Response assessment in advanced differentiated thyroid cancer.

Purpose:Automatic quantification of longitudinal changes in PET scans for lymphoma patients has proven challenging, as residual disease in interim-therapy scans is often subtle and difficult to detect. Our goal was to develop a longitudinally-aware segmentation network (LAS-Net) that can quantify serial PET/CT images for pediatric Hodgkin lymphoma patients.Materials and Methods:This retrospective study included baseline (PET1) and interim (PET2) PET/CT images from 297 patients enrolled in two Children’s Oncology Group clinical trials (AHOD1331 and AHOD0831). LAS-Net incorporates longitudinal cross-attention, allowing relevant features from PET1 to inform the analysis of PET2. Model performance was evaluated using Dice coefficients for PET1 and detection F1 scores for PET2. Additionally, we extracted and compared quantitative PET metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in PET1, as well as qPET and ΔSUVmax in PET2, against physician measurements. We quantified their agreement using Spearman’s ρ correlations and employed bootstrap resampling for statistical analysis.Results:LAS-Net detected residual lymphoma in PET2 with an F1 score of 0.606 (precision/recall: 0.615/0.600), outperforming all comparator methods (P<0.01). For baseline segmentation, LAS-Net achieved a mean Dice score of 0.772. In PET quantification, LAS-Net’s measurements of qPET, ΔSUVmax, MTV and TLG were strongly correlated with physician measurements, with Spearman’s ρ of 0.78, 0.80, 0.93 and 0.96, respectively. The quantification performance remained high, with a slight decrease, in an external testing cohort.Conclusion:LAS-Net demonstrated significant improvements in quantifying PET metrics across serial scans, highlighting the value of longitudinal awareness in evaluating multi-time-point imaging datasets.

Residual thyroid tissue after total thyroidectomy in differentiated thyroid cancers is considered an independent risk factor for recurrence. Guidelines recommend following up patients after surgery with thyroglobulin (Tg), neck ultrasonography, and occasionally whole-body radioactive scan. However, the results of serum thyroglobulin and whole-body radioiodine scan are often discordant. The present study was undertaken to determine the levels of serum-stimulated thyroglobulin to complement the findings of residual thyroid tissue in the radioactive whole-body scan. One hundred twenty-six patients had undergone a radioiodine (131 I) whole-body scan (WBS) during the study duration, and 121 were available for analysis. The thyroglobulin level (measured by the CLIA method) was recorded at the time of these scans. The data was analysed to determine the level of stimulated thyroglobulin correlating with residual thyroid tissue, locoregional, and distant metastasis as assessed by WBS. The presence of residual thyroid tissue was noted in an overwhelmingly high 94% of cases. Twenty-four of the 28 patients with stimulated Tg < 2ng/dl had residual thyroid tissue on a WBS. The discordancy rate (positive moderate - large WBS and negative serum thyroglobulin) of 64.28% was seen. Using ROC the serum thyroglobulin cut-offs levels for the loco-regional disease were found to be 27.705ng/dl and 94.770ng/dl for distant metastasis. The results highlight the fact that serum Tg levels cannot be used as an accurate predictor of the extent of the remnant thyroid tissue. Irrespective of the quality of surgery, which was analysed based on the centre and surgical specialty, over 90% of cases had residual thyroid tissue on WBS. The use of only stimulated Tg levels for follow-up may be inaccurate. Serum Tg is a useful test along with radioactive whole-body scans to distinguish local disease, loco-regional disease, and distant metastasis.

Some patients with elevated serum thyroglobulin (Tg) but a negative diagnostic whole body scan (WBS) after initial therapy for differentiated thyroid carcinoma may benefit from empirical radioactive iodine (RAI) therapy. However, previous studies enrolled patients with negative diagnostic WBS, regardless of neck ultrasonography (USG) and/or (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), which have become the preferred diagnostic procedures in such patients. The aim of this study was to evaluate the usefulness of empirical RAI therapy in patients with elevated stimulated Tg level and negative USG/FDG-PET findings after initial therapy for papillary thyroid carcinoma (PTC). This comparative study enrolled 39 patients with elevated stimulated Tg, negative diagnostic WBS, and negative USG/FDG-PET 1 yr after initial treatment. Empirical RAI therapy was performed in 14 patients (treatment group), whereas 25 patients were followed up without therapy (control group). There was no significant between-group difference in basal clinicopathological parameters. None of the 14 patients in the treatment group showed iodine uptake on posttreatment WBS. Five of 14 patients (36%) in the treatment group and eight of 25 (32%) in the control group had recurrence during the median 37 months of follow-up (P = 0.99). Changes in serum stimulated Tg concentrations did not differ between the two groups. Empirical RAI therapy and posttreatment WBS were not useful diagnostically or therapeutically in patients with positive serum stimulated Tg if such patients had negative USG and negative FDG-PET findings after initial treatment of PTC.

Mutual interference between serum thyroglobulin and antithyroglobulin antibody in an automated chemiluminescent immunoassay

A 38-year-old woman with papillary carcinoma of the thyroid who underwent total thyroidectomy followed by high-dose radioiodine ablation was called for Iodine-131 (I-131) whole-body follow-up scan. Her follow-up scan revealed focal tracer accumulation in the lower aspect of the right posterior neck region. Her stimulated serum thyroglobulin and anti-thyroglobulin antibodies were 0.27 ng/ml and undetectable, respectively. Further clinical examination of the patient revealed a black scab in the same region. The patient revealed a history of wasp bite 2 days before iodine administration.

(1) To investigate whether elevated serum anti-thyroglobulin antibody (ATG) reflects the recurrence of cancer in patients with differentiated thyroid carcinoma (DTC) in whom thyroglobulin was undetectable after radioiodine ablation. (2) To assess the sensitivity of disease detection for (99m)Tc-MIBI whole-body scans (WBSs) in these patients and investigate the correlation between MIBI WBS results and high serum ATG levels. In this retrospective study, we evaluated 14 patients (13 women and 1 man; mean age 44 +/- 19 years) with DTC who underwent total or near-total thyroidectomy followed by an ablative dose of I at various time intervals. According to histopathological findings, 10 patients (71.4%) who were diagnosed as having papillary carcinoma and four patients (28.6%) as having follicular cell carcinoma, had high serum ATG concentrations (> 40 IU x ml(-1); range, 62-2000 IU x ml(-1)), but low serum thyroglobulin concentrations (< 1.6 ng x ml). Post-therapeutic and diagnostic (131)I WBSs and (99m)Tc-MIBI WBSs were performed. Scans were visually evaluated for detecting recurrence. If necessary, bone scans, chest X-rays, computerized tomography, ultrasonography and histopathological evaluation were performed. Recurrent and/or persistent disease was found in 12 of the patients. This was confirmed pathologically in four patients and by using other imaging methods in eight (bone scans, computerized tomography, ultrasonography). The sensitivity and specificity of disease detection for MIBI WBSs was 66.7% and 100%, respectively. For (131)I WBSs, the sensitivity of disease detection was 55.6%. Among these 12 patients, 10 responded to treatment (three underwent surgery, seven received radioiodine therapy, and two had surgery + radioiodine therapy). ATG levels decreased in eight of the 10 patients, but remained persistently elevated in two despite treatment. (1) Persistently elevated ATG levels appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum tyroglobulin levels. Thus, the routine measurement of ATG antibody in such patients is of great value. (2) In these patients, (99m)Tc-MIBI has a relatively high sensitivity in the diagnosis of a recurrence of thyroid cancer or metastases. So, in patients with elevated ATG but undetectable serum thyroglobulin levels, (99m)Tc-MIBI can be used to determine whether there is a recurrence of DTC or metastases.

Anti-thyroglobulin antibodies in differentiated thyroid carcinoma patients: Study of the clinical and biological parameters

The occurrence of thyroid disorders relies on I nutrition and monitoring of all populations is recommended. Measuring I in urine is standard but thyroglobulin in serum is an alternative. This led us to assess the reliability of studies using serum thyroglobulin compared with urinary I to assess the I nutrition level and calculate the number of participants needed in a study with repeated data sampling in the same individuals for 1 year. Diet, supplement use and life style factors were assessed by questionnaires. We measured thyroglobulin and thyroglobulin antibodies in serum and I in urine. Participants were thirty-three Caucasians and sixty-four Inuit living in Greenland aged 30-49 years. Serum thyroglobulin decreased with rising I excretion (Kendall's τ -0·29, P=0·005) and did not differ with ethnicity. Variation in individuals was lower for serum-thyroglobulin than for urinary I (mean individual CV: 15·1 v. 46·1 %; P<0·01). It required 245 urine samples to be 95 % certain of having a urinary I excretion within 10 % of the true mean of the population. For serum-thyroglobulin the same precision required 206 samples. In an individual ten times more samples were needed to depict I deficiency when using urinary I excretion compared with serum-thyroglobulin. In conclusion, more participants are need to portray I deficiency in a population when using urinary I compared with serum-thyroglobulin, and about ten times more samples are needed in an individual. Adding serum-thyroglobulin to urinary I may inform surveys of I nutrition by allowing subgroup analysis with similar reliability.

Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma.

SUMMARYAlthough thyroid nodule is a common presentation, malignancy is rare. The present study investigated biochemical predictors of malignancy in enlarged thyroid. This is a prospective study of all willing patients 18 to 70 years presenting with a complaint of thyroid swelling and who underwent definitive surgery over a period of 19 months. All subjects were initially evaluated with detailed history, physical examination, ultrasonography of neck and fine needle aspiration cytology (FNAC). Preoperative estimation of serum thyroid stimulating hormone (TSH), thyroglobulin (Tg) and anti-thyroglobulin (anti Tg) antibody was obtained. The treatment plan was based on FNAC results and included hemi- or total thyroidectomy. During the study period, 110 patients underwent thyroidectomy, and met the selection criteria, of which 47 patients had malignancy on final histopathology. The majority were females, 30 to 60 years old. Median serum Tg, TSH and anti Tg levels in the benign group were, respectively 29 ng/ml, 1,6 mIU/L and 1,1 IU/ml, whereas in malignant nodules they were 162 ng/ml. 1,7 mIU/L and 0,9 IU/ml. On receiver operating characteristic curve analysis, a Tg cut off value of 53 ng/ml predicted malignancy risk with a sensitivity and specificity of 72% and 73%, respectively (p < 0.001). Our study showed the utility of preoperative Tg in predicting risk of malignancy. Its role should be further explored especially in the backdrop of indeterminate cytology through a larger study.

(131)I whole-body scan (WBS) and serum thyroglobulin (TG) are important in detecting thyroid remnants or recurrent disease in patients with differentiated thyroid cancer. Usually, a diagnostic WBS is carried out 6 months after ablation to exclude residual disease. We retrospectively analysed results of a second routine diagnostic WBS and TG measurements at 1 year after thyroablation and correlated these to the risk profile of patients with long-term follow-up. A total of 197 patients were followed up after thyroidectomy and ablative (131)I therapy. Follow-up included clinical examination, radioiodine WBS and thyroid-stimulating hormone (TSH), free thyroxine and TG measurements at 3-6 months and 1 year after ablation. WBS (+) patients received a therapeutic activity of (131)I. The risk profile of patients was defined according to clinical results before the 1-year control. Clinical results at 1 year after ablation were analysed in correlation to the patient risk profile and long-term follow-up data (mean 7.2 years). One year after thyroablation, 95.8% of low-risk patients had no residual disease when diagnostic WBS was carried out using 370 MBq (131)I; 4.2% of low-risk patients had residual disease at this time point. In the high-risk group of this cohort, 54.5% were disease-free 1 year after ablation, but 45.5% demonstrated residual disease. After the 1-year control, 94% of all applied radioiodine therapies were executed in the high-risk group, compared with 6% in the low-risk group (p < 0.01). A second routine WBS 1 year after thyroablation is not indicated in low-risk patients. Risk stratification according to the early clinical course effectively identified patients with higher likelihood of persistent or recurrent disease in the long-term follow-up.

Background: In patients with differentiated thyroid cancer (DTC) and raising serum thyroglobulin (Tg) after total or near-total thyroidectomy and 131I remnant ablation an empiric 131I therapy may be considered. However, outcome data after empiric therapy in did not show a clear evidence of improved survival. We assessed the efficacy of such empiric 131I therapy in patients with DTC and evaluated the long-term outcome.Methods: A total of 100 patients with DTC showing raised Tg level during follow-up after thyroidectomy and 131I ablation were treated with a further 131I therapy (6.1 ± 1.7 GBq). Whole-body scan (WBS) was performed 5–7 days after therapy. Tg value at 12 months after 131I therapy was considered as an indicator of treatment response: ≤1.5 ng/ml complete remission (CR), >50% decrease partial remission (PR), higher than pre-therapy progression disease (PD), all other cases stable disease (SD). Patients were followed-up for 96 ± 75 months.Results: After 12 months, 62% of patients were in CR, 16% in PR, 8% in SD, and 14% in PD. WBS was positive in 41% of patients and negative in 59% (P = NS). Among patients with local recurrences at WBS 89% showed either CR or PR, while 71% of patients with distant metastases were in SD or PD (P < 0.001). Distant metastases at WBS (P < 0.05), CR (P < 0.0001), and CR + PR (P < 0.0001) were predictors of both progression free survival and overall survival.Conclusion: There is a beneficial effect of 131I therapy on outcome of patients with DTC treated on the basis of elevated Tg value. In these patients, survival is affected by achievement of CR or PR at 12 months evaluation after 131I therapy and by the presence of distant metastases at WBS.

To investigate the usefulness of whole body scan (WBS) and serum thyroglobulin (Tg) measurement after thyroxine withdrawal during sequential follow-ups in patients with differentiated thyroid cancer (DTC). Two hundred and sixty-five consecutive DTC patients were enrolled. They were previously treated with near-total thyroidectomy and I-131 remnant ablation, without initial metastases or Tg antibodies. All had the first follow-up WBS and serum Tg measurement 6-12 months after initial treatment, and 165 patients received the second follow-up without further therapy. Positive/negative predictive values (PPV/NPV) were calculated by the outcome of patients being followed up for more than 8 years (mean+/-SD: 133+/-26 months). Serum Tg levels while the patients were off thyroxine therapy decreased spontaneously in 39.3% of the cases without further therapy. The NPV of the first follow-up serum Tg level was excellent: <2 microg/L and <0.5 microg/L were 95.1% and 98.2%, respectively. However, the PPV of the first follow-up serum Tg level was low: >10 microg/L and 2-10 microg/L were 40% and 9.6%, respectively. The trend of Tg levels was more informative; the PPV was 62.5% in cases with an increase of serum Tg of >10 microg/L and 16.6% with an increase of <5 microg/L. However, decreasing Tg levels may associate with rapid deterioration of disease, in which cases decrease of Tg indicated dedifferentiation of the tumor. The diagnostic WBS showed the same picture in 91.5% of the patients. Only one patient (0.6%) turned from negative study to positive during the follow-up. In the meanwhile his serum Tg levels increased from 0.56 to 13.6 microg/L. It is most informative when both the trend and the levels of Tg during sequential follow-up are considered. The diagnostic WBS may be performed for selected patients with indication based on Tg levels to localize the disease.

The work described in this thesis is concerned with investigating certain aspects of human behaviour in control tasks requiring cognitive skill. The first chapter reviews evidence in the process control literature on, (i) the characteristics of control behaviour, (ii) development of process control skills, (iii) individual differences, (iv) factors that affect performance, (v) structure of operators' behaviour, (vi) models of the process operator, (vii) methodology. The next chapter describes a preliminary field study of the behaviour of gas grid control engineers. The investigation was carried out using observations and reports from the controllers as the main source of data. The results indicated that the verbal protocol technique might give useful and more detailed data on control behaviour. Chapter 3 investigates the controllers' behaviour using verbal protocols. Previous methods of analysing protocol data are reviewed. Three methods are used to analyse the protocols of the grid controllers. The results indicate that: (a) peak activity occurred during the afternoon shifts, (b) individual differences between controllers were associated with different types of predictive behaviour, (c) some of the controllers appeared to make more accurate predictions than others. The next chapter describes a comparative study of electricity grid control engineers. The procedures for investigation are similar to those of the previous two chapters. Results from the three types of analysis indicate that, (a) morning was the most active part of the day, (b) only 32% of goal orientated behaviour was concerned with predicting and decision making compared with 88% in the gas task. A detailed analysis of decisions shows several types of decision behaviour, which are combined into a general model of decision behaviour. Chapter 5 describes an experiment in which a simulation of a simplified version of the gas control task is used to examine the effect of certain types of predictive information on the performance of naïve subjects, and to test their understanding of particular aspects of the task. Results show that although subjects’ performance improved over trials, it was not affected by the additional predictive information. Results also show that only knowledge about certain task variables seemed to be relevant to good control performance. Chapter 6 describes another experiment using the simulator in which naive subjects are given predictive information but for more trials than in the previous chapter. Changes in behaviour due to skill acquisition during the trials are investigated using verbal protocols. The results indicate that even with twice as many trials subjects could not learn to use the predictive information effectively. The protocol data shows an increase in purposive behaviour and in particular an increase in predictive behaviour. Chapter 7 describes an experiment in which the grid controllers used a simulated version of the gas control task. The purpose of the experiment was to investigate controller behaviour under more difficult and controlled conditions, using verbal protocols. The results show that behaviour on the simulator was similar to behaviour on the real task with slight modifications to cope with the more difficult task. Performance was assessed using several criteria; only small differences were found between the controllers. Chapter 8 summarises and discusses the results of the experiments and field studies and relates these to the various areas of research reviewed in Chapter 1. In particular the possibility of fundamental cognitive abilities underlying control behaviour is discussed, as well as possible limitations in the information combining processes of the prediction and decision procedures. A suggested approach for further work on cognitive skills is also mentioned.

Human antithyroglobulin (anti-HTg) in serum and tissue cultures can be assayed by coprecipitation with 125I-labelled human thyroglobulin (HTg). Co-precipitation of the antibody from different sera gives roughly parallel curves, so that a standard serum can be used for quantitiation of other sera. By assessing the binding of 125I-labelled HTg in antigen excess we estimate the antibody content of the standard serum to be 0.14 ng anti-HTg per ml. Shortened incubation minimizes non-specific binding of HTg to serum globulins and obviates pre-assay absorption of HTg. Radioassay for thyroglobulin antibodies in serum correlated with values obtained by solid-phase competitive-binding assay (SPCB). One unit in our assay corresponds to 0.014 unit by the latter assay and to 0.12 units of MRC. Research Standard A. We confirm that serum thyroglobulin seriously interferes with SPCB assay, giving what appears to be positive results for anti-HTg where none is detected with our assay. Values for anti-HTg are depressed by serum HTg but only in the presence of very high concentrations in serum.