NCOA4-RET fusion

These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.

Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities. A multidisciplinary approach with early genomic profiling to guide personalized neoadjuvant use of tyrosine kinase inhibitors is essential. Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management.

SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RET and NTRK3 fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologic similarities to EFH, we propose the diagnostic term "myxoid spindle cell variant of epithelioid fibrous histiocytoma."

Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2-14.9). ICIs for PD-L overexpression and treatment naive patients offer comparable benefits for RET fusion-positive NSCLC, warranting further investigation.

She responded to selpercatinib treatment with the elimination of supplemental oxygen need, marked reduction in pulmonary nodules and mediastinal lymphadenopathy, and biomarker decline. The response was maintained despite 2 dose reductions for possibly related weight gain.

Selpercatinib increases RAI avidity in adolescents with metastatic RET fusion‐positive PTC. Further investigations into the use of targeted therapies prior to RAI therapy or to resensitize patients to RAI therapy in patients with metastatic fusion positive PTC are warranted.

The patients examined in our study could serve as a model representative of a significant proportion of the U. S. military. Tumors from individuals with history of exposure to radiation in adulthood have pronounced invasive features. A significant proportion of these tumors harbor gene fusions suggesting a possible association between irradiation in adulthood and development of radiation‐inducible PTCs.

RET fusions were identified in multiple tumor types. With a higher median TMB and commonly MSI-H, RET fusion positive CRC may be a unique molecular subset of CRC.

Conclusions Molecular screening in non-BRAF PTC patients is useful to identify patients harboring RET fusions who may benefit from targeted therapies. As other potentially actionable gene fusions are also found in these patients, routine implementation of NGS analysis warrants a comprehensive biomarker study.

We treated both mouse models with multikinase inhibitors (MKI) (cabozantinib, lenvatinib and axitinib) or with a selective RET inhibitor (BLU667)...Such immune reaction affected the gene expression of both cancer (human) and stroma (mouse) cells. Conclusions These results pave the way for a rational combination of RET inhibitors and immunotherapy in the two scenarios, as primary therapy to reduce the minimal residual disease and at time of resistance to selective RET inhibition.

Although selective tyrosine kinase inhibitors (TKI) (selpercatinib and pralsetinib) are available in several countries, there are no real-world data on the characteristics and outcomes of Hispanic patients with RET fusions treated with various regimens. This retrospective study included patients with advanced-stage RET-positive NSCLC from five Latin American countries. Hispanic patients with RET-fusion NSCLC exhibited homogeneous biological behavior. The results of the first-line treatment were in agreement with the literature. However, the number of patients treated with RETsi in the first- and second-line treatment was small, although it showed benefits in OS and PFS for the 2nd line.

Selpercatinib demonstrated clinically meaningful and durable intracranial activity in Chinese patients with brain metastases from RET-altered NSCLC, consistent with the global LIBRETTO-001 trial.