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
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)
- et al.
Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography
Int J Radiat Oncol Biol Phys
(1996) - et al.
Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure
Int J Radiat Oncol Biol Phys
(1992) - et al.
Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
(2006) - et al.
Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control
Int J Radiat Oncol Biol Phys
(2004) - et al.
Pretreatment F-18 fluorodeoxyglucose-positron emission tomography standardized uptake value predicts survival after radiation therapy in nasopharyngeal carcinoma
Proc Am Soc Ther Radio Oncol 49th Ann Meeting
(2007) - et al.
Paranasal sinuses and nasopharynx CT and MRI
Eur J Radiol
(2000) - et al.
Paranasopharyngeal space involvement in nasopharyngeal cancer: detection by CT and MRI
Clin Oncol (R Coll Radiol)
(2000) - et al.
The prognostic significance of parapharyngeal tumour involvement in nasopharyngeal carcinoma
Radiother Oncol
(1996) - et al.
Prognostic significance of parapharyngeal space venous plexus and marrow involvement: potential landmarks of dissemination for stage I–III nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
(2005) - et al.
Improved local control for early T-stage nasopharyngeal carcinoma – a tale of two hospitals
Radiother Oncol
(2000)
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
Systemic treatment strategies and therapeutic monitoring for advanced nasopharyngeal carcinoma
Expert Rev Anticancer Ther
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
Cited by (17)
Correlation of PET-CT, MRI and histopathology findings in the follow-up of patients with nasopharyngeal cancer
2021, Brazilian Journal of OtorhinolaryngologyCitation Excerpt :MRI is an invaluable diagnostic tool due to its ability to evaluate soft tissue with ideal contrast and resolution without reliance on radioactivity. However, it is not always reliable in the evaluation of residual disease, recurrence and post-chemoradiotherapy fibrosis.4 18f-FDG PET/CT imaging is a technology that eliminates the need for plain radiography, ultrasound, (CT) and bone-scan combinations.
Prediction of distant metastases from nasopharyngeal carcinoma: Improved diagnostic performance of MRI using nodal volume in N1 and N2 stage disease
2017, Oral OncologyCitation Excerpt :One possible explanation for the low sensitivity is that the current staging system is unable to take into account bulky N1 (unilateral) or N2 (bilateral) disease where patients have multiple nodes but none of these reach the 6 cm threshold for N3 disease. In this situation nodal volume (NV) may be a more valuable indicator of nodal size than unidimensional measurements, but NV is under reported [19–22,26,27] and only one study has found NV to be an independent predictor of distant metastases free survival (DMFS) [27]. It is also important to note that imaging parameters currently used to identify patients at risk of DM at presentation, were derived from clinical trials which assessed the effect of treatment on DMFS and therefore tended to exclude patients with DM at presentation from their analyses.
Prognostic efficacy of combining tumor volume with Epstein-Barr virus DNA in patients treated with intensity-modulated radiotherapy for nasopharyngeal carcinoma
2016, Oral OncologyCitation Excerpt :To date, there have been three series of studies on the relationship between pre-treatment EBV DNA and tumor volume [21–23]. The first study of 57 patients with advanced NPC who were treated with 2D-RT, found a positive correlation between pre-treatment plasma EBV DNA levels and tumor volumes delineated in diagnostic MRI [21,24]. A more recent study of 165 cases with NPC treated with IMRT confirmed this conclusion [22].
Updates on MR imaging and <sup>18</sup>F-FDG PET/CT imaging in nasopharyngeal carcinoma
2014, Oral OncologyCitation Excerpt :18F-FDG PET/CT imaging has the advantage of combined anatomic and functional information in one examination, precluding the need of a combination of plain radiograph, ultrasound, computed tomography (CT) and bone scan. Indeed, it helps to improve the overall survival especially in patients with advanced-stage disease due to better delineation of initial disease extent, better irradiation planning and better treatment delivery.1,2 In this article, we will review the roles of MR and 18F-FDG PET/CT imaging in the diagnosis, staging, treatment monitoring and post-treatment assessment of NPC.
The role of pretreatment FDG-PET in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy
2012, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :However, similar to the results of multivariate analysis, SUVmax could not predict any differences within the T categories for overall survival. Most previous studies did not evaluate the role of SUVmax within the T stage (11, 15, 16, 26, 27). On the basis of our findings and other studies with similar results, SUVmax is a potential indicator for tailoring the treatment policy for higher-risk NPC patients.