Site

Elective Neck Dissections

Li hTP.

Figure 15-8. Incidence of metastasis to lymph node levels by primary site in N+ and N0 patients. (Data from Shah JP, et al. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 1990;66:109-13, and Shah JP Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg 1990;160:405-9.)

Li hTP.

Site

Figure 15-8. Incidence of metastasis to lymph node levels by primary site in N+ and N0 patients. (Data from Shah JP, et al. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 1990;66:109-13, and Shah JP Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg 1990;160:405-9.)

of a clinical N0 stage. They concluded that the incidence of metastases to level V was small in general, and extremely unlikely in the clinically N0 patient.

Evaluation of the Neck

Pre-surgical staging of the neck has become more complex over the years. Clinical assessment of the neck by palpation, while providing critical information, is inadequate in its sensitivity for detecting metastatic disease to the cervical nodes. Error rates as high as 40 percent have been reported when physical examination alone is used to evaluate the neck.21 Patient factors such as a short, obese neck, as well as prior irradiation play a role in decreasing the accuracy of this technique. Clearly, radiologic assessment of the neck adds to the sensitivity and specificity of preoperative neck evaluation.

Computerized tomography (CT) and magnetic resonance imaging (MRI) have become the workhorses of imaging modalities in head and neck squamous cell carcinoma (HNSCC). Size criteria are frequently used as indicators of metastatic involvement. Other features such as central necrosis or ring-enhancement aid in specificity but are relatively infrequent findings. Generally, a subdigastric node measuring >15 mm, a submandibular node >12 mm, and other nodes >10 mm are suspicious for involvement. Using criteria such as these, the accuracy of detecting neck disease approaches 90 percent.22,23 Size, however, is certainly not pathognomonic for cancerous involvement of lymph nodes. Even in the patient with an identified squamous cell carcinoma of the upper aerodigestive tract, a myriad of alternative causes of enlarged lymph nodes exist. Further, microscopic foci of disease may exist in nodes of normal size. As CT or MRI is often employed to evaluate the primary lesion, inclusion of the neck in the area of study incurs nominal additional expense and no morbidity. Although CT and MRI provide excellent anatomic detail and are the current modalities of choice, they provide little information on the biology of the lymph node.

Due to its non-invasiveness and affordability, ultrasound (US) has been investigated as a potential tool in evaluating neck disease. Factors such as size, irregular margins, and echo characteristics of lymph nodes have been shown to have predictive value in assessing involved nodes. The overall sensitivity of this approach, however, is limited due to the operator-dependent nature of ultrasound.24 Some authors have proposed ultrasound in combination with ultrasound-guided fine needle aspiration as an approach to diagnosis. Takes and colleagues25 examined, with ultra-sonography, 64 necks staged N0 based on physical examination. Those with nodes greater than 5 mm in size underwent ultrasound-guided needle biopsy. Results were further verified with histopathologic examination and the findings compared with CT of the neck for detection of involved nodes. They found a 48 percent sensitivity, 100 percent specificity, and 79 percent accuracy for ultrasound versus 54, 92, and 77 percent respectively for CT. These results demonstrate that, in experienced hands, ultrasound can be a useful tool. Its widespread application, however, is limited by the technical expertise required for accurate interpretation.

Positron emission tomography (PET) has been employed to assess metabolic changes in a variety of tissues including those of the head and neck. PET localizes regions of increased glucose metabolism by using the radionuclide 2-[18F]-fluoro-2-deoxy-D-glucose. Hanasono26 and colleagues demonstrated a potential role of this technique in evaluating unknown primaries, distant metastases, and for tumor surveillance. They suggest that it may be effective as an adjuvant to CT and MRI in selected cases. Another study, however, found sensitivity of 78 percent and specificity of 100 percent when PET was used to evaluate patients clinically staged N0.27 Although their numbers were small, the results compare favorably to other imaging modalities. Another interesting approach attempts to combine the sensitivity of PET with the anatomic detail of CT and MRI. Wong and col leagues28 used computer-combined imaging to evaluate primary lesions in the head and neck. They found enhanced detail and accuracy as compared to clinical exam or single modality imaging alone. Whether this approach can be extended to evaluation of nodal disease is unclear, and cost-benefit issues may preclude its widespread utilization.

Selection of Surgical Therapy

The proliferation of different types of modified neck dissection has the potential to lead to confusion regarding what type of neck dissection is appropriate for a particular clinical situation. This is complicated by the lack of data from randomized studies comparing the effectiveness of the variations of neck dissection. The goal of any neck dissection, however, should be: to remove all clinically obvious metastatic disease, to sample the lymph node levels at highest risk for metastasis in order to detect the presence of occult metastasis, and to perform this in such a way as to minimize the morbidity of the procedure without compromising the 2 previous goals. With this in mind, 2 dominant clinical scenarios emerge: the clinically N0 and the clinically N+ neck. A general algorithm is presented in Figure 15-9.

In the clinically N0 setting, the first decision to be made is whether to perform a neck dissection at all or to simply observe the neck for the development of metastasis. There is no firm data to suggest that elective neck dissection improves survival; in fact the only randomized trial addressing this question failed to find any survival advantage to elective neck dis-section.29 However, some authors have reported improved survival in patients treated during a time period when elective neck dissection is frequently performed as compared to earlier periods where observation of the neck was more common.30 It seems likely, however, that if elective neck treatment is to improve survival, that it will be of most benefit to those patients with a high risk of occult metasta-sis—thus some authors have recommended elective neck treatment in patients with a greater than 20 to 25 percent risk of occult metastasis.31 In addition it is often assumed that if the neck is observed closely, any metastatic disease that occurs will be detected at an early stage. This assumption is, in fact, erroneous, as Andersen and colleagues32 reported on a series of 47 patients who recurred in the neck during observation. In these patients, 60 percent were pathologically N2 or greater and extracapsular spread was present in half when the failure was detected.

Due to the high rates of occult metastasis in patients with primary tumors located in the hypophar-ynx, oropharynx, and supraglottic larynx, elective treatment of the neck (with neck dissection if surgical resection of the primary tumor is planned, or with radiotherapy if the primary tumor is to be irradiated for cure) is indicated.15 Occult metastasis from tumors of the oral cavity (specifically tongue and floor of mouth) has been correlated with tumor stage15 and tumor thickness33 (Figure 15-10). Therefore, elective treatment of the neck is indicated in patients with tumor greater than 2 mm thick or in T3 or T4 primaries. Other indications for elective neck dissection include the need to enter the neck, either to resect the primary tumor (eg, mandibulotomy, lateral pharyngo-tomy, supraglottic laryngectomy), or for reconstruction (eg, free tissue transfer). In these situations it is convenient to electively dissect the neck. Another factor, which may lead the surgeon to electively dissect the neck, is the case of the patient is believed unlikely to return for the close follow-up that is necessary if observation of the neck is to be employed.

When deciding the type of neck dissection to perform in the elective setting, 2 factors must be considered: the likelihood of occult metastasis, and the most likely location of the metastases based on the location of the primary tumor. Since in the clinically N0 patient the majority of neck dissections are likely to be negative for occult metastasis,21-34'35 the neck dissection chosen must be the least morbid possible. Selective neck dissections are ideally suited for the elective setting. On examining Figure 15-8, the operations that remove the nodal levels most at risk are

Clinical Nodal Metastasis

Perform comprehensive ND (MRND I) if

SAN not involved. May consider selective ND in N1 setting1

'Oral cavity-SOHND

Oropharynx -LND orALND Hypopharynx/larynx - LND

2 Mandibulotomy, lateral pharyngotomy, supraglottic laryngectomy for example

3 Primary located in oropharynx, hypopharynx or supraglottic larynx. Oral cavity tumor greater than 2

mm thick

Observe neck Perform elective selective ND1

Figure 15-9. General algorithm for selection of neck dissection.

Mucosa

Sub Mucosa

Risk of Occult Metastasis

Sub Mucosa

Figure 15-10. Risk of occult nodal metastasis with increasing thickness of oral cavity cancers (tongue and floor of mouth). Data from Spiro RH, et al. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth.33

Tumor Thickness

Figure 15-10. Risk of occult nodal metastasis with increasing thickness of oral cavity cancers (tongue and floor of mouth). Data from Spiro RH, et al. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth.33

obvious. Primary tumors in the oral cavity should undergo supraomohyoid neck dissection (SOHND); oropharyngeal tumors would best be treated with lateral neck dissection (LND). However, since surgical resection of the primary often involves an approach through level I, anterolateral neck dissection (ALND) may be a better choice, while tumors located in the hypopharynx or larynx should undergo LND. If the surgeon desires only one operation that is appropriate in all situations (for proficiency or for instruction of residents) then ALND is an excellent operation for the elective treatment of the neck in patients with head and neck cancer.

In the clinically N+ patient, the existence of lymphatic metastasis is established and therefore it is acceptable to perform a neck dissection with a greater potential for morbidity. It has been shown that preservation of the spinal accessory nerve in the N+ neck is not associated with increased risk of recurrence in the neck as long as the nerve is not involved by the tumor,36 therefore even in this setting it is possible to potentially ameliorate some of the morbidity of RND. As Figure 15-8 demonstrates, the incidence of metastasis at all levels in the neck increases in the setting of clinically obvious neck metastasis. Therefore in the N+ patient, an acceptable and safe neck dissection to perform is a comprehensive neck dissection that spares the spinal accessory nerve if it is not involved with tumor (MRND I).

The use of selective neck dissections in the N+ patient is controversial. While Shah's study17 shows that the rate of metastasis to all levels increases in the N+ neck, it also shows that the pattern of metastasis still follows the general pattern seen in the N0 neck. There is in fact some evidence that selective neck dissection in the N+ neck yields control rates similar to more comprehensive neck dissections.37,38 The efficacy of selective neck dissection in the N+ neck is still a matter of debate; however, its use in low-stage neck disease such as the N1 neck is not unreasonable. The type of selective neck dissection employed should be based on the patterns of nodal metastasis shown in Figure 15-8. Given the low risk of metastasis to level V reported by Davidson20 and the increased risk of involvement of level IV in the N+ neck, the ALND might be the selective neck dissection of choice if one is to perform this type of operation in the N+ setting.

Radiation Therapy

The ability of radiotherapy to improve outcomes in squamous cell carcinoma of the head and neck is well demonstrated. Its efficacy in early T1 and T2 lesions of the upper aerodigestive tract approaches that of surgical management. Treatment of disease metastatic to the neck with radiation has also shown benefit. Studies have shown that, in the N0 neck, radiotherapy is as effective as elective neck dissection (END) in reducing locoregional recurrence.39 Surgery combined with radiation has been shown to reduce local failure rates to 18 percent in N1 necks.40 The timing of neck irradiation, however, has been a subject of debate. Preoperative radiation had been favored in the past due to the theoretical advantage of treating while the vascular supply of the tumor was undisturbed. Preoperative therapy may also help to reduce bulky disease and thus facilitate surgical extirpation. However, the increased incidence of radiation-related surgical complications following high-dose preoperative radiotherapy has led to the currently accepted practice of administering radiotherapy in the postoperative period. Typically, surgeons prefer postoperative radiation to avoid the wound healing difficulties encountered in operating on previously irradiated tissue. Further, Leemans et al has shown that histopathologic evaluation of the neck specimen can be used to select those patients who are more likely to benefit from combined therapy.41 Patients with neck disease found to be metastatic to multiple nodes or extending beyond the lymph node capsule have been shown to have better locoregional control and survival with the addition of postoperative radiotherapy.42 Delaying radiation allows the surgeon to select patients with these risk factors for further treatment. In fact, an RTOG study with long-term follow-up showed that patients treated with postoperative radiation had lower locoregional failure rates than those treated pre-operatively. Due to a higher incidence of distant disease, however, they demonstrated no difference in survivals.43

More recently, neoadjuvant chemotherapy has shown some promise in management of advanced head and neck squamous cell carcinoma. Various organ preservation protocols have been proposed in which combined chemotherapy and radiation have been used as initial therapy of the primary lesion and neck metastases. These approaches reserve surgery for salvage in patients failing to develop a complete response. Their proponents suggest that for partial responders, following neoadjuvant multi-modality therapy, an oncologically sound surgical procedure can be performed that has a greater chance of preserving speech or swallowing. This potential benefit must be weighed against the increased risk of surgical complications that has been associated with preoper-ative therapy. Chemoradiotherapy protocols designed at preserving function at the primary site often fail to eradicate disease in the neck. This necessitates post-treatment surgical management of the neck even for those achieving a dramatic response at the primary site. Lavertu44 and colleagues demonstrated a 46 percent complication rate in patients treated with neoad-juvant chemotherapy. Only 12 percent of these, how ever, were major complications, and they found no increased risk in those patients undergoing chemora-diotherapy. Other studies have shown similarly low wound-related complication rates; this is consistent with historically reported rates of neck wound complications following neck dissection alone.45

Controversies

A key controversy in management of the neck in head and neck squamous cell carcinoma relates to which and how much therapy is appropriate. In management of the N0 neck, it is generally accepted that a metastatic risk in excess of 20 percent warrants elective therapy. Although some advocates of a watchful waiting policy exist, current data supports liberal use of prophylactic therapy. Though little information in regard to impact on survival exists, a study from Memorial Sloan-Kettering Cancer Center demonstrated that, despite close follow-up, patients who were observed rather than electively treated presented with advanced neck disease. Sixty percent of patients who recurred in the neck presented with N2 or greater disease and 77 percent had evidence of extracapsular spread.32 Such patients required more extensive therapy than if they had undergone elective treatment.

What therapy is indicated for treatment of the N0 neck is an issue of some debate. Advocates of elective radiotherapy suggest that its ability to control microscopic foci of disease render it comparable to neck dissection in control of neck disease. Its sequelae, including often-debilitating xerostomia, however, make it a more morbid treatment option, as compared to selective neck dissection. Certainly, selective lateral or supraomohyoid neck dissection can be performed quickly, safely and with minimal postoperative morbidity. The oncologic efficacy of selective neck dissection has been discussed earlier, and those factors make it the treatment of choice for the clinically uninvolved neck, unless radiotherapy is to be employed for the treatment of the primary site.

Management of the N1 neck is more controversial. Conventionally, radical neck dissection (RND) has been the treatment of choice for patients presenting with disease in the neck. Modifications of RND, including those sparing the eleventh nerve, in the past were criticized for their violation of tradi tional surgical oncologic principles. An en bloc resection is not possible and lymphatic channels must be cut to preserve such structures. It is now accepted that tumor metastasizes in an embolic fashion and therefore, effective treatment can still be rendered. This has been borne out by the work of Bocca.46 An extensive review of functional neck dissection, preserving the eleventh nerve, sternocleido-mastoid muscle, and internal jugular vein routinely showed a recurrence rate comparable to RND even in N1 disease in 171 patients. So long as nodes are not adherent to the structures of concern and a connective tissue plane of dissection can be established, it may be possible to preserve these structures. That the important structures traversing the neck are maintained within their own aponeurotic sheaths is validated by the work of Byers.47 In an extensive review of functional and selective neck dissection, he found a 4.7 percent local recurrence rate for patients with pathologically positive jugulodigastric nodes despite preservation of the eleventh nerve, so long as postoperative radiotherapy was used.

As it has become more accepted to preserve important structures in the neck, the concept of removing only at-risk nodal groups even in the N+ neck has been considered. Spiro and colleagues48 reviewed the Memorial Sloan-Kettering Cancer Center experience with supraomohyoid neck dissection and found that in 31 patients undergoing therapeutic dissection and radiotherapy, there was a 6 percent local failure rate. Traynor and colleagues49 examined 29 patients with N1-N2C neck disease treated with various forms of selective neck dissection (SND) and found local recurrence rates of only 4 percent. Their group emphasized the importance of careful selection of patients. Shah demonstrated that, even in patients with clinically evident neck disease, of 776 pathologically evaluated RNDs only 3.7 percent had involvement of the level V nodes.36 This data, in addition to early studies of patterns of lymphatic spread of head and neck squamous cell carcinoma, have led to broader application of selective neck dissection (SND) in management of the N1 neck, particularly if postoperative radiotherapy is utilized. Those with massive adenopathy, fixed nodes or gross extracapsu-lar spread should be treated with classic radical neck dissection. They suggest, however, that the type of neck dissection can be individualized: nodal groups resected as well as structures of the neck to be preserved are based on known patterns of lymphatic spread as well as findings at the time of surgery.

FUTURE DIRECTIONS

As with many neoplastic diseases, the future of head and neck squamous cell carcinoma management likely will include emerging treatments such as immunotherapy. Novel approaches such as gene therapy, T cell manipulation, and cytokine therapy have been employed in experimental treatment of other solid tumors with limited success. While the application of such strategies is based on a limited understanding of tumor immunology at the primary site, even less is known about the immunoregulatory role of the draining lymphatics. Current treatment protocols focus on the goal of complete extirpation of the tumor. As Collins points out, however, HNSCC is more likely a systemic disease with a predilection for sites in the head and neck.50 The role of lymph nodes in this process is unclear. Extrapolating conventional immunology to tumor biology, tumor antigens are transported from the primary site either by antigen-presenting cells (macrophages, dendritic cells, B cells) or by tumor cells themselves to the regional lymph node where an immunologic response is initiated. The propagation of this response is systemic rather than local. It follows, then, that lymph nodes are biologic rather than mechanical barriers to tumor advancement. Several investigators have found evidence of increased antitumor activity in lymph nodes draining HNSCC. Vetto and colleagues51 found higher expression of the T cell activation marker OX40 on cells from draining lymph nodes than in the peripheral blood. Other studies have also shown that the draining lymph nodes have been exposed to tumor antigens.52,53 Clearly, through tolerance or immunosup-pression, this systemic immune response is ineffective in controlling disease. One study demonstrated a tumor-induced inhibitory effect on lymph node cells that was more pronounced in first echelon nodes than in nodes outside the primary drainage basin.54 As our understanding of the immunologic interactions between the tumor and the host pro gresses, therapy guided at manipulating and enhancing the immune response may be developed. It is possible that the key to understanding this relationship lies within the draining lymph nodes.

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