Elsevier

Oral Oncology

Volume 44, Issue 11, November 2008, Pages 1067-1072
Oral Oncology

The prognostic significance of tumor vascular invasion and its association with plasma Epstein-Barr virus DNA, tumor volume and metabolic activity in locoregionally advanced nasopharyngeal carcinoma

https://doi.org/10.1016/j.oraloncology.2008.02.001Get rights and content

Summary

Parapharyngeal tumor invasion is a known predictor of distant recurrence in stage II–III nasopharyngeal carcinoma (NPC). This study evaluated the prognostic significance of parapharyngeal and cavernous sinus vascular invasion in stage III–IV NPC, and its association with plasma Epstein-Barr virus (pEBV) DNA, disease stage, tumor volume and metabolic activity. Eligible patients underwent magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) and blood sampling for pEBV DNA before undergoing concurrent chemoradiotherapy. Relationship between treatment outcome and tumor vascular invasion was analyzed using Cox regression. Logistic regression was used to analyze the association between vascular invasion and other cofactors. Fifty seven patients with predominantly T3–T4 or N2–N3 stage disease were enrolled. Parapharyngeal invasion was present in 56% and cavernous sinus invasion in 19% of tumors. Multivariate analysis showed that tumor vascular invasion did not predict treatment outcome, while tumor FDG-uptake was the only significant factor that predicted survival and recurrence. Tumor vascular invasion was associated with T-stage, but not pEBV DNA or tumor volume. Parapharyngeal and cavernous sinus invasion were not significant predictors of distant recurrence following chemoradiotherapy in our cohort with locoregionally advanced NPC.

Introduction

Phase III studies have consistently demonstrated that the addition of concurrent chemotherapy to radiotherapy (RT) improves treatment outcome in patients with stage III–IV nasopharyngeal carcinoma (American Joint Committee on Cancer, AJCC stage, 6th edition).1 Unfortunately 25–30% of such patients still develop distant recurrence,2, 3 thus early identification of patients who are at risk of such failures is an essential step towards improving existing treatments. Several factors have been linked to an increased risk of distant recurrence and these include advanced tumor (T)-stage, nodal (N)-stage, parapharyngeal tumor invasion and an elevated post-treatment level of plasma Epstein-Barr virus (pEBV) DNA.4, 5, 6, 7, 8 Other putative factors such as tumor volume9, 10 and F-18 fluorodeoxyglucose (FDG)-uptake of the primary tumor11 have been evaluated, but their association with distant recurrence is unclear.

Direct infiltration of the rich vascular network located at the parapharyngeal space and skull base has been proposed as a pathway for distant dissemination in NPC, and magnetic resonance imaging (MRI) is regarded as a modality of choice for assessing tumor invasion at these sites.12, 13 Parapharyngeal tumor invasion has been consistently shown to predict distant failure in patients with T2N014 or N1–2 NPC15 in retrospective studies. The cavernous sinus is also another highly vascularized area that may be involved in NPC, but little is known about its relationship with distant failure after chemoradiotherapy. This study focused predominantly on patients with locoregionally advanced NPC (e.g. N3–N4 or T3–T4) who were treated in a prospective trial of concurrent chemoradiotherapy. The primary objective was to determine if parapharyngeal and cavernous sinus tumor invasion might predict treatment outcome, and the secondary objective was to correlate the presence of tumor vascular invasion with other prognostic factors in NPC such as disease stage, pre-treatment level of pEBV DNA, primary tumor volume and metabolic activity in terms of FDG-uptake.

Section snippets

Patient selection

This study was conducted at the Prince of Wales Hospital (Hong Kong) where the ‘standard’ treatment for stage III–IV NPC is concurrent chemoradiotherapy with weekly cisplatin (intravenous, i.v., 40 mg/m2).16 Patients with stage T2b disease (i.e. parapharyngeal extension) are treated additionally with “parapharyngeal boost” of 14Gy/7 fractions if they received prior two-dimensional radiotherapy (2D-RT). Intracavitary brachytherapy boost is given to patients with stages T1 and 2a NPC, or those

Results

Fifty seven patients participated in this study and their characteristics are summarized in Table 1. Twenty-five patients were treated with concurrent chemoradiotherapy alone, while 32 patients received additional neoadjuvant cisplatin–docetaxel 19. Parapharyngeal tumor invasion was present on MRI in 32 (56%) patients, while cavernous sinus invasion was present in 11 patients (19%). Both parapharyngeal and cavernous sinus tumor invasion were present in 10 patients (17%). With a median follow-up

Discussion

Parapharyngeal tumor invasion is an important prognostic factor for patients with N-stage N0–N2 disease,14, 15and has been shown to predict the risk of distant recurrence in stage I–III NPC.15 In one study where MRI-staging was used in a group of patients who were analyzed as a low-risk (stage I–IIa) and intermediate-risk (stage IIb–III) group, the presence of parapharyngeal space and base of skull invasion was associated with a poorer 5-year metastasis-free survival.15 However, in the current

Conflict of Interest Statement

None declared.

References (26)

  • A.S. Allal et al.

    Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro-2-deoxy-d-glucose

    Int J Radiat Oncol Biol Phys

    (2004)
  • B.B. Ma et al.

    Systemic treatment strategies and therapeutic monitoring for advanced nasopharyngeal carcinoma

    Expert Rev Anticancer Ther

    (2006)
  • A.T. Chan et al.

    Concurrent chemotherapy–radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial

    J Clin Oncol

    (2002)
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