前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值

doi:10.19401/j.cnki.1007-3639.2022.12.004

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (12): 1168-1177.doi: 10.19401/j.cnki.1007-3639.2022.12.004

前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值

邹孜瑊¹(), 孙伟¹, 胡涂¹, 王春萌¹, 严望军¹, 罗志国², 刘欣³, 钟景钦¹, 林馨怡¹, 徐宇¹, 陈勇¹()

1.复旦大学附属肿瘤医院骨软组织外科，复旦大学上海医学院肿瘤学系，上海 200032
2.复旦大学附属肿瘤医院消化肿瘤内科，复旦大学上海医学院肿瘤学系，上海 200032
3.复旦大学附属肿瘤医院头颈及神经内分泌肿瘤内科，复旦大学上海医学院肿瘤学系，上海 200032

收稿日期:2022-11-02 修回日期:2022-12-01 出版日期:2022-12-30 发布日期:2023-02-02
通信作者: 陈勇（ORCID: 0000-0002-7188-4566），主任医师，复旦大学附属肿瘤医院骨软组织外科副主任。
作者简介:邹孜瑊（ORCID: 0000-0002-4891-478X），硕士研究生在读。
基金资助:
国家自然科学基金(82272857);国家自然科学基金(81802636);临港实验室基金(LG-QS-202205-11);上海市科学技术委员会研究项目(19411951700)

Clinical value of sentinel lymph node biopsy in patients with cutaneous and acral melanoma

ZOU Zijian¹(), SUN Wei¹, HU Tu¹, WANG Chunmeng¹, YAN Wangjun¹, LUO Zhiguo², LIU Xin³, ZHONG Jingqin¹, LIN Xinyi¹, XU Yu¹, CHEN Yong¹()

1. Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
2. Department of Digestive System Tumors, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
3. Department of Head & Neck Tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Received:2022-11-02 Revised:2022-12-01 Published:2022-12-30 Online:2023-02-02
Contact: CHEN Yong

摘要/Abstract

摘要：

背景与目的：前哨淋巴结活检（sentinel lymph node biopsy，SLNB）是评估皮肤型和肢端型黑色素瘤区域淋巴结转移情况及病理学分期的重要手段。SLNB作为外科诊疗规范的重要环节，已在各大诊疗指南中被推荐，也已在中国临床应用近10年。自2017年靶向和免疫治疗应用于中国黑色素瘤治疗领域，患者预后得到显著改善。本研究旨在分析复旦大学附属肿瘤医院近5年恶性黑色素瘤患者的临床资料，评估在新药治疗时代前哨淋巴结（sentinel lymph node，SLN）状态在临床应用的价值和对预后的影响。方法：对2017—2021年在复旦大学附属肿瘤医院黑色素瘤诊治中心接受诊治的381例恶性黑色素瘤患者的临床资料进行回顾性分析。每例患者均接受原发灶扩大切除和相应的SLNB，手术后随访至少6个月。SLN定位使用美兰染色或同位素示踪。结果：本研究共入组381例恶性黑色素瘤患者，平均Breslow浸润深度为3.10 mm，69.8%为肢端型，溃疡率为57.1%，SLN阳性率为34.6%，中位无复发生存率（relapse-free survival，RFS）为17个月。SLN状态是显著影响患者预后的独立危险因素。在N_1a和T₄亚组，SLN活检数>2枚的患者具有更好的RFS。接受完整的区域淋巴结清扫（complete lymph node dissection，CLND）和未清扫患者的RFS差异无统计学意义，在SLN活检数>2枚和SLN微转移直径<1 mm的亚组未清扫者反而具有更优的RFS。结论：SLN状态仍是影响临床无显性转移的黑色素瘤预后的重要因素，对于恶性黑色素瘤患者应常规开展SLNB，在保证微创的前提下，提高SLN定位的准确性，保证SLNB充分。SLN阳性后行即刻CLND对于皮肤型和肢端型黑色素瘤患者未能带来进一步的预后改善。

关键词: 恶性黑色素瘤, 前哨淋巴结活检, 区域淋巴结清扫, 预后

Abstract:

Background and purpose: For cutaneous and acral malignant melanoma, sentinel lymph node biopsy (SLNB) is an effective tool to evaluate the situation of regional lymph node metastasis and to determine the pathological stage. As an important part of the standard procedure for surgical diagnosis and treatment, SLNB has been recommended in major guidelines and already has a ten-year clinical application. Since the introduction of targeted therapy and immune therapy for malignant melanoma in 2017, the prognosis of patients has been significantly improved. This study aimed to collect the clinical data of Chinese malignant melanoma cases in recent five years so as to discover, in the era of new drug treatment, the significance of sentinel lymph node (SLN) status in clinical application and its influence on survival outcome. Methods: Data of 381 patients with histologically diagnosed malignant melanoma were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. SLNB was performed with wide resection of the primary lesion for each case, and follow-ups of at least 6 months were taken afterwards. Lymphoscintigraphy or methylene blue dye was applied for identification of SLN. Results: A total of 381 patients were included. The mean Breslow thickness was 3.10 mm, among the 381 patients, 69.8% with acral lesion, 59.7% with ulceration, 34.6% with positive SLN, and the median relapse-free survival (RFS) was 17 months. Patient’s survival was significantly influenced by SLN status. Patients with more than 2 biopsied SLN had significantly better RFS in subgroups of N_1a stage and T₄ stage. There was no significant difference in RFS between patients who received complete lymph node dissection (CLND) and those who did no, and the latter even showed better RFS in subgroups of SLN biopsied number >2 and SLN micrometastasis diameter <1 mm. Conclusion: SLN status remained an important factor influencing the prognosis of melanoma cases with no clinical evidence of significant metastasis, and SLNB should be applied as a routine surgical procedure for malignant melanoma patients. While keeping the operation minimally invasive, the accuracy of SLN locating should be improved, and the sufficiency of biopsy should be ensured. Immediate CLND provides no improvement in the prognosis of cutaneous and acral melanoma patients with positive SLN status.

Key words: Malignant melanoma, Sentinel lymph node biopsy, Complete lymph node dissection, Prognosis

中图分类号:

R739.5

邹孜瑊, 孙伟, 胡涂, 王春萌, 严望军, 罗志国, 刘欣, 钟景钦, 林馨怡, 徐宇, 陈勇. 前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值[J]. 中国癌症杂志, 2022, 32(12): 1168-1177.

ZOU Zijian, SUN Wei, HU Tu, WANG Chunmeng, YAN Wangjun, LUO Zhiguo, LIU Xin, ZHONG Jingqin, LIN Xinyi, XU Yu, CHEN Yong. Clinical value of sentinel lymph node biopsy in patients with cutaneous and acral melanoma[J]. China Oncology, 2022, 32(12): 1168-1177.

图/表 7

表1

不同SLN状态的患者临床病理学资料"

Item	Total (n=381)	SLN negative (n=249)	SLN positive (n=132)	P value
Gender				0.035^*
Female	210 (55.1)	147 (59.0)	63 (47.7)
Male	171 (44.9)	102 (41.0)	69 (52.3)
Age/year				0.031^*
<60	202 (53.0)	142 (57.0)	60 (45.5)
≥60	179 (47.0)	107 (43.0)	72 (54.5)
Subtype				0.226
Acral	266 (69.8)	179 (71.9)	87 (65.9)
Cutaneous	115 (30.2)	70 (28.1)	45 (34.1)
Primary location				0.850
Upper extremity	54 (14.2)	37 (14.9)	17 (12.9)
Trunk	56 (14.7)	37 (14.9)	19 (14.4)
Lower extremity	271 (71.1)	175 (70.3)	96 (72.7)
Palm	2 (0.5)	0 (0.0)	2 (1.5)
Sole	200 (52.5)	133 (53.4)	67 (50.8)
Nail	56 (14.6)	42 (16.8)	14 (10.6)
SLNB basin				0.770
Groin	281 (73.8)	183 (73.5)	98 (74.2)
Axilla	81 (21.3)	53 (21.3)	28 (21.2)
Popliteal	3 (0.8)	3 (1.2)	0 (0)
Bilateral	7 (1.8)	4 (1.6)	3 (2.3)
Multi-basin	9 (2.4)	6 (2.4)	3 (2.3)
Breslow thickness				<0.001
0-1	55 (14.4)	46 (18.5)	9 (6.8)
>1-2	91 (23.9)	68 (27.3)	23 (17.4)
>2-4	123 (32.3)	76 (30.5)	47 (35.6)
>4	112 (29.4)	59 (23.7)	53 (40.2)
Clark level				<0.001
Ⅰ	5 (1.3)	5 (2.0)	0 (0.0)
Ⅱ	25 (6.6)	21 (8.4)	4 (3.0)
Ⅲ	19 (5.0)	14 (5.6)	5 (3.8)
Ⅳ	225 (59.1)	136 (54.6)	89 (67.4)
Ⅴ	57 (15.0)	29 (11.6)	28 (21.2)
Unknown	50 (13.1)	44 (17.7)	6 (4.5)
Ulceration				0.011
No	184 (48.3)	132 (53.0)	52 (39.4)
Yes	197 (51.7)	117 (47.0)	80 (60.6)
Number of biopsied SLN				0.971
1-2	216 (56.7)	141 (56.6)	75 (56.8)
>2	165 (43.3)	108 (43.4)	57 (43.2)
N stage				0.000
N₀	248 (65.1)	-	-
N₁	76 (19.9)	1 (0.4)^#	75 (56.8)
N₂	50 (13.1)	-	50 (37.9)
N₃	7 (1.8)	-	7 (5.3)
TNM stage				<0.001
Ⅰ	95 (24.9)	95 (38.2)	-
Ⅱ	153 (40.2)	153 (61.4)	-
Ⅲ	133 (34.9)	1 (0.4)^	132 (100.0)
Gene mutation				<0.001
BRAF	85 (22.3)	43 (17.3)	42 (31.8)
NRAS	42 (11.0)	26 (10.4)^#	16 (12.1)
C-KIT	24 (6.3)	12 (4.8)	12 (9.1)
BNK wild type	156 (40.9)	105 (42.2)	51 (38.6)
Unknown	74 (19.4)	63 (25.3)	11 (8.3)
Adjuvant therapy				<0.001
Observation	138 (36.2)	114 (45.8)	24 (18.2)
IFN	89 (23.3)	74 (19.4)	15 (11.4)
PD-1	124 (32.5)	53 (21.3)	71 (53.8)
Targeted therapy	22 (5.8)	6 (2.4)	16 (12.1)
Others	8 (2.1)	2 (0.8)	6 (4.5)

表1

表2

图1

表3

图2

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表4

参考文献 15

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Item	Risk	Univariate analysis			Multivariable analysis
Item	Risk	OR	95% CI	P value	OR	95% CI	P value
Gender	Female vs male	0.634	0.414-0.969	0.035^*
Age	<60 years vs ≥60 years	0.628	0.411-0.960	0.032^*	0.610	0.393-0.947	0.028^*
Subtype	Acral vs cutaneous	0.756	0.480-1.190	0.227
Breslow thickness	0-1 mm	1.000	-	<0.001^*	1.000	-	<0.001^*
Breslow thickness	1-2 mm	1.729	0.734-4.072	0.210	1.927	0.810-7.620	0.138
Breslow thickness	2-4 mm	3.161	1.418-7.046	0.005^*	3.394	1.512-4.583	0.003^*
Breslow thickness	>4 mm	2.053	2.053-10.269	<0.001^*	4.868	2.162-10.959	<0.001^*
Ulceration	Yes vs no	1.736	1.130-2.665	0.012^*
Number of biopsied SLN	>2 vs ≤2	0.992	0.648-1.519	0.992

Item	Risk	Univariate analysis			Multivariable analysis
Item	Risk	OR	95% CI	P value	OR	95% CI	P value
Gender	Female vs male	0.575	0.379-0.872	0.009^*
Age	<60 years vs ≥60 years	0.751	0.497-1.136	0.176
Subtype	Acral vs cutaneous	1.169	0.916-1.492	0.210
SLN status	Positive vs negative	2.862	1.885-4.346	<0.001^*	2.103	1.377-3.213	0.001^*
Breslow thickness	0-1 mm	1.000	-	<0.001^*	1.000	-	<0.001^*
Breslow thickness	1-2 mm	2.747	0.593-12.715	0.196	2.240	0.481-10.430	0.304
Breslow thickness	2-4 mm	8.935	2.140-37.304	0.003^*	4.420	1.022-19.117	0.047^*
Breslow thickness	>4 mm	20.295	4.903-84.010	<0.001^*	8.635	1.983-37.604	0.004^*
Ulceration	Yes vs no	5.007	3.017-8.312	<0.001^*	2.813	1.561-4.631	<0.001^*
Number of biopsied SLN	>2 vs ≤2	0.774	0.505-1.186	0.239

Item	CLND (n=101)	No CLND (n=31)	P value	Item	CLND (n=101)	No CLND (n=31)	P value
Gender			0.620	Breslow thickness/mm			0.507
Male	54 (53.5)	15 (48.4)		0-1	7 (6.9)	2 (6.5)
Female	47 (46.5)	16 (51.6)		1-2	16 (15.8)	7 (22.6)
Age/year				2-4	34 (33.7)	13 (41.9)
<60	50 (49.5)	10 (32.3)	0.092	>4	44 (43.6)	9 (29.0)
≥60	51 (50.5)	21 (67.7)		Ulceration			0.741
Subtype			0.806	No	39 (38.6)	13 (41.9)
Acral	66 (65.3)	21 (67.7)		Yes	62 (61.4)	18 (58.1)
Cutaneous	35 (34.7)	10 (32.3)		Positive SLN number			0.766
Primary location			0.950	1	70 (68.6)	23 (74.2)
Upper extremity	13 (12.9)	4 (12.9)		2	28 (27.5)	7 (22.6)
Trunk	14 (13.9)	5 (16.1)		3	2 (2.0)	1 (3.2)
Lower extremity	74 (73.3)	22 (71.0)		4	1 (1.0)	0 (0.0)

前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值

Clinical value of sentinel lymph node biopsy in patients with cutaneous and acral melanoma

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