BRAF突变甲状腺乳头状癌淋巴结转移预测模型的构建及临床验证OA
BRAF-mutant papillary thyroid carcinoma lymph node metastasis prediction model construction
背景与目的:甲状腺乳头状癌(papillary thyroid carcinoma,PTC)是内分泌系统最常见的恶性肿瘤,全球发病率持续上升.BRAF V600E突变作为PTC中最常见的基因突变,与肿瘤侵袭性特征密切相关,包括淋巴结转移(lymph node metastasis,LNM)、腺外侵犯及患者预后不良等.LNM是PTC患者复发和预后不良的重要危险因素,术前准确预测LNM风险对制订个体化手术方案(如确定预防性中央区或侧颈区淋巴结清扫范围)具有关键性指导意义.然而,现有预测模型多基于传统临床病理学指标,鲜有研究将患者心理状态纳入评估体系.本研究旨在基于BRAF突变PTC患者的临床病理学特征及心理健康指标,构建术前LNM预测模型,并通过内部验证评估其预测效能,为临床术前决策提供客观依据.方法:回顾性收集2023年10-12月天津医科大学肿瘤医院甲状腺颈部肿瘤科接受手术治疗的BRAF突变PTC患者,按85%∶15%随机分为训练集和验证集.纳入标准:① 术后病理学检查证实为PTC;② 术前或术后病理学检测BRAF V600E突变阳性;③ 接受甲状腺全切除或近全切除+中央区淋巴结清扫术,部分患者接受侧颈区淋巴结清扫;④ 实验室相关检查及临床病理学资料完整.排除标准:① 既往甲状腺手术史或颈部放疗史;② 合并其他恶性肿瘤;③ 存在远处转移;④ 病理学类型为甲状腺滤泡癌、髓样癌或未分化癌;⑤临床病理学资料不完整.收集患者的基本信息、实验室检查、术后病理学资料及患者健康问卷抑郁量表9项版(Patient Health Questionnaire-9,PHQ-9)评分等资料.以术后病理学检查为LNM诊断金标准.采用LASSO回归进行变量初筛,多因素logistic回归筛选独立危险因素并构建预测模型,绘制列线图.采用受试者工作特征(receiver operating characteristic,ROC)曲线及曲线下面积(area under the curve,AUC)评估区分度,采用校准曲线评估校准度,采用决策曲线分析(decision curve analysis,DCA)评估临床实用性.结果:共纳入144例患者,LNM发生率为52.8%(76/144).训练集与验证集基线特征均衡.LASSO回归和多因素分析确定3个独立危险因素:PHQ-9评分>3.5分[比值比(odds ratio,OR)=7.802,95%CI:2.862~25.477]、肿瘤最大径>0.94 cm(OR=4.317,95%CI:2.031~9.532)和肿瘤个数>1.50个(OR=2.419,95%CI:1.083~5.573).训练集AUC为0.757 4(95%CI:0.670 3~0.844 5),验证集AUC为0.750 0(95%CI:0.535 8~0.964 2).校准曲线显示,预测概率与实际观测概率在预测概率0.4~1.0范围内一致性良好.Hosmer-Lemeshow检验提示模型校准度良好(P>0.05).DCA显示,阈值概率0.2~0.6范围内均获得正向净获益,最大净获益为0.41~0.43,优于"全部干预"和"不干预"极端策略.结论:本研究构建的基于PHQ-9评分、肿瘤最大径和肿瘤病灶个数的预测模型可有效地预测BRAF突变PTC患者的术前LNM风险,具有良好的区分度、校准度和临床实用性.本研究创新性地将心理健康指标纳入术前预测体系,为个体化手术决策提供客观量化工具.
Background and purpose:Papillary thyroid carcinoma(PTC)is the most common malignancy of the endocrine system,with its global incidence continuing to rise.The BRAF V600E mutation,as the most common genetic mutation in PTC,is closely associated with aggressive clinicopathological features,including lymph node metastasis(LNM),extrathyroidal extension and poor prognosis.LNM is an important risk factor for recurrence and poor prognosis in PTC patients.Accurate preoperative prediction of LNM risk is of critical guiding significance for formulating individualized surgical plans(such as the extent of prophylactic central or lateral neck lymph node dissection).However,existing prediction models are mostly based on traditional clinicopathological indicators,and few studies have incorporated patients'mental health indicators into the evaluation system.This study aimed to construct a preoperative LNM prediction model based on the clinicopathological characteristics and mental health indicators of BRAF-mutant PTC patients,and to evaluate its predictive efficacy through internal validation,thereby providing an objective basis for clinical preoperative decision-making.Methods:BRAF-mutant PTC patients who underwent surgical treatment at the Department of Thyroid and Neck Oncology,Tianjin Medical University Cancer Institute&Hospital from October to December 2023,were retrospectively collected and randomly divided into the training set and the validation set at a ratio of 85%:15%.Inclusion criteria:① Postoperative pathological examination confirmed PTC;② Preoperative or postoperative pathological detection of BRAF V600E mutation positivity;③ Undergoing total or near-total thyroidectomy combined with central neck lymph node dissection,with some patients additionally undergoing lateral neck lymph node dissection;④ Complete laboratory examination and clinicopathological data.Exclusion criteria:① History of thyroid surgery or neck radiotherapy;② Concomitant other malignancies;③ Distant metastasis;④ Pathological types of follicular thyroid carcinoma,medullary thyroid carcinoma,or anaplastic thyroid carcinoma;⑤ Incomplete clinicopathological data.Basic patient information,laboratory examinations,postoperative pathological data,and Patient Health Questionnaire-9(PHQ-9)scores were collected.Postoperative pathological examination served as the gold standard for LNM diagnosis.LASSO regression was used for preliminary variable screening,followed by multivariate logistic regression to screen for independent risk factors and construct the prediction model,and a nomogram was drawn.The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate discrimination,the calibration curve was used to evaluate calibration,and decision curve analysis(DCA)was used to evaluate clinical utility.Results:A total of 144 patients were included,with an LNM incidence of 52.8%(76/144).Baseline characteristics were balanced between the training set and validation set.LASSO regression and multivariate analysis identified three independent risk factors:PHQ-9 score>3.5[odds ratio(OR)=7.802,95%CI:2.862-25.477],maximum tumor diameter>0.94 cm(OR=4.317,95%CI:2.031-9.532)and tumor number>1.50(OR=2.419,95%CI:1.083-5.573).The AUC of the training set was 0.757 4(95%CI:0.670 3-0.844 5),and the AUC of the validation set was 0.750 0(95%CI:0.535 8-0.964 2).The calibration curve demonstrated good agreement between predicted probabilities and actual observed probabilities within the range of 0.4-1.0.The Hosmer-Lemeshow test(P>0.05)indicated satisfactory model calibration.DCA showed positive net benefits within the threshold probability range of 0.2-0.6,with maximum net benefits of 0.41-0.43,which were superior to the extreme strategies of"treat all"and"treat none".Conclusion:The prediction model constructed in this study based on the PHQ-9 score,maximum tumor diameter and tumor number can effectively predict the preoperative LNM risk in BRAF-mutant PTC patients,with good discrimination,calibration,and clinical utility.This study innovatively incorporated mental health indicators into the preoperative prediction system,providing an objective and quantitative tool for individualized surgical decision-making.
刘依萌;刘天翔;秦璇;阮先辉;郑向前
天津医科大学肿瘤医院甲状腺颈部肿瘤科,国家肿瘤临床医学研究中心,肿瘤防治重点实验室,天津市肿瘤临床医学研究中心,天津 300060南开大学医学院,天津 300000天津医科大学肿瘤医院甲状腺颈部肿瘤科,国家肿瘤临床医学研究中心,肿瘤防治重点实验室,天津市肿瘤临床医学研究中心,天津 300060天津医科大学肿瘤医院甲状腺颈部肿瘤科,国家肿瘤临床医学研究中心,肿瘤防治重点实验室,天津市肿瘤临床医学研究中心,天津 300060天津医科大学肿瘤医院甲状腺颈部肿瘤科,国家肿瘤临床医学研究中心,肿瘤防治重点实验室,天津市肿瘤临床医学研究中心,天津 300060
医药卫生
甲状腺乳头状癌BRAF基因心理健康指标淋巴结转移预测模型列线图
Papillary thyroid carcinomaBRAF geneMental health indicatorLymph node metastasisPrediction modelNomogram
《中国癌症杂志》 2026 (8)
717-730,14
非传染性慢性病国家科技重大专项(2026ZD0553103)天津市教委科研计划项目(自然科学)(2022KJ216)天津市医学重点学科建设资助(TJYXZDXK-3-003A). Noncommunicable Chronic Diseases-National Science and Technology Major Project(2026ZD0553103)The Scientific Research Program of Tianjin Municipal Education Commission(Natural Science)(2022KJ216)Tianjin Key Medical Discipline Construction Project(TJYXZDXK-3-003A).
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