Xing Yang1, Ke Xue2, Zhen Tian1, Jingbo Wang1, Yongming Dai2, and Yingwei Wu1
1Shanghai Ninth People’s Hospital, affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China, 2MR Collaboration, Central Research Institute, Shanghai United Imaging Healthcare, Shanghai, China
Synopsis
Keywords: Head & Neck/ENT, DSC & DCE Perfusion
Evaluating the heterogeneous characteristics and lymph
node metastasis status of the tumor would be of importance to stratify patients
to have the individually tailored management. In this study, we investigated
the feasibility of pixel-by-pixel TIC method in evaluating tumor heterogeneity
and predicting histological tumor grade and LNM in tongue SCC. We found that the
pixel-by-pixel TIC analysis approach allowed the detection of the internal
heterogeneity of the whole tumor. Ratio of Type 2 TIC pattern would facilitate
the distinction of SCCs with different histological grades and LNM status,
implying its tremendous potential in tumors with high heterogeneity.
Introduction
Tongue cancer is the most common type of Oral cavity cancer (OCC) in Asia,
and >90% of these cancers are squamous cell carcinomas (SCC)1. Although
tongue SCC arise in one histological type, the intra- and inter-individual
heterogeneity, has been proved to greatly contribute to the poor prognosis2.
Thus evaluating the heterogeneous characteristics and lymph node metastasis
(LNM) status of the tumor would be of importance to stratify patients to have
the individually tailored management3.
The overall semi-quantitative time-intensity curves (TIC) patterns derived
from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) have been proved
to be promising in differentiating tumors from benign to malignant ones or
predicting LNM4-6. However, this approach somehow led to the loss of
identification of intra-tumoral heterogeneity. In comparison, the voxel-based
TIC analysis is more spatial- and texture-oriented, where the analysis is not
averaged over a selected ROI but rendered in a pixel-by-pixel way7.
Thus,
the aim of our study was to determine whether the pixel-by-pixel TIC analysis
of DCE-MRI is better able to capture the heterogeneous of tongue SCC than the
overall TIC and investigate the feasibility of pixel-by-pixel TIC for
predicting histological tumor grade and LNM in tongue SCC.Methods
Totally 42 patients (23 patients with cervical lymph node metastases, 26 low
grade) with pathologically proven SCC were included. All MRI examinations
including T2-weighted imaging (T2WI), DWI and DCE-MRI were performed on a 1.5T
scanner (uMR560, United Imaging Healthcare,Shanghai,China) with a
twelve-channel head-neck coil.
Regions of interest (ROIs) were drawn on all slices of the tumor to gain
overall TIC curve type, excluding visually identifiable cystic and necrotic
areas. Besides, TIC shapes on a pixel-by-pixel basis for the whole tumor were
defined as the previous study4: Five types of TICs were determined based
on the enhancement ratio (ER), maximum time (MT), and washout ratio (WR)
values. Type 1 TICs are those with ERs ≤ 20%. Type 2 TICs are those with ERs ˃ 20%
and MTs ≥ 120s, Type 3 TICs are those having ERs ˃ 20%, with MTs < 120s and
with WRs < 30%. Type 4 TICs are those displaying ERs ˃ 20%, with MTs <
120s and with WRs ≥ 30% and < 70%. Type 5 TICs are those that were not
categorized into any of the above types. Then the total number of enhancing
pixels was calculated and the percentage of voxels expressing each TIC shape
type was calculated8.
The
Mann-Whitney U test or Chi-square test were performed to determine difference between
low-grade and high-grade and between with LNM and without LNM. Multivariate
binary logistic regression analysis was used to determine independent
predictors of tumor grade and LNM of tongue SCC. The capability in predicting
tumor grade and LNM was quantified by the receiver operating characteristic
(ROC) analysis. P-value of less than 0.05 indicated a significant difference.Results
For the overall TIC, there were no statistical differences in Types of TIC
patterns either between low- and high-grade groups or with different LMN status
(p= 0.072 and 0.508, respectively). While for the pixel-by-pixel TIC approch, a
significantly higher ratio of Type 2 TIC (0.49±0.13) and a lower ratio of Type
3 TIC (0.46±0.12) were observed in patients with low-grade SCC than those in
patients with high-grade (ratio of Type 2 TIC: 0.37±0.15 and ratio of Type 3
TIC: 0.55±0.15), with p=0.006, and 0.035, respectively (Figure 1). Besides, higher ratio of Type 3
TIC was seen in LNM+ patients than that in LNM- patients (0.54±0.13 vs.
0.45±0.13, p=0.032) (Figure 2).
Multivariate
logistic regression analysis revealed that only the ratio of Type 2 TIC pattern
was an independent predictor for histological tumor grade and LNM status (p =
0.004 and 0.036, respectively) with an odds ratio (OR) of 0.003 and 0.044. Moreover,
the ratio of Type 2 TIC yielded great discriminative ability in differentiating
low and high histological grade and the LNM, with AUC of 0.75 and 0.68,
respectively.Discussion
In this study, we used volume-based pixel-by-pixel TIC analysis approach
to assess the intra-tumor heterogeneity and determined whether the
semi-quantitative analysis way could help to predict the histological
tumor-grade and LNM status. As shown in our study, although the overall TIC
analysis displayed a single pattern of TIC type, the pixel-by-pixel analysis
showed the coexistence of heterogeneous patterns of TIC types within the tumor,
suggesting that this approach could detect tumor heterogeneity.
Moreover, the quantitative ratio of Type 2 TIC
pattern proved to be significantly discriminatory both in low and high
histological groups and lymph nodes with or without metastasis and was an
independent predictor for histological tumor grade and LNM status, which
indicating the prognostic value of the pixel-by-pixel TIC analysis. Conclusion
In summary, the pixel-by-pixel TIC analysis approach allows the detection
of the internal heterogeneity of the whole tumor. Ratio of Type 2 TIC pattern
would facilitate the distinction of SCCs with different histological grades and
LNM status, implying its tremendous potential in tumors with high
heterogeneity.Acknowledgements
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