External beam radiation therapy for recurrent or residual thyroid cancer: What is the best treatment time and the best candidate for long-term local disease control?

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.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

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.

Hiperplasia adrenal congênita / Congenital adrenal hyperplasia

A hiperplasia adrenal congênita (HAC) é um grupo de doenças de transmissão autossômica recessiva, em que os defeitos enzimáticos levam à síntese deficiente do cortisol e excesso de androgênios adrenais. A deficiência da 21?-hidroxilase é a forma mais frequente. Na HAC clássica o excesso de androgênios resulta em virilização e desenvolvimento de genitália ambígua no recém-nascido do sexo feminino e, quando não diagnosticada, alta mortalidade no sexo masculino. É necessário um diagnóstico preciso e urgência no início do tratamento para prevenir a mortalidade e as morbidades que acompanham esta doença. Os autores apresentam de forma prática e concisa como diagnosticar, tratar e prevenir complicações.

Health related quality of life of children and adolescents with congenital adrenal hyperplasia in Brazil.

BACKGROUND: Congenital Adrenal Hyperplasia (CAH) is an endocrine disorder characterized by enzymatic deficiency in adrenal steroidogenesis, leading to adrenal insufficiency and hyperandrogenism. Patients need continuous hormone replacement therapy, but adequate control has proven challenging, exposing patients to undesirable consequences of both disease and treatment. OBJECTIVE: To evaluate the health related quality of life (HRQoL) of children and adolescents with CAH due to 21-hydroxylase deficiency. METHODS: In an analytical study, generic questionnaires, validated and translated versions, Pediatric Quality of Life Inventory 4.0 (for self-assessment of patients) and Child Health Questionnaire - PF50 (for parents) were applied and mean scores were analyzed with Student's t-test. RESULTS: We included 25 patients (19 female) with classical CAH (14 salt wasting/11 simple virilizing), mean age ± standard deviation (SD) of 11.4 ± 3.6 years (5-17.9), and their parents. Self-assessment of HRQOL showed decrease in mean scores: overall (67.8 ± 15.5 vs. 88.9 ± 7.4, p value = 0.015) and in the physical (75.2 ± 15.0 vs. 95.9 ± 5.8, p value = 0.014) and psychosocial (63.9 ± 17.8 vs. 85.0 ± 9.6, p value = 0.023) dimensions of patients, compared to healthy controls (previously published national data on children and adolescents). The assessment of the parent's view was concordant, also showing losses in the physical (43.7 ± 8.0 vs. 55.1 ± 3.6, p value = 0.013) and psychosocial (41.9 ± 9.7 vs. 53.0 ± 7.0, p value = 0.025) dimensions. The comparison of HRQOL between subgroups 1) males versus females and 2) salt-wasting versus simple virilizing showed no significant differences. CONCLUSION: There seems to be a loss of HRQOL in children and adolescents with classical CAH. The self-assessment was concordant in key areas with the assessment made by their parents. No differences were observed between genders or clinical presentation of the disease.