示踪用盐酸米托蒽醌注射液与核素用于乳腺癌前哨淋巴结活检的疗效对比研究

doi:10.19401/j.cnki.1007-3639.2023.02.005

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (2): 126-133.doi: 10.19401/j.cnki.1007-3639.2023.02.005

示踪用盐酸米托蒽醌注射液与核素用于乳腺癌前哨淋巴结活检的疗效对比研究

杨犇龙¹^,²(), 焦得闯³, 陈嘉健¹^,², 王春建⁴, 金利丹⁵, 赵文和⁵, 高学强⁶, 王海波⁶, 李珺⁷, 赵海东⁷, 吴迪⁸, 范志明⁸, 王淑君⁹, 刘真真³(), 王永胜⁴(), 吴炅¹^,²()

1.复旦大学附属肿瘤医院乳腺外科，复旦大学上海医学院肿瘤学系，上海 200032
2.中国上海肿瘤医学协同创新中心，上海 200032
3.郑州大学附属肿瘤医院，河南省肿瘤医院乳腺科，河南郑州 450003
4.山东省肿瘤医院乳腺外科，山东济南 250117
5.浙江大学医学院附属邵逸夫医院肿瘤外科，浙江杭州 310016
6.青岛大学附属医院乳腺外科，山东青岛 266000
7.大连医科大学附属第二医院乳腺外科，辽宁大连 116021
8.吉林大学白求恩第一医院乳腺外科，吉林长春 130021
9.沈阳药科大学药学院药剂学系，辽宁沈阳 110016

收稿日期:2022-12-27 修回日期:2023-02-03 出版日期:2023-02-28 发布日期:2023-03-22
通信作者: 吴炅（ORCID: 0000-0002-8103-0505），博士，主任医师，复旦大学附属肿瘤医院副院长；王永胜（ORCID: 0000-0001-6252-684X），博士，主任医师，山东省肿瘤医院乳腺病中心主任；刘真真（ORCID: 0000-0002-3878-1258），博士，主任医师，郑州大学附属肿瘤医院乳腺科主任。
作者简介:杨犇龙（ORCID: 0000-0003-1343-728X），博士，副主任医师。
吴炅，主任医师，教授，博士研究生导师，复旦大学附属肿瘤医院副院长，药物临床试验机构主任。学术任职包括：中国抗癌协会乳腺癌专业委员会主任委员，中国医师协会外科医师分会乳腺外科医师专业委员会副主任委员，中国医师协会肿瘤医师分会副主任委员，中华医学会肿瘤学分会常委，中华医学会外科分会乳腺外科学组副组长，上海市医学会肿瘤分会候任主委，上海市抗癌协会乳腺癌专业委员会荣誉主任委员，上海市医学会肿瘤靶分子专科分会前任主任委员。擅长乳腺癌的综合治疗，特别是新的外科诊疗技术在乳腺疾病中的应用，包括乳腺癌保乳手术、乳腺癌前哨淋巴结活检、乳腺癌一期乳房重建手术。作为一期临床研究负责人，牵头主持8项抗肿瘤新药Ⅰ期注册研究。主持编撰了《乳腺肿瘤整形与乳房重建专家共识（2018年版）》、《乳腺肿瘤整形与乳房重建专家共识（2022年版）》和《保留乳房治疗专家共识（2020年版）》，并连续12年主办上海市乳房重建论坛。以第一作者及通信作者在SCI收录期刊上发表论文70余篇；主编《乳腺癌术后乳房重建》、《乳腺癌的乳房重建手术》、Reconstruction Surgery in Breast Cancer，参编《现代乳腺肿瘤学进展》、《肿瘤外科手术学》、《乳腺肿瘤学》等专著。曾被授予上海市卫生局首批“医苑新星”、上海市卫生局先进工作者、复旦大学“世纪之星”，获得上海市科技启明星、上海市教委曙光计划、上海市科委优秀学术带头人计划等人才基金。目前承担国家重大慢病非传染性疾病防控研究课题及国家自然科学基金面上项目等。2004年以第三完成人获国家科技进步二等奖（乳腺癌的临床和基础研究），并多次以主要完成人获得多项上海市科技进步奖；以第一完成人获得上海市临床医学成果奖。

Compared the efficacy of mitoxantrone hydrochloride injection for tracing with radionuclide in sentinel lymph node biopsy of breast cancer

YANG Benlong¹^,²(), JIAO Dechuang³, CHEN Jiajian¹^,², WANG Chunjian⁴, JIN Lidan⁵, ZHAO Wenhe⁵, GAO Xueqiang⁶, WANG Haibo⁶, LI Jun⁷, ZHAO Haidong⁷, WU Di⁸, FAN Zhimin⁸, WANG Shujun⁹, LIU Zhenzhen³(), WANG Yongsheng⁴(), WU Jiong¹^,²()

1. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
2. Department of Collaborative Innovation Center for Cancer Medicine, Fudan University, Shanghai 200032, China
3. Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450003, Henan Province, China
4. Department of Breast Surgery, Shandong Cancer Hospital Fudan University, Jinan 250117, Shandong Province, China
5. Department of Oncological Surgery, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
6. Department of Breast Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
7. Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116021, Liaoning Province, China
8. Department of Breast Surgery, The First Bethune Hospital of Jilin University, Changchun 130021, Jilin Province, China
9. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China

Received:2022-12-27 Revised:2023-02-03 Published:2023-02-28 Online:2023-03-22
Contact: LIU Zhenzhen, WANG Yongsheng, WU Jiong

摘要/Abstract

摘要：

背景与目的： 国内外指南均推荐核素用作前哨淋巴结活检术（sentinel lymph node biopsy，SLNB）示踪剂，但多种原因导致该技术在国内未得到普及。示踪用盐酸米托蒽醌注射液（mitoxantrone hydrochloride injection for tracing，MHI）是一种新型乳腺癌前哨淋巴结（sentinel lymph node，SLN）示踪剂，其在乳腺癌SLNB中的效果尚未明确。本研究是一项大样本阳性对照临床试验，旨在评价MHI和核素在SLNB中的示踪差异。方法： 试验纳入了2019年12月—2020年7家医院的早期乳腺癌患者。所有入组的早期乳腺癌患者均在手术前注射MHI和核素作为SLN示踪剂。分别统计MHI和核素的SLN检出数量和SLN检出率，分析两种示踪剂示踪效果的差异。结果： MHI的SLN检出率为96.9%（370/382），核素的SLN检出率为97.4%（372/382），两者检出率差异无统计学意义（P>0.05）。两种示踪剂共同检测到362例（94.7%）受试者的SLN；16例（4.1%）发生可能与试验药物相关的不良事件。结论： 本研究发现MHI示踪效果不劣于核素。且MHI的使用无需特殊仪器/设备辅助。

关键词: 乳腺癌, 前哨淋巴结活检, 示踪用盐酸米托蒽醌注射液, 淋巴示踪剂, 核素, 腋窝淋巴结

Abstract:

Background and purpose: Both domestic and foreign guidelines recommend the use of radionuclide as sentinel lymph node (SLN) biopsy (SLNB) tracer, however this technique has not been popularized in China for a variety of reasons. Mitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate the differences between MHI and radionuclide in SLNB tracing. Methods: The trial was conducted across 7 hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and radionuclide (technetium 99 labeled sulfur colloid, ^99mTc-Sc) as SLN tracers during the surgery. The number of SLNs detected and sentinel node detection rates of MHI and radionuclide were counted to evaluate differences in the tracing effects between the two tracers. Results: SLN detection rates of MHI and radionuclide were 96.9% (370/382) and 97.4% (372/382), respectively, with no significant difference (P>0.05). SLNs were co-detected by both tracers in 362 (94.7%) patients; 16 (4.1%) had adverse events possibly related to the trial drugs. Conclusion: In this study, it was found that the lymphatic tracing ability of MHI was not inferior to that of radionuclide. Meanwhile, the use of MHI does not require special instrument/equipment assistance.

Key words: Breast cancer, Sentinel lymph node biopsy, Mitoxantrone hydrochloride injection for tracing, Lymphatic tracer, Radionuclide, Axillary lymph node

中图分类号:

R737.9

杨犇龙, 焦得闯, 陈嘉健, 王春建, 金利丹, 赵文和, 高学强, 王海波, 李珺, 赵海东, 吴迪, 范志明, 王淑君, 刘真真, 王永胜, 吴炅. 示踪用盐酸米托蒽醌注射液与核素用于乳腺癌前哨淋巴结活检的疗效对比研究[J]. 中国癌症杂志, 2023, 33(2): 126-133.

YANG Benlong, JIAO Dechuang, CHEN Jiajian, WANG Chunjian, JIN Lidan, ZHAO Wenhe, GAO Xueqiang, WANG Haibo, LI Jun, ZHAO Haidong, WU Di, FAN Zhimin, WANG Shujun, LIU Zhenzhen, WANG Yongsheng, WU Jiong. Compared the efficacy of mitoxantrone hydrochloride injection for tracing with radionuclide in sentinel lymph node biopsy of breast cancer[J]. China Oncology, 2023, 33(2): 126-133.

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参考文献 21

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Item	Patients in MHI and ^99mTc-Sc group (n=382)	Item	Patients in MHI and ^99mTc-Sc group (n=382)
Age/year [mean (range)]	53 (26-70)	Tumor site n (%)
Body mass index [mean (range)]	23.8 (16.6-38.8)	Outer	175 (45.8)
Tumor type n (%)		Outer bottom	30 (7.8)
Invasive breast cancer	308 (80.6)	Inner top	96 (25.1)
Carcinoma in situ	47 (12.3)	Inferior	20 (5.2)
Other	27 (7.1)	Central area	61 (16.0)
Pathological diagnosis n (%)		Procedure n (%)
T_1a	4 (1.0)	Breast conservation	161 (42.1)
T_1b	2 (8.4)	Total mastectomy	221 (57.9)
T_1c	184 (48.2)
T₂	157 (41.1)
T₃	5 (1.3)

^99mTc-Sc	MHI
^99mTc-Sc	Blue staining	No blue staining	Total
Positive SLN
Hot spots	102 (70.8)	12 (8.3)	114 (79.2)
No hot spot	15 (10.4)	15 (10.4)	30 (20.8)
Total	117 (81.2)	27 (18.8)	144 (100.0)
Positive patients
Hot spots	75 (79.8)	5 (5.3)	80 (85.1)
No hot spot	9 (9.6)	5 (5.3)	14 (14.9)
Total	84 (89.4)	10 (10.6)	94 (100.0)

System organ class preferred term	Number of patients (n = 387)
All adverse events	16 (4.1)
Infections and infestations	1 (0.3)
Pustular rash	1 (0.3)
Investigations	16 (4.1)
Alanine aminotransferase increased	16 (4.1)
Aspartate aminotransferase increased	15 (3.9)
Gamma-glutamyltransferase increased	5 (1.3)
Blood alkaline phosphatase increased	2 (0.5)

示踪用盐酸米托蒽醌注射液与核素用于乳腺癌前哨淋巴结活检的疗效对比研究

Compared the efficacy of mitoxantrone hydrochloride injection for tracing with radionuclide in sentinel lymph node biopsy of breast cancer

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