**1. Introduction**

122 Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

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Yu E, O'Sullivan B, Kim J, Siu L, Bartlett E (2010). Magnetic resonance imaging of nasopharyngeal carcinoma. *Expert Rev. Anticancer Ther.* 10(3): 365-375. Yu MC, Mo CC, Chong WX *et al*. Preserved foods and nasopharyngeal carcinoma: a case–

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necrosis and extracapsular spread in cervical lymph nodes: MR imaging versus CT.

between PET/CT and MRI in diagnosing lymph node metastasis and N staging of

The incidence of cranial nerve (CN) palsy is not uncommon in patients with untreated nasopharyngeal cancer (NPC). In the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, the AJCC recommended that CN involvement be assessed by neurological evaluation rather than by cross-sectional imaging (computed tomography [CT] and magnetic resonance imaging [MRI]), because CN involvement is considered a poor prognostic indicator in NPC patients, those with CN involvement are staged as T4.

However, evaluation of CN palsy by clinical symptoms and physical examination has limitations. First, the accuracy of the neurological examination depends on the expertise of the examiner and the subjective report of the patient. Second, because CN involvement may be asymptomatic, it is difficult to diagnose CN palsy at an early stage by clinical neurological evaluation. In addition, neurological evaluation is not an optimal diagnostic method for assessing lesion localization and extension, which are critical factors in planning treatment, particularly in delineation of target volume.

With the excellent soft tissue contrast resolution and multiplanar imaging capability of MRI, direct visualization of smaller nerves and nerve branches is possible, making MRI a valuable tool in detecting and defining the extent of CN involvement in NPC. The difference and relationship between MRI findings of CN involvement and the symptoms and signs of CN dysfunction have not been fully addressed.

The goal of this study was to detect the difference and relationship between MRI findings suggestive of CN involvement and the symptoms and signs of CN dysfunction, and to evaluate the prognostic value of MRI-detected CN involvement in a large sample of consecutive patients. These information may contribute to understanding the patterns of spread and biological nature of NPC, and may also prove references in tumor staging and treatment planning.

#### **2. Patients and methods**

**Patients:** From January 2003 to December 2004, 924 consecutive patients with newly diagnosed untreated NPC were included in our study. There were 685 male patients and 239 female patients, with a male-female ratio of 2.9:1, and the median age was 45 years (range, 11-78 years). All patients had a pretreatment evaluation that consisted of a

MRI-Detected Cranial Nerve Involvement in Nasopharyngeal Carcinoma 125

as T4 [4]. Thus, all MRI findings that were suggestive of CN involvement were classified

into 2 categories: 1) extracranial or basicranial or 2) intracranial or orbital.

Fig. 1. A palsied cranial nerve V3. The enhanced coronal T1-weighted coronal fat

**2.2 Treatment** 

previously [5-7].

persisted despite therapy.

suppression image at the level of the foramen ovale shows the enhancing tumor extending intracranially via the enlarged right foramen ovale along V3 and into the trigeminal cistern.

All patients were treated by definitive-intent radiation therapy. Our policy was to cover the nasopharynx and the retropharyngeal lymph nodes within the primary target in every radical attempt, and to treat patients with gross lymphadenopathy with whole-neck irradiation. Most patients (773 of 924 or 83.7%) were treated with conventional techniques, 12.7% (118 of 924) with intensity-modulated radiation therapy (IMRT), and 3.6% (33 of 924) with 3-dimensional conformal radiation therapy (3-DCRT). Details regarding the radiation therapy techniques at the Cancer Center of Sun Yat-sen University have been reported

Most patients (517 of 629 or 82.2%) with stage III or stage IV disease (classified as T3-T4 or N2-N3) received neoadjuvant (137 of 629 or 21.8%), concomitant (374 of 629 or 59.5%), or adjuvant chemotherapy (6 of 629 or 1.0%), in conjunction with a platinum-based therapeutic clinical trial. When possible, salvage treatments (including afterloading, surgery, and chemotherapy) were provided in the event of documented relapse or when the disease

complete history, physical and neurologic examination, hematology and biochemistry profiles, MRI scan of the neck and nasopharynx, chest radiography, and abdominal sonography. Medical records and imaging studies were reviewed retrospectively, and all patients were staged according to criteria in the 6th edition of the AJCC Cancer Staging Manua.

**Imaging Protocol:** MR scanning was performed with a 1.5-Tesla system (Signa CV/i, General Electric Healthcare) and a head and neck combined coil. The area from the suprasellar cistern to the inferior margin of the sternal end of the clavicle was examined. T1 weighted fast spin-echo images in the axial, coronal, and sagittal planes (repetition time of 500–600 milliseconds, echo time of 10–20 milliseconds, 5-mm slice thickness with 1-mm interslice gap for the axial plane, 6-mm slice thickness with 1-mm interslice gap for coronal and sagittal planes, and a 512\*512 matrix) and T2-weighted fast spinecho MR images in the axial plane (repetition time of 4000–6000 milliseconds, echo time of 95–110 milliseconds, 5 mm slice thickness with 1-mm interslice gap, and a 512\*512 matrix) were obtained before injection of contrast agent. After intravenous gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Magnevist, Schering, Berlin) injection at a dose of 0.1 mmol/kg of body weight, spin-echo T1-weighted axial and sagittal sequences, and spin-echo T1- weighted fatsuppressed coronal sequences were performed sequentially, with parameters similar to those used before Gd-DTPA injection.

#### **2.1 Image assessment and diagnostic criteria**

Medical records and imaging studies were retrospectively analyzed. Cranial nerve palsy was diagnosed separately by two radiation oncologists who were unaware of the clinical findings, and clinical nerve palsy was diagnosed by others on the basis of clinical symptoms and a physical examination before treatment. Any disagreements were resolved by consensus. Two radiologists specializing in head and neck cancers, who were unaware of the clinical findings, evaluated the MRI images separately. Any disagreements were resolved by consensus. Soft tissue tumor was observed as intermediate signal intensity on pre-Gd-DTPA T1- and T2-weighted images and an enhancing mass on post-Gd-DTPA T1 weighted images, replacing the normal anatomy of the structure. MRI-detected CN involvement had to meet one of the following criteria: 1) enhancement of soft tissue tumor along the course of the ipsilateral related nerve and replacing the normal structures of the CN on gadolinium-enhanced T1-weighted images [Fig.1]; or 2) perineural spread, defined as an enlargement or abnormal enhancement of the nerve, obliteration of the neural fat pads adjacent to the neurovascular foramina, and neuroforaminal enlargement [Fig.1] [1-3]. Because CNs in the parapharyngeal space could not be identified as isolated structures on MRI, parapharyngeal space invasion could not be regarded as evidence of CN involvement in our study.

MRI-detected CN involvement at the following sites were assessed: extracranial segment of the maxillary nerve (V3), pterygopalatine fossa, foramen rotundum, foramen ovale, jugular foramen, hypoglossal canal, inferior orbital fissure, orbital apex, superior orbital fissure, cavernous sinus segment of CNs III-VI, trigeminal ganglion, and CNs in the cistern. By AJCC criteria, parapharyngeal and skull base invasion were classified as T2 and T3, respectively, and intracranial, infratemporal, hypopharynx, or orbital disease was classified as T4 [4]. Thus, all MRI findings that were suggestive of CN involvement were classified into 2 categories: 1) extracranial or basicranial or 2) intracranial or orbital.

Fig. 1. A palsied cranial nerve V3. The enhanced coronal T1-weighted coronal fat suppression image at the level of the foramen ovale shows the enhancing tumor extending intracranially via the enlarged right foramen ovale along V3 and into the trigeminal cistern.
