[Show abstract][Hide abstract] ABSTRACT: Patient-specific 3-dimensional radiobiologic dosimetry (3D-RD) was used for (131)I treatment planning for an 11-y-old girl with differentiated papillary thyroid cancer, heavy lung involvement, and cerebral metastases. (124)I PET was used for pharmacokinetics. Calculation of the recommended administered activity, based on lung toxicity constraints, was performed in real time (i.e., during the data-acquisition interval). The results were available to the physician in time to influence treatment; these estimates were compared with conventional dosimetry methodologies. In subsequent, retrospective analyses, the 3D-RD calculations were expanded to include additional tumor dose estimates, and the conventional methodologies were reexamined to reveal the causes of the differences observed. A higher recommended administered activity than by an S-value-based method with a favorable clinical outcome was obtained. This approach permitted more aggressive treatment while adhering to patient-specific lung toxicity constraints. A retrospective analysis of the conventional methodologies with appropriate corrections yielded absorbed dose estimates consistent with 3D-RD.
Journal of Nuclear Medicine 11/2009; 50(11):1844-7. · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to assess prospectively the impact of recombinant human TSH (rhTSH) administration on positron emission tomography (PET)/computed tomography (CT) imaging in differentiated thyroid cancer patients who, after primary treatment, had a suppressed or stimulated serum thyroglobulin greater than 10 ng/ml and no radioactive iodine uptake consistent with thyroid cancer on a whole body scan.
PET/CT was performed before (basal PET) and 24-48 h after rhTSH administration (rhTSH-PET) in 63 patients (52 papillary and 11 follicular thyroid cancers). Images were blindly analyzed by two readers. The proposed treatment plan was prospectively assessed before basal PET, after basal PET, and again after rhTSH-PET.
A total of 108 lesions were detected in 48 organs in 30 patients. rhTSH-PET was significantly more sensitive than basal PET for the detection of lesions (95 vs. 81%; P = 0.001) and tended to be more sensitive for the detection of involved organs (94 vs. 79%; P = 0.054). However, basal PET and rhTSH-PET did not have significantly different sensitivity for detecting patients with any lesions (49 vs. 54%; P = 0.42). Changes in treatment management plan occurred in 19% of the patients after basal PET. Lesions found only by rhTSH-PET contributed to an altered therapeutic plan in eight patients, among whom only four were true-positive on pathology (6%).
The use of rhTSH for 2-[18F]-fluoro-2-deoxy-D-glucose-PET/CT significantly increased the number of lesions detected, but the numbers of patients in whom any lesion was detected were no different between basal and rhTSH-stimulated PET/CT scans. Treatment changes due to true positive lesions occurred in 6% of cases.
The Journal of Clinical Endocrinology and Metabolism 01/2009; 94(4):1310-6. · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serum DNA methylation markers may potentially be useful in diagnosing thyroid cancer and monitoring its recurrence.
The objective of the study was to assess the utility of serum DNA methylation as a diagnostic test for patients with thyroid nodules and a monitoring test to detect thyroid cancer recurrence in previously treated patients.
Using real-time quantitative methylation-specific PCR, we analyzed the methylation status of five genes (CALCA, CDH1, TIMP3, DAPK, and RARbeta2) on 96 bisulfite-treated serum DNA samples isolated preoperatively from either solid thyroid nodule patients or patients in follow-up for history of treated thyroid cancer.
Diagnostic sensitivity, specificity, and accuracy of serum DNA methylation marker for thyroid cancer were measured.
For the patients with thyroid nodules, when a positive result was defined by a serum methylation level above the appropriately chosen cutoff value for any one of the five genes, the preoperative diagnostic sensitivity for thyroid cancer was 68% (26 of 38), the specificity was 95% (18 of 19), and the overall preoperative diagnostic accuracy was 77%, with positive and negative predictive values of 96 and 60%, respectively. In a subset of patients with cytologically indeterminate thyroid nodules, serum DNA methylation testing could correctly diagnose eight of 11 (73%) cancers and four of four (100%) benign tumors, with a diagnostic accuracy of 80%. We also analyzed these serum DNA methylation markers in 39 previously treated thyroid cancer patients. Among the 10 patients proved to have recurrent disease by conventional measures, seven (70%) were positive on methylation testing. Among the 29 patients who had no corroboration of residual or recurrent disease by conventional studies, six (21%) were positive for serum DNA methylation markers.
We have demonstrated the potential usefulness of serum DNA methylation markers as a novel tool for differential diagnosis of solid thyroid nodules and thyroid cancer recurrence monitoring.
[Show abstract][Hide abstract] ABSTRACT: Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer.
The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC.
In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed.
Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured.
We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3-29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1-14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease.
In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.
[Show abstract][Hide abstract] ABSTRACT: Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the "gold standard" in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.
[Show abstract][Hide abstract] ABSTRACT: TSH stimulates thyrocyte metabolism, glucose transport, and glycolysis. 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) is a glucose analog used in positron emission tomography (PET) to detect occult well-differentiated thyroid carcinoma. The objective of this study was to examine the effects of recombinant human TSH (rTSH) on FDG PET uptake in patients with residual or recurrent disease. Seven patients with well-differentiated thyroid carcinoma, negative 131-I scintigraphy, and biochemical evidence of residual disease were randomized and prospectively studied with FDG PET both on thyroid hormone suppression and rTSH stimulation within 1 wk. All lesions seen on the TSH suppression scans were seen on the rTSH stimulation studies. rTSH stimulation studies identified four additional lesions not seen on TSH suppression. One patient was positive on rTSH stimulation alone. The mean (2.54 +/- 0.72 vs. 1.79 +/- 0.88) and maximum (2.49 +/- 0.95 vs. 1.74 +/- 0.81) lesion to background ratios were significantly higher with rTSH stimulation, compared with TSH suppression (P = 0.02 for both). rTSH stimulation improves the detectability of occult thyroid metastases with FDG PET, compared with scans performed on TSH suppression.