Positron emission tomography scan for a hepatic mass

Breast cancer is the most common malignancy among women, leading to approximately 45 000 deaths per annum in the United States (1). The presence of axillary lymph node metastases has major prognostic implications in breast cancer patients (2,3), and it is an important criterion in determining the need for adjuvant chemotherapy (4). Sentinel lymph node (SLN) biopsy has become routine practice in the surgical treatment of patients with breast cancer because the disease status of the SLNs accurately reflects the status of the remaining axillary lymph nodes (5–7). Hence, patients who present with a negative SLN (no metastases) can be spared from having a more traumatic axillary lymph node dissection (ALND), which has been shown to be associated with substantial shortand long-term sequelae (8,9). Despite the enormous advantages of SLN biopsy over ALND in regard to post-operative complications in nodenegative patients, it would be of great clinical benefit if a reliable non-invasive method to assess lymph node status in breast cancer patients could be found. Positron emission tomography (PET) reflects the biochemical and physiologic processes occurring in the tissues being imaged and has been used in diagnosing a variety of malignancies (10, 11). The most frequently used positron emitting radiopharmaceutical is 18-fluor labeled 2-deoxy-D-glucose (F-FDG), a radioactively labeled glucose analog. The clinical use of F-FDG–PET is based on the premise that cancer cells exhibit a higher glycolytic rate than do non-neoplastic cells. Thus, F-FDG accumulates predominantly in the tumor tissue and can be visualized by a PET camera. Since the first reported visualization of lymph node metastases with F-FDG–PET in a preclinical animal study in 1990 (12), several investigations (13–19) have assessed the accuracy of PET in evaluating the nodal status of patients with breast cancer. These investigations have yielded conflicting results, with some investigators doubting that F-FDG–PET is capable of accurately assessing the nodal status of breast cancer patients (13–16) and others believing that a noninvasive PET scan could replace SLN biopsy at predicting the disease status of the axillary lymph nodes (17–19). In a recent investigation by an Italian group (18), preoperative F-FDG–PET was compared with the histologic findings of ALND in 167 clinically node-negative T1 (tumor size 2cm) and T2 (tumor size >2cm to 5cm) breast cancer patients, the largest patient collective published. F-FDG–PET detected 68 of 72 patients with axillary metastases, resulting in an overall sensitivity for PET of 94%. In the subset of T2 patients, the sensitivity was even higher (98%; 48/49), with only one false-negative finding. Based on these results, the authors claimed that F-FDG–PET can safely predict axillary lymph node status in patients with breast cancer and is a reliable and accurate method to identify patients who can avoid ALND. In the second largest published patient collective (19), preoperative F-FDG–PET was compared with the histologic findings of ALND in 124 pT1–T3 (T3 tumor size >5cm) breast cancer patients. PET scanning correctly identified all 44 patients with axillary lymph node metastases, resulting in an overall sensitivity for PET of 100%. These findings led the investigators of that study to suggest that F-FDG–PET should be considered as the initial test in evaluating axillary lymph nodes in breast cancer patients and that those patients without increased axillary F-FDG-uptake may not require ALND. Other investigations (17,20–23) with smaller patient numbers have reported similar findings, with sensitivities of pre-operative F-FDG–PET at detecting axillary lymph-node metastases ranging from 90% to 100%. In contrast to the above-mentioned investigations, several studies have found that F-FDG–PET has a low sensitivity at detecting SLN or axillary lymph node metastases. Indeed, Avril et al. (14) suggest that F-FDG–PET scanning cannot substitute for histologic analyses of axillary lymph nodes. Their study compared the diagnostic potential of F-FDG–PET with ALND in 41 breast cancer patients and reported an overall sensitivity for PET of 79% (19/24). PET sensitivity in the subset of patients with pT1 tumors was, however, only 33%; four of six patients had false-negative results, and the largest metastasis undetected by F-FDG–PET measured 12 mm in diameter. Kelemen et al. (15) also found low PET sensitivity when they compared F-FDG–PET scanning with the histolopathologic findings of SLN biopsies in clinically node-negative T1 and T2 breast cancer patients. If the SLN biopsies were negative by hematoxylin and eosin (H&E) staining, further biopsy sections were obtained for immunohistochemical (IHC) analyses using polyclonal anticytokeratin (CK) antibodies. Four of five patients with SLN metastases had false-negative F-FDG–PET scans (i.e., F-FDG–PET sensitivity was only 20%), and the missed metastases ranged from a micro-metastasis (defined as a cohesive cluster of malignant cells >0.2 mm to 2.0 mm in diameter), which was identified by IHC only, to macro-metastases up to 11 mm in

Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma

The detection of increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography (PET) is based on the enhanced glucose metabolism of tumor cells. Because the detection and staging of hepatocellular carcinoma (HCC) in patients with liver cirrhosis can be difficult, we prospectively evaluated the sensitivity of 18F-FDG PET in 14 consecutive patients with HCC. Whole body and regional 18F-FDG PET of the liver were obtained. The results were compared with ultrasonography, contrast-enhanced, helical CT, histological grading, p53 protein expression of HCC, and serum alpha-fetoprotein (AFP) level. In 7 patients PET demonstrated increased tumor 18F-FDG uptake, whereas HCC was not distinguishable from nonmalignant liver tissue in 7 other patients. Hepatic lesions were detected by ultrasonography in all patients, whereas only 11 of 14 HCCs could be identified by CT. In 3 patients extrahepatic spread was demonstrated by 18F-FDG PET. Patients with increased tumor 18F-FDG uptake had significantly larger hepatic lesions and higher serum AFP levels than those with normal 18F-FDG uptake. Lesions could be visualized by 18F-FDG PET in 7 of 8 patients with moderately or poorly differentiated HCC, whereas none of the six well-differentiated tumors was detected. Two patients with strong p53 expression demonstrated increased tumor 18F-FDG uptake and extrahepatic metastases. The sensitivity of 18F-FDG PET for the imaging of HCC is low. Nevertheless, in patients with moderately or poorly differentiated HCC, tumors >5 cm, or with markedly elevated AFP levels 18F-FDG PET may contribute to an effective noninvasive staging.

PET Scanning in Thymic Neuroendocrine Tumors

18F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can be used to image synovial inflammation in patients with rheumatoid arthritis (RA). Recently, clinical application of novel therapies for RA, such as tumor necrosis factor-α (TNF-α) inhibitor and anti-interleukin-6 receptor antibody, has been introduced. The radiological assessment of disease activity changes of patients who underwent these therapies will help the clinicians to obtain more information about the patients and to decide drug withdrawal or change of medication. It is considered that 18F-FDG PET scan is generally very expensive; however, the information from 18F-FDG PET about patients during biological treatments helps discontinuation of these treatments with incomplete response despite its high costs and with possible side effects such as malignant lymphoma. In this study, we evaluated if the 18F-FDG uptake of the affected joints represented by standardized uptake value (SUV) correlated with the clinical assessment of patients with RA. In addition, we would like to evaluate if there was a correlation between the difference of SUV and improvement of clinical findings in RA patients undergoing anti TNF therapies. RA patients who underwent anti-TNFα therapies in a tertiary care hospital were assessed using whole-body 18F-FDG PET/computed tomography (CT). PET assessments were performed on hip joints, knees, shoulders, wrists, ankles, MCP, and PIP for a total of 28 joints in each patient. The 18F–FDG uptake was then quantified using the maximum SUV (SUVmax) prior to, and 6 months after the initiation of treatment with anti-TNF-α drugs. Disease activity score (DAS28 and DAS28-C-reactive protein [CRP]) were recorded and white blood cell, matrix metalloproteinases (MMP-3) and rheumatoid factor (RF) were examined in all patients. The average of SUVmax among measured joints, or the sum of these joints (total SUVmax), correlated with DAS28 (r = 0.671, P < 0.001), DAS28-CRP (r = 0.623, P < 0.001), ESR (r = 0.542, P < 0.001), CRP (r = 0.411, P = 0.002), MMP-3 (r = 0.399, P = 0.006), and RF (r = 0.447, P = 0.002). There were correlations between ΔSUV and ΔDAS28 (r = 0.651, P < 0.001), ΔSUV and ΔDAS28-CRP (r = 0.682, P < 0.001), ΔSUV and ΔESR (r = 0.449, P = 0.023), and ΔSUV and ΔMMP-3 (r = 0.457, P = 0.027), respectively. The number of PET-positive joints and the cumulative SUV significantly correlated with the DAS28, which is a composite disease activity score (DAS) that combines the swollen and tender joint counts, the erythrocyte sedimentation rate (DAS28-ESR) or CRP serum levels (DAS28 − CRP) or RF (DAS28 − RF) or metalloproteinases-3 (DAS28-MMP-3). At baseline and at 6 months' post-treatment with anti-TNFα drugs, there was a significant correlation between the PET results, either visual, the cumulative SUVs or the composite SUV index, and the comprehensive clinical assessment (DAS28), the CRP levels and the number of joints positive for RA, and cumulative synovial thickness. By reflecting inflammatory activity, 18F-FDG PET may enhance the diagnostic performance and expectation of disease prognosis in RA, especially with early synovial inflammation. The intensity of uptake varied from mild to intense (SUVmax values from 3.10 to 6.0). Overall, these values correlated well with the clinical evaluation of involved joints. 18F–FDG PET imaging data provided a distribution of joint involvement with varying degrees of severity and phase of disease activity (moderate, low, and remission) in the same patient. PET/CT imaging with 18F-FDG shows better image quality, provides more confirmative diagnostic information, and will be promising imaging modality in diagnosis and management of RA.

1094: The Influence of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography (PET) on the Clinical Management of Patients With Head and Neck Cancer

Comparison of 18F-fluorodeoxyglucose PET and 68Ga-fibroblast Activation Protein Inhibitor PET in Head and Neck Cancers: ASystematic Review and Meta-analysis.

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) has been widely used not only for detecting and staging malignant tumours but also for monitoring therapy response and for differentiating malignant lesions...

Stage IIIA non–small-cell lung cancer with mediastinal node metastases (N2 non–small-cell lung cancer) is actually a spectrum of diseases with widely divergent prognoses. Each subset has been traditionally defined by the tests that are necessary to detect the N2 disease, which in itself is an indication of the extent and bulk of the nodal deposits. The subset with the worst prognosis has such gross N2 disease that it could be detected clinically as the patient enters the clinic. Survival in such patients is usually measured in months. The subset with the best prognosis has such subtle nodal disease that it eludes clinical examination, chest radiology, CT scanning, and even mediastinoscopy, and it is ultimately called unexpected N2 disease when found at thoracotomy. According to several authors, patients in this subset have a 20% survival at 5 years if, despite the mediastinal nodal disease, complete resection proves feasible. Even this subset is an amalgam of cases. Some unexpected N2 disease is not so much unexpected as unconfirmed; others might have small deposits, even widespread involvement, in nodes below the size threshold that would normally trigger a mediastinoscopy. Some cases are the result of a falsely negative mediastinoscopy, and others involve nodes beyond the reach of the mediastinoscope. The realization that N2 disease might elude even the most diligent preoperative evaluation led surgeons to undertake an increasingly detailed intrathoracic re-evaluation at thoracotomy. A central part of this has become the removal of apparently normal lymph nodes in the mediastinum and hilum for subsequent histologic examination. Such techniques have improved staging and have often discovered N2 disease that was not visualized by naked-eye assessment of the sliced nodal tissue but was discovered on subsequent histologic– even immunohistologic–examination after surgery. All of the component groups within the unexpected N2 subset had one unifying and comforting characteristic: in patients whose disease could not be confirmed before thoracotomy, complete resection was feasible in the majority of cases, and the survival rates justified the added risks of continuing with resection. The widespread use of positron emission tomography (PET) scanning with fluorodeoxyglucose has reshuffled the pack. The greater accuracy with which this technique detects N2 disease compared with computed tomography (CT) scanning and even with mediastinoscopy has resulted in some patients with “unexpected” N2 disease being identified before surgery. These patients, if their disease is confirmed histologically, now join the proven N2 cases, for which the current standard of care is induction therapy. Presumably, those cases of N2 disease that elude PET scanning and are discovered at thoracotomy will have even more subtle nodal disease. The principles of stage migration suggest that both groups should have an improved survival when compared with the older subsets. However, PET scanning has spawned two new problems. The specificity with which PET scanning identifies nodal disease is less than perfect, with around 10% false-positive rates in studies. How do we ensure that these patients proceed appropriately with surgical treatment? In those patients whose PET scan suggestion of N2 disease is confirmed histologically, how do we select patients who should then proceed with resection? The simple answer to the first question is to undertake mediastinoscopy in all PET-positive cases without extrathoracic disease. Studies have shown that the answer to the second question lies in selecting patients in whom induction therapy has downstaged the patients and eradicated the mediastinal nodal deposits. This favorable response in the mediastinal lymph nodes is presumably a surrogate for the eradication of occult distant metastases by induction therapy. Those with persistent N2 disease have low survival chances with surgery and are probably better served by consolidation therapy with chemoradiotherapy. The article by De Leyn et al from the Leuven Lung Cancer Group in Belgium seeks to answer the resulting dilemma. How, after induction chemotherapy, do we identify which patients have persistent N2 disease and should go on to chemoradiotherapy and which have been downstaged and should proceed with second-line surgery? Can further PET scanning undertake this reliably, or do we have to accept the problems inherent in repeat mediastinoscopy? They conclude that the sensitivity and accuracy of PET are sufficiently superior to those of repeat mediastinoscopy to justify its use as the technique of choice in these circumstances. This conclusion, and the magnitude of the difference between the results with these investigations, will surprise many. The sensitivity with which PET scanning after induction therapy identifies residual disease in the mediastinal lymph nodes, summarized in the De Leyn et al Table 6, is around 50% to 60%. This is considerably worse than the 83% sensitivity reported for PET scanning in the primary staging of lung cancer. However, the sensitivity of repeat PET in the study by De Leyn et al is 77%—within the range reported in the primary setting. Is this, as the authors claim, the result of coregistering PET and CT images in the newer generation of scanners? One study suggests that, in the primary setting, integrated PET-CT is superior to the visual correlation of images from separate PET and CT studies. However, in this study, the accuracy JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 21 JULY 2

To evaluate and compare diagnostic sensitivity of positron emission tomography (PET) scanning in carcinoid and islet cell tumor patients with a serotonin and a catecholamine precursor as tracers. Carcinoid (n = 24) or pancreatic islet cell tumor (n = 23) patients with at least one lesion on conventional imaging including somatostatin receptor scintigraphy (SRS) and computed tomography (CT) scan underwent (11)C-5-hydroxytryptophan ((11)C-5-HTP) PET and 6-[F-18]fluoro-L-dihydroxy-phenylalanine ((18)F-DOPA) PET. PET findings were compared with a composite reference standard derived from all available imaging along with clinical and cytologic/histologic information. In carcinoid tumor patients, per-patient analysis showed sensitivities for (11)C-5-HTP PET, (18)F-DOPA PET, SRS, and CT of 100%, 96%, 86%, 96%, respectively, and in islet cell tumors of 100%, 89%, 78%, 87%, respectively. In carcinoid patients, per-lesion analysis revealed sensitivities for (11)C-5-HTP PET, (11)C-5-HTP PET/CT, (18)F-DOPA PET, (18)F-DOPA PET/CT, SRS, SRS/CT, and CT alone of, respectively, 78%, 89%, 87%, 98%, 49%, 73%, and 63% and in islet cell tumors of 67%, 96%, 41%, 80%, 46%, 77%, and 68%, respectively. In all carcinoid patients (18)F-DOPA PET and (11)C-5-HTP PET detected more lesions than SRS (P < .001). (11)C-5-HTP PET was superior to (18)F-DOPA PET in islet cell tumors (P < .0001). In all cases, CT improved the sensitivity of the nuclear scans. (18)F-DOPA PET/CT is the optimal imaging modality for staging in carcinoid patients and (11)C-5-HTP PET/CT in islet cell tumor patients.

PurposeTo evaluate the potential utility of 123I-metaiodobenzylguanine (123I-MIBG) scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether 18F-FDG PET is as beneficial as 123I-MIBG imaging.MethodsWe selected 8 NBL patients with significant residual mass after operation and who had paired 123I-MIBG and 18F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans.ResultsBoth scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, 123I-MIBG might be superior to 18F-FDG PET. The sensitivity of 123I-MIBG and 18F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. 18F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive 123I-MIBG. For bone-BM metastatic sites, the sensitivity of 123I-MIBG and 18F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. 123I-MIBG scan showed higher false positivity (20.8%) than 18F-FDG PET (0%).Conclusion123I-MIBG is superior for delineating primary tumor sites, and 18F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.

A pulmonary lesion is an extremely common and clinically challenging disorder worldwide, and an accurate diagnosis of lung cancer is crucial for early treatment and management. The aim of the present study was to perform a comprehensive meta analysis to compare the diagnostic performance of 18F-fluorothymidine (18F-FLT) positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) PET in evaluating patients with pulmonary lesions. Relevant studies were identified using the PubMed, EMBASE and Cochrane library databases. The pooled estimated sensitivity, specificity, positive-likelihood ratio, negative-likelihood ratio, and diagnostic odds ratio (DOR) for 18F-FLT PET versus 18F-FDG PET were calculated as the main outcome measures. Summary receiver operating characteristic curves were also constructed by Meta-Disk 1.4 software using a Mose's constant of linear model. The meta analysis showed that 18F-FLT PET had a higher specificity (0.70; 95% CI, 0.61-0.77), but lower sensitivity (0.81; 95% CI, 0.74-0.87) compared to 18F-FDG PET (0.50; 95% CI, 0.41-0.58 for specificity; 0.92; 95% CI 0.86-0.95 for sensitivity). For DOR, 18F-FLT PET (12.58; 95% CI, 6.81-23.24) was higher compared to 18F-FDG PET (10.72; 95% CI, 5.51-20.87). The area under the curve was 0.8592 and 0.9240 for 18F-FLT PET and 18F-FDG PET, respectively (Z=0.976, P>0.05). In conclusion, 18F-FLT PET and 18F-FDG PET had good diagnostic performance for the overall assessment of pulmonary lesions, and 18F-FLT PET had a higher specificity compared to 18F-FDG PET, but was less sensitive than 18F-FDG PET. Therefore, 18F-FLT and 18F-FDG together could add diagnostic confidence for pulmonary lesions.

Role of Positron Emission Tomography in the Treatment of Occult Disease in Head-and-Neck Cancer: A Modeling Approach

The aim of this study is to test the hypothesis that positron emission tomography (PET) with 3'-deoxy-3'-[(18)F]-fluorothymidine ((18)F-FLT) can differentiate malignancy from benign leiomyoma better than PET with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), and to evaluate whether (18)F-FLT and (18)F-FDG uptake correlate with immunohistochemical index of cell proliferation. The protocol of this prospective study was approved by the institutional ethics committee, and all patients gave written informed consent. Fifteen patients (aged 26-65 years, median 44 years) with uterine corpus tumor which has the possibility of being leiomyosarcoma underwent (18)F-FLT and (18)F-FDG PET scans. Maximum standard uptake value (SUV(max)) of PET scans and Ki-67 labeling index of surgical specimens were evaluated. Mann-Whitney's U test was used for comparing uptakes between benign and malignant, and linear regression analysis was used for evaluating the correlation between Ki-67 labeling index and SUV(max). Five cases were diagnosed as malignant (leiomyosarcoma for 3 cases, and carcinoma for 2 cases), and the others were benign leiomyoma. Sensitivity and negative predictive value of both tracers for detecting malignancy was 100%. Specificity, positive predictive value and accuracy of (18)F-FLT PET were higher than those of (18)F-FDG PET. Difference in SUV(max) between malignant and benign was significant for (18)F-FLT PET (P < 0.01), but not for (18)F-FDG PET. While all the malignant cases showed positive uptake in both tracers, a case of leiomyosarcoma with huge necrosis showed relatively low uptake. Uptake of (18)F-FLT showed better correlation with Ki-67 labeling index compared with (18)F-FDG (R(2) = 0.91 vs. R(2) = 0.26). Negative findings on additional (18)F-FDG or (18)F-FLT PET may rule out the possibility of malignancy for the patients with suspected leiomyosarcoma diagnosed by conventional methods. (18)F-FLT PET is superior to (18)F-FDG PET in differentiating malignant from benign leiomyoma. Moreover, (18)F-FLT uptake correlated well with the immunohistochemical index of cell proliferation.

The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.