Nasopharyngeal carcinoma (NPC) is the most commonly diagnosed head and neck cancer in Southeast Asia, with a reported annual incidence of 30-80 per 105
population in endemic regions [1
]. Like most other squamous cell carcinomas (SCC) of the head and neck primaries, lymphatic drainage of the nasopharynx is predominantly to the cervical lymph nodes. However, NPC has the highest preponderance for regional lymph node metastasis among head and neck SCC [2
]. Radiation has been the mainstay of definitive treatment for NPC. The fields of radiation therapy for NPC traditionally encompass the primary disease and involved neck nodes, as well as the entire draining lymphatic regions to the lower neck. In a retrospective study reported by Lee et al
, 57 (30%) of the 189 patients who did not receive elective neck irradiation subsequently developed cervical lymph node recurrence. However, none of the seven regionally treated patients relapsed [3
]. Results from this and other similar studies have led to the practice of empirical irradiation of the entire neck in treating NPC,[4
] regardless of the stage of NPC at diagnosis.
However, treatment of a large field to the neck is associated with substantial morbidities, both early and late: Early toxicities include brisk radiation dermatitis and odynophagia, especially if concurrent chemo-radiation is utilized; late toxicities may include neck fibrosis, lymphedema, brachial plexopathy, and thyroid dysfunction [5
]. The therapeutic ratio may be maintained or improved if selective neck irradiation can be safely implemented in patients with limited nodal disease burden. Such practice may improve the tolerability of radiation therapy, as well as the compliance and quality of life of the patients.
A more accurate definition of target volume of regional lymph node region in radiation therapy also becomes possible because of the significant improvements made in imaging technology. Compared to computed tomography (CT), magnetic resonance imaging (MRI) has improved soft tissue contrast and multi-planar capability [6
]. MRI scans have been shown to be particularly useful in the assessment of retropharyngeal and cervical lymphadenopathy [7
]. Ng et al found that the nodal status was changed from negative on CT to positive on MRI in 4 of 67 patients (6%). This led them to conclude that MRI allows more accurate evaluation of the extent of NPC than CT and should be the primary mode of investigation [8
]. Sakata et al also showed that MR was better than CT at identifying metastases to lymph nodes in the carotid and retropharyngeal spaces, with significant prognostic implications [9
]. Liao et al demonstrated a significant difference between CT and MRI in demonstrating involvement in the retropharyngeal lymph nodes (CT, 52.1% vs. MRI, 69.0%). MRI resulted in changes in 10.7% of N stage cases and 38.6% of clinical stage cases [6
]. A small study involving patients suspected of having NPC has demonstrated that MRI had a sensitivity of 100%, specificity of 95%, negative predictive value of 100%, positive predictive value of 43%, and an overall accuracy of 95% when verified with biopsy. (AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1288-91. Magnetic resonance imaging for the detection of nasopharyngeal carcinoma. King AD, Vlantis AC, Tsang RK, Gary TM, Au AK, Chan CY, Kok SY, Kwok WT, Lui HK, Ahuja AT) On the basis that MRI has a high overall accuracy rate, possesses good imaging characteristics, and is the current standard of care, we choose to focus our efforts on MRI for this study.
Advances in radiation therapy, including image guidance and intensity-modulated radiation therapy (IMRT), have also allowed oncologists to be highly selective and accurate in treatment delivery. In the IMRT era, it is often up to the clinical judgment of the radiation oncologist to decide how much of the neck to irradiate and to what dose [10
]. While a standardized atlas [11
] is already in routine clinical use for the delineation clinical target volumes in the neck, there is currently no consensus as to the optimal volume for elective irradiation of the neck for NPC, especially for patients with node negative disease.
Several authors have described the pattern of nodal metastases in NPC,[2
] with a common view that cervical node metastases appear to occur in an orderly fashion with infrequent skip metastases. However, the actual distribution of nodal metastases as described in terms of lymph node levels differs between studies. Additionally, the reported rate of "skip" metastases varies between studies, ranging from 0.5% to 7.9% [14
]. As such, we embarked on this review to examine the pattern and probability of regional node metastasis through a systematic analysis of published evidence using MRI for diagnosis and staging of NPC. Additionally, we sought to identify low risk regional node groups in NPC, thereby providing an evidence-based proposal for lymphatic target selection in conformal radiation therapy for NPC.