Nasopharyngeal cancer: Impact of skull base invasion on patients prognosis and its potential implications on TNM staging

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Abstract

Purpose

To evaluate patterns of skull base invasion and its possible impact on tumor (T)-staging in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI).

Materials and methods

838 consecutive newly diagnosed by biopsy proven and untreated patients with NPC underwent MRI. The skull-base invasion of NPC was classified according to their incidence from proximal sites to more distant sites surrounding the nasopharynx as: high (≥35%), medium (≥5–35%), and low (<5%) groups. A retrospective analysis of data consisting of a 5-year follow-up was carried out. The skull base invasion was related to their tumor (T) staging and prognosis at the 5-year follow-up after treatment with definitive radiation therapy. In addition, a survival health-related quality of life (QOL), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were also assessed among the three groups.

Results

The total incidence of skull-base invasion was 65.51% (549/838). The differences in T-stage distribution, and the total survival health-related QOL, among the three groups were statistically significant (χ2 = 160.45, p < 0.005; χ2 = 38.43, p < 0.005, respectively). The differences between any two of the three groups were also significant, except when the medium grade was compared to the low grade. Significant differences were observed with regard to 5-year OS (83.2%, 74.7%, 59.2%, p = 0.000) and DMFS (95.0%, 88.0%, 88.0%, p = 0.016); no significant difference was observed in LRFS (95.3%, 95.6%, 91.23%, p = 0.450).

Conclusions

The results indicate that medium and low group displayed similar findings of skull base invasion, and survival status. We, therefore, propose that patients in these two groups be grouped under T4 in the TNM classification that might have a bearing in implementing optimum treatment.

Introduction

Nasopharyngeal carcinoma (NPC) is unique in its prevalence in China, being common in southern China compared to other regions. Because of its deep and hidden anatomical location, the infiltrating ability of the tumor, and the non-specific nature of symptoms, NPC is not diagnosed until it has reached an advanced stage [1]. NPC usually originates in the lateral wall of the nasopharynx and can then extend to the other lateral wall, posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx.

Skull base invasion may affect 25–63% of patients with NPC [2], [3], [4]. Skull base invasion represents one of the poor prognostic factors in NPC, and hence accurate evaluation of skull base invasion is needed, when present [5], [6], [7], [8], [9], [10], [11]. The recent (7th edition) American Joint Committee on Cancer and the International Union for Cancer Control update on the tumor-node-metastasis (TNM) cancer staging designates [12], skull base and/or paranasal sinus invasion without cranial nerve (CN) deficits as stage T3. This classification has become effective for cancers diagnosed on or after January 1, 2010. There might still be scope to offer evidence to further modify this classification.

It has been reported that 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) and PET/CT play important roles in the staging, treatment planning, and detecting local recurrence of NPC [13], [14]. However, 18F-FDG PET/CT lacks sensitivity for the T staging of locally advanced NPC, especially in the delineation of skull base and intracranial erosion compared with magnetic resonance imaging (MRI) [15], [16]. In recent studies on NPC, magnetic resonance imaging (MRI) has been shown to be better than other imaging modalities for evaluation of tumor invasion as the technique offers ideal soft tissue contrast and multi-planar imaging capability [17], [18]. With gadolinium contrast and fat suppression sequences, it has greater sensitivity and specificity over other imaging methods in detecting skull-base invasion and perineural invasion.

The purpose of this study was to retrospectively analyze MRI findings and clinical reports of patients with NPC with skull-base invasion, and stage their tumors (T stage) into three groups according to their anatomic sites and assess their prognostic value. We hoped that this analysis might play a role in deciding an optimal treatment course.

Section snippets

Patient characteristics

This study was retrospectively designed. Institutional review board approval was obtained for this study, and informed consent was obtained from all patients or their next of kin.

From December 2002 to January 2005, 838 consecutive patients (641 men [mean age: 45.8 years; age range: 13–76 years], 197 women [mean age: 41.7 years; age range: 20–75 years]) with newly-biopsy proved, untreated, and non-disseminated NPC were enrolled in our study. Patients with additional, known head-and-neck cancers

Incidence and distribution of skull base erosions

Five hundred and forty-nine of the 838 patients with NPC (65.51%) met with our study inclusion criteria for skull base erosion on MRI. The most common site of bone invasion was the base of the sphenoid bone (511/549, 93.08%), followed by the base of pterygoid process (358/549, 65.21%). The grades (high, medium, and low) of the skull base invasion according to their anatomic site, and incidence are detailed in Table 1.

Comparison of T-stage among three groups

In the high group, T category distribution was as follows: T3 lesions, 190

Patterns of skull base invasion

Multiple earlier studies have reported that skull base erosion may be seen in 25–63% of cases [2], [3], [4], [19], [25]. Our analysis indicated the incidence of skull base invasion to be 65.51% (549/838), which is much higher. This may be because some of the earlier studies were based on CT scanning, and MRI was done without the use of fat saturation techniques, unlike the sensitive method used in our study cohort.

In our study, the high group (≥35%) included the base of the sphenoid bone,

Conclusions

In conclusion, the results of this retrospective analysis indicate that medium and low groups displayed similar findings of skull base invasion, and survival status. We, therefore, propose that patients in these two groups be grouped under T4 in the TNM classification that might have a bearing in implementing optimum treatment.

Author contribution

Yi-Zhuo Li, Pei-Qiang Cai, Pei-Hong Wu carried out the studies, participated in the sequence and drafted the manuscript. Chuan-Miao Xie, Zi-Lin Huang, Ci-Yong lu, Yao-Pai Wu participated in the design of the study and performed the statistical analysis. Yi-Zhuo Li, Li-Zhi Liu, Guo-Yi Zhang and Rui Zhong conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Conflicts of interest

None.

Acknowledgements

We thank our colleagues in the department of medical records and the institutional review board, who provided the follow-up data and approved this study.

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    These two authors contributed equally to this study.

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