治疗前18F-FLT和18F-FDG PET/CT摄取异质性在局部晚期鼻咽癌疗效预测中的价值

doi:10.19401/j.cnki.1007-3639.2022.04.003

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (4): 309-315.doi: 10.19401/j.cnki.1007-3639.2022.04.003

治疗前¹⁸F-FLT和¹⁸F-FDG PET/CT摄取异质性在局部晚期鼻咽癌疗效预测中的价值

马光¹()(), 区晓敏², 胡超苏², 宋少莉¹, 杨忠毅¹()()

1.复旦大学附属肿瘤医院核医学科,复旦大学上海医学院肿瘤学系,复旦大学生物医学影像研究中心,上海分子影像探针工程技术研究中心 200032
2.复旦大学附属肿瘤医学放疗科、复旦大学上海医学院肿瘤学系 200032

收稿日期:2021-11-30 修回日期:2022-02-22 出版日期:2022-04-30 发布日期:2022-05-07
通信作者: 杨忠毅 E-mail:18121299445@163.com;yangzhongyi21@163.com
作者简介:马光（ORCID: 0000-0003-4787-201X）,硕士,主治医师 E-mail: 18121299445@163.com

Value of pretreatment ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT uptake heterogeneity for early prediction of treatment outcome in locally advanced nasopharyngeal carcinoma

MA Guang¹()(), OU Xiaomin², HU Chaosu², SONG Shaoli¹, YANG Zhongyi¹()()

1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Center for Biomedical Imaging, Fudan University; Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai 200032, China
2. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Received:2021-11-30 Revised:2022-02-22 Published:2022-04-30 Online:2022-05-07
Contact: YANG Zhongyi E-mail:18121299445@163.com;yangzhongyi21@163.com

摘要/Abstract

摘要：

背景与目的：鼻咽癌是东南亚地区常见的头颈部恶性肿瘤之一,对于局部晚期鼻咽癌患者来说,放疗联合化疗为主要治疗方式,但不同患者间治疗反应存在个体差异。因此,早期准确评估局部晚期鼻咽癌放化疗预后能力对于临床治疗决策的制定具有重要意义。本研究评估和比较治疗前¹⁸F-胸苷（fluorothymidine,FLT）、¹⁸F-脱氧葡萄糖（fluorodeoxyglucose,FDG）正电子发射断层显像/X线计算机体层成像仪（positron emission tomography/computed tomography,PET/CT）显像参数在局部晚期鼻咽癌患者放化疗预后预测中的价值。方法：回顾性分析复旦大学附属肿瘤医院2012年5月—2015年1月局部晚期鼻咽癌患者,所有患者均接受新辅助化疗（neoadjuvant chemotherapy,NACT）及调强放射治疗（intensity-modulated radiation therapy, IMRT）。随访结点为无进展生存期（progression-free survival,PFS）,定义为从治疗开始至肿瘤进展或者发生任何原因死亡的时间。病灶评估依据实体瘤疗效评价标准1.1（Response Evaluation Criteria in Solid Tumor 1.1,RECIST 1.1）。所有患者均于治疗前分别行¹⁸F-FLT 和¹⁸F-FDG PET/CT显像,两次显像时间间隔均保持在1周以内,并测量其主要参数,包括：最大标准化摄取值（maximal standardized uptake value,SUV_max）、平均标准化摄取值（mean standardized uptake value,SUV_mean）、增殖性肿瘤体积（proliferative tumor volume,PTV）/代谢性肿瘤体积（metabolic tumor volume,MTV）、病灶腺苷代谢总量（total lesion thymidine,TLT）/病灶葡萄糖代谢总量（total lesion glucose,TLG）及肿瘤异质性（heterogeneity index,HI）。采用Spearman等级相关系数分析上述PET/CT参数与局部晚期鼻咽癌患者转移/复发的相关性。随后,采用受试者工作特征（receiver operating characteristic,ROC）曲线筛选最佳界值,并评价其预测效能。同时建立Kaplan-Meier模型绘制生存曲线,并采用log-rank检验进行比较。结果：24例局部晚期鼻咽癌患者中,复发或转移共6例,中位随访时间为74.51个月。Spearman等级相关系数分析结果显示,仅在¹⁸F-FLT PET/CT显像组中,以70%SUV_max为阈值测得原发灶肿瘤内异质性指数,即HI_{（T-FLT-70%SUVmax）}与肿瘤转移/复发具有相关性（P=0.04）;ROC曲线分析显示其HI_{（T-FLT-70%SUVmax）}预测转移/复发的灵敏度为80.00%,特异度为79.90%（P=0.043）,生存分析结果显示当HI_{（T-FLT-70%SUVmax）}>0.828时,其中位PFS为57.99个月,明显短于HI_{（T-FLT-70%SUVmax）} ≤0.828的患者（P=0.014）。结论：基于¹⁸F-FLT PET/CT显像的肿瘤内HI具有预测局部晚期鼻咽癌放化疗效果的潜在价值。

关键词: PET/CT, 局部晚期鼻咽癌, 预测, 预后

Abstract:

Background and purpose: Nasopharyngeal carcinoma is one of the most common head and neck malignancies in Southeast Asia. Radiotherapy combined with chemotherapy is the main treatment for patients with locally advanced nasopharyngeal carcinoma (LANPC), however, different patients have various levels of clinical benefit. Therefore, early and accurate evaluation of the prognosis of LANPC after radiotherapy and chemotherapy is of great significance for clinical treatment decision-making. This paper aimed to evaluate and compare the value of ¹⁸F-Fluorothymidine (FLT) and ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging parameters in predicting the prognosis of patients with LANPC after radiotherapy and chemotherapy. Methods: Patients with LANPC who all received intensity-modulated radiation therapy (IMRT) and neoadjuvant chemotherapy (NACT) in Fudan University Shanghai Cancer Center from May 2012 to January 2015 were retrospectively selected. Clinical follow-up endpoint was progression-free survival (PFS), defined as the time from the beginning of treatment to tumor progression or death from any cause. The focus evaluation was based on the Response Evaluation Criteria in Solid Tumor 1.1 (RECIST 1.1). Pretreatment ¹⁸F-FLT and ¹⁸F-FDG PET/CT imaging were performed respectively. And the time interval between the two imaging was maintained within 1 week. The main parameters were measured, including maximal standardized uptake value (SUV_max), mean standardized uptake value (SUVmean), proliferative tumor volume (PTV)/metabolic tumor volume (MTV), total lesion thymidine (TLT)/ total lesion glucose (TLG) and tumor heterogeneity index (HI). Spearman rank correlation coefficient was used to analyze the correlation between the above PET/CT parameters and patients with metastasis/recurrence of LANPC. Then, the best cut-off value was determined by the receiver operating characteristic (ROC) curve, and the predictive ability was evaluated by the ROC curve. PFS was evaluated by the Kaplan-Meier method and log-rank test. Results: Among the 24 patients, 6 had metastasis or recurrence. The median follow-up time was 74.51 months. Spearman rank correlation coefficient analysis showed that HI_{(T-FLT-70%SUVmax)} was associated with metastasis or recurrence (P=0.04); ROC curve analysis showed that the sensitivity of HI_{(T-FLT-70%SUVmax)} in predicting metastatic or recurrent nasopharyngeal carcinoma was 80.00%, and the specificity was 79.90% (P=0.043). Survival analysis showed that when HI_{(T-FLT-70%SUVmax)}>0.828, the median PFS was 57.99 months, which was significantly shorter compared with patients with HI_{(T-FLT-70%SUVmax)}0≤0.828 (P=0.014). Conclusion: HI based on ¹⁸F-FLT PET/CT may be useful for predicting the prognosis of patients with LANPC receiving radiotherapy and chemotherapy.

Key words: PET/CT, Locally advanced nasopharyngeal carcinoma, Predicting, Prognosis

中图分类号:

R739.6

马光, 区晓敏, 胡超苏, 宋少莉, 杨忠毅. 治疗前¹⁸F-FLT和¹⁸F-FDG PET/CT摄取异质性在局部晚期鼻咽癌疗效预测中的价值[J]. 中国癌症杂志, 2022, 32(4): 309-315.

MA Guang, OU Xiaomin, HU Chaosu, SONG Shaoli, YANG Zhongyi. Value of pretreatment ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT uptake heterogeneity for early prediction of treatment outcome in locally advanced nasopharyngeal carcinoma[J]. China Oncology, 2022, 32(4): 309-315.

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参考文献 20

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Threshold	FLT			Threshold	FDG
Threshold	Parameters	r value	P value	Threshold	Parameters	r value	P value
1.5	SUV_max-T	-0.096	0.654	2.5	SUV_max-T	-0.215	0.313
	PTV_-T	-0.067	0.757		MTV_-T	-0.245	0.249
	TLT_-T	-0.082	0.705		TLG_-T	-0.111	0.605
	HI_-T	0.111	0.605		HI_-T	0.289	0.171
	SUV_max-N	-0.14	0.544		SUV_max-N	0.150	0.516
	PTV_-N	0.108	0.649		MTV_-N	0.022	0.928
	TLT_-N	0.022	0.928		TLG_-N	0.108	0.649
	HI_-N	-0.043	0.856		HI_-N	-0.650	0.785
40%	PTV_-T	-0.067	0.757	40%	MTV_-T	-0.052	0.810
	TLT_-T	-0.052	0.810		TLG_-T	-0.082	0.705
	HI_-T	0.141	0.512		HI_-T	0.363	0.081
	PTV_-N	-0.080	0.730		MTV_-N	-0.020	0.931
	TLT_-N	-0.120	0.604		TLG_-N	0.100	0.666
	HI_-N	-0.180	0.434		HI_-N	0.240	0.294
50%	PTV_-T	-0.007	0.973	50%	MTV_-T	0.007	0.973
	TLT_-T	-0.052	0.810		TLG_-T	-0.067	0.757
	HI_-T	0.111	0.605		HI_-T	0.304	0.149
	PTV_-N	-0.100	0.666		MTV_-N	0.080	0.730
	TLT_-N	-0.140	0.544		TLG_-N	0.120	0.604
	HI_-N	-0.180	0.434		HI_-N	0.040	0.863
60%	PTV_-T	0.111	0.605	60%	MTV_-T	0.067	0.757
	TLT_-T	-0.007	0.973		TLG_-T	-0.052	0.810
	HI_-T	0.333	0.111		HI_-T	0.274	0.195
	PTV_-N	0.000	1.000		MTV_-N	0.160	0.488
	TLT_-N	-0.100	0.666		TLG_-N	0.140	0.544
	HI_-N	-0.320	0.157		HI_-N	-0.180	0.434
70%	PTV_-T	0.037	0.864	70%	MTV_-T	0.160	0.488
	TLT_-T	-0.022	0.918		TLG_-T	0.140	0.544
	HI_-T	0.423	0.040		HI_-T	-0.180	0.434
	PTV_-N	-0.060	0.796		MTV_-N	0.140	0.544
	TLT_-N	-0.100	0.666		TLG_-N	0.160	0.488
	HI_-N	0.140	0.544		HI_-N	-0.100	0.666

Factors	Number	PFS t/month	χ²	P value
Gender			0.794	0.373
Male	21	NR
Female	3	NR
Age/year			0.330	0.566
≤45	12	NR
>45	12	NR
AJCC staging			0.007	0.936
Ⅲ	14	NR
ⅣA	10	NR
HI_{(T-FLT-70%SUVmax)}			6.036	0.014
>0.828	8	57.99
≤0.828	16	NR

治疗前¹⁸F-FLT和¹⁸F-FDG PET/CT摄取异质性在局部晚期鼻咽癌疗效预测中的价值

Value of pretreatment ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT uptake heterogeneity for early prediction of treatment outcome in locally advanced nasopharyngeal carcinoma

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