基于分子分型的髓母细胞瘤复发相关影响因素分析

doi:10.3969/j.issn.1672-6731.2021.12.011

摘要/Abstract

摘要：

目的分析基于分子分型的髓母细胞瘤复发率并筛查其相关危险因素。方法纳入2011年3月至2013年11月首都医科大学附属北京天坛医院收治并经术后病理证实的67例髓母细胞瘤患者，均行MRI检查（包括肿瘤部位、肿瘤浸润程度、肿瘤播散、肿瘤分期、手术切除程度）以及病理学检查（包括组织学分型和分子分型），记录复发率。绘制Kaplan-Meier生存曲线，采用单因素和多因素Cox回归分析筛查髓母细胞瘤复发相关危险因素。结果共67例髓母细胞瘤患者，总生存率为71.64%（48/67），无进展生存率为67.16%（45/67）、复发率为32.84%（22/67），病死率为28.36%（19/67），其中复发组病死率显著高于未复发组［81.82%（18/22）对2.22%（1/45）；χ²=46.078，P=0.000］。Kaplan-Meier生存曲线显示，外侧型患者中位生存期短于中央型（18个月对51个月，P=0.000），大细胞型/间变性患者中位生存期短于经典型、促纤维增生/结节型、广泛结节型（10个月对50、44和31个月，P=0.000），SHH活化型患者中位生存期短于WNT活化型、3组型、4组型（19个月对32、33和57个月，P=0.003），复发患者中位生存期短于未复发患者（19个月对60个月，P=0.000）。多因素Cox回归分析显示，外侧型（RR=3.514，95% CI：1.262~9.781；P=0.016）、大细胞型/间变性（RR=6.452，95% CI：1.320~31.537；P=0.021）和3组型（RR=4.289，95% CI：1.359~13.533；P=0.013）是髓母细胞瘤复发的危险因素。结论外侧型、大细胞型/间变性组织学亚型、SHH型分子亚型和复发性髓母细胞瘤的生存期更短，且外侧型、大细胞型/间变性组织学亚型和3组型分子亚型髓母细胞瘤更易复发。

关键词: 髓母细胞瘤, 生物标记, 肿瘤, 肿瘤复发, 局部, 存活率分析, 危险因素, 回归分析

Abstract:

Objective To investigate the recurrence rate and risk factors for the patients with medulloblastoma based on the molecular subgroups. Methods A retrospective study was conducted for the clinicopathological data of 67 medulloblastoma patients who were admitted in Department of Radiotherapy and Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from March 2011 to November 2013. All the cases received the MRI examinations to identify the location, aggressiveness, dissemination, stage and resection as well as the histological and molecular pathology in order to analyze the recurrence rate. The Kaplan-Meier survival curve and Cox regression were performed to detect the risk factors for medulloblastoma recurrences. Based on the recurrence, this cohort of samples were divided into recurrence group (n=22) and non-recurrence group (n=45). Results Among the patients, the overall survival rate was 71.64% (48/67), the progression-free survival rate was 67.16% (45/67), the recurrece rate was 32.84% (22/67), and the fatality rate was 28.36% (19/67). The fatality rate in the recurrence group was significantly higher than that in the non-recurrence group[81.82% (18/22) vs. 2.22% (1/45); χ²=46.078, P=0.000]. The Kaplan-Meier survival curves showed that patients with lateral medulloblastoma have a shorter median survival time than those with middle medulloblastoma (18 months vs. 51 months, P=0.000), patients with large cell/anaplasitc medulloblastoma suffered from a poorer median survival time compared with the classic medulloblastoma, desmoplastic/nodular medulloblastoma and medulloblastoma with extensive nodularity (10 months vs. 50, 44 and 31 months; P=0.000), median survival time of patients with SHH-activated subtype was shorter than that of patients with the other three subgroups (19 months vs. 32, 33 and 57 months; P=0.003), and median survial time of patients with recurrence was shorter than that of patients with non-recurrence (19 months vs. 60 months, P=0.000). The Cox regression analysis showed that lateral medulloblastoma (RR=3.514, 95%CI:1.262-9.781; P=0.016), large cell/anaplasitc medulloblastoma (RR=6.452, 95%CI:1.320-31.537; P=0.021) and Group 3 (RR=4.289, 95%CI:1.359-13.533; P=0.013) subtype were the risk factors for medulloblastoma recurrence. Conclusions Patients with lateral medulloblastoma, large cell/anaplasitc medulloblastoma and SHH-activated subtype suffered from a poorer survival. Patients with lateral, large cell/anaplasitc medulloblastoma and Group 3 subtype were prone to recurrence.

Key words: Medulloblastoma, Biomarkers, tumor, Neoplasm recurrence, local, Survival analysis, Risk factors, Regression analysis

刘海龙, 田雨, 王嘉义, 李亚农, 冯谨, 李春德, 姜涛, 邱晓光. 基于分子分型的髓母细胞瘤复发相关影响因素分析[J]. 中国现代神经疾病杂志, 2021, 21(12): 1095-1102.

LIU Hai-long, TIAN Yu, WANG Jia-yi, LI Ya-nong, FENG Jin, LI Chun-de, JIANG Tao, QIU Xiao-guang. Analysis of risk factors of medulloblastoma recurrence based on the molecular subgroups[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(12): 1095-1102.

http://journal11.magtechjournal.com/cjcnn/CN/Y2021/V21/I12/1095

参考文献

[1] Hovestadt V, Ayrault O, Swartling FJ, Robinson GW, Pfister SM, Northcott PA. Medulloblastomics revisited:biological and clinical insights from thousands of patients[J]. Nat Rev Cancer, 2020, 20:42-56.
[2] Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, McLendon RE, Bigner DD, Lipp ES, Perreault S, Cho YJ, Grant G, Kim SK, Lee JY, Rao AAN, Giannini C, Li KKW, Ng HK, Yao Y, Kumabe T, Tominaga T, Grajkowska WA, Perek-Polnik M, Low DCY, Seow WT, Chang KTE, Mora J, Pollack IF, Hamilton RL, Leary S, Moore AS, Ingram WJ, Hallahan AR, Jouvet A, Fèvre-Montange M, Vasiljevic A, Faure-Conter C, Shofuda T, Kagawa N, Hashimoto N, Jabado N, Weil AG, Gayden T, Wataya T, Shalaby T, Grotzer M, Zitterbart K, Sterba J, Kren L, Hortobágyi T, Klekner A, László B, Pócza T, Hauser P, Schüller U, Jung S, Jang WY, French PJ, Kros JM, van Veelen MC, Massimi L, Leonard JR, Rubin JB, Vibhakar R, Chambless LB, Cooper MK, Thompson RC, Faria CC, Carvalho A, Nunes S, Pimentel J, Fan X, Muraszko KM, López-Aguilar E, Lyden D, Garzia L, Shih DJH, Kijima N, Schneider C, Adamski J, Northcott PA, Kool M, Jones DTW, Chan JA, Nikolic A, Garre ML, Van Meir EG, Osuka S, Olson JJ, Jahangiri A, Castro BA, Gupta N, Weiss WA, Moxon-Emre I, Mabbott DJ, Lassaletta A, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup:a retrospective integrated clinical and molecular analysis[J]. Lancet Oncol, 2016, 17:484-495.
[3] Ramaswamy V, Taylor MD. Medulloblastoma:from myth to molecular[J]. J Clin Oncol, 2017, 35:2355-2363.
[4] Zhang ZY, Xu J, Ren Y, Li KK, Ng HK, Mao Y, Zhong P, Yao Y, Zhou LF. Medulloblastoma in China:clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy[J]. PLoS One, 2014, 9:e99490.
[5] Jiang T, Wang JM, Du J, Qiu XG, Li CD. Analysis of clinical prognosis and risk factors for children with medulloblastoma[J]. Zhonghua Shen Jing Wai Ke Za Zhi, 2016, 32:338-343. [姜涛, 王军梅, 杜江, 邱晓光, 李春德. 儿童髓母细胞瘤的临床预后及危险因素分析[J]. 中华神经外科杂志, 2016, 32:338-343.]
[6] Chang CH, Housepian EM, Herbert C Jr. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas[J]. Radiology, 1969, 93:1351-1359.
[7] Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system:a summary[J]. Acta Neuropathol, 2016, 131:803-820.
[8] Johnston DL, Keene D, Strother D, Taneva M, Lafay-Cousin L, Fryer C, Scheinemann K, Carret AS, Fleming A, Afzal S, Wilson B, Bowes L, Zelcer S, Mpofu C, Silva M, Larouche V, Brossard J, Bouffet E. Survival following tumor recurrence in children with medulloblastoma[J]. J Pediatr Hematol Oncol, 2018, 40:e159-e163.
[9] Millard NE, De Braganca KC. Medulloblastoma[J]. J Child Neurol, 2016, 31:1341-1353.
[10] Jiang T, Zhang Y, Wang J, Du J, Raynald, Qiu X, Wang Y, Li C. A retrospective study of progression-free and overall survival in pediatric medulloblastoma based on molecular subgroup classification:a single-institution experience[J]. Front Neurol, 2017, 8:198.
[11] Partap S, Curran EK, Propp JM, Le GM, Sainani KL, Fisher PG. Medulloblastoma incidence has not changed over time:a CBTRUS study[J]. J Pediatr Hematol Oncol, 2009, 31:970-971.
[12] Schneider C, Ramaswamy V, Kulkarni AV, Rutka JT, Remke M, Tabori U, Hawkins C, Bouffet E, Taylor MD. Clinical implications of medulloblastoma subgroups:incidence of CSF diversion surgery[J]. J Neurosurg Pediatr, 2015, 15:236-242.
[13] Garcia-Lopez J, Kumar R, Smith KS, Northcott PA. Deconstructing sonic hedgehog medulloblastoma:molecular subtypes, drivers, and beyond[J]. Trends Genet, 2021, 37:235-250.
[14] Northcott PA, Robinson GW, Kratz CP, Mabbott DJ, Pomeroy SL, Clifford SC, Rutkowski S, Ellison DW, Malkin D, Taylor MD, Gajjar A, Pfister SM. Medulloblastoma[J]. Nat Rev Dis Primers, 2019, 5:11.
[15] Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri S, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhakar R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, López-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Moore AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimentel J, Faria CC, Saad AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpeña-Diazconti M, Chico Ponce de León F, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks PB, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD. Intertumoral heterogeneity within medulloblastoma subgroups[J]. Cancer Cell, 2017, 31:737-754.
[16] Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO classification of tumors of the central nervous system:a summary[J]. Neuro Oncol, 2021, 23:1231-1251.
[17] Yang XJ, Yin HF, Li Z, Yu SZ. Chinese version of simplified table of 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition) and translational interpretations[J]. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2021, 21:746-750.[杨学军, 尹洪芳, 李智, 于士柱. 2021 年世界卫生组织中枢神经系统肿瘤分类(第五版)简表中译版及说明[J]. 中国现代神经疾病杂志, 2021, 21:746-750.]
[18] Liu X, Chen HY, Zou WJ, Li GL. Interpretation on the diagnostic molecular parameters in the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition)[J]. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2021, 21:751-763. [刘幸, 陈慧媛, 邹婉婧, 李桂林. 2021 年世界卫生组织中枢神经系统肿瘤分类(第五版)分子诊断指标解读[J]. 中国现代神经疾病杂志, 2021, 21:751-763.]
[19] Wang Y. Interpretation on embryonal tumors in the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition)[J]. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2021, 21:817-822. [汪洋. 2021 年世界卫生组织中枢神经系统肿瘤分类(第五版)胚胎性肿瘤解读[J]. 中国现代神经疾病杂志, 2021, 21:817-822.]
[20] Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children:conclusions from the Children's Cancer Group 921 randomized phase Ⅲ study[J]. J Clin Oncol, 1999, 17:832-845.
[21] Khatua S, Song A, Citla Sridhar D, Mack SC. Childhood medulloblastoma:current therapies, emerging molecular landscape and newer therapeutic insights[J]. Curr Neuropharmacol, 2018, 16:1045-1058.
[22] Aref D, Croul S. Medulloblastoma:recurrence and metastasis[J]. CNS Oncol, 2013, 2:377-385.
[23] Sabel M, Fleischhack G, Tippelt S, Gustafsson G, Doz F, Kortmann R, Massimino M, Navajas A, von Hoff K, Rutkowski S, Warmuth-Metz M, Clifford SC, Pietsch T, Pizer B, Lannering B; SIOP-E Brain Tumour Group. Relapse patterns and outcome after relapse in standard risk medulloblastoma:a report from the HIT-SIOP-PNET4 study[J]. J Neurooncol, 2016, 129:515-524.
[24] Padovani L, Horan G, Ajithkumar T. Radiotherapy advances in paediatric medulloblastoma treatment[J]. Clin Oncol (R Coll Radiol), 2019, 31:171-181.
[25] Juraschka K, Taylor MD. Medulloblastoma in the age of molecular subgroups:a review[J]. J Neurosurg Pediatr, 2019, 24:353-363.

选择文件类型/文献管理软件名称

选择包含的内容

2 基于分子分型的髓母细胞瘤复发相关影响因素分析

Analysis of risk factors of medulloblastoma recurrence based on the molecular subgroups

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张轩, 薛蓉. 特发性快速眼动睡眠期行为障碍向神经系统变性疾病转化的生物学标志物研究进展[J]. 中国现代神经疾病杂志, 2023, 23(8): 668-673.
[2]	任修德, 李涛, 范吉康, 王希森, 贾晓丹, 杨学军. 胶质母细胞瘤FGFR3-TACC3融合基因介导丙酮酸激酶M2入核促进DNA损伤修复基础研究[J]. 中国现代神经疾病杂志, 2023, 23(8): 745-757.
[3]	张晨, 张延铭, 佟小光. 内镜下经鼻入路联合显微镜下开颅手术治疗复杂鼻颅沟通颅底肿瘤初探[J]. 中国现代神经疾病杂志, 2023, 23(7): 575-579.
[4]	刘俊其, 王蠡, 王振霖, 张秋航, 齐岩, 危维. 内镜下经口鼻联合入路手术切除颅底脊索瘤[J]. 中国现代神经疾病杂志, 2023, 23(7): 580-585.
[5]	贾亮, 周航, 张晓炜, 张庆九, 吕中强. 内镜下扩大经鼻入路手术切除鞍上侵袭性垂体腺瘤[J]. 中国现代神经疾病杂志, 2023, 23(7): 586-590.
[6]	马晓丽, 童家杰, 张秀智, 杜倩, 隋爱霞, 赵焕芬. 表现为垂体腺瘤卒中的黄色瘤性垂体炎[J]. 中国现代神经疾病杂志, 2023, 23(7): 599-603.
[7]	冯珊珊. 基于危险因素的库欣病患者视力视野客观检查卫生经济学分析[J]. 中国现代神经疾病杂志, 2023, 23(7): 613-620.
[8]	邹婷婷, 马莉, 潘文静, 李长秀, 胡乃霞, 王擂. 重型颅脑创伤并发颅内感染危险因素分析及列线图预测模型构建[J]. 中国现代神经疾病杂志, 2023, 23(6): 496-502.
[9]	刘臣超, 刘慧权, 袁小勇, 王健, 陈绅, 王义义, 柳兴军. 重症结核性脑膜炎预后不良影响因素分析[J]. 中国现代神经疾病杂志, 2023, 23(6): 522-529.
[10]	宫剑. 积极促进我国小儿神经外科的发展[J]. 中国现代神经疾病杂志, 2023, 23(5): 383-387.
[11]	郭中印, 彭鹏, 陈籽荣, 张晓琳, 董民海, 曾括, 万丽君, 向网, 万锋. 幕上肿瘤患儿手术后行脑室-腹腔分流术危险因素分析[J]. 中国现代神经疾病杂志, 2023, 23(5): 412-417.
[12]	彭小娇, 葛明, 吴迪, 蔡英杰, 陈佳树, 梁琛. 单中心儿童颅咽管瘤手术后下丘脑性肥胖危险因素分析[J]. 中国现代神经疾病杂志, 2023, 23(5): 418-424.
[13]	冯增伟, 丁平, 廖先文, 焦永辉, 左云龙, 韩宏彦. 烟雾病脑血管重建术后发生脑过度灌注综合征的临床分析[J]. 中国现代神经疾病杂志, 2023, 23(5): 460-466.
[14]	余彩遥, 叶兰, 冯占辉. 癫痫患者认知功能障碍相关危险因素研究进展[J]. 中国现代神经疾病杂志, 2023, 23(4): 287-291.
[15]	孙艳, 范茹雪, 陈慧丰, 尹洁, 张楠. 天津市部分城市社区老年人群轻度认知损害患病情况及影响因素分析[J]. 中国现代神经疾病杂志, 2023, 23(4): 303-309.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 基于分子分型的髓母细胞瘤复发相关影响因素分析

Analysis of risk factors of medulloblastoma recurrence based on the molecular subgroups

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价