Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging

Abstract

Objective: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC.

Methods: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method.

Results: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001).

Conclusions: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging.

Clinical relevance statement: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning.

Key points: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

Keywords: Depth of invasion; Magnetic resonance imaging; Squamous cell carcinoma; Tongue cancer; Tumor thickness.

Fig. 1

Study flowchart. Flowchart depicting (A) inclusion and exclusion criteria of the patients and (B) statistical steps for determining the optimal MR measurement through multiple MR sequences for non-pT4 OTSCC primary tumor staging. Abbreviations: KM, Kaplan–Meier; DCA, decision curve analysis; RCS, restricted cubic spline; CE, contrast-enhanced; OTSCC, oral tongue squamous cell carcinoma; rDOI, radiological depth of invasion; rTT, radiological tumor thickness; LD, longest diameter

Fig. 2

Diagram of tumor location, morphology, and corresponding MR images and pathology. For tumor location (A1–A3), we defined tip (asterisk), dorsum (thick arrow), ventral (arrowhead), and lateral (thin arrow) parts on sagittal, coronal, and axial views of MR according to anatomic criteria, respectively. For tumor morphology (B1–B3), the diagram depicts the measurement of rTT, rDOI, and LD in flat, ulcerative, and exophytic types, respectively. The red line refers to the measurement of rDOI from the vertical distance between the simulated normal mucosal junction to the deepest point of tumor infiltration. The black line refers to measurement of rTT by drawing a vertical line from the tumor surface to the deepest point of infiltration. In the following columns (C1–C3), the short red arrow refers to the lesions of corresponding morphology on the MR imaging, and the long black arrow refers to the pDOI on histological sections (D1–D3). Specifically for the histological sections, the short black arrow refers to the level of epithelial basement membrane but no DOI was obtained due to the AJCC criteria (D3). Abbreviations: DOI, depth of invasion; LD, longest diameter; rDOI, radiological depth of invasion; rTT, radiological tumor thickness; AJCC, American Joint Committee on Cancer

Fig. 3

Diagram of tumor measurement of different morphologies. Upper (A1–A4), middle (B1–B4), and lower (C1–C4) row from left to right using black, red, and white dashed line representing measurement of rTT, rDOI, and LD in flat, ulcerative, and exophytic case on axial T2WI, and axial, fat-suppressed coronal, and sagittal CE-T1WI sequence, respectively. Yellow line represents the simulated normal mucosal junction. Abbreviations: rTT, radiological tumor thickness; rDOI, radiological depth of invasion; LD, largest diameter

Fig. 4

Graphical representation of rDOI, rTT, and LD measurements per sequence and correlation with pDOI. A Boxes show the upper and lower quartiles, and horizontal lines within boxes represent median values. Whiskers represent the 95th and 5th percentiles, and the jittering dot indicates the MR measurement for each patient. All measurements were significantly larger than pDOI. B The correlation coefficient between pDOI and each MR measurement. C–E Bland–Altman plots showing the agreement between pDOI and rDOIs. Dashed horizontal lines represent the mean bias, and top and bottom dashed lines represent the upper and lower limits of agreement, respectively. Abbreviations: pDOI, pathological depth of invasion; rDOI, radiological depth of invasion; LD, longest diameter; TT, tumor thickness; aT2WI, axial T2WI; aCE-T1WI, axial contrast-enhanced T1WI; cCE-T1WI, coronal fat-suppressed CE-T1WI; sCE-T1WI, sagittal CE-T1WI

Fig. 5

Kaplan–Meier overall survival (OS) curves. Kaplan–Meier curves of OS according to the current pDOI category and proposed optimal MR measurement category in patients with non-pT4 OTSCC. A Current pDOI category. B Proposed optimal MR measurement category. Abbreviations: OS, overall survival; OTSCC, oral tongue squamous cell carcinoma; pDOI, pathological depth of invasion; rDOI, radiological depth of invasion; aCE-T1WI, axial contrast-enhanced T1WI