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1.  Hounsfield units upon PET/CT are useful in evaluating metastatic regional lymph nodes in patients with oesophageal squamous cell carcinoma 
The British Journal of Radiology  2012;85(1013):606-612.
Objectives
This study evaluated the usefulness of measurements of X-ray attenuation (in Hounsfield units) obtained from unenhanced CT images for attenuation correction of the positron emission tomography (PET) data from PET/CT in the assessment of regional lymph node metastasis in oesophageal squamous cell carcinoma.
Methods
17 patients with oesophageal squamous cell carcinoma underwent surgery after evaluation with PET/CT. After the excised lymph nodes were reviewed, we compared the histopathology and PET/CT findings, and analysed the lymph node metastasis. When 18-F fludeoxyglucose (FDG) uptake in the lymph nodes was focally prominent in comparison with background mediastinal activity (regardless of lymph node size), the lymph nodes were considered to be positive for malignancy by PET/CT. The mean Hounsfield units of mediastinal lymph nodes showing abnormally increased FDG uptake in PET/CT was retrospectively evaluated using images from the unenhanced CT component of PET/CT. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value of mean Hounsfield units for detecting individual lymph node metastases.
Results
For depiction of malignant nodal groups in each lymph node group, the sensitivity, specificity and accuracy of PET/CT based on increased FDG uptake were 58.8%, 74.5% and 70.8%, respectively. For patients with nodal groups that were positive for uptake by PET/CT, the mean attenuation in lymph nodes as measured by CT was 48±13 HU for malignant nodes and 75±18 HU for benign nodes. This difference was statistically significant (p<0.001). Using ROC curve analysis, we determined the cut-off as 71 HU. When we excluded lymph nodes with attenuation higher than 71 HU from the nodes determined as malignant by PET/CT, the specificity and accuracy for detecting metastatic lymph nodes improved to 90.9% and 83.3%, respectively.
Conclusions
When interpreting lymph node metastasis in oesophageal squamous cell carcinoma using PET/CT, the assumption that any lymph node with mean HU>71 is benign can improve diagnostic accuracy.
doi:10.1259/bjr/73516936
PMCID: PMC3479874  PMID: 21304006
2.  Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer 
BMC Cancer  2008;8:165.
Background
Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC).
Methods
One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging.
Results
In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03).
Conclusion
The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis.
doi:10.1186/1471-2407-8-165
PMCID: PMC2430574  PMID: 18541009
3.  Maximum standardized uptake value on PET/CT in preoperative assessment of lymph node metastasis from thoracic esophageal squamous cell carcinoma 
Chinese Journal of Cancer  2014;33(4):211-217.
The presence of lymph node metastasis is an important prognostic factor for patients with esophageal cancer. Accurate assessment of lymph nodes in thoracic esophageal carcinoma is essential for selecting appropriate treatment and forecasting disease progression. Positron emission tomography combined with computed tomography (PET/CT) is becoming an important tool in the workup of esophageal carcinoma. Here, we evaluated the effectiveness of the maximum standardized uptake value (SUVmax) in assessing lymph node metastasis in esophageal squamous cell carcinoma (ESCC) prior to surgery. Fifty-nine surgical patients with pathologically confirmed thoracic ESCC were retrospectively studied. These patients underwent radical esophagectomy with pathologic evaluation of lymph nodes. They all had 18F-FDG PET/CT scans in their preoperative staging procedures. None had a prior history of cancer. The pathologic status and PET/CT SUVmax of lymph nodes were collected to calculate the receiver operating characteristic (ROC) curve and to determine the best cutoff value of the PET/CT SUVmax to distinguish benign from malignant lymph nodes. Lymph node data from 27 others were used for the validation. A total of 323 lymph nodes including 39 metastatic lymph nodes were evaluated in the training cohort, and 117 lymph nodes including 32 metastatic lymph nodes were evaluated in the validation cohort. The cutoff point of the SUVmax for lymph nodes was 4.1, as calculated by ROC curve (sensitivity, 80%; specificity, 92%; accuracy, 90%). When this cutoff value was applied to the validation cohort, a sensitivity, a specificity, and an accuracy of 81%, 88%, and 86%, respectively, were obtained. These results suggest that the SUVmax of lymph nodes predicts malignancy. Indeed, when an SUVmax of 4.1 was used instead of 2.5, FDG-PET/CT was more accurate in assessing nodal metastasis.
doi:10.5732/cjc.013.10039
PMCID: PMC3975187  PMID: 24559853
SUVmax; esophageal squamous cell carcinoma; cutoff value; esophagectomy; lymph nodes
4.  Diagnostic Value of EBUS-TBNA for Lung Cancer with Non-Enlarged Lymph Nodes: A Study in a Tuberculosis-Endemic Country 
PLoS ONE  2011;6(2):e16877.
Background
In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET.
Methods
We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA.
Results
The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET.
Conclusion
In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.
doi:10.1371/journal.pone.0016877
PMCID: PMC3045379  PMID: 21364919
5.  Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer 
Frontiers in Oncology  2013;2:208.
The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.
doi:10.3389/fonc.2012.00208
PMCID: PMC3539654  PMID: 23316478
PET; non-small cell lung cancer; staging; response assessment; follow-up
6.  Paraaortic lymph node metastasis in patients with intra-abdominal malignancies: CT vs PET 
AIM: To compare the diagnostic accuracy of computed tomography (CT) and positron emission tomography (PET) for the preoperative detection of paraaortic lymph node (PAN) metastasis in patients with intra-abdominal malignancies.
METHODS: Sixty-six patients with intra-abdominal malignancies who underwent both CT and PET before lymphadenectomy were included in this study. Histopathologically, 13 patients had metastatic PAN, while 53 had non-metastatic PAN. The CT criteria for metastasis were: short diameter of > 8 mm, lobular or irregular shape, and/or combined ancillary findings, including necrosis, conglomeration, vessel encasement, and infiltration. The PET criterion was positive fluorodeoxyglucose (FDG) uptake. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of both modalities were compared with the pathologic findings, and the false positive and false negative cases with both CT and PET were analyzed.
RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy of CT were 61.5%, 84.9%, 50%, 90% and 80.3%, respectively. For PET, the percentages were 46.2%, 100%, 100%, 88.3%, and 89.4%. Additionally, there were 8 false positive CT cases (8/53, 15.1%) and zero false positive PET cases. Of the 13 metastatic PANs, there were 5 false negative CT scans (38.5%) and 7 (53.9%) false negative PET scans.
CONCLUSION: For detecting PAN metastasis, CT is more sensitive than PET, while PET is more specific.
doi:10.3748/wjg.15.4434
PMCID: PMC2747065  PMID: 19764096
Malignancy; Paraaortic lymph node; Computed tomography; Positron emission tomography; Sensitivity; Specificity
7.  Staging the axilla in breast cancer patients with 18F-FDG PET: how small are the metastases that we can detect with new generation clinical PET systems? 
Purpose
Point spread function (PSF) reconstruction improves spatial resolution throughout the entire field of view of a PET system and can detect smaller metastatic deposits than conventional algorithms such as OSEM. We assessed the impact of PSF reconstruction on quantitative values and diagnostic accuracy for axillary staging of breast cancer patients, compared with an OSEM reconstruction, with emphasis on the size of nodal metastases.
Methods
This was a prospective study in a single referral centre in which 50 patients underwent an 18F-FDG PET examination before axillary lymph node dissection. PET data were reconstructed with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by a pathologist who measured the largest nodal metastasis per axilla. This size was used to evaluate PET diagnostic performance.
Results
On pathology, 34 patients (68 %) had nodal involvement. Overall, the median size of the largest nodal metastasis per axilla was 7 mm (range 0.5 – 40 mm). PSF reconstruction detected more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM SUVmax ratio was 1.66 (95 % CI 1.01 – 2.32). The sensitivities of PSF and OSEM reconstructions were, respectively, 96 % and 92 % in patients with a largest nodal metastasis of >7 mm, 60 % and 40 % in patients with a largest nodal metastasis of ≤7 mm, and 92 % and 69 % in patients with a primary tumour ≤30 mm. Biggerstaff graphical comparison showed that globally PSF reconstruction was superior to OSEM reconstruction. The median sizes of the largest nodal metastasis in patients with nodal involvement not detected by either PSF or OSEM reconstruction, detected by PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6 and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected by PSF reconstruction but not by OSEM reconstruction, the smallest detectable metastasis was 1.8 mm.
Conclusion
As a result of better activity recovery, PET with PSF reconstruction performed better than PET with OSEM reconstruction in detecting nodal metastases ≤7 mm. However, its sensitivity is still insufficient for it to replace surgical approaches for axillary staging. PET with PSF reconstruction could be used to perform sentinel node biopsy more safely in patients with a primary tumour ≤30 mm and with unremarkable PET results in the axilla.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-014-2689-7) contains supplementary material, which is available to authorized users.
doi:10.1007/s00259-014-2689-7
PMCID: PMC4006125  PMID: 24562642
PET/CT; Breast cancer; Axillary staging; Fluorodeoxyglucose; PSF reconstruction
8.  A pilot study of 4′-[methyl-11C]-thiothymidine PET/CT for detection of regional lymph node metastasis in non-small cell lung cancer 
EJNMMI Research  2014;4:10.
Background
4′-[methyl-11C]-thiothymidine (4DST) is a novel positron emission tomography (PET) tracer to assess proliferation of malignancy. The diagnostic abilities of 4DST and 2-deoxy-2-18 F-fluoro-d-glucose (FDG) for detecting regional lymph node (LN) metastases of non-small cell lung cancer (NSCLC) were prospectively compared. In addition, the relationship between the PET result and the patient's prognosis was evaluated.
Methods
A total of 31 patients with NSCLC underwent 4DST PET/computed tomography (CT) and FDG PET/CT. The PET/CT images were evaluated qualitatively and quantitatively for focal uptake of each PET tracer, according to the staging system of the American Joint Committee on Cancer. Surgical and histological results provided the reference standards. Patients were followed for up to two years to assess disease-free survival.
Results
On a per-lesion basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for LN staging were 82%, 72%, 32%, 96%, and 73%, respectively, for 4DST, and 29%, 86%, 25%, 88%, and 78%, respectively, for FDG. The sensitivity of 4DST was significantly higher than that of FDG (P < 0.001). The disease-free survival rate with positive 4DST uptake in nodal lesions was 0.35, which was considerably lower than the rate of 0.83 with negative findings (P = 0.04). Among the factors tested, nodal staging by 4DST was the most influential prognostic factor (P = 0.05) in predicting the presence of a previously existing spread lesion or of a recurrence over the course of 2 years.
Conclusion
4DST PET/CT is sensitive for detecting mediastinal lymph node metastasis in NSCLC, but its low specificity is a limitation. However, it may be helpful in predicting the prognosis of NSCLC.
doi:10.1186/2191-219X-4-10
PMCID: PMC3976537  PMID: 24593883
4DST; FDG-PET/CT; Lymph node metastasis; Non-small cell lung cancer (NSCLC); Cell proliferation
9.  Positron Emission Tomography for the Assessment of Myocardial Viability 
Executive Summary
Objective
The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques.
Background
Left Ventricular Viability
Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization.
For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left ventricular (LV) viability is, therefore, critical in deciding whether a patient with coronary artery disease and severe LV dysfunction should undergo revascularization, receive a heart transplant, or remain on medical therapy.
Assessment of Left Ventricular Viability
Techniques for assessing myocardial viability depend on the measurement of a specific characteristic of viable myocytes such as cell membrane integrity, preserved metabolism, mitochondria integrity, and preserved contractile reserve. In Ontario, single photon emission computed tomography (SPECT) using radioactive 201thallium is the most commonly used technique followed by dobutamine echocardiography. Newer techniques include SPECT using technetium tracers, cardiac magnetic resonance imaging, and PET, the subject of this review.
Positron Emission Tomography
PET is a nuclear imaging technique based on the metabolism of radioactive analogs of normal substrates such as glucose and water. The radiopharmaceutical used most frequently in myocardial viability assessment is F18 fluorodeoxyglucose (FDG), a glucose analog. The procedure involves the intravenous administration of FDG under controlled glycemic conditions, and imaging with a PET scanner. The images are reconstructed using computer software and analyzed visually or semi-quantitatively, often in conjunction with perfusion images. Dysfunctional but stunned myocardium is characterized by normal perfusion and normal FDG uptake; hibernating myocardium exhibits reduced perfusion and normal/enhanced FDG uptake (perfusion/metabolism mismatch), whereas scar tissue is characterized by reduction in both perfusion and FDG uptake (perfusion/metabolism match).
Review Strategy
The Medical Advisory Secretariat used a search strategy similar to that used in the 2001 ICES review to identify English language reports of health technology assessments and primary studies in selected databases, published from January 1, 2001 to April 20, 2005. Patients of interest were those with CAD and severe ventricular dysfunction being considered for revascularization that had undergone viability assessment using either PET and/or other noninvasive techniques. The outcomes of interest were diagnostic and predictive accuracy with respect to recovery of regional or global LV function, long-term survival and cardiac events, and quality of life. Other outcomes of interest were impact on treatment decision, adverse events, and cost-effectiveness ratios.
Of 456 citations, 8 systematic reviews/meta-analyses and 37 reports on primary studies met the selection criteria. The reports were categorized using the Medical Advisory Secretariat levels of evidence system, and the quality of the reports was assessed using the criteria of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) developed by the Centre for Dissemination of Research (National Health Service, United Kingdom). Analysis of sensitivity, specificity, predictive values and likelihood ratios were conducted for all data as well as stratified by mean left ventricular ejection fraction (LVEF). There were no randomized controlled trials. The included studies compared PET with one or more other noninvasive viability tests on the same group of patients or examined the long-term outcomes of PET viability assessments. The quality assessment showed that about 50% or more of the studies had selection bias, interpreted tests without blinding, excluded uninterpretable segments in the analysis, or did not have clearly stated selection criteria. Data from the above studies were integrated with data from the 2001 ICES review for analysis and interpretation.
Summary of Findings
The evidence was derived from populations with moderate to severe ischemic LV dysfunction with an overall quality that ranges from moderate to low.
PET appears to be a safe technique for assessing myocardial viability.
CAD patients with moderate to severe ischemic LV dysfunction and residual viable myocardium had significantly lower 2-year mortality rate (3.2%) and higher event-free survival rates (92% at 3 years) when treated with revascularization than those who were not revascularized but were treated medically (16% mortality at 2-years and 48% 3-year event-free survival).
A large meta-analysis and moderate quality studies of diagnostic accuracy consistently showed that compared to other noninvasive diagnostic tests such as thallium SPECT and echocardiography, FDG PET has:
Higher sensitivity (median 90%, range 71%–100%) and better negative likelihood ratio (median 0.16, range 0–0.38; ideal <0.1) for predicting regional myocardial function recovery after revascularization.
Specificity (median 73%, range 33%–91%) that is similar to other radionuclide imaging but lower than that of dobutamine echocardiography
Less useful positive likelihood ratio (median 3.1, range 1.4 –9.2; ideal>10) for predicting segmental function recovery.
Taking positive and negative likelihood ratios together suggests that FDG PET and dobutamine echocardiography may produce small but sometimes important changes in the probability of recovering regional wall motion after revascularization.
Given its higher sensitivity, PET is less likely to produce false positive results in myocardial viability. PET, therefore, has the potential to identify some patients who might benefit from revascularization, but who would not have been identified as suitable candidates for revascularization using thallium SPECT or dobutamine echocardiography.
PET appears to be superior to other nuclear imaging techniques including SPECT with 201thallium or technetium labelled tracers, although recent studies suggest that FDG SPECT may have comparable diagnostic accuracy as FDG PET for predicting regional and global LV function recovery.
No firm conclusion can be reached about the incremental value of PET over other noninvasive techniques for predicting global function improvement or long-term outcomes in the most important target population (patients with severe ischemic LV dysfunction) due to lack of direct comparison.
An Ontario-based economic analysis showed that in people with CAD and severe LV dysfunction and who were found to have no viable myocardium or indeterminate results by thallium SPECT, the use of PET as a follow-up assessment would likely result in lower cost and better 5-year survival compared to the use of thallium SPECT alone. The projected annual budget impact of adding PET under the above scenario was estimated to range from $1.5 million to $2.3 million.
Conclusion
In patients with severe LV dysfunction, that are deemed to have no viable myocardium or indeterminate results in assessments using other noninvasive tests, PET may have a role in further identifying patients who may benefit from revascularization. No firm conclusion can be drawn on the impact of PET viability assessment on long-term clinical outcomes in the most important target population (i.e. patients with severe LV dysfunction).
PMCID: PMC3385418  PMID: 23074467
10.  Implications of False Negative and False Positive Diagnosis in Lymph Node Staging of NSCLC by Means of 18F-FDG PET/CT 
PLoS ONE  2013;8(10):e78552.
Background
Integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is widely performed in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC). However, the diagnostic efficiency of PET/CT remains controversial. This retrospective study is to evaluate the accuracy of PET/CT and the characteristics of false negatives and false positives to improve specificity and sensitivity.
Methods
219 NSCLC patients with systematic lymph node dissection or sampling underwent preoperative PET/CT scan. Nodal uptake with a maximum standardized uptake value (SUVmax) >2.5 was interpreted as PET/CT positive. The results of PET/CT were compared with the histopathological findings. The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficiency of PET/CT. Univariate and multivariate analysis were conducted to detect risk factors of false negatives and false positives.
Results
The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/ CT in detecting HMLN metastases were 74.2% (49/66), 73.2% (112/153), 54.4% (49/90), 86.8% (112/129), and 73.5% (161/219). The ROC curve had an area under curve (AUC) of 0.791 (95% CI 0.723-0.860). The incidence of false negative HMLN metastases was 13.2% (17 of 129 patients). Factors that are significantly associated with false negatives are: concurrent lung disease or diabetes (p<0.001), non-adenocarcinoma (p<0.001), and SUVmax of primary tumor >4.0 (p=0.009). Postoperatively, 45.5% (41/90) patients were confirmed as false positive cases. The univariate analysis indicated age > 65 years old (p=0.009), well differentiation (p=0.002), and SUVmax of primary tumor ≦4.0 (p=0.007) as risk factors for false positive uptake.
Conclusion
The SUVmax of HMLN is a predictor of malignancy. Lymph node staging using PET/CT is far from equal to pathological staging account of some risk factors. This study may provide some aids to pre-therapy evaluation and decision-making.
doi:10.1371/journal.pone.0078552
PMCID: PMC3808350  PMID: 24205256
11.  Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET) 
Thorax  1997;52(5):438-441.
BACKGROUND: A study was undertaken to investigate the accuracy of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D- glucose (FDG) in the thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty six patients with focal pulmonary tumours who underwent preoperative computed tomographic (CT) and FDG- PET scanning were evaluated retrospectively. Thirty two patients had NSCLC and 14 patients had a benign process. The final diagnosis was established by means of histopathological examination at thoracotomy, and the nodal classification in patients with lung cancer was performed by thorough dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80% sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and 59.4% accurate. The absence of lymph node tumour involvement was identified by FDG-PET in all 12 patients with NO disease compared with nine by CT scanning. Lymph node metastases were correctly detected by FDG-PET in three of five patients with N1 disease compared with two by CT scanning, in nine of 11 with N2 disease compared with six by CT scanning, an in all four with N3 nodes compared with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to resectability, FDG-PET could differentiate reliably between patients with N1/N2 disease and those with unresectable N3 disease. 



PMCID: PMC1758560  PMID: 9176535
12.  FDG-PET-based Prognostic Nomograms for Locally Advanced Cervical Cancer 
Gynecologic oncology  2012;127(1):136-140.
Purpose:
Patients with cervical cancer of the same clinical FIGO stage can have distinctly different outcomes. We previously found that several individual factors determined by positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG), including primary cervical tumor maximum standardized uptake value (SUVmax), cervical tumor volume, and highest level of lymph node (LN) involvement, provide prognostic information about patient outcome. For this study, we aimed to evaluate the combined prognostic value of these three factors assessed on pretreatment FDG-PET for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS).
Patients and Methods:
The study included 482 cervical cancer patients, FIGO stage Ia2-IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, LN status, and tumor SUVmax were recorded. Using these PET-based factors, prognostic nomograms based on Cox regression were created for RFS, DSS, and OS. The prediction accuracies of the nomograms were measured using the concordance index (c-statistic).
Results:
Fifty-seven percent of patients had FDG-avid lymph nodes on PET; the highest level of nodal involvement was pelvic in 186, para-aortic in 65, and supraclavicular in 26. The average cervix tumor SUVmax was 11.8 (range, 2.0–50.4). PET tumor volume ranged from 3.0 to 535.7 cm3 (average, 65.2 cm3). The median follow-up was 57.5 months for patients alive at the time of last follow-up. PET LN status had the greatest influence on outcome and SUVmax was the second most important factor for all 3 endpoints. The c-statistics for the 3 nomograms were 0.756 for RFS, 0.733 for DSS, and 0.649 for OS.
Conclusions:
Pretreatment FDG-PET LN status, cervical tumor SUVmax, and PET tumor volume combined in a nomogram create good models for cervical cancer RFS, DSS, and OS.
doi:10.1016/j.ygyno.2012.06.027
PMCID: PMC3991305  PMID: 22735785
FDG-PET; lymph node; prognosis; cervix; nomogram
13.  Role and interpretation of FDG-PET/CT in HIV patients with fever of unknown origin: a prospective study 
Purpose of the study
Fever of unknown origin (FUO) is a challenging clinical entity in HIV patients. FDG-PET/CT is well validated in the work-up of FUO in HIV-negative patients but in HIV viremic patients, metabolism of HIV reactive lymph nodes could decrease its specificity. We prospectively evaluated the usefulness of FDG-PET/CT in FUO in HIV-positive patients and in particular whether HIV viremia impacts on FDG-PET/CT performance.
Methods
FDG-PET/CT was performed in 20 HIV patients with FUO and compared with FDG-PET/CT in 10 HIV viremic patients without FUO. Final diagnosis for FUO was based on histopathology, microbiology, or clinical and imaging follow-up. Mode of diagnosis, accordance of FDG-PET/CT with final diagnosis, localization of invasive diagnosis procedures was recorded in order to assess usefulness of FDG-PET/CT.
Results
FDG-PET/CT showed a different pattern in FUO and asymptomatic viremic patients. Reactive HIV lymph nodes in asymptomatic viremic patients were mostly peripheral with mean SUVmax of 6.5. In patients with FUO and underlying focal pathologies, hypermetabolic lymph nodes were central with mean SUVmax of 11.6. Presence of central lymph nodes with high FDG uptake in had a 100% specificity for focal pathology, even in viremic patients and absence of these had 100% negative predictive value. Lymph node biopsy in central hypermetabolic areas allowed identifying underlying disease in all FUO patients. For peripheral lymph nodes, a ROC curve was built in order to define the best cut-off of SUVmax for biopsy: SUVmax of 6–8 showed a sensitivity of 62.5% and specificity of 75%. Lymph nodes with SUVmax<4 had sensitivity of 0%.
Conclusions
FDG-PET/CT contributed to the diagnosis or exclusion of a focal etiology of the febrile state in 80% of HIV patients with FUO. Although number of patients was small, we could highlight several clear-cut features to help interpreting FDG-PET/CT in HIV patients with FUO. As in HIV-negative patients, we showed the usefulness of FDG-PET/CT in FUO in HIV patients even if they are viremic.
doi:10.7448/IAS.15.6.18107
PMCID: PMC3512434
14.  Integrated FDG‐PET/CT does not make invasive staging of the intrathoracic lymph nodes in non‐small cell lung cancer redundant: a prospective study 
Thorax  2007;62(8):696-701.
Background
Staging of non‐small cell lung cancer (NSCLC) is important for determining choice of treatment and prognosis. The accuracy of FDG‐PET scans for staging of lymph nodes is too low to replace invasive nodal staging. It is unknown whether the accuracy of integrated FDG‐PET/CT scanning makes invasive staging redundant.
Methods
In a prospective study, the mediastinal and/or hilar lymph nodes in patients with proven NSCLC were investigated with integrated FDG‐PET/CT scanning. Pathological confirmation of all suspect lymph nodes was obtained to calculate the accuracy of the fusion images. In addition, the use of the standardised uptake value (SUV) in the staging of intrathoracic lymph nodes was analysed.
Results
105 intrathoracic lymph node stations from 52 patients with NSCLC were characterised. The prevalence of malignancy in the lymph nodes was 36%. The sensitivity of the integrated FDG‐PET/CT scan to detect malignant lymph nodes was 84% and its specificity was 85% (positive likelihood ratio 5.64, negative likelihood ratio 0.19). SUVmax, SUVmean and the SUVmax/SUVliver ratio were all significantly higher in malignant than in benign lymph nodes. The area under the receiver operating curve did not differ between these three quantitative variables, but the highest accuracy was found with the SUVmax/SUVliver ratio. At a cut‐off value of 1.5 for the SUVmax/SUVliver ratio, the sensitivity and specificity to detect malignant lymph node invasion were 82% and 93%, respectively.
Conclusion
The accuracy of integrated FDG‐PET/CT scanning is too low to replace invasive intrathoracic lymph node staging in patients with NSCLC. The visual interpretation of the fusion images of the integrated FDG‐PET/CT scan can be replaced by the quantitative variable SUVmax/SUVliver without loss of accuracy for intrathoracic lymph node staging.
doi:10.1136/thx.2006.072959
PMCID: PMC2117288  PMID: 17687098
15.  Factors Associated with Positive F-18 Flurodeoxyglucose Positron Emission Tomography Before Thyroidectomy in Patients with Papillary Thyroid Carcinoma 
Thyroid  2012;22(7):725-729.
Background
The role for pre-thyroidectomy (pre-Tx) imaging with F-18 flurodeoxyglucose (FDG) positron emission tomography (PET), FDG PET–computed tomography (CT), in differentiated thyroid cancer is controversial as is the significance of positive and negative FDG uptake in this setting. We reviewed the records of patients with papillary thyroid carcinoma (PTC) who had pre-Tx FDG PET-CT to determine whether FDG uptake was associated with features noted on pre-Tx ultrasonography (US) and parameters determined after post-Tx.
Methods
Patients were selected for a retrospective review of their records if they had a total Tx with central lymph node dissection for PTC and pre-Tx FDG PET-CT and US between 2006 and 2009. Sixty patients who met these criteria were studied. Patients who had a history of head and neck irradiation, surgery, or sclerotherapy with ethanol in the last 3 months were excluded. The clinicopathologic factors—age, sex, size, tumor–node–metastasis (TNM) staging, the presence of extrathyroidal extention, multifocality, cervical lymph node metastases (CLNM), Hashimoto thyroiditis, and US characteristics—were evaluated to determine whether they were associated with positive pre-Tx FDG uptake.
Results
Forty-three (71.6%) of patients in the study had positive FDG uptake. Larger tumors and the presence of CLNM were associated with a greater likelihood of positive FDG uptake. The sensitivity, specificity, positive predictive value, and negative predictive value for CLNM detection by FDG PET-CT showed low statistical values. When considering the excellence of US for evaluating a thyroid nodule size and the presence of CLNM, the clinical value of pre-Tx FDG PET-CT is comparatively limited.
Conclusion
Pre-Tx FDG PET is not recommended for routine use in patients with PTC.
doi:10.1089/thy.2011.0031
PMCID: PMC3387768  PMID: 22524470
16.  The Role of 18F-FDG PET/CT in the Evaluation of Gastric Cancer Recurrence after Curative Gastrectomy 
Yonsei Medical Journal  2010;52(1):81-88.
Purpose
18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans are frequently performed for the screening or staging of malignant tumors. This study aimed to assess the usefulness of 18F-FDG PET/CT in detection of gastric cancer recurrence after curative gastrectomy.
Materials and Methods
Eighty nine patients who had undergone curative gastrectomy due to gastric cancer and had 18F-FDG PET/CT and contrast CT scans within 2 weeks for surveillance in asymptomatic patients (n = 11) or to clarify suspected recurrence (n = 78) were consecutively collected and retrospectively analyzed. They had clinical follow-up for at least 12 months after PET/CT and CT scans.
Results
Fifteen of the 89 patients (16.9%) were diagnosed with recurrent gastric cancer in 21 organs. Forty one organs showed an increase in FDG uptake, and only 9 of these organs were diagnosed with recurrent gastric cancer by 18F-FDG PET/CT. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the 18F-FDG PET/CT were 42.9%, 59.7%, 29.3%, 78.2%, and 57.3%, respectively. On the CT scan, 18 of 21 recurrent gastric cancers were detected, and 7 cases were in agreement with the 18F-FDG PET/CT. The sensitivity and specificity of the CT scan were 85.8% and 87.3%, respectively, which are superior to the 18F-FDG PET/CT. When we diagnosed a recurrence based on either 18F-FDG PET/CT or CT scans, the sensitivity increased to 95.2% and the specificity decreased to 45.6%, when compared with the contrast CT scan alone.
Conclusion
18F-FDG PET/CT is an insufficient diagnostic method in detection of recurrence after curative gastrectomy, and even less accurate than contrast CT scan alone.
doi:10.3349/ymj.2011.52.1.81
PMCID: PMC3017712  PMID: 21155039
Gastric cancer; recurrence; 18F-FDG PET/CT scan; contrast CT scan
17.  Bone Scan or 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography; Which Modality Better Shows Bone Metastases of Breast Cancer? 
Breast Care  2012;7(5):389-393.
Background
In this multicenter study, we aimed to compare concurrent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and bone scan results of breast cancer patient.
Patients and Methods
162 patients with breast cancer (158 female, 4 male; mean age 50.6 years) were included in the study. FDG PET/CT examination was performed in all patients, and concurrent bone scintigraphy in 68 patients. The results of FDG PET/CT and bone scan were compared.
Results
132 of the 162 patients were operated on because of breast cancer. 89 patients had metastasis, and 4 had recurrent disease according to FDG PET/CT results. Metastatic sites in order of frequency were lymph nodes, bone, lung, liver, adrenal gland, local skin or muscle, brain, and peritoneum (peritonitis carcinomatosa). The sensitivity, specificity, accuracy, and negative and positive predictive value of bone scintigraphy versus FDG PET/CT were 96 vs. 100%, 100 vs. 98%, 100 vs. 83%, 100 vs. 100%, and 90 vs. 100%, respectively.
Conclusion
Although the 2 modalities were in concordance with each other, in 5 (21%) cases, FDG PET/CT could not show bone metastasis which were detected on bone scintigraphy. Hence, bone scintigraphy was superior to FDG PET/CT in the determination of bone metastasis derived from breast cancer. However, FDG PET/CT should be considered for soft tissue metastasis.
doi:10.1159/000341559
PMCID: PMC3518943  PMID: 24647778
Breast cancer; Bone metastasis; FDG PET/CT; Bone scintigraphy
18.  PET/CT versus body coil PET/MRI: how low can you go? 
Insights into Imaging  2013;4(4):481-490.
Objectives
The purpose of this study was to evaluate if positron emission tomography (PET)/magnetic resonance imaging (MRI) with just one gradient echo sequence using the body coil is diagnostically sufficient compared with a standard, low-dose non-contrast-enhanced PET/computed tomography (CT) concerning overall diagnostic accuracy, lesion detectability, size and conspicuity evaluation.
Methods and materials
Sixty-three patients (mean age 58 years, range 19–86 years; 23 women, 40 men) referred for either staging or restaging/follow-up of various malignant tumours (malignant melanoma, lung cancer, breast cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, CUP, gynaecology tumours, pleural mesothelioma, oesophageal cancer, colorectal cancer, stomach cancer) were prospectively included. Imaging was conducted using a tri-modality PET/CT-MR set-up (full ring, time-of-flight Discovery PET/CT 690, 3 T Discovery MR 750, both GE Healthcare, Waukesha, WI). All patients were positioned on a dedicated PET/CT- and MR-compatible examination table, allowing for patient transport from the MR system to the PET/CT without patient movement. In accordance with RECIST 1.1 criteria, measurements of the maximum lesion diameters on CT and MR images were obtained. In lymph nodes, the short axis was measured. A four-point scale was used for assessment of lesion conspicuity: 1 (>25 % of lesion borders definable), 2 (25–50 %), 3 (50–75 %) and 4 (>75 %). For each lesion the corresponding anatomical structure was noted based on anatomical information of the spatially co-registered PET/CT and PET/MRI image sections. Additionally, lesions were divided into three categories: “tumour mass”, “lymph nodes” and “lesions”. Differences in overall lesion detectability and conspicuity in PET/CT and PET/MRI, as well as differences in detectability based on the localisation and lesion type, were analysed by Wilcoxon signed rank test.
Results
A total of 126 PET-positive lesions were evaluated. Overall, no statistically significant superiority of PET/CT over PET/MRI or vice versa in terms of lesion conspicuity was found (p = 0.095; mean score CT 2.93, mean score MRI 2.75). A statistically significant superiority concerning conspicuity of PET/CT over PET/MRI was found in pulmonary lesions (p = 0.016). Additionally, a statistically significant superiority of PET/CT over PET/MRI in “lymph nodes” regarding lesion conspicuity was also found (p = 0.033). A higher mean score concerning bone lesions were found for PET/CT compared with PET/MRI; however, these differences did not achieve statistical significance.
Conclusion
Overall, PET/MRI with body coil acquisition does not match entirely the diagnostic accuracy of standard low-dose PET/CT. Thus, it might only serve as a back-up solution in very few patients. Overall, more time needs to be invested on the MR imaging part (higher matrix, more breath-holds, additional surface coil acquired sequences) to match up with the standard low-dose PET/CT.
Main Messages
• Evaluation of whether PET/MRI with one sequence using body coil is diagnostically sufficient compared with PET/CT
• PET/MRI with body coil does not match entirely the diagnostic accuracy of standard low-dose PET/CT
• PET/MRI might only serve as a backup solution in patients.
doi:10.1007/s13244-013-0247-7
PMCID: PMC3731468  PMID: 23673453
PET/CT; PET/MRI; Body coil MRI; Lesion detection; Cancer imaging; Diagnostic accuracy
19.  Role of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in the detection of recurrence in patients with cervical cancer 
Introduction:
Treatment of cervical cancer is usually surgery in the early stages and radiotherapy or chemoradiotherapy in more advanced stages of the disease. Recurrence may occur in multiple sites following primary treatment. Although recurrent metastatic disease is not curable, surgical treatment may be of great help if locoregional recurrence is detected early. Fluorine-18 Fluorodeoxyglucose positron emission tomography - computed tomography (F-18 FDG PET/CT) forms an important part of investigations in the diagnosis of clinically suspicious recurrent cervical cancer.
Objective:
To assess the role of F-18 FDG PET/CT in diagnosing recurrence in patients with clinical suspicion of recurrent cervical cancer.
Materials and Methods:
We retrospectively evaluated 53 histopathologically proved patients of cervical cancer. All the patients had been treated with either surgery/radiation therapy with or without chemotherapy. The standard PET/CT acquisition protocol, with delayed post void static pelvic images, wherever required, was followed in all patients. Significant uptake of FDG in the lymph nodes was considered to be a recurrence suggestive of metastasis. Para-aortic lymph nodal involvement was considered to be distant metastasis. Any significant uptake in the lung nodule on FDG PET was evaluated either by histological confirmation, by taking fine needle aspiration cytology (FNAC), or by a follow-up chest CT done after three months.
Results:
Of the 53 patients with clinically equivocal recurrence, FDG PET/CT suggested recurrence in 41 patients (local recurrence in 14 patients and distant recurrence/metastasis with or without local recurrence in 27 patients). It had a sensitivity of 97.5%, a specificity of 63.6%, positive predictive value of 90.9%, and negative predictive value of 87.5%.
Conclusion:
PET/CT appears to have an important role in detecting recurrence following primary treatment of cervical cancer. The high positive and negative predictive values of PET/CT may be helpful in planning management of recurrent cervical cancer.
doi:10.4103/0972-3919.121966
PMCID: PMC3866666  PMID: 24379531
Cancer of the cervix; chemoradiotherapy; fluorine-18 fluorodeoxyglucose; positron emission tomography - computed tomography; recurrence
20.  F18-fluorodeoxyglucose-positron emission tomography and computed tomography is not accurate in preoperative staging of gastric cancer 
Purpose
To investigate the clinical benefits of F18-fluorodeoxyglucose-positron emission tomography and computed tomography (18F-FDG-PET/CT) over multi-detector row CT (MDCT) in preoperative staging of gastric cancer.
Methods
FDG-PET/CT and MDCT were performed on 78 patients with gastric cancer pathologically diagnosed by endoscopy. The accuracy of radiologic staging retrospectively was compared to pathologic result after curative resection.
Results
Primary tumors were detected in 51 (65.4%) patients with 18F-FDG-PET/CT, and 47 (60.3%) patients with MDCT. Regarding detection of lymph node metastasis, the sensitivity of FDG-PET/CT was 51.5% with an accuracy of 71.8%, whereas those of MDCT were 69.7% and 69.2%, respectively. The sensitivity of 18F-FDG-PET/CT for a primary tumor with signet ring cell carcinoma was lower than that of 18F-FDG-PET/CT for a primary tumor with non-signet ring cell carcinoma (35.3% vs. 73.8%, P < 0.01).
Conclusion
Due to its low sensitivity, 18F-FDG-PET/CT alone shows no definite clinical benefit for prediction of lymph node metastasis in preoperative staging of gastric cancer.
doi:10.4174/jkss.2011.81.2.104
PMCID: PMC3204564  PMID: 22066108
Gastric cancer; 18F-FDG-PET/CT; MDCT; Preoperative staging
21.  A Prospective Analysis of Positron Emission Tomography and Conventional Imaging for Detection of Stage IV Metastatic Melanoma in Patients Undergoing Metastasectomy 
Annals of surgical oncology  2004;11(8):731-738.
Background
Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy.
Methods
This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations.
Results
Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively.
Conclusions
Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.
doi:10.1245/ASO.2004.01.023
PMCID: PMC2227906  PMID: 15249335
Melanoma; Cancer; FDG-PET; Imaging; Metastasectomy; Surgery
22.  Clinical usefulness of 18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy 
AIM: To evaluate the clinical usefulness of 18F-fluorodeoxyglucose positron emission and computed tomography (18F-FDG PET/CT) in restaging of esophageal cancer after surgical resection and radiotherapy.
METHODS: Between January 2007 and Aug 2008, twenty histopathologically diagnosed esophageal cancer patients underwent 25 PET/CT scans (three patients had two scans and one patient had three scans) for restaging after surgical resection and radiotherapy. The standard reference for tumor recurrence was histopathologic confirmation or clinical follow-up for at least ten months after 18F-FDG PET/CT examinations.
RESULTS: Tumor recurrence was confirmed histopathologically in seven of the 20 patients (35%) and by clinical and radiological follow-up in 13 (65%). 18F-FDG PET/CT was positive in 14 patients (68.4%) and negative in six (31.6%). 18F-FDG PET/CT was true positive in 11 patients, false positive in three and true negative in six. Overall, the accuracy of 18F-FDG PET/CT was 85%, negative predictive value (NPV) was 100%, and positive predictive value (PPV) was 78.6%. The three false positive PET/CT findings comprised chronic inflammation of mediastinal lymph nodes (n = 2) and anastomosis inflammation (n = 1). PET/CT demonstrated distant metastasis in 10 patients. 18F-FDG PET/CT imaging-guided salvage treatment in nine patients was performed. Treatment regimens were changed in 12 (60%) patients after introducing 18F-FDG PET/CT into their conventional post-treatment follow-up program.
CONCLUSION: Whole body 18F-FDG PET/CT is effective in detecting relapse of esophageal cancer after surgical resection and radiotherapy. It could also have important clinical impact on the management of esophageal cancer, influencing both clinical restaging and salvage treatment of patients.
doi:10.3748/wjg.15.1836
PMCID: PMC2670410  PMID: 19370780
18F-fluorodeoxyglucose; Positron emission tomography/computed tomography; Esophageal cancer; Surgical resection; Radiotherapy radiation; Restaging
23.  Value of Surveillance 18F-FDG PET/CT in Colorectal Cancer: Comparison with Conventional Imaging Studies 
Purpose
To assess the value of PET/CT for detecting local or distant recurrence in patients who undergo surgery for colorectal cancer (CRC) and to compare the accuracy of PET/CT to that of conventional imaging studies (CIS).
Methods
Tumor surveillance PET/CT scans done between March 2005 and December 2009 of disease-free patients after surgery with or without adjuvant chemotherapy for CRC were retrospectively studied. CIS (serial enhanced CT from lung base to pelvis and plain chest radiograph) were performed within 1 month of PET/CT. We excluded patients with distant metastasis on initial staging, a known recurrent tumor, and a lack of follow-up imaging. The final diagnosis was based on at least 6 months of follow-up with colonoscopy, biopsy, and serial imaging studies in combination with carcinoembryonic antigen levels.
Results
A total of 262 PET/CT scans of 245 patients were included. Local and distant recurrences were detected in 27 cases (10.3%). On case-based analysis, the overall sensitivity, specificity, and accuracy were 100, 97.0, and 97.3% for PET/CT and 85.1, 97.0, and 95.8% for CIS, respectively. On lesion-based analysis, PET/CT detected more lesions compared to CIS in local recurrence and lung metastasis. PET/CT and CIS detected the same number of lesions in abdominal lymph nodes, hepatic metastasis, and peritoneal carcinomatosis. PET/CT detected two more metachronous tumors than did CIS in the lung and thyroid gland.
Conclusion
PET/CT detected more recurrences in patients who underwent surgery for CRC than did CIS and had the additional advantage of evaluating the entire body during a single scan.
doi:10.1007/s13139-012-0145-9
PMCID: PMC4043040  PMID: 24900059
Colorectal cancer; PET/CT; Surveillance
24.  Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients 
Purpose
The aim of this study was to assess the accuracy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to visualize lymph node metastases before the start of neoadjuvant chemotherapy and to determine how often the visualization is sufficiently prominent to allow monitoring of the axillary response.
Methods
Thirty-eight patients with invasive breast cancer of >3 cm and/or lymph node metastasis underwent FDG PET/CT before neoadjuvant chemotherapy. The results of the FDG PET/CT were compared with those from ultrasonography with fine-needle aspiration (FNA) cytology or sentinel node biopsy. Patients suitable for response monitoring of the axilla were defined as having either a maximum standardized uptake value (SUVmax) ≥ 2.5 or a tumour to background ratio ≥5 in the most intense lymph node.
Results
The sensitivity and specificity of FDG PET/CT in detecting axillary involvement were 97 and 100%, respectively. No difference existed between the SUVmax of the primary tumour and that from the related most intense lymph node metastasis. Moreover, the mean tumour to background ratio was 90% higher in the lymph nodes compared to the primary tumour (p = 0.006). Ninety-three per cent of the patients had sufficient uptake in the lymph nodes to qualify for subsequent response monitoring of the axilla. A considerable distinction in metabolic activity was observed between the different subtypes of breast cancer. The mean SUVmax in lymph node metastases of oestrogen receptor (ER)-positive, triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumours was 6.6, 11.6 and 6.6, respectively.
Conclusion
The high accuracy in visualizing lymph node metastases and the sufficiently high SUVmax and tumour to background ratio at baseline suggest that it is feasible to monitor the axillary response with FDG PET/CT, especially in triple-negative tumours.
doi:10.1007/s00259-009-1343-2
PMCID: PMC2869017  PMID: 20130860
Breast cancer; Axillary lymph node metastasis; FDG-PET/CT; Neoadjuvant chemotherapy
25.  The correlation of SUVmax with pathological characteristics of primary tumor and the value of Tumor/ Lymph node SUVmax ratio for predicting metastasis to lymph nodes in resected NSCLC patients 
Background
We aimed to investigate the correlation of maximum standardized uptake value (SUVmax) with pathological characteristics of primary tumor and to determine a Tumor/ Lymph node (T/LN) SUVmax ratio predicting metastasis to lymph nodes in NSCLC patients.
Methods
Eighty-one NSCLC patients who had PET/CT examination at initial staging and subsequently underwent surgical resection were retrospectively evaluated. There were 100 PET/CT positive mediastinal or hilar lymph node stations. Pathological characteristics of the tumor such as largest tumor diameter, tumor histology, differentiation, number of mitosis, degree of stromal inflammation, necrosis; etiology of PET/CT positive lymph node stations; SUVmax of primary tumor and positive lymph node stations were recorded. A T/LN SUVmax ratio was calculated for each lymph node station.
Results
SUVmax of the primary tumor was positively correlated with the largest tumor diameter (p = 0.001, r = 0.374), number of mitosis (p < 0.001, r = 0.405), and postoperative pathological stage (p = 0.007, r = 0.298). Patients with squamous cell carcinoma had a statistically significant higher mean SUVmax, number of mitosis and advanced N stages compared to adenocarcinoma. The etiology of 100 PET/CT positive lymph node stations were metastasis in 14, anthracosis in 40, reactive in 39, granulomatous in 4, and silicosis in 3 patients. A T/LN SUVmax ratio of 5 or lower was suggestive for a malignant lymph node with a sensitivity of 92.8% and specificity of 47%.
Conclusions
SUVmax of a primary tumor is related to certain pathological characteristics, such as largest diameter, histology, and number of mitosis. A T/LN SUVmax ratio lower than 5 predicts the metastasis to lymph nodes with a high sensitivity.
doi:10.1186/1749-8090-8-63
PMCID: PMC3622559  PMID: 23557204

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