Thyroid Diseases: Oyen WJ

Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E, Anonymous00011. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #18670773 No free full text.

Abstract: INTRODUCTION: The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine ((131)I) activities. DISCUSSION: For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with (131)I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.

De Klerk JM, Oyen WJ. · Department of Nuclear Medicine Meander Medical Center, Amersfoort, The Netherlands. · Minerva Endocrinol. · Pubmed #19209128 No free full text.

Abstract: Radioiodine plays an important role in the treatment of thyroid cancer. It is used for thyroid remnant ablation as well as for treatment of metastatic disease. Despite the fact that it is used all over the world for these indications, the exact administered dose is still a subject for DISCUSSION: Two methods are widely available: the so-called fixed empiric method and the dosimetric one. This review will highlight the aspects of radioiodine in treatment of thyroid cancer and discuss the advantages and disadvantages of the several methods for the calculation of the administered dose.

Oyen WJ, Bodei L, Giammarile F, Maecke HR, Tennvall J, Luster M, Brans B. · Therapy Committee of the European Association of Nuclear Medicine, Hollandstrasse 14 / Mezzanine, A-1020 Vienna, Austria. · Ann Oncol. · Pubmed #17434893 links to  free full text

Abstract: In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.

Brans B, Bodei L, Giammarile F, Linden O, Luster M, Oyen WJ, Tennvall J. · Department of Nuclear Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. · Eur J Nucl Med Mol Imaging. · Pubmed #17268773 links to  free full text

Abstract: INTRODUCTION: Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. REVIEW: This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. DEVELOPMENTS: In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.

Zuijdwijk MD, Vogel WV, Corstens FH, Oyen WJ. · Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. · Nucl Med Commun. · Pubmed #18528186 No free full text.

Abstract: AIM: In differentiated thyroid carcinoma, persistent plasma thyroglobulin (Tg) is a specific marker for persistent or recurrent disease after thyroidectomy and radioiodine ablation. When Tg remains elevated and no substrate can be found on whole-body radioiodine imaging (131I-WBS), or even when recurrent disease is suspected with normal Tg, conventional imaging (CI) is often insufficient. As fluorodeoxyglucose (FDG)-PET has proven to be an effective modality for detecting various types of cancer, the utility of FDG-PET was analysed and compared with CI in this retrospective study in patients with differentiated thyroid cancer. PATIENTS AND METHODS: After total thyroidectomy and radioiodine ablation, 68 FDG-PET scans were performed in 39 patients with elevated Tg levels or clinical suspicion of recurrent disease. At the time of FDG-PET, 54 131I-WBS (in 30 patients) were negative, 14 (in 11 patients) were equivocal. Tg was normal at the time of 14 scans (10 patients) and elevated in 54 (in 33 patients). FDG-PET results were compared with histology, 131I-WBS and CI and clinical follow-up. Sensitivity and specificity were evaluated in various subgroups. RESULTS: Overall, there were 35 true-positive, two false-positive, 20 true-negative and three false-negative FDG-PET scans. In six of these cases (one true positive, five true negative) FDG-PET was repeated without intervention and in an additional eight FDG-PET scans no definite conformation of abnormal FDG-PET could be obtained, so these results were not used for statistical analysis. Sensitivity, specificity, PPV and NPV for the whole group were 92, 88, 94 and 83%, respectively. In 38 scans performed on 31 patients with elevated Tg levels, who were not known with recurrence, this was 84, 100, 100 and 75%, respectively. In 16 scans in 10 patients with known recurrence (all with elevated Tg), sensitivity and PPV were 100% without false-positive or false-negative results. When Tg was not detectable (14 scans in 10 patients), sensitivity, specificity, PPV and NPV were 100, 75, 60 and 100%, respectively. After 35 FDG-PET scans (51%), there was a change in patient management by avoiding ineffective 131I treatment, by guiding surgical reintervention, or avoiding futile surgery. One FP FDG-PET resulted in an unnecessary surgical procedure. In 33 cases, FDG-PET did not lead to a change in treatment policy, which retrospectively would have been beneficial in six cases. CONCLUSION: FDG-PET affected patient management in patients with differentiated thyroid cancer and negative 131I-WBS, not only when Tg is elevated, but also when Tg is not detectable and therefore the use of FDG-PET as a diagnostic tool is justified in these patients.

Gotthardt M, Rubner C, Bauhofer A, Berce F, Oyen WJ, Goecke J, Pfestroff A, Schlieck A, Corstens FH, Béhé M, Behr TM. · Department of Nuclear Medicine, St. Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmergen, The Netherlands. · Nuklearmedizin. · Pubmed #17043731 No free full text.

Abstract: PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Gotthardt M, Béhé MP, Beuter D, Battmann A, Bauhofer A, Schurrat T, Schipper M, Pollum H, Oyen WJ, Behr TM. · Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands. · Eur J Nucl Med Mol Imaging. · Pubmed #16832634 No free full text.

Abstract: PURPOSE: Radiopeptide imaging is a valuable imaging method in the management of patients with neuroendocrine tumours (NET). To determine the clinical performance of gastrin receptor scintigraphy (GRS), it was compared with somatostatin receptor scintigraphy (SRS), computed tomography (CT) and (18)F-FDG positron emission tomography (PET) in patients with metastasised/recurrent medullary thyroid carcinoma (MTC). METHODS: Twenty-seven consecutive patients underwent imaging with GRS, SRS (19 patients), CT and PET (26 patients). GRS and SRS were compared with respect to tumour detection and uptake. CT, PET, magnetic resonance imaging (MRI), ultrasound (US) and follow-up were used for verification of findings. In addition, GRS, CT and PET were directly compared with each other to determine which method performs best. RESULTS: Nineteen patients underwent both GRS and SRS. Among these, GRS showed a tumour detection rate of 94.2% as compared to 40.7% for SRS [mean number of tumour sites (+/-SD) and 95% confidence intervals (CI): GRS 4.3+/-3.1/2.8-5.7, SRS 1.8+/-1.6/1.1-2.6]. In 26 patients, GRS, CT and PET were compared. Here, GRS showed a tumour detection rate of 87.3% (CT 76.1%, PET 67.2%; mean number of tumour sites and 95% CI: GRS 4.5+/-4.0/2.9-6.1, CT 3.9+/-3.5/2.5-5.3, PET 3.5+/-3.3/2.1-4.8). If GRS and CT were combined, they were able to detect 96.7% of areas of tumour involvement. CONCLUSION: GRS had a higher tumour detection rate than SRS and PET in our study. GRS in combination with CT was most effective in the detection of metastatic MTC.

de Geus-Oei LF, Pieters GF, Bonenkamp JJ, Mudde AH, Bleeker-Rovers CP, Corstens FH, Oyen WJ. · Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · J Nucl Med. · Pubmed #16644746 links to  free full text

Abstract: Fine-needle aspiration biopsy (FNAB) is inconclusive in up to 20% of patients with solitary thyroid nodules. In these cases, hemithyroidectomy is necessary, but only 20% of the nodules prove to be thyroid carcinoma. The aim of this study was to explore the potential of (18)F-FDG PET to reduce the number of unnecessary hemithyroidectomies in the preoperative assessment of thyroid nodules with inconclusive FNAB results. METHODS: Forty-four consecutive patients, scheduled for hemithyroidectomy because of inconclusive FNAB findings, participated in this prospective study. (18)F-FDG PET of the thyroid region was performed before hemithyroidectomy, and standardized uptake values were calculated. The final histopathologic diagnosis served as a standard of reference. RESULTS: Histopathologic examination of the surgical specimens revealed 7 well-differentiated thyroid carcinomas in 6 patients, all accumulating (18)F-FDG (negative predictive value, 100%). (18)F-FDG accumulated in 13 of 38 benign nodules. The pre-PET probability for cancer in this study population was 14% (6/44), and the post-PET probability increased to 32% (6/19). The percentage of unnecessary hemithyroidectomies in a hypothetical algorithm using (18)F-FDG PET was only 30% (13/44), compared with 86% (38/44) without (18)F-FDG PET. (18)F-FDG PET reduced the number of futile hemithyroidectomies by 66% (25/38) (95% confidence interval, 49%-80%; Fisher's exact test, P = 0.0038). Semiquantitative analysis using standardized uptake values did not help to further reduce this number. CONCLUSION: In addition to data in the literature demonstrating accurate detection of thyroid cancer by (18)F-FDG PET, this study showed that (18)F-FDG PET should play an important role in the management of patients with inconclusive cytologic diagnosis of a thyroid nodule. (18)F-FDG PET reduced the number of futile hemithyroidectomies by 66%. Although PET is a relatively costly procedure, this cost outweighs the costs and risks associated with unnecessary thyroid surgery.

van den Hoogen FJ, Oyen WJ. · Universitair Medisch Centrum St Radboud, afd. Keel-, Neus- en Oorheelkunde en Hoofd-halschirurgie, Postbus 9101, 6500 HB Nijmegen. · Ned Tijdschr Geneeskd. · Pubmed #12908347 No free full text.

Abstract: A 48-year-old woman had a lump in her throat and dysphagia. On examination an oropharyngeal mass was seen which was diagnosed as a lingual thyroid.

Oyen WJ, Verhagen C, Saris E, van den Broek WJ, Pieters GF, Corsten FH. · Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands. · J Nucl Med. · Pubmed #10768565 links to  free full text

Abstract: For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered.