化疗对于肾母细胞瘤肺转移灶的疗效观察

doi:10.12372/jcp.2022.21e1243

摘要/Abstract

摘要：

目的观察肾母细胞瘤（WT）肺转移灶的转归,探讨不同化疗方案的疗效。方法回顾性分析2012年至2020年就诊并规律随访的WT肺转移患儿的临床资料,分析肿瘤肺转移灶对不同化疗的应答差异。结果 20例WT肺转移患儿,男11例、女9例,中位年龄38.0（20.0~5.8）月;其中预后良好型17例,预后不良型3例;单肺转移13例,双肺转移7例;初诊时肿瘤分期Ⅰ期1例,Ⅱ期5例,Ⅲ期3例,Ⅳ期9例,2例患儿外院首诊分期不明;12例术前发现肺转移, 8例术后发现;合并其他远处转移者8例;化疗后转移应答为8例完全缓解,4例部分缓解,4例稳定,4例进展。采用有序logistic回归分析进行多因素分析,结果显示化疗方案CCCG-WT-2016的偏回归系数为-2.05,并呈现出0.05检验水准的显著性（Z=-2.03,P=0.043）,采用CCCG-WT-2016方案化疗患儿的肺转移灶转移应答优于NWTS-5方案。结论采用WT-2016方案化疗的患儿转移应答明显优于采用NWTS-5方案化疗的患儿。

关键词: 肾母细胞瘤, 肿瘤肺转移, 化疗, 疗效, 儿童

Abstract:

Objective To observe the outcome of lung metastases in Wilms’ tumor (WT) and to explore the efficacy of different chemotherapy regimens. Methods The clinical data of WT children with lung metastases who were treated and followed up regularly from 2012 to 2020 were retrospectively analyzed to explore the difference in response to different chemotherapy regimens. Results There were 20 WT children (11 boys and 9 girls) with lung metastases, and the median age was 38.0(5.8~20.0) months. There were 17 cases of favorable histology (FH) type and 3 cases of unfavorable histology (UFH) type. Single lung metastasis was found in 13 cases and bilateral lung metastases were in 7 cases. At the initial diagnosis, 1 case was diagnosed as stageⅠ, 5 cases as stageⅡ, 3 cases as stage Ⅲ and 9 cases as stage Ⅳ. Two cases were first diagnosed in other hospitals with unknown stage. Lung metastases were found preoperatively in 12 cases and postoperatively in 8 cases. Eight cases were complicated with other distant metastases. After chemotherapy, the metastatic response was complete remission in 8 cases, partial remission in 4 cases, stable in 4 cases and progressive in 4 cases. Ordered logistic regression analysis was used for multivariate analysis. The results showed that the partial regression coefficient of CCCG-WT-2016 chemotherapy regimen was -2.05, presenting significance at the test level of 0.05 (Z=-2.03, P=0.043). It was suggested that CCCG-WT-2016 regimen was superior to NWTS-5 regimen in lung metastasis response. Conclusions The objective response in children treated with CCCG-WT-2016 regimen was significantly better than that of children treated with NWTS-5 regimen.

Key words: nephroblastoma, tumor pulmonary metastasis, chemotherapy, efficacy, child

石艳, 杨猛, 黄一天, 许俊杰, 温晟, 何大维, 魏光辉, 华燚. 化疗对于肾母细胞瘤肺转移灶的疗效观察[J]. 临床儿科杂志, 2022, 40(9): 696-700.

SHI Yan, YANG Meng, HUANG Yitian, XU Junjie, WEN Sheng, HE Dawei, WEI Guanghui, HUA Yi. Therapeutic effect of chemotherapy on lung metastases of nephroblastoma[J]. Journal of Clinical Pediatrics, 2022, 40(9): 696-700.

图/表 4

表1

图1

图2

表2

参考文献 22

[1]	Illade L, Hernandez-Marques C, Cormenzana M, et al. Wilms' tumour: A review of 15 years recent experience[J]. An Pediatr (Engl Ed), 2018, 88(3): 140-149.
[2]	Stokes CL, Stokes WA, Kalapurakal JA, et al. Timing of Radiation Therapy in Pediatric Wilms Tumor: A Report From the National Cancer Database[J]. Int J Radiat Oncol Biol Phys, 2018, 101(2): 453-461. doi: 10.1016/j.ijrobp.2018.01.110
[3]	Leslie SW, Sajjad H, Murphy PB. Wilms Tumor[M]. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing
[4]	Irtan S, Ehrlich PF, Pritchard-Jones K. Wilms tumor: "State-of-the-art" update, 2016[J]. Semin Pediatr Surg, 2016, 25(5): 250-256. doi: 10.1053/j.sempedsurg.2016.09.003
[5]	SIOP Renal Tumour Study Group. Paediatric renal tumours: perspectives from the SIOP-RTSG[J]. Nat Rev Urol, 2017, 14(1): 3-4.
[6]	Ansari S, Miri-Aliabad G, Rakhshani N. Bilateral wilms' tumor metastasis to right spermatic cord[J]. Int J Hematol Oncol Stem Cell Res, 2013, 7(4): 45-48.
[7]	Grundy PE, Green DM, Dirks AC, et al. Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group[J]. Pediatr Blood Cancer, 2012, 59(4): 631-635. doi: 10.1002/pbc.24123 pmid: 22422736
[8]	Berger M, Fernandez-Pineda I, Cabello R, et al. The relationship between the site of metastases and outcome in children with stage IV Wilms Tumor: data from 3 European Pediatric Cancer Institutions[J]. J Pediatr Hematol Oncol, 2013, 35(7): 518-524. doi: 10.1097/MPH.0b013e318288634d
[9]	刘唐彬. NWTS-5试验性治疗和生物学研究简介[J]. 中华小儿外科杂志, 1998, (1): 60-62.
[10]	Perlman EJ. Pediatric renal tumors: practical updates for the pathologist[J]. Pediatr Dev Pathol, 2005, 8(3): 320-338. doi: 10.1007/s10024-005-1156-7
[11]	Ko EY, Ritchey ML. Current management of Wilms' tumor in children[J]. J Pediatr Urol, 2009, 5(1): 56-65. doi: 10.1016/j.jpurol.2008.08.007
[12]	汤静燕, 徐敏, 孙晓非. 儿童肾母细胞瘤诊断治疗建议(CCCG-WT-2016)[J]. 中华儿科杂志, 2017, 55(2): 90-94.
[13]	Warmann SW, Furtwängler R, Blumenstock G, et al. Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases: results from SIOP 93-01/GPOH and SIOP 2001/GPOH[J]. Ann Surg, 2011, 254(1): 155-162. doi: 10.1097/SLA.0b013e318222015e pmid: 21670612
[14]	Oue T, Koshinaga T, Takimoto T, et al. Anaplastic histology Wilms' tumors registered to the Japan Wilms' Tumor Study Group are less aggressive than that in the National Wilms' Tumor Study 5[J]. Pediatr Surg Int, 2016, 32(9): 851-855. doi: 10.1007/s00383-016-3929-7
[15]	郭涛, 张敬悌, 葛文安, 等. 儿童肾母细胞瘤合并肺转移的临床特征和治疗经验[J]. 临床检验杂志(电子版), 2016, 5(2): 72-74.
[16]	Georgiadi ECh, Dionysiou DD, Graf N, et al. Towards in silico oncology: adapting a four dimensional nephroblastoma treatment model to a clinical trial case based on multi-method sensitivity analysis[J]. Comput Biol Med, 2012, 42(11): 1064-1078. doi: 10.1016/j.compbiomed.2012.08.008 pmid: 23063290
[17]	Gratias EJ, Dome JS, Jennings LJ, et al. Association of chromosome 1q gain with inferior survival in Favorable-Histology wilms tumor: A report from the children's oncology group[J]. J Clin Oncol, 2016, 34(26): 3189-3194. doi: 10.1200/JCO.2015.66.1140 pmid: 27400937
[18]	Grundy PE, Breslow NE, Li S, et al. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: A report from the National Wilms Tumor Study Group[J]. J Clin Oncol, 2005, 23(29): 7312-7321. pmid: 16129848
[19]	Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ(R)):Health Professional Version. 2002.In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US).
[20]	van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al. Position paper: Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol[J]. Nat Rev Urol, 2017. 14(12): 743-752. doi: 10.1038/nrurol.2017.163 pmid: 29089605
[21]	中华医学会小儿外科学分会泌尿外科学组. 儿童肾母细胞瘤诊疗专家共识[J]. 中华小儿外科杂志, 2020, 41(7): 585-590.
[22]	洪博, 董瑞. 肾母细胞瘤治疗研究进展[J]. 临床小儿外科杂志, 2021, 20(6): 569-575.

项目	例数	CR	PR	SD	PD	Z值	P
性别						0.80	0.427
男	11	5 (45.5)	3 (27.3)	1 (9.1)	2 (18.2)
女	9	3 (33.3)	1 (11.1)	3 (33.3)	2 (22.2)
年龄						2.16	0.031
≤2岁	7	5 (71.4)	1 (14.3)	1 (14.3)	0 (0.0)
>2岁	13	3 (23.1)	3 (23.1)	3 (23.1)	4 (30.8)
诊断						0.89	0.376
FH	17	8 (47.1)	3 (17.7)	2 (11.8)	4 (23.5)
UFH	3	0 (0.0)	1 (33.3)	2 (66.7)	0 (0.0)
分期						1.08	0.282
Ⅰ/Ⅱ	6	2 (33.3)	4 (66.7)	0 (0.0)	0 (0.0)
Ⅲ/Ⅳ	12	5 (41.7)	0 (0.0)	3(25.0)	4 (30.7)
肺转移						1.33	0.185
单肺	13	4 (30.8)	2 (15.4)	4 (30.8)	3 (23.1)
双肺	7	4 (57.1)	2 (28.6)	0 (0.0)	1 (14.3)
转移灶						0.95	0.343
单发	10	4 (40.0)	3 (30.0)	3 (30.0)	0 (0.0)
多发	10	4 (40.0)	1 (10.0)	1 (10.0)	4 (40.0)
其他部位转移						1.29	0.197
否	12	6 (50.0)	3 (25.0)	1 (8.3)	2 (16.7)
是	8	2 (25.0)	1 (12.5)	3 (37.5)	2 (25.0)
发现肺转移时期						0.65	0.519
术前	12	4 (33.3)	3 (25.0)	2 (16.7)	3 (25.0)
术后	8	4 (50.0)	1 (12.5)	2 (25.0)	1 (12.5)
新辅助化疗						0.80	0.427
否	11	5 (45.5)	2 (18.2)	3 (27.3)	1 (9.1)
是	9	3 (33.3)	2 (22.2)	1 (11.1)	3 (33.3)
化疗方案						2.54	0.011
NWTS-5	11	2 (18.2)	2 (18.2)	3 (27.3)	4 (36.4)
CCCG-WT2016	9	6 (66.7)	2 (22.2)	1 (11.1)	0 (0.0)

变量	偏回归系数	标准误	Z值	P	OR(95%CI)
CR	-0.87	2.52	-0.35	0.729
PR	0.36	2.50	0.15	0.884
SD	1.71	2.52	0.68	0.498
年龄（对照为≤2岁）
>2岁	1.60	1.07	1.50	0.133	4.97(0.61~40.38)
化疗方案（对照为NWTS-5）
CCCG-WT2016	-2.05	1.01	-2.03	0.043	0.13(0.02~0.94)