SHH型髓母细胞瘤患儿临床特点及预后因素分析

doi:10.12372/jcp.2022.21e1607

摘要/Abstract

摘要：

目的回顾性分析SHH（sonic hedgehog）型髓母细胞瘤（medulloblastoma，MB）患儿的临床特点，探讨其预后影响因素。方法回顾性分析2015年6月至2019年10月儿科收治的SHH型MB患儿的临床资料。通过Kaplan-Meier法计算总体生存率及无事件生存率，组间生存率比较采用log-rank检验，采用Cox比例风险回归模型进行多因素分析。结果共纳入99例SHH型MB患儿。中位年龄6.0（3.3~6.0）岁，≥3岁75例，<3岁24例；男62例，女37例；M₀ 66例，M₊33例；手术全切72例，近全切27例。病理分型以促纤维/结节型（DMB）为主，肿瘤起源部位以中线部位（四脑室、后颅窝、小脑蚓部）多见，2例存在SUFU胚系变异。中位随访时间3.2（2.2~4.1）年，3年EFS率（61.0±5.0）%，3年OS率（72.2±4.6）%，39例（39.4%）出现进展或复发。<3岁DMB、广泛结节型MB（MBEN）的3年OS率分别为（80.0±10.3）%、（57.1±18.7）%，其中12例M₀、无MYCN扩增及SUFU胚系变异者仅行化疗未放疗。Cox回归模型分析发现M₊，存在TP53变异或MYCN、GLI2扩增，病理分型为大细胞/间变型者为影响预后的独立危险因素（P<0.05）。结论 SHH型MB患儿的预后与M分期、病理分型、TP53变异、MYCN或GLI2扩增相关。病理分型为DMB及MBEN的婴幼儿无上述危险因素且无SUFU胚系变异者预后较好，可不放疗。

关键词: 髓母细胞瘤, 预后, 儿童

Abstract:

Objective To retrospectively analyze the clinical characteristics of sonic hedgehog (SHH) medulloblastoma (MB) in children, and to explore the prognostic factors. Methods The clinical data of SHH MB children from June 2015 to October 2019 were retrospectively analyzed. The overall survival rate and event-free survival rate were calculated by the Kaplan-Meier method. The survival rate between groups was compared by log-rank test. Cox proportional hazards regression model was used for multivariate analysis. Results A total of 99 children (62 boys and 37 girls) with SHH MB were enrolled. The median age was 6.0 (3.3-6.0) years, of which 75 children were ≥3 years old and 24 children were <3 years old. There were 66 cases of M₀ stage and 33 cases of M₊ stage. Total resection was performed in 72 children and near total resection in 27 children. The main pathological type was desmoplastic/nodular MB (DMB). Tumor origin sites were commoner in midline sites (fourth ventricle, posterior fossa, cerebellar vermis). SUFU germline variation was found in two children. The median follow-up time was 3.2 (2.2-4.1) years, the 3-year EFS rate was (61.0±5.0) %, the 3-year OS rate was (72.2±4.6) %, and 39 children (39.4%) had progression or recurrence. The 3-year OS rates of DMB and MB with extensive nodularity (MBEN) <3 years old are (80.0±10.3) % and (57.1±18.7) %, respectively. Among them, 12 patients with M₀ stage, without MYCN amplification and SUFU germline variation only received chemotherapy without radiotherapy. Cox regression model analysis showed that M₊ stage, TP53 mutation or MYCN, GLI2 amplification, and pathological type of large-cell/anaplastic was an independent risk factor for the prognosis of the disease (P<0.05). Conclusions The prognosis of SHH MB children is related to M stage, pathological type, TP53 mutation, MYCN or GLI2 amplification. Infants with pathological types of DMB and MBEN without the above risk factors and SUFU germline variation have a better prognosis, so radiotherapy is not necessary.

Key words: medulloblastoma, prognosis child

高文超, 孙艳玲, 李苗, 任思其, 杜淑旭, 武万水, 孙黎明. SHH型髓母细胞瘤患儿临床特点及预后因素分析[J]. 临床儿科杂志, 2022, 40(12): 919-924.

GAO Wenchao, SUN Yanling, LI Miao, REN Siqi, DU Shuxu, WU Wanshui, SUN Liming. Clinical features and prognostic factors of SHH medulloblastoma in children[J]. Journal of Clinical Pediatrics, 2022, 40(12): 919-924.

图/表 2

表1

SHH患儿总体OS率及EFS率的单因素生存分析结果($\bar{x} \pm s$)"

因素		例数	3年OS率/%	χ²值	P	3年EFS率/%	χ²值	P
性别	男	62	77.0±5.4	1.63	0.202	60.8±6.3	0.00	0.975
	女	37	63.8±8.1			62.2±8.0
年龄	≥3岁	75	72.7±5.2	0.14	0.706	63.4±5.7	0.93	0.334
	<3岁	24	70.8±9.3			53.8±10.2
肿瘤部位	中线^1）	69	79.2±5.0	7.26	0.027	68.8±5.7	6.18	0.045
	小脑半球	18	49.4±11.9			44.4±11.7
	播散	12	54.7±15.4			40.0±14.6
手术范围	GTR	72	76.2±5.1	1.369	0.242	64.7±5.7	1.580	0.209
	NTR	27	60.2±10.1			50.9±9.8
肿瘤分期	M₀	66	80.1±5.0	7.736	0.005	70.5±5.7	9.711	0.002
	M₊	33	56.3±8.9			41.7±8.7
病理分型	DMB	62	79.5±5.3	21.60	<0.001	68.2±6.1	9.60	0.022
	MBEN	17	70.6±11.1			58.8±11.9
	CMB	18	55.6±11.7			44.4±11.7
	LC/A	2	0			0
危险度	标危	57	89.4±4.1	35.79	<0.001	78.1±5.6	34.714	<0.001
	高危	34	57.9±8.7			43.7±8.6
	极高危	8	12.5±11.7			12.5±11.7
GLI2	有	3	0	17.39	<0.001	0	37.072	<0.001
	无	96	74.5±4.5			62.9±5.0
MYCN	有	6	0	65.18	<0.001	0	32.27	<0.001
	无	93	76.8±4.5			64.9±5.0
TP53	有	9	11.1±10.5	26.56	<0.001	11.1±10.5	22.63	<0.001
	无	90	78.5±4.4			66.0±5.1
PTCH1	有	14	85.7±9.4	1.66	0.197	57.1±13.2	0.04	0.845
	无	85	69.9±5.1			61.1±5.4
SMO	有	6	83.3±15.2	0.28	0.598	66.7±19.2	0.32	0.574
	无	93	71.4±4.8			60.6±5.2
SUFU	有	7	53.6±20.1	0.64	0.423	42.9±18.7	1.44	0.230
	无	92	73.4±4.7			62.4±5.1
7q⁺	有	29	67.9±8.9	0.73	0.391	52.4±9.9	0.31	0.578
	无	70	74.0±5.3			64.3±5.7
17q⁺	有	38	77.7±7.0	0.61	0.436	66.4±8.1	1.65	0.199
	无	61	68.6±6.0			57.3±6.3
7p⁺	有	23	77.1±9.1	0.06	0.814	57.4±11.1	0.01	0.936
	无	76	70.8±5.3			61.8±5.6
9q^-	有	9	68.4±16.5	0.03	0.853	44.4±16.6	1.12	0.290
	无	90	73.1±4.7			62.6±5.2
10q^-	有	7	85.7±13.2	0.75	0.387	71.4±17.1	0.51	0.477
	无	92	71.1±4.8			60.2±5.2
17p^-	有	4	75.0±21.7	0.00	0.963	75.0±21.7	0.17	0.679
	无	95	72.1±4.7			60.5±5.1

表1

表2

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影响因素	偏回归系数	标准误	χ²值	P	RR (95.0%CI)
肿瘤为中线部位	-0.02	0.15	0.01	0.910	0.98(0.74~1.31)
肿瘤分期为M₊	1.48	0.53	7.93	0.005	4.40(1.57~12.36)
病理为LC/A型	0.57	0.21	7.41	0.006	1.76(1.17~2.65)
危险度为极高危	0.20	0.41	0.23	0.633	1.22(0.55~2.71)
基因变异	2.16	0.68	9.96	0.002	8.66(2.27~33.11)