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Background: Many countries have national guidelines for the management of differentiated thyroid cancer (DTC), including a risk stratification system to predict recurrence of disease. Studies whether these guidelines could also have relevance, beyond their original design, in predicting survival are lacking. Additionally, no studies evaluated these international guidelines in the same population, nor compared them with the TNM system. Therefore, we investigated the prognostic value of 6 stratification systems used by 10 international guidelines, and the TNM system with respect to predicting disease-specific survival (DSS). Methods: We retrospectively studied adult patients with DTC from a Dutch university hospital. Patients were classified using the risk classification described in the British, Dutch, French, Italian, Polish, Spanish, European Society of Medical Oncology, European Thyroid Association, the 2009 and 2015 American Thyroid Association (ATA) guidelines, and the latest TNM system. DSS was analyzed using the Kaplan-Meier method, and the statistical model performance using the C-index, Akaike information criterion, Bayesian information criterion, and proportion of variance explained. Results: We included 857 patients with DTC (79% papillary thyroid cancer, 21% follicular thyroid cancer). Median follow-up was 9 years, and 67 (7.8%) died because of DTC. The Dutch guideline had the worst statistical model performance, whereas the 2009 ATA/2014 British guideline had the best. However, the (adapted) TNM system outperformed all stratification systems. Conclusions: In a European population of patients with DTC, of 10 international guidelines using 6 risk of recurrence stratification systems and 1 mortality-based stratification system, our optimized age-adjusted TNM system (8th edition) outperformed all other systems. [ABSTRACT FROM AUTHOR]

Objective: To examine the predictive value of unremarkable nonstimulated highly sensitive thyroglobulin (hsTg) measurement with regard to the results of stimulated thyroglobulin (Tg) measurement, diagnostic whole‐body scintigraphy, recurrence and differentiated thyroid cancer (DTC)‐related death. Design, Patients and Measurements: We retrospectively analysed the data of all 461 (410 without anti‐Tg‐antibodies [TgAbs], 51 with) DTC patients who were referred to our department for treatment and follow‐up care of differentiated thyroid cancer from 2004 onwards, and in whom at least one posttreatment Tg value was measured in our hospital at least 3 months after I‐131 ablation. Results: In the group of TgAb‐negative patients, 2.0% of patients with an unstimulated Tg < 0.1 ng/ml showed a stimulated Tg ≥ 1.0 ng/ml, whereas this happened in 77.6% with an unstimulated Tg ≥ 0.1 but <1.0 ng/ml. An unstimulated hsTg ≥ 0.1 ng/ml had a sensitivity specificity positive and negative predictive value of 90.0%, 94.1%, 77.6% and 97.6%, respectively, for a stimulated Tg ≥ 1.0 ng/ml. In TgAb‐positive patients, this was 75%, 97%, 75% and 97%, respectively. An unstimulated Tg ≥ 0.1 ng/ml did not significantly discriminate with regard to the risk of DTC‐related death (p =.06), but ≥1.0 ng/ml did (p =.012), as did a stimulated Tg ≥ 1.0 ng/ml (p =.029). Excluding patients with distant metastases at diagnosis nullifies this significance. Conclusion: Except for patients with distant metastases, both TgAb negative and TgAb positive patients with an undetectable nonstimulated hsTg measurement have a very good prognosis. The high net present value of unstimulated hsTg testing means that further diagnostic procedures can be omitted in such patients. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) is the only cancer entity for which the UICC/AJCC (Union for International Cancer Control and American Joint Committee on Cancer) TNM (tumor–node–metastasis) staging system involves an age cutoff as a prognostic criterion. However, the optimal age cutoff has not yet been determined in detail. The aim of our study was therefore to investigate the optimal age cutoff for the TNM staging system to predict disease-specific survival (DSS) with a focus on differences between patients with papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Methods: We retrospectively studied two large well-described cohorts of adult DTC patients from a Dutch and a German university hospital. DSS was analyzed for DTC overall, and for PTC and FTC separately, using several age cutoffs (per 5-year increment between 20 and 85 years and subsequently 1-year increments between 35 and 55 years), employing the histopathological criteria from the TNM staging system, eighth edition. Results: We included 3074 DTC patients (77% PTC and 23% FTC; mean age at diagnosis was 49 years). Median follow-up was seven years. For DTC and for PTC and FTC separately, the majority of the age cutoffs had a better statistical model performance than a model with no age cutoff. For DTC overall and for PTC, an age cutoff of 50 years had the best statistical model performance, while it was 40 years for FTC. Conclusions: In this large European population of DTC patients, when employing the histopathological criteria of the TNM system (eighth edition), the optimal age cutoff to predict DSS is 50 years rather than the 55 years currently in use. With the optimal age cutoff being 50 years for PTC and 40 years for FTC, there was a substantial difference in age cutoff for the respective histological entities. Therefore, implementation of different age cutoffs for PTC and FTC could improve the predictive value of the TNM staging system. [ABSTRACT FROM AUTHOR]

Summary: Background: After partial resection of the thyroid gland, a second operation referred to as "completion thyroidectomy" may be required if histopathological analysis indicates the presence of differentiated thyroid cancer (DTC). Although there is little evidence, it is assumed that the time point of completion thyroidectomy is not critical for oncological prognosis of patients with DTC. We assessed whether patients with total thyroidectomy (TTx) in a two‐step procedure have an equal long‐term prognosis with regard to disease‐specific survival (DSS) compared to patients immediately undergoing total thyroidectomy in a one‐step procedure. Methods: A database study using the Würzburg thyroid cancer database with 2258 patients with pT1a‐pT4b tumours DTC who were operated between 1980 and 2016 was carried out. Results: A total of 277 patients with papillary microcarcinoma pT1aN0M0 were treated by hemithyroidectomy. TTx as one‐step procedure was performed in 1114 patients compared to 867 with TTx as a two‐step procedure. Patients with papillary thyroid cancer more frequently had a TTx as one‐step procedure than follicular thyroid cancer patients (59.4% vs 47%; P < 0.001). Compared to a one‐step thyroidectomy, overall complication rate was not different compared to patients undergoing a single operation. Multivariate analysis showed that the presence of distant metastases, T‐stage and age at diagnosis were the only independent determinants for DTC‐specific survival, regardless of a one‐ or two‐time thyroidectomy. Conclusion: The present study on the largest of such patient collectives provides evidence that a delayed completion operation does not affect DSS in DTC, nor does it lead to a significant increase in complication rates. [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess the changes resulting from the changes from UICC/AJCC TNM version 7 to version 8 and to subsequently determine whether TNM version 8 is an improvement compared to previous iterations of the TNM system and other staging systems for differentiated thyroid cancer (DTC) with regard to prognostic power. Design: Database study of DTC patients treated in our centre between 1978 up to and including 1 July 2014. Results were compared to our previous comparison of prognostic systems using the same data set. Patients: 2257 DTC patients. Measurements: Staging in accordance with TNM 7 and TNM 8. Thyroid cancer‐specific mortality; comparison was based on p‐values of univariate Cox regression analyses as well as analysis of the proportion of variance explained (PVE). Results: There is a redistribution from stage 3 to lower stages affecting 206 (9.1%) patients. DTC‐related mortality according to Kaplan‐Meier for younger and older patients in TNM 7 had a slightly lower prognostic power than that in accordance with TNM 8 (P = 8.0 10−16 and P = 1.5 10−21, respectively). Overall staging is lower in 627/2257 (27.8%) patients. PVE (TNM 7: 0.29; TNM 8: 0.28) and the P‐value of Cox regressions (TNM 7: P = 7.1*10−52; TNM 8: P = 3.9*10−49) for TNM version 8 are marginally lower than that for TNM version 7, but still better than for any other DTC staging system. Conclusion: TNM 8 results in a marked downstaging of patients compared to TNM 7. Although some changes, like the change in age boundary, appear to be associated with an improvement in prognostic power, the overall effect of the changes does not improve the predictive power compared to TNM 7. [ABSTRACT FROM AUTHOR]

The objective of the work was to investigate the relationship between thyroglobulin doubling time (TgDT) as a marker of speed of response to 131I-therapy and the differentiated thyroid cancer (DTC) recurrence rate, DTC specific mortality rate, and relative survival rate in a DTC population followed over a long period of time after 131I-therapy. From our database, data of 1354 patients were reviewed. TgDT could be calculated in 174 patients, however, 376 patients did not have sufficient Tg values available for TgDT calculation and 804 patients reached biochemical remission before a sufficient number of Tg measurements for TgDT calculation was acquired. Main outcome measures were recurrence-free, DTC specific, and relative survival rates. In patients < 45 years, TgDT in multivariate analysis was identified as the solitary significant determinant of DTC specific and relative survival. In patients ≥ 45 years of age at diagnosis, TgDT is an independent, but not the only determinant of recurrence free, DTC specific, and relative survival. Importantly, in this age group life expectancy is normal in patients reaching rapid biochemical remission (i. e., before TgDT can be calculated); it was reduced in patients with a negative TgDT, which normally is deemed a marker of response to therapy. Only DTC patients with a rapid biochemical remission have a very good prognosis with a normal life expectancy. If no rapid biochemical remission occurs, both biochemically progressive disease and a slower biochemical remission of disease are associated with a reduced prognosis, especially in older DTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. Methods: A total of 1,873 patients without distant metastases referred for postoperative adjuvant I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Results: Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates ( p = 0.34), recurrence-free survival ( p = 0.29) or DTC -elated mortality ( p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant ( p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l ( p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l ( p = 0.53). Conclusion: The precise endogenous TSH levels at the time of I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of I ablation can be discarded. [ABSTRACT FROM AUTHOR]

Purpose: In adult differentiated thyroid cancer (DTC) patients, successful ablation and the number of I therapies needed carry a prognostic significance. The goal was to assess the prognosis of DTC in children and adolescents treated in our centre in relation to the number of treatments needed and to establish the determinants of both complete remission (CR) and successful ablation. Methods: Seventy-six DTC patients <21 years of age at diagnosis were included. Recurrence and death rates, rates of CR (=negative stimulated thyroglobulin, negative neck ultrasound and negative I whole-body scintigraphy) and successful ablation (=CR after initial I therapy) were studied. Results: No patients died of DTC. Seven patients were treated by surgery alone and did not show signs of recurrence during follow-up. Of the 69 patients also treated with I therapy, 47 patients achieved CR, 25 of whom had successful ablation. In multivariate analysis, female gender and the absence of distant metastases were independent determinants of a higher CR rate. Female gender, lower T stage and higher I activity (successful ablation, median activity 3.1 GBq, unsuccessful ablation 2.6 GBq) were determinants of a higher rate of successful ablation. After I therapy no patient showed recurrence after reaching CR or disease progression if CR was not reached. Conclusion: In our paediatric DTC population prognosis is extremely good with no deaths or recurrences occurring regardless of the number of I therapies needed or whether CR was reached. The determinants of CR and successful ablation can be used to optimize the chance of therapy success. [ABSTRACT FROM AUTHOR]

Purpose: To assess the risk of differentiated thyroid cancer (DTC) recurrence, DTC-related mortality and life expectancy in relation to the number of courses of I therapy (RIT) and cumulative I activities required to achieve complete remission (CR). Methods: The study was a database review of 1,229 patients with DTC, 333 without and 896 with CR (negative TSH-stimulated thyroglobulin and negative I diagnostic whole-body scintigraphy) after one or more courses of RIT. Results: The median follow-up was 9.0 years (range 0.1 - 31.8 years) after CR. Recurrence rates at 5 years, 10 years and the end of follow-up were 1.0 ± 0.3 %, 4.0 ± 0.7 % and 6.2 ± 1.1 %, and DTC-related mortality was 0.1 ± 0.1 %, 0.5 ± 0.3 % and 3.4 ± 1.1 %, respectively. Recurrence rates also increased with an increasing number of RIT courses required ( p = 0.001). DTC-related mortality increased from four RIT courses. In patients with CR after one RIT course, there were no differences in recurrence or DTC-related mortality rates between low-risk and high-risk patients. In patients requiring two RIT courses these rates remain elevated in high-risk patients. Recurrence and DTC-related mortality rates were only significantly elevated in those requiring a cumulative activity over 22.2 GBq (600 mCi) from multiple RIT courses for CR. Regardless of the number of RIT courses or activity needed, life expectancy was not significantly lowered. Conclusion: If more than one RIT course is needed to achieve CR, higher recurrence and DTC-related mortality rates are observed, especially in high-risk patients. Patients requiring >22.2 GBq I for CR should be followed in the same way as patients in whom CR is never reached as long-term mortality rates are similar. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prognostic value of O-(2-[F]fluoroethyl)- l-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas. Methods: We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax. Results: Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality ( p = 0.005) and progression-free survival ( p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade ( p = 0.001) and SUVmax ≥ 2.6 ( p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 ( p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation ( p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. Conclusion: In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval. [ABSTRACT FROM AUTHOR]

Summary Objectives To assess (i) the influence of Thyrotropin (TSH) suppression at a level of <0·1 mU/l and (ii) whether FT3 and FT4 levels have a prognostic significance independently of TSH values with regard to survival in patients with differentiated thyroid carcinoma (DTC) and distant metastases. Patients and methods In a retrospective patient chart study, we reviewed survival in 157 DTC patients with distant metastases treated between September 1985 and 1 July 2010. Patients with at least three available FT3 and FT4 values during TSH suppression were eligible. Results Fifty-three of 157 patients died from DTC. DTC-specific survival was significantly better in patients with a median TSH level ≤0·1 mU/l (median survival 15·8 years) than those with a non-suppressed TSH level (median survival 7·1 years; P < 0·001). However, there was no further improvement in survival caused by TSH suppression to a level ≤0·03 mU/l ( P = 0·24). FT3 and FT4 levels were also significantly associated with poorer survival; of these, only the prognostic value of FT3 was independent from that of TSH levels. Conclusion The care of patients with DTC and distant metastases is like walking an endocrinological tightrope: non-suppressed TSH levels, that is, >0·1 mU/l, are associated with an impaired prognosis. There is, however, no prognostic benefit from suppressing TSH to levels lower than 0·1 mU/l. On the contrary, an improvement in prognosis might be achieved by keeping FT3 levels as low as possible. [ABSTRACT FROM AUTHOR]

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) comprise a group of rare malignant tumours with heterogeneous behaviour. This study aimed to assess long-term survival and prognostic factors associated with survival, in order to optimise counselling. This population-based study included all GEP-NENs diagnosed between 1989 and 2016 in the Netherlands, selected from the Netherlands Cancer Registry. Overall survival (OS) and relative survival (RS) were calculated. A Cox Proportional Hazard analysis was used to identify prognostic factors (gender, age, tumour stage, location and treatment) for OS. Analyses were stratified by metastatic disease status and tumour grade. In total, 9697 patients were included. In grade 1, 2 and 3 non-metastatic GEP-NENs (N = 6544), 5-year OS and RS were 81% and 88%, 78% and 83%, and 26% and 30%, respectively. In grade 1 non-metastatic GEP-NENs 10-year OS and RS were 68% and 83%. In grade 1, 2 and 3 metastatic GEP-NENs (N = 3153), 5-year OS and RS rates were 47% and 52%, 38% and 41%, and 5% and 5%, respectively. The highest (relative) survival rates were found in appendicular and rectal NENs, demonstrating 10-year OS and RS of 87% and 93%, and 81% and 95%, respectively. These long-term follow-up data demonstrate significant differences in survival for different grades, tumour stage, and primary origin of GEP-NENs, with the most favourable overall and RS rates in patients with non-metastatic grade 1 appendicular and rectal NENs. This study demonstrates unique long-term OS and RS rates using combined stratification by tumour site, grade and stage. • GEP-NENs are a rare, diverse and complex group of malignant tumours. • Non-metastatic grade 1 GEP-NENs show 10-year relative survival rates of 83%. • Metastatic GEP-NENs show 10-year relative survival rates of 3–36%. • The highest survival rates were found in grade 1 non-metastatic appendicular NENs. • Gender, age, stage, grade, and location are important prognostic factors in GEP-NEN. [ABSTRACT FROM AUTHOR]

Aim: to determine whether [(18)F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography and X-ray computed tomography (PET/CT) findings and metabolic parameters before combined chemo- and radiotherapy (CRT) have a prognostic value in patients with anal carcinoma. Materials and Methods: 45 patients with anal cancer who underwent pre-treatment FDG-PET/CT were included. Metabolic parameters, recurrence and anal carcinoma specific survival were analyzed. Results: SUV max and metabolic volume of the primary tumour were significantly higher in patients with lymph node or distant metastases than in those with locally confined disease (p=0.020 and p=0.015, respectively). The extent of disease (local tumour only, lymph node or distant metastases) was highly predictive of both for recurrence free and disease specific survival (p=0.010 and p<0.001, respectively). Recurrence free (p=0.010) and anal carcinoma specific survival (p=0.006) differed significantly between patients with a metabolic volume ≤45ml and >45ml. Multivariate analysis revealed that a metabolic volume >45ml was the only significant independent determinant (p=0.19) for recurrence free survival whereas for anal carcinoma specific survival the extent of disease was identified as the only significant independent determinant (p=0.002). Conclusions: the extent of disease on FDG PET/CT before combined radio-chemotherapy is strongly predictive of prognosis in anal cancer. Furthermore, patients with a large metabolic volume of the primary tumour (>45ml) are at significantly higher risk of recurrence. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of the present study was to investigate the diagnostic and prognostic value of combined 18F-2-fluorodeoxyglucose positron emission tomography and contrast enhanced X-ray computed tomography (FDG-PET/CT) in women with a suspicion of recurrent ovarian cancer. Patients and methods: We retrospectively reviewed 48 patients with a suspicion of recurrent ovarian cancer who were referred to our department for combined FDG-PET/CT. Results: Median follow-up was 25 months. 38/48 (79%) patients showed pathological findings on PET/CT. 17/48 (35%) of patients died of ovarian cancer. One FDG-PET/CT was false positive and one was false negative, leading to a sensitivity and positive predictive value of 97% and a specificity and negative predictive value of 90%. 33/48 (69%) underwent a change in therapy following FDG-PET/CT. There was a significantly better survival in FDG-PET/CT negative than in positive patients (p =0.04). In the FDG-PET/CT negative group no patients had died of ovarian cancer during follow-up. Remarkably, there was no difference in survival between patients who only had peritoneal metastases on FDG-PET/CT and those who also had extraperitoneal metastases (p =0.71). Conclusion: A negative FDG-PET/CT has a high negative predictive value for the presence of disease and, more importantly, is associated with a very good disease-specific survival rate. [Copyright &y& Elsevier]