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Objective We aimed to determine outcome predictors of papillary thyroid cancer ( PTC) persistence and recurrence, separately. Context The factors contributing to either persistence or recurrence of PTC are poorly defined, as both outcomes are usually evaluated together. Design and patients In this 10-year follow-up cohort study, 190 PTC patients were evaluated (18-85 years old; registered from 1 January 1990 to31 December 1999 at a Brazilian Cancer Care referral Hospital). After initial surgery, we examined persistence (disease detected up to 1 year), recurrence (disease detected after 1 year) and PTC-free status (disease absence during follow-up). Measurements Outcome predictors were modelled using multinomial logit regression analysis. Results The univariate analysis showed that persistence and recurrence were significantly associated with lymph node metastasis ( OR = 12·33; OR = 2·84, respectively), local aggressiveness ( OR = 5·22; OR = 3·35) and extrathyroidal extension ( OR = 5·07; OR = 7·11). Persistence was associated with male sex ( OR = 3·49), age above 45 years old at diagnosis ( OR = 1·03), macroscopic lymph node metastasis ( OR = 5·85), local aggressiveness ( OR = 5·22), each 1-cm tumour size increase ( OR = 1·34), a cancer care referral hospital as the place of initial surgery ( OR = 2·3), thyroidectomy or near total thyroidectomy( OR = 3·03) and neck dissection ( OR = 3·19). Recurrence was associated with the time of radioactive iodine (131I) therapy ( OR = 3·71). After data modelling, persistence was associated with macroscopic lymph node metastasis ( OR = 6·17), 1-cm increases in tumour size ( OR = 1·30) and thyroidectomy or near total thyroidectomy ( OR = 3·82), while recurrence was associated with surgery at referral hospital ( OR = 3·79). Conclusions The best predictors of persistence were tumour size and macroscopic lymph node metastasis; when the initial surgery is of quality, the recurrence depends more on tumour's biology aspects. [ABSTRACT FROM AUTHOR]

Angiotensin I-converting enzyme (ACE), in addition to its role in the renin angiotensin system, has a physiological function in the fibrinolysis pathway, the accurate control of which is critical for the normal development of pregnancy. Recently, the ACE I/D polymorphism was found to be associated with recurrent spontaneous miscarriages (RM). The present study analysed the relationship between ACE I/D polymorphism and the number of spontaneous miscarriages, the number of pregnancies and the number of children in a sample of 88 Italian women born before 1930, with a pre-modern reproductive behaviour. The ACE DD genotype was more prevalent among women with RM (p = 0.02). However, the women carrying the DD genotype not only had the highest number of miscarriages (p = 0.03), but also the highest number of pregnancies with an eventual complete fertility (children no = 4.4), similar to that of women carrying the other ACE genotypes. In contrast, published data on contemporary women with RM seem to indicate that the DD genotype could now be associated with a reduced reproductive success compared to the other ACE genotypes. It is suggested that this phenomenon may be the effect of the interaction between ACE genotypes and contemporary reproductive behaviours (delay in childbearing, below-replacement fertility). [ABSTRACT FROM AUTHOR]

Introduction: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population., Purpose: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC., Materials and Methods: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up., Results: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs., Conclusions: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial., Purpose: To identify clinical and molecular factors associated with control of cervical disease with EBRT., Methods: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed., Results: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04)., Conclusion: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT., (© 2024 Wiley Periodicals LLC.)

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility., Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI., Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured., Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments., Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Purpose: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS)., Methods: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status., Conclusion: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Calcitonin measurement is widely used in the diagnosis, prognosis, and follow-up of patients with medullary thyroid carcinoma (MTC). The prognostic value of undetectable postoperative calcitonin (POCal) in long-term disease outcomes remains uncertain. Objective: The aim of this study is to evaluate POCal as a prognostic marker for long-term MTC disease status. Methods: A retrospective cohort study was carried out. We collected data from the medical records of patients with MTC attending two tertiary teaching hospitals. Patients were divided according to POCal into two groups: undetectable (below the detection limit) or detectable. The outcome was determined at the last medical visit and defined as disease free (undetectable calcitonin and no evidence of disease on imaging), persistent disease (detectable calcitonin with or without structural disease), or disease-related death. Results: Three hundred thirty-four MTC patients were included in the study. The mean age at diagnosis was 41.1 ± 18.6 years; 202 patients (60.5%) were women; and 167 patients (50.0%) had sporadic MTC. The median tumor size was 2.0 cm (1.1-3.5 cm); 164 patients (49.1%) had lymph node metastasis and 63 patients (18.9%) had distant metastasis. At the first postoperative evaluation (3-6 months after surgery), 141 patients had undetectable POCal (mean age = 37.9 years, 70.9% women, median tumor size 1.5 cm [0.7-2.5 cm]; 28 [19.9%] had lymph node metastasis and none had distant metastasis). After a median follow-up of 7.7 years (2.1-13.2 years), 127 (90.1%) of these patients were free of disease, whereas 14 (9.9%) had persistent biochemical disease with stable calcitonin levels. No patient with undetectable POCal died of the disease. In the detectable POCal group (mean age = 42.9 years, 52.8% women, median tumor size 3.0 cm [1.8-4.2 cm]; 136 [70.5%] had lymph node metastasis and 63 [32.6%] had distant metastasis), 18 (9.2%) patients achieved disease-free status, 51 (26.6%) had biochemical disease, and 61 (31.6%) had persistent structural disease. Sixty-three (32.6%) patients died of disease-related events. Further analysis using a multivariate model identified undetectable POCal as an independent prognostic variable for disease-free status (HR = 5.33, CI = 2.86-9.94; p  < 0.001). Conclusions: POCal is a strong prognostic marker for long-term disease-free survival and might help define follow-up strategies for MTC patients.

Purpose: Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is a palliative therapeutic option for advanced Neuroendocrine Tumors (NETs). Prognostic factors can predict long-term outcomes and determine response to therapy. Among those already explored, biomarkers from full blood count, including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) has shown value for other solid tumors and for NETs patients submitted to other forms of therapy. However, its relation to PRRT response and patients' prognosis is still to be determined., Methods: Medical records from 96 patients submitted to PRRT between 2010 and 2017 were reviewed, median NLR and PLR were calculated from baseline flood blood count and dichotomized as high or low. Progression-free survival (PFS) and Overall Survival (OS) were calculated., Results: NLR and PLR median values were 1.8 and 123, respectively. Patients with low NLR had a significantly longer OS (estimated median of 77.5 months, 95% CI: 27.3-127.7) when compared to patients with high NLR (estimated median of 47.7 months, 95% CI: 34.7-60.8); p = 0.04. Patients with low NLR had a trend toward a longer median PFS when compared to patients with high NLR [estimated medians of 77 months (95% CI: 27.3-127.7), and 47.7 months, (95% CI: 34.7-60.7)], respectively, p = 0.08., Conclusion: Patients with advanced-stage NET with NLR higher than 1.8 have worse long term clinical outcomes after PPRT. Larger studies are needed to validate the optimal cutoff for this biomarker., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)