RET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype

Ullmann, Timothy M.; Thiesmeyer, Jessica W.; Lee, Yeon Joo; Beg, Shaham; Mosquera, Juan Miguel; Elemento, Olivier; Fahey, Thomas J.; Scognamiglio, Theresa; Houvras, Yariv

doi:10.1245/s10434-022-11418-2

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…Among all rearrangement forms, RET /PTC3 and RET /PTC1 are the most common, accounting for >90% of all rearrangements. The prognostic role of RET rearrangements has been confirmed in other studies as the presence of RET /PTC3 rearrangements and both large tumors size and advanced tumor stage at the time of diagnosis are positively associated; these studies highlight that RET /PTC3 has a significant role in metastatic spread ( 10 – 13 ). However, RET /PTC1 rearrangement is more prevalent than RET /PTC3 in less aggressive classical variants ( 14 , 15 ).…”

Section: Introductionsupporting

confidence: 55%

Ultrasound images-based deep learning radiomics nomogram for preoperative prediction of RET rearrangement in papillary thyroid carcinoma

Zhang²,

Zheng³

et al. 2022

Front. Endocrinol.

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PurposeTo create an ultrasound -based deep learning radiomics nomogram (DLRN) for preoperatively predicting the presence of RET rearrangement among patients with papillary thyroid carcinoma (PTC).MethodsWe retrospectively enrolled 650 patients with PTC. Patients were divided into the RET/PTC rearrangement group (n = 103) and the non-RET/PTC rearrangement group (n = 547). Radiomics features were extracted based on hand-crafted features from the ultrasound images, and deep learning networks were used to extract deep transfer learning features. The least absolute shrinkage and selection operator regression was applied to select the features of nonzero coefficients from radiomics and deep transfer learning features; then, we established the deep learning radiomics signature. DLRN was constructed using a logistic regression algorithm by combining clinical and deep learning radiomics signatures. The prediction performance was evaluated using the receiver operating characteristic curve, calibration curve, and decision curve analysis.ResultsComparing the effectiveness of the models by linking the area under the receiver operating characteristic curve of each model, we found that the area under the curve of DLRN could reach 0.9545 (95% confidence interval: 0.9133–0.9558) in the test cohort and 0.9396 (95% confidence interval: 0.9185–0.9607) in the training cohort, indicating that the model has an excellent performance in predicting RET rearrangement in PTC. The decision curve analysis demonstrated that the combined model was clinically useful.ConclusionThe novel ultrasonic-based DLRN has an important clinical value for predicting RET rearrangement in PTC. It can provide physicians with a preoperative non-invasive primary screening method for RET rearrangement diagnosis, thus facilitating targeted patients with purposeful molecular sequencing to avoid unnecessary medical investment and improve treatment outcomes.

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Section: Introductionsupporting

confidence: 55%

Ultrasound images-based deep learning radiomics nomogram for preoperative prediction of RET rearrangement in papillary thyroid carcinoma

Zhang²,

Zheng³

et al. 2022

Front. Endocrinol.

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“…Currently, pathological examination, especially cytology, does not classify pathological subtypes, which is due to subjective factors in ultrasonic material selection by physicians or film reading by pathologists, which can often lead to negative results or insufficient material selection 66 . BRAF V600E and RAS are associated with LNM, invasion, and recurrence 67 . METTL7B may promote thyroid cancer metastasis through the epithelial‐mesenchymal transition, 68 and overexpression of circRNA _102171 promotes PTC progression 69 .…”

Section: Resultsmentioning

confidence: 99%

Ultrasound‐guided thermal ablation for papillary thyroid microcarcinoma: A systematic review

Zhang

2022

Clinical Endocrinology

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Objective Thyroidectomy is the first‐line treatment for papillary thyroid microcarcinoma (PTMC), but often involves aggressive overtreatment. Thermal ablation (TA) has been gradually used for the treatment of recurrent PTMC. However, it is not recommended for the treatment of primary PTMC according to the Korean and Italian guidelines. Therefore, this systematic review aimed to analyse the indications, efficacy, and safety of TA in the treatment of PTMC. Design Systematic review. Patients and Measurements A search strategy was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. A total of 27 articles were included in this study until January 2022. Results According to current guidelines and studies, we divided the indications of TA for PTMC into six primary and three secondary indications. Laser ablation (LA) has the advantages of a small needle, accurate output energy and precision ablation, and it is safe to important organs around the lesion. The patients recover quickly after radiofrequency ablation (RFA), with no major complications, recurrence, or lymph node metastasis. The volume reduction rate after RFA was the highest, followed by microwave ablation and LA, and the improvement in patient quality of life after TA was significantly better than after thyroidectomy. Conclusions TA is an effective alternative method for surgery in the treatment of low‐risk PTMC and has the advantages of being minimally invasive, economical, having less bleeding and having a high postoperative quality of life.

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“…Another clinical study from east China reported 10.4% RET fusions in 193 PTC patients, 31 7.08% RET fusion reported in a study from 14 tertiary hospitals of China. 32 Ullmann et al 33 also reported that RET-driven tumors are more likely to have extrathyroidal extension, multifocal disease and distant metastases in American.…”

Section: Discussionmentioning

confidence: 99%

Landscape of gene mutation in Chinese thyroid cancer patients: Construction and validation of lymph node metastasis prediction model based on clinical features and gene mutation marker

Wang

Zhang

et al. 2023

Cancer Medicine

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Objectives Reporting the clinicopathological information of thyroid cancer (TC) patients from a central medical center of east China, and constructing the nomogram predicting lymph node metastasis (LNM). Methods We collected the patients who underwent thyroid cancer surgery in our institute from July 1, 2019 to July 31, 2021, a total of 253 subjects were enrolled. We used HiPure FFPE DNA Kit to extract DNA and RNApure FFPE Kit to extract RNA from the paraffin sections of tumor tissue, the extracted DNA samples and RNA samples were used for NGS sequencing. The clinical and pathological information of TCGA‐THCA cohort was obtained as the validation cohort. Multivariate logistic regression analysis was performed to identify the independent prognostic factor, and the nomogram was subsequently constructed by “rms” R package. Results Secondary cases contained more mutation of BRAF (90.48% vs. 62.07%) and TERT (33.0% vs. 3.0%), as compared with primary cases. Primary patients with positive lymph node were younger (40.9 ± 10.8 vs. 45.3 ± 11.8, p = 0.0031) and contained advanced TI‐RADS levels (4c: 22.8% vs. 8.3%, 5: 6.5% vs. 0/0%, p = 1.878e‐03), as well as more RET genetic alteration (16.3% vs. 2.7%, p = 2.566e‐03). We chose age, tumor diameter, RET fusion, and gender to construct the LNM predicting nomogram. Calibration plot, DCA curve, and the clinical impact plot verified the preferable prognostic value of the nomogram, with an AUC value of 0.724 (0.656–0.792). We successfully validated the prognostic value of the nomogram in TCGA‐THCA cohort. RET fusion might impact the process of protein digestion and absorption, cytokine‐cytokine receptor interaction, ECM‐receptor interaction, focal adhesion. Conclusion We provide a novel nomogram to predict the LNM for TC patients, including the features of patient's age, gender, tumor diameter, and RET alteration. Further studies from multiple medical centers are essential to validate the nomogram.

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RET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype

Cited by 10 publications

References 20 publications

Ultrasound images-based deep learning radiomics nomogram for preoperative prediction of RET rearrangement in papillary thyroid carcinoma

Ultrasound images-based deep learning radiomics nomogram for preoperative prediction of RET rearrangement in papillary thyroid carcinoma

Ultrasound‐guided thermal ablation for papillary thyroid microcarcinoma: A systematic review

Landscape of gene mutation in Chinese thyroid cancer patients: Construction and validation of lymph node metastasis prediction model based on clinical features and gene mutation marker

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