25 Management of the Neck with Radiation Therapy

The management of lymph node metastases is influenced by several factors, including the location, histologic differentiation, the size of the primary tumor, and the availability of capillary lymphatics.^1,2,3,4 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 25.1.¹ Recurrent tumors have a higher risk of lymphatic involvement with a less predictable drainage pattern than untreated tumors.

Computed tomography (CT), magnetic resonance imaging (MRI), fluorodeoxyglucose–positron emission tomography (FDGPET), and ultrasound may be used to evaluate cervical metastatic disease.⁵ 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. Radiation therapy (RT) can be used in the treatment of cervical lymph node metastases as elective treatment when there is no clinically positive adenopathy, as the only treatment for clinically positive lymph nodes,⁶ or as adjuvant preoperative or postoperative treatment in combination with neck dissection.⁷ RT treatment planning of the neck is guided by several factors, including the location of the primary lesion, the estimated risk of subclinical disease in clinically negative lymph nodes, and the size, location, and number of clinically positive nodes.

Intensity-modulated RT (IMRT) is the most common RT technique used to treat head and neck squamous cell cancers of the mucosa; however, a low anterior neck field can be used to better limit the dose to the larynx when treating the lower neck nodes ( Fig. 25.1, Fig. 25.2). Advantages of IMRT over conventional RT include 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.⁸ The most important disadvantage of using IMRT versus conventional RT is the increased risk of a marginal miss.⁸ Additionally, the utilization of IMRT versus conventional RT results in increased treatment costs. A summary of typical IMRT treatment volumes when treating patients with head and neck squamous cell cancers is detailed in Table 25.2.

25.2 Elective Radiation Therapy of Cervical Lymph Nodes When the Primary Tumor Is Treated by Radiation Therapy

Several factors influence the decision to irradiate the neck electively. The most important factors are the site and size of the primary lesion. Other factors that influence this decision include histologic grade of the tumor, relative morbidity for adding lymph node coverage, likelihood of the patient’s returning for follow-up examinations, and suitability of the patient for a neck dissection if the tumor recurs. If a patient has a primary lesion that is to be treated with RT and the risk of subclinical neck disease is 15% or greater, elective neck irradiation to a minimum dose equivalent to 45 to 50 Gy over 4.5 to 5 weeks is indicated ( Table 25.1).

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 RT is not indicated.^11,12

Patients with lesions arising from the oral cavity, oropharynx, nasopharynx, subglottic larynx, and hypopharynx who have indications for RT at the primary site do receive elective neck irradiation due to the risk of clinically lymph node–negative subclinical disease. Elective neck irradiation for oral cavity tumors includes the bilateral level Ib, II, III, and IV lymph nodes. For primary lesions located in the oropharynx, nasopharynx, and supraglottic larynx, level V nodes are also included. Patients with hypopharyngeal cancers and those with T3–T4 glottic carcinomas also receive RT to level VI nodes.

Fig. 25.1 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 2–3-cm inferior margin. The lower border of the field is placed at the thyroid notch and slants superiorly as the junction line proceeds posteriorly. 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). (Reproduced with permission of Mendenhall et al.⁹)

Fig. 25.2 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 (a) and (b) shows that sparing of the central portion of the larynx is shielded in an anterior low-neck field. (Reproduced with permission of Amdur et al.¹⁰)

Table 25.2 Intensity-modulated radiation therapy target definitions at the University of Florida

Clinically positive cervical lymph nodes require a higher dose of radiation to achieve local control when compared to subclinical disease. The required dose to these nodes is directly correlated with the size of the lymph node^6,13 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.¹⁴ Patients treated at the authors’ institution routinely receive hyperfractionation or simultaneous integrated boost (SIB) combined with weekly cisplatin 30 mg/m². SIB consists of 70 Gy in 35 fractions over 30 treatment days in 6 weeks with 1 twice-daily fraction during the last 5 weeks with a minimum 6-hour interfraction interval. The high-risk planning treatment volume (PTV) receives 70 Gy at 2 Gy per fraction, intermediate PTV receives 63 Gy at 1.8 Gy per fraction, and the standard risk PTV receives 56 Gy at 1.6 Gy per fraction. Other dose regimens that are acceptable include IMRT with a sequential boost, or hyperfractionation with twice-daily fractionation. Positive nodes receive approximately 70 to 74 Gy, regardless of size or rate of regression. Acceptable dose regimens are detailed in Table 25.3.

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.^15,16,17,18 At the authors’ institution, at PET-CT scan is obtained 12 weeks post-RT to evaluate for residual nodal disease. If a patient has PET-avid cervical adenopathy at this time, a neck dissection is recommended.

Johnson et al¹⁹ reported on 81 patients with node-positive stages III and IV squamous cell carcinoma (SSC) of the head and neck treated with concomitant boost accelerated hyperfractionated RT at the Medical College of Virginia (Richmond). A total of 58 patients (72%) had a complete response in the neck and were followed; 3 patients (5%) subsequently developed an isolated recurrence in the neck, and 1 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 or less compared with 86% for those more than 3 cm. Peters et al²⁰ reported on 100 node-positive patients with SSC 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 or less, 87%; and more than 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.

Table 25.3 Dose regimens for head and neck cancer

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.^7,21,22

Liauw et al²³ 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 greater than 1.5 cm and no focal abnormalities such as focal lucency, enhancement, or calcification.²³ The outcomes are depicted in Table 25.4. Thirty-two patients who had an rCR were followed, and did not undergo a neck dissection; the neck control rate was 97%. Recent data published by Yeung et al²⁴ 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.

Goenka et al²⁵ reported on 302 patients with node-positive oropharyngeal SCCs treated with IMRT and concomitant chemotherapy at the Memorial Sloan Kettering Cancer Center between 2002 and 2009. Patients underwent a PET-CT following treatment to assess response. A clinical and radiographic complete response was observed in 260 (86.1%) patients, and the patients were observed. The neck control rate was 97.7%. Three of four patients who recurred in the neck were successfully salvaged. Patients who underwent a neck dissection had the following rates of pathologically visible tumor: PET-CT positive, 52%; and PET-CT negative, 25%.

Mehanna et al²⁶ reported on a prospective trial where 564 node-positive patients were randomized to chemoradiation followed by PET-CT and either planned neck dissection (282 patients) or observation in the event of a CR (282 patients). Patients in the latter group underwent fewer neck dissections: the 2-year survival rates were comparable.

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