Sentinel Lymph Node Biopsy Using Preoperative Computed Tomographic Lymphography and Intraoperative Indocyanine Green Fluorescence Imaging in Patients With Localized Tongue Cancer | Head and Neck Cancer | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Figure 1.  Computed Tomographic (CT) Lymphography for T2N0 Tongue Cancer
Computed Tomographic (CT) Lymphography for T2N0 Tongue Cancer

A, Control CT image before iopamidol injection. B, CT image 3 minutes after iopamidol injection (section at sentinel lymph node [SLN] level). The black arrowhead indicates SLN, representing the first enhanced lymph node. C, 3-Dimensional (3D) CT lymphography reconstructed from images after injection. The arrowhead indicates SLN.

Figure 2.  Intraoperative View of Sentinel Lymph Node (SLN) Biopsy With HyperEye Medical System (HEMS)
Intraoperative View of Sentinel Lymph Node (SLN) Biopsy With HyperEye Medical System (HEMS)

A, Incision line for SLN biopsy. The black arrowhead indicates marking of SLN, made in accordance with images from computed tomographic (CT) lymphography. B, An injection of 2 mL of 5 mg/mL indocyanine green (ICG) into the peritumor area. The black arrowheads indicate the points of injection. Image of the primary lesion using a near-infrared (NIR) fluorescence camera just after ICG injection. HEMS can detect color and NIR at the same time under bright light. Images are derived from intraoperative video.

Figure 3.  Fluorescence Signal in SLN Detected With HEMS
Fluorescence Signal in SLN Detected With HEMS

Arrowheads indicate sentinel lymph node (SLN) at level 1 without (A) or with (B) illumination under near-infrared light. Removed SLN without (C) or with (D) illumination under near-infrared light. Images are derived from intraoperative video. HEMS indicates HyperEye Medical System.

Table 1.  Clinical Data of the Enrolled Patients
Clinical Data of the Enrolled Patients
Table 2.  Modality for Sentinel Lymph Nodes (SLNs) Identification
Modality for Sentinel Lymph Nodes (SLNs) Identification
1.
Yuen  AP, Wei  WI, Wong  YM, Tang  KC.  Elective neck dissection versus observation in the treatment of early oral tongue carcinoma.  Head Neck. 1997;19(7):583-588. doi:10.1002/(SICI)1097-0347(199710)19:7<583::AID-HED4>3.0.CO;2-3PubMedGoogle ScholarCrossref
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Kaneko  S, Yoshimura  T, Ikemura  K,  et al.  Primary neck management among patients with cancer of the oral cavity without clinical nodal metastases: a decision and sensitivity analysis.  Head Neck. 2002;24(6):582-590. doi:10.1002/hed.10101PubMedGoogle ScholarCrossref
3.
Song  T, Bi  N, Gui  L, Peng  Z.  Elective neck dissection or “watchful waiting”: optimal management strategy for early stage N0 tongue carcinoma using decision analysis techniques.  Chin Med J (Engl). 2008;121(17):1646-1650. doi:10.1097/00029330-200809010-00010PubMedGoogle ScholarCrossref
4.
Fasunla  AJ, Greene  BH, Timmesfeld  N, Wiegand  S, Werner  JA, Sesterhenn  AM.  A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck.  Oral Oncol. 2011;47(5):320-324. doi:10.1016/j.oraloncology.2011.03.009PubMedGoogle ScholarCrossref
5.
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. doi:10.1056/NEJMoa1506007PubMedGoogle ScholarCrossref
6.
Ho  CM, Lam  KH, Wei  WI, Lau  SK, Lam  LK.  Occult lymph node metastasis in small oral tongue cancers.  Head Neck. 1992;14(5):359-363. doi:10.1002/hed.2880140504PubMedGoogle ScholarCrossref
7.
Suzuki  S, Honda  K, Nanjo  H,  et al.  CD147 expression correlates with lymph node metastasis in T1-T2 squamous cell carcinoma of the tongue.  Oncol Lett. 2017;14(4):4670-4676. doi:10.3892/ol.2017.6808PubMedGoogle ScholarCrossref
8.
Civantos  FJ, Zitsch  RP, Schuller  DE,  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;28(8):1395-1400. doi:10.1200/JCO.2008.20.8777PubMedGoogle ScholarCrossref
9.
Höft  S, Maune  S, Muhle  C,  et al.  Sentinel lymph-node biopsy in head and neck cancer.  Br J Cancer. 2004;91(1):124-128. doi:10.1038/sj.bjc.6601877PubMedGoogle ScholarCrossref
10.
Paleri  V, Rees  G, Arullendran  P, Shoaib  T, Krishman  S.  Sentinel node biopsy in squamous cell cancer of the oral cavity and oral pharynx: a diagnostic meta-analysis.  Head Neck. 2005;27(9):739-747. doi:10.1002/hed.20228PubMedGoogle ScholarCrossref
11.
de Bree  R, Nieweg  OE.  The history of sentinel node biopsy in head and neck cancer: From visualization of lymphatic vessels to sentinel nodes.  Oral Oncol. 2015;51(9):819-823. doi:10.1016/j.oraloncology.2015.06.006PubMedGoogle ScholarCrossref
12.
Kusano  M, Tajima  Y, Yamazaki  K, Kato  M, Watanabe  M, Miwa  M.  Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer.  Dig Surg. 2008;25(2):103-108. doi:10.1159/000121905PubMedGoogle ScholarCrossref
13.
Aoyama  K, Kamio  T, Ohchi  T, Nishizawa  M, Kameoka  S.  Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green.  World J Surg Oncol. 2011;9:157. doi:10.1186/1477-7819-9-157PubMedGoogle ScholarCrossref
14.
Zhang  X, Li  Y, Zhou  Y,  et al.  Diagnostic performance of indocyanine green-guided sentinel lymph node biopsy in breast cancer: a meta-analysis.  PLoS One. 2016;11(6):e0155597. doi:10.1371/journal.pone.0155597PubMedGoogle ScholarCrossref
15.
Honda  K, Ishiyama  K, Suzuki  S,  et al.  Sentinel lymph node biopsy using computed tomographic lymphography in patients with early tongue cancer.  Acta Otolaryngol. 2015;135(5):507-512. doi:10.3109/00016489.2015.1010126PubMedGoogle ScholarCrossref
16.
Polom  K, Murawa  D, Rho  YS, Nowaczyk  P, Hünerbein  M, Murawa  P.  Current trends and emerging future of indocyanine green usage in surgery and oncology: a literature review.  Cancer. 2011;117(21):4812-4822. doi:10.1002/cncr.26087PubMedGoogle ScholarCrossref
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Christensen  A, Juhl  K, Charabi  B,  et al.  Feasibility of real-time near-infrared fluorescence tracer imaging in sentinel node biopsy for oral cavity cancer patients.  Ann Surg Oncol. 2016;23(2):565-572. doi:10.1245/s10434-015-4883-7PubMedGoogle ScholarCrossref
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Peng  H, Wang  SJ, Niu  X, Yang  X, Chi  C, Zhang  G.  Sentinel node biopsy using indocyanine green in oral/oropharyngeal cancer.  World J Surg Oncol. 2015;13:278. doi:10.1186/s12957-015-0691-6PubMedGoogle ScholarCrossref
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van der Vorst  JR, Schaafsma  BE, Verbeek  FP,  et al.  Near-infrared fluorescence sentinel lymph node mapping of the oral cavity in head and neck cancer patients.  Oral Oncol. 2013;49(1):15-19. doi:10.1016/j.oraloncology.2012.07.017PubMedGoogle ScholarCrossref
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Iwai  T, Maegawa  J, Hirota  M, Tohnai  I.  Sentinel lymph node biopsy using a new indocyanine green fluorescence imaging system with a colour charged couple device camera for oral cancer.  Br J Oral Maxillofac Surg. 2013;51(2):e26-e28. doi:10.1016/j.bjoms.2012.03.002PubMedGoogle ScholarCrossref
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van den Berg  NS, Brouwer  OR, Klop  WM,  et al.  Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid.  Eur J Nucl Med Mol Imaging. 2012;39(7):1128-1136. doi:10.1007/s00259-012-2129-5PubMedGoogle ScholarCrossref
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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. doi:10.1371/journal.pone.0170322PubMedGoogle ScholarCrossref
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Murase  R, Tanaka  H, Hamakawa  T,  et al.  Double sentinel lymph node mapping with indocyanine green and 99m-technetium-tin colloid in oral squamous cell carcinoma.  Int J Oral Maxillofac Surg. 2015;44(10):1212-1217. doi:10.1016/j.ijom.2015.05.008PubMedGoogle ScholarCrossref
Original Investigation
June 27, 2019

Sentinel Lymph Node Biopsy Using Preoperative Computed Tomographic Lymphography and Intraoperative Indocyanine Green Fluorescence Imaging in Patients With Localized Tongue Cancer

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • 2Department of Radiology, Akita University Graduate School of Medicine, Akita, Japan
  • 3Department of Otorhinolaryngology–Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan
JAMA Otolaryngol Head Neck Surg. 2019;145(8):735-740. doi:10.1001/jamaoto.2019.1243
Key Points

Question  Is sentinel lymph node biopsy using preoperative computed tomographic (CT) lymphography and intraoperative indocyanine green fluorescence useful?

Findings  In this cohort study of 18 patients with localized squamous cell carcinoma of the tongue, sentinel lymph nodes could be mapped by preoperative CT lymphography in 16 of 18 patients, and using intraoperative indocyanine green fluorescence, at least 1 sentinel lymph node was successfully identified and excised in each of these 16 patients.

Meaning  Preoperative CT lymphography mapping with intraoperative indocyanine green fluorescence has clinical potential as a sentinel lymph node biopsy technique that does not require radioisotopes.

Abstract

Importance  The indocyanine green method alone is unsuitable for sentinel lymph node biopsy in patients with oral cancer because of poor transcutaneous identification of the fluorescent signal through the platysma and sternocleidomastoid muscles.

Objective  To assess the utility of a novel sentinel lymph node biopsy technique using preoperative computed tomographic (CT) lymphography followed by the intraoperative indocyanine green fluorescence method.

Design, Setting, and Participants  In this prospective study performed at Akita University Hospital, Akita, Japan, participants comprised 18 patients with previously untreated cN0 tongue cancer (squamous cell carcinoma) were enrolled from November 2012 to November 2016. Median observer period was 38 (range, 14-62) months. Analysis was completed between January 10 and March 10, 2018.

Interventions  For preoperative sentinel lymph node mapping, CT lymphography was performed the day before sentinel lymph node biopsy. For sentinel lymph node biopsy, a minimum skin incision was made according to the predetermined location of sentinel lymph nodes. Sentinel lymph nodes were excised under indocyanine green fluorescence guidance.

Main Outcomes and Measures  Identification rate of preoperative sentinel lymph node mapping by CT lymphography and the number of sentinel lymph node successfully identified by the intraoperative indocyanine green fluorescence method.

Results  Among 18 patients (8 men, 10 women; median age, 65.5 [range, 40-83] years), sentinel lymph nodes could be mapped by preoperative CT lymphography in 16 patients (89%). At least 1 sentinel lymph node was successfully identified and excised in each of these 16 patients using intraoperative indocyanine green fluorescence. Among the 16 patients in whom sentinel lymph nodes were excised, metastases to sentinel lymph nodes were found in 5 patients (31%).

Conclusions and Relevance  The novel sentinel lymph node biopsy technique of preoperative CT lymphography mapping with intraoperative indocyanine green fluorescence has a high potential for identifying sentinel lymph nodes in patients with cN0 tongue cancer. Because the intraoperative indocyanine green method alone cannot identify sentinel lymph nodes in the neck region, this combined method has clinical potential as a sentinel lymph node biopsy technique that does not require radioisotopes.

Introduction

The optimal treatment strategy for N0 tongue cancer, whether to use simultaneous elective neck dissection or careful observation, remains controversial.1-5 The rate of occult nodal metastasis in N0 tongue cancer has been estimated as 25% to 40%.6,7 Elective neck dissection for N0 tongue cancer might thus result in unnecessarily invasive procedures in at least 60% of patients. Recently, the sentinel lymph node (SLN) concept has been accepted in local-stage oral cancer treatment.8-10 Although preoperative lymphoscintigraphy using radioisotopes (RI) and intraoperative γ-probe detection with or without blue dye mapping are generally used to detect SLNs, the RI method has disadvantages such as exposure to radiation, masking of the SLN owing to shine-through radioactivity when the SLN is close to the RI injection site, and high cost.11 Recently, to increase the detection rate of SLNs through better visualization, indocyanine green (ICG) fluorescence imaging-guided SLN biopsy has been developed as a new non-RI technique for breast cancer and gastrointestinal cancer.12-14 Although this new method has shown clinical potential for axillary and abdominal lymph nodes, the ICG method alone is unsuitable for cervical SLN biopsy because of poor transcutaneous identification of the fluorescent signal. We recently reported a new method of preoperative SLN mapping using computed tomographic (CT) lymphography in cases with localized tongue cancer.15 The CT lymphographic method of SLN mapping is simple and quite useful for accurately localizing SLNs, lymph vessels, and the tumor before SLN biopsy without using RI. We hypothesized that combining preoperative CT lymphography mapping and intraoperative ICG fluorescence-guided SLN biopsy would provide a good method without using RI and may have clinical potential for SLN biopsy of cN0 tongue cancer. This study evaluated the identification rate of SLNs using the new technique of combined preoperative CT lymphography and intraoperative ICG fluorescence for cN0 localized tongue cancer.

Methods

This study was approved by the ethics committee of Akita University School of Medicine (approval 373), and written informed consent was obtained from all patients. Data analysis was completed by January 31, 2018.

Patients

From November 2012 to November 2016, 18 patients (8 men, 10 women) with previously untreated cN0 early tongue cancer (squamous cell carcinoma) including 7 patients with T1N0 and 11 patients with T2N0 (7th edition of the AJCC/UICC TNM classification) were enrolled in this study. The patients with T2 disease were divided into 2 groups: localized T2, with tumor diameter smaller than 3 cm (n = 4); and advanced T2, with tumor diameter of 3 cm or larger (n = 7). Median age was 65.5 (range, 40-83) years. The median observation period was 38 (range, 14-62) months.

Preoperative SLN Mapping With CT Lymphography

Sentinel lymph node mapping was performed by CT lymphography the day before SLN biopsy, as described previously.15 Briefly, a lattice marker (CT guidelines; FLAIR [fluid attenuated inversion recovery]) developed for CT-guided needle biopsy was attached to the skin at the neck and non–contrast-enhanced CT of the oral cavity and neck (helical thickness, 0.625 mm) was performed using a 64 multidetector-row CT scanner (Discovery 750 HD; GE Healthcare). A mixture of 1.5 mL of iopamidol (iopamiron 370; Bayer Healthcare) and 0.5 mL of 1% lidocaine hydrochloride was then injected into the peritumoral area with a 25-g needle. Computed tomographic images were obtained 1, 3, 5, and 10 minutes after administration of the iopamidol. Following enhancement of the lymphatic duct, the first lymph node to show enhancement was defined as the SLN (Figure 1). The location of the SLN was marked on the skin using the crossing points of the lattice marker and the CT plane lights.

SLN Biopsy With Intraoperative ICG Fluorescence Imaging

For SLN biopsy, a minimum skin incision was made according to preoperative SLN mapping in patients with T1N0 and localized T2N0 disease. In patients with advanced T2N0 disease, wide skin incisions were made, as for selective neck dissection (level s1-3). After the skin flap was elevated, 2 mL of 5-mg/mL ICG (Daiichi Pharmaceutical) was injected into the peritumor area (Figure 2). A handheld near-infrared (NIR) fluorescence camera (HyperEye Medical System [HEMS]; Mizuho Ikakogyo) or Photo Dynamic Eye (PDE, Hamamatsu Photonics Co) was used to search for the ICG fluorescence signal. The HEMS system can simultaneously detect color and NIR rays under bright light. Near-infrared light with a wavelength of 780 nm was shone on the specimen and fluorescence signals in SLNs were detected on the monitor 1 or 2 minutes after injection (Figure 3).

Main Outcome Measures

The identification rate of preoperative SLN mapping by CT lymphography was determined, and the number of SLNs successfully identified by the intraoperative ICG fluorescence method and excised by SLN biopsy was counted. Following the removal of SLNs, they were frozen and serially sectioned at 2-mm intervals along their long axis to assess metastasis to SLNs.

Treatment Strategy

For the patients with T1N0 and localized T2N0 disease with negative SLNs, only partial glossectomy was performed without elective neck dissection. For the patients with advanced T2N0 with negative SLNs, selective neck dissection (levels 1-3) and glossectomy were performed. In cases with positive metastasis to the SLN, glossectomy and neck dissection were performed regardless of the T stage.

Results

Using preoperative CT lymphography, SLNs were successfully mapped in 16 of 18 patients (89%). In all 18 patients, the number of SLNs detected with CT lymphography was 0 in 2 patients (11%), 1 in 8 patients (44%), 2 in 7 patients (39%), and 3 in 1 patient (6%). Of the 16 patients in whom SLNs were successfully detected, 10 patients had SLNs at level 1, 7 patients at level 2, 2 patients at level 3, 2 patients at level 4, and 1 patient at level 1 on the contralateral side, with some overlap (Table 1).

One day after SLN mapping by CT lymphography, SLN biopsy using intraoperative ICG fluorescence imaging was performed for the 16 patients who underwent successful mapping of SLNs. Table 1 shows the number and location of SLNs detected by preoperative CT lymphography and the intraoperative ICG method. In all these 16 patients, at least 1 SLN was successfully identified with the intraoperative ICG fluorescence method.

Among the 16 patients for whom SLNs were excised, metastases to SLNs were found in 5 patients (31%): 2 patients with T1N0 and 3 with advanced T2N0 (Table 1). Among the total of 30 SLNs surgically excised, 24 (80%) were identified by both the preoperative CT lymphography and intraoperative ICG fluorescence methods, 5 (17%) were identified by only the ICG method, and 1 (3%) was identified by only CT lymphography. All metastasis-positive SLNs were successfully identified by both preoperative CT lymphography and the intraoperative ICG fluorescence method (Table 2). Of the 11 patients with negative SLNs, 3 patients with advanced T2N0 disease (patients 14, 16, 17) underwent elective neck dissection (levels 1-3), which revealed no nodal metastases. During follow-up, neck recurrence was found in 2 of the 11 patients (1 each for T1N0 and localized T2M0) who initially showed metastasis-negative SLNs, whereas all patients with SLN-positive results who underwent elective neck dissection showed no locoregional recurrence.

Discussion

A previous a meta-analysis on SLN biopsy in patients with breast cancer revealed that the intraoperative ICG fluorescence method offers very high diagnostic performance with high sensitivity and specificity (98% detection rate, 92% sensitivity, and 100% specificity).14 The benefit of ICG is its well-known safety profile (rate of adverse reactions, ICG: 0.005%, isosulfan dye: 0.7%-1.1%, patent blue: 0.4%).16 Another important benefit is the simple logistics of the surgery (1-step procedure; SLNs can be visualized only a few minutes after injection) and relatively small cost of the ICG compound and fluorescence imaging device, which is also less expensive than a γ probe. For SLN biopsy in patients with head and neck cancer, however, only 10% of excised SLNs could be transcutaneously visualized by ICG fluorescence before skin incision in a previous report.17 A subsequent wide subplatysmal flap and retraction of the sternocleidomastoid muscle with a long incision were thus needed for SLN biopsy using the ICG method,18 making this no longer a pin point biopsy, especially for patients with SLN metastasis-negative results. Another problem is the rapid transportation of ICG, which is a small molecule (2-3 nm) that binds with albumin, owing to rapid lymphatic flow in the neck, leading to the risk of secondary and not sentinel nodes being inadvertently biopsied in patients with oral cavity cancer.19 In our study, to overcome the poor transcutaneous identification of the fluorescent signal with the ICG method, we added preoperative CT lymphography to the intraoperative ICG method. In our study, SLNs could be mapped in 16 of 18 patients (89%) by preoperative CT lymphography and the SLN was successfully identified in all these 16 patients by the intraoperative ICG fluorescence method. Among the total of 30 SLNs surgically excised, 5 (17%) were only identified by the intraoperative ICG fluorescence method, presumably because these were the 4 patients with advanced T2 disease who were scheduled for selective neck dissection (levels 1-3). Relatively wide incision for this purpose enabled determination of the SLNs. In 1 patient with T1 disease, a lymph node that was adjacent to the SLN detected by CT lymphography was also identified by the ICG method. In a previous study, we performed preoperative SLN mapping using CT lymphography and an intraoperative blue dye method for early tongue cancer. The identification ratio in finding the SLN using the intraoperative blue dye method was 67%.15 We could therefore improve the intraoperative detection rate from 67% to 100% using ICG instead of blue dye. The present study used HEMS, a new device for detecting ICG fluorescence that can detect both color and near-infrared rays at the same time under bright light.20 Recent advances in ICG methods using the HEMS fluorescence detector thus enabled SLN biopsy under room light.

Recently, the use of ICG for SLN biopsy in patients with oral cancer has also been reported to offer a high detection rate (100%) compared with RI with or without the blue dye method (90%-100%).18,21-24 Moreover, reports have described injection of combined fluorescent and radioactive tracers, followed by preoperative lymphoscintigraphy and SPECT/CT to define SLNs in patients with oral cancer, and intraoperative detection of SLNs using a γ probe and handheld near-infrared fluorescence camera.17,25 Compared with the high detection rate of this RI with ICG fluorescence method, the detection rate of our current combined method was slightly low, but freedom from the need for RI offers many benefits, including no exposure to radiation, no need for facility approval, and lower cost. In this study, there were 2 false-negative results and 2 no-detection results with CT lymphography. To improve the sensitivity of the preoperative CT lymphography method, use of other agents with lower osmolality and viscosity, such as iomeprol, might be worth considering.

Limitations

The biggest advantage of the current method is the lack of RI injection. This study was limited by its retrospective analysis and the small number of patients. Additional studies are required to confirm the accuracy of this combination method in detecting SLNs.

Conclusions

Computed tomographic lymphography mapping provides localization of SLNs preoperatively and ICG fluorescence-guided SLN biopsy has a high potential to provide clear visualization with high sensitivity, even if the SLN is located close to the primary injection site. Preoperative CT lymphography mapping and intraoperative ICG fluorescence-guided SLN biopsy is a simple, cost-effective, and useful combination method for SLN biopsy in local-stage tongue cancer without using RI.

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Article Information

Accepted for Publication: April 17, 2019.

Published Online: June 27, 2019. doi:10.1001/jamaoto.2019.1243

Correction: This article was corrected on August 15, 2019, to fix errors in the author affiliations.

Corresponding Author: Kohei Honda, MD, Department of Otolaryngology–Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuoku, Niigata 951-8510, Japan (koheih4691@gmail.com).

Author Contributions: Dr Honda had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Honda, Ishiyama.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Honda, Ishiyama, Kawasaki, Saito, Horii.

Critical revision of the manuscript for important intellectual content: Honda, Suzuki, Horii.

Statistical analysis: Honda.

Obtained funding: Honda.

Administrative, technical, or material support: Honda, Ishiyama, Suzuki, Kawasaki.

Study supervision: Honda, Horii.

Conflict of Interest Disclosures: None reported.

Meeting Presentation: These data were orally presented at 2019 American Head & Neck Society (AHNS) Meeting; May 2, 2019; Austin, Texas.

References
1.
Yuen  AP, Wei  WI, Wong  YM, Tang  KC.  Elective neck dissection versus observation in the treatment of early oral tongue carcinoma.  Head Neck. 1997;19(7):583-588. doi:10.1002/(SICI)1097-0347(199710)19:7<583::AID-HED4>3.0.CO;2-3PubMedGoogle ScholarCrossref
2.
Kaneko  S, Yoshimura  T, Ikemura  K,  et al.  Primary neck management among patients with cancer of the oral cavity without clinical nodal metastases: a decision and sensitivity analysis.  Head Neck. 2002;24(6):582-590. doi:10.1002/hed.10101PubMedGoogle ScholarCrossref
3.
Song  T, Bi  N, Gui  L, Peng  Z.  Elective neck dissection or “watchful waiting”: optimal management strategy for early stage N0 tongue carcinoma using decision analysis techniques.  Chin Med J (Engl). 2008;121(17):1646-1650. doi:10.1097/00029330-200809010-00010PubMedGoogle ScholarCrossref
4.
Fasunla  AJ, Greene  BH, Timmesfeld  N, Wiegand  S, Werner  JA, Sesterhenn  AM.  A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck.  Oral Oncol. 2011;47(5):320-324. doi:10.1016/j.oraloncology.2011.03.009PubMedGoogle ScholarCrossref
5.
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. doi:10.1056/NEJMoa1506007PubMedGoogle ScholarCrossref
6.
Ho  CM, Lam  KH, Wei  WI, Lau  SK, Lam  LK.  Occult lymph node metastasis in small oral tongue cancers.  Head Neck. 1992;14(5):359-363. doi:10.1002/hed.2880140504PubMedGoogle ScholarCrossref
7.
Suzuki  S, Honda  K, Nanjo  H,  et al.  CD147 expression correlates with lymph node metastasis in T1-T2 squamous cell carcinoma of the tongue.  Oncol Lett. 2017;14(4):4670-4676. doi:10.3892/ol.2017.6808PubMedGoogle ScholarCrossref
8.
Civantos  FJ, Zitsch  RP, Schuller  DE,  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;28(8):1395-1400. doi:10.1200/JCO.2008.20.8777PubMedGoogle ScholarCrossref
9.
Höft  S, Maune  S, Muhle  C,  et al.  Sentinel lymph-node biopsy in head and neck cancer.  Br J Cancer. 2004;91(1):124-128. doi:10.1038/sj.bjc.6601877PubMedGoogle ScholarCrossref
10.
Paleri  V, Rees  G, Arullendran  P, Shoaib  T, Krishman  S.  Sentinel node biopsy in squamous cell cancer of the oral cavity and oral pharynx: a diagnostic meta-analysis.  Head Neck. 2005;27(9):739-747. doi:10.1002/hed.20228PubMedGoogle ScholarCrossref
11.
de Bree  R, Nieweg  OE.  The history of sentinel node biopsy in head and neck cancer: From visualization of lymphatic vessels to sentinel nodes.  Oral Oncol. 2015;51(9):819-823. doi:10.1016/j.oraloncology.2015.06.006PubMedGoogle ScholarCrossref
12.
Kusano  M, Tajima  Y, Yamazaki  K, Kato  M, Watanabe  M, Miwa  M.  Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer.  Dig Surg. 2008;25(2):103-108. doi:10.1159/000121905PubMedGoogle ScholarCrossref
13.
Aoyama  K, Kamio  T, Ohchi  T, Nishizawa  M, Kameoka  S.  Sentinel lymph node biopsy for breast cancer patients using fluorescence navigation with indocyanine green.  World J Surg Oncol. 2011;9:157. doi:10.1186/1477-7819-9-157PubMedGoogle ScholarCrossref
14.
Zhang  X, Li  Y, Zhou  Y,  et al.  Diagnostic performance of indocyanine green-guided sentinel lymph node biopsy in breast cancer: a meta-analysis.  PLoS One. 2016;11(6):e0155597. doi:10.1371/journal.pone.0155597PubMedGoogle ScholarCrossref
15.
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