Sentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: A diagnostic meta-analysis

doi:10.1016/j.oraloncology.2013.04.006

Oral Oncology

Volume 49, Issue 8, August 2013, Pages 726-732

https://doi.org/10.1016/j.oraloncology.2013.04.006 Get rights and content

Summary

Background

The aim of the study was to systematically assess the accuracy of a sentinel lymph node biopsy (SLNB) in cT1/T2N0 oral cavity and oropharyngeal squamous cell carcinoma patients.

Methods

We searched electronic databases, including EMBASE and MEDLINE (Pubmed) up to November 7 2012, by combining oral cancer keywords with sentinel node biopsy keywords. We included diagnostic accuracy studies which used neck dissection as a reference test for the sentinel node biopsy. Study characteristics and measures of accuracy were extracted. Diagnostic accuracy was calculated from 2 × 2 tables.

Results

21 Studies (847 patients) could be included. Most of these patients had oral cavity squamous cell carcinoma (OCSCC). The pooled data showed an overall sensitivity of 0.93 [95% CI 0.90–0.95]. Subgroup analysis showed no significant differences in subgroups.

Conclusion

The high sensitivity of SLNB supports a role in the diagnostic work-up of OCSCC.

Introduction

Oral cavity and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) are considered an important part of the global burden of cancer, mainly due to the widespread use of tobacco and alcohol.¹ The most important prognostic factor is the presence of cervical lymph node metastases, which can decrease the 5-year survival rates to lower than 50%.² Exact staging of the neck is therefore crucial in managing this type of cancer.

Staging by palpation and imaging techniques (e.g. MRI, CT, ultrasound-guided fine needle aspiration cytology (USgFNAC) are not sensitive enough in detecting micrometastases, resulting in a high incidence of occult metastases in the neck.³ In the literature rates between 23% and 43% have been reported.⁴ Because of this, elective neck dissection (END) is the standard of care in clinically negative necks (cN0) of early stage (T1/T2) oral cavity and oropharyngeal squamous cell carcinomas in most institutions. However, this implies overtreatment and treatment associated morbidity in the majority of patients.⁵

Sentinel lymph node biopsy (SLNB) has emerged as an alternative or additional staging procedure. The SLNB procedure is based on the concept that tumor cells will spread from the primary site to a single node or group of nodes (the sentinel nodes), before progressing to the remainder of the lymph nodes. A radiotracer, possibly in conjunction with colored dye injected into the primary tumor allows for identifying the sentinel nodes. Radiolocalization of the sentinel node consists of a preoperative lymphoscintigraphy either or not with SPECT/CT and the intraoperative use of a hand-held gamma probe and/or portable gamma-camera.⁶ Histopathological evaluation of sentinel nodes may allow accurate prediction of the disease status. False negative results can have several causes including uneven radionuclide injection, obscuring of sentinel lymph nodes by the radioactive signal of the primary tumor, and lymphatic obstruction by gross tumor, resulting in redirection of lymphatic flow.⁷

Although SLNB is still an invasive procedure, it gives less morbidity than selective neck dissection by sparing relevant structures.[8], [9] Therefore, SLNB can have great consequences for the treatment of OCSCC and OPSCC patients. More accurate staging of the neck by SLNB could be a serious alternative for direct elective neck dissection.

The aim of this diagnostic meta-analysis therefore was to study the diagnostic accuracy of SLNB in cT1/T2N0 oral cavity and oropharyngeal squamous cell cancer patients.

Section snippets

Data sources and searches

We searched electronic databases, including EMBASE and MEDLINE (Pubmed) from inception up to November 7 2012, by combining oral cavity cancer keywords with sentinel node biopsy keywords. No restrictions on language were used in the search. All citations identified by the search were imported into a EndNote bibliographic database.¹⁰

Study selection

Initially the titles and abstracts of the search results were screened. Subsequently, the reports were reviewed according to pre-defined inclusion and exclusion

Results

In total 1884 studies were identified. After removal of duplicates and screening of titles and abstracts, 116 studies were selected for a full text evaluation. 21 Studies fulfilled the inclusion criteria and a data extraction form was completed for these studies (Fig. 1).[7], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34]

The studies contained 847 cases in total. Most studies also mentioned the detection rate of sentinel

Discussion

The results of this diagnostic meta-analysis demonstrate that sentinel node biopsy appears to be a sensitive method in the detection of neck metastases in cT1/T2N0 OCSCC. In almost all patients at least one sentinel node was detected and therefore a biopsy could be taken which means that the procedure appears to be applicable as well.

These results are in line with a previous conducted meta-analysis which also showed a high sensitivity of SLNB in CT1/T2N0 patients.¹⁶ The major strengths of our

Conflict of interest statement

None declared.

Acknowledgements

The authors thank Maarten de Rooij of the department of Radiology, Radboud University Medical Centre, the Netherlands, and Hans Reitsma of the Julius Centre, University Medical Centre Utrecht, The Netherlands for their advice and help with the analyses.

References (34)

T. Minamikawa et al.
Reliability of sentinel lymph node biopsy with squamous cell carcinoma of the oral cavity
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
(2005)
R. Lambert et al.
Epidemiology of cancer from the oral cavity and oropharynx
Eur J Gastroenterol Hepatol
(2011)
A. Capote et al.
Elective neck dissection in early-stage oral squamous cell carcinoma–does it influence recurrence and survival?
Head Neck
(2007)
M.T. Hornstra et al.
Predictive factors for failure to identify sentinel nodes in head and neck squamous cell carcinoma
Head Neck
(2008)
A. Ebrahimi et al.
Improved survival with elective neck dissection in thick early-stage oral squamous cell carcinoma
Head Neck
(2012)
P.J. Bradley et al.
Neck treatment and shoulder morbidity: still a challenge
Head Neck
(2011)
L. Vermeeren et al.
A portable gamma-camera for intraoperative detection of sentinel nodes in the head and neck region
J Nucl Med: Off Publ, Soc Nucl Med
(2010)
F.J. Civantos et al.
Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1–T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial
J Clin Oncol
(2010)
F. Schiefke et al.
Function, postoperative morbidity, and quality of life after cervical sentinel node biopsy and after selective neck dissection
Head Neck
(2009)
K. Murer et al.
Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma
Head Neck
(2011)

Reuters T. Endnote v5, Inc., Philadelphia,...

P.F. Whiting et al.

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies

Ann Intern Med

(2011)

Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration,...

Takwoingi Y, Deeks J. MetaDAS: a SAS macro for meta-analysis of diagnostic accuracy studies. User Guide Version 1.3....

The SAS system, 8.2. SAS Institute Inc., Cary, NC,...

L.W. Alkureishi et al.

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

Ann Surg Oncol

(2010)

J. Alvarez Amezaga et al.

Diagnostic efficacy of sentinel node biopsy in oral squamous cell carcinoma. Cohort study and meta-analysis

Med Oral Patol Oral Cir Bucal

(2007)

Cited by (134)

In Reply
2024, International Journal of Oral and Maxillofacial Surgery
The optimal number of examined lymph nodes for accurate nodal staging and favorable prognosis of oral tongue squamous cell carcinoma
2023, Oral Oncology
The study aimed to determine the optimal count of examined lymph nodes (ELN) for accurate assessment of lymph node status and favorable long-term survival in patients with oral tongue squamous cell carcinoma (OTSCC) who received radical resection.
Patients with OTSCC who received radical resection between 2004 and 2015 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) and were randomly divided into two cohorts. The association of ELN count with nodal migration and overall survival (OS) was analyzed using a multivariate regression model with the adjustment of relevant factors. Locally weighted scatterplot smoothing (LOWESS) and ‘strucchange’ package were adopted to identify the optimal cut points using R.
A total of 2077 patients were included in this study. The optimal cut points of ELN count for accurate nodal staging and favorable OS were 19 and 15, respectively. The probability of detecting positive lymph nodes (PLN) significantly increased in patients with ELN count ≥ 19 in comparison to those with ELN count < 19 (training set, P < 0.001; validation set, P = 0.012). A better postoperative prognosis was observed in patients with ELN count ≥ 15 than those with fewer ELN (training set, P = 0.001, OR: 0.765; validation set, P = 0.016, OR: 0.678).
The optimal cut point of ELN count to ensure the accuracy of nodal staging and to achieve a favorable postoperative prognosis were 19 and 15, respectively. The ELN count beyond the cutoff values might improve the accuracy of cancer staging and OS.
Does Sentinel Lymph Node Biopsy Accurately Stage the Clinically Negative Neck in Early Oral Cavity Squamous Cell Carcinoma?
2022, Journal of Oral and Maxillofacial Surgery
Citation Excerpt :
Both these situations occurred in our study that reduced sentinel node detection and retrieval rates, respectively. However, previous SLNB studies have shown both a cost advantage2 and superior results concerning morbidity, quality of life, and shoulder function compared with END.18 Garrel et al19 recently presented evidence from their multi-institutional equivalence RCT comparing END and SLNB (and neck dissection only if SLNB was positive) in patients with T1/T2 oral cancer involving 155 patients in each arm.
Sentinel lymph node biopsy (SLNB) is being increasingly used worldwide as a minimally invasive option to stage the clinically node-negative neck (N0) in patients with early oral cavity squamous cell carcinomas (OCSCC). We performed this trial to assess the reliability and validity of the technique.
We did this prospective interventional nonrandomized study in patients with early (cT1-T2 OCSCC) and with negative neck. All patients underwent preoperative lymphoscintigraphy; SLNB was followed immediately by completion neck dissection (CND), thus each patient serving as their own control. The primary outcomes evaluated are sentinel lymph node (SLN) detection rate, SLN retrieval rate, and SLN status (positive or negative) compared with pathology of CND specimen to detect any false negatives. The secondary outcomes included SLN analyses (tumor burden, location in different levels of the neck, laterality, extracapsular spread, and total nodes positive) and overall survival.
Of 60 patients, 59 (98%) had successful SLN detection with the lymphoscintigram failing to localize in 1 patient. Of the remaining 59 patients, 58 (96%) had all the SLNs retrieved, resulting in 96.4% sentinel node retrieval rate. In total, 24 (41%) SLNs were positive with 1 false negative. Using a combination of SLN and CND findings as the gold standard for lymph node involvement status, SLNB had a sensitivity of 96% (95% confidence interval [CI]: 80-100%), a specificity of 100% (95% CI: 90-100%), and negative predictive value of 97% (95% CI: 85-100%).
The results of this study suggest that SLNB is an accurate technique to assess the nodal status in patients with cT1-T2 N0 OCSCC and should be considered for eligible patients.
Tumor–stroma ratio is a crucial histological predictor of occult cervical lymph node metastasis and survival in early-stage (cT1/2N0) oral squamous cell carcinoma
2022, International Journal of Oral and Maxillofacial Surgery
Occult cervical lymph node metastasis is a significant prognostic factor in patients with early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the potential value of the tumor–stroma ratio (TSR) as a histological predictor of occult cervical metastasis and survival in early-stage OSCC. This retrospective study included 151 patients who underwent excision of the primary lesion and elective neck dissection from 2013 to 2017. The clinicopathological features of the tumor, risk factors associated with occult neck metastasis, and prognostic factors for overall survival (OS) and disease-free survival (DFS) were studied. A significant correlation of TSR (P = 0.009) was found with occult neck metastasis in the multivariate logistic regression model. Multivariate Cox proportional hazards regression analysis showed that the TSR (P = 0.002) and perineural invasion (P = 0.011) were associated with OS. Occult neck metastasis (P = 0.032) was associated with DFS. These findings indicate that assessment of the TSR might be useful in prognostication for early-stage OSCC patients. Moreover, the TSR is effective in allowing an accurate evaluation of the risk of occult neck metastasis, and this may be easily applicable in the routine pathological diagnosis and clinical decision-making for elective neck dissection.
Systematic review and meta-analysis of randomized controlled trials comparing elective neck dissection versus sentinel lymph node biopsy in early-stage clinically node-negative oral and/or oropharyngeal squamous cell carcinoma: Evidence-base for practice and implications for research
2022, Oral Oncology
Management of clinically node-negative (N0) neck in early-stage (T1-T2) oral and/or oropharyngeal squamous cell carcinoma (OOSCC) has been controversial. The purpose of this systematic review and meta-analysis was to compare sentinel lymph node biopsy (SLNB) with elective neck dissection (END) in early-stage OOSCC.
Studies comparing SLNB versus END in early-stage clinically node-negative OOSCC were identified using validated search strategy. To be considered eligible, trials had to include patients with early-stage, clinically node-negative OOSCC who had been randomly assigned to either SLNB or END. Primary outcome of interest was overall survival (OS), while secondary outcomes included isolated neck nodal recurrence (NNR), loco-regional recurrence (LRR), and neck-shoulder function. Outcome data was pooled using random-effects model and reported as hazard ratio (HR) or risk ratio (RR) with 95% confidence interval (CI). Any p-value < 0.05 was considered statistically significant.
A total of 608 patients from three trials comparing SLNB versus END in early-stage clinically node-negative OOSCC were included. The pooled HR of death for SLNB versus END was 1.18 (95% CI: 0.79–1.78, p = 0.41) which was not statistically significant. The rates of isolated NNR (pooled RR = 1.11, 95% CI: 0.69–1.80, p = 0.66) and LRR (pooled RR = 1.18, 95% CI: 0.81–1.72, p = 0.39) were also similar. Pooled analysis of the neck-shoulder function significantly favoured SLNB arm (pooled RR = 1.21, 95% CI: 1.12–1.32, p < 0.00001).
There is low-certainty evidence that SLNB is oncologically non-inferior to END and is associated with potentially lesser functional morbidity making it an emerging alternative standard of care in patients with early-stage clinically node-negative OOSCC.
Detecting head and neck lymph node metastases with white light reflectance spectroscopy; a pilot study
2021, Oral Oncology
A challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases.
We performed intraoperative SFR spectroscopy measurements of LNs with and without malignancies. We analyzed if physiological and scattering parameters were significantly altered in positive LNs.
Nine patients with a total of nineteen LNs were included. Three parameters, blood volume fraction (BVF), microvascular saturation (StO₂), and Rayleigh amplitude, were significantly lower in positive LNs. They were combined into one optical parameter ‘delta’, using discriminant analysis. Delta was significantly decreased in positive LNs, p = 0,0006. It had a high diagnostic accuracy where the sensitivity, specificity, PPV, and NPV were 90,0%, 88.9%, 90,0%, and 88.9%, respectively. The area under the ROC curve was 96.7% (95% confidence interval 89.7–100.0%).
This proof of principle study is a first step in the development of an SFR spectroscopy technique to detect LN metastases in real time. A next step towards this goal is replicating these results in LNs with smaller metastases and in a larger cohort of patients. This future study will combine SFR spectroscopy with fine-needle aspiration, using the same needle, to perform preoperative in vivo measurements.

View all citing articles on Scopus

View full text

ReviewSentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: A diagnostic meta-analysis

Summary

Background

Methods

Results

Conclusion

Introduction

Section snippets

Data sources and searches

Study selection

Results

Discussion

Conflict of interest statement

Acknowledgements

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Epidemiology of cancer from the oral cavity and oropharynx

Eur J Gastroenterol Hepatol

Elective neck dissection in early-stage oral squamous cell carcinoma–does it influence recurrence and survival?

Head Neck

Predictive factors for failure to identify sentinel nodes in head and neck squamous cell carcinoma

Head Neck

Improved survival with elective neck dissection in thick early-stage oral squamous cell carcinoma

Head Neck

Neck treatment and shoulder morbidity: still a challenge

Head Neck

A portable gamma-camera for intraoperative detection of sentinel nodes in the head and neck region

J Nucl Med: Off Publ, Soc Nucl Med

Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1–T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial

J Clin Oncol

Function, postoperative morbidity, and quality of life after cervical sentinel node biopsy and after selective neck dissection

Head Neck

Comparison of morbidity between sentinel node biopsy and elective neck dissection for treatment of the n0 neck in patients with oral squamous cell carcinoma

Head Neck

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies

Ann Intern Med

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

Ann Surg Oncol

Diagnostic efficacy of sentinel node biopsy in oral squamous cell carcinoma. Cohort study and meta-analysis

Med Oral Patol Oral Cir Bucal

Review
Sentinel node biopsy for squamous cell carcinoma of the oral cavity and oropharynx: A diagnostic meta-analysis