The efficacy of adjuvant radioactive iodine after reoperation in patients with persistent or recurrent differentiated thyroid cancer: a systematic review.

OBJECTIVE: The effectiveness of adjuvant radioiodine (RAI) after reoperation in patients with persistent or recurrent differentiated thyroid cancer (DTC) is controversial. Although various organizations recognize that strong evidence for the use of RAI is lacking, they continue to recommend the use of adjuvant RAI therapy for select groups of patients. This is concerning as RAI therapy has potential side effects such as gastrointestinal symptoms, bone marrow suppression, and gonadal damage. METHODS: Four electronic databases were systematically searched for randomized trials or observational studies that examined the outcomes of adjuvant RAI after reoperation for recurrent DTC, among patients of any age. The baseline characteristics, treatment response, disease progression, and overall survival of these studies were synthesized and reported. A meta-analysis of the use of RAI on progression-free survival was also performed. RESULTS: Six observational studies, comprising a combined cohort of 437 patients who underwent reoperation, were included from 1212 records. Adjuvant RAI after reoperation in recurrent DTC was not associated with longer progression-free or overall survival. There was also no association of RAI with excellent structural or biochemical treatment response, lower thyroglobulin levels, nor a lower rate of second recurrence or distant metastases. CONCLUSIONS: Adjuvant RAI after reoperation in recurrent DTC was not associated with improved cancer or treatment-related outcomes. However, as the included studies were of inadequate quality, there is an urgent need for randomized trials and well-analyzed cohort studies. Physicians should exercise clinical judgment to prescribe adjuvant RAI for only selected, high-risk patients.

A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients.

BACKGROUND: The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19-40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly. METHODS: We identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence. RESULTS: The multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state. CONCLUSION: Using a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.

Calcium, Vitamin D, and Bone Derangement in Nephrotic Syndrome.

INTRODUCTION: Derangement in calcium homeostasis is common in nephrotic syndrome (NS). It is postulated that low serum total calcium and vitamin D levels are due to loss of protein-bound calcium and vitamin D. It is unclear if free calcium and free vitamin D levels are truly low. The guideline is lacking with regards to calcium and vitamin D supplementation in NS. This study aims to examine calcium and vitamin D homeostasis and bone turnover in NS to guide practice in calcium and vitamin D levels supplementation. METHODOLOGY: This is a prospective pilot study of ten patients diagnosed with NS, and eight healthy controls. Calcium, vitamin D, and bone turnover-related analytes were assessed at baseline, partial and complete remission in NS patients and in healthy controls. RESULTS: NS patients had low free and total serum calcium, low total 25(OH)D, normal total 1,25(OH)D levels and lack of parathyroid hormone response. With remission of disease, serum calcium and vitamin D metabolites improved. However, nephrotic patients who do not attain complete disease remission continue to have low 25(OH)D level. CONCLUSION: In this study, the vitamin D and calcium derangement observed at nephrotic syndrome presentation trended towards normalisation in remission. This suggested calcium and vitamin D replacement may not be indicated in early-phase nephrotic syndrome but may be considered in prolonged nephrotic syndrome.