparing FDG-PET with SLN biopsy in the same series of patients, the results seem to indicate that the lower sensitivity of PET is restricted to micrometastases. Of course, this limitation of PET has to be analysed in relation to the importance of such small axillary metastases for the outcome of patients with breast cancer. The added value offered by PET in breast cancer staging in comparison with intraoperative detection of the sentinel node lies in the fact that FDG-PET is a non-invasive procedure that allows, within a single examination, the biological characterisation of breast cancer and viewing of the entire body.     

Primary staging of lymphomas: cost-effectiveness of FDG-PET versus computed tomography

The objective of this study was to measure the incremental cost-effectiveness of 2-(fluorine-18) fluorodeoxyglucose positron emission tomography (FDG-PET) versus computed tomography (CT) as diagnostic procedures in the primary staging of malignant lymphomas. The study was based on 22 patients of a clinical study who underwent the diagnostic procedures at Ulm University Hospital between April 1997 and May 1998. Direct costs of FDG-PET and CT, including staff, materials, investment, maintenance and overheads, were valued using a micro-costing approach. The effectiveness of both diagnostic procedures was measured as the percentage of correctly staged patients, given a gold standard for staging. The incremental cost-effectiveness ratio was the main outcome measure. Costs per patient of FDG-PET were 257 euros for FDG production and 704 euros for the FGD-PET scan, thus totalling 961 euros (in 1999 prices). The cost per patient of CT scans was found to be 391 euros. Verified PET findings induced an upstaging in four patients such that the effectiveness was 81.8% (18/22) for CT and 100% (22/22) for PET. Incremental cost-effectiveness ratios (interpreted as the additional costs of a more effective diagnostic strategy per additional unit of effectiveness, i.e. additionally correctly staged patient, achieved) were 478 euros per correctly staged patient for CT versus "no diagnostics" and 3133 euros for FDG-PET versus CT. Great potential for cost saving was identified in sensitivity analyses for FDG-PET. It is concluded that diagnostic accuracy and the costs of the diagnostic procedures could be measured precisely. FDG-PET was more accurate than CT. Decision-makers who consider savings in treatment costs significant may find the cost-effectiveness ratio of PET to lie within an acceptable range. However, more research is needed to assess the long-term treatment and cost effects of more accurate staging. There is significant potential to improve the technical efficiency of PET.     

FDG-PET in the Locoregional Lymph Node Staging of Non-small Cell Lung Cancer. A Comprehensive Review of the Leuven Lung Cancer Group Experience

Exact staging of locoregional lymph node (LN) disease in non-small cell lung cancer (NSCLC) is of considerable clinical interest. Computed tomography (CT) is not very accurate for this purpose. In the past years, we performed several prospective studies examining the role of [18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in this setting. We compared the accuracy of CT, PET, and PET read with the anatomical aid of CT images in the distinction of early-stage operable cases (i.e., without metastatic LN or with only hilar metastatic LN) versus locally advanced cases (with metastatic mediastinal LN). LNs on PET were recorded as metastatic if the FDG-uptake was more intense than the mediastinal blood pool activity. In 105 patients (or an analysis of 980 LN stations), the accuracy of PET (85%) was significantly better than that of CT (64%; P = 0.0003). Visual correlation with CT images further improved the results to an accuracy of 90%. We also examined the value of different acquisition protocols and interpretation algorithms. The use of Standardized Uptake Values (SUVs) of LNs, or of anatometabolic PET-CT-fusion images, did not prove to be of additional value compared to visual PET-reading and correlation with the CT images. On the condition that positive-LN findings on PET are always confirmed by mediastinoscopy, a simple whole-body acquisition protocol is adequate. We conclude that FDG-PET plays an important role in LN-staging in NSCLC. The very high negative predictive value of mediastinal FDG-PET is able to reduce the need for invasive surgical staging substantially.