William M. Mendenhall, Anthony A. Mancuso, Robert J. Amdur, and John W. Werning
ANATOMY
The locations of the various lymph node groups in the head and neck are shown in Figure 49.1.1 Under normal conditions, the right and left lymphatic networks do not shunt from one side to the other.2
The internal jugular chain (IJC) lymph nodes lie adjacent to the internal jugular vein and extend from the skull base to the clavicle. The most superior group of lymph nodes in this chain lies near the base of the skull in the posterior aspect of the lateral pharyngeal space and is often referred to as the parapharyngeal or junctional lymph nodes. These lymph nodes lie deep to the sternocleidomastoid muscle, the posterior belly of the digastric muscle, and the tail of the parotid gland. The remaining IJC lymph nodes are artificially divided into the subdigastric, middle jugular, and lower jugular groups.
The spinal accessory chain (SAC) lymph nodes are distributed along the course of cranial nerve XI. The superior nodes of the SAC blend with the upper IJC nodes. The supraclavicular lymph nodes merge laterally with the SAC lymph nodes and medially with the lower IJC lymph nodes.
There are three to six submandibular lymph nodes. They may be either preglandular or postglandular; there are no lymph nodes in the substance of the submandibular gland. The submental lymph nodes lie in the midline between the anterior bellies of the digastric muscles, anterior to the hyoid bone and external to the mylohyoid muscle. The lateral retropharyngeal lymph nodes lie within the retropharyngeal space, which is bounded anteriorly by the pharyngeal constrictor muscles, superiorly by the skull base, and posteriorly by the prevertebral fascia. They are usually at the level of the C1 and C2 vertebral bodies but may be found as inferiorly as C3. The medial retropharyngeal nodes are small, inconstant intercalated nodes that are located near midline and empty into the lateral retropharyngeal lymph nodes.
The neck nodes are divided into levels as follows: level I, submental (IA) and submandibular (IB) nodes; level II, upper internal jugular nodes, from the skull base to the level of the hyoid bone; level III, middle internal jugular nodes, from the level of the hyoid bone to the omohyoid muscle; level IV, inferior internal jugular nodes, from the level of the omohyoid muscle to the clavicle; level V, spinal accessory lymph nodes; and level VI, anterior neck nodes, bounded by the hyoid bone, the sternum, and the common carotid arteries. Included in level VI are the paratracheal, pretracheal, precricoid (Delphian), and tracheoesophageal groove nodes.3
FIGURE 49.1. Arrangement of lymph nodes in the head and neck. (Redrawn from Rouviere H. Anatomy of the human lymphatic system, Tobias MJ [trans]: Ann Arbor, MI: Edwards Brothers, 1938:27.)
TABLE 49.1 DEFINITION OF RISK GROUPS
NATURAL HISTORY
The risk of lymph node metastases is influenced by the location of the primary tumor, histologic differentiation, size of the lesion, and the availability of capillary lymphatics.4–7 The estimated risk of subclinical disease in the clinically negative neck as a function of primary site and tumor (T) stage is shown in Table 49.1.4 Recurrent lesions have a higher risk of lymphatic involvement than untreated lesions.
The relative incidence of clinically positive lymph nodes in the neck by anatomic site and T stage is shown in Table 49.2.5 The most commonly involved lymph nodes in the head and neck are the level II lymph nodes, followed by the level III lymph nodes. Lesions that are well lateralized almost always spread first to the ipsilateral neck nodes. Lesions on or near the midline as well as lateralized base of tongue and nasopharyngeal lesions may spread to both sides of the neck.
Patients who have clinically positive lymph nodes on the ipsilateral side of the neck may be at risk for contralateral lymph node spread if the metastatic masses produce significant obstruction of the lymphatic trunks. In addition, patients who have undergone previous surgery on one side of the neck develop shunting of lymph across the submental region to the opposite side of the neck. When contralateral lymph node metastases occur, the level II lymph nodes are most frequently involved, followed by the level III and level IV lymph node groups.
As tumor grows within a lymph node, the node becomes indurated and more rounded, and enlarges. Tumor eventually extends through the capsule of the lymph node and invades surrounding structures. Extension to the neurovascular bundle is common and may produce a mass that is considered fixed to palpation. The incidence of tumor involvement and the likelihood of capsular penetration as a function of lymph node size are shown in Table 49.3.6
The risk of lateral retropharyngeal lymph node involvement is related to primary site and neck stage7; the medial retropharyngeal nodes are almost never the site of metastatic disease. The incidence of positive retropharyngeal nodes based on pretreatment computed tomography (CT) and, in selected cases, magnetic resonance imaging (MRI) is shown in Table 49.4.7
DIAGNOSTIC WORKUP
Physical Examination
The patient is examined in the sitting position, the examiner behind the patient with one hand on the occiput to flex the patient’s head forward and the other hand on the side of the neck to be examined. To examine the IJC lymph nodes, which lie deep to the sternocleidomastoid muscle along the internal jugular vein, place the thumb and index finger around the sternocleidomastoid muscle in the form of a “C” and then gently proceed from the sternal notch to the angle of the mandible. Both sides of the neck should not be examined simultaneously. The level Ib and level Ia nodes may be evaluated by direct palpation of these areas as well as by a bimanual examination with the index finger placed in the floor of the mouth.8
The following features of metastatic lymph nodes should be recorded: anatomic location, size, consistency, mobility, and clinical impression as to whether the node is involved with cancer.
TABLE 49.2 CLINICALLY DETECTED NODAL METASTASES ON ADMISSION CORRELATED WITH T STAGE
TABLE 49.3 RELATIONSHIP BETWEEN NODE SIZE, THE PRESENCE OF TUMOR IN THE NODE, AND CAPSULAR PENETRATION IN 519 NODESA
Radiographic Evaluation
CT, MRI, fluorodeoxyglucose–positron emission tomography (FDG-PET), and ultrasound may be used to evaluate cervical metastatic disease.9 At the University of Florida, CT remains the primary method of examination of most carcinomas arising in the upper aerodigestive tract and the regional lymphatic system. MRI is the primary study only in patients with nasopharyngeal malignancies. MRI also may be used in patients who are allergic to intravenous contrast medium. Ultrasound has been used mainly in Europe to evaluate the cervical nodes. FDG-PET may be used to evaluate equivocal suspicious lymph nodes if the results of the scan would alter the treatment plan. Positive nodes <1 cm will not be reliably detected on a PET scan. FDG-PET remains unproven with regard to improving accuracy rates over those available with properly performed and interpreted CT.
Small metastases may be seen as lucent foci in normal-sized nodes. Such metastases have been identified and surgically confirmed in nodes as small as 6 to 8 mm; however, most subclinical disease in normal-sized nodes remains undetected on CT. FDG-PET has a marginal capability to improve on CT in detecting the subclinical disease in small (<1 cm) nodes.
Lucent foci in normal-sized nodes must be differentiated from hilar fat or volume-averaging artifacts. As the metastasis grows, the node becomes more spherical than elliptical. Areas of necrosis are almost always present in nodal metastases larger than 2 cm. As the metastasis enlarges, the capsule of the node becomes hyperemic and is seen radiographically as a contrast-enhanced rim. When the capsule becomes indistinct and irregular along its outer margin, it is highly suggestive of early capsular penetration. Continued growth causes obliteration of the fat planes surrounding the nodes. Finally, no clear plane of normal tissue lies between the mass and the adjacent structures, at which point the clinician usually notes fixation (Fig. 49.2). Penetration of the prevertebral fascia and fixation to the scalene muscles are uncommon in untreated patients. Largely necrotic nodes may be negative on FDG-PET examinations.
If a node shows evidence of capsular penetration and envelops more than 50% of the circumference of the carotid artery, clinical evidence of fixation to the artery is likely. Ultrasound and MRI may prove useful in evaluating tumor extension to the carotid, as suggested by CT. MRI tends to be better at excluding extension to the neurovascular bundle when it is suspected on CT, whereas ultrasound can help show invasion of the vessel wall, thus confirming focal extension to the artery.
FIGURE 49.2. T1 squamous cell carcinoma of the lateral wall of the right pyriform sinus (open arrow) and a fixed N3B neck node that abuts but does not surround the carotid artery (solid arrow). Mendenhall WM, Parsons JT, Mancuso AA, et al. Head and neck: management of the neck. In: Perez CA, Brady LW, Halperin EC, et al., eds. Principles and practice of radiation oncology. Philadelphia: Lippincott Williams and Wilkins 2004:1158–1178.
TABLE 49.4 INCIDENCE OF POSITIVE RETROPHARYNGEAL NODES FOR VARIOUS PRIMARY SITES AND CLINICAL NECK STAGES (794 TUMORS)
STAGING
The staging systems shown in Table 49.5 are those of the American Joint Committee on Cancer (AJCC). Because all University of Florida data presented in this chapter were analyzed using the 1983 AJCC staging system,10 both the 1983 and 2010 systems are outlined in Table 49.5. Stage N3C in the 1983 system is rare and should alert the clinician to search for another primary lesion. The 2010 AJCC staging system classifies bilateral or contralateral nodes not more than 6 cm in diameter as N2C; N3 is defined as a metastasis in a lymph node more than 6 cm in diameter.11 The AJCC nodal staging system for head and neck cancer has not changed appreciably since the 1997 edition. The AJCC nodal staging for nasopharyngeal carcinoma differs from other head and neck primary sites and will be discussed in the chapter devoted to that topic.
SURGERY
Standard radical neck dissection involves removal of the superficial and deep cervical fascia with its lymph nodes in levels I to V in continuity with the sternocleidomastoid muscle, omohyoid muscle, internal and external jugular veins, spinal accessory nerve, and submandibular gland. Sacrifice of cranial nerve XI often, but not always, results in atrophy of the trapezius muscle, with shoulder drop and discomfort.
Modified radical neck dissection removes the superficial and deep cervical fascia with its enclosed lymph nodes and leaves one or more of the nonlymphatic structures such as the sternocleidomastoid and digastric muscles, internal jugular vein, and spinal accessory nerve. Currently, almost all of the patients treated with neck dissection at the authors’ institution undergo this operation with at least preservation of cranial nerve XI. The advantages of the functional neck dissection are less cosmetic deformity and better function.
For a selective neck dissection, one or more of lymph node groups I to V are not removed. The advantage of the selective neck dissection is that it provides equivalent efficacy and less morbidity in appropriately selected cases. Supraomohyoid neck dissection removes the lymph nodes in levels I to III and is most commonly used for patients with small oral cavity cancers and a clinically negative neck. The lateral neck dissection entails removal of level II to IV nodes and is most often used in the treatment of laryngeal, oropharyngeal, and hypopharyngeal cancers. If significant metastatic adenopathy is encountered during a selective neck dissection, it should be converted to a radical or modified radical dissection.
An extended radical neck dissection implies removal of additional lymph node groups or nonlymphatic structures in addition to the structures removed in a radical neck dissection. Bilateral neck dissections may be performed simultaneously or separately (staged) in patients with bilateral neck disease as long as one internal jugular vein can be preserved. At one time, simultaneous neck dissection appeared to be associated with a higher incidence of complications and operative mortality compared with staged neck dissections.12,13 The authors’ more recent experience suggests that this is no longer the case.
Complications of Neck Dissection
Complications of neck dissection include hematoma, seroma, lymphedema, wound infection, wound dehiscence, chyle fistula, damage to cranial nerves VII, X, XI, and XII, carotid exposure, and carotid rupture. The incidence of complications is higher when neck dissection is combined with resection of the primary lesion or when it follows a course of radiation therapy (RT). The postoperative mortality rate for unilateral neck dissection after RT was 3% for patients treated between 1964 and 1982.14
The incidence of postoperative complications in a series of patients treated with RT to the primary lesion and neck followed by unilateral or bilateral neck dissection(s) is shown in Tables 49.614 and 49.7.15 Two of 10 patients undergoing a staged bilateral neck dissection experienced a moderately severe complication compared with 4 of 40 patients undergoing a simultaneous bilateral neck dissection. None of the 10 patients who underwent a staged bilateral neck dissection experienced a severe complication, compared with 6 of 40 patients (15%) who underwent a simultaneous bilateral neck dissection (P = .24).15
Taylor et al.16 analyzed the incidence of moderate (2+) and severe (3+) wound complications in a series of 205 patients who underwent a planned unilateral neck dissection after RT at the University of Florida. RT was given once daily in 123 patients, twice daily in 80 patients, and with both techniques in the remaining two patients. The incidence of wound complications increased with total dose and dose per fraction (Fig. 49.3).
FIGURE 49.3. Complication rate (2+ or 3+) versus total dose. Separate analysis for once a day (filled square, solid curve) and twice a day (circle, dashed curve). Data are plotted at the midpoints of the range 45 to 60 Gy, 60 to 70 Gy, and 75 to 90 Gy. Error bars denote 95% confidence intervals. The curves are the results of separate logistic regression analysis. (From Taylor JMG, Mendenhall WM, Parsons JT, et al. The influence of dose and time on wound complications following post-radiation neck dissection. Int J Radiat Oncol Biol Phys1992;23:41–46, with permission.)
TABLE 49.5 1983 AND 2010 AMERICAN JOINT COMMITTEE ON CANCER STAGING FOR NECK LYMPH NODES
TABLE 49.6 POSTOPERATIVE COMPLICATIONS OF UNILATERAL NECK DISSECTION AFTER IRRADIATION TO THE PRIMARY LESION AND NECK (143 PATIENTS)
RADIATION THERAPY
RT may be used in the treatment of cervical lymph node metastases as elective treatment when there are no palpable lymph nodes, as the only treatment for clinically positive lymph nodes,17 or as preoperative or postoperative treatment in combination with neck dissection for clinically positive lymph nodes.18
The regional lymph nodes are considered in the treatment planning of the primary lesion. With clinically negative neck nodes, treatment planning depends on the estimated risk of subclinical disease in the nodes. With clinically positive lymph nodes, the plan is influenced by the number of lymph nodes, size, and location.
Elective Radiation Therapy of Cervical Lymph Nodes When the Primary Tumor Is Treated by Radiation Therapy
Factors that influence the decision to irradiate the neck electively are site and size of the primary lesion, histologic grade, difficulty in neck examination, relative morbidity for adding lymph node coverage, likelihood of the patient’s returning for follow-up examinations, and suitability of the patient for a radical neck dissection if the tumor appears in the neck at a later date. Patients in whom the primary lesion is to be treated by RT, who have clinically negative nodes, and in whom the risk of subclinical disease is 20% or greater usually receive elective neck irradiation to a minimum dose equivalent to 45 to 50 Gy over 4.5 to 5 weeks (see Table 49.1). Patients with lesions arising in the lip, nasal vestibule, nasal cavity, or paranasal sinuses have a low risk of subclinical neck disease, and the neck is not treated electively unless the lesion is recurrent, advanced, or poorly differentiated. Similarly, the risk of occult neck disease is essentially 0% for T1 and 1.7% for T2 glottic carcinomas, and elective neck radiation therapy is not indicated.19,20
The lateral treatment portals used to encompass cancers in the oropharynx, supraglottic larynx, and hypopharynx include the upper jugular and often the midjugular chain lymph nodes. RT portals used for primary lesions of the oral cavity, nasopharynx, glottis, nasal cavity, and paranasal sinuses must be enlarged to include the lymph nodes. The treatment portals for irradiation of the cervical lymph nodes must be designed in such a way as to minimize additional mucosal irradiation. A common error in irradiating oropharyngeal and nasopharyngeal cancers is to enlarge the lateral (primary) portals inferiorly to unnecessarily include all of the larynx in the lateral portals (Fig. 49.4).21Because the midneck is smaller in circumference than the upper neck, the total dose and dose per fraction are higher in the larynx than along the central axis of the beam, leading to double trouble. Although a field junction through a positive node(s) may be avoided with intensity-modulated radiation therapy (IMRT), the larynx still receives a substantially higher dose compared with a separate anterior low neck portal with a midline laryngeal block junctioned at the thyroid notch (Figs. 49.5, 49.6, and 49.7).22 Treating an unnecessarily large field increases the acute and late effects of RT and, by increasing the risk of an unplanned split, reduces the probability of disease control.21,22
IMRT may be used to treat patients if there is a goal that can be achieved to reduce the toxicity of irradiation. These goals are usually parotid sparing to reduce the risk of long-term xerostomia, avoiding a low neck match in patients with a low-lying larynx, and improved coverage of the poststyloid parapharyngeal space in patients with nasopharyngeal cancer.23 If one or more of these goals cannot be achieved, the patients may be better off being treated with conventional RT because of the disadvantages of IMRT, which include increased risk of a marginal miss, less homogeneous dose distribution, and increased cost and complexity.23
Elective neck irradiation for early oral cavity lesions includes the level Ib and level II lymph nodes. The level III and level IV lymph nodes are treated as well by using a narrow anterior field. For primary lesions located in the oropharynx, nasopharynx, supraglottic larynx, and hypopharynx, the lower neck nodes are also routinely included. The low neck is treated with a single anterior field (Fig. 49.8). A tapered midline larynx or trachea shield is added to protect the spinal cord, the larynx, and the pharynx. For primary lesions lying below the thyroid notch, a small midline tracheal block 5- to 10-mm wide is placed in the low-neck field, primarily to avoid field overlap at the spinal cord. A 1-cm wide midline block made of Lipowitz’s metal may be used to shield the trachea, esophagus, and spinal cord below the level of the cricoid.
FIGURE 49.4. Carcinoma of the base of the tongue: large radiation portals. A: Parallel-opposed lateral portals include the primary lesion, larynx, hypopharynx, most of the cervical spinal cord, and the upper portion of the trachea and cervical esophagus. Treatment through this portal tangentially irradiates the skin of the anterior neck unnecessarily. If an anterior field is not used to irradiate the low neck, the inferior border of the lateral field may be placed near the clavicle (dashed line). B: Anterior low-neck portal. The wide midline tracheal block partially shields the low internal jugular lymph nodes, which are located adjacent to the trachea. The supraclavicular lymph nodes, which are less likely to be involved with tumor than the low jugular nodes, are adequately covered. C: Central axis dosimetry at the level of the base of tongue primary lesion. The contours were obtained from a RANDO phantom using parallel cobalt-60 fields weighted equally. The base of tongue tumor is outlined, and the tumor dose is specified at 97% of maximum dose. D: Off-axis contour through larynx. The minimum dose to the entire larynx is 104% of the maximum dose specified at the central axis, and the maximum dose on this off-axis contour is 113%. If the base of tongue tumor dose is specified as 50 Gy at 2 Gy per fraction, the minimum larynx dose is 53.61 Gy at 2.14 Gy per fraction, and the maximum larynx dose is 58.25 Gy at 2.33 Gy per fraction. If the tumor dose is specified as 60 Gy at 2 Gy per fraction, the minimum larynx dose is 64.33 Gy at 2.14 Gy per fraction, and the maximum larynx dose is 69.9 Gy at 2.33 Gy per fraction. (From Mendenhall WM, Parsons JT, Million RR. Unnecessary irradiation of the normal larynx [editorial]. Int J Radiat Oncol Biol Phys 1990;18:1531–1533, with permission.)
FIGURE 49.5. Laryngeal dose in a model patient with a stage T2N2b carcinoma of the tonsil with positive nodes on the right side at the level of the larynx. The primary site is irradiated with either intensity-modulated radiation therapy or lateral opposed fields. The cervical lymphatics inferior to the primary site fields are treated with an anterior low-neck field. A: Digitally reconstructed radiograph of the low-neck fields. The larynx was contoured and appears as a red color-wash structure. The larynx is shielded with a narrow midline block that does not cover the entire width of the larynx. In this model patient, the entire low-neck field received 50 Gy, and then the field size was reduced to boost the positive nodes on the right of the larynx to 70 Gy. Irradiation was given with a 6-MV photon beam with source to axis distance of 100 cm. B: Axial dose distribution at the level of the true vocal cords showing that the dose to the central portion of the larynx is extremely low when the larynx is shielded in the anterior low-neck field. (From Amdur RJ, Li JG, Liu C, et al. Unnecessary laryngeal irradiation in the IMRT era. Head Neck 2004;26:257–264, with permission.)
FIGURE 49.6. Dose distribution using intensity-modulated radiation therapy as described in the text to treat the model patient with a stage T2N2b carcinoma of the tonsil with positive nodes on the right side at the level of the larynx. The plan was optimized to minimize the dose to the larynx while delivering 70 Gy to gross disease and 59.4 Gy to areas at risk for subclinical disease. A: Coronal projection near the middle of the larynx. B: Axial projection at the level of the true vocal cords. A comparison of Figures 49.5B and 49.6B shows that sparing of the central portion of the larynx is shielded in an anterior low-neck field. (From Amdur RJ, Li JG, Liu C, et al. Unnecessary laryngeal irradiation in the IMRT era. Head Neck 2004;26:257–264, with permission.)
FIGURE 49.7. Dose–volume histogram of the larynx for the model patient described in Figures 49.5 and 49.6. The thicker line is the dose–volume histogram when the larynx is included in the intensity-modulated ration therapy (IMRT) fields shown in Figure 49.6. The thinner line is the dose–volume histogram when the larynx is shielded in the anterior low-neck field shown in Figure 49.5. There is a major difference in the portion of the larynx that receives an extremely low dose. For example, when the larynx is included in the IMRT fields, the entire larynx receives more than 10 Gy, whereas when the larynx is shielded in the low-neck field, approximately 45% of the larynx receives <10 Gy. (From Amdur RJ, Li JG, Liu C, et al. Unnecessary laryngeal irradiation in the IMRT era. Head Neck 2004;26:257–264, with permission.)
Treatment of Clinically Positive Cervical Lymph Nodes When the Primary Tumor Is Treated by Radiation Therapy
The dose required to control a clinically positive lymph node that is included within the RT portals depends on the size of the lymph node17,24 and whether concomitant chemotherapy is administered. Relatively recent data suggest that advanced disease has a better chance of cure after altered fractionation or concomitant chemotherapy.25 Patients treated at the authors’ institution routinely receive hyperfractionation when using three-dimensional conformal RT and the concomitant boost technique when using IMRT, combined with weekly cisplatin 30 mg/m2. Positive nodes receive approximately 70 to 74 Gy, regardless of size or rate of regression.
The decision to add a neck dissection after RT for multiple unilateral positive nodes or bilateral lymph node disease is individualized and is based on the diameter of the largest node, node fixation, and number of clinically positive nodes in the neck. If clinically positive lymph nodes disappear completely during RT, the likelihood of control by RT alone is improved and a neck dissection may be withheld.26–29 Peters et al.30 reported on 100 node-positive patients with squamous cell carcinoma of the oropharynx treated with concomitant boost RT between 1984 and 1993 at the MD Anderson Cancer Center (Houston, TX). Sixty-two patients had a complete response in the neck and received no further therapy. Three patients (5%) subsequently developed an isolated recurrence in the neck and four patients (6%) developed a recurrence in the neck in conjunction with other sites of relapse. The 2-year neck disease control rates did not vary significantly with pretreatment nodal size: ≤3 cm, 87%; and >3 cm, 85%. The incidence of subcutaneous fibrosis was similar following RT alone compared with another group of patients who underwent a neck dissection in addition to RT. Johnson et al.31 reported on 81 patients with node-positive stages III and IV squamous cell carcinoma of the head and neck treated with concomitant boost accelerated hyperfractionated RT at the Medical College of Virginia (Richmond). Fifty-eight patients (72%) had a complete response in the neck and were followed; three patients (5%) subsequently developed an isolated recurrence in the neck and one additional patient developed recurrent cancer in the neck and in the primary site. The 3-year neck disease control rates were 94% for nodes ≤3 cm compared with 86% for those >3 cm.
Both of these series of patients received aggressive altered fractionated RT and it is unclear whether these data can be broadly extrapolated to patients with head and neck cancer from a variety of head and neck primary sites that are treated less aggressively. It is also unclear whether the addition of concomitant chemotherapy results in a lower likelihood of needing a neck dissection. However, multiple subsequent studies evaluating neck control rates after RT alone or combined with chemotherapy suggest that the likelihood of an isolated failure in the neck is low if there is a complete response after treatment.18,32–36
FIGURE 49.8. Lateral and anterior fields are used to irradiate a patient with a carcinoma limited to the base of tongue. A: Parallel-opposed fields include the primary lesion with a 2- to 3-cm inferior margin. The lower border of the field is placed at the thyroid notch and slants superiorly as the junction line proceeds posteriorly as the junction line proceeds posteriorly. This substantially reduces the amount of mucosa larynx and spinal cord included in the primary treatment portals. B: En face low-neck portal with tapered midline larynx and tapered midline larynx block. It is not necessary to treat the supraclavicular fossa unless clinically positive nodes are found in that particular hemineck. A 5-mm midline tracheal block may be placed in the low-neck portal (dashed line). (From Mendenhall WM, Parsons JT, Million RR. Unnecessary irradiation of the normal larynx [editorial]. Int J Radiat Oncol Biol Phys 1990;18:1531–1533, with permission.)
FIGURE 49.9. Dose distribution for anterior and posterior wedge cobalt-60 portals, both fields weighted 1.0.
TABLE 49.7 COMPLICATIONS AFTER RADIATION THERAPY FOLLOWED BY A BILATERAL NECK DISSECTION (N = 50 PATIENTS)
The authors’ policy at the University of Florida has changed to the extent that we now evaluate patients with clinically positive nodes with CT 4 weeks after RT and withhold neck dissection in the subset of patients with a complete response thought to have ≤5% risk of residual disease.37–41 Liauw et al.40 evaluated a series of 550 patients treated with definitive RT at the University of Florida between 1990 and 2002; 341 patients (62%) underwent a post-RT planned neck dissection. CT images obtained at approximately 4 weeks post-RT were reviewed for 211 patients; radiographic complete response (rCR) was defined as no nodes >1.5 cm and no focal abnormalities such as focal lucency, enhancement, or calcification.34 The outcomes are depicted in Table 49.8. Thirty-two patients had an rCR and were followed and did not undergo a neck dissection; the neck control rate was 97%. Recent data published by Yeung et al.37 suggest that for those who have a partial response to RT, neck dissection may be safely limited to only those levels that remain suspicious after RT. PET-CT may also be useful to determine whether to proceed with a neck dissection following RT. Patients undergo PET-CT 3 months after completion of RT to minimize the risk of a false positive scan; those with a negative PET-CT are followed, the remainder undergo a neck dissection.
If a neck dissection is planned to follow RT in patients with clinically positive lymph nodes, the preoperative dose varies with the size and location of the lymph node, fixation, and response to RT. Preoperative doses of 50 Gy are sufficient for mobile lymph nodes 3 to 4 cm in size, but 60 Gy or more is recommended for 5- to 6-cm nodes and for fixed nodes. Lymph nodes measuring 7 to 8 cm are almost always fixed to adjacent structures and often require doses of 70 to 75 Gy for the surgeon to achieve a complete resection. If the lymph node lies behind the plane of the spinal cord, electrons may be used to boost the dose after the primary fields have been reduced off the spinal cord after 45 to 50 Gy.14 Patients in whom the decision is made to add a neck dissection after completion of RT receive full-dose irradiation to the clinically positive neck nodes.
Another technique commonly used for boosting the dose to the neck mass after spinal cord tolerance has been reached and the treatment to the primary lesion has been completed is opposed anterior and posterior fields with wedges. The final dose to the neck node (not to the entire neck) may be 70 to 80 Gy without exceeding the spinal cord tolerance (Fig. 49.9). The anterior and posterior wedge-pair technique is preferable to an appositional electron boost field because high-energy electron beams increase the skin and mucosal dose.
When the cervical lymph nodes are located superficially, sometimes within 1 cm from the skin or fixed to it, treatment with high-energy photon beams (≥6 MV) may underdose these nodes. Treatment should be initiated with cobalt-60 or 4-MV x-rays for the initial 45 to 50 Gy, after which a higher energy photon beam can be used to continue RT of the primary tumor if the neck nodes are clinically negative or if a neck dissection is planned to follow RT (Fig. 49.10). Parallel-opposed 6-MV x-ray beams may adequately treat the upper neck nodes included in the primary treatment fields; however, the supraclavicular nodes in the en face low-neck field may be underdosed with a 6-MV beam in very thin patients. Although electrons alone may be used to treat cervical nodes, it is preferable to combine them with photons because of the high surface dose with high electron energies. Use of both 20-MeV electrons and 17-MV x-rays is compared with treatment by 20-MeV electrons alone in a patient with a lateralized lesion of the oropharynx (Fig. 49.11).42 The addition of the 17-MV x-rays to the 20-MeV electrons decreases the surface dose while still adequately irradiating the cervical nodes that are within the primary field. The addition of the x-ray beam also produces a dose distribution that is less affected by bone than that from the electron beam alone.
Large lymph nodes may not show much regression during the course of RT but often show significant regression from completion of treatment to the time the patient returns for neck dissection, usually after 4 to 6 weeks. The mass frequently has a thick capsule that facilitates its removal at the time of neck dissection.
Patients with bilateral neck disease require individualized treatment planning jointly by the radiation oncologist and the surgeon. If disease is minimal on one side, RT alone may be used to control the disease on that side of the neck, and a neck dissection may be used on the side with more disease. If major bilateral disease is present, bilateral neck dissection should follow RT.
FIGURE 49.10. Dose distribution for parallel-opposed cobalt-60 portals, each weighted 1.0, with reduced 17-MV x-ray portals, each weighted 0.4.
FIGURE 49.11. A: Dose distribution for 20-MeV electrons, field size 8.5 cm by 8.5 cm, SSD 100 cm. B: Dose distribution for 20-MeV electrons, field size 8.5 cm by 8.5 cm, and 17-MV x-rays, field size 7 cm by 7 cm, SSD 100 cm for both. The given doses are weighted 1 to 1. The addition of the 17-MV x-ray beam reduces the surface dose and gives a dose distribution that is affected less by bone. (From Bova FJ. Treatment planning for irradiation of head and neck cancer. In: Million RR, Cassisi NJ, eds. Management of head and neck cancer: a multidisciplinary approach. 2nd ed. Philadelphia: JB Lippincott, 1994: fig. 14–18:306, with permission.)
TABLE 49.8 PREDICTIVE VALUE OF POSTRADIOTHERAPY COMPUTED TOMOGRAPHY FINDINGS AT 4 WEEKS IN THE HEMINECK CORRELATED TO NECK DISSECTION PATHOLOGY (N = 193 HEMINECKS)
Complications of Neck Irradiation
The complications of neck irradiation include subcutaneous fibrosis and lymphedema of the larynx and submentum. The latter complications may be minimized by sparing an anterior strip of skin when designing the parallel-opposed lateral portals used to encompass the primary lesion. The probability of complications is directly related to the radiation dose with little, if any, morbidity observed with the doses used for elective radiation therapy of the neck.
Complications of neck treatment in patients who receive RT in conjunction with resection of the primary lesion and a neck dissection are essentially the same as those occurring after neck dissection. However, they occur with an increased incidence depending on the RT dose and extent of surgery.
Treatment of the Neck After Incisional or Excisional Biopsy
Open biopsy of a clinically positive neck node before definitive treatment potentially spills tumor cells along tissue planes that may not be removed with a radical neck dissection. McGuirt and McCabe13 reported that incisional or excisional biopsy of positive neck nodes before definitive surgery increased the risk of neck failure and worsened the prognosis for patients with squamous cell carcinoma of the head and neck. Parsons et al.43 reported their experience with incisional or excisional biopsy of positive neck nodes followed by RT as the initial step in the treatment of the patient; these data were updated by Mack et al.44 After excisional biopsy of a single lymph node, RT alone to the primary lesion and to the neck resulted in a 95% rate of neck control.44 If residual disease remained in the neck after biopsy, RT followed by neck dissection was more successful than RT alone for controlling neck disease (see Table 49.17).
If the primary lesion is to be treated surgically, the patient’s neck is also treated with preoperative RT to the primary lesion and neck, followed by resection. If the primary lesion is to be treated with RT, the patient is treated with RT. If there is no palpable disease remaining in the neck after excisional biopsy of a positive node, the neck may be treated with RT alone. If an incisional biopsy of the node has been performed (leaving gross disease) or if other positive nodes remain after an excisional neck node biopsy, RT is followed by a neck dissection. The dose of RT preceding a neck dissection depends on the amount of gross disease in the neck and the degree of fixation.14
TABLE 49.9 CONTROL OF DISEASE IN THE CLINICALLY NEGATIVE NECK WITH ELECTIVE NECK IRRADIATION (NUMBER CONTROLLED/NUMBER TREATED)
TABLE 49.10 FAILURE OF INITIAL IPSILATERAL NECK TREATMENT: 596 PATIENTS WITH CARCINOMA OF THE TONSILLAR FOSSA, BASE OF TONGUE, SUPRAGLOTTIC LARYNX, OR HYPOPHARYNX
RESULTS OF TREATMENT
Clinically Negative Nodes
Elective neck dissection and elective neck irradiation are equally effective in controlling subclinical disease. The decision whether to use surgery or RT for the purpose of electively treating the neck nodes depends on the method used to treat the primary lesion. Patients with a relatively early primary lesion and clinically negative nodes should be treated with one modality. Patients whose primary lesion is treated surgically may undergo an elective neck dissection, and those whose primary lesion is to be treated with RT should be considered for elective neck irradiation.
The results of elective neck irradiation at the University of Florida for patients with squamous cell carcinoma of the head and neck in whom the primary lesion was controlled are shown in Table 49.9.4,45 Patients were divided into three risk categories based on the estimated risk of subclinical disease in the neck as follows: group I, low risk (<20% likelihood of occult disease); group II, moderate risk (20% to 30% risk of occult disease); and group III, high risk (more than 30% likelihood of occult disease). There were 6 neck failures (21%) in 28 patients who did not receive elective neck irradiation and 8 neck failures (5%) in 162 patients who received elective neck irradiation. Of the eight failures in patients receiving elective neck irradiation, two occurred within the irradiation fields, one at the field margin, and five in out-of-field areas. No correlation was found between the rate of tumor control in the first-echelon lymph nodes and the irradiation dose for doses ranging from 40 to 55 Gy or greater.4 Only one failure occurred in the first-echelon lymph nodes, and this was after 48 Gy in 25 fractions using continuous-course irradiation.4 The low neck, defined as that part of the neck located below the treatment portals used to treat the primary lesion, received either 50 Gy in 25 fractions or 40.5 Gy in 15 fractions, specified at Dmax (0.5 cm depth). Both dose-fractionation protocols were equally effective in sterilizing subclinical disease in the low neck.46 Elective neck irradiation is equally efficacious for squamous cell carcinoma arising from various head and neck primary sites.
If the primary lesion recurs, there is a renewed risk of lymphatic spread to the neck even after elective neck irradiation has been administered because of the possibility of reseeding the neck lymphatics. However, this risk is probably <10% in the first echelon lymph nodes because the prior elective neck irradiation likely fibrosed some of the lymphatic vessels.47 In patients in whom primary failure occurs in addition to failure in the clinically negative nodes, the chances of surgical salvage are poor. In patients in whom the primary lesion is controlled and in whom failure develops in the initially negative neck, the chances of salvage with neck dissection are approximately 60%.
Although elective neck irradiation significantly reduces the risk of neck recurrence, there is no definite evidence that it improves survival. It would be necessary to conduct a large randomized trial to detect a survival difference, if one exists. Another problem is that the first-echelon lymph nodes are often included in the treatment portals used to treat the primary lesion so that it is often impossible to avoid at least partial elective neck irradiation. Therefore, such a trial would have to be restricted to primary sites where the portals would have to be enlarged to electively irradiate the neck or to patients treated with elective neck dissection rather than elective neck irradiation. Vandenbrouck et al.48 and Fakih et al.49 have conducted randomized trials comparing elective neck dissection with no elective neck treatment for patients with oral cavity carcinoma and oral tongue cancer, respectively. No survival advantage was noted for patients undergoing elective neck dissection in either study. However, because of the small number of patients in both trials, it is likely that even if a survival difference existed, it would have been missed.
Dearnaley et al.50 reported on a series of 148 patients treated with an interstitial implant, alone or combined with external-beam RT, for cancer of the tongue or floor of mouth. Of 131 patients with negative neck nodes at diagnosis, 59 (45%) received elective neck irradiation to a dose of 40 Gy or greater. A multivariate analysis showed that elective neck irradiation significantly improved survival and reduced the risk of dying of cancer. Piedbois et al.51 reported a series of 233 patients with T1-2N0 carcinoma of the oral cavity treated with interstitial iridium brachytherapy: 123 patients received no elective neck treatment, and 110 patients underwent an elective neck dissection. Patients who received an elective neck dissection tended to have more advanced primary lesions. Although the ultimate rates of neck control were similar, a multivariate analysis showed that elective neck dissection was significantly associated with improved survival.
TABLE 49.11 FIVE-YEAR RATE OF NECK CONTROL BY 1983 AJCC STAGE AND TREATMENT (459 PATIENTS; 593 HEMINECKS)A
TABLE 49.12 CERVICAL METASTASIS APPEARING IN THE CONTRALATERAL N0 NECK: 596 PATIENTS WITH CARCINOMA OF THE TONSILLAR FOSSA, BASE OF TONGUE, SUPRAGLOTTIC LARYNX, OR HYPOPHARYNX
FIGURE 49.12. Rate of neck disease control (life table method77) for patients treated with twice-daily irradiation (RT) alone or combined with neck dissection (radiotherapy plus RND) for clinically positive neck nodes. A: N2B, N3B. B: N2 A, N3 A. (From Parsons JT, Mendenhall WM, Cassisi NJ, et al. Neck dissection after twice-a-day radiotherapy: morbidity and recurrence rates. Head Neck 1989;11:400–404, with permission.)
Clinically Positive Nodes
The incidence of treatment failure in the neck by N stage and treatment category has been reported by the MD Anderson Cancer Center (Table 49.10) and the University of Florida (Table 49.11 and Fig. 49.12).52,53 In patients in whom the neck is treated with combined modalities, RT precedes surgery when the primary site is to be treated with irradiation or when the node is fixed. Surgery precedes RT when the primary site is to be treated operatively and the nodes are resectable.
When the initial treatment is surgery, a neck dissection is sufficient treatment for patients with a single positive lymph node <3 cm unless there is extracapsular spread of disease. RT may be added for control of subclinical disease in the contralateral side of the neck (Table 49.12).52 The presence of multiple positive nodes in the surgical specimen is an indication for postoperative RT of the neck, especially when positive nodes are found at more than one level.6,54,55
Olsen et al.56 reported a series of 284 patients who underwent neck dissection at the Mayo Clinic for pathologic stage N1 and N2 squamous cell carcinoma of the head and neck; no patient received adjuvant therapy. Neck recurrence-free survival rates at 5 years were as follows: N1, 76%; N2, 60%; and overall, 69%. A multivariate analysis showed that four or more positive nodes (P = .005), invasion of lymphatic or vascular spaces (P = .003), invasion of soft tissue (P = .0008), and a desmoplastic stromal pattern (P = .0001) were significantly associated with an increased risk of recurrence in the neck.56
The postoperative dose prescribed is usually 60 Gy in 30 fractions to 65 Gy in 35 fractions over 6 to 7 weeks for patients with negative margins; higher doses may be prescribed when residual disease is present in the neck.54,57,58 If RT is to be added after surgery, it is usually initiated within 4 to 6 weeks after the operation, although it has been reported that a delay to 10 weeks is not associated with an increased risk of neck failure.54
The rate of control for neck nodes treated with RT alone as a function of node size, treatment scheme, and dose is shown in Table 49.13. RT alone is sufficient for patients with N1 (up to 2 cm) disease as long as the fraction size (2 Gy) and the total dose are sufficient.38 RT followed by neck dissection has provided better rates of disease control than RT alone for patients with more advanced neck disease. The rate of neck disease control for patients treated with twice-daily RT, alone or followed by neck dissection, is shown in Figure 49.12 and shows a significant improvement in the control rates when neck dissection was added in selected cases.59,60 As shown in a multivariate analysis by Ellis et al.61 the addition of neck dissection after RT is independently related to a significantly decreased risk of dying from cancer. At least 50 Gy should be given preoperatively to the lymph nodes, although doses vary according to the size and degree of fixation of the lymph node. For example, large, fixed lymph nodes require 70 to 75 Gy of preoperative RT (Table 49.14). The likelihood of disease control in each side of the neck treated with irradiation and neck dissection is decreased when the node is fixed before treatment or when residual tumor is found in the pathologic specimen (Tables 49.15 and 49.16).14 No difference is seen in the rate of control as a function of the interval between RT and neck dissection when comparing patients who have surgery within 6 weeks with those who have neck dissection more than 6 weeks after RT.14 If a local recurrence occurs, prior combined treatment of the neck does not diminish the chance of successful surgical salvage of the patient.62 The likelihood of disease control at the primary site was not found to be related to neck stage at diagnosis in patients treated with RT alone or followed by neck dissection at the University of Florida;63 this finding is different from what others have reported.64
Results After Incisional or Excisional Biopsy
Patients who have undergone an incisional or excisional biopsy of a metastatic lymph node before referral do not have an increased risk of neck failure or a decreased cure rate if RT is the next step in treatment.43 The likelihood of control and the cure rate are probably diminished if an operation without prior RT follows incisional or excisional biopsy of a metastatic neck node because of the risk that the biopsy procedure disseminated tumor cells into tissues not removed by neck dissection.13
Ellis et al.61 reported on 508 patients with 660 positive heminecks treated at the University of Florida with RT alone or followed by a planned neck dissection. Pretreatment node biopsy did not influence outcome when RT was the next step in treatment (Table 49.17).61 The results of the forward stepwise log-rank tests of prognostic factors for predicting time to recurrence are shown in Table 49.18.61
TABLE 49.13 LYMPH NODE DISEASE CONTROL BY RADIATION TREATMENT TECHNIQUE (NUMBER CONTROLLED/NUMBER TREATED)
TABLE 49.14 CERVICAL LYMPH NODE DISEASE CONTROL WITH RADIATION THERAPY FOLLOWED BY NECK DISSECTION, WITH PRIMARY LESION TREATED INITIALLY BY RADIATION THERAPY (NUMBER CONTROLLED/NUMBER TREATED)
TABLE 49.15 CONTROL OF DISEASE IN THE NECK AS A FUNCTION OF NODE MOBILITY (109 PATIENTS; 121 HEMINECKS)
TABLE 49.16 NECK DISEASE CONTROL AS A FUNCTION OF PATHOLOGIC FINDINGS IN THE NECK DISSECTION SPECIMEN (108 PATIENTS; 120 EVALUABLE HEMINECKS)A
TABLE 49.17 EFFECT OF NECK NODE BIOPSY ON 5-YEAR RATE OF NECK CONTROL (660 HEMINECKS)
CERVICAL LYMPH NODE METASTASIS WITH UNKNOWN PRIMARY TUMOR
In a small percentage of patients with enlarged cervical lymph nodes, the primary lesion cannot be found, even after extensive evaluation.65–67 Patients with enlarged lymph nodes in the upper neck have a good prognosis when treated aggressively, compared with those with enlarged lymph nodes in the low internal jugular chain or supraclavicular fossa. The latter patients are more likely to have primary lesions located below the clavicles, which carry a much worse prognosis. The majority of patients have either squamous cell or poorly differentiated carcinoma. Those with adenocarcinoma almost always have a primary lesion below the clavicles, although if the nodes are located in the upper neck, one must exclude a salivary gland, thyroid, or parathyroid primary tumor. This section deals with patients presenting with squamous cell or poorly differentiated carcinoma in the upper or middle neck.
Patients should be evaluated with a thorough physical examination including careful evaluation of the head and neck. A needle biopsy of the lymph node should be performed. After chest roentgenography, a CT or MRI of the head and neck is obtained to detect an unknown primary lesion arising from the mucosa of the head and neck. It is unclear whether FDG-PET scans may identify primary lesions that would not otherwise be identifiable.68 The available data suggest that some patients will benefit from these studies. Direct laryngoscopy and examination under anesthesia are performed with directed biopsies of the nasopharynx, tonsils, base of the tongue, and pyriform sinuses, and of any abnormalities noted on CT or MRI or suspicious mucosal lesions noted at laryngoscopy. Patients with adequate lymphoid tissue in their tonsillar fossae should undergo an ipsilateral tonsillectomy. The diagnostic evaluation for the patient with cervical metastasis from an unknown head and neck primary lesion is summarized in Table 49.19. The results of a diagnostic evaluation for an unknown primary site in 236 patients at the University of Florida are depicted in Table 49.20.69 Overall, 132 primary sites were discovered in 126 patients (53%) and were most often located in the oropharynx: tonsillar fossa, 59 (45%); base of tongue, 58 (44%); pyriform sinus, 10 (8%); pharyngeal wall, 3 (2%); and supraglottic larynx, 1 (1%).69
Some patients may be cured with treatment directed only to the involved area of the neck70; however, the authors usually irradiate the nasopharynx and oropharynx as well as both sides of the neck. The hypopharynx and larynx were irradiated as well until 1997 when it was decided to eliminate them because they are rarely the site of the primary cancer and because irradiation of these sites significantly increases the morbidity of treatment. It is not necessary to irradiate the oral cavity unless the patient has submandibular adenopathy, in which case the authors either do a neck dissection and observe the patient or irradiate the oral cavity and oropharynx and not the nasopharynx. Patients are treated with parallel-opposed fields at 1.8 Gy per fraction to a midline dose of 64.8 Gy with reduction off the spinal cord at 45 Gy tumor dose (Fig. 49.13). An alternative is to use IMRT to spare the contralateral parotid gland in patients with ipsilateral neck nodes. The lower neck is treated through a separate en face anterior field. IMRT may be used if patients have unilateral neck disease to reduce the dose to the contralateral parotid.
Erkal et al.66 reported on 126 patients treated with curative intent at the University of Florida between 1964 and 1997 with follow-up for at least 2 years. RT was delivered to head and neck mucosal sites and both sides of the neck in 119 patients and to the neck alone in 7 patients. Twelve patients (10%) developed squamous cell carcinoma in a head and neck mucosal site at 0.5 to 10.9 years (median, 1.8 years) after treatment. The 5-year results were as follows: head and neck mucosal failure, 13%; neck node control, 78%; distant metastases, 14%; absolute survival, 47%; and cause-specific survival, 67%. Wallace et al.71 reported a combined series of 179 patients treated at the University of Florida (139 patients) and the University of Wisconsin (40 patients). The 5-year mucosal control rate was 92%; the head and neck mucosa was irradiated in 174 patients (97%). For the subset of 28 patients where the mucosal RT was limited to the nasopharynx and oropharynx, the 5-year mucosal control rate was 100%. Barker et al.65 subsequently reported on 17 patients treated with the larynx-sparing technique described above between 1997 and 2002 at the authors’ institution; none of these patients developed a head and neck mucosal squamous cell carcinoma after receiving RT.
Colletier et al.72 reported on 136 patients treated with neck dissection followed by RT to head and neck mucosal sites and bilateral lymph nodes. Six percent of patients developed carcinomas in head and neck mucosal sites within RT portals, and 4% of patients developed carcinomas in head and neck mucosal sites outside the RT portals. The absolute survival rate at 5 years was 60%. The authors recommended RT to head and neck mucosal sites. Reddy and Marks73 reported on 16 patients with RT to ipsilateral lymph nodes and 36 patients with RT to head and neck mucosal sites and bilateral lymph nodes. The authors concluded that RT reduced the rate of developing carcinomas in head and neck mucosal sites. For patients with no RT to head and neck mucosal sites, the rate of developing carcinomas in head and neck mucosal sites was 46% and the absolute survival rate at 5 years was 47%. For patients treated with RT to head and neck mucosal sites, the rates were 8% and 53%, respectively. Grau et al.74 reported on 273 patients treated with curative intent at five cancer centers in Denmark between 1975 and 1995 with surgery alone (23 patients), RT to the ipsilateral neck alone or combined with surgery (26 patients), and RT to the neck and head and neck mucosa alone or combined with surgery (224 patients). The ipsilateral oropharynx unintentionally received some RT in patients treated to the ipsilateral neck alone, depending on the treatment technique. The 5-year rates of freedom from failure in the head and neck mucosa were as follows: surgery alone, 45%; RT with or without surgery to the ipsilateral neck, 77%; and RT to the head and neck mucosa with or without surgery, 87%. The oropharynx, particularly the base of tongue, was the most common location of mucosal site failure.
The incidence of subsequent mucosal primary lesions was compared by Erkal et al.25 for 1,112 patients with a known primary site (oropharynx, hypopharynx, and supraglottis) and a series of 126 patients treated for an unknown primary site at the University of Florida. The incidence of a subsequent mucosal head and neck cancer was similar for both groups, suggesting either that mucosal irradiation significantly reduced the risk of primary site failure or that patients with unknown primary sites have a much lower risk of a second primary head and neck cancer developing subsequently (Fig. 49.14).66
A subset of patients presenting with squamous cell carcinoma metastatic to the neck nodes from an unknown head and neck primary site are treated with palliative intent because of poor medical condition, extensive nodal involvement, or distant metastases at presentation. Treatment of the neck depends on the extent and location of the adenopathy. Forty of 166 patients (24%) were treated palliatively at the University of Florida between 1964 and 1997.75 Treatment was delivered to the neck alone to a dose of 30 Gy in 10 fractions over 2 weeks or 20 Gy in 2 fractions with a 1-week interfraction interval. The nodal response rate was 65% and the symptomatic response rate was 57% at 1 year. The 1-year absolute and cause-specific survival rates were 25%.
The main complication of RT for patients treated for an unknown head and neck primary tumor is xerostomia. The complications of treatment of the neck, which have been discussed previously, depend on whether a neck dissection is added.76
TABLE 49.18 PROGNOSTIC FACTORS, IN ORDER OF THEIR IMPORTANCE, FOR PREDICTING THE TIME TO OCCURRENCE OF VARIOUS EVENTS
TABLE 49.19 DIAGNOSTIC WORKUP FOR CERVICAL LYMPH NODE METASTASES: UNKNOWN PRIMARY TUMOR
TABLE 49.20 DETECTION OF PRIMARY SITE VERSUS PATIENT GROUP
FIGURE 49.13. Radiation therapy portals used starting from 1997 to treat head and neck mucosal sites and upper cervical lymph nodes (A) and lower cervical and supraclavicular lymph nodes (B). The inferior border for lateral portals is placed at the superior anterior border of the thyroid cartilage, shielding the hypopharynx and larynx. (From Erkal HS, Mendenhall WM, Amdur RJ, et al. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys 2001;50:55–63, with permission.)
FIGURE 49.14. The rate of developing carcinomas in head and neck mucosal sites for patients treated for carcinomas with an unknown head and neck mucosal site compared to the rate of developing metachronous carcinomas in head and neck mucosal sites for patients treated for carcinomas with a known head and neck mucosal site. (From Erkal HS, Mendenhall WM, Amdur RJ, et al. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys 2001;50:55–63, with permission.)
ACKNOWLEDGMENT
We thank the research support staff of the Department of Radiation Oncology for their help with statistics, editing, and manuscript preparation.
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