Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology Review Intraoral ultrasonography to measure tumor thickness of oral cancer: A systematic review and meta-analysis Thomas J.W. Klein Nulent a,b, ⁎ ,1 , Rob Noorlag a,b,1 , Ellen M. Van Cann a,b , Frank A. Pameijer c , Stefan M. Willems d , Adrian Yesuratnam e , Antoine J.W.P. Rosenberg a , Remco de Bree b , Robert J.J. van Es a,b a Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands b Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands c Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands d Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands e Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia ARTICLE INFO Keywords: Head and neck squamous cell carcinoma Oral cancer Tongue cancer Ultrasonography Ultrasound Histopathology Resection margin Tumor thickness Depth of invasion ABSTRACT Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo) radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT- stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer. Introduction Head and neck cancer is the sixth most common malignancy worldwide of which approximately one third consists of oral squamous cell carcinoma (OSCC) [1,2]. For early OSCC (Stage I-II), surgery is the preferred treatment choice. Its complete removal is essential for lo- coregional control and disease-free survival [3]. Most authors agree that adequate histopathological resection margins are crucial, although it is debated how wide surgical margins should be [4–9]. For all T- stages, free margins of at least 5 mm to the tumor invasive front are accepted as “negative” resection margins. Resection margins between 1 and 5 mm are considered “close” and resection margins less than 1 mm “positive”. In early OSCC a 3 mm clear margin proves to be as safe as 5 mm [4,9]. “Unfavorable growth patterns” of the tumor front, such as non-co- hesive growth, perineural invasion and lymphovascular invasion may increase the risk of residual microscopic disease. Re-resection or ad- juvant (chemo)radiation is indicated in case of positive resection mar- gins and/or close margins in combination with one or more unfavorable growth patterns. Routine clinical follow-up is justified in case of ne- gative margins and close margins without unfavorable growth patterns [10]. Adjuvant radiotherapy may cause significant morbidity and (oral) discomfort affecting quality of life: patients may experience acute and https://doi.org/10.1016/j.oraloncology.2017.12.007 Received 18 August 2017; Received in revised form 20 November 2017; Accepted 9 December 2017 ⁎ Corresponding author at: Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, G05.129, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. 1 Contributed equally to this work. E-mail address: t.j.w.kleinnulent@umcutrecht.nl (T.J.W. Klein Nulent). Oral Oncology 77 (2018) 29–36 1368-8375/ © 2017 Elsevier Ltd. All rights reserved. T