Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal.

INTRODUCTION: The clinical benefits of recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen) are well established as an alternative stimulation procedure to thyroid hormone withdrawal in the diagnostic follow-up of thyroid cancer patients. By avoiding periods of hypothyroidism, patients do not suffer from a decreased quality of life and keep their ability to work. This study compared the frequency, the duration and the cost of sick leave for follow-up control between rhTSH and withdrawal. METHODS: The study population consisted of patients with thyroid carcinoma first treated by thyroidectomy and radioiodine ablation. Patients were recruited at their control visit between October 2004 and May 2006 in three hospitals, both prospectively and retrospectively. Collection data consisted of patient information, job characteristics and duration of sick leave during the month before and the month after control. The valuation of sick leave used the friction cost method. RESULTS: Among the 306 patients included, 292 (95%) completed the entire questionnaire. The mean age was 46.7 years. Among the 194 active patients, patients treated with rhTSH, when compared with patients treated by withdrawal, were less likely to require sick leave (11 vs 33%; P=0.001). The mean duration of sick leave was shorter (3.1 vs 11.2 days; P=0.002) and indirect costs due to absenteeism accounted for 454 Euro +/- 1673 vs 1537 Euro +/- 2899 for withdrawal stimulation. CONCLUSION: For active patients, rhTSH treatment reduced the length and the cost of sick leave by 8.1 days and 1083 Euro per control respectively, when compared with withdrawal treatment.

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.

CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

[Report of 2 cases of pleural recurrences of surgically treated bronchogenic carcinoids. Diagnostic and therapeutic problems]. / A propos de 2 récidives pleurales de carcinoïdes bronchiques opérés. Problèmes diagnostique et thérapeutique.

Recurrence after surgery for bronchial carcinoid tumors is very uncommon in cases of typical tumors and occasionally seen in cases of atypical tumors. We observed two cases of recurrence in an unusual location, the pleura. Somatostatin analog and MIBG scinigrams were useful for diagnosis. Treatment required surgical excision of the relapsing tumor, cytoreductive hepatic surgery or hepatic arterial chemoembolization for liver metastases, chemotherapy, interferon, radionuclide therapy, and somatostatin analogs for carcinoid syndrome.

Assessment of the incremental value of recombinant thyrotropin stimulation before 2-[18F]-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging to localize residual differentiated thyroid cancer.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Follow-up of low-risk differentiated thyroid cancer patients who underwent radioiodine ablation of postsurgical thyroid remnants after either recombinant human thyrotropin or thyroid hormone withdrawal.

BACKGROUND: We previously demonstrated comparable thyroid remnant ablation rates in postoperative low-risk thyroid cancer patients prepared for administration of 3.7GBq (131)I (100 mCi) after recombinant human (rh) TSH during T(4) (L-T4) therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared the outcomes of these patients 3.7 yr later. PATIENTS AND METHODS: Fifty-one of the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight received rhTSH and serum thyroglobulin (Tg) sampling. A (131)I whole-body scan was performed in 43 patients, and successful ablation was defined by criteria from the previous study. Based on the criterion of uptake less than 0.1% in thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was used, five patients (four euthyroid, one hypothyroid) had minimal visible activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml. RESULTS: No patient in either group died, and no patient declared disease free had sustained tumor recurrence. Nine (four euthyroid, five hypothyroid) had received additional (131)I between the original and current studies due to detectable Tg or imaging evidence of disease; with follow-up, all now had a negative rhTSH-stimulated whole-body scan and seven (three euthyroid, four hypothyroid) had a stimulated serum Tg less than 2 ng/ml. CONCLUSIONS: In conclusion, after a median 3.7 yr, low-risk thyroid cancer patients prepared for postoperative remnant ablation either with rhTSH or after L-T4 withdrawal were confirmed to have had their thyroid remnants ablated and to have comparable rates of tumor recurrence and persistence.

[1959-1999: from serum markers to 18-FDG in oncology. The experience of the René-Huguenin Center]. / 1959-1999: des marqueurs sériques au 18-FDG en oncologie. L'expérience du centre René-Huguenin.

Blood tumour markers are widely used in the follow up of patients treated for a malignant tumour. In many cases where the tumour associated marker is increasing the clinical and radiological evaluations remain normal. PET and CDET-scan with 18-FDG have been demonstrated as powerful tools in oncology and their use in such situations may give a new appraisal on the development of the disease. Seventy patients with an isolated increasing of a tumour associated marker (CEA or CA19.9, CA15.3, CA125) were tested. Accuracy and sensitivity of the method were 82.8 and 96.5%, specificity 25%, and positive and negative predictive values 50% and 87%. Focusing on breast carcinomas and CA15.3 as well as ovarian cancers and CA125, the sensitivity and the predictive value are reaching 100%. Patients exhibiting a tumor target associated to an increasing in blood tumour marker may be treated earlier with dedicated protocols.

Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d'Etude des Tumeurs à Calcitonine (GETC).

Combinations of doxorubicin and streptozocin and 5-FU and dacarbazine were given alternately to 20 patients with metastatic medullary thyroid carcinoma. Three partial responses and 10 long-term stabilizations were observed. No unexpected toxicity occurred.