Disclosure N3 disease of the neck is defined as any single lymph node metastasis measuring more than 6 cm. History of the Procedure: Induction chemotherapy, followed by surgery, then radiation was a standard method of treatment for advanced cancer of the tonsil in the 1970s and early 1980s but is no longer used. Surgery followed by radiation is the currently preferred therapy (see Surgical therapy). Problem: A patient with N3 disease of the neck is automatically categorized as having stage IV disease, and the average 2-year survival rate, considering all head and neck sites, is approximately 20%. The goal of treatment in most patients with this degree of disease is palliation, but cure may still be possible. Clinical: Systematically approach the N3 neck to simplify management. The single factor that most influences the treatment plan is operability. Inoperable disease is almost synonymous with incurability and is a crucial consideration in decision making for these patients. Therefore, the first step in patient assessment is to determine operability of the N3 neck mass and the primary lesion. Physical examination findings of fixation and/or skin involvement suggest inoperability. Further evaluation with CT scanning may confirm physical examination findings of inoperability if carotid artery encasement is present. Inoperability may also be confirmed in the presence of paraspinous muscles or vertebral column invasion. MRI is preferred by some for delineating soft tissue involvement, but CT scanning is superior in assessment of bony invasion. Of course, imagery is not always accurate, and some tumors are found unresectable only upon surgery. In cases of mobile N3 neck mass or mobile N3 neck mass with skin involvement (both rare), surgery may be considered. Once operability has been determined, evaluate distant metastases. The presence of nodal metastases is the most significant prognostic factor in patients with head and neck cancer. Extracapsular spread has been found to decrease survival rates by 50%. Distant metastasis obviously is an ominous finding, especially when present at the time of diagnosis. A chest CT scan is recommended for advanced disease of the primary site (T4) or neck (N3). Isolated pulmonary metastases may be controlled easily by wide local excision, but make this decision with the patient's overall disease status in mind. Bone scans are not performed routinely and are recommended only with a history of bone pain.
Surgical treatment of the N3 neck is indicated in the following situations:
In cases of mobile N3 neck mass or mobile N3 neck mass with skin involvement (both rare), surgery may be considered. Radiation therapy for the N3 neck is indicated in the following situations:
Relevant Anatomy: See Surgical therapy. Contraindications: Physical findings of fixation and skin involvement suggest that the lesion is inoperable. CT scanning may confirm carotid artery encasement, indicating inoperability. Paraspinous muscle involvement or vertebral column invasion also indicates inoperability. |
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Lab Studies:
Imaging Studies:
Other Tests:
Diagnostic Procedures:
Medical therapy: Treat inoperable N3 metastases with concurrent radiation and chemotherapy. This has been found to be more effective than sequential therapy. If the patient has a partial response, salvage surgery is indicated if both the neck disease and the primary lesion are resectable. Surgical therapy: Operable N3 neck disease may be managed with surgery followed by radiation with or without chemotherapy. Surgery consists of management of the primary tumor and radical or extended neck dissection. Extended neck dissection includes resection of muscle, nerve, or cartilage in addition to structures encompassed by traditional radical neck dissection. Selective or functional neck dissections are rarely indicated in patients with N3 disease.
The current standard of treatment for advanced cancer of the tonsil is surgery (composite resection of the tonsil and neck contents) followed by radiation. If extracapsular spread is present, chemotherapy has been shown to improve the results when used with postoperative radiation. The role of combined-modality chemotherapy and radiation is under investigation (see Future and Controversies) but results in similar survival. Surgical salvage is the next step for residual disease with or without brachytherapy.
Palliative neck dissection may be warranted in patients who have an unresectable primary tumor and a painful draining neck mass after treatment. Formal neck dissection is unnecessary in such patients, and removal of most of the tumor bulk and draining sinuses is often sufficient to bring relief. Patients with a complete response may be observed, although neck dissection may be useful for persistent abnormalities and operable recurrences. Preoperative details: Consider the primary site during treatment planning. Generally, primary site management dictates the plan for the neck. N3 neck disease control is difficult and should be a primary focus of the therapeutic plan. Radiation alone is generally not effective against the bulk of disease unless concomitant chemotherapy is used. If a curative approach is taken, residual neck disease can be resected following treatment of the primary site with chemotherapy and radiation. Direct palliative surgery for N3 disease at local and regional control. Specifically, if the neck mass were painful or difficult to care for (eg, drainage, infection, bleeding unresponsive to conservative measures of wound care), a patient with an inoperable primary tumor may be a candidate for a palliative neck dissection. Carefully weigh the risks of creating a worse wound and having the patient hospitalized for his or her remaining life against potential quality-of-life improvements. Postoperative details: Use radiation postoperatively for patients with operable N3 neck disease. Preliminary studies indicate that chemotherapy may improve results in patients with advanced neck disease. Patients' general conditions limit routine use of chemotherapy with radiation, and many patients who are elderly, immunocompromised, or malnourished may not be candidates for adjuvant therapy.
Complications of treating N3 neck disease include skin breakdown and carotid artery rupture. Skin breakdown may occur secondary to extensive radiation and tumor growth. Skin breakdown may pose significant morbidity to the patient and results in pain, drainage, complex wound care, and carotid artery exposure. If the carotid artery is exposed, coverage is usually necessary and may be obtained with a regional muscle flap, dermal graft, or myocutaneous flap. Family members often find that skin breakdown and drainage are difficult problems to tend to, and professional nursing help is often required for wound care. Discuss end-of-life issues with patients and their families. Consider a hospice role early once cure is not the goal. Carotid artery rupture is a dreaded complication of advanced neck disease. Rupture may be preceded by a sentinel bleed, wherein a patient has a short-lived episode of bleeding from the mouth, neck, or stoma. After bleeding subsides, all may appear to be well, but hospitalized patients may need to be placed on carotid artery rupture precautions if resuscitation attempts have not been refused. Precautions include a prepositioned stretcher to quickly bring the patient to the operating room (OR) and rolled-gauze bandages to obtain adequate pressure on the artery. Postpone attempts to clamp the vessel until the patient reaches the OR. The appropriate sequence of events in management of carotid artery blowout is (1) apply pressure, (2) transfer to the OR, and (3) obtain proximal and distal control.
Outcome in patients with N3 neck disease is poor, despite advances in treatment of head and neck cancer. Average cure rate varies from 10-20%, with most patients living only 8-12 months after presentation. Results in patients undergoing successful carotid artery resection are slightly better. Although the overall survival rate in this group is only 20%, a significant number of patients survive 2 years after treatment. Survival results of brachytherapy used for microscopic residual disease reach 30%, but when gross disease is not considered, control rates drop to less than 20%. Cure is not always the focus of treating the N3 neck. In these patients, the goal is often palliation, which is usually achievable if the clinician considers available treatments.
Specific issues regarding management of the N3 neck include extended neck dissection, brachytherapy, and investigational therapy. Anatomic structures that limit operability include the carotid artery, paraspinous muscles, and cranial nerves. Carotid artery resection has long been controversial. A recent study has shown no survival improvement in patients undergoing this procedure, but local/regional disease control is reasonable. Other studies have noted favorable survival rates but admit that vascular reconstruction is absolutely necessary to avoid catastrophic neurologic complications. Resection of the deep muscles of the neck leads to significant morbidity (eg, pain, decreased range of motion, possible brachial plexus injury) and has not been demonstrated to increase survival. Although sacrifice of cranial nerves is not uncommon during neck dissection for advanced disease, carefully consider this prior to resection. While the patient may be able to accommodate loss of the vagus, additional loss of the ipsilateral hypoglossal nerve may lead to intractable dysphagia and aspiration. This is an extremely important point for these patients because the goal in palliation is to alleviate suffering and not to increase morbidity. Brachytherapy is the administration of radiation through small catheters placed through the tumor bed. Brachytherapy allows a patient already treated with external beam radiation to receive additional radiation by delivering doses directly to the tumor while sparing surrounding normal tissues. Brachytherapy may be used in patients with minimal residual disease at the time of neck dissection. Implanting iodine or other high-activity seeds intraoperatively may also be considered. Brachytherapy offers improved local control and has been demonstrated to have little deleterious effect on the carotid artery. Investigational therapy is particularly applicable to patients with N3 disease. New chemotherapeutic agents and gene therapy are currently the most commonly used experimental methods of treating inoperable neck disease. New compounds directed against epithelial growth factor and angiogenesis are currently being used in trials at many hospital cancer centers. Gene therapy targets gene mutations in tumors, specifically the TP53 tumor suppressor gene. This gene is missing in 55% of patients with head and neck cancer. Gene therapy involves introducing a copy of a normal or wild-type TP53 gene into the tumor's DNA via a viral transvector. Unfortunately, gene therapy has not yet had a significant impact on controlling advanced disease. The complex nature of tumorigenesis, which may be controlled by multiple genetic defects, probably will not be halted by altering a single gene. Also, as of yet, a systematic method to administer the normal TP53 gene is not possible, and many patients succumb to distant metastases. However, the role of gene therapy in head and neck cancer is important to improve understanding of this disease and to progress toward an effective treatment in the future.
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