Catherine E. Mercado and William M. Mendenhall
Abstract
Patients with a clinically negative neck undergo elective neck treatment if the risk of subclinical disease is 15% or higher. Elective neck dissection is employed if the primary site is treated with definitive radiotherapy (RT). Patients with clinically positive nodes who are treated with definitive RT undergo a post-RT neck dissection if the nodes do not completely respond. Patients who undergo definitive surgery receive postoperative RT for close or positive margins, 2 or more positive nodes, extracapsular extension, perineural invasion, > 1cm subglottic extension, and involvement of the apex of the pyriform sinus.
Keywords: radiotherapy, neck dissection, head and neck cancer, elective neck treatment
25.1 Introduction
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 (FDG- PET), 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.
Table 25.1 Risk of subclinical disease in the neck
|
Group |
Estimated risk of subclinical neck disease |
Stage |
Site |
|
I: Low risk |
<20% |
T1 |
Floor of mouth, retromolar trigone, gingiva, hard palate, buccal mucosa |
|
II: Intermediate risk |
20-30% |
T1 |
Oral tongue, soft palate, pharyngeal wall, supraglot- tic larynx, tonsil |
|
T2 |
Floor mouth, oral tongue, retromolar trigone, gingiva, hard palate, buccal mucosa |
||
|
III: High risk |
>30% |
T1-T4 |
Nasopharynx, pyriform sinus, base of tongue |
|
T2-T4 |
Soft palate, pharyngeal wall, supraglottic larynx, tonsil |
||
|
T3-T4 |
Floor of mouth, oral tongue, retromolar trigone, gingiva, hard palate, buccal mucosa |
Source: Adapted from Mendenhall and Million.1
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 dissec- tion.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
|
Target Definition |
|
|
GTV primary |
Gross tumor in primary site or post-op bed |
|
GTV node |
Gross tumor in lymph nodes |
|
CTV HR |
GTV primary+ 1-cm isotropic expansion AND GTV node + 5-mm isotropic expansion |
|
CTV IR |
CTV HR + completion of positive and adjacent nodal stations |
|
CTV SR |
CTV IR +elective nodal regions |
|
PTV HR, IR, SR |
3-mm isotropic margin of each CTV |
|
Abbreviations: CTV, clinical target volume; GTV, gross tumor volume; HR, high risk; IR, intermediate risk; PTV, planning target volume; SR, standard risk. |
|
25.3 Treatment of Clinically Positive Cervical Lymph Nodes When the Primary Tumor Is Treated by Radiation Therapy
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 node6,13 and whether concomitant chemotherapy is administered.
Relatively recent data suggest that advanced disease has a better chance of cure after altered fractionation or concomitant che- motherapy.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
|
Standard fractionation: one fraction per day |
PTV SR: 56 Gy at 1.6 Gy/fx |
|
IMRT SIB |
PTV IR: 63 Gy at 1.8Gy/fx |
|
Total treatment days: 35 |
PTV HR: 70 Gy at 2Gy/fx |
|
Accelerated fractionation: one fraction per day with two fractions 1 day per week starting on week 2 |
PTV SR: 56 Gy at 1.6 Gy/fx |
|
IMRT SIB |
PTV IR: 63 Gy at 1.8Gy/fx |
|
Total treatment days: 30 |
PTV HR: 70 Gy at 2Gy/fx |
|
Accelerated fractionation: two fractions per day |
PTV SR: 50.4 Gy at1.2Gy/fx |
|
IMRT sequential boost |
PTV IR: 9.6Gy at 1.2 Gy/fx boost (total dose 60 Gy) |
|
Total treatment days: 31 |
PTV HR: 14.4 Gy at 1.2 Gy/fx boost (total dose 74.4Gy) |
|
Abbreviations: fx, fraction; HR, high risk; IMRT, intensity-modulated radiation therapy; IR, intermediate risk; PTV, planning target volume; SIB, simultaneous integrated boost; SR, standard risk. Note: Accelerated fractionation is preferred |
|
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.
Table 25.4 Predictive value of postradiotherapy computed tomography findings at 4 weeks in the hemineck correlated with neck dissection pathology (N = 193 heminecks)
|
Findings |
NPV Number/ Percent total number |
PPV Number/ Percent total number |
||
|
Any lymph node > 1.5 cm |
85/118 |
72 |
24/75 |
32 |
|
Any lymph node with focal lucency |
49/57 |
86 |
49/136 |
36 |
|
Any focally abnormal lymph nodes |
75/98 |
77 |
34/95 |
36 |
|
Any lymph node with enhancement |
111/147 |
76 |
21/46 |
46 |
|
Any lymph node with calcification |
102/144 |
71 |
15/49 |
31 |
|
Two or more focally abnormal lymph nodes3 |
90/113 |
80 |
34/80 |
43 |
|
Any lymph node > 1.5 cm and any focally abnormal lymph node |
32/34 |
94 |
55/159 |
35 |
|
Abbreviations: NPV, negative predictive value; PPV, positive predictive value. aFocally abnormal lymph nodes equal grade 3 or 4 focal lucency, focal enhancement, or focal calcification. |
||||
At the University of Florida, all patients with clinically positive nodes are evaluated with a PET-CT at 3 months after the completion of RT. This time period between the completion of RT and the PET-CT minimizes the risk of a false-positive scan. Neck dissection is withheld in the subset of patients with a complete response, who are thought to have 5% or less risk of residual disease; the remainder of patients undergo a neck dissection.
If a neck dissection is planned to follow RT in patients with clinically positive lymph nodes, the preoperative dose can vary with the size and location of the lymph node, fixation, and response to RT. At the authors’ institution, clinically positive lymph nodes regardless of morphology are treated within in the high- risk PTV to a dose of 70 to 75 Gy.
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. Performing a unilateral versus bilateral neck dissection requires individualized treatment planning jointly by the radiation oncologist and the surgeon. RT alone may be sufficient to control the disease on the side of the neck with minimal disease, 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.
25.4 Treatment of the Neck After Incisional or Excisional Biopsy
Incisional or excisional biopsy of a clinically positive lymph node prior to definitive treatment can potentially spill malignant cells along tissue planes precluding the ability for the removal of all tumor cells with radical neck dissection. Therefore, an open biopsy before definitive treatment of the neck is strongly discouraged. McGuirt and McCabe27 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 SCC of the head and neck. Parsons et al28 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.29 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.29 If residual disease remained in the neck after biopsy, RT followed by neck dissection was more successful than RT alone for controlling neck disease (Table 25.5).
If there is indication to treat the primary tumor surgically, the patient will undergo a complete neck dissection followed by RT. Alternatively, the patient is treated with preoperative RT followed by resection of the primary site and a neck dissection. If the primary lesion is to be treated with definitive RT, the patient’s neck is treated with RT followed by a neck dissection if residual cervical adenopathy is present at the completion of RT. The dose of RT preceding a neck dissection depends on the amount of gross disease in the neck and the degree of fixation.
25.5 Ipsilateral Neck Irradiation
In patients without a history of previous neck surgery, the right and left lymphatic networks do not usually shunt from one side to the other. The utilization of ipsilateral radiation therefore can be considered in highly selected patients. Ipsilateral neck irradiation minimizes dose to the contralateral normal structures and potentially decreases acute and long-term morbidity from RT. However, a concern of ipsilateral therapy is the potential for contralateral neck nodal relapse. Therefore, this modality is primarily used in patients with well-lateralized T1-T2, N0-N2 stage tonsillar cancers without base of tongue or soft palate involvement.31
Kennedy et al32 reported their experience with ipsilateral neck RT for early-stage SCC of the tonsillar area with no base of tongue or soft palate extension. Definitive RT to the primary site and ipsilateral neck resulted in a 5-year local-regional control rate of 92.6%. Of the 76 patients treated, only 1 patient failed in the contralateral, nonirradiated neck 3 years after primary RT (Fig. 25.3).
Huang et al31 from Princess Margaret Hospital reported on their experience of treatment of T1-T2, N0-N2b tonsillar cancer patients who received ipsilateral RT and bilateral RT between 1999 and 2014. At a median follow-up of 5 years, the overall survival, local control, and regional control rates were similar for the ipsilateral versus bilateral RT group. Contralateral neck failure occurred in 2 of the 86 patients (2.3%) who received ipsilateral RT.
At the authors’ institution, unilateral RT is recommended for patients with tonsillar SSC when their risk of cancer in the contralateral lymph nodes is less than 10%. This subset includes patients with T1-T2, N0-N2b tonsillar fossa or anterior tonsillar pillar tumors with no soft palate or base of tongue invasion. Concurrent chemotherapy with weekly cisplatin (30 mg/m2) is given to patients with two or more positive lymph nodes.
Table 25.5 Effect of neck node biopsy on 5-year rate of neck control (660 heminecks)
|
No neck biopsy Neck biopsy |
|||||
|
Hemineck stage |
Number of heminecks |
Probability of hemineck control (%) |
Number of heminecks |
Probability hemineck of control (%) |
Significance of difference between curves |
|
N1 |
253 |
87 ± 3 |
12 |
100 |
p = 0.22 |
|
N2A |
53 |
73 ± 8 |
15 |
93 ± 6 |
p = 0.18 |
|
N2B |
218 |
78 ± 3 |
23 |
72 ± 11 |
p = 0.86 |
|
N3A |
69 |
54 ± 7 |
17 |
81 ± 10 |
p = 0.30 |
Source: Adapted from Ellis et al.30
Fig. 25.3 Kaplan-Meier curve illustrating local control and local-regional control rates at 10 years of patients treated with definitive ipsilateral RT for early-stage squamous cell carcinoma of the tonsillar region. (Reproduced with permission of Kennedy et al.32)
25.6 Treatment of the Neck After Surgery
Patients who are treated with primary surgery for their head and neck mucosal cancer generally undergo resection of their primary tumor and a unilateral or bilateral neck dissection. The surgical management of the neck is dependent on the location, extent of the primary tumor, and the extent of positive neck nodes. Indications for postoperative RT include positive or close (< 5 mm) margins, initially positive margins with negative, separately submitted margins, extracapsular extension, multiple positive nodes, perineural invasion, bone or cartilage invasion, extension into the soft tissues of the neck, invasion of the apex of the pyriform sinus, and subglottic extension of 1 cm or more.33 The highest risk indications are positive margins and extracapsular extension and require the addition of concomitant cisplatin during the course of postoperative RT.
Potentially hypoxic tissues secondary to surgery can increase the risk of the radio resistance of tumor cells; hence, the minimum postoperative radiation dose recommended is 60 Gy at 2 Gy per once-daily fraction. Areas within the neck that are at the highest risk for microscopic disease should receive a higher dose in the range of 66 to 70 Gy. Treating the primary site alone if the neck nodes are pathologically negative may be considered, particularly for frail patients and those with significant postoperative complications. However, postoperative RT is not employed for the indication to electively treat the clinically negative neck in lieu of a neck dissection.
25.7 Complications of Neck Irradiation
The complications of neck irradiation include subcutaneous fibrosis and lymphedema of the larynx and submentum. The probability of complications is directly related to the radiation dose delivered and the location of the irradiated tumor relative to normal structures, such as the mandible and hearing apparatus. There is little, if any, morbidity observed with the doses used for elective RT 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.
25.8 Results of Treatment
25.8.1 Clinically Negative Nodes
Elective neck dissection and elective neck irradiation are equivalent in locally controlling subclinical disease. In addition, elective neck irradiation is equally efficacious for SCC arising from various head and neck primary sites. 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 who receive definitive RT to their primary lesion should be considered for elective neck irradiation, while those who are primarily treated surgically should undergo an elective neck dissection if indicated. Patients who develop a local recurrence or a metachronous second primary after RT for an SCC with a cN0 neck in whom the neck has been irradiated may be treated with surgery to the primary site alone and the neck observed because the likelihood of subclinical disease in the cervical lymphatics is less than 10%.34,35
The University of Florida has reported its results of elective neck irradiation for patients with SSC of the head and neck in whom the primary lesion was treated with definitive RT. The results are illustrated in Table 25.6.1 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 (20-30% 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 great- er.1 Only one failure occurred in the first-echelon lymph nodes, and this was after 48 Gy in 25 fractions using continuous-course irradiation.1 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.36
Vandenbrouck et al37 and Fakih et al38 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. Subsequently, a randomized trial was conducted at the Tata Memorial Hospital (Mumbai) where 596 patients with T1-T1 N0 SCCs of the oral cavity were randomized to resection of the primary and observation of the neck or to resection of the primary and elective neck dissection. Those in the latter group had significantly improved overall survival at 3 years (80 vs. 68%; p = 0.01).39
Although elective neck irradiation significantly reduces the risk of recurrence in the neck, there is no definite evidence that it improves survival. A large randomized trial would be necessary to detect a survival difference, if one exists. Additionally, it is likely that if elective neck dissection improves survival, elective neck irradiation would as well.
Table 25.6 Control of disease in the clinically negative neck with elective neck irradiation (number controlled/number treated)
|
Risk group |
No ENI (%) |
Partial ENI (%) |
Total ENI (%) |
|
I (<20%) |
13/15 (87) |
16/17 (94) |
1/1 (100) |
|
II (20-30%) |
6/9 (67) |
34/38 (89) |
10/11 (91) |
|
III (> 30%) |
3/4 (75) |
32/33 (97) |
61/62 (98) |
Abbreviation: ENI, elective neck irradiation.
Source: Adapted from Mendenhall and Million.1
Patients treated with primary RT who have a local recurrence in addition to a recurrence in the neck have a very poor chance of surgical salvage (< 10%). In patients in whom the primary lesion is controlled with RT and in whom disease recurs in the initially negative neck, the chances of salvage with neck dissection are approximately 50 to 60%.
25.8.2 Clinically Positive Nodes
The rate of controlling clinically positive cervical nodes with RT alone or with combined RT and neck dissection is directly correlated with a patient’s volume of neck disease. 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 25.7. RT alone is sufficient for patients with N1 (up to 2 cm) disease if the total dose is sufficient.40 However, RT followed by neck dissection has provided better rates of disease control than RT alone for patients with more advanced neck disease. The incidence of treatment failure in the neck by N stage and treatment category has been reported by the MD Anderson Cancer Center (Table 25.8) and the University of Florida (Table 25.9).
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 incompletely resectable. Surgery precedes RT when the primary site is to be treated operatively and the nodes are resectable.
Table 25.7 Lymph node disease control by radiation treatment technique (number controlled/number treated)
|
Node size (cm) |
Continuous course (%) |
Split course (%) |
Excludeda |
Total (%) |
|
<1.0 |
5/5 |
2/2 |
1/1 |
8/8 |
|
1.0 |
29/35 (83) |
19/23 (85) |
3/4 |
51/62 (82) |
|
1.5-2.0 |
43/49 (88) |
20/24 (83) |
5/9 |
68/82 (83) |
|
2.5-3.0 |
14/19 (74) |
10/18 (56) |
0/3 |
24/40 (60) |
|
3.5-6.0 |
14/20 (70) |
10/17 (59) |
0/1 |
24/38 (63) |
|
> 7.0 |
0/2 |
0/5 |
0/1 |
0/8 |
Source: Modified from Mendenhall et al.40
aLess than 50 Gy for nodes equal to 1.0 cm and <55 Gy for nodes equal to 1.5 cm.
Table 25.8 Failure of initial ipsilateral neck treatment: 596 patients with carcinoma of the tonsillar fossa, base of tongue, supraglottic larynx, or hypopharynx
|
Treatmenta |
N0 |
N1 (%) |
N2A (%) |
N2B (%) |
N3A (%) |
N3B (%) |
||
|
No treatment |
Partial treatment |
Complete treatment |
||||||
|
Irradiation |
15% |
2% |
15 |
27 |
27 |
38 |
34 |
|
|
Surgery |
55% (16/29) |
35% |
7% |
11 |
8 |
23 |
42 |
41 |
|
Combined |
1/5 |
0/6 |
0 |
0 |
0 |
23 |
25 |
Source: Modified from Barkley et al.41
aMD Anderson Cancer Center data; patients treated in 1948-1967.
Table 25.9 Five-year rate of neck control by 1983 AJCC stage and treatment (459 patients; 593 heminecks)3
|
Stage |
Irradiation alone Number heminecks Control (%) |
Irradiation + neck dissection Number heminecks Control (%) |
Significance |
||
|
N1 |
215 |
86 |
38 |
93 |
p = 0.28 |
|
N2A |
29 |
79 |
24 |
68 |
p = 0.6 |
|
N2B |
138 |
70 |
80 |
91 |
p <0.01 |
|
N3A |
29 |
33 |
40 |
69 |
p <0.01 |
Abbreviation: AJCC, American Joint Committee on Cancer.
Note: University of Florida data; patients treated from October 1964 to October 1985; analysis in December 1988 by Eric R. Ellis, MD. aExcludes 67 heminecks on which incisional or excisional biopsy was done before treatment.
Table 25.10 Cervical metastasis appearing in the contralateral N0 neck: 596 patients with the carcinoma of tonsillar fossa, base of tongue, supraglottic larynx, or hypopharynx
|
Treatmenta |
Stage |
||||
|
N0 (%) |
N1 (%) |
N2A (%) |
N2B (%) |
N3A (%) |
|
|
Irradiation |
4 |
2 |
9 |
7 |
0 |
|
Surgery |
25 |
17 |
23 |
43 |
33 |
|
Combined |
0 |
0 |
0 |
11 |
0 |
|
Source: Adapted from Barkley et al.41 3MD Anderson Hospital data; patients treated in |
1948-1967 |
||||
When the initial treatment is surgery, a neck dissection is sufficient treatment for patients with a single positive lymph node less than 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 25.10).41 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.
The postoperative dose prescribed is usually 60 Gy in 30 fractions to 66 Gy in 33 fractions over 6 to 7 weeks for patients with negative margins; higher doses to 70 to 75 Gy may be prescribed when residual disease is present in the neck. If RT is to be added after surgery, it is usually initiated within 4 to 6 weeks after the operation. 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. The dose for clinically positive lymph nodes in the preoperative or definitive RT setting is 70 to 75 Gy.
25.8.3 Results After Incisional or Excisional Biopsy
Open biopsy is not recommended prior to the definitive treatment of metastatic cervical lymph nodes due to the increased risk of tumor cell spillage. Patients in this scenario do not have an increased risk of neck failure or decreased cure rate if RT is the next step in treatment.28 However, the possibility of regional control in this situation likely diminishes if an operation without prior RT is performed because surgery is unable to remove all microscopic malignant cells into disrupt tissues not removed by neck dissection.
Table 25.11 Prognostic factors, in order of their importance, for predicting the time to occurrence of various events
|
Event |
Rank order |
Factor |
Level of significance |
|
|
Recurrence in neck (N = 660 heminecks) |
1 |
Increasing N stage Treatment of neck |
p = 0.0001 |
|
|
2 |
p = 0.0001 |
|||
|
with RT alone |
||||
|
3 |
Fixed nodes |
p = 0.0001 |
||
|
4 |
T stagea |
p = 0.0350 |
||
|
Death with disease present (N = 508 patients) |
1 |
Recurrence above clavicles |
p = 0.0001 |
|
|
2 |
Increasing N stage |
p = 0.0003 |
||
|
3 |
Fixed nodes |
p = 0.0053 |
||
|
4 |
Treatment of neck RT alone |
p = 0.0121 |
||
|
For occurrence of distant metastasis (N = 508 patients) |
1 |
Recurrence above clavicles |
p = 0.0001 |
|
|
2 |
Increasing N stage |
p = 0.0003 |
||
|
3 |
Fixed nodes |
p = 0.0704 |
||
|
4 |
Nodes below thyroid notch |
p = 0.1032 |
Abbreviations: RT, radiotherapy.
Source: Adapted from Ellis et al.30
aThis factor is thought to be correlated with the censoring pattern.
Ellis et al30 reported on 508 patients with 660 positive hemi- necks 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 25.5).30 The results of the forward stepwise log-rank tests of prognostic factors for predicting time to recurrence are shown in Table 25.11.30
Zenga et al42 reported on 45 patients treated between 1998 and 2012 who underwent open biopsy for human papillomavirus-positive oropharyngeal cancer. All patients underwent definitive surgical treatment. Disease specific survival was 98 versus 99% in a control group who did not undergo an open biopsy. Approximately 7% of patients in the open biopsy group were found to have dermal metastases in the excised skin—thus illustrating the importance of excision of the skin in the biopsied area along with a neck dissection if surgery is the primary treatment for patients with previously violated cervical nodes. In these scenarios, adjuvant RT with 60 to 70 Gy is recommended to minimize the likelihood of regional recurrence.
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