{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:34:37Z","timestamp":1786458877621,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor\u2013stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and \u22653 tumor buds. In addition, the prognostic factors for distant metastasis included \u22654 lymph node metastases, \u22657 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers.<\/jats:p>","DOI":"10.3390\/jcm13040976","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T09:04:01Z","timestamp":1707469441000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Fumitaka","family":"Obayashi","sequence":"first","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4878-3959","authenticated-orcid":false,"given":"Koichi","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-7274","authenticated-orcid":false,"given":"Nanako","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1589-5041","authenticated-orcid":false,"given":"Mirai","family":"Higaki","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-3097","authenticated-orcid":false,"given":"Atsuko","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-7014","authenticated-orcid":false,"given":"Sachiko","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-5412","authenticated-orcid":false,"given":"Ryouji","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-8347","authenticated-orcid":false,"given":"Souichi","family":"Yanamoto","sequence":"additional","affiliation":[{"name":"Department of Oral Oncology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/hed.21809","article-title":"Improved survival with elective neck dissection in thick early-stage oral squamous cell carcinoma","volume":"34","author":"Ebrahimi","year":"2012","journal-title":"Head Neck"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1056\/NEJMoa1506007","article-title":"Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer","volume":"373","author":"Vaish","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/s41416-021-01678-2","article-title":"Correction to: Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort","volume":"126","author":"Hutchison","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/hed.25506","article-title":"Depth of invasion as a predictor of nodal disease and survival in patients with oral tongue squamous cell carcinoma","volume":"41","author":"Tam","year":"2019","journal-title":"Head Neck"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104940","DOI":"10.1016\/j.oraloncology.2020.104940","article-title":"Depth of invasion in early stage oral cavity squamous cell carcinoma: The optimal cut-off value for elective neck dissection","volume":"111","author":"Klazen","year":"2020","journal-title":"Oral. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1600-0714.2011.01041.x","article-title":"Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma","volume":"40","author":"Wang","year":"2011","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/jso.25334","article-title":"Tumor budding and adjacent tissue at the invasive front correlate with delayed neck metastasis in clinical early-stage tongue squamous cell carcinoma","volume":"119","author":"Yamakawa","year":"2019","journal-title":"J. Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s12105-023-01531-3","article-title":"Relationship Between Worst Pattern of Invasion and Extranodal Extension in Oral Tongue Squamous Cell Carcinomas","volume":"17","author":"Yasuda","year":"2023","journal-title":"Head Neck Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/his.14202","article-title":"Addition of the tumour-stroma ratio to the 8th edition American Joint Committee on Cancer staging system improves survival prediction for patients with oral tongue squamous cell carcinoma","volume":"77","author":"Mascitti","year":"2020","journal-title":"Histopathology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/modpathol.2017.46","article-title":"Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016","volume":"30","author":"Lugli","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/01.pas.0000149687.90710.21","article-title":"Oral squamous cell carcinoma: Histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival","volume":"29","author":"Teixeira","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/his.13481","article-title":"Prognostic impact of tumour\u2013stroma ratio in early-stage oral tongue cancers","volume":"72","author":"Almangush","year":"2018","journal-title":"Histopathology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00428-018-2408-z","article-title":"Scoring the tumor-stroma ratio in colon cancer: Procedure and recommendations","volume":"473","author":"Morreau","year":"2018","journal-title":"Virchows Arch."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1001\/archotol.1994.01880310005001","article-title":"Use of decision analysis in planning a management strategy for the stage N0 neck","volume":"120","author":"Weiss","year":"1994","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.oraloncology.2009.03.013","article-title":"Decision analysis and treatment threshold in a management for the N0 neck of the oral cavity carcinoma","volume":"45","author":"Okura","year":"2009","journal-title":"Oral. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00405-009-0955-2","article-title":"Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma","volume":"266","author":"Stoeckli","year":"2009","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00405-010-1215-1","article-title":"What is the role of sentinel lymph node biopsy in the management of oral cancer in 2010?","volume":"267","author":"Civantos","year":"2010","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11912-010-0090-7","article-title":"Oral cavity squamous cell carcinoma and the clinically n0 neck: The past, present, and future of sentinel lymph node biopsy","volume":"12","author":"Coughlin","year":"2010","journal-title":"Curr. Oncol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1245\/s10434-018-07089-7","article-title":"A Multicenter Retrospective Study of Elective Neck Dissection for T1-2N0M0 Tongue Squamous Cell Carcinoma: Analysis Using Propensity Score-Matching","volume":"26","author":"Otsuru","year":"2019","journal-title":"Ann. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103511","DOI":"10.1016\/j.amjoto.2022.103511","article-title":"The impact of microscopic versus macroscopic extranodal extension in oral cavity squamous cell carcinoma: National cancer database analysis and review of the literature","volume":"43","author":"Quinton","year":"2022","journal-title":"Am. J. Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.5794\/jjoms.48.301","article-title":"Risk factors for neck failure in patients with squamous cell carcinoma of tongue\u2014Analysis of the pattern of cervical lymph node metastases","volume":"48","author":"Harada","year":"2002","journal-title":"Jpn. J. Oral. Maxillofac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/hed.23945","article-title":"Analysis of sentinel node biopsy combined with other diagnostic tools in staging cN0 head and neck cancer: A diagnostic meta-analysis","volume":"38","author":"Liao","year":"2016","journal-title":"Head Neck"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0002-9610(86)90303-X","article-title":"Relation of thickness of floor of mouth stage I and II cancers to regional metastasis","volume":"152","author":"Sobel","year":"1986","journal-title":"Am. J. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0002-9610(86)90302-8","article-title":"Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth","volume":"152","author":"Spiro","year":"1986","journal-title":"Am. J. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.otohns.2004.04.008","article-title":"Multivariate predictors of occult neck metastasis in early oral tongue cancer","volume":"131","author":"Sparano","year":"2004","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S1368-8375(02)00142-2","article-title":"Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer","volume":"39","author":"Charoenrat","year":"2003","journal-title":"Oral. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/(SICI)1097-0347(199705)19:3<205::AID-HED7>3.0.CO;2-6","article-title":"Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma","volume":"19","author":"Fukano","year":"1997","journal-title":"Head Neck"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/hed.10130","article-title":"Risk factors for late cervical lymph node metastases in patients with stage I or II carcinoma of the tongue","volume":"24","author":"Kurokawa","year":"2002","journal-title":"Head Neck"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1002\/(SICI)1097-0142(19980415)82:8<1443::AID-CNCR2>3.0.CO;2-A","article-title":"Tumor thickness predicts cervical metastasis in patients with stage I\/II carcinoma of the tongue","volume":"82","author":"Asakage","year":"1998","journal-title":"Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1368-8375(01)00081-1","article-title":"Importance of tumour thickness measurement in prognosis of tongue cancer","volume":"38","author":"Esteban","year":"2002","journal-title":"Oral. Oncol."},{"key":"ref_31","first-page":"425","article-title":"Appropriate area of selective neck dissection for tongue carcinoma","volume":"38","author":"Shimbashi","year":"2012","journal-title":"Head Neck Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Iandelli, A., Marchi, F., Chen, A.C., Young, C.K., Liao, C.T., Tsao, C.K., Kang, C.J., Wang, H.M., Chang, T.J., and Huang, S.F. (2022). Adequacy of Disease Control by Supraomohyoid Neck Dissection in cT1\/T2 Tongue Cancer. J. Pers. Med., 12.","DOI":"10.3390\/jpm12091535"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e6894","DOI":"10.1002\/cam4.6894","article-title":"Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?","volume":"13","author":"Chen","year":"2024","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"106366","DOI":"10.1016\/j.oraloncology.2023.106366","article-title":"Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study","volume":"140","author":"Chien","year":"2023","journal-title":"Oral. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/hed.23494","article-title":"Prospective study of 583 neck dissections in oral cancers: Implications for clinical practice","volume":"36","author":"Pantvaidya","year":"2014","journal-title":"Head Neck"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jcms.2020.06.004","article-title":"Management of the clinically N (0) neck in early-stage oral squamous cell carcinoma (OSCC). An EACMFS position paper","volume":"48","author":"Vassiliou","year":"2020","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1177\/0194599812439664","article-title":"Isolated skip nodal metastasis is rare in T1 and T2 oral tongue squamous cell carcinoma","volume":"147","author":"Balasubramanian","year":"2012","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"(1998). Results of a prospective trial on elective modified radical classical versus supraomohyoid neck dissection in the management of oral squamous carcinoma. Brazilian Head and Neck Cancer Study Group. Am. J. Surg., 176, 422\u2013427.","DOI":"10.1016\/S0002-9610(98)00230-X"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/1097-0142(197206)29:6<1446::AID-CNCR2820290604>3.0.CO;2-C","article-title":"Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts","volume":"29","author":"Lindberg","year":"1972","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.bjoms.2011.09.007","article-title":"A double blind randomised trial of IIb or not IIb neck dissections on electromyography, clinical examination, and questionnaire-based outcomes: A feasibility study","volume":"50","author":"Parikh","year":"2012","journal-title":"Br. J. Oral. Maxillofac. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1159\/000091209","article-title":"Accessory nerve function in lateral selective neck dissection with undissected level IIb","volume":"68","author":"Inal","year":"2006","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck","volume":"350","author":"Cooper","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_43","first-page":"e9316","article-title":"Prognostic Role of Tumor Budding in Carcinoma Tongue: A Systemic Review and Meta-Analysis","volume":"12","author":"Karjol","year":"2020","journal-title":"Cureus"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E1582","DOI":"10.1002\/hed.24282","article-title":"Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth","volume":"38","author":"Seki","year":"2016","journal-title":"Head Neck"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1177\/1066896914565022","article-title":"Tumor budding is an independent prognostic factor for prediction of lymph node metastasis in oral squamous cell carcinoma","volume":"23","author":"Angadi","year":"2015","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5794\/jjoms.64.48","article-title":"Clinical study of tumor budding as a predictive factor of occult lymph node metastasis in stage I to II Squamous cell carcinoma of the tongue","volume":"64","author":"Sekikawa","year":"2018","journal-title":"Jpn. J. Oral. Maxillofac. Surg."},{"key":"ref_47","first-page":"S45","article-title":"The treatment for cwevical lymph node with stage II tongue cancer","volume":"55","author":"Asakage","year":"2009","journal-title":"Otologia Fukuoka"},{"key":"ref_48","first-page":"1","article-title":"Depth of invasion (DOI) introduced in UICC 8th T classification in tongue carcinoma\u2014Evaluation of histopathological DOI and clinical DOI in consideration of shrinkage rate of the specimen","volume":"45","author":"Harada","year":"2019","journal-title":"Head Neck Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5843\/jsot.24.129","article-title":"IzunoT: Evaluation of tumor extension in tongue cancer by ultrasound: Comparison of ultrasound images and histological findings in living and fresh material","volume":"24","author":"Ishii","year":"2012","journal-title":"J. Jpn. Soc. Oral. Tumors"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e059615","DOI":"10.1136\/bmjopen-2021-059615","article-title":"Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)","volume":"12","author":"Yanamoto","year":"2022","journal-title":"BMJ Open"},{"key":"ref_51","first-page":"1105","article-title":"Randomized phase III study to evaluate the value of omission of prophylactic neck dissection for stage I\/II tongue cancer: Japan Clinical Oncology Group study (JCOG1601, RESPOND)","volume":"48","author":"Tanaka","year":"2018","journal-title":"Jpn. J. Clin. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/4\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:57:00Z","timestamp":1760104620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/4\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["jcm13040976"],"URL":"https:\/\/doi.org\/10.3390\/jcm13040976","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}