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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang jugao fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central Laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively ***: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low ***: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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Construction of a novel six-gene signature to predict tumour response to induction chemotherapy and overall survival in locoregionally advanced laryngeal and hypopharyngeal carcinoma

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Genes & Diseases 2024年第3期11卷 148-150页

作者： Chen Tan Lingwa Wang Yifan Yang Shizhi He George G.Chen Jason YK.Chan Michael CF.Tong C.A.van Hasselt Wenbin Xu Ling Feng Ru Wang jugao fang Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Key Laboratory of Otolaryngology Head and Neck Surgery(Ministry of Education of China) Beijing Institute of OtolaryngologyBeijing 100730China Department of Otorhinolaryngology Head and Neck SurgeryThe Chinese University of Hong KongPrince of Wales HospitalHongKong SAR999077China Department of Medical Genetics Institute of Basic Medical ScienceChinese Academy of Medical Science&Peking Union Medical CollageBeijing 100730China

Locoregionally advanced laryngeal and hypopharyngeal cancers(LA-LHCs)are traditionally treated with surgery followed by postoperative radiotherapy,which impairs speech and swallowing functions and reduces the quality of life.^(1,2)The use of induction chemotherapy(IC)as a larynxpreserving approach for LA-LHCs has been verified and refined.^(3)However,the short-term tumor response to IC varies,non-responders usually show poor survival and little benefit.

关键词： chemotherapy laryngeal surgery

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甲状腺癌手术中双荧光显影识别中央区淋巴结及甲状旁腺的效果

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中华医学杂志 2024年第12期104卷 938-943页

作者：王哓艳钟琦房居高时倩郭伟丁硕赵延明何雨蓉李齐佳首都医科大学附属北京同仁医院头颈外科耳鼻咽喉头颈科学教育部重点实验室，北京100730

目的探讨甲状腺癌手术中双荧光显影识别中央区淋巴结及甲状旁腺的效果。方法该研究为横断面研究。前瞻性纳入2022年1月至2023年9月于首都医科大学附属北京同仁医院头颈外科行甲状腺乳头状癌(PTC)手术的患者,均行甲状腺腺叶切除或全切除... 详细信息

目的探讨甲状腺癌手术中双荧光显影识别中央区淋巴结及甲状旁腺的效果。方法该研究为横断面研究。前瞻性纳入2022年1月至2023年9月于首都医科大学附属北京同仁医院头颈外科行甲状腺乳头状癌(PTC)手术的患者,均行甲状腺腺叶切除或全切除术,同期行中央区淋巴结清扫。术中采用示踪用盐酸米托蒽醌注射液及785 nm、660 nm双荧光显影技术,测量甲状旁腺、中央区淋巴结及背景荧光强度(FI),校正得到标准化FI后采用配对t检验比较标准化甲状旁腺及中央区淋巴结FI,并采用Spearman秩相关分析其与多种临床指标的关系。结果共纳入30例患者,男8例,女22例,年龄(41.8±10.4)岁。双荧光显影下共发现甲状旁腺76枚,中央区淋巴结234枚。标准化甲状旁腺FI小于标准化中央区淋巴结(44.7±16.8比99.5±28.4,P0.05)。结论中央区淋巴结及甲状旁腺双荧光显影可在辅助甲状腺癌手术中央区淋巴结清扫的同时,提高甲状旁腺识别能力。

关键词：甲状腺肿瘤甲状旁腺中央区淋巴结荧光显影淋巴示踪

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Factors contributing to lymph node occult metastasis in supraglottic laryngeal carcinoma cT2-T4 N0M0 and metastasis predictive equation

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Chinese Journal of Cancer Research 2014年第6期26卷 685-691页

作者： Hongzhi Ma Meng Lian Ling Feng Pingdong Li Lizhen Hou Xiaohong Chen Zhigang Huang jugao fang Department of Otolaryngology-Head and Neck Surgery Beijing Tongren Hospital Capital Medical University Key Laboratory of Otorhinolaryngology Head and Neck Surgery Ministry of Education Beijing Institute of Otorhinolaryngology Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology

Objective： To investigate factors that contribute to lymph node metastasis（LNM） from clinical cT2-T4 N0M0（cN0） supraglottic laryngeal carcinoma（SLC）, and to predict the risk of occult metastasis before ***： A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis. Results： The overall metastatic rate of c N0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows： Pn=e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）/[1＋e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference（P=0.029）.Conclusions： Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

关键词： Larynx lymph nodes neoplasm metastasis prediction

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Clinical applications of free medial tibial flap with posterior tibial artery for head and neck reconstruction after tumor resection

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Chinese Journal of Cancer Research 2017年第3期29卷 231-236页

作者： Qi Zhong jugao fang Zhigang Huang Xiaohong Chen Lizhen Hou Yang Zhang Pingdong Li Hongzhi Ma Hongbo Xu Department of Otolaryngology Head and Neck Surgery Beijing Tongren Hospital Capital Medical University Beijing Institute of Otolaryngology Key Laboratory of Otolaryngology Head and Neck Surgery (Capital Medical University) Ministry of Education

Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.

关键词： Head and neck free flap posterior tibial artery reconstruction

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Microarray gene expression analysis of chemosensitivity for docetaxel,cisplatin and 5-fluorouracil(TPF)combined chemotherapeutic regimen in hypopharyngeal squamous cell carcinoma

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Chinese Journal of Cancer Research 2017年第3期29卷 204-212页

作者： Meng Lian Haizhou Wang jugao fang Jie Zhai Ru Wang Xixi Shen Yifan Yang Zhihong Ma Honggang Liu Department of Otorhinolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology Beijing 100730China

Objective: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. Methods: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Through microarray analysis, 1,579 differentially expressed genes were identified, of which 815 were up-regulated in TPF chemotherapy-responsive tissues whereas 764 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including transcription and its regulation, cellular signal transduction and metabolic process. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that MAPK and Jat/STAT signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of IL-6, MAPK14, JUN, CDK5 and CAMK2A exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemotherapeutic response in HSCC. Conclusions: These results provided a battery of genes related to TPF chemotherapeutic sensitivity and might act as molecular targets in HSCC treatment. Moreover, these candidate biomarkers could contribute to HSCC individualized treatment.

关键词： Microarray HSCC induction chemotherapy MAPK

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规范化个体化治疗提高晚期甲状腺癌患者生存率和生存质量

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中华医学杂志 2023年第40期103卷 3152-3154页

作者：房居高首都医科大学附属北京同仁医院耳鼻咽喉头颈外科耳鼻咽喉头颈科学教育部重点实验室（首都医科大学），北京100730

分化型甲状腺癌总体预后良好,但仍有部分患者就诊时进展为局部晚期。目前局部晚期甲状腺癌的诊治仍存在一些尚未完全明确的问题,也为临床治疗造成了一定困扰。本文针对局部晚期甲状腺癌术式选择、喉神经及气管受累的处理、分期手术时机... 详细信息

分化型甲状腺癌总体预后良好,但仍有部分患者就诊时进展为局部晚期。目前局部晚期甲状腺癌的诊治仍存在一些尚未完全明确的问题,也为临床治疗造成了一定困扰。本文针对局部晚期甲状腺癌术式选择、喉神经及气管受累的处理、分期手术时机选择及靶向治疗等问题进行分析阐述,旨在促进晚期甲状腺癌的规范化个体化治疗,提高生存率,改善生存质量。

关键词：甲状腺肿瘤规范化个体化治疗

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局部晚期分化型甲状腺癌的外科治疗

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中华耳鼻咽喉头颈外科杂志 2022年第9期57卷 1140-1144,1134页

作者：房居高首都医科大学附属北京同仁医院耳鼻咽喉头颈外科北京100730

分化型甲状腺癌(DTC)总体预后良好,但仍有部分患者就诊时已为局部晚期。局部晚期DTC发生率较低,尚需要系统的、推广性强的管理方法。本文从局部晚期DTC的概念和整体治疗状况入手,结合甲状腺癌的临床特征,介绍了局部晚期甲状腺癌的外科... 详细信息

分化型甲状腺癌(DTC)总体预后良好,但仍有部分患者就诊时已为局部晚期。局部晚期DTC发生率较低,尚需要系统的、推广性强的管理方法。本文从局部晚期DTC的概念和整体治疗状况入手,结合甲状腺癌的临床特征,介绍了局部晚期甲状腺癌的外科治疗手段,以期推广局部晚期DTC的规范化治疗,提高晚期DTC的生存率和生存质量。

关键词：分化型甲状腺癌规范化治疗预后良好外科治疗手段整体治疗局部晚期生存质量 DTC

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分化型甲状腺癌诊治中的热点及争议问题

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中华医学杂志 2022年第48期102卷 3801-3805页

作者：房居高首都医科大学附属北京同仁医院耳鼻咽喉头颈外科北京100730

甲状腺癌是目前最为常见的内分泌肿瘤,尽管对甲状腺癌的研究已经相对深入,但仍有较多的问题尚无定论。本文从分化型甲状腺癌的常规筛查、术前评估、外科处理与辅助治疗及基础转化研究等多角度分析,并对目前甲状腺肿瘤领域从基础到临床... 详细信息

甲状腺癌是目前最为常见的内分泌肿瘤,尽管对甲状腺癌的研究已经相对深入,但仍有较多的问题尚无定论。本文从分化型甲状腺癌的常规筛查、术前评估、外科处理与辅助治疗及基础转化研究等多角度分析,并对目前甲状腺肿瘤领域从基础到临床研究的部分相关热点及争议问题加以评述,旨在进一步推动甲状腺肿瘤的分层管理与精准诊治。

关键词：甲状腺肿瘤诊断术前评估治疗

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颈外入路腔镜下甲状腺手术

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中华耳鼻咽喉头颈外科杂志 2020年第10期55卷 889-892页

作者：房居高首都医科大学附属北京同仁医院耳鼻咽喉头颈外科 100730

本述评对目前基本成熟的各种颈外入路腔镜下甲状腺手术进行了综合评价,包括操作的便利性和容易程度、创伤的大小、手术的适应证和禁忌证、美容效果、并发症以及费用效益比值等。

关键词：禁忌证费用效益比腔镜下甲状腺手术美容效果综合评价适应证便利性并发症

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