Sentinel lymph node biopsy for early oral cancer – accuracy and considerations in patient selection

Sentinel lymph node biopsy (SLNB) for staging oral squamous cell carcinoma (OSCC) patients presenting with early (T1 and T2 N0) disease in preference to elective neck dissection (END) remains controversial worldwide. A retrospective analysis of 145 patients who underwent sentinel lymph node biopsy for a previously untreated early oral cancer between 2010 and 2020 was performed. The primary outcome measures were predictors of occult metastases, accuracy of SLNB and disease specific plus overall survival. The negative predictive value, the false negative rate, and sensitivity for SLNB were 97%, 7.8%, and 92%, respectively. Depth of invasion (DOI) was a significant predictor of N status, overall survival, and disease specific survival. There was a significant difference in the incidence of the neck node metastasis in patients with DOI <5mm compared to those with DOI >5mm. For tumours >5mm there was a moderate to good correlation between radiological depth on contrast enhanced computed tomography (CECT) and histopathological DOI. Preoperative estimation of DOI may be a useful tool in the counselling of patients in the selection of either SLNB or END for N staging purposes in early OSCC.     

前哨淋巴结活检在口腔鳞状细胞癌治疗中的临床意义

目的 探讨前哨淋巴结活检（sentinel lymph node biopsy，SLNB）在口腔鳞状细胞癌临床应用中的可行性、准确性。方法 对31例口腔鳞状细胞癌患者术前使用核素扫描法行前哨淋巴结（sentinellymphnode，SLN）示踪，体表定位；术中γ-探测仪进一步识别SLN行前哨淋巴结活检，同时行颈淋巴清扫；术后对SLN和颈淋巴清扫的病理检查结果进行分析。结果 SLNB对全组病例颈部淋巴结转移状况评价的准确率为96．8％。灵敏度为92，3％，假阴性率为7．7％。结论 SLNB是口腔鳞状细胞癌治疗中的一项新技术，能高灵敏度的反映颈淋巴结状态，具有临床可实用性。     

Challenges and outcomes in establishing a sentinel lymph node biopsy service for oral squamous cell carcinoma in a regional district specialist hospital

UK national guidelines in 2016 recommended that sentinel lymph node biopsy (SLNB) should be offered to patients with early oral squamous cell carcinoma (OSCC). We review the establishment of an OSCC SLNB service with specific consideration to resources, service implications and patient outcomes. A review of processes was performed to identify key stages in establishing the service, and subsequently a retrospective cohort study consisting of 46 consecutive patients with T1/T2 N0 OSCC was undertaken. The key stages identified were: coordinating a nuclear medicine pathway and reliable cost-appropriate pathology service, constructing a Trust business case, and gaining approval of a new interventional service policy. A median (range) of 3.3 (1-8) sentinel nodes (SLN) were removed, with 17 patients having a positive SLN. The negative predictive value of SLNB was 100%, with 12 having a SLN outside the field if elective neck dissection (END) was planned. There was a significantly increased risk of a positive SLN with increasing depth of invasion (DOI) (p=0.007) and increased diameter (p=0.036). We also identified a longer-than-ideal time to completion neck dissection and inadequate ultrasound follow up of negative SLNB patients. Establishment of a service requires careful planning. Our results were in keeping with those reported in the literature, and showed that SLNB for OSCC has a high negative predictive value and can identify at-risk SLN outside the traditional END levels, even in well-lateralised tumours. Our findings show that DOI and size of SLN were significantly associated with a positive SLN, and also identified areas requiring improvement.     

Sensitivity and specificity of sentinel lymph node biopsy in patients with oral squamous cell carcinomas using indocyanine green fluorescence imaging

Purpose

The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer.

老年口腔鳞癌前哨淋巴结活检的临床病理研究

目的:探讨前哨淋巴结活检(sentinel lymph node biopsy,SLNB)预测老年口腔鳞癌患者颈部淋巴结转移的价值及提高病理准确性的方法。方法:对18例临床及影像学检查阴性的老年口腔鳞癌患者,采用1%美兰示踪定位识别前哨淋巴结,随后行全颈淋巴结清扫,将SLN做连续病理切片检查。结果:18例患者中检出SLN14例,其中13例的SLN能准确预测颈部淋巴结的转移状况。结论:应用美兰能准确定位SLN,前哨淋巴结连续病理切片活检结果,能准确预测颈部淋巴结的转移状况,具有潜在的临床应用价值。     

Diagnostic yield of sentinel lymph node biopsy in oral squamous cell carcinoma T1/T2-N0: systematic review and meta-analysis

The objective of this study was to conduct a systematic review and meta-analysis on the efficacy of sentinel lymph node biopsy (SLNB) in T1/T2-N0 oral squamous cell carcinoma (OSCC). A systematic review of the literature on SLNB until March 2019 was conducted. The review was organized according to the PRISMA protocol, considering the following PICO (population, intervention, comparison, outcome) question: What is the sensitivity of sentinel lymph node biopsy in OSCC? ‘P’ was patients with head and neck squamous cell carcinoma T1/2-N0; ‘I’ was SLNB; ‘C’ was neck treated with elective neck dissection and haematoxylin–eosin histopathology; ‘O’ was sensitivity and specificity. A meta-analysis and meta-regression were performed on the selected studies. The sensitivity of SLNB was up to 88% (95% confidence interval (CI) 72–96%) and specificity was up to 99% (95% CI 96–100%). The area under the summary receiver operating characteristic curve was 0.99 (95% CI 0.98–1.00). In the four studies where immunohistochemistry was performed, both the sensitivity and specificity were higher than in the studies without immunohistochemistry: 93% (95% CI 88–97%) and 98% (95% CI 96–100%), respectively. In conclusion, SLNB is an effective technique for treating patients with some types of stage T1/2-N0 OSCC. Some parameters such as immunohistochemistry could determine the level of diagnostic accuracy.     

前哨淋巴结SPECT显像在老年口腔鳞癌隐匿转移中的评价

目的：探讨术前前哨淋巴结（SLN）的同位素显像（SPECT）在老年口腔鳞癌颈部隐匿转移中的诊断价值。方法：选择临床检测淋巴转移阴性的老年患者20例,肿瘤旁粘膜下注射99Tcm标记的右旋糖酐（DX）术前淋巴显像定位SLN,对SLN和非SLN采用连续病理切片行常规病理检测,对比SLN和非SLN淋巴结转移数据。结果：同位素淋巴显像法检测出17例口腔鳞癌的SLN共计36枚,平均2.3枚,SLN检测转移阳性5例,其中1例同时伴NSLN转移.未发现单独的NSLN转移。结论：同位素显像（SPECT）对前哨淋巴结（SLN）具有较高的检出率,前哨淋巴结（SLN）的检测结果可真实反映cN0期老年口腔鳞癌隐匿转移中的状况.     

The relative cost of sentinel lymph node biopsy in early oral cancer

IntroductionThe European Sentinel Node (SENT) trial addressed the question of the clinically lymph node negative (cN0) neck in early oral squamous cell carcinoma (OSCC). Apart from reducing neck dissection numbers, sentinel lymph node biopsy (SLNB) may reduce treatment cost. Using a treatment model derived from SENT trial information, estimates were produced of relative treatment costs between patients managed through a traditional surgical or SLNB pathway.MethodsThe model created two management approaches, the traditional surgical pathway and SLNB pathway. Using SENT trial data regarding the proportion of patients with positive, negative and false negative SLNB's a relative cost ratio (RCR) for 100 hypothetical patients passing down each pathway was generated.ResultsFrom a cohort of 481 patients, 25% had a positive SLNB, 75% a negative result and 2.5% a false negative result. Treatment of 100 hypothetical patients using the SLNB pathway is 0.35–0.60 the cost of treating the same cohort using traditional surgery techniques. Even if 100% of SLNB's are positive the SLNB approach is 0.91 of the cost of the traditional surgical approach.ConclusionThe SLNB approach appears to be cheaper relative to the traditional surgical approach, especially when extrapolated to 100 hypothetical patients.     

复发性口腔鳞癌挽救性手术近期疗效

目的　探讨不同期复发性口腔鳞癌挽救性手术治疗的疗效。方法　对 30例首次复发的复发性口腔鳞癌患者临床再分期后行挽救性手术并跟踪随访。结果　复发性口腔鳞癌早期患者的总生存时间及无瘤生存时间均比复发进展期者长 ,且复发早期 1年生存率及 1年无瘤生存率均高于复发进展期。结论　对复发性口腔鳞癌进行临床的再分期有利于评价预后及制定治疗方案 ;挽救性手术是复发性口腔鳞癌的有效治疗手段 ,尤其对复发性口腔鳞癌早期的患者     

Is the addition of extranodal extension and lymph node yield of pN0 to the lymph node ratio useful as a prognostic parameter for patients with oral squamous cell carcinoma?

We investigated the value of the weighted lymph node ratio (WLNR), a new marker in pN0 patients that incorporates the number of metastatic lymph nodes with extranodal extension and the lymph node yield, for the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). We designed a retrospective study and enrolled patients with OSCC who were treated by neck dissection (ND). The predictor variable was WLNR, and the outcome variable was overall survival (OS). The Cox proportional-hazards model was used to identify independent prognostic factors. In 133 patients with OSCC, the WLNR cut-off value for predicting OS was 0.0363 (area under the curve 0.723, p<0.001). When stratified according to WLNR, there was a significant difference in OS (88.4% for low WLNR and 63.0% for high WLNR, p<0.001). Univariate analyses showed close associations between OS and age, dissection area, postoperative management, extranodal extension, number of positive lymph nodes, pN stage, WLNR, and nodal disease area. Cox multivariate analysis identified the WLNR as an independent predictive factor for OS (HR 3.273, 95% CI 1.227 to 8.731, p=0.018). As a predictive factor, a high WLNR (≥0.0363) in patients with pN0 disease, which included the addition of extranodal extension and lymph node yield to the LNR, was associated with diminished survival.     

An update on the latest evidence for managing the clinically negative neck (cN0) in oral squamous cell carcinoma

The single most important prognostic indicator for survival in oral squamous cell carcinoma (OSCC) is the presence of lymph node metastases in the neck. While the treatment of the clinically node positive (cN+) neck is well established, the management of the clinically negative neck (cN0) is controversial. Various strategies have been advocated including close observation including regular ultrasound imaging, elective neck dissection and sentinel lymph node biopsy. Neck dissection surgery is not without potential morbidity with shoulder dysfunction being the main complication. A number of factors are associated with increased risk of neck node metastasis including primary tumour thickness and peri‐neural invasion. A recent prospective randomised trial has found survival benefit following neck dissection even in patients with a cN0 neck at presentation. We discuss the latest evidence for managing the cN0 in OSCC and include our own experience on the role of neck dissection in certain cases.     

Sentinel lymph node biopsy in malignant melanoma of the head and neck

Background

The aim of this retrospective study was to investigate sentinel lymph node biopsy in patients with head and neck melanoma.

Oral squamous cell carcinoma with microscopic extracapsular spread in the cervical lymph nodes

The purpose of this study was to determine the detailed background of cases of oral squamous cell carcinoma (OSCC) with microscopic extracapsular spread (ECS) in the cervical lymph nodes. The cases of 78 patients with primary OSCC, who attended hospital from October 2007 to July 2011 and underwent resection of the primary tumour with neck dissection, were reviewed. The subjects were classified into three categories: pN0, pN+/ECS−, and pN+/ECS+; the outcomes of pN+/ECS+ patients were compared in detail with those of the other categories. Thirty-one cases (39.7%) were pN0, 25 cases (32.1%) were pN+/ECS−, and 22 cases (28.2%) were pN+/ECS+. The 3-year overall survival rate was 82.1% in pN0, 74.1% in pN+/ECS−, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P = 0.0004; pN+/ECS− vs. pN+/ECS+, P = 0.0086). The 3-year disease-specific survival rate was 96.2% in pN0, 77.2% in pN+/ECS−, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P < 0.0001; pN+/ECS− vs. pN+/ECS+, P = 0.0038). Patients with poorly differentiated carcinoma, those with three or more ECS+ nodes, and those with ECS+ node(s) located at levels III, IV, and V, had the worst prognosis among pN+/ECS+ subjects.     

Sentinel lymph node biopsy for early stage tongue cancer—a 14-year single-centre experience

This study was performed to report the usage of sentinel lymph node biopsy (SLNB) in clinical stage I or II tongue cancer patients with cN0 necks seen over a 14-year period. Data were collected prospectively, and a retrospective analysis was performed of 41 patients with early stage oral squamous cell carcinoma of the tongue and a cN0 neck. Sentinel lymph node (SLN)-positive patients underwent elective neck dissection, whereas SLN-negative patients were kept under careful observation. Seven of the 41 (17%) patients enrolled in the study were found to have occult metastases. The patients were followed up for a mean duration of 92 months (range 60–144 months). The neck recurrence rate for SLN-positive patients was 0% and for SLN-negative patients was 3%. The authors recommend the routine use of SLNB in patients with early stage oral squamous cell carcinoma of the tongue and a cN0 neck. Furthermore, special focus should be placed on isolated tumour cells, as their presence is of high clinical relevance.     

Expression of vascular endothelial growth factor-C does not predict occult lymph-node metastasis in early oral squamous cell carcinoma

Strong vascular endothelial growth factor-C (VEGF-C) expression has been correlated to occurrence of lymph-node metastases in patients with oral squamous cell carcinoma (OSCC). The incidence of occult lymph-node metastasis remains a decisive factor in the prognosis of patients with early OSCC. The aim of this study was to evaluate VEGF-C expression as a predictor of occult lymph-node metastasis in OSCC. Eighty-seven patients with primary OSCC arising in the tongue or floor of mouth, clinically T1N0M0 or T2N0M0, with (pN+) and without (pN0) occult lymph-node metastases were analyzed for VEGF-C expression by malignant cells. Occult lymph-node metastases (pN+) were detected in 22% of the 64 patients who were submitted to elective neck dissection. No statistically significant difference was found between OSCC with and without occult lymph-node metastasis in regard to VEGF-C immunoexpression by malignant cells and clinicopathologic features. Independently of VEGF-C expression, lymph-node metastasis (pN+) was the most significant prognostic factor for overall survival of patients with OSCC (p=0.030). These findings indicate that isolated VEGF-C expression by malignant cells is not of predictive value for occult lymph-node metastasis in the early stages of OSCC.     

Sentinel lymph node biopsy for melanoma of the head and neck: a multicentre study to examine safety,efficacy, and prognostic value

Sentinel lymph node biopsy (SLNB) is an accurate staging procedure for malignant melanoma but its use in patients with melanoma of the head and neck has been questioned in the past because of a perceived record of poor safety and accuracy. Technical improvements have sought to redress this. Vital structures and variable lymphatic pathways can make its use in the head and neck challenging. In our study we have examined the data and the experiences of clinicians from University Hospital Southampton and the Royal Surrey County Hospital. We retrospectively analysed the data and case notes of 143 patients who had SLNB to establish its safety, efficacy, and prognostic value. The detection rate of at least one sentinel lymph node was 100%. Nodes positive for metastatic melanoma were found in 20% of patients. Of them, 76% went on to have completion lymphadenectomy. Multivariate Cox regression analysis suggested that positive SLNB was a strong predictor of reduced overall survival for all Breslow-thickness melanomas (HR = 3.9, p = 0.019) and intermediate melanomas (HR = 6.3, p = 0.007). It predicted reduced recurrence-free survival for all melanomas (HR = 7.4, p < 0.001) and was a strong predictor for those of intermediate thickness (HR = 8.3, p < 0.001). The false negative rate was 9.4% and false omission rate 2.6%. Temporary and permanent morbidity rates were 2.1% and 0%, respectively. SLNB for melanoma in the head and neck is a safe, accurate staging procedure that offers prognostically useful information. The upstaging of disease allows access to trial-based targeted treatments.     

Neck failure following pathologically node-negative neck dissection (pN0) in oral squamous cell carcinoma: a systematic review and meta-analysis

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.     

Eosinophils may predict occult lymph node metastasis in early oral cancer

Objective

The aim of this study was to investigate whether tumor-associated tissue eosinophilia (TATE) in early oral squamous cell carcinoma (OSCC) would aid in predicting occult lymph node metastasis.

Patients and methods

Seventy-one patients undergoing elective neck dissection for T1 and T2 OSCC were evaluated for clinical features, prognosis, and TATE. The degree of TATE in OSCC was statistically analyzed in relation to the clinicopathological features, tumor invasion, occult lymph node metastasis, and survival using χ ² test and Kaplan–Meier method.

Results

Statistical analysis revealed that intense TATE was a significant feature (p?=?0.004) to predict occult lymph node metastasis in patients with early OSCC. All regional recurrences of the OSCC occurred in patients showing intense TATE.

Conclusions

These results suggest that intense TATE can be clinically used as a predictive factor for occult lymph node metastasis.

Clinical relevance

The presence of intense TATE is an adjunctive histopathological marker to reinforce the indication of elective neck dissection of the patients with early OSCC.     

口腔鳞癌颈部转移淋巴结的包膜外扩散与术后复发的关系探讨

目的探讨口腔鳞癌颈部转移淋巴结的包膜外扩散与术后复发的关系。方法74例口腔鳞癌经术后病理证实均有颈部淋巴结转移，按照有、无包膜外扩散将患者分为两组，回顾临床和病理资料，随访患者术后复发的情况，分析包膜外扩散和其他相关临床病理因素对术后复发的影响。结果无包膜外扩散和有包膜外扩散两组患者的术后总复发率分别为47．6％和75．0％，颈部复发率分别为9．5％和46．9％，差异均具有统计学意义（P〈0．001）。多因素分析显示，包膜外扩散是术后颈部复发的独立预后因素，但它不是影响总复发率的独立因素。结论包膜外扩散与口腔鳞癌术后复发明显相关，是颈部复发的重要危险因素。     

Evaluation of neck dissection with frozen section biopsy – Management of levels IV and V

IntroductionNeck dissection is an essential component of oral cancer therapy. Based on a standardised approach to cervical lymph node management, we seek to define the relevance of neck dissection extension in cN + cases.Material and methodsA retrospective analysis from January 2009 to February 2017 identified 84 patients with oral squamous cell carcinoma with a cN + neck or histologically proven lymph node involvement in intraoperative frozen sectioning and who received modified radical neck dissection according to the presented neck dissection algorithm.ResultsOverall 11 patients showed lymph node metastasis level IV or V, whereas 19 developed disease recurrence, of which 5 cases were neck recurrences. A total of 30 patients died within the time of observance (overall survival of n = 54). None of those patients with pN + status in levels IV and V reached a 5-year survival.DiscussionWith a look to the possibility of a 5-year survival in patients with a N+ status in level IV and V, the justification for a radical approach to the neck appears questionable. However, modified radical neck dissection appears to be a suitable for a high-risk oral cancer subgroup. A randomised controlled trial is needed to define guidelines for the neck dissection extent in c/pN + cases.