BRAF positive

In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

P1, N=53, Terminated, ABM Therapeutics Corporation | N=112 --> 53 | Trial completion date: Jan 2025 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Apr 2024; Not related to safety concerns or lack of efficacy

Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

This case adds to the evidence that both RCCs and papillary CPs may be the spectrum of the same disease. Further, papillary CPs may be an evolution from the RCCs.

Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.

P1, N=33, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2026

Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

A subset (10.3%) of multifocal PTCs had discordant molecular drivers and 90.0% of them were a combination of BRAF-positive and kinase gene fusion-associated PTCs, mostly with different histologic subtypes. Half of the cases had nodal metastasis and 40% (2/5) of them showed simultaneous involvement by tumors with discordant molecular drivers. These findings highlight the clinical importance of identifying such cases given the potentially different management with specific targeted therapies.

Compared to BRAF mutation-negative, BRAF-positive PTC lesions were more likely to be found in female patients and were characterized by irregular shape. However, the CT imaging finding is not enough to predict BRAF status, but an indication.

P1, N=112, Active, not recruiting, ABM Therapeutics Corporation | Recruiting --> Active, not recruiting

P2, N=64, Active, not recruiting, University of Sydney | Recruiting --> Active, not recruiting

P2, N=36, Recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Oct 2023 --> Oct 2024

Performing BRAF gene testing only on the medium-risk groups (modified combination method) significantly reduced the rate of BRAF gene testing (P<0.001) without increasing the false-negative rate (P=0.818 and P=0.394 for ACR and ATA, respectively). Incorporating the BRAF gene test exclusively for nodules in the medium-risk group significantly improved diagnostic efficacy, reduced the utilization of gene tests, and maintained a consistent false-negative rate.

BRAF-positive CM possessed a slightly higher mitotic rate (p = 0.015) and Breslow thickness (p = 0.028) but did not relate to tumor-infiltrating lymphocytes. The high rate of BRAF mutations in CM patients in the Ukrainian cohort was associated with superficial spreading histology, higher depth of invasion and proliferation.

In low risk of both ultrasound and FNA results, the positive BRAF was significant increased in patients over 50 years old, which have higher risk of malignancy. Thus, the BRAF mutation detection and further surgery should be strengthened in older patients with benign cytological and US results thyroid nodules.

Stratification of thyroid lesions with uncertain results of fine-needle cytology using genetic markers can help to deliver more tailored medical treatment (Tab. 6, Ref. 19).

In the BRAF-negative group, age had no impact on recurrence risk. These results contribute to tailored treatment strategies and informed patient management.

Among individuals with advanced melanoma not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 &lsqb;95% CI: 0.97, 1.16], rwPFS aHR: 1.02 &lsqb;95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

Notably, we found the anti-AXL CAR-NK cells could inhibit the BRAFi-resistant melanoma growth and metastasis in vivo preclinical mouse models. Conclusions Our findings propose that Anti-AXL CAR-NK cell immunotherapy is a promising approach to target BRAF inhibitor drug-resistant and metastatic melanoma.

P=N/A, N=1961, Completed, Novartis Pharmaceuticals