BRAF V600

P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029

P1, N=124, Recruiting, Pfizer | Trial completion date: Sep 2028 --> Aug 2029

P1, N=122, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.

P1, N=46, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Nov 2025

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

The ability to detect SNVs and indels below 5% VAF increases the diagnostic yield of actionable genomic alterations. This enables additional patients to consider FDA-approved on-label targeted therapies as a treatment option. Taken together, CGP assays that couple high sensitivity and low LOD can maximize identification of therapeutically relevant alterations across solid tumor types.

OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

SMAD4 p.G365S (c.1093G >A) is a novel inactivating missense mutation. Although this patient presented with aggressive disease, the clinical significance of this SMAD4 mutation is still uncertain. Additional meta-analytic studies are needed to determine the significance of SMAD4 alteration in patients with malignant melanoma.

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

P2, N=101, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P1/2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P=N/A, N=12, Not yet recruiting, Huashan Hospital, Fudan University; Huashan Hospital, Fudan University | N=20 --> 12

P=N/A, N=135, Not yet recruiting, Affiliated Hospital of Guilin Medical University; Affiliated Hospital of Guilin Medical University

P2, N=60, Not yet recruiting, Fujian Cancer Hospital; Fujian Cancer Hospital

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib, and osimertinib; 99.25% for osimertinib plus vemurafenib; 98.92% for osimertinib, encorafenib, and cetuximab; and 62.83% for pemetrexed plus carboplatin. NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism. EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.

The use of NGS enhances mutation detection, highlighting the need for personalized treatment approaches in NSCLC management. The varying responses to treatments among the patients emphasize the complexity of NSCLC management and the necessity for a personalized approach.

The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features.The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations.These mutations have been suggested to be associated with an increased risk of recurrence,poorer efficacy of postoperative radioactive iodine therapy,and reduced survival.The pathologic subtypes of PTC include classic,follicular,tall cell,hobnail,columnar cell,diffuse sclerosing,solid/trabecular,oncocytic,Warthin-like,clear cell,and spindle cell subtypes,which have different aggressiveness and linked with varied clinical prognosis.Therefore,detecting the gene mutations and pathologic subtypes of PTC is of great importance for therapeutic regimen selection and prognosis evaluation.Ultrasound imaging with non-invasiveness,convenience,and high resolution has become the primary examination method for the diagnosis and treatment of thyroid cancer.This paper reviews the correlations of gene mutations and pathologic subtypes with the ultrasound features of PTC,aiming to give new insights into the application of ultrasound imaging in predicting gene mutations and pathologic subtypes of PTC before surgery as well as provide new ideas for accurate assessment of preoperative prognosis.

P2, N=24, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=40 --> 24

We describe a very rare case of co-occurring pulmonary Langerhans cell histiocytosis with multiple cutaneous reticulohistiocytomas with a common BRAF-V600E mutation as the driver genetic event in both the lung and skin lesions. The presence of a common BRAF-V600E mutation provides evidence of their clonal relation and contributes to our understanding in the pathogenesis of multiple, co-occurring histiocytic proliferations.

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

P1, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P3, N=300, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

These findings underscore the importance of TERT alterations in aggressive phenotypes and offer insights into molecular mechanisms guiding targeted therapies. Further research is necessary to confirm their significance as diagnostic and prognostic markers in thyroid cancer.

Importantly, LNM and LNMN could be distinguished by differential mRNA expression of nine genes. Our study demonstrates that there is a spectrum of LNMTs and that the clinicopathological diagnosis of LNM, for which we support the term 'late-onset nested naevoid melanomas', can be significantly strengthened by the presence of lentiginous pattern, nest bridging, gene CNV and differential mRNA expression.

We did a comprehensive assessment of cellular delivery, and biological activity of the miR211-5p carried by UCL-211 in vitro and their permeation through the epidermis of intact skin using ex vivo human skin tissue explants. We also demonstrated, in vivo , that topical delivery of miR211-5p by UCL-211 stabilized BRAFV600E+ nevi melanocytes in a benign nevi state.

This work reveals a surprising field effect of melanoma initiation in vivo in which tumors arise from within a zone of morphologically distinct, but clinically covert, precursors with altered transcriptional fate. Our studies identify novel targets that could improve early diagnosis and prevention of melanoma.

Furthermore, ROC curve analysis highlighted the diagnostic significance of the positive expression of the immunohistochemical markers CLU, SSTR2, and RB in identifying NET G3. To guide more suitable treatment strategies, it is essential to develop and apply valuable and more targeted immunohistochemical and molecular pathological markers for a comprehensive analysis.

P1/2, N=13, Terminated, Achilles Therapeutics UK Limited | N=40 --> 13 | Trial completion date: Jul 2027 --> Sep 2024 | Recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Sep 2024; Sponsor decision

The BRAFV600E and TERT-p double mutation in PTC was significantly associated with relatively old age, larger tumor size, lobulated configuration in tumor margin, papillary excrescences on the cut surface, solid-cut surface, ETE, and high Ki-67 LI. These features are suggestive of the presence of the double mutation and should be analyzed at the molecular level in patients with PTC.

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

This review confirms an association between CM and HM within the same patient. The link is primarily attributed to genetic factors involving BRAF-V600K, tyrosine kinase pathway genes, CDKN2A (P16), and BCL-2. Additionally, risk factors such as ultraviolet radiation and compromised immune function are associated with the incidence of these cancers.

Our AI-driven NLP pipeline demonstrated the potential for annotating biomarker testing and mutation rates. The difficulties we encountered highlight the need for more advanced AI-powered literature searching and data extraction, and more consistent reporting of testing rates. These improvements would reduce the risk of misinterpretation or misunderstanding of testing and mutation rates by AI-based technologies and the health care community, with beneficial impacts on clinical decision-making, research, and trial design.

Subsequently, salvage chemotherapy with a combination of temozolomide and irinotecan was administered, resulting in effective control of the tumor. Conclusion To our knowledge, this is the first reported case of ganglioglioma with anaplastic features harboring MAP2K1 mutation and homozygous deletion of CDKN2A/B. These findings may shed light on the genetic features of ganglioglioma and offers insights into potential therapeutic approaches for this rare neoplasm.

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.

No abstract available

P3, N=480, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

The calibration graph drawn based on the prediction and the actual situation is close to the 45° diagonal. By adding microsatellite status and primary tumor site on the basis of pathological stage, we improved the discriminability and prediction accuracy of the model and successfully established a prognosis model for patients with BRAF V600E mutation of colorectal cancer.

Vemurafenib cannot be considered cost-effective in terms of what has normally been considered a reasonable willingness to pay (WTP) in Tunisia. A significant price reduction would be necessary to bring the incremental cost-effectiveness ratio to an acceptable level.