Abstract
Background
Sentinel lymph node biopsy (SLNB) helps to determine accurate pathological stages and facilitates strategies for regional disease control in melanoma. However, whether the number of biopsied sentinel lymph nodes (SLNs) influences the patients' survival is rarely investigated.
Methods
Acral or cutaneous melanoma patients with no history of nodal disease who received SLNB in Fudan University Shanghai Cancer Center (FUSCC) from January 1, 2017, to December 31, 2021 were retrospectively enrolled. Clinicopathological variables including Breslow index, ulceration, number of positive SLNs, SLN/non‐SLN status were analyzed. The pathologic nodal (pN) stage and pathological stage were defined.
Results
A total of 381 eligible patients were enrolled in this study, of whom 132 (34.7%) patients were diagnosed with SLN‐positive. The median number of biopsied SLNs was 2 (range: 1 to 20). Different numbers of biopsied SLNs did not influence the release‐free survival (RFS) of the general patients. However, patients with >2 SLNs had a longer RFS than those with 1–2 SLNs in T4, N1a group and those who rejected complete lymph node dissection (CLND).
Conclusions
In patients with T4 melanomas, N1a melanomas and those that did not undergo a CLND, the prognosis of those with three or more SLNs retrieved seemed to be improved.
Keywords: lymph node metastasis, melanoma, prognosis, sentinel lymph node biopsy
1. INTRODUCTION
Sentinel lymph node biopsy (SLNB) has become a standard treatment for clinically node‐negative cutaneous and acral melanoma patients. To detect micro‐metastasis in the regional lymph node basin in a timely manner, SLNB helps to identify the pathological stage precisely and thereby facilitates therapeutic strategy decisions and improves regional disease control. It also aids to pick out potential patients who might benefit from postoperative adjuvant therapy and improve the prognosis ultimately. 1 The metastatic status of sentinel lymph nodes is an independent prognostic factor of melanoma, as well as primary tumor thickness. 2 , 3 SLNB is suggested for primary melanoma patients with Breslow thickness more than 0.8 mm, or less than 0.8 mm with risk factors, for instance, regression, ulceration, neurovascular invasion, and young age. 3 Our previous study also showed that non‐SLN positivity was also negatively correlated with disease‐free survival (DFS) and overall survival (OS) in patients who received completion lymph node dissection (CLND) after identification of one positive SLN. 4 In addition, numerous studies have implicated that tumor burden in SLN, such as maximum diameter and location of micro‐metastatic lesions, number of metastatic foci, or presence of lymph node extracapsular extension, has significant effects on postoperative outcomes for patients with melanoma. 5 , 6 , 7 , 8 , 9 Macro‐metastasis of SLN invasion was associated with higher risk of non‐SLN involvement and always indicated a poor prognosis with respect to micro‐metastases. 10
However, few studies have concentrated on the prognostic role of other indicators of SLNB. One major concern is the accuracy of SLNB, which depends on the lymphatic mapping and adequacy of nodal biopsy. The number of biopsied SLNs was rarely discussed in previous studies, because SLNB is generally considered as a minimally invasive procedure to prevent limb swelling and numbness. On the other hand, more than one node is detected in clinical practice during SLNB. The biopsy of all identified SLNs might lead to more accurate pathological stagging. According to the stagging criteria, more regional nodes involved with metastatic melanoma is always classified as higher stage and is related to bad prognosis. However, Jakub et al. found if the positive lymph nodes is confined to the SLNs without positive non‐SLNs, the number of regional lymph nodes involved with metastatic disease does not affect DFS and OS. 11 In addition, inadequate number of SLNs was found to increase the positivity rate in non‐SLNs. 12 Thus, except for a minimal requirement on the number of lymph nodes evaluated after CLND, 13 it is still essential to indicate minimal SLNs that should be biopsied during SLNB. Therefore, the present single‐center retrospective study aimed to further investigate the prognostic value of the number of biopsied SLNs for Chinese patients with melanoma.
2. PATIENTS AND METHODS
Primary cutaneous or acral melanoma patients with no clinical nodal disease, who underwent SLNB at Fudan University Shanghai Cancer Center (FUSCC; Shanghai, China) from January 1, 2017, to December 31, 2021 were retrospectively enrolled in the study. Patients with incomplete medical data or with a follow‐up of less than 6 months were excluded from the study. Clinicopathological variables, including gender, age, Clark level, Breslow thickness, ulceration, number of positive SLNs, SLN/non‐SLN status, and adjuvant therapy, were recorded. The pathologic nodal (pN) stage and pathological stage of patients were defined based on the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual. 14
2.1. SLNB
SLNB was routinely performed under lymphatic mapping through lymphoscintigraphy by technetium‐99 sulfur colloid, methylene blue dye, or both. The pathological examination of resected SLN was described in our previously published study. 15 Briefly, each of SLNs was dissected at 3 mm thickness or along the longest axis on the largest surface, fixed by 3.7% neutral formaldehyde, then dehydrated, conventionally embedded into paraffin and finally stained with hematoxylin and eosin (HE). The metastatic status of SLNs was also determined by immunohistochemical staining of HMB45, S‐100, SOX10 and Melan A. The antibodies against S‐100 and Melan A were purchased from Dako Co., Ltd. (Copenhagen, Denmark). The antibody against HMB45 was purchased from MaiXin Biotechnologies Co., Ltd. (Fuzhou, China). The antibody against SOX10 was purchased from Gene Tech Co., Ltd. (Shanghai, China). Each section was observed under a light microscope by two pathologists. The majority of patients with metastatic SLNs received CLND within 1 month.
2.2. Follow‐up
Patients were assessed through clinical examinations, such as routine physical checkup, ultrasound, computed tomography and/or magnetic resonance imaging every 3 months for the first 2 years, every 6 months for 3–5 years, and then annually. Patients were followed up through reexamination or telephone follow‐up until death or December 31, 2021. The survival of patients was censored at the date of the last follow‐up (December 31, 2021). Relapse‐free survival (RFS) was defined as the interval between radical surgery and the first recurrence or distant metastasis. Recurrence or metastasis was confirmed by pathology or imaging follow‐up.
2.3. Statistical analyses
Categorical variables were described by the frequency and component ratio. The Pearson's chi‐squared test or the Fisher's exact test was used for univariable analysis between patients with 1 to 2 biopsied SLNs and those with more than 2 biopsied SLNs. The Kaplan–Meier method and the log‐rank test were adopted to describe and compare the impacts of some prognostic factors (SLN‐positivity, acral subtype, N1a stage, T4 stage and SLN‐positivity without CLND) on RFS between these two groups. p‐Values less than .05 were considered statistically significant. The statistical analysis was performed using SPSS 22.0 software (IBM, Armonk, NY, USA). This study was approved by the Ethics Committee of FUSCC, and every participant signed an informed consent form before enrollment.
3. RESULTS
3.1. Baseline characteristics
A total of 381 eligible patients were enrolled in this study, and their median age was 58 years, ranging from 19 to 89 years. Totally 171 (44.9%) patients were male, 266 (69.8%) patients had acral melanoma, and 115 (30.2%) patients had cutaneous melanoma. Of all the patients, melanoma was at the upper extremities in 54 (14.2%) patients, at the trunk in 56 (14.7%) patients, and at the lower extremities in 271 (71.1%) patients. Among the eligible patients, melanoma was of T1 stage in 55 (14.4%) patients, of T2 stage in 91 (23.9%) patients, of T3 stage in 123 (32.3%) patients, and of T4 stage in 112 (29.4%) patients (Table 1).
TABLE 1.
Comparison of clinicopathological variables between groups with different numbers of sentinel lymph nodes.
| SLN biopsied 1–2 n = 216 case (%) | SLN biopsied > 2 | Total | p‐Value | |
|---|---|---|---|---|
| n = 165 case (%) | case (%) | |||
| Gender | ||||
| Female | 119 (55.1%) | 91 (55.2%) | 210 (55.1%) | .991 |
| Male | 97 (44.9%) | 74 (44.8%) | 171 (44.9%) | |
| Age (median) | ||||
| <60 years | 114 (52.8%) | 88 (53.3%) | 202 (53.0%) | .914 |
| ≥60 years | 102 (47.2%) | 77 (46.7%) | 179 (47.0%) | |
| Subtype | ||||
| Acral | 164 (75.9%) | 102 (61.8%) | 266 (69.8%) | .003 |
| Cutaneous | 52 (24.1%) | 63 (38.2%) | 115 (30.2%) | |
| Primary location | ||||
| Upper extremity | 20 (9.3%) | 34 (20.6%) | 54 (14.2%) | <.001 |
| Trunk | 20 (9.3%) | 36 (21.8%) | 56 (14.7%) | |
| Lower extremity | 176 (81.5%) | 95 (57.6%) | 271 (71.1) | |
| SLNB basin | ||||
| Groin | 184 (85.2%) | 97 (58.8%) | 275 (72.2%) | <.001 |
| Axilla | 26 (12.0%) | 55 (33.3%) | 81 (21.3%) | |
| Popliteal | 3 (1.4%) | 0 (0.0%) | 3 (0.8%) | |
| Bilateral | 1 (0.5%) | 6 (3.6%) | 7 (1.8%) | |
| Multi‐basin | 2 (0.9%) | 7 (4.2%) | 9 (2.4%) | |
| Breslow thickness (T stage) | ||||
| 0–1 mm | 34 (15.7%) | 21 (12.7%) | 55 (14.4%) | .272 |
| >1–2 mm | 55 (25.5%) | 36 (21.8%) | 91 (23.9%) | |
| >2–4 mm | 72 (33.3%) | 51 (30.9%) | 123 (32.3%) | |
| >4 mm | 55 (25.5%) | 57 (34.5%) | 112 (29.4%) | |
| Clark level | ||||
| I | 4 (1.9%) | 22 (13.3%) | 26 (6.8%) | .462 |
| II | 13 (6.0%) | 1 (0.6%) | 14 (3.7%) | |
| III | 13 (6.0%) | 12 (7.3%) | 25 (6.6%) | |
| IV | 131 (60.6%) | 6 (3.6%) | 137 (36.0%) | |
| V | 27 (12.5%) | 94(57.0%) | 121 (31.8%) | |
| Unknown | 27 (12.5%) | 30 (18.2%) | 57 (15.0%) | |
| Ulceration | ||||
| No | 99 (45.8%) | 85 (51.5%) | 184 (483%) | .271 |
| Yes | 117 (54.2%) | 80 (48.5$) | 197 (51.7) | |
| SLN status | ||||
| Negative | 141 (65.3%) | 108 (65.5%) | 249 (65.4%) | .971 |
| Positive | 75 (34.7%) | 57 (34.5%) | 132 (34.6%) | |
| Non‐SLN status | ||||
| Negative | 41 (19.0%) | 38 (23.0%) | 79 (59.4%) | .161 |
| Positive | 18 (8.3%) | 5 (3.0%) | 23 (17.3%) | |
| No dissection | 17 (7.9%) | 14 (8.5%) | 31 (23.3%) | |
| N stage | ||||
| N0 | 141 (65.3%) | 107 (64.8%) | 248 (65.1%) | .630 |
| N1 | 45 (20.8%) | 31 (18.8%) | 76 (19.9%) | |
| N2 | 25 (11.6%) | 25 (15.2%) | 50 (13.1%) | |
| N3 | 5 (2.3%) | 2 (1.2%) | 7 (1.8%) | |
| TNM stage | ||||
| Stage I | 57 (26.4%) | 38 (23.0%) | 95 (24.9%) | .731 |
| Stage II | 84 (38.9%) | 69 (41.8%) | 153 (40.2%) | |
| Stage III | 75 (34.7%) | 58 (35.2%) | 133 (34.9%) | |
| Gene mutation | ||||
| BRAF | 43 (19.9%) | 42 (25.5%) | 85 (22.3%) | .669 |
| NRAS | 27 (12.5%) | 15 (9.1%) | 43 (11.3%) | |
| CKIT | 14 (6.5%) | 10 (6.1%) | 24 (63.0%) | |
| BNK wide‐type | 90 (41.7%) | 66 (40.0%) | 156 (40.9%) | |
| Unknown | 42 (19.4%) | 32 (19.4%) | 74 (19.4%) | |
| Adjuvant therapy | ||||
| Observation | 86 (39.8%) | 52 (31.5%) | 138 (36.2%) | .135 |
| IFN | 50 (23.1%) | 39 (23.6%) | 89 (23.4%) | |
| Immunotherapy | 65 (30.1%) | 59 (35.8%) | 124 (32.5%) | |
| Targeted therapy | 9 (4.2%) | 13 (7.9%) | 22 (5.8%) | |
| Chemotherapy | 1 (0.5%) | 0 (0.0%) | 1 (0.3%) | |
| IO + Chemo | 4 (1.9%) | 1 (0.6%) | 5 (1.3%) | |
| IO + TT | 0 (0.0%) | 1 (0.6%) | 1 (0.3%) | |
| Radiation | 1 (0.5%) | 0 (0.0%) | 1 (0.3%) | |
| Relapse pattern (initial) | .435 | |||
| Regional | 34 (15.7%) | 19 (11.5%) | 53(13.9%) | .778 |
| LN | 19 (8.8%) | 10 (6.1%) | 29(7.6%) | .372 |
| Basin | 7 (3.2%) | 7 (4.2%) | 14(3.7%) | |
| Other | 12 (5.6%) | 3 (1.9%) | 15(3.9%) | |
| LR + ITT | 11 (5.1%) | 7 (4.2%) | 18(4.7%) | |
| Mixed | 4 (1.9%) | 2 (1.2%) | 6(1.6%) | |
| Systemic | 22 (10.2%) | 15 (9.1%) | 37(9.7%) | .395 |
| Oligo | 12 (5.6%) | 4 (2.4%) | 16(4.2%) | |
| Multi | 10 (4.6%) | 19 (11.5%) | 29(7.6%) | |
| In‐transit a | 18 (8.3%) | 11 (6.7%) | 29(7.6%) |
.543 |
| No relapse | 160 (74.1%) | 131 (79.4%) | 291(76.4%) | |
Abbreviations: Chemo, chemotherapy; IFN, interferon; IO, immunotherapy; ITT, in‐transit; LR, local relapse; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; TT, targeted therapy.
In‐transit occurrence overall.
Among patients who underwent SLNB, SLNB was performed on 281 patients (73.8%) within the groin. Of all these patients, 132 (34.7%) patients were pathologically diagnosed with SLN‐positive. Among them, 101 (76.5%) patients received CLND within 1 month, while the others declined. Of 101 patients who underwent CLND, 23 (22.8%) patients were found to have non‐SLN‐positive. The median follow‐up was 24 (range: 5–62) months. Besides, 291 (76.4%) patients had no relapse during the follow‐up period, while 82 (21.5%) patients were identified with local/satellite/in‐transit metastases or regional lymph node metastases and 37 (9.7%) patients with systemic metastases.
3.2. Number of biopsied SLNs and positivity rates
As the median number of biopsied SLNs was equal to 2 (range: 1 to 20), patients were assigned into two groups: 216 (56.7%) patients with 1 to 2 biopsied SLNs in group one, and 165 (43.3%) patients with more than 2 biopsied SLNs in group two. Upon Pearson's chi‐squared test and the Fisher's exact test, no significant difference in the clinicopathological variables, such as gender, age, Breslow index, ulceration rate, N stage, TNM stage, gender, the Clark level, gene mutation, and pattern of relapses between the two groups. Of all these patients, 243 (63.8%) patients received adjuvant therapy and no significant difference was found in adjuvant therapies between these two groups (Table 1). As melanoma of acral type was dominant in our country and in which lower extremity was the most common primary tumor location, groin became the most common SLNB basin of these two groups, accounting for 85.2% and 58.8% respectively. The rate of SLN‐positivity was 34.7% in group one and 34.5% in group two, while the rate of non‐SLN‐positivity in the two groups was 8.3% and 3.0% (p = .161), respectively. It was revealed that in patients with Breslow >4 mm and N1a status, the rate of non‐SLN‐positive was 40.7% (11/27) in group one, which was higher than that in group two (17.6%, 3/17), but not statistically significant (p = .109). Furthermore, there were more cases with acral melanoma (n = 164, 75.9%, p = .003), more patients with melanoma at the lower extremities (n = 176, 81.5%, p < .001), and a higher rate of SLNB in groin (n = 184, 85.2%, p < .001) in group one (Table 1). Besides, 17 (7.9%) patients in group one and 14 (8.5%) patients in group two declined CLND, and no significant difference was detected.
3.3. Survival rates
The Kaplan–Meier method was used to identify the survival data of patients with different number of SLNs. The median RFS of all patients was 46.4 (95% CI: 42.9–50.0) months. The 1‐ and 2‐year RFS rates of SLN‐positive and SLN negative patients were 77.4% and 61.3%, and 93.5% and 81.4%, respectively (p = .235). With the log‐rank test between subgroups, the median RFS in group one was 41.9 (95% CI: 37.9–45.8) months, with no significant difference compared with group two (mRFS: 48.6 months, 95% CI: 43.4–53.7 months) (p = .235, Figure 1A). Similar results were found in patients with SLN‐positive (p = .076) and acral subtype (p = .070) (Figure 1B,C). However, a longer RFS was found in group two with Breslow thickness >4 mm (mRFS: 19 vs. 35 months, respectively, p = .010), N1a stage (mRFS: 33 months vs. not reached, respectively, p = .004), and patients without CLND after SLN‐positive (mRFS: 33 months vs. not reached respectively, p = .044) (Figure 2A–C).
FIGURE 1.
Relapse‐free survival of patients with different numbers of biopsied sentinel lymph nodes (SLNs). (A) All patients; (B) Patients with SLN‐positive; (C) Patients with acral subtype.
FIGURE 2.
Relapse‐free survival of patients with different numbers of biopsied SLNs in specific subtypes. (A) Patients with N1a stage; (B) Patients with T4 stage; (C) Patients with SLN‐positive but without completion lymph node dissection (CLND).
4. DISCUSSION
In this retrospective study involving Chinese melanoma patients with no nodal disease who received SLNB, identification and retrieval of 3 and more SLNs did not correspond in a different RFS compared to patients with only 1 or 2 SLNs. In patients with 3 or more SLN, there was a trend towards a longer RFS for patients with severe Breslow thickness (>4 mm), N1a stage, and those with SLN‐positive without plan of CLND. This result implied the underling importance of the number of SLNs in melanoma, which was rarely mentioned before.
In melanoma, SLN is mainly identified by using lymphoscintigraphy after injecting radioactive technetium adjacent into the primary lesion, or injecting methylene blue dye preoperatively into four quadrants at derma layer around the primary site. Detection of the SLNs was then finished by using a gamma probe and visual observation of methylene blue dye lymphatic drained into the regional lymph node field. Despite splendid progress in the techniques and expertise of SLN mapping, SLNB still possesses a false‐negative rate of about 10%–20%. 16 , 17 , 18 Indocyanine green is a new method mapping the lymph node without using radioactive tracer and without the risk of tattooing that is associated with the use of blue dye. 19 However, success rates for SLN identification are insufficient, because they merely indicate the proportion of patients in which at least one SLN was identified and removed, while they do not define the proportion of patients in which all SLNs were identified by accurate preoperative lymphoscintigraphy. 20
According to the final reports of German Dermatologic Cooperative Oncology Group trial (DeCOG‐SLT) and Multi‐Center Selective Lymphadenectomy Trial II (MSLT‐II), immediate CLND did not bring survival benefits to SLN‐positive patients. 21 , 22 With the dominant subtype was acral melanoma in Asian population, Chinese melanoma patients tended to have a higher Breslow index (mean Breslow thickness: 2.7 mm), ulceration rate (51.6%), and especially, a higher proportion of positive SLNs (34.7%) and non‐SLNs (22.8%) than Western patients. 23 , 24 , 25 Thus, whether CLND is still unbeneficial for OS in Asian patients requires validation in a larger sample‐sized study, although it is the question if such a trial will ever be conducted. As Chinese patients always have more tumor burden, higher rates of non‐SLN metastasis and adjuvant systemic therapy in acral melanoma might be less effective than in other cutaneous melanomas, CLND for patients with SLN‐positive is still strongly recommended in daily practice, followed by adjuvant systemic therapy. Patients who rejected CLND were featured by a slight tumor burden in lymph nodes, primary site at shallow layer of skin, and older age. In this study, the rate of CLND in patients with SLN‐positive was 73.8%.
Several studies have concentrated on the relationship between SLN status and prognosis, in which the pathological evaluation and tumor burden in SLN were particularly addressed. However, technical requirements of SLNB still require further attention. To date, some studies showed the number of SLNs‐positive was associated with the survival of patients. Gershenwald et al. demonstrated that 5‐year survival rates ranged from 70% for patients with one SLN and micro‐metastatic lesions to 39% for patients with four or more involved nodes or with nodes that were extensively involved. 3 However, further study is required to indicate whether the number of biopsied SLNs influences the prognosis of these patients. Generally, the number of SLNs is more than one. A total of 63 377 cases of cutaneous and acral melanoma who received SLNB were recorded in the database of Surveillance, Epidemiology, and End Results (SEER) from 2000 to 2020, of which the median number of SLNs is 2. Similarly, the median number of SLNs was also 2 in the present study, which was in accordance to the results of previous studies. 22 , 26 The present study showed that different numbers of biopsied SLNs had no influence on the RFS in the general population, while no significant difference was found in the exact number of positive lymph nodes or the rate of SLNB‐positive between the two groups.
However, patients with >2 SLNs had a longer RFS than those with 1–2 SLNs in T4, N1a group and those who rejected CLND. The underlying reasons might be summarized as follows: (i) identification of more SLNs might be associated with a higher accuracy of estimating N stage, and a lower false‐negative rate; (ii) the median number of SLNs in acral subtype was less than that of the cutaneous subtype, indicating that for acral melanoma, especially in patients with lesions at lower extremities and biopsied in groin, there might be a higher risk of incomplete nodal detection; (iii) for primary lesion site with Breslow thickness >4 mm and a higher rate of SLN‐ positive, evaluation of adequate SLNs might be more critical; and (iv) a higher number of biopsied SLNs‐positive reduced the probability of residual tumor, and lowered the relapse risk in patients who rejected CLND. In addition, the rate of non‐SLN‐positive was 40.7% in cohort with 1–2 SLNs in patients with Breslow >4 mm and N1a stage, which was higher than that of cohort with >2 SLNs (17.6%). This result was in accordance with findings from Rossi et al. that fewer nodes excised was a risk factor for non‐SLNs involvement of metastasis. 12 This might further explain why SLN‐positive (>2 SLNs) patients without plan of CLND had a significantly longer RFS. As higher SLNs were extracted from the basin, the residual tumor burden in lymph nodes decreased correspondingly. Thus, 3 and more SLNs seem essential for patients with Breslow thickness >4 mm and those with no plan of CLND.
Although the present study provided new insights into the effects of the number of SLNs on the RFS of melanoma patients, its limitations are also noteworthy. Due to the retrospective design of the study, the risk of selection bias is inevitable, indicating the necessity of further prospective study. Furthermore, the effects of different adjuvant therapies on the disease relapse and OS were not assessed. It is noteworthy that targeted therapy might be more efficacious than other adjuvant therapies, such as immunotherapy, during the early period of disease. In addition, data were collected from one single‐center, demonstrating that further multicenter studies are required to indicate the potential influence of the number of SLNs on the prognosis of melanoma patients and to explore its intrinsic mechanism.
5. CONCLUSIONS
In conclusion, we found that the number of identified and retrieved SLNs did not significant impact on RFS. In patients with T4 melanomas, N1a melanomas and those that did not undergo a CLND, the prognosis of those with three or more SLNs retrieved seemed to be improved. Three and more SLNs are essential for patients with Breslow thickness >4 mm and those with no plan of CLND.
AUTHOR CONTRIBUTIONS
Tu Hu: Data curation (equal); investigation (equal); writing – original draft (equal). Yu Xu: Conceptualization (equal); formal analysis (equal); writing – review and editing (equal). Wangjun Yan: Investigation (equal); project administration (equal). Chunmeng wang: Data curation (equal); software (equal). Wei Sun: Data curation (equal); formal analysis (equal); validation (equal). YunYi Kong: Methodology (equal); validation (equal). Yong Chen: Conceptualization (equal); project administration (equal); writing – review and editing (equal).
FUNDING INFORMATION
This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no conflict of interest.
ACKNOWLEDGMENTS
We thank Song Na from MSD medical affairs for the medical support.
Hu T, Xu Y, Yan W, et al. Prognostic value of the number of biopsied sentinel lymph nodes for Chinese patients with melanoma: A single‐center retrospective study. Cancer Reports. 2024;7(2):e1958. doi: 10.1002/cnr2.1958
Tu Hu and Yu Xu contributed equally to this work.
DATA AVAILABILITY STATEMENT
Not applicable.
REFERENCES
- 1. Balch CM, Gershenwald JE. Clinical value of the sentinel‐node biopsy in primary cutaneous melanoma. N Engl J Med. 2014;370(7):663‐664. [DOI] [PubMed] [Google Scholar]
- 2. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel‐node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355(13):1307‐1317. [DOI] [PubMed] [Google Scholar]
- 3. Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node biopsy and Management of Regional Lymph Nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology clinical practice guideline update. J Clin Oncol. 2018;36(4):399‐413. [DOI] [PubMed] [Google Scholar]
- 4. Sun W, Xu Y, Yang J, et al. The prognostic significance of non‐sentinel lymph node metastasis in cutaneous and acral melanoma patients‐a multicenter retrospective study. Cancer Commun (Lond). 2020;40(11):586‐597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Dewar DJ, Newell B, Green MA, Topping AP, Powell BWEM, Cook MG. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol. 2004;22(16):3345‐3349. [DOI] [PubMed] [Google Scholar]
- 6. Starz H, Balda BR, Krämer KU, Büchels H, Wang H. A micromorphometry‐based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer. 2001;91(11):2110‐2121. [PubMed] [Google Scholar]
- 7. Starz H, Siedlecki K, Balda BR. Sentinel lymphonodectomy and s‐classification: a successful strategy for better prediction and improvement of outcome of melanoma. Ann Surg Oncol. 2004;11(3 Suppl):162s‐168s. [DOI] [PubMed] [Google Scholar]
- 8. van Akkooi AC, de Wilt JH, Verhoef C, et al. Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol. 2006;17(10):1578‐1585. [DOI] [PubMed] [Google Scholar]
- 9. van der Ploeg AP, van Akkooi AC, Rutkowski P, et al. Prognosis in patients with sentinel node‐positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol. 2011;29(16):2206‐2214. [DOI] [PubMed] [Google Scholar]
- 10. Quaglino P, Ribero S, Osella‐Abate S, et al. Clinico‐pathologic features of primary melanoma and sentinel lymph node predictive for non‐sentinel lymph node involvement and overall survival in melanoma patients: a single Centre observational cohort study. Surg Oncol. 2011;20(4):259‐264. [DOI] [PubMed] [Google Scholar]
- 11. Jakub JW, Huebner M, Shivers S, et al. The number of lymph nodes involved with metastatic disease does not affect outcome in melanoma patients as long as all disease is confined to the sentinel lymph node. Ann Surg Oncol. 2009;16(8):2245‐2251. [DOI] [PubMed] [Google Scholar]
- 12. Rossi CR, Mocellin S, Campana LG, et al. Prediction of non‐sentinel node status in patients with melanoma and positive sentinel node biopsy: an Italian melanoma intergroup (IMI) study. Ann Surg Oncol. 2018;25(1):271‐279. [DOI] [PubMed] [Google Scholar]
- 13. Rossi CR, Mozzillo N, Maurichi A, et al. Number of excised lymph nodes as a quality assurance measure for lymphadenectomy in melanoma. JAMA Surg. 2014;149(7):700‐706. [DOI] [PubMed] [Google Scholar]
- 14. Gershenwald JE, Scolyer RA. Melanoma staging: American joint committee on cancer (AJCC) 8th edition and beyond. Ann Surg Oncol. 2018;25(8):2105‐2110. [DOI] [PubMed] [Google Scholar]
- 15. Ren M, Kong YY, Cai X, Shen XX, Lyu JJ. Application of sentinel lymph node biopsy in patients with melanoma. Zhonghua Bing Li Xue Za Zhi. 2018;47(5):360‐365. [DOI] [PubMed] [Google Scholar]
- 16. Caracò C, Marone U, Celentano E, Botti G, Mozzillo N. Impact of false‐negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma. Ann Surg Oncol. 2007;14(9):2662‐2667. [DOI] [PubMed] [Google Scholar]
- 17. Jones EL, Jones TS, Pearlman NW, et al. Long‐term follow‐up and survival of patients following a recurrence of melanoma after a negative sentinel lymph node biopsy result. JAMA Surg. 2013;148(5):456‐461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Lee DY, Huynh KT, Teng A, et al. Predictors and survival impact of false‐negative sentinel nodes in melanoma. Ann Surg Oncol. 2016;23(3):1012‐1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Gilmore DM, Khullar OV, Gioux S, et al. Effective low‐dose escalation of indocyanine green for near‐infrared fluorescent sentinel lymph node mapping in melanoma. Ann Surg Oncol. 2013;20(7):2357‐2363. [DOI] [PubMed] [Google Scholar]
- 20. Manca G, Rubello D, Romanini A, et al. Sentinel lymph node mapping in melanoma: the issue of false‐negative findings. Clin Nucl Med. 2014;39(7):e346‐e354. [DOI] [PubMed] [Google Scholar]
- 21. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel‐node metastasis in melanoma. N Engl J Med. 2017;376(23):2211‐2222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Leiter U, Stadler R, Mauch C, et al. Final analysis of DeCOG‐SLT trial: No survival benefit for complete lymph node dissection in patients with melanoma with positive sentinel node. J Clin Oncol. 2019;37(32):3000‐3008. [DOI] [PubMed] [Google Scholar]
- 23. Kim HJ, Seo JW, Roh MS, Lee JH, Song KH. Clinical features and prognosis of Asian patients with acral lentiginous melanoma who have nodal nevi in their sentinel lymph node biopsy specimen. J Am Acad Dermatol. 2018;79(4):706‐713. [DOI] [PubMed] [Google Scholar]
- 24. Fujisawa Y, Yoshikawa S, Minagawa A, et al. Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma. Cancer Med. 2019;8(5):2146‐2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Higgins S, Nazemi A, Feinstein S, Chow M, Wysong A. Clinical presentations of melanoma in African Americans, Hispanics, and Asians. Dermatol Surg. 2019;45(6):791‐801. [DOI] [PubMed] [Google Scholar]
- 26. Hocevar M, Bracko M, Pogacnik A, et al. The role of preoperative ultrasonography in reducing the number of sentinel lymph node procedures in melanoma. Melanoma Res. 2004;14(6):533‐536. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Not applicable.