24 Recurrent Nasopharyngeal Carcinoma

William I. Wei and Anthony P. W. Yuen

Nasopharyngeal carcinoma (NPC) is a nonlymphomatous, squamous cell carcinoma that originates from the epithelial cells lining the pharyngeal recess located medial to the medial crura of the eustachian tube. This malignant disease is common in southern China, especially among Cantonese speakers. The incidence is around 25 cases per 100,000 population.1 NPC is radiosensitive; therefore, external radiotherapy is the primary treatment modality. As there is a high propensity for NPC to metastasize to cervical lymph nodes, the neck is always included in the irradiation field even when there is no clinical positive neck node. The nasopharynx and upper neck nodes are usually treated in one target volume, using two lateral opposing facial fields and one anterior facial field delivering a total of 60 to 70 Gy. In recent years, concurrent chemoradiation with cisplatinum (cisplatin), followed by three courses of adjuvant chemotherapy using cisplatinum and fluorouracil, has significantly improved both the 3-year progression-free survival and the 3-year overall survival.² The overall 5-year survival is stage dependent and ranges from 70 to 80% for stage I disease and 20 to 30% for stage IV disease.^3,4 In some patients, however, despite radical therapy with chemotherapy and radiation, the primary tumor persists or recurs. When the disease is localized in the nasopharynx, and in the absence of regional or distant metastasis, salvage therapy may be possible.

Assessment of Tumor

Salvage therapy is performed only after accurate assessment of the recurrent tumor. The choice of salvage treatment also depends on the findings of the assessment.

A metastatic work-up should be performed to ensure that the tumor is localized in the nasopharynx. The work-up should include a clinical examination, tests on blood biochemistry, such as liver and renal function tests, a chest x-ray, and, when indicated, a positron emission tomography of the body.

Assessment of a local tumor in the nasopharynx should be performed by an endoscopic examination to visualize its mucosal extent. Computed tomography is useful to evaluate the extent of bone erosion, especially at the skull base. Magnetic resonance imaging should also be performed to assess the three-dimensional extension of the tumor in the nasopharynx.

Options of Salvage Therapy

Re-irradiation

For re-irradiation to be effective, a radiotherapeutic dose of 60 Gy or more is required.⁵ Although the reported 5-year disease-free survival rate with re-irradiation ranges from 18.7 to 50%, the associated morbidities are significant. Trismus and the effects of cranial nerve damage can be incapacitating. Complications related to neuroendocrine damage and poor nonverbal memory recall have been reported.⁶ In a large retrospective review of treatment results after local recurrence, it was shown that successful local salvage was achieved in 32% of patients who received re-irradiation. The cumulative incidence of late post-re-irradiation sequelae was 24%, and the treatment mortality was 1.8%.⁷

To avoid the high incidence of complication resulting from re-irradiation brachytherapy, surgical resection and stereotactic radiosurgery can be considered for patients with relatively small and localized tumors.

Stereotactic Radiotherapy

Stereotactic radiotherapy for the management of recurrent NPC can achieve a local tumor control rate of 10 to 60%. However, only a small number of patients have been treated this way, and long-term follow-up data are not available.⁸ In the future, 3-D conformal radiotherapy, stereotactic radiotherapy, and intensity modulated radiotherapy may permit larger recurrent tumors to be treated with high conformity. This would allow dose escalation, better local control, and fewer complications.

Brachytherapy

When the recurrent cancer in the nasopharynx is small (< 2 cm diameter) and does not involve underlying bony structures, brachytherapy with split palate implantation of radioactive gold grains (Au¹⁹⁸) can achieve a good local tumor control rate.⁹ This technique involves splitting the palate under general anesthesia. The mucoperiosteum over the hard palate is then retracted to expose the tumor in the nasopharynx. This allows radioactive gold grains to be inserted accurately into the tumor under direct vision. The palatal wound is then closed in layers.¹⁰

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