Novel prognostic nomogram for predicting recurrence-free survival in medullary thyroid carcinoma.

AIMS: Recently, there have been attempts to improve prognostication and therefore better guide treatment for patients with medullary thyroid carcinoma (MTC). In 2022, the International MTC Grading System (IMTCGS) was developed and validated using a multi-institutional cohort of 327 patients. The aim of the current study was to build upon the findings of the IMTCGS to develop and validate a prognostic nomogram to predict recurrence-free survival (RFS) in MTC. METHODS AND RESULTS: Data from 300 patients with MTC from five centres across the USA, Europe, and Australia were used to develop a prognostic nomogram that included the following variables: age, sex, AJCC stage, tumour size, mitotic count, necrosis, Ki67 index, lymphovascular invasion, microscopic extrathyroidal extension, and margin status. A process of 10-fold cross-validation was used to optimize the model's performance. To assess discrimination and calibration, the area-under-the-curve (AUC) of a receiver operating characteristic (ROC) curve, concordance-index (C-index), and dissimilarity index (D-index) were calculated. Finally, the model was externally validated using a separate cohort of 87 MTC patients. The model demonstrated very strong performance, with an AUC of 0.94, a C-index of 0.876, and a D-index of 19.06. When applied to the external validation cohort, the model had an AUC of 0.9. CONCLUSIONS: Using well-established clinicopathological prognostic variables, we developed and externally validated a robust multivariate prediction model for RFS in patients with resected MTC. The model demonstrates excellent predictive capability and may help guide decisions on patient management. The nomogram is freely available online at https://nomograms.shinyapps.io/MTC_ML_DFS/.

Tumour volume is a predictor of lymphovascular invasion in differentiated small thyroid cancer.

Objectives: For small thyroid cancers (≤2 cm), tumour volume may better predict aggressive disease, defined by lymphovascular invasion (LVI) than a traditional single measurement of diameter. We aimed to investigate the relationship between tumour diameter, volume and associated LVI. Methods: Differentiated thyroid cancers (DTC) ≤ 2 cm surgically resected between 2007 and 2016 were analysed. Volume was calculated using the formula for an ellipsoid shape from pathological dimensions. A 'larger volume' cut-off was established by receiver operating characteristic (ROC) analysis using the presence of lateral cervical lymph node metastasis (N1b). Logistic regression was performed to compare the 'larger volume' cut-off to traditional measurements of diameter in the prediction. Results: During the study period, 2405 DTCs were surgically treated and 523 met the inclusion criteria. The variance of tumour volume relative to diameter increased exponentially with increasing tumour size; the interquartile ranges for the volumes of 10, 15 and 20 mm diameter tumours were 126, 491 and 1225 mm3, respectively. ROC analysis using volume to predict N1b disease established an optimal volume cut-off of 350 mm3 (area under curve = 0.59, P = 0.02) as 'larger volume'. 'Larger volume' DTC was an independent predictor for LVI in multivariate analysis (odds ratio (OR) = 1.7, P = 0.02), whereas tumour diameter > 1 cm was not (OR = 1.5, P = 0.13). Both the volume > 350 mm3 and dimension > 1 cm were associated with greater than five lymph node metastasis and extrathyroidal extension. Conclusion: In this study for small DTCs ≤ 2 cm, the volume of >350 mm3 was a better predictor of LVI than greatest dimension > 1 cm.

International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS: Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS: Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION: This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.

Focused parathyroidectomy without intraoperative parathyroid hormone measurement in primary hyperparathyroidism: Still a valid approach?

BACKGROUND: Concern regarding suboptimal cure rates has led to some endocrine surgery units abandoning focused parathyroidectomy for primary hyperparathyroidism in favor of open bilateral neck exploration or making intraoperative parathyroid hormone estimation mandatory in focused parathyroidectomy. This study explores whether focused parathyroidectomy for radiologically localized primary hyperparathyroidism without intraoperative parathyroid hormone is still a valid approach. METHODS: Retrospective review of a tertiary referral endocrine surgery unit database. All parathyroidectomies for primary hyperparathyroidism over 6 years (2013-2019) were included. Lithium-induced hyperparathyroidism, reoperations, familial disease, and concurrent thyroid surgery were excluded. Characteristics and outcomes for focused parathyroidectomy and open bilateral neck exploration were compared by intention-to-treat and treatment delivered. Persistence and recurrence, conversions and complications were analyzed as endpoints. RESULTS: A total of 2,828 parathyroidectomies were performed and 2,421 analyzed. By intention to treat there were 1,409 focused parathyroidectomies and 1,012 open bilateral neck explorations. Focused parathyroidectomy patients were younger: 63 vs 66 years (P < .01); however, gender (77%, 79% female), preoperative peak serum calcium (2.72, 2.70 mmol/L [P = .23]), and serum parathyroid hormone (11.5, 11.0 pmol/L [P = .52]) did not differ. In total, 229 (16.3%) focused parathyroidectomies were converted to open bilateral neck exploration. Multiple gland disease was confirmed in 54.5% of converted patients. Median follow-up was 41 months (3-60 months). Persistence or recurrence requiring reoperation totaled 2.2% and did not differ between focused parathyroidectomy and open bilateral neck exploration in either intention to treat or final treatment analyses. Complications occurred in 1.2% of focused parathyroidectomy and 3.2% open bilateral neck exploration (P < .01). CONCLUSIONS: In experienced hands and with a ready-selective approach to conversion, focused parathyroidectomy based on concordant imaging and without intraoperative parathyroid hormone may deliver equivalent cure rates to open bilateral neck exploration with significantly fewer complications. Focused parathyroidectomy without intraoperative parathyroid hormone should therefore be maintained in the endocrine surgeon's armamentarium.