Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Papillary thyroid cancer ( PTC) is the most common pathological type of thyroid cancer, and its morbidity raises rapidly in the global world. V-raf murine sarcoma viral oncogene homolog B1 ( BRAF) V600E mutation and telomerase reverse transcriptase ( TERT) promoter mutations are the most com-mon molecular markers of PTC. Nowadays, more and more studies find that the coexistence of BRAFV600E and TERT promoter mutations plays a synergistic role in the invasion and prognosis of PTC. This article re-views the recent advance in the synergism of BRAFV600E and TERT promoter mutations in PTC.

Objective To investigate the rate of hippocampus injury during whole brain radiotherapy for intracranial metastasis and explore the effect of whole brain radiotherapy in reducing the radiotherapy induced neurocognitive dysfunction of hippocampu and provide reference for the treatment of intracranial metastatic tumors. Methods The intracranial metastases in 123 patients from January 2015 to December 2016 were enrolled in this study. The MRI image data before and after radiotherapy were analyzed retrospectively.The anatomical position of tumor and the hippocampus in patients with intracranial metastasis was outlined.According to outlined position, the relationship between location of intracranial metastatic tumor and the hippocampus was analyzed, and the probability of the hippocampal damage by tumor radiotherapy was calculated in the treatment of intracranial metastatic brain. Neurocognitive dysfunction improvement by protective irradiation of hippocampus was compared between different radiotherapy methods. Results Four hundred and seventeen intracranial metastatic tumors were observed in 123 patients, among which the sites of 15 tumors(3.60%) were within the 5mm of hippocampus, the sites of 146 tumors(35.01%)were 5-10 mm from the hippocampus, and the sites of 256 tumors(61.39%) were beyond 10 mm of hippocampus. The distribution of 417 metastatic tumors in the brain was as followings: 137 tumors (32.85%) were in frontal lobe, 98 tumors(23.50%) were in temporal lobe, 59 tumors(14.15%)were in parietal lobe, 46 tumors(11.03%)were in occipital lobe, 41 tumors (9.83%) were in cerebellum and 36 tumors (8.63%) were in basal ganglia. Using helical tomotherapy, intracranial metastasis radiotherapy and volumetric modulated arc radiotherapy, the rate of patients with cognitive dysfunction induced by hippocampal injury was 1.96%(1/51), 10.26%(4/39)and 18.18% (6/33), and there was significant difference (χ2= 6.595, P = 0.000). Conclusions The hippocampus injury possibility is very small, when whole brain radiotherapy is used in the treatment of intracranial metastatic tumors. Avoiding the hippocampus in radiation therapy of intracranial metastasis has high feasibility, among which the helical tomotherapy can effectively reduce hippocampus injury and improve patients'cognitive function.