Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients

Aims: Sentinel lymph node (SLN) -positive melanoma patients are usually recommended completion lymph node dissection (CLND) with the aim to provide regional disease control and improve survival. Nevertheless, only 20% these patients have additional metastases in non-sentinel lymph nodes (NSLN), indicating that CLND may be unnecessary in the majority of patients. In this retrospective study, we (i) sought to identify clinico-pathological features predicting NSLN status, as well as disease-free (DFS) and -specific (DSS) survival and (ii) evaluated the applicability of previously published algorithms, which were able to define a group of patients at zero-risk for NSLN-metastasis.     

Assessment of a new scoring system for predicting non-sentinel node positivity in sentinel node-positive melanoma patients

Background

When completion lymph node dissection (CLND) is performed in sentinel node (SN)-positive melanoma patients, a positive non-sentinel node (NSN) is found in approximately 20% of them. Recently, Murali et al. proposed a new scoring system (non-sentinel node risk score, N-SNORE) to predict the risk of NSN positivity in SN-positive patients. The objectives of the current study were to identify factors predicting NSN positivity and to assess the validity of the N-SNORE in an independent patient cohort.

Methods

All SN-positive patients who underwent CLND at a single institution between 1995 and 2010 were analyzed. Characteristics of the patient, primary melanoma, and SN(s) were tested for association with NSN positivity. Missing values were reconstructed using multiple imputation to enable multivariable analysis.

Results

CLND revealed positive NSNs in 30 (23%) of 130 SN-positive patients. Primary melanoma regression (p = 0.03) was independently associated with NSN positivity. After adjustment because of missing data on perinodal lymphatic invasion, N-SNORE proved to be a significant stratification model in our patient cohort (p = 0.003): 5.9% NSN positivity in the very low risk category and 75.0% NSN positivity in the very high risk category.

Conclusions

Presence of regression in the primary melanoma was independently associated with a higher risk of NSN positivity. The slightly modified N-SNORE scoring system provided useful stratification of the risk for NSN positivity. However, lack of perinodal lymphatic invasion data may have reduced its predictive value.     

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.     

Sentinel node biopsy versus elective lymph node dissection in patients with cutaneous melanoma in a Japanese population

Background In Japan, elective lymph node dissection (ELND) has been the standard treatment for patients with possible nodal melanoma. Sentinel node biopsy (SNB) has now replaced ELND, not only in Japan but also worldwide. The objective of this study was to compare the interim outcomes of SNB and ELND. Methods A retrospective study was conducted among patients with clinically node-negative disease treated at our institute with either SNB (n = 30) or ELND (n = 72). Results The background was similar in the two groups. Nodal metastases were found in 40.0% of patients in the SNB group, but in only 26.4% in the ELND group (P = 0.173). The median follow-up was 31.5 months for the SNB group and 82 months for the ELND group. The incidence of locoregional recurrence and distant metastasis in the SNB group was 10.0% and 16.7%, respectively, and for the ELND group the incidence was 5.6% and 31.9%, respectively. The 3-year disease-free survival rate was similar in the two groups (P = 0.280), and the 3-year disease-free survival rates for node-positive patients were also similar in the two groups (P = 0.90), as were the 3-year disease-free survival rates for node-negative patients (P = 0.193). Conclusion This interim result in a Japanese melanoma population with clinically node-negative disease demonstrated that SNB identified more nodal micrometastases than ELND. This increase in accurate staging likely resulted from the reliable identification of the lymph node field by lymphoscintigraphy, as well as the more detailed pathologic examination of the nodes removed in SNB. It is quite reasonable to perform SNB instead of ELND in this population.     

早期乳腺癌腋窝前哨淋巴结阳性患者腋窝非前哨淋巴结转移风险预测

目的 分析前哨淋巴结活检(SLNB)1~2个阳性乳腺癌患者中非前哨淋巴结(NSLN)转移的影响因素并构建预测模型。方法 回顾分析2008-2014年中国医学科学院北京协和医学院肿瘤医院未行新辅助化疗前哨淋巴结 1~2个阳性并行腋窝淋巴结清扫的乳腺癌患者的临床病理因素。计数资料组间比较采用χ²检验,多因素分析采用Logistic回归模型。以AUC值和校正曲线对Nomogram预测模型进行评估。结果 共 270例患者纳入研究,87例(32.2%)存在NSLN转移。中位年龄46(21~80)岁,中位SLN送检个数4(1~10)个,中位腋窝淋巴结清扫个数20(10~41)个。单因素分析结果显示病理分级、SLN宏转移、阳性SLN个数和阴性SLN个数是腋窝NSLN转移的影响因素(P=0.001~0.045)。多因素分析结果显示病理分级、阳性SLN个数和阴性SLN个数是NSLN转移的独立影响因素(P=0.000~0.041)。乳腺癌NSLN转移Nomogram预测模型AUC=0.70,当预测患者的NSLN转移率≤15%时,假阴性率仅为10.5%。结论 Nomogram预测模型可作为临床医师进行腋窝处理时的决策参考,对于NSLN转移概率低的患者可以避免行腋窝淋巴结清扫或腋窝放疗。     

Therapeutic neck dissection in head and neck melanoma patients: Comparing extent of surgery and clinical outcome in two cohorts

BackgroundThe extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach.MethodsSixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I–V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3–4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).ResultsClinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92).ConclusionThis study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.     

Accuracy of the non-sentinel node risk score (N-SNORE) in patients with cutaneous melanoma and positive sentinel lymph nodes: A retrospective study

Background

Sentinel node (SLN) biopsy in patients with melanoma permits identification of those at risk for further metastases in non-sentinel lymph nodes (NSLN). However, a mere 20% of SLN-positive patients have metastases in NSLN. Therefore we need criteria to predict NSLN-positivity. A new score system known as the non-sentinel risk score, (N-SNORE) based on five clinical and pathological characteristics (gender, regression in primary melanoma, proportion of SNs containing melanoma, perinodal lymphatic invasion, and SN tumor burden), was first published in 2010. In this study, the accuracy of N-SNORE was validated in melanoma patients with positive SLN.

Methods

A total of 106 melanoma patients with positive SLN, who had undergone complete lymph node dissection (CLND) subsequently, were included in the study. The N-SNORE was calculated in all patients, and the risk was compared to the frequency of NSLN metastases. Statistical analysis of the data was performed.

Results

Thirteen patients were at very low risk for NSN metastasis (score 0), 63 patients at low risk (score 1–3), 19 at intermediate risk (score 4–5), 6 at high risk (score 6–7), and 5 at very high risk (score >8). NSLN positivity rates for these 5 risk groups were 7.7%, 18.2%, 21.1%, 33.3%, and 80%, respectively. According to Fisher's exact test, the contingency coefficient was .322; the p-value was .025.

Conclusion

An increasing N-SNORE was clearly correlated with a higher risk of NSLN positivity. Based on the p-value and the contingency coefficient, the overall accuracy of the N-SNORE was proven on statistical calculation.     

乳腺癌前哨淋巴结和非前哨淋巴结转移的影响因素分析

目的 探讨影响乳腺癌前哨淋巴结和非前哨淋巴结转移的相关因素.方法 回顾性分析2010年7月至2011年8月收治的、行前哨淋巴活检的283例女性乳腺癌患者的临床资料.结果 单因素分析结果显示,患者年龄、是否绝经、肿瘤大小、病理类型和脉管瘤栓均与前哨淋巴结转移(SLNM)有关(均P＜0.05);年龄、恶性肿瘤家族史、绝经情况、局部切除术、示踪技术、前哨淋巴结阳性、肿瘤大小、病理类型、分化程度、雌激素受体(ER)阳性、孕激素受体阳性、人表皮生长因子受体2阳性数目、脉管瘤栓和Ki-67≥15％等均与非前哨淋巴结转移无关(均P＞0.05).Logistic回归分析结果显示,患者年龄、肿瘤大小和脉管瘤栓均与SLNM有关(均P＜0.05).结论 患者年龄、肿瘤大小和脉管瘤栓是影响SLNM的独立因素,其中年龄是保护因素.而病理类型、病理分级和ER状态是否与SLNM有关存在争议.     

皮肤恶性黑素瘤的前哨淋巴结活检技术

目的:评估前哨淋巴结活检(sentinel lymph node biopsy,SLNB)应用于皮肤恶性黑素瘤诊断和治疗中的临床价值。方法:对18例临床评估无区域淋巴结转移的皮肤恶性黑素瘤患者,应用淋巴核素显像以及术中核素扫描等方法定位前哨淋巴结(sentinel lymph node,SLN);切除SLN后进行快速冰冻和常规石蜡切片病理检查,若SLN为阳性,则加行相应区域淋巴结清扫。结果:18例患者中共检出SLN34枚,其中阳性7枚(20.6%)。5例SLN阳性患者加行区域淋巴结清扫,包括3例腹股沟清扫、1例腋窝清扫和1例颈部清扫;除SLN以外,共清扫淋巴结84枚,其中阳性39枚(46.4%)。结论:SLNB有助于诊断皮肤恶性黑素瘤的淋巴转移,为实施区域淋巴清扫提供重要的临床依据。     

Management of the axilla in patients with breast cancer and positive sentinel lymph node biopsy: An evidence-based update in a European breast center

The surgical approach to the axilla in breast cancer has been a controversial issue for more than three decades. Data from recently published trials have provided practice-changing recommendations in this scenario. However, further controversies have been triggered in the surgical community, resulting in heterogeneous diffusion of these recommendations.The development of clinical guidelines for the management of the axilla in patients with breast cancer is a work in progress. A multidisciplinary team discussion was held at the research hospital Policlinico San Matteo from the Università degli Studi di Pavia with the aim to update recommendations for the management of the axilla in patients with breast cancer. An evidence-based approach is presented.Our multidisciplinary panel determined that axillary dissection after a positive sentinel lymph node biopsy may be avoided in cN0 patients with micro/macrometastasis to ≤2 sentinel nodes, with age ≥40y, lesions ≤3 cm, who have not received neoadjuvant chemotherapy and have planned breast conservation (BCS) with whole breast radiotherapy (WBRT). Cases with gross (>2 mm) ECE in SLNs are evaluated on individual basis for completion ALND, axillary radiotherapy or omission of both. Patients fulfilling the criteria listed above who undergo mastectomy, may also avoid axillary dissection after multidisciplinary discussion of individual cases for consideration of axillary irradiation. Women 70 years or older with hormone receptors positive invasive lesions ≤3 cm, clinically negative nodes, and serious or multiple comorbidities who undergo BCS with WBRT, may forgo axillary staging/surgery (if mastectomy or larger tumor, comorbidities and life expectancy are taken into account).     

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

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。     

甲状腺乳头状癌颈部淋巴结转移的处理态度和诊疗现状

甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)虽以惰性居多,但颈部淋巴结转移的患者并不少见,而颈淋巴结转移的发生也意味着死亡率增加和复发风险的提高,甲状腺手术前应使用彩超充分评估颈部淋巴结的状态,对直径较大的淋巴结行超声引导下淋巴结细针抽吸(Echo-guided fine needle aspiration of the lymph node,LN-FNA)或联合测定洗脱液的甲状腺球蛋白水平,在怀疑远处转移或肿瘤浸润性生长时可联合CT、PET-CT或磁共振检查。建议临床医生在有技术保证的前提下对术中冰冻为阴性的cN0患者行单侧的预防性中央区淋巴结清扫术(Prophylactic central neck dissection,pCND),对术中冰冻为阳性的cN0患者行双侧的中央区淋巴结清扫术,在降低患者复发率的同时减少术后并发症的发生,应严格按照指南评估患者术后是否需行放射性碘治疗,以减少不必要的放射性治疗,更好地服务于患者,提升患者的生存质量。     

头颈部肿瘤前哨淋巴结活检及示踪剂应用

前哨淋巴结活检（SLNB）可通过示踪法确定前哨淋巴结（SLN）并进行活检来评估头颈部肿瘤的区域淋巴结转移而指导颈淋巴结清扫术的进行。常用示踪法有染料识别法、放射性核素示踪法或二者联合应用法,常用染料示踪剂有异硫蓝、专利蓝和美蓝3种,常用核素示踪剂为^99mTc。SLNB在乳腺癌研究中应用较广,近年来已应用于头颈部肿瘤的研究中。     

头颈部肿瘤前哨淋巴结活检及示踪剂应用

前哨淋巴结活检(SLNB)可通过示踪法确定前哨淋巴结(SLN)并进行活检来评估头颈部肿瘤的区域淋巴结转移而指导颈淋巴结清扫术的进行。常用示踪法有染料识别法、放射性核素示踪法或二者联合应用法,常用染料示踪剂有异硫蓝、专利蓝和美蓝3种,常用核素示踪剂为~(99m)Tc。SLNB在乳腺癌研究中应用较广,近年来已应用于头颈部肿瘤的研究中。     

200 Sentinel lymph node biopsies without axillary lymph node dissection -- no axillary recurrences after a 3-year follow-up

The aim of this study is to evaluate the rate of axillary recurrences in sentinel lymph node (SLN)-negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Between May 1999 and February 2002, 333 consecutive patients with primary invasive breast cancer up to 4 cm and clinically negative axillae were entered into this prospective study. Sentinel lymph nodes were identified using the combined method with blue dye (Patent blue V) and technetium 99m-labelled albumin (Nanocoll). Sentinel lymph nodes were examined by frozen sections, standard haematoxylin and eosin staining and immunohistochemistry staining. In SLN-positive patients, ALND was performed. Sentinel lymph node-negative patients had no further ALND. The SLN identification rate was 98.5% (328 out of 333). In all, 128 out of 328 (39.0%) patients had positive SLNs and complete ALND. A total of 200 out of 328 (61.0%) patients were SLN negative and had no further ALND. The mean tumour size of SLN-negative patients was 16.5 mm. The mean number of SLNs removed was 2.1 per patient. There were no local or axillary recurrences at a median follow-up of 36 months. The absence of axillary recurrences after SLNB without ALND in SLN-negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity than ALND. Short-term results are very promising that SLNB without ALND in SLN-negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumours.     

1~2枚腋窝前哨淋巴结转移的乳腺癌患者非前哨淋巴结转移影响因素分析

目的探讨前哨淋巴结活组织检查(SLNB)后非前哨淋巴结(SLN)转移的影响因素。 方法回顾性分析2015年3月至2020年9月湖北省十堰市太和医院收治的837例双染料示踪法SLNB有1~2枚转移且行腋窝淋巴结清扫的乳腺癌患者资料,分为非SLN有转移组(54例)和无转移组(783例),采用χ²检验比较2组患者的肿瘤直径、病灶位置、脉管侵犯、病理类型、多发病灶、SLN转移灶类型、分子分型、ER、PR、HER-2、Ki-67等临床病理特征,采用秩和检验比较2组患者的组织学分级和SLN转移率。采用Logistic回归分析影响乳腺癌患者腋窝非SLN转移的危险因素。 结果2组患者的肿瘤直径、脉管侵犯、组织学分级、SLN转移率比较,差异均有统计学意义(χ²＝3.940、45.882,Z＝-2.225、-4.540,P＝0.047、<0.001、0.027、<0.001)。多因素分析结果显示：有脉管侵犯、SLN转移率≥50%且<100%和SLN转移率为100%均为影响非SLN转移的独立危险因素( OR ＝4.826,95%CI: 2.675~8.706,P <0.001;OR＝3.822,95%CI：1.538~9.501,P＝0.004;OR＝4.761,95%CI: 2.014~11.256,P<0.001)。 结论有脉管侵犯或SLN转移率≥50%的乳腺癌患者,非SLN转移的风险增加,应行腋窝淋巴结清扫术。     

前哨淋巴结活检指导保留乳房手术患者行选择性腋窝淋巴结清除术的研究

目的研究通过前哨淋巴通道（SLC）行前哨淋巴结活检（SLNB）以指导保留乳房手术（breast—conservingtherapy,BCT）患者行选择性腋窝淋巴结清除术（ALND）的可行性。方法采用非随机对照研究,在BCT患者中采用联合示踪法通过SLC行SLNB。对术中检出的前哨淋巴结（SLN）行细胞印片和冰冻切片检查,根据SLN的术中病理结果行选择性ALND,其中SI。N阳性、行ALND者为A组,SI。N阴性仅行SLNB者为B组。定性资料的比较选用Y。检验,两组均数的比较采用t检验。结果2009年1月至2009年12月采用联合示踪法行SLNB的BCT患者共43例,检出42例,A组28例,B组14例。两组患者的SLC均被显影。每例患者被检出SLN1～3枚,平均1．4枚,共被检出59枚。SLNB检出率为97．7％（42／43）。术后病理检查共检出阳性SI,N29例,其中术中细胞印片、冰冻切片及二者联合病理检测分别检出阳性淋巴结27、27、28例。A组ALND相关并发症发生率明显高于B组（P=0．003）。结论通过SLC行SLNB有助于准确定位SLN,能够指导BCT患者行选择性ALND,降低术后并发症。     

Accuracy of sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with locally advanced breast cancer and clinically positive axillary nodes

Background

Feasibility and accuracy of sentinel node biopsy (SLNB) after the delivery of neo-adjuvant chemotherapy (NAC) is controversial. We here report our experience in NAC-treated patients with locally advanced breast cancer and clinically positive axillary nodes, and compare it with the results from our previous randomized trial assessing SLNB in early-stage breast cancer patients.

Patients and methods

Sixty-four consecutive patients with large infiltrating tumor and clinically positive axillary nodes received NAC and subsequent lymphatic mapping, SLNB and complete axillary lymph node dissection (ALND). The status of the sentinel lymph node (SLN) was compared to that of the axilla.

Results

At least one SLN was identified in 60 of the 64 patients (93.8%). Among those 60 patients, 37 (61.7%) had one or more positive SLN(s) and 23 (38.3%) did not. Two of the patients with negative SLN(s) presented metastases in other non-sentinel nodes. SLNB thus had a false-negative rate, a negative predictive value and an overall accuracy of 5.1%, 91.3% and 96.7%, respectively. All these values were similar to those we reported for SLNB in the settings of early-stage breast cancer.

Conclusion

SLNB after NAC is safe and feasible in patients with locally advanced breast cancer and clinically positive nodes, and accurately predicts the status of the axilla.