Radiation Therapy and Management of the Cervical Lymph Nodes and Malignant Skull Base Tumors

Incidence and Distribution of Neck Node Metastasis

Incidence and Distribution of Lymph Node Metastasis From Clinical and Radiologic Assessment

The metastatic spread of head and neck tumors into the cervical LNs is rather consistent and follows predictable pathways, at least in the neck that has not been violated by previous surgery or RT. In Figs. 117.2 to 117.6 , the frequency of metastatic LNs is expressed as a percentage of node-positive patients.

The frequency of neck node metastases and the distribution of clinically involved nodes depend to a major extent on the primary tumor site. Typically, hypopharyngeal tumors have the highest propensity for nodal involvement, which occurs in 70% of cases. Cranial and anterior tumors, such as oral cavity tumors, mainly drain into levels I, II, and III, whereas more caudally located tumors, such as laryngeal tumors, mainly drain into levels II and III, and to a lesser extent into Levels IV and V. Contralateral nodes are rarely involved except for midline tumors or tumors in those sites where bilateral lymphatic drainage has been reported, such as the soft palate, base of the tongue, and pharyngeal wall. Even in these tumors, the incidence of contralateral involvement is much lower; for example, in base-of-tongue tumors with clinically positive nodes, it reaches 31% in contralateral level II compared with 73% in ipsilateral level II (data not shown). Interestingly, node distribution follows the same pattern in the contralateral neck as in the ipsilateral neck. Except for nasopharyngeal tumors, involvement of ipsilateral level V is a rather rare event and occurs in less than 1% of all oral cavity tumors, in less than 10% of all oropharyngeal and laryngeal tumors, and in about 15% of all hypopharyngeal tumors. It almost never occurs in contralateral level V. Nasopharyngeal tumors behave differently than other head and neck tumors. These highly lymphophilic tumors carry almost the same risk of nodal involvement in the ipsilateral and contralateral neck, with the preferential involvement of level V in almost one-third of patients. On the other hand, the incidence of level I infiltration is much lower.

Metastatic LN involvement in the neck depends on the size of the primary tumor, and it increases with the T stage. In the series reported by Bataini and colleagues, 44% of patients with a T1 tumor had clinical LN involvement; this increased to 70% for patients with T4 lesions. However, there are no data to suggest that the relative distribution of involved neck levels varies with the T stage.

Retropharyngeal LNs represent a special entity inasmuch as they are usually not clinically detectable. The incidence of retropharyngeal LN involvement can only be precisely estimated from series in which CT or MRI of the retropharynx has been systematically performed as part of the diagnostic procedure. Retropharyngeal node involvement occurs in primary tumors that arise from or invade the mucosa of the occipital and cervical somites (e.g., of the nasopharynx, pharyngeal wall, and soft palate). Interestingly, the incidence of retropharyngeal LNs is higher in patients in whom involvement of other neck node levels has also been documented. However, in clinically N0 patients with nasopharyngeal tumors, and to a lesser extent in those with posterior pharyngeal wall tumors, the incidence of retropharyngeal nodes is still significant, between 16% and 40%. Also, as already described for the other LN levels, involvement depends on the T stage and is typically lower for T1 tumors. However, accurate figures are not available.

Recommendations for the Selection of Target Volumes in the Neck

The data presented in the previous sections indicate that metastatic LN involvement of primary SCC of the oral cavity, pharynx, and larynx typically follows a predictable pattern. Data on both clinical and pathologic neck node distribution and on neck recurrence after selective dissection procedures support the concept that not all the neck node levels should be treated as part of the initial management strategy of head and neck primaries of squamous cell origin. However, the clinician should bear in mind that the data on which such a concept is based have come from retrospective series, and thus they may include possible bias (e.g., patient selection, series from the pre-imaging area), which could limit their validity.

Tables 117.4 to 117.7 present recommendations for the selection of the target volumes in the neck for oral cavity and pharyngo-laryngeal SCCs . These guidelines can be applied irrespective of the treatment modality (surgery or RT) . The discussion of the choice between these two modalities is beyond the objective of this chapter but should be considered relative to the neck stage, treatment options for the primary tumor, performance status of the patient, toxicity and functional outcome of the two modalities, and the institutional policy agreed on by a multidisciplinary head and neck tumor board. The denomination of the levels is an extension of the Robbins classification to also include levels that are not routinely removed during a neck dissection procedure.

For clinically N0 patients with HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx, selective treatment of the neck is appropriate. Typically, levels I to III should be treated for oral cavity tumors, and levels II to IVa are treated for oropharyngeal, hypopharyngeal, and laryngeal tumors. Robbins has suggested that elective treatment of level IIb is probably not necessary for N0 patients with a primary tumor of the oral cavity, larynx, or hypopharynx. On the other hand, two studies have suggested that level IVa be included in the treatment of the mobile tongue because of the high incidence (>10%) of skip metastases. However, this finding has not always been observed. Retropharyngeal nodes should be treated in tumors of the posterior pharyngeal wall. For subglottic tumors, tumors with subglottic or transglottic extension, or hypopharyngeal tumors with esophageal extension, level VI nodes also should be included in the treatment volume.

As proposed by Byers, similar guidelines also could be recommended for N1 patients without radiologic evidence of extracapsular infiltration. However, when an involved LN is located at the boundary with a level that has not been selected in the target volume, it has been recently recommended to extend the selection to include the adjacent level. Typically, this will only apply for oropharyngeal tumors with a single LN in level II at the boundary with level Ib or for an oral cavity tumor with an N1 node in level III at the boundary with level IV.

For patients with multiple involved nodes (N2b), the available data suggest that adequate treatment should include levels I through V. However, Level I could be omitted for laryngeal tumors, and level V could be omitted for oral cavity tumors with neck involvement limited to levels I through III. Elective treatment of the retropharyngeal nodes should be recommended for oropharyngeal and hypopharyngeal tumors. As for N0 patients, level VI nodes also should be treated for subglottic tumors, those with subglottic or transglottic extension, or hypopharyngeal tumors with esophageal extension. Recently, for patients with involved nodes in the upper neck (i.e., upper level II), it has been proposed to extend the upper limit of the target volume to include the retrostyloid space (level VIIa). Similarly, the supraclavicular fossae also should be included in the target volume in case of lower neck involvement (i.e., level IVb or Vb nodes).

No data on the distribution of pathologic metastatic neck nodes in patients who come to medical attention with a single ipsilateral large node (N2a or N3) or with bilateral or contralateral nodes (N2c) are available. For patients with a single large node, in the absence of data, it appears prudent not to recommend selective treatment. Also, for N3 patients, the type of treatment of the neck is likely to be dictated by the local extension of the node into the adjacent structures (e.g., paraspinal muscles, parotid gland, blood vessels). For N2c patients, one proposal is to consider each side of the neck separately (e.g., selective treatment in both sides for a small single node in each side, selective treatment for a small single node in one side, and more extensive treatment in the other side in the case of multiple nodes). The rationale behind this proposal is that although patients with bilateral neck nodes harbor a worse global prognosis, regional control will only be affected by the extent of disease on each side of the neck.

Elective treatment of the contralateral N0 neck is still a gray area, and treatment is likely to be based on clinical judgment rather than on strong scientific evidence. Typically, patients with midline tumors or tumors that originate from or extend to a site that has bilateral lymphatic drainage—base of tongue, vallecula, posterior pharyngeal wall—are thought to benefit from bilateral neck treatment, whereas well-lateralized tumors, such as those at the lateral border of the tongue or in the retromolar trigone or tonsillar fossae, can be spared contralateral treatment. Also, it has been reported in tumors of the oral cavity, pharynx, and larynx that the risk of contralateral neck metastases increases with involvement of the ipsilateral neck. Putting all these data together, the clinician could recommend restricting the treatment to the ipsilateral neck for N0 and N1 tumors of the lower gum (not approaching the midline), lateral border of the mobile tongue, upper gum, cheek, retromolar trigone, tonsillar fossa (without extension to the base of the tongue, soft palate, or posterior pillar), and lateral wall of the piriform sinus. For those tumors that manifest with larger or multiple ipsilateral nodes (N2a, N2b), it is not known whether a unilateral neck treatment is adequate, and the decision is left to the treating physician. In the other situations, where elective contralateral neck treatment is recommended, the selection of the node levels to be treated should follow similar rules to those for the ipsilateral neck.

In patients with p16-positive oropharyngeal SCC, there are no data to suggest that the selection of the neck node levels should be different than for the p16-negative tumors. Owing to the new TNM classification, it is recommended to consider the number, the location, and the laterality of the positive nodes to select the levels to be treated.

Because of the lymphophilicity of NPC tumors, bilateral treatment of levels II through V and treatment of retropharyngeal nodes is recommended even for patients with a node-negative neck ( Table 117.8 ). For patients with bulky involvement of level II, additional treatment of level Ib might be considered.

In principle, a similar approach should apply for the definition of the node levels to be irradiated postoperatively. However, if the selection criteria for postoperative RT can be agreed upon (i.e., extracapsular spread, patients with a metastatic node >3 cm in diameter or with more than one metastatic node), irradiation of levels I through V is typically performed. As for primary RT, the retrostyloid space (level VIIb) and the supraclavicular fossae (level IVb) should be included in the target volume, depending on the location of the metastatic nodes. For laryngeal tumors, level I could be omitted. For oral cavity tumors, postoperative irradiation of level V could be omitted in the case of metastatic nodes located in level I and/or II only. Retropharyngeal and level VI nodes should be treated as mentioned earlier.

The clinician should question the necessity of systematic bilateral postoperative irradiation in situations where a proper bilateral neck node dissection has been performed and where one side of the neck was free of disease on pathologic examination. In a retrospective study from St-Luc University Hospital in Brussels (Belgium) involving 105 patients with HNSCC (50% oral cavity, 85% pathologic stages III and IV) treated primarily with up-front surgery, including unilateral or bilateral neck dissection according to tumor location, and for whom postoperative irradiation was only delivered on the positive neck after pathologic examination, the locoregional disease control rate reached 78% at 5 years (V. Grégoire, unpublished data). Among the 24 patients who had locoregional recurrence, only seven patients did so in an area treated by surgery but that did not receive postoperative irradiation; it is unknown whether postoperative irradiation on that area would have prevented a locoregional recurrence. This study suggests that a new paradigm should be properly tested and validated regarding the extent of postoperative irradiation.

Delineation of the Clinical Target Volume

Since the late 1990s, several authors have proposed recommendations for the delineation of the neck node levels. A critical review of the various proposals was undertaken in 2003 in collaboration with representatives of the major European and North American clinical cooperative groups to generate an international set of guidelines for the delineation of the neck node levels in the node-negative neck. Subsequently, few amendments were proposed to take into account the node-positive neck, the delineation of extranodal structures in case of muscular infiltration, the inclusion of the retrostyloid space in case of infiltration of level II, and the inclusion of the supraclavicular fossae in case of infiltration of level IV and/or Vb.

Although it appears that these recommendations are well accepted and used among the radiation oncology community, they are also associated with some shortcomings. First, not all the neck node areas described in the TNM atlas were included, and in particular, the nodal areas in the lower and posterior neck typically involved in NPC were not properly discussed; also the LN regions draining the face, the scalp, and those nodal regions close to the base of skull received inadequate attention. Second, it appears that the description of the anatomic boundaries of some of these levels (e.g., in the lower neck) was not sufficiently accurate and thus required some interpretation from the users. Third, in the guidelines for the node-positive neck, the proposed extension around positive nodes into normal structures to generate the clinical target volume (CTV) was both arbitrary and potentially imprecise. In this context, a new set of international guidelines applicable to the node-negative, the node-positive, and the postoperative neck was proposed. It is beyond the scope of this chapter to present an in-depth discussion of the boundaries of the various levels. Interested readers are invited to refer to the original publication. Fig. 117.7 presents several CT cuts of the neck with selected levels.

Irradiation Techniques

With the use of intensity-modulated radiation therapy (IMRT), there is no longer a standard recipe for how to set up the field sizes and borders according to bony landmarks. Instead, the irradiation technique should be selected and adapted so that the entire planning target volume receives the prescribed dose within the adopted dose-volume constraints and in full respect of the International Commission on Radiation Units and Measurements recommendations.

The dose prescription depends on various factors—such as elective versus therapeutic irradiation, the use of combined modality treatment, planned neck node dissection, and postoperative irradiation—that are beyond the scope of this section for comprehensive review. Typically, for primary RT, an elective dose equivalent to a dose of 50 Gy in about 2 Gy per fraction over 5 weeks and a therapeutic dose equivalent to a dose of 70 Gy in about 2 Gy per fraction over 7 weeks will be prescribed. In 2018, irradiations are typically performed using a simultaneous integrated boost (SIB) approach with therapeutic dose of 70 Gy (35 × 2 Gy per fraction over 7 weeks) and an elective dose of 54.25 Gy (35 × 1.55 Gy per fraction over 7 weeks).

For postoperative irradiation, depending on the risk factors, doses will range from 60 to 66 Gy, in 2-Gy fractions over 6 to 6.5 weeks. A typical example of neck irradiation is presented in Fig. 117.8 .