Mark A. Nathan

Characterization of the Solitary Pulmonary Nodule: 18F-FDG PET Versus Nodule-Enhancement CT

OBJECTIVE The purpose of this study was to directly compare nodule-enhancement CT and 18F-FDG PET in the characterization of indeterminate solitary pulmonary nodules (SPNs) greater than 7 mm in size. MATERIALS AND METHODS Examinations from patients undergoing both nodule-enhancement CT and 18F-FDG PET to characterize the same indeterminate SPN were reviewed. For nodule-enhancement CT, an SPN was considered malignant when it showed an unenhanced to peak contrast-enhanced increase in attenuation greater than 15 H. Fluorine-18-FDG PET studies were blindly reinterpreted by two qualified nuclear radiologists. SPNs qualitatively showing hypermetabolic activity greater than the mediastinal blood pool were interpreted as malignant. These interpretations were compared with the original prospective clinical readings and to semiquantitative standardized uptake value (SUV) analysis. Results were compared with pathologic and clinical follow-up. RESULTS Forty-two pulmonary nodules were examined. Twenty-five (60%) were malignant, and 17 (40%) were benign. Nodule-enhancement CT was positive in all 25 malignant nodules and in 12 benign nodules, with sensitivity and specificity of 100% and 29%, respectively, and with a positive predictive value (PPV) and negative predictive value (NPV) of 68% and 100%, respectively. Qualitative 18F-FDG PET interpretations were positive in 24 of the 25 malignant nodules and in four benign nodules. Fluorine-18-FDG PET was considered negative in one malignant nodule and in 13 of the 17 benign nodules. This correlates with a sensitivity and specificity of 96% and 76%, respectively, and with a PPV and NPV of 86% and 93%, respectively. Original prospective 18F-FDG PET and semiquantitative SUV analysis showed sensitivity, specificity, PPV, and NPV of 88%, 76%, 85%, and 81% and 84%, 82%, 88%, and 78%, respectively. CONCLUSION Due to its much higher specificity and only slightly reduced sensitivity, 18F-FDG PET is preferable to nodule-enhancement CT in evaluating indeterminate pulmonary nodules. However, nodule-enhancement CT remains useful due to its high NPV, convenience, and lower cost. Qualitative 18F-FDG PET interpretation provided the best balance of sensitivity and specificity when compared with original prospective interpretation or SUV analysis.

Comparison of positron emission tomography, computed tomography, and endoscopic ultrasound in the initial staging of patients with esophageal cancer

IntroductionImprovement in esophageal cancer staging is needed. Positron emission tomography (PET), computed tomography (CT), and endoscopic ultrasound (EUS) in the staging of esophageal carcinoma were compared.MethodsPET, CT, and EUS were performed and interpreted prospectively in 75 patients with newly diagnosed esophageal cancer. Either tissue confirmation or fine needle aspiration (FNA) was used as the gold standard of disease. Sensitivity and specificity for tumor, nodal, and metastatic (TNM) disease for each test were determined. TNM categorizations from each test were used to assign patients to subgroups corresponding to the three treatment plans that patients could theoretically receive, and these were then compared.ResultsLocal tumor staging (T) was done correctly by CT and PET in 42% and by EUS in 71% of patients (P value > 0.14). The sensitivity and specificity for nodal involvement (N) by modality were 84% and 67% for CT, 86% and 67% for EUS, and 82% and 60% for PET (P value > 0.38). The sensitivity and specificity for distant metastasis were 81% and 82% for CT, 73% and 86% for EUS, and 81% and 91% for PET (P value > 0.25). Treatment assignment was done correctly by CT in 65%, by EUS in 75%, and by PET in 70% of patients (P value > 0.34).ConclusionsEUS had superior T staging ability over PET and CT in our study group. The tests showed similar performance in nodal staging and there was a trend toward improved distant disease staging with CT or PET over EUS. Assignment to treatment groups in relation to TNM staging tended to be better by EUS. Each test contributed unique patient staging information on an individual basis.

Detection of Recurrent Prostate Cancer After Radical Prostatectomy: Comparison of 11C-Choline PET/CT with Pelvic Multiparametric MR Imaging with Endorectal Coil

The aim of this study was to compare 11C-choline PET/CT with pelvic multiparametric MR imaging for detection of recurrent prostate carcinoma in patients with suspected recurrence after radical prostatectomy and to identify an optimal imaging method to restage these patients. Methods: This was a retrospective, single-institution study of 115 prostatectomy patients with suspected tumor recurrence who underwent both 11C-choline PET/CT and multiparametric MR imaging with endorectal coil. The reference standard included histopathology, treatment change, and imaging follow-up for determination of locally recurrent tumor, lymph node (LN) metastases, and skeletal metastases. Two nuclear medicine and 2 genitourinary radiologists independently and in a masked manner reviewed PET/CT and multiparametric MR imaging, respectively. The reviewers assessed for local recurrence in the prostatectomy bed as well as LN and bone metastases, rating their diagnostic confidence with a 5-point scoring system for each location. Receiver-operating-characteristic analysis was used to compare the 2 modalities. Results: The standard of reference (either positive or negative) for the diagnosis of local recurrence and pelvic LN and bone metastases was met in 87, 70, and 95 patients, respectively. Documented local recurrence and pelvic LN and bone metastases was present in 61 of 87 (70.1%), 50 of 70 (71.4%), and 16 of 95 (16.8%) patients, respectively. Patient-based area under the receiver-operating-characteristic curves of multiparametric MR imaging versus PET/CT for the diagnosis of local recurrence and pelvic LN and bone metastases were 0.909 versus 0.761 (P = 0.0079), 0.812 versus 0.952 (P = 0.0064), and 0.927 versus 0.898 (P = 0.69), respectively. Among 61 patients with local recurrence, 32 patients (52.4%) were correctly diagnosed as having local recurrence by both multiparametric MR imaging and PET/CT, 22 (36.1%) were correctly diagnosed by multiparametric MR imaging only, 6 (9.8%) could not be diagnosed by either modality, and 1 (1.6%) was correctly diagnosed by PET/CT only. The patient-based sensitivity, specificity, and accuracy of multiparametric MR imaging for diagnosing local recurrence were 88.5% (54/61), 84.6% (22/26), and 87.4% (76/87) whereas those of PET/CT for detecting body LN or bone metastases were 92.3% (72/78), 100% (18/18), and 93.8% (90/96), respectively. Conclusion: Multiparametric MR imaging with endorectal coil is superior for the detection of local recurrence, PET/CT is superior for pelvic LN metastasis, and both were equally excellent for pelvic bone metastasis. 11C-choline PET/CT and pelvic multiparametric MR imaging are complementary for restaging prostatectomy patients with suspected recurrent disease.

The value of quantifying 18F-FDG uptake in thyroid nodules found incidentally on whole-body PET-CT.

ObjectiveTo determine if quantification of [18F]fluorodeoxyglucose (18F-FDG) uptake in a thyroid nodule found incidentally on whole-body 18F-FDG positron emission tomography–computed tomography (PET–CT) can be used to discriminate between malignant and benign aetiology. MethodsA retrospective review of all patients with focally high uptake in the thyroid as an incidental finding on 18F-FDG PET–CT from May 2003 through May 2006. The uptake in the nodules was quantified using the maximum standardized uptake value (SUVmax). The aetiology was determined by cytology and/or ultrasound, or on histopathology. ResultsIncidental focally high uptake was found in 79/7347 patients (1.1%). In 31/48 patients with adequate follow-up, a benign aetiology was determined. Median SUVmax for the benign group was 5.6, range 2.5–53. Malignancy was confirmed in 15/48 patients. The malignancies were papillary thyroid carcinoma in 12, metastasis from squamous cell carcinoma in one, and lymphoma in two. Median SUVmax for the malignant lesions was 6.4, range 3.5–16. Cytology suspicious for follicular carcinoma was found in 2/48 patients. No statistical difference (P=0.12) was found among the SUVmax between the benign and malignant groups. ConclusionFocally high uptake of 18F-FDG in the thyroid as an incidental finding occurred in 1.1% of the patients. Malignancy was confirmed or was suspicious in 17/48 (35%) of the patients that had adequate follow-up. There was no significant difference in the SUVmax between benign and malignant nodules.

Clinical Significance of Diffusely Increased 18F-FDG Uptake in the Thyroid Gland

Our purpose was to determine the clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland as an incidental finding on PET/CT. Methods: All patients who were found to have diffuse thyroid uptake on 18F-FDG PET/CT in our institution between November 2004 and June 2006 were investigated and compared with an age- and sex-matched control group. The 18F-FDG uptake in the thyroid was semiquantified using maximum standardized uptake value and correlated to the available serum thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPO) antibody levels using regression analysis. Results: Of the 4,732 patients, 138 (2.9%) had diffuse thyroid uptake. Clinical information was available for 133 of the 138 patients. Sixty-three (47.4%) had a prior diagnosis of hypothyroidism or autoimmune thyroiditis, of whom 56 were receiving thyroxine therapy. In the control group, consisting of 133 patients with no thyroid uptake, there were 13 (9.8%) with a prior diagnosis of hypothyroidism, 11 of whom were receiving thyroxine therapy. In the study group, 38 (28.6%) of 133 patients did not undergo any further investigation for thyroid disease, whereas 32 (24.1%) of 133 patients were examined for thyroid disease after PET. Nineteen were found with autoimmune thyroiditis or hypothyroidism, and replacement therapy was initiated in 12. No significant correlation was found between maximum standardized uptake value and TSH (P = 0.09) or TPO antibody (P = 0.68) levels. Conclusion: The incidental finding of increased 18F-FDG uptake in the thyroid gland is associated with chronic lymphocytic (Hashimotos) thyroiditis and does not seem to be affected by thyroid hormone therapy. SUV correlated neither with the degree of hypothyroidism nor with the titer of TPO antibodies.

18F-FDG PET in the management of patients with anaplastic thyroid carcinoma.

BACKGROUND Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC. METHODS All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded. RESULTS Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management. CONCLUSIONS ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

18F-FDG PET/CT in primary central nervous system lymphoma in HIV-negative patients

ObjectiveTo determine the value of 18F-FDG PET/CT in the different manifestations of primary central nervous system lymphoma (PCNSL) in HIV-negative patients. MethodsAll PCNSL and HIV-negative patients referred for PET/CT in our institution from July 2001 to June 2006 were retrospectively studied. PET/CT examinations were reviewed by two experienced readers and evaluated for each possible anatomical site of nervous system involvement: cerebral, spinal/nerve and ocular. PET/CT results were characterized as true positive or negative and false positive or negative according to the status of the disease, which was determined after the evaluation of biopsies, laboratory, clinical and imaging examinations, and follow-up. ResultsForty-two PET/CT examinations were carried out in 25 PCNSL patients. For intracerebral disease, PET/CT was true positive in 13 cases, true negative in 27 and false negative in two. For disease involving spinal cord and/or nerves, PET/CT was true positive in four cases, true negative in 37 and false negative in one. For ocular disease, PET was true positive in only one case and false negative in four. The sensitivity of PET/CT in detecting active disease in the brain was 87% (13/15), in the spine/nerves 80% (4/5), and in the eyes only 20% (1/5). ConclusionPET/CT seems to be sensitive for the detection of viable intracerebral as well as for spinal and peripheral nerve disease, but not for the detection of ocular involvement.

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease

BACKGROUND Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

18F-FDG PET and PET/CT in Burkitt's lymphoma

OBJECTIVE To explore the value of (18)F fluorodeoxy-glucose (FDG) positron emission tomography (PET) in Burkitts lymphoma. METHODS All Burkitts lymphoma patients referred for FDG PET or FDG PET/computed tomography (CT) exams at our institution from June 2003 to June 2006 were included. Selected patients were followed and clinical information was reviewed retrospectively. Results from FDG PET-PET/CT, as blindly reviewed by a consensus of two experienced readers, were compared with the status of the disease as determined by other laboratory, clinical and imaging exams and clinical follow-up. FDG PET-PET/CT results were classified as true positive or negative and false positive or negative. The degree of FDG uptake in the positive lesions was semiquantified as maximum standard uptake value (SUVmax). RESULTS Fifty-seven FDG PET-PET/CT exams were done in 15 patients. Seven exams were done for initial staging, 8 during and 14 after the completion of therapy, and 28 for disease surveillance. For nodal disease FDG PET-PET/CT was true positive in 8, true negative in 47 and false positive in 2 exams (sensitivity 100%, specificity 96%). For extranodal disease FDG PET-PET/CT was true positive in 6, true negative in 48 and false positive in 3 exams (sensitivity 100%, specificity 94%). The mean SUVmax for the positive nodal lesions was 15.7 (range 6.9-21.7, median 18.5) and for extranodal lesions was 14.2 (range 6.2-24.3, median 12.4). CONCLUSIONS FDG PET-PET/CT is sensitive for the detection of viable disease in Burkitts lymphoma. Affected areas demonstrated high degree of uptake that was reversible upon successful implementation of treatment.

The Prognostic Value of 2-Deoxy-2-[18F]Fluoro-d-Glucose Positron Emission Tomography in Patients With Suspected Residual or Recurrent Medullary Thyroid Carcinoma

PurposeTo explore the prognostic value of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET) in patients with suspected residual or recurrent medullary thyroid carcinoma (MTC).ProceduresThis retrospective study included all patients with MTC examined with FDG-PET at Mayo Clinic, Rochester, Minnesota, from October 1999 to March 2008. The PET results were compared with other imaging studies and clinical findings, including carcinoembryonic antigen and calcitonin levels.ResultsTwenty-nine patients with MTC were included. PET was positive in 14 patients, with follow-up information for 11; six died from metastatic disease, four had disease progression, and one remained in stable condition. PET was negative in 15 patients, with follow-up for 12; one had recurrent disease, and 11 had no evidence of clinical disease. Calcitonin doubling time was shorter for PET-positive than for PET-negative patients.ConclusionFDG-PET has high prognostic value in patients with suspected residual or recurrent MTC.