CAR-T在甲状腺癌免疫治疗中的研究进展

大多数甲状腺癌患者进行以外科治疗为主的综合治疗可以取得良好的预后,但目前晚期甲状腺癌治疗手段匮乏。采用体外基因编辑技术的嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)免疫疗法在血液系统肿瘤中得到应用并取得了良好的治疗效果。以此为基础,CAR-T开始在实体肿瘤中尝试使用,但效果欠佳。CAR-T在晚期甲状腺癌中的研究已有开展,目前仍局限在临床前的基础研究,相关临床试验较少且缺乏试验结果报道。本文将相关报道进行综述,旨在为今后的研究提供参考。

术前临床及原发肿瘤超声影像学特征对散发性甲状腺髓样癌侧颈淋巴结转移预测分析

目的:探讨散发性甲状腺髓样癌(sporadic medullary thyroid carcinoma,sMTC)患者侧颈淋巴结转移的危险因素。方法:回顾性分析2011年2月至2017年3月期间就诊于天津医科大学肿瘤医院94例MTC患者的临床及超声特征资料,采用Fisher’s精确检验及Logistic回归分析侧颈淋巴结转移的危险因素。结果:单因素Logistic分析显示,性别(F=5.234,P=0.022)、术前降钙素水平(F=21.327,P<0.001)、最大径(F=5.875,P=0.015)、位置(F=6.088,P=0.014)、肿物性质(F=5.224,P=0.047)、形状(F=8.754,P=0.003)、边缘(F=15.971,P<0.001)均与侧颈区淋巴结转移有显著性差异;多因素分析显示男性、术前降钙素>319 pg/mL、位于上极、边缘不规则、低回声是影响MTC侧颈区淋巴结转移的独立危险因素(均P<0.05)。结论:男性、术前降钙素>319 pg/mL、位于上极、边缘不规则、低回声与MTC患者侧颈淋巴结转移显著相关,且随着危险因素个数的增多,发生侧颈淋巴结转移概率增加。

Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: a study of 1,587 patients

Objective: The purposes of this study were to identify risk factors for cervical lymph node metastasis and to examine the association between BRAF^(V600E) status and clinical features in papillary thyroid microcarcinoma(PTMC).Methods: A total of 1,587 patients with PTMC, treated in Tianjin Medical University Cancer Institute and Hospital from January2011 to March 2013, underwent retrospective analysis. We reviewed and analyzed factors including clinical results, pathology records, ultrasound results, and BRAF^(V600E) status.Results: Multivariate logistic regression analyses demonstrated that gender(male) [odds ratio(OR) = 1.845, P = 0.000], age(< 45 years)(OR = 1.606, P = 0.000), tumor size(> 6 mm)(OR = 2.137, P = 0.000), bilateralism(OR = 2.011, P = 0.000) and extrathyroidal extension(OR = 1.555, P = 0.001) served as independent predictors of central lymph node metastasis(CLNM).Moreover, CLNM(OR = 29.354, P = 0.000) served as an independent predictor of lateral lymph node metastasis(LLNM). Among patients with a solitary primary tumor, those with tumor location in the lower third of the thyroid lobe or the isthmus were more likely to experience CLNM(P < 0.05). Univariate analyses indicated that CLNM, LLNM, extrathyroidal extension, and multifocality were not significantly associated with BRAF^(V600E) mutation.Conclusions: The present study suggested that prophylactic neck dissection of the central compartment should be considered in patients with PTMC, particularly in men with tumor size greater than 6 mm, age less than 45 years, extrathyroidal extension, and tumor bilaterality. Among patients with PTMC, BRAF^(V600E) mutation is not significantly associated with prognostic factors. For a better understanding of surgical management of PTMC and the risk factors, we recommend multicenter research and long-term follow-up.

Prediction of cervical lymph node metastases in papillary thyroid microcarcinoma by sonographic features of the primary site

Objective: To study the sonographic features of the primary site of papillary thyroid microcarcinoma(PTMC) for the prediction of cervical lymph node metastasis during preoperative diagnosis.Methods: A total of 710 PTMC patients between 2013 and 2016 with a diagnosis of cervical lymph node metastases were reviewed.We analyzed the sonographic features of the PTMC primary site to predict ipsilateral or central lymph node metastases in univariate and multivariate models.The ratio of abutment/perimeter of the PTMC primary site was utilized to evaluate cervical lymph node status.Results: Regarding clinical characteristics, multifocality and extrathyroidal extension were associated with cervical lymph node involvement.In the multivariate regression model, calcification and the abutment/perimeter ratio of lesions were evaluated as independent factors in level Ⅵ, ipsilateral or skip cervical lymph node metastases.The cut-off value of the ratio of abutment/perimeter of the PTMC primary site(25%) was significantly correlated with cervical lymph node metastases(P = 0.000).Conclusions: Independent sonographic features, including lesion size, lesion location, calcification, and the ratio of abutment/perimeter of the primary site, were associated with cervical lymph node metastases in PTMC patients.

Active surveillance as a management strategy for papillary thyroid microcarcinoma

Active surveillance(AS)can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma(PTMC),with the absence of clinically apparent lymph nodes,extrathyroidal extensions,and distant metastasis.After reviewing the reports on AS of low risk PTMCs worldwide,we introduced AS,and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules.Moreover,the requirement of cytological diagnosis,progression evaluation methods,necessity of thyrotropin suppression,and medical costs were issues that both clinicians and patients considered.The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk.Clinicians may adopt measures like dynamic monitoring,risk stratification,and making personal follow-up schedules to minimize these potential risks.By appropriately selecting PTMC patients,AS can be an effective alternative treatment to immediate surgery.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

2017 Chinese expert consensus on the clinical application ofserum marker for thyroid cancer

In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.

Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human malignancies.However,its functions in non-small cell lung cancer(NSCLC)are poorly understood.The goal of the present study was to identify the role of HBXIP in the regulation of NSCLC development.Methods:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically evaluated.The effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in vitro.The mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation assays.In addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP knockdown.Results:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of NSCLC.The high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 phase.The results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of MEK1.In addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor growth.Conclusions:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.

Improved diagnosis of thyroid cancer aided with deep learning applied to sonographic text reports:a retrospective,multi-cohort,diagnostic study

Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis.Methods:Sonographic EHR data were obtained from the EHR database.Pathological reports were used as the gold standard for diagnosing thyroid cancer.We developed thyroid cancer diagnosis based on natural language processing(THCaDxNLP)to interpret unstructured sonographic text reports for thyroid cancer diagnosis.We used the area under the receiver operating characteristic curve(AUROC)as the primary metric to measure the performance of the THCaDxNLP.We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs.those without THCaDxNLP using 5 independent test sets.Results:We obtained a total number of 788,129 sonographic radiological reports.The number of thyroid sonographic data points was 132,277,18,400 of which were thyroid cancer patients.Among the 5 test sets,the numbers of patients per set were 439,186,82,343,and 171.THCaDxNLP achieved high performance in identifying thyroid cancer patients(the AUROC ranged from 0.857–0.932).Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy(93.8%vs.87.2%;one-sided t-test,adjusted P=0.003),precision(92.5%vs.86.0%;P=0.018),and F1 metric(94.2%vs.86.4%;P=0.007).Conclusions:THCaDxNLP achieved a high AUROC for the identification of thyroid cancer,and improved the accuracy,sensitivity,and precision of thyroid ultrasound radiologists.This warrants further investigation of THCaDxNLP in prospective clinical trials.

CACA guidelines for holistic integrative management of thyroid cancer

Purpose:In recent years,thyroid cancer is a common clinical problem.Since guidelines for the diagnosis and treatment of thyroid nodules and diferentiated thyroid cancer were revised in 2012,signifcant scientifc advances have occurred in the feld.The aim of this guidelines is to inform clinicians,researchers,patients and health policy makers on published evidence and expert consensus relating to the diagnosis and management of thyroid malignancy.Methods:In order to better promote the clinical management of thyroid cancer in China,Chinese Association of Thyroid Oncology(CATO)organized relevant experts to write these guidelines based on latest relevant literatures and clinical experience of multiple centers.The specifc clinical issues and topics addressed in these guidelines were based on published evidence,prior versions of the Chinese guidelines and expert consensus.Results and conclusion:The guidelines provide recommendations for the management of diferent types of thyroid carcinoma,including papillary,follicular,medullary,and anaplastic carcinomas.