Surgical Therapy
Metastases from squamous cell carcinoma of the upper aerodigestive tract have a predictable pattern. This fact has permitted modifications of the classic radical neck dissection described by Crile in the early 20th century. Knowledge of the patterns of cervical lymph node metastases has led to various neck dissections, including the modified radical neck dissection, extended radical neck dissection, and selective neck dissections, which include the supraomohyoid neck dissection, anterior compartment neck dissection, posterolateral neck dissection, and lateral neck dissection.
The classic radical neck dissection removes all of the ipsilateral lymph nodes, the submandibular salivary gland, sternocleidomastoid, internal jugular vein, and spinal accessory nerve. This is associated with multiple functional and cosmetic deformities. This is often combined with resection of the primary malignancy, which is achieved by several different approaches. A newer way of resecting some oral cavity, oropharyngeal, and hypopharyngeal primaries is through a transoral robotic surgical approach (TORS), which is actively being investigated at multiple centers.
Sacrifice of the spinal accessory nerve (cranial nerve XI) results in impaired shoulder movement and the potential development of a painful fixed shoulder from denervating the trapezius muscle.
Removal of the sternocleidomastoid muscle results in a cosmetic deformity, including flattening of the neck on the side of surgery. In most people, the removal of this muscle results in no real functional deficit.
Removal of the ipsilateral internal jugular vein is tolerated in most people, particularly with modern anesthetic techniques. In most patients, limiting intravenous hydration, both intraoperatively and postoperatively, is important to prevent a syndrome of inappropriate antidiuretic hormone secretion, which has been demonstrated to occur in patients undergoing surgery for head and neck malignancies. Collateral veins, contralaterally and retropharyngeally, prevent significant postoperative edema.
Removal of both internal jugular veins results in significant venous edema and chronic lymphedema of the face and can be fatal in 10% of patients when performed simultaneously. When bilateral jugular vein removal is necessary, stage the procedures at least 1 week apart to permit formation of these collaterals.
For these reasons, various modifications have supplanted most radical neck dissections. The modified neck dissection can preserve the internal jugular vein, the spinal accessory nerve, and the sternocleidomastoid muscle, provided that lymph nodes containing tumor are not violated.
Comparisons of the classic radical neck dissection with modified neck dissection have demonstrated that they are equally effective in controlling metastatic squamous cell carcinoma in patients with no clinical evidence of metastatic disease or with early metastatic disease. However, the functional neck dissection, in which the lymph nodes are removed, preserving the internal jugular vein, spinal accessory nerve, and sternocleidomastoid, [3] is not as effective for multiple cervical metastases or for bulky neck metastases. The radical neck dissection also is indicated if signs of extranodal spread involving the skin, carotid sheath, or deeper soft tissues of the neck are present.
Preoperative Details
The modified neck dissection is an oncologically sound concept. The regional lymph nodes at highest risk for metastasis from carcinomas of the upper aerodigestive tract are removed. It not only removes lymph nodes at risk, but it also allows for extensive pathologic evaluation of those lymph nodes. This enables the clinician to determine if adjuvant treatment, either in the form of radiation therapy or chemotherapy, is needed.
The suprahyoid neck dissection includes the submandibular salivary gland and the lymph nodes of the submandibular triangle. It has limited applicability and is usually reserved for a tumor believed to arise from the salivary gland.
The supraomohyoid neck dissection removes the submandibular salivary gland and the lymph nodes above the omohyoid muscle (levels I, II, III, V [upper part of posterior triangle]). This is particularly useful in treating carcinomas of the oral cavity.
The lateral neck dissection encompasses levels II, III, and IV and is applicable to carcinomas of the oropharynx, hypopharynx, and larynx.
The posterolateral neck dissection and suboccipital triangle lymph node dissection are useful in treating patients with primary carcinomas of the skin or with melanoma, particularly melanomas originating from behind the ear and the occipital scalp.
Other lymph node basins are at risk for metastasis depending on the site of the primary tumor. Periparotid lymph nodes are at risk for carcinomas of the facial skin. Paratracheal lymph nodes are at risk for carcinomas of the thyroid and subglottis. Retropharyngeal lymph nodes are at risk from carcinomas of the nasopharynx, oropharynx, hypopharynx, and the palate and base of the tongue. Metastases to the submental lymph nodes most likely are associated with cancer of the lower lip, floor of the mouth, anterior tongue, and buccal mucosa; include the submental triangle (level Ia) in a neck dissection performed for a carcinoma of one of these primary sites.
A retrospective study by Moratin et al found that ipsilateral and contralateral neck metastases can occur even in early stage (T1 and T2) squamous cell carcinoma of the tongue, with the rate of primary metastasis in the report’s patients being 28.6% for T1 neoplasms, and 22.4% for T2 lesions. The investigators cited this as evidence that elective bilateral neck dissection is important in such tongue cancers. [4]
Some evidence exists that carcinomas of the oral tongue can involve the inferior deep jugular lymph nodes (level IV) as skip metastases. Therefore, consider including this area in a neck dissection that includes levels I-III and is performed for cancer of the oral tongue.
Modified or selective neck dissections are not merely staging procedures. Certain patients with node-positive disease can be treated effectively with modified neck dissections, provided that postoperative radiation therapy is used. Postoperative radiation therapy further reduces the risk of regional failure following modified neck dissections. Indications for postoperative radiation therapy are several. Patients with invasive cancer at the surgical margin or a close margin have a much better prognosis with postoperative radiation therapy than do similar patients treated with surgery alone. Multiple positive lymph nodes in the surgical specimen also indicate postoperative radiation therapy. To summarize, concern on the part of the surgeon or pathologist about the margins is an indication for postoperative radiation therapy.
A retrospective study by Aboelkheir et al of patients with clinical metastatic mucosal primary squamous cell carcinoma to cervical lymph nodes indicated that with the administration of postoperative radiotherapy, with or without chemotherapy, to the primary tumor bed and neck, overall survival and disease-specific death rates do not differ significantly between patients who undergo selective neck dissection (SND) and those who are treated with comprehensive neck dissection (CND). The investigators found the 3-year overall survival rate in the SND group to be 51.8%, versus 61.1% in the CND group. Among the SND and CND patients who died, the disease-specific death rates were 74.1% and 71.4%, respectively. [5]
A discussion about radical neck dissection is not complete without addressing cutaneous malignancies of the head and neck as well as salivary gland malignancies. Although cutaneous squamous cell carcinomas of the head and neck rarely metastasize (and basal cell carcinomas even less frequently), occasionally they can metastasize, as can melanomas. Those lesions of the face in front of the tragus have a potential for metastasizing to the parotid (usually to intraparotid lymph nodes), and a parotidectomy should be considered in the treatment of these malignancies when radical neck dissection must be performed.
Primary malignancies of the parotid, submandibular, or sublingual salivary glands, as well as the minor salivary glands of the aerodigestive system, also may metastasize to the regional lymph nodes. Therefore, a high-grade malignancy of any of these salivary glands probably includes a regional lymphadenectomy with the resection of these primary tumors.
Intraoperative Details
Many different approaches to skin incisions are available in performing a neck dissection. Some surgeons prefer a single trifurcated incision to gain access to the lymph nodes, while others prefer a double trifurcated incision. Many prefer 2 parallel incisions (ie, MacFee incisions). These are more difficult to perform but afford an intact segment of skin and muscle to cover the carotid without placing any incisions directly over the great vessels, which may leave them vulnerable if poor wound healing occurs.
The standard neck dissection removes the fascia and lymphatics deep to the platysma en bloc. In many instances, dissecting along the spinal accessory nerve is important, liberating it from its fibrofatty envelope from the skull base to the point where it enters the sternocleidomastoid and to the point where it enters the trapezius. Often, lymph nodes at risk are present posterior to this nerve, which may be ignored if this skeletonization is not performed. Removal of the jugular vein on one side of the neck is well tolerated in most patients. Usually, sufficient collaterals are present, both retropharyngeally and contralaterally, to prevent significant brain edema.
If bilateral neck dissection is planned, either because of bilateral nodal disease or bilateral lymph nodes that are at risk for metastatic disease, performing a modified neck dissection is usually prudent, at least on the side of the lesser nodal disease, preserving the internal jugular vein. If this cannot be accomplished for oncologic reasons, perform bilateral neck dissections in a staged surgical procedure, preferably at least 1 week apart. This allows sufficient collaterals to develop and enlarge to prevent brain edema. Furthermore, instruct the anesthesiologist to limit the amount of fluid administered intraoperatively and postoperatively. Patients undergoing radical neck dissection can develop a syndrome of inappropriate antidiuretic hormone secretion. Limiting the administered fluid can help to prevent this as well as cardiac sequelae from fluid overload.
Intraoperative bradycardia from manipulation of the carotid bulb during neck dissection can be easily corrected in most instances with the administration of lidocaine by injection into the carotid bulb fascia.
Postoperatively, a closed suction drain is usually used to prevent fluid collections beneath the flaps and to allow skin flaps to adhere to the underlying structures.
Postoperative Details
See the list below:
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Hematoma formation, particularly when the primary tumor has been resected in conjunction with neck dissection, is potentially disastrous, since the hematoma frequently becomes infected and establishes the formation of a fistula from the aerodigestive tract to the skin.
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The risk of carotid artery rupture has been virtually eliminated because of several factors. Firstly, radiation therapy is usually administered postoperatively (within 4-6 wk of surgery), which allows for healing prior to the start of effects. Furthermore, the advent of muscle flaps that can cover the carotid artery, providing it with a healthy source of uninvolved, unirradiated tissue, has dramatically decreased the incidence of this devastating condition. Carotid rupture today, when it occurs, usually is preceded by a history of radiation therapy, tumor erosion into the carotid artery, and the development of a fistula to the aerodigestive tract. Unfortunately, this condition is almost always fatal.
Adjuvant radiotherapy and chemotherapy
See the list below:
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Radiation therapy for squamous cell carcinoma of the head and neck involves the delivery of high-energy ionizing radiation to targeted tissues. The radiation damages the DNA of targeted cells, mostly through the formation of free radicals. Cancerous cells, which often lack effective repair mechanisms, are less able to repair DNA damage than are normal cells. Following radiation therapy, cells that are unable to repair DNA damage effectively undergo cell death.
Radiation doses can be delivered by different methods, including fractionation, hyperfractionation, accelerated fractionation, and intensity-modulated radiation therapy (IMRT).
The goal of these methods is to deliver lethal radiation to cancer cells while limiting damage to adjacent healthy tissues.
One study suggests that the use of IMRT may significantly reduce the incidence of xerostomia, a common and significant side effect of radiation therapy, by sparing the parotid glands. [6]
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Chemotherapy for squamous cell carcinoma of the head and neck involves the systemic administration of cytotoxic drugs that target rapidly dividing cells.
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Individual chemotherapeutic agents effective in the therapy of head and neck cancer include cisplatin, methotrexate, 5-fluorouracil, taxanes, ifosfamide, and bleomycin, among others.
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The benefit of postoperative radiotherapy in the treatment of cervical lymphatics in advanced squamous cell carcinomas of the upper aerodigestive tract is well documented. [7]
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Traditionally, adjuvant radiation has been used after surgical resection for patients with advanced (stage III or IV) disease who are at particularly high risk of local and regional recurrence.
Factors that increase the risk for local and regional recurrence after surgical resection, neck dissection, or both include inadequate resection margins, involvement of multiple lymph nodes, and extranodal spread of the tumor.
Despite improved outcomes with surgery plus postoperative radiotherapy compared with surgery alone, the rates of local or regional recurrence, distant metastasis, and 5-year survival stand at 30%, 25%, and 40%, respectively.
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Several recent prospective trials now suggest that the addition of adjuvant cisplatin chemotherapy to postoperative radiotherapy may benefit select high-risk patients who have undergone neck dissection.
Specifically, combined chemoradiotherapy in patients with extracapsular lymph node extension of the tumor and positive surgical margins improved locoregional failure rates (18-22%) and 5-year, disease-free survival rates (47%) compared with the rates of patients who received postoperative radiotherapy alone (31-33% and 36%, respectively).
One study found overall 5-year survival rates to be significantly improved (from 40% to 53%) in high-risk patients who received combined chemoradiation compared with patients who received postoperative radiation alone.
Follow-up
Postoperatively, patients who have undergone neck dissection for head and neck malignancies need to be observed on a regular basis for 2 reasons.
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Firstly, recurrences must be identified, should they occur. Since most recurrences of squamous cell carcinoma (>90%) occur within 3 years of the initial treatment, perform frequent complete postoperative examinations. Many recurrences remain treatable.
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Secondly, a patient who has been treated for an aerodigestive malignancy is at risk (5-30%) of developing a second primary tumor of the aerodigestive tract, which often can be detected when it is still treatable. All patients probably should undergo an annual chest radiograph to detect distant metastatic disease and to search for a primary lung malignancy. Many physicians also obtain a liver chemistry profile on an annual basis and thyroid function tests, particularly if the patient has had radiation therapy, which may result in hypothyroidism over time.
For excellent patient education resources, visit eMedicineHealth's Cancer Center. Also, see eMedicineHealth's patient education article Cancer of the Mouth and Throat.
Complications
Hematoma formation, particularly when the primary tumor has been resected in conjunction with neck dissection, is potentially disastrous, since the hematoma frequently becomes infected and establishes the formation of a fistula from the aerodigestive tract to the skin.
The risk of carotid artery rupture has been virtually eliminated because of several factors. Firstly, radiation therapy is usually administered postoperatively (within 4-6 wk of surgery), which allows for healing prior to the start of effects. Furthermore, the advent of muscle flaps that can cover the carotid artery, providing it with a healthy source of uninvolved, unirradiated tissue, has dramatically decreased the incidence of this devastating condition. Carotid rupture today, when it occurs, usually is preceded by a history of radiation therapy, tumor erosion into the carotid artery, and the development of a fistula to the aerodigestive tract. Unfortunately, this condition is almost always fatal.
In a prospective study of patients with oral cancer who were treated with radical surgery with neck dissection, along with reconstructive surgery, the risk of postoperative dysphagia was found to be increased in those with stage T3 or T4 cancer (odds ratio [OR] = 79.71) or who underwent bilateral neck dissection (OR = 20.66) or resection of unilateral or bilateral suprahyoid muscles (OR = 17.00). [8]
Outcome and Prognosis
Patients with squamous cell carcinoma should not be deemed unsalvageable, since many live normal, productive lives after treatment of head and neck malignancies, with minimal morbidity and mortality.
The prognosis following treatment for a squamous cell carcinoma depends on the tumor stage. Patients with earlier (stage I) malignancies can have a cure rate in excess of 90%, depending on the site of the tumor. Even those with more advanced tumors (stage IV) can have cure rates in excess of 50%. This is attributed to several factors, including combined therapy (adjuvant radiotherapy, chemotherapy) and the fact that tumors can be determined as stage IV because of the extent of the primary tumor or the extent of nodal disease. A small primary tumor with advanced regional nodal disease can be stage IV, as can a large primary tumor with no nodal disease. These situations are disparate; nevertheless, the current staging system has some limitations, and therefore these 2 vastly different situations are staged similarly. Thus, they are considered similarly in various retrospective studies on clinical outcomes, even if they are treated differently or respond differently to treatment.
In a study of oral tongue squamous cell carcinoma, Zhang et al reported that in patients in whom positive margins were detected intraoperatively, immediate resection of these margins led to a local recurrence–free 3-year survival rate (92%) comparable to that of patients with negative margins (91%) and superior to that of patients with positive margins who did not undergo margin resection (73%). Invasive carcinoma/high-grade dysplasia situated less than 1 mm from the inked edge was designated as a positive margin. [9]
Future and Controversies
Future research must address several issues. These include improved methods of administering radiation therapy, whether fractionated daily or by other techniques, including brachytherapy. Newer forms of chemotherapeutic agents need to be addressed in controlled randomized clinical trials. Other techniques for prevention of head and neck malignancies are being studied, including education and chemoprevention. Lastly, gene therapy may hold potential for future research and treatment.
A prospective, randomized, controlled trial by Mehanna et al suggested that in patients with advanced nodal disease (stage N2 or N3) in head and neck squamous cell carcinoma who have undergone primary treatment with chemoradiotherapy, the use of PET-CT scan–guided surveillance results in a similar survival rate to that achieved with planned neck dissection. In the study, neck dissection was carried out in patients undergoing PET-CT scan surveillance only in the event of an incomplete or equivocal therapy response. The surveillance group had a 2-year overall survival rate of 84.9%, versus 81.5% in the planned-surgery group, although fewer neck dissections were performed in the surveillance patients. [10]
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Levels of metastasis to cervical lymph nodes.