Anil K.D. Cruz, Harsh Dhar, and Manish Mair Abstract
Neck metastasis is an important prognostic factor in head and neck cancers. Elective neck dissection implies prophylactic removal of lymph nodes at the highest risk of metastasis. Incidence and patterns of spread are unique to the different subsites of the upper aerodigestive tract and this has influenced management for decades. There has been a shift in the philosophy with regard to the elective treatment of the neck in upper aerodigestive tract cancers in the recent past with the development of transoral surgical procedures, recognition of a change in the epidemiology of oropharyngeal cancers, but more importantly the emergence of new evidence. This chapter discusses the indications and extent of elective neck dissection in light of the available literature. Issues specific to each subsite are alluded to in distinct sections.
Keywords: neck dissection/methods, mouth neoplasms, laryngeal neoplasms/surgery, pharyngeal neoplasms/surgery
Neck metastasis is one of the most important prognostic factors in head and neck cancers. Its presence even with the smallest of primary cancer upstages the disease to stage III, impacting survival and necessitating the addition of adjuvant therapy. Prognosis worsens with increasing size, number of lymph nodes, as well as the presence of extracapsular spread (ECS).1 Early detection and appropriate treatment of the neck is therefore of paramount importance. When the primary modality of treatment is surgery, management of the neck could be elective or therapeutic. Elective neck dissection (END) is a nodal dissection procedure performed in a clinico-radiologically node-negative neck. Surgery is usually a selective procedure which entails removal of nodes at the highest risk of metastasis for the index cancer. Nodes harvested at surgery, if they contain metastases, are usually occult in nature. A therapeutic neck dissection (TND) in contrast is a procedure performed when nodal metastases are clinico-radiologically manifested. A TND entails a comprehensive dissection of the neck which usually is a modified neck dissection with removal of all levels of nodes (levels I-V) while preserving nonlymphatic structures (sternocleidomastoid, internal jugular vein, and spinal accessory nerve) unless involved by disease.
The role of END has been a contentious issue in the management of early oral cancers where surgery is the primary treatment modality. With an increasing role of transoral robotic surgery (TORS) and transoral laser microsurgery (TOLM) in oro- and laryngopharyngeal cancers, the role of END has gained attention in recent years.
20.2 Elective Neck Dissection in Oral Cancers
The role of END for early oral cancer has been a debate that has plagued the head and neck community worldwide for over five decades. The primary cancer is usually treated by excision via per-oral route. Controversy surrounds the appropriate management of the neck in this clinical scenario. There are two schools of thought—one in favor of END and the other which proposes a wait and watch (WW) policy followed by TND in patients who develop a nodal relapse.
The proponents of the WW group cite a lack of robust evidence for disease control or survival in favor of performing an END. Furthermore, they state that up to 70% of patients who are true node negative undergo unnecessary surgery with associated morbidity and costs. They believe that intensive follow-up will ensure early detection of nodal relapse and timely salvage without compromise in disease control.
Proponents of END, on the other hand, cite a definite advantage in terms of locoregional control and survival. They allude to the fact that both the neck and the primary tumor are treated at a single stage. Moreover, neck dissection in this scenario is usually a selective procedure and not associated with significant morbidity or prolonged hospitalization. Being a staging procedure, nodal metastasis is identified at an occult stage in contrast to a WW approach, where recurrences are known to present at a higher N stage with possible ECS, necessitating larger surgery, and an increased need for adjuvant treatment with resultant worsening of overall prognosis. Given the fact that published studies had small sample sizes and were predominantly retrospective in nature, the management of the neck in this situation remained in the state of clinical equipoise. This in turn resulted in gross variability in practice across the globe.
Elective neck treatment was generally recommended in patients in whom the probability of occult metastasis was greater than 20%. This was based on the findings of Weiss et al2 who using a decision tree analysis suggested 20% as the threshold for elective neck treatment. Clinicians therefore attempted to identify patients who were node positive using advances in imaging or at an increased propensity to nodal metastasis using adverse tumor factors as a surrogate. This guided treatment philosophy for the elective treatment of the neck.
20.2.2 Imaging to Predict Nodal Metastasis
Multiple imaging modalities in the form of ultrasonography (USG; with or without guided fine needle aspirate cytology [FNAC]), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been used in an attempt to accurately stage the neck prior to surgery. The diagnostic accuracy of these various imaging modalities was assessed in a meta-analysis by Liao et al3 who looked at 32 studies specifically in the node-negative situation. This meta-analysis showed no significant difference in sensitivity and specificity across the various imaging modalities, with the sensitivity ranging between 52 and 66% and the specificity between 78 and 83%. Although CT was seen to be more specific than USG, the overall diagnostic accuracy of the various imaging techniques was more or less similar and no single modality stood out as being the most reliable imaging tool for occult neck metastasis. Similarly, Kyzas et al4 in a meta-analysis looking at the role of 18 FDG PET concluded that the sensitivity was just 50% in the clinically node-negative neck. In this context, it is pertinent to note that in the recently published Sentinel European Node Trial (SENT)5 of 415 patients labeled as node negative following an extensive preoperative workup that included either CT and/or MRI with or without USG-guided FNAC, 23% of nodes still turned out to be positive when the sentinel node was examined. This was despite a rigorous workup in a trial setting which would be definitely more intense than in routine clinical practice. Given, therefore, the low sensitivity of imaging in the preoperative setting, this approach did not seem reliable in identifying patients with occult nodal metastasis.
20.2.3 Tumor Characteristics
Various histological factors associated with the primary tumor were used to identify patients at a higher risk for metastasis. While increasing tumor size logically would be the most practical and easiest to use, this often does not hold true with a number of smaller tumors exhibiting biological aggressiveness and an increased risk of metastasis. Tumor grade, thickness, and aggressive histological factors (lymphovascular embolism, perineural invasion) have been described as predictors of occult metastasis in early oral cancers. Among them, the most extensively studied is tumor thickness. Spiro et al6 conducted a study on tongue and floor of the mouth cancers to look at the predictive value of the tumor thickness. The results showed that the risk of occult nodal metastasis in tumors < 2 mm, 3 to 8 mm, and >8 mm was 7, 26, and 41%, respectively. They also concluded that disease-related death increases with the increase in tumor thickness. Subsequent studies from different authors corroborated these findings but used different depths as cutoff. In a meta-analysis of 16 studies with 1,136 patients from the published literature, Huang et al7 looked at the nodal metastasis rates at sequential cutoff points of tumor thickness and found that there was a statistically significant increase in the risk of occult nodal metastasis between 4 and 5 mm (4.5 vs. 16.6%, p = 0.007). They thus concluded that the neck should be electively addressed at tumor thickness 4 mm and beyond. The association of PNI and grade with increased risk of nodal metastasis has also been extensively researched. While these pathological features were helpful in identifying patients at risk of metastasis, they were available only on postoperative histopathology, thus limiting their application in preoperative planning.
20.2.4 Previous Attempts to Address the Issue
There have been attempts to address this issue through numerous retrospective studies, as well as prospective randomized controlled trials (RCT). However, all these studies had serious limitations such as small number of patients and varying endpoints to draw meaningful conclusions. In an attempt to overcome these shortcomings, Fasunla et al8 conducted a metaanalysis on the four RCTs that had been published to date. The findings were in favor of END reducing the risk of disease- specific death. However, even this meta-analysis when critically analyzed seemed to have statistical limitations which included small numbers (283 patients) and wide variations with respect to time periods of accrual, analysis, end points, as well as gross heterogeneity of these studies. Moreover, the findings of one study seemed to be at variance with the others and could have thus influenced results. Given these limitations, therefore, there was still a need for generation of robust level I evidence to address the issue.
20.2.5 Current Evidence in the Management of the N0 Neck
Recently, results of a large single institutional RCT9 (NCT00193765) with adequate statistical power published by our group demonstrated the benefit of END. The trial initiated in 2004 was designed to demonstrate a 10% increase in overall survival (OS) by an END over the WW policy assuming a baseline 5-year OS of 60%. A total of 596 patients were randomized from trial initiation till June 2014 at which point the Data and Safety Monitoring Committee observing a difference in event rate in the two arms ordered an interim analysis. Out of the 596 patients, 500 who had undergone a minimum of 9 months of follow-up at that point in time were included in the final analysis. The arms were equally balanced for both stratification factors (site, sex, preoperative imaging, and T size) as well as grade, LVE and/or PNI, depth of invasion, and the receipt of adjuvant RT, all factors known to influence outcomes in these patients. The median depth of invasion of patients included was 6 mm indicative of the early nature of patients included in the trial. There was a highly significant difference in the OS (80 vs. 67.5%;p = 0.014) and in disease-free survival (DFS; 69.5 vs. 45.9%; p <0.001) in favor of elective neck treatment. This translated into one life being saved for every eight patients (OS difference of 12.5%) and one less recurrence for every four patients (DFS difference of 23.6%) electively operated in this setting. After adjusting for covariates in a cox proportional hazard model for multivariate analysis, the study intervention of END showed a significantly improved OS.
The findings of our study were corroborated in an updated meta-analysis10 that included the findings of five RCTs of 779 patients. Adjusting for heterogeneity between the trials, this meta-analysis suggested that END at the time of resection of the primary tumor confers an improved DFS and OS in patients with clinically node-negative oral cancer. Thus, with strong level I evidence in favor of END, it should become the standard of care for early-stage node-negative oral cancers. A WW approach results in a statistically significant detriment in OS as well as DFS.
20.2.6 Is the Benefit Seen in all Groups of Patients?
While the OS benefit favors most subgroups, there was a sug- gestion9 that patients with thinner tumors less than 3 mm may not benefit from an END. While it is known that thinner tumors would have a lower propensity for neck node metasta- sis,6 and therefore fewer event rates, a study would need a very large sample size to conclusively confirm or disprove this issue. Moreover, at present there is no validated method of estimating depth of invasion of tumors preoperatively or at the time of primary surgery. Therefore, it would be safer to offer END to all patients irrespective of the tumor thickness. However, the only time it may seem logical against advocating an END is when a patient seeks opinion after surgery was performed elsewhere with tumor thickness on histopathology not more than 3 mm given the lack of definite evidence of support from published literature.
The other area of contention is whether the results of the benefit of END could be extrapolated to buccal and alveolar cancers, given that the majority of published literature is focused on tongue cancers. The findings of our RCT9 did show a benefit in favor of buccal mucosa as well, although with lesser statistical power. This could be attributed to the smaller number of patients with buccal cancer randomized on the trial, despite the fact that these cancers are common in our part of the world. Buccal cancers usually need a cheek flap approach for excision or reconstruction, except for a small minority that require entry into the neck; therefore, the neck would be addressed.
20.2.7 Beyond Histopathology—The Use of Molecular Markers
Recently, there has been an interest in the use of gene expression signatures for predicting tumors at an increased risk of nodal metastasis. In a large multicentric cohort11 using a diagnostic DNA microarray, the negative predictive value of the diagnostic signature on early stage oral cancers was 89%. This study also suggested that the rate of undetected nodal mets would decrease from 28 to 11%. This approach would decrease the rate of overtreatment and avoid the need of unnecessary neck dissections in a significant proportion of patients. While gene expression signatures do show promise, the findings of this initial observation need to be validated in larger patient cohorts and by others before they are incorporated into clinical practice.
20.2.8 Intensity of Follow-up
Nodal relapses in the WW approach are known to present at an advanced stage and are responsible for a poor outcome. This was shown in a study by Andersen et al12 where despite a regular 3 monthly follow-up, 77% of the patients who were clinically node negative at initial observation had a pathologically adverse feature (N greater than N1 and ECS) at the time of neck dissection. The randomized trial conducted by our group9 attempted to answer this question by way of a second randomization, as to whether intensifying follow-up by the addition of neck sonography to regular clinical follow-up would detect nodes earlier and impact salvage and survival. In the same cohort of 500 patients with a median follow-up of 39 months, 252 were randomized to clinical examination with USG and 244 to clinical examination alone. A significantly higher proportion of patients had N2-N3 nodes as well as presence of ECS in the WW arm. The findings of this study revealed that neck ultrasound confers no survival advantage over recommended clinical examination (p = 0.89). Cox regression analysis continued to demonstrate the overriding benefit of END (p = 0.02).13
20.2.9 Extent of Neck Dissection in the Elective Setting
Numerous publications have revealed that the highest risk of occult metastasis in oral cancers is at levels I to III. In a retrospective study of 967 patients who underwent a selective neck dissection, Byers14 concluded that the supraomohyoid neck dissection (levels I-III) was adequate for all pN0 oral cancer patients and for selected p N1 in the absence of ECS. In a subsequent publication, the same group of authors15 reported a 15.8% incidence of skip metastasis and advocated an extended supraomohyoid neck dissection encompassing levels I to IV particularly for tongue cancers. However, this publication had inherent flaws and the true incidence of isolated level IV metastasis was less than 5%. An RCT conducted by the Brazilian Head and Neck Group16 showed the safety of a supraomohyoid neck dissection in the node-negative setting and there was no need to do more than a levels I to III clearance. Dissection of level IV as advocated by some is without evidence and unnecessary dissection, particularly when done in the left neck, runs the risk of chyle duct injury.
Supraomohyoid dissection is known to be associated with shoulder dysfunction. This has been attributed to excessive handling and clearance of the lymph nodes in and around the accessory nerve (level IIb). There has been interest in the recent past at attempts to avoid dissection of this nodal basin which in turn would result in safeguarding the accessory nerve and better shoulder function. Paleri et al17 in a meta-analysis of 904 patients reported that metastasis to the level IIb was seen only in 3.4% of oral cancer patients.
To address these issues, our group conducted a study18 evaluating the pattern of nodal metastasis in early oral cancers. This was a prospective study of 583 neck dissections, the surgical procedure performed by the same group of authors where nodal stations were harvested on table and sent in separate prelabeled containers for pathological assessment ensuring accuracy of reporting metastatic patterns. It was observed that 91% of nodal metastasis was concentrated at levels I to III, and 96% at levels I to IV. Skip metastasis was most commonly seen in tongue cancers at level III (17.5%). However, skip metastasis to levels IV and V were never observed in the absence of metastasis to levels I to III. Multivariate analysis identified the presence of level IIa as the single most important factor to predict metastasis at level IIb. The study also showed that positive levels IIb and III are statistically significant factors predicting level V metastasis. From this large prospective study, it would be reasonable to conclude that clearance of levels I to III is adequate in the clinically node-negative neck. Dissection in and around level IIb could be avoided in the absence of metastasis to level IIa.
20.2.10 Role of Sentinel Node Biopsy
Sentinel node biopsy (SNB) is a well-established procedure particularly for cancers of the breast and melanoma. It has been shown to be fairly accurate in these cancers avoiding the morbidity associated with nodal dissection of the axilla and groin. Conceptually extrapolating these findings to the elective management of the neck is attractive and would result in better function and cosmetic outcomes and therefore has been tried in head and neck cancers (see Chapter 21). Results of the largest multicenter, prospective (SENT) trial5 which included 415 patients from 14 European centers showed a sensitivity of 86% with a high negative predictive value of 95%. In a subsequent meta-analysis by Liu et al19 of 66 studies including data from the SENT trial composing of 3,566 patients with cT1-T2 N0 OSCC, the pooled sentinel node identification rate was 96.3% (95% CI: 95.3-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85 ± 0.89), pooled negative predictive value was 0.94 (95% CI: 0.93 ± 0.95), and AUC was 0.98 (95% CI: 0.97 ± 0.99). Thus, SNB is an efficient diagnostic tool to detect occult nodal metastasis with a high negative predictive value. Given that the failure rate of around 6% following a SNB is similar to that of an END, it is unlikely to be an RCT comparing the two. If such a trial is needed to be done with a noninferiority randomized controlled design, the minimum number of patients required would be over 1,000, with a conservative margin of 7%. Other endpoints would therefore have to be used such as function, costs, and time of procedure. Given that SNB has a steep learning curve, needs a nuclear medicine facility, and requires immunohisto- chemistry and serial step sectioning of the sentinel node and a second surgery if the node is positive, it is unlikely to replace selective neck dissection as standard of care. Performing an END with an appropriately placed scar in a skin crease and avoidance of excessive handling of the accessory nerve at level IIb seems to be a reasonable alternative rather than an SNB in light of its above limitations. However, the SNB continues to be an approach practiced by some centers in Europe.
20.2.11 Elective Management of the Contralateral Neck
Unilateral neck dissection is done for well lateralized lesions, while bilateral neck dissection is recommended for lesions that cross the midline. Debate surrounds the management of the contralateral neck in lesions that approach the midline. A study conducted by our group20 consisting of 243 tongue cancer patients identified the involvement of the contralateral neck in this situation. The overall incidence of contralateral nodal metastasis was seen in 71 (29%) patients. Importantly 69 patients (97%) had ipsi- lateral nodal metastasis. The findings of this study confirm that contralateral nodal metastasis is extremely rare in a negative ip- silateral neck and therefore need not be treated electively.
20.3 Elective Neck Dissection for Pharyngeal and Laryngeal Cancers
While surgery forms the mainstay of treatment for oral cancers, radiation/chemoradiation is often the primary treatment modality in tumors of the larynx and pharynx, largely due to the impact on function and cosmesis associated with surgical procedures. Evolution of the minimally invasive techniques of TOLM and TORS resulted in many of these patients being considered for surgery. As the neck is not violated while addressing the primary tumor in these procedures, the role of elective management of the neck needs to be reviewed.
20.3.1 Oropharyngeal Cancers
There has been a steep rise in the prevalence of oropharyngeal cancers in the last decade with the recognition of the human papilloma virus as a significant epidemiological risk factor.21 Given the morbidity associated with open surgeries, management of oropharyngeal cancers has traditionally been nonsurgical (radiation/chemoradiation). However, there has been a recent recognition that these nonsurgical treatments were also associated with significant late toxicities in as high as 43% of pa- tients.22 These included pharyngeal dysfunction in 27%, laryngeal dysfunction in 12%, and 13% of patients being feeding tube dependent primarily due to the radiation effects on the pharyngeal constrictors and larynx. Simultaneously it was found that these cancers are biologically different and associated with a better prognosis raising the possibility of downstaging these cancers as well as decreasing the intensity of treatment.23 It therefore seemed conceptually attractive to factor surgery into the treatment algorithm and decrease the dose of chemoradia- tion, thus avoiding serious consequences. The possibility of resection of these cancers, with the advent of TORS, with good oncological outcomes as well as preservation of swallowing function made this possible.24 Given that these procedures were performed via the mouth without violation of the neck, appropriate management of the neck in the node-negative situation needed to be considered.
Incidence of Occult Neck Metastasis and Extent of Elective Neck Dissection
The oropharynx is a lymphatic-rich region with a high predilection for nodal spread. The incidence of occult nodal metastasis even in small T1 -T2 tumors is as high as 25 to 30%.25 This therefore necessitates addressing the neck electively for clinically node-negative tumors.
Extent of Elective Neck Dissection
Levels II to IV are the first echelon of nodal spread in oropharyngeal cancers.25 Isolated skip metastasis to level IV is rare. In addition, the levels I and V were involved only in the presence of positive nodes at other levels. This finding is consistent across most reported series with isolated level I metastasis being negligible.26 Thus, it would be logical to address levels II to IV when the neck is being addressed. Some centers advocate only dissection of levels II and III avoiding dissection of level IV if these stations are negative. This is done with the aim to prevent postoperative chyle leak, particularly in left neck dissec- tion.26 Both sides of the neck need to be addressed electively when the tumor approaches the midline as well as for centrally located tumors since the incidence of bilateral nodal metastasis is high. Moore et al have also recommended addressing the contralateral neck electively for posterior tonsillar pillar involvement citing spread via the retropharyngeal route with the incidence of contralateral nodal metastasis to be as high as 22%.27 The presence of occult contralateral nodal metastasis has also been reported to be high in the presence of multiple positive ipsilateral nodes. Therefore, addressing the contralateral neck electively is advised in the presence of midline tumors (base tongue, soft palate, and posterior pharyngeal wall), lesions crossing the midline or involving the posterior tonsillar pillar and in the presence of ipsilateral positive nodes.
Timing of Elective Neck Dissection in Oropharyngeal Cancers
Neck dissection at the time of the TORS procedure is known to be associated with pharyngocutaneous fistula, particularly when the submandibular triangle and level II are dissected. This has prompted some to suggest an interval neck dissection rather than simultaneously at the time of resection of the primary. In a metaanalysis of 12 series on TORS for oropharyngeal cancer, of 654 neck dissections, 61% were concurrent while 39% were staged neck dissections.24 The overall rate of pharyngocutaneous fistulae in this meta-analysis was 2.5%. Moore et al in their series of 148 patients similarly reported intraoperative pharyngocutaneous communications in 29% of patients which were all addressed at the time of surgery with only 4% subsequently developing subcutaneous fluid accumulation in the postoperative period. Given that the incidence of pharyngocutaneous fistula after on-table repair is low, simultaneous neck dissection along with the primary may be safely performed. In a retrospective comparative analy- sis,28 there was no reported difference in oncological outcomes or postoperative complications between those who underwent concurrent neck dissection and those who underwent staged neck dissection. Moreover, the duration of hospital stay was also significantly longer in the group that underwent staged neck dissection (median stay of 15 vs. 8 days). Given the lack of consensus in support of either approach, the timing of neck dissection with TORS for oropharyngeal cancers is still a matter of debate with the majority, however, favoring a simultaneous approach. Interestingly, those who recommend interval neck dissection cite that there is a potential logistical advantage of scheduling more robotic procedures per day in the operating room.28
20.3.2 Laryngeal and Hypopharyngeal
The development of the TOLM procedure resulted in a shift in the treatment philosophy of early laryngopharyngeal cancers (particularly for glottic tumors) in the last two decades. The primary could be excised via the oral route and was shown to be oncologically safe in a number of reported series. Given the fact that surgery required a single sitting, without significant alteration in function and that radiation could be avoided, there was an increasing acceptance of TOLM procedures particularly among European centers. The need to electively address the neck thus became a consideration in a subset of these patients.
Treatment philosophy in the management of the neck in this situation is again dictated by the probability of the development of nodal metastasis. Given the fact that the glottis has sparse lymphatics and the incidence of neck metastasis is less than 5% for early lesions,29 elective dissection is not recommended if the neck is clinically and radiographically negative. On the contrary, supraglottis and hypopharynx are lymphatic-rich areas with a high (30-40%) incidence of occult nodal metastasis even in early (T1, T2) cancers.25.29 END is thus warranted for early cancers in these locations when the primary tumor is surgically addressed.
The Extent of Elective Neck Dissection in Laryngo-Hypopharyngeal Tumors
Neck metastasis in laryngo-hypopharyngeal cancers predominantly occurs to levels II to IV.25,29 In contrast, the occurrence of metastasis to levels I and V was seen only in the presence of nodal metastasis at other levels and never in isolation. Thus, performing an END of the jugular group of nodes (II-IV) is considered oncologically safe in a cN0 neck.
The Contralateral Neck
The contralateral neck needs to be electively addressed in situations where the disease is proximal to or has crossed the midline. In well-lateralized lesions, the incidence of contralateral occult neck nodes is minimal (< 5%)25.29 and need not be addressed if the ipsilateral neck is negative. However, the presence of metastasis to the ipsilateral neck is associated with a high risk of contralateral nodal disease, thus necessitating an elective contralateral neck dissection in these cases.
Timing of Neck Dissection in Laryngeal and Hypopharyngeal Cancers
As with oropharyngeal cancers, there is debate as to whether END should be simultaneous or as an interval procedure. Proponents of the staged procedure cite the possibility of intransit metastasis within lymphatics which might not be addressed if the neck is addressed simultaneously resulting in a higher incidence of regional recurrence.30 Performing a staged neck dissection, therefore, would ensure comprehensive clearance of these nodes and ensure better locoregional control. In addition, there is a possibility of an increased incidence of pharyngocutaneous fistula, particularly for resections of hypopharyngeal cancers. A theoretical possibility of improved healing of the raw surface with better swallowing outcomes has also been postulated if the neck is addressed in a staged manner. Given the lack of evidence in favor of either timing of neck dissection in this situation, it is usually dictated by individual treatment philosophies. Fortunately, the majority of these patients are treated by radiation/chemora- diation protocols given the complexity of resection of supra- glottic and hypopharyngeal cancers and, therefore, timing of addressing the neck is a moot issue.
Addressing Level IIb in Oro- and Laryngopharyngeal Cancers
Recent recognition of shoulder morbidity associated with dissection of level IIb (supraspinal region) has raised the debate as to the need of dissection of this area in order to minimize handling of the accessory nerve. Paleri et al, in a systematic review of 14 studies, found a low incidence of isolated metastasis to level IIb (5.2% in oropharyngeal and 0.3% in laryngeal tumors).17 They suggested that there appears to be no advantage in performing dissection in this area, particularly for laryngeal primaries. Thus, aggressive dissection in the region of level IIb may not be necessary in the elective setting for node-negative necks.
Elective dissection of the neck should be standard of care whenever surgery is preferred as the primary modality of treatment. This is because of the strong level I evidence in its favor and the limitations of identifying patients at a higher propensity of neck metastasis preoperatively in those with early oral cancers. For oropharyngeal and laryngopharyngeal cancers, END is safer, as these are lymphatic-rich areas with a high propensity to metastasis. Early glottis cancers are the only exception being devoid of lymphatics. The nodal levels needed to be addressed during an END are guided by the site of the primary tumor and nodal basins at the highest risk for metastasis. Debate still surrounds the decision between interval and simultaneous neck dissection at the time of transoral procedures for oro- and laryngopharyngeal cancers. Decision is based on individual institutional preference with the majority, however, performing neck dissection at the time of primary surgery.
 Wreesmann VB, Katabi N, Palmer FL, et al. Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma. Head Neck. 2016; 38 Suppl 1:E1192-E1199
 Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg. 1994; 120(7):699-702
 Liao L-J, Lo W-C, Hsu W-L, Wang C-T, Lai M-S. Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck- a meta-analysis comparing different imaging modalities. BMC Cancer. 2012; 12:236
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 Schilling C, Stoeckli SJ, Haerle SK, et al. Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer. 2015; 51 (18):2777-2784
 Spiro RH, Huvos AG, Wong GY, Spiro JD, Gnecco CA, Strong EW. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg. 1986; 152(4):345-350
 Huang SH, Hwang D, Lockwood G, Goldstein DP, O'Sullivan B. Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity: a meta-analysis of reported studies. Cancer. 2009; 115(7):1489-1497
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 D'Cruz AK, Vaish R, Kapre N, et al. Head and Neck Disease Management Group. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015; 373(6):521-529
 Ren Z-H, Xu J-L, Li B, Fan T-F, Ji T, Zhang C-P. Elective versus therapeutic neck dissection in node-negative oral cancer: evidence from five randomized controlled trials. Oral Oncol. 2015; 51(11):976-981
 van Hooff SR, Leusink FKJ, Roepman P, et al. Validation of a gene expression signature for assessment of lymph node metastasis in oral squamous cell carcinoma. J Clin Oncol. 2012; 30(33):4104-4110
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 Pantvaidya GH, Pal P, Vaidya AD, Pai PS, D'Cruz AK. Prospective study of 583 neck dissections in oral cancers: implications for clinical practice. Head Neck. 2014; 36(10):1503-1507
 Liu M, Wang SJ, Yang X, Peng H. Diagnostic efficacy of sentinel lymph node biopsy in early oral squamous cell carcinoma: a meta-analysis of 66 studies. PLoS One. 2017; 12(1)-e0170322
 Singh B, Nair S, Nair D, Patil A, Chaturvedi P, D'Cruz AK. Ipsilateral neck nodal status as predictor of contralateral nodal metastasis in carcinoma of tongue crossing the midline. Head Neck. 2013; 35(5):649-652
 Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29 (32):4294-4301
 Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008; 26(21):3582-3589
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