Mingyann Lim and Mark Zafereo Abstract
A salvage neck dissection is defined as a neck dissection in a neck that has been previously treated with radiation, chemotherapy, surgery, or a combination of these three modalities. This procedure can be planned or unplanned, and there is mounting evidence to suggest that planned salvage neck dissection is unnecessary in most circumstances. Salvage neck dissection should be performed for nodal disease that is in partial remission following radiation or chemoradiation, as well as cases of recurrent disease. Preoperative workup may include cross-sectional imaging (CT or MRI), PET scan, and/or ultrasound-guided fine-needle aspiration (FNA). Following definitive chemoradiation of neck disease, PET scan has a very high negative predictive value, such that patients with a negative PET at 12 weeks posttreatment have an exceedingly low risk of residual nodal disease. Selective or superselective salvage neck dissections are generally favored over a comprehensive neck dissection in the salvage setting. Important intra- and postoperative considerations with salvage neck surgery include awareness of the importance of en bloc disease resection, achieving negative margin status, possible need for vascularized tissue, and potential indication for adjuvant external beam radiation or brachytherapy.
Keywords: salvage neck dissection, radiation therapy, brachy-therapy, head and neck squamous cell carcinoma, recurrence
Salvage neck dissection is defined as a neck dissection for a neck that has been previously treated with radiation, chemotherapy, surgery, or a combination of these three modalities. Salvage neck dissection can be either a planned or unplanned dissection. A planned neck dissection occurs following radiotherapy or chemoradiotherapy (CRT), where, in anticipation of possible residual disease, the neck dissection is sequentially performed as part of the overall initial treatment plan. Unplanned neck dissection refers to the scenario where there is initially no plan to perform neck dissection after therapy, but the decision for the neck dissection follows later due to residual disease or disease recurrence. In the literature, the terminology can be confusing as some authors refer to only unplanned neck dissections as salvage neck dissections, whereas others refer to both planned and unplanned posttreatment neck dissections as salvage dissections.
Salvage neck dissections are characterized by a technically more challenging surgery, due to the presence of scarring and fibrosis from previous treatments (Fig. 10.1). In general, the potential acute and long-term morbidity of a salvage neck dissection is higher than in primary procedures. It is also well documented that after radiation, neck dissection has an increased rate of postsurgical complications, in addition to increased subdermal fibrosis, neck and shoulder stiffness, pain, and dysphagia.1 Additionally, disease control with salvage neck dissection is poorer than with primary neck dissection, as the disease tends to be biologically more aggressive and may be resistant to adjuvant treatment. Furthermore, fewer adjuvant treatment options may be available due to toxicity from previous therapies.2 Finally, it is critically important to place salvage neck surgery in the overall context of the patient, and the overall disease burden. Patients with local disease recurrence in addition to regional disease recurrence often have poorer prognosis and are faced with more significant morbidity and radical changes to their quality of life in the setting of salvage surgery. In these patients, the prognosis and morbidity tend to be highly correlated with the site of recurrence. Generally, among patients presenting with synchronic local and regional recurrence, those with laryngeal or oral cavity primaries tend to fare better than those with oropharyngeal disease.3 Given these inherent challenges, it is crucial for clinicians to be familiar with the workup, decision-making process, and technical considerations associated with nodal disease that may necessitate a salvage neck dissection.
Fig. 10.1 Salvage modified radical neck dissection after chemoradia- tion therapy for squamous cell carcinoma of the oropharynx, with sacrifice of the internal jugular vein, and preservation of the sternocleidomastoid muscle and spinal accessory nerve. Vagus and hypoglossal nerves are preserved and visible. Dense fibrotic tissue in the neck encasing the cervical rootlets demonstrates the extent of treatment-related soft-tissue fibrosis and scarring.
There are several clinical scenarios in which a salvage neck dissection may be considered: (1) partial nodal remission following (chemo)radiation therapy; (2) complete nodal remission in a post(chemo)radiotherapy neck as part of a planned neck dissection; (3) disease recurrence in the neck following previous surgery (with or without radiation); (4) local disease recurrence in a previously treated N0 neck. These four potential indications for salvage surgery will be sequentially reviewed in subsequent subsections.
10.2.1 Partial Nodal Remission Following (Chemo)radiation Therapy or Complete Remission in a Post(chemo) radiotherapy Neck as Part of a Planned Neck Dissection
The most common scenario in which a salvage neck dissection is performed is in the context of a patient who has had (chemo) radiotherapy as initial treatment for a head and neck cancer. Chemoradiation—as a combined modality for advanced head and neck cancer—has allowed for improved organ preservation, with generally equivalent rates of locoregional control compared to surgery and adjuvant treatment. A patient who has been treated with (chemo)radiotherapy can have either a complete or an incomplete response to treatment.
There is an inverse relationship between the likelihood of complete response to treatment in relation to the size and overall burden of nodal disease,4 with N1 nodal disease showing the best complete response to (chemo)radiotherapy, with relatively less complete response among patients with N2 and N3 dis- ease.5 For patients with less than complete response in neck lymph nodes, salvage neck dissection should be performed assuming the disease is surgically resectable.6,7 For patients who have had complete remission of disease in response to therapy, those with original N1 disease do not require a salvage neck dissection.8,9 It is among the N2 and N3 group patients wherein controversy has existed over whether a salvage neck dissection should be performed, even with complete response in the neck to (chemo)radiotherapy. The evidence for and against planned neck dissection for patients with N2/N3 disease will be explored in the following three subsections.
10.2.2 Evidence Supporting Planned Neck Dissection for N2/N3 Disease Following (Chemo)radiotherapy
Several studies lend support to planned neck dissection following irradiation only for head and neck squamous cell carcinoma (SCC) patients with N2/N3 disease. Mendenhall et al looked at 161 patients (oral cavity, oropharynx, nasopharynx, hypophar- ynx, supraglottic larynx, unknown head and neck primary) and found that after radiotherapy, initial control of neck disease dropped from 92% for N1 disease to 65% for N2a disease.10 Du- bray et al found similar poor results for N2/N3 necks after radiotherapy. In a series of 1,251 consecutive patients with nodepositive oropharyngeal or pharyngolaryngeal SCC, the overall 3-year actuarial neck failure rates were 33% for N2 (n = 103) and 45% for N3 disease (n = 699).11
Studies incorporating both, radiotherapy arms and concurrent CRT arms, show similar results. In Lavertu et al’s9 retrospective review of a 100-patient, phase III randomized clinical trial comparing definitive concurrent CRT with radiotherapy alone, 35 of 53 patients with N2/N3 disease had a neck dissection. None of the patients in this cohort who had a complete response in the neck, and who also underwent a posttreatment neck dissection, experienced regional recurrence. In contrast, 25% of the patients who had a clinically complete response but did not undergo posttreatment neck dissection had regional neck recurrence.
From a histopathologic perspective, several studies have shown that a significant proportion of patients with N2/N3 disease continue to have pathologic disease, despite achieving a clinically complete response post-CRT.1213 McHam et al,12 for example, looked at a series of 109 patients with head and neck SCC (excluding nasopharynx, paranasal sinus, and salivary gland tumors) who had N2 and N3 disease. All patients underwent CRT and a subsequent planned neck dissection at least 6 weeks after treatment. The authors found that 28% of N2 disease patients, and 42% of N3 disease patients had pathologic evidence of disease in the neck dissection specimens.
Additionally, it is also argued that salvage surgery in an unplanned fashion, when disease recurs, is often not successful, with local control rates ranging from 22 to 35%.14 This is due to difficulty in achieving microscopically clear margins in a treated/fibrotic neck, coupled with limited adjuvant treatment options for microscopic disease. Finally, despite increased technical challenge, the immediate reported postoperative complication rates of planned neck dissection remain relatively low. Lavertu et al looked at a series of 100 patients treated in a phase 3 trial comparing radiotherapy alone with concurrent CRT for stage III and IV head and neck SCC. Twenty-nine planned neck dissections were performed for persistent neck disease or initial-stage N2 or greater. They found a major complication rate of 7% after neck dissection for radiation only, and 0% after neck dissection for chemoradiation.15
10.2.3 Evidence Refuting Planned Neck Dissection for N2/N3 Disease Following (Chemo)radiotherapy
Other studies have shown relatively low rates of neck failure after treatment with radiotherapy and CRT. Greven et al retrospectively reviewed 103 patients with stage III/IV, node-positive SCC (larynx, oropharynx, oral cavity, and hypopharynx) who had been treated with definitive radiotherapy or chemoradiation at a single institution with median follow-up of 42 months. CT scans were performed at a median of 4 weeks after treatment. The authors found that patients who had a radiographic complete response on posttreatment CT, and who underwent a neck dissection, had a nodal control rate of 94%, compared with 97% among those without neck dissection. On the other hand, patients with partial radiographic response who were treated with neck dissection had a nodal control rate of 94% compared with 73% among those without neck dissection. The authors concluded that patients who had a complete radiographic response on posttreatment imaging 4 to 6 weeks after radiation did not need a neck dissection.16
A series of 62 node-positive patients with oropharyngeal cancer from MD Anderson Cancer Center were treated with concomitant boost radiation and observed following complete response. The isolated neck failure rate was less than 5%, suggesting that observation is a reasonable approach in patients with nodal complete remission.17 Subsequently, the same group looked at 880 patients with T1-T4, N1-N3 M0 SCC of the oropharynx, larynx, or hypopharynx who received CRT or radiotherapy alone. Nodal complete response occurred in 377 (43%) patients, of whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with complete response was 92%. Two hundred sixty-eight (53%) of the remaining 503 patients without complete response underwent salvage neck dissections, and the 5-year actuarial regional control rate for patients without a complete response was 84%. Those who had a neck dissection fared better, with 5-year actuarial regional control rates of 90% for those operated, versus 76% for those not operated (p < 0.001). Following initial (chemo) radiotherapy, this large study thus supports observation for patients with complete nodal response, but salvage surgery for patients with partial nodal response.18
10.2.4 Planned Neck Dissection for N2/N3 Disease: Current Evidence-Based Recommendations
Drawing conclusions from studies that support and refute the decision for planned salvage neck dissection for N2/N3 disease can be challenging, due to significant heterogeneous and confounding factors inherent in individual studies. Many factors influence neck disease remission following CRT, including location of the primary tumor (e.g., the high response rate observed in nasopharyngeal and human papillomavirus-associated oropharyngeal cancer) and nodal disease burden.
In particular, for posttreatment neck dissections that demonstrate positive pathologic disease, the timing of the neck dissection may be crucial in interpreting results. Even among patients with complete radiologic response to therapy, as many as 30 to 40% of neck dissection pathologic specimens may contain cancer.1920 However, neck dissections in such studies were performed relatively early posttreatment (4-6 weeks). Surgical pathology from an early (4-6 week) posttreatment neck dissection may produce falsely positive results related to tumor cells that are in the process of dying, but yet appear histopathologically positive in the initial posttreatment period. The use of proliferation markers such as Ki-67 may be useful in differentiating active proliferating tumor cells versus nonviable tumor cells.21 When long-term clinical outcomes are analyzed, rather than analysis of early neck dissection pathology results, patients who obtain a complete clinical and radiological response to chemoradiation have a low (< 5%) risk of isolated neck recurrence.22
It has been difficult to prove significant benefit of salvage planned neck surgery for post(chemo)radiotherapy patients with complete radiographic response in the neck, regardless of the initial N staging.9,23,24 It is now generally agreed that it is reasonable to observe an N2/N3 neck after (chemo)radiother- apy if there is no evidence of disease on cross-sectional imaging at 6 weeks after treatment. A negative PET scan at 12 weeks (to be discussed in subsequent sections) makes this approach even more attractive. A routine neck observation approach following CRT is especially favored if patients are reliable to undergo appropriate follow-up imaging at regular intervals. Hence, patient factors and relevant resources of the health care system may also be taken into account. Surveillance post-CRT, rather than planned neck dissection, is now widely accepted as a recommended practice.25,26 However, in select cases, a planned neck dissection may be appropriate in the setting of adverse risk factors, which predispose to poorer ultimate regional control. For example, one may consider a planned salvage neck dissection in the context of large nodal disease burden (especially N3 disease) in non-nasopharyngeal, nonoropharyngeal SCC.
10.2.5 Disease Recurrence in the Neck Following Previous Surgery (with or without Radiation)
Salvage neck dissection may also be performed after a patient has been treated with previous neck dissection (with or without adjuvant postoperative therapy after the neck dissection). Disease recurrence may result from missed lymph nodes in dissected neck levels, extracapsular nodal disease extension that recurs in the soft tissues of the neck, or recurrence in lymph nodes in areas not previously dissected. Aggressive tumor histology has been found to be associated with recurrent neck disease.27 In general, patients with recurrent nodal disease following a neck dissection should be offered a salvage neck dissection provided the disease is grossly resectable.
In a retrospective review of 699 radical neck dissections, Jones et al found that 119 patients who had undergone a radical neck dissection developed a nodal recurrence; of these, 69 were considered candidates for salvage surgery. Factors that increased the risk of neck recurrence were neck node (N) status and absence of adjuvant radiotherapy. The 5-year survival for salvage neck dissection was 31%, with younger patients and low T and N classification having improved survival.28
10.2.6 Local Disease Recurrence in an N0 Neck Previously Treated with (Chemo)radiation Therapy
Salvage neck dissection may be considered in the context of a patient with local disease recurrence, and an N0 neck after previous (chemo)radiotherapy. Salvage neck dissections in this scenario typically yield relatively low rates of neck nodal involvement (< 10%).29 Radiation causes hyalinization and fibrosis of lymphatic structures, resulting in eventual narrowing of these structures,30 which may explain the relative lower rates of subsequent nodal involvement when the primary tumor recurs.
Additionally, neck dissection performed in this setting seems to increase late adverse effects of radiation therapy (RT). In an analysis of three separate Radiation Therapy Oncology Group (RTOG) trials, severe late toxicity after CRT was quite common at 43%, and neck dissection after CRT was an independent risk factor for severe late toxicity with an odds ratio of 2.4.31
Dagan et al performed a retrospective review of patients treated with elective nodal radiation for T1 -T4 N0 M0 SCC of the oropharynx, hypopharynx, or larynx who later developed an isolated local recurrence and remained N0. Fifty-seven patients were salvaged, 40 with neck dissection and 17 with neck observation. Four of 46 (9%) heminecks were found to have occult metastases in the surgical specimen. The 5-year local-regional control rate was 75% for all patients. Neck dissection resulted in poorer outcomes compared with observation. In the dissected group, the 5-year local control, regional control, cause-specific survival, and overall survival rates were 71, 87, 60, and 45%, respectively, compared to 82, 94, 92, and 56%, respectively, for the observation group. Toxicity was more likely with neck dissection. The authors concluded that in the setting of previous elective nodal irradiation, routine elective neck dissection should not be included during salvage surgery for locally recurrent head and neck SCC. The risk of occult neck disease is low, outcomes do not improve, and the likelihood of adverse effects increases.29 For the case of elective salvage neck dissection associated with larynx cancer, the rate of occult nodal metastases has been shown to be about 5%, and there has not been demonstrated a regional control benefit to elective salvage neck dissection in this setting.32
In summary, elective salvage neck dissection in the locally recurrent primary with an already treated neck is not typically recommended. However, it should be recognized that many patients with local recurrence for head and neck SCC require free flap reconstruction of the primary site. Since in these cases the neck must be explored for flap recipient blood vessels, it is reasonable to resect any nodal basin(s) in the area of the respective exploration.
10.3.1 Confirmation of Disease
Some authors make an arbitrary distinction between residual and recurrent diseases, wherein residual disease is disease that remains after treatment (i.e., no disease-free interval) and recurrent disease is disease that becomes apparent after at least 6 months of complete regression. Regional, residual, or recurrent disease can be detected on clinical or radiologic followup. Depending on the philosophy and resources of the treating institution, follow-up imaging may be performed at various intervals in the first 5 years after treatment, and may take the form of ultrasound, CT, MRI, or PET scan.
CT scan with contrast is a quick and efficient means of obtaining a radiologic evaluation of the neck nodal status. The performance of CT scan in the post-CRT setting has been reported as 57 to 85% sensitivity, 24 to 79% specificity, 22 to 59% positive predictive value, and 73 to 94% negative predictive value.20 33 34 In some institutions, MRI is the preferred modality of imaging for surveillance. MRI, with the use of diffusion weighted imaging (DWI) protocols based on tissue cellularity, may aid in discriminating between metastatic and benign neck adenopathy, with metastatic adenopathy demonstrating significantly higher apparent diffusion coefficient.35
Additionally, some have suggested that MRI may be better in distinguishing posttreatment changes versus recurrence in the primary tumor bed, based on T2 signal characteristics.36 Hence, the neck is followed with the same imaging modality as the primary in this setting. However, other studies suggest that the superiority of MRI over CT scan in the follow-up of the primary bed is exclusively for nasopharyngeal cancers, rather than laryngeal and pharyngeal neoplasms.37 A large meta-analysis by de Bondt et al comparing CT and MRI in the detection of lymph node metastases pretreatment in head and neck cancer showed that MRI and CT scan had similar accuracy.38 In many centers, CT is employed as a relatively cheap, quick, and readily available means of imaging surveillance.
While ultrasound-guided FNA biopsy is not first line in the routine surveillance of neck disease, it can be useful to confirm the presence of disease suspected on imaging on CT/MRI before committing to salvage surgery. In the de Bondt et al meta-analysis, the authors concluded that ultrasound-guided FNA biopsy was the most accurate imaging modality to detect cervical lymph node metastases. Ultrasound-guided FNA biopsy showed the highest diagnostic odds ratio (DOR) of 260, compared to ultrasound without FNA (DOR = 40), CT (DOR = 14), and MRI (DOR = 7).38 Nonetheless, it must be stated that ultrasound- guided FNA biopsy is only useful with a positive result. In situations where cytological proof cannot be obtained from an ultrasound-guided FNA biopsy, intraoperative frozen section can be performed to confirm presence of disease before proceeding with surgical resection. In most cases, however, intraoperative frozen section is not feasible due to potential oncologic compromise in obtaining the samples (vs. favored en bloc specimen removal). As such, preoperative counseling and disclosure regarding the possibility of a pathologically negative specimen is a recommended practice.
PET-CT scan has a very high negative predictive value in the posttreatment neck. If the PET-CT is negative, it is very unlike that there is viable tumor present in the lymph nodes, even if there are persistent lymphadenopathies on other imaging modalities (CT, MRI, ultrasound). Its negative predictive value of 93 to 95% for the primary site, and of 94 to 100% for the neck, makes this imaging modality an attractive choice for the initial posttreatment follow-up regimen.39 PET scans have the additional advantage of simultaneous assessment of distant disease; although these tests are resource intensive, patients with negative PET scan at 12 weeks posttreatment have a very low risk of subsequent failure.40,41
A large, multicentric randomized phase 3 trial involving 37 head and neck cancer centers in the United Kingdom recruited 564 patients to study the utility of PET in the evaluation of planned neck dissection post-CRT. The patients were randomized to planned neck dissection before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10 to 12 weeks post- CRT with neck dissection only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). There were 54 neck dissections performed in the surveillance arm, with 22 surgical complications, and 221 neck dissections in the neck dissection arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. The authors concluded that PET-CT-guided active surveillance after CRT showed similar survival outcomes compared to planned neck dissection but resulted in considerably fewer neck dissections, fewer complications, and lower cost, supporting the routine use of PET imaging in the posttreatment setting.42 Although PET is useful in surveillance of the primary and neck after CRT, the resources of the treating institution and country must be taken into account when considering this as an standard practice. A resource-balanced approach that is employed in many centers in the United States is a single PET scan at 12 weeks posttreatment to rule out residual active tumor in nodal remnants, with further follow-up imaging (if necessary) limited to more cost-efficient modalities such as CT.
10.3.2 Extent of Disease and Operative Planning
Imaging is not only important in oncologic surveillance, but also in determining the extent of recurrent disease in order to assess resectability, develop an appropriate surgical plan, and counsel the patient on the potential morbidity of the procedure. Crosssectional imaging (CT or MRI) can delineate disease extending beyond the confines of a lymph node to include involvement of the sternocleidomastoid muscle or internal jugular vein, either of which may require sacrifice with a salvage surgery. Sacrifice of a unilateral internal jugular vein has little functional consequence other than increased preponderance for postoperative lymphedema, while sacrifice of the entire sternocleidomastoid muscle will generally require vascularized tissue transfer (often a pector- alis muscle rotational flap into the neck) to cover the carotid artery. Most importantly, extranodal disease near the carotid sheath or in levels I and II of the neck may involve the vagus, hypoglossal, and/or spinal accessory nerves, all of which have important functional consequences in the event of sacrifice. Extranodal disease extending above the mandible or below the clavicle has implications on surgical access, which generally render disease not meaningfully resectable in a salvage setting for SCC. Carotid artery encasement (>270 degrees) and involvement of the prevertebral fascia or brachial plexus are general contraindications to salvage surgery for SCC due to the combination of high morbidity and low prospects of long-term regional control.
10.3.3 Timing of Posttreatment Imaging
The timing of posttreatment imaging is critically important. False-positive results commonly occur if imaging is performed too early, as nodal remnants and hypermetabolic activity often continue to resolve over time.43 However, delaying posttreatment imaging too long may result in loss of opportunity to intervene in the optimal surgical window following (chemo) radiation therapy. This window represents a short time frame, when fibrosis is less marked and surgery is technically easier to perform, or between resolution of the acute CRT injury and the onset of chronic CRT injury. Another obvious risk in delaying too long is the risk for disease progression. It is, therefore, recommended that CT or MRI be performed approximately 8 to12 weeks after completion of CRT.22
For PET and PET-CT, the timing posttreatment is equally important. As treatment-related inflammation abates, false-positive results on posttreatment PET scan decrease proportionally (increased specificity and negative predictive as time from treatment completion increases).40 The current recommendation for optimal timing of PET is approximately 12 weeks post- treatment.22,40
10.4 Technical Considerations
10.4.1 Which Neck Levels Should Be Included in Salvage Dissection?
The appropriate neck level to address in salvage dissection depends on the primary site, extent of original nodal disease, and current nodal status post(chemo)radiotherapy. Historically, neck dissection performed for presumed residual disease after (chemo)radiotherapy was performed as a comprehensive radical neck dissection to encompass all levels of disease (Fig. 10.2a). However, in recent decades, modified radical and selective neck dissections have been demonstrated to offer equivalent disease control and decreased morbidity, unless there is invasion of the sternocleidomastoid muscle, internal jugular vein, and/or spinal accessory nerve.
Neck dissection after chemoradiation for advanced head and neck cancer is not without risks, especially related to wound healing. Davidson et al showed that a preoperative radiotherapy dose greater than 70 Gy was associated with complications in 58% of the patients, versus 29% if the dose was less than 70 Gy (p = 0.09). This trend was reflected primarily in wound complications, and reached significance for skin flap necrosis.44 Others have shown initial increased incidence of spinal accessory nerve dysfunction, and a negative impact on quality of life, when all five neck levels were dissected.45 In general, more extensive neck dissections with associated removal of fibrofatty tissue result in greater long-term fibrosis with subsequent deleterious effects on swallowing and neck mobility.46
Selective neck dissection is generally preferred to comprehensive neck dissection in the salvage setting. A selective neck dissection is one that involves the removal of at least three contiguous neck levels (Fig. 10.3), whereas a superselective neck dissection is a neck dissection where only two contiguous levels are addressed (Fig. 10.4). The concept of selective neck dissection is based on predictable patterns of lymphatic drainage, and lymphatic tumor spread in association with upper aerodiges- tive tract cancers.4748 However, this philosophy is based on the understanding of lymphatic drainage and lymphatic tumor spread in the untreated neck. In the situation of previous CRT, drainage patterns may potentially change. Nonetheless, several studies have shown that a selective or even superselective neck dissection is generally the preferred salvage option to both limit morbidity and ensure appropriate oncologic disease control.49 50
A study examining 28 postradiotherapy neck dissections for SCC found that only 1 of 28 neck dissections (23 of which were comprehensive) revealed cancer outside nodal levels II, III, and IV. Primary sites in this study were oropharynx (n =19), nasopharynx (n = 3), and larynx/hypopharynx (n = 3). The one case with nodal disease outside levels II to IV was a patient with a 10-cm neck mass.51 Another study by Stenson et al13 suggests that level V need not be addressed unless there is gross disease in this level prior to RT.
Robbins et al examined a series of 106 neck dissections performed after concurrent intra-arterial chemoradiation. The extent of neck dissection was determined by extent of disease, as elucidated by posttreatment imaging. Three subgroups of patients were delineated by the extent of neck dissection: radical or modified radical neck dissection, selective neck dissection, and superselective neck dissection. With a median follow-up of 58 months, regional failure occurred in 11 (5%) of 240 patients: 2/12 (17%) in the modified radical neck dissection group, 3/65 (5%) in the selective neck dissection group, 0/7 in the superselective neck dissection group, and 6/156 (4%) in the no neck dissection group. The rates of overall survival and distant metastases were not significantly different among the three neck dissection subsets. Notwithstanding the selection bias among treatment groups, the authors concluded that selective and superselective neck dissections are viable therapeutic alternatives for patients with residual disease confined to one neck level after intra-arterial chemoradiation, and possibly other chemoradiation protocols.52
Fig. 10.2 (a) Radical neck dissection (with sacrifice of the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle for recurrent neck squamous cell carcinoma, 2.5 years after definitive chemoradiation therapy an oropharyngeal primary. Dense, fibrotic scar tissue can be seen along the floor of the neck. (b) Harvesting of a pectoralis muscle flap for coverage of the carotid artery. (c) Closer view of the pectoralis muscle flap with several vascular pedicles. Note the thinning of the flap around the pedicle to allow for maximum length, so as to reach to the mastoid area. (d) Intraoperative insertion of brachycatheters. Catheters are typically placed at about 1-cm intervals along the tumor bed. The pectoralis muscle flap is then rotated into the neck to cover the brachycatheters.
In another study by Robbins et al involving intra-arterial chemotherapy with concurrent radiation, 57 salvage neck dissections (the majority of which were selective neck dissections rather than modified radical neck dissections) were performed in 54 patients. A comparison was made between clinical and radiological findings, prior to neck dissection and review of final pathology. Only 2 of the 54 patients had evidence of pathologic disease extending beyond a single neck level: one had disease in a contiguous neck level, and the other had disease in a noncontiguous level. The use of superselective neck dissection with removal of only two contiguous neck levels would have encompassed known disease in all but one patient. The authors concluded that superselective neck dissection is a reasonable option for persistent nodal disease confined to one neck level.49
In summary, with the exception of oral cavity and nasopharyngeal cancers, levels I and V have a low incidence of nodal in- volvement,13.50 implying that a comprehensive neck dissection is not generally necessary for a curative resection post-CRT/RT. Selective and superselective neck dissections are favored in the salvage setting, and levels of dissection should be based on the presence of residual disease, and the site of origin of the primary tumor.
10.4.2 Timing of Neck Dissection
For cases where there is residual disease posttreatment (or in the setting of a planned salvage neck dissection), the timing of a salvage neck dissection is in many cases associated with the timing of posttreatment imaging (See section 3.1.3). Several studies have suggested that performing a salvage neck dissection between 8 and 12 weeks following completion of RT may be an optimal time frame as indicated by a low surgical complication rate for neck dissections performed in this interval.13.15 This has been described as a surgical window between resolution of the acute (chemo)radiation injury and the onset of chronic chemo(radiation) injury. Lavertu et al observed a statistically significant higher rate of major surgical complications (20 vs. 3%), and overall complications (60 vs. 31%) after salvage neck dissection as compared to earlier planned neck dissection.15
Fig.1.3 Selective neck dissection of levels I, II, and III following chemoradiation for oral cavity squamous cell carcinoma. Important neurovascular and muscular structures are labeled as follows:
1= external carotid artery; 2 = internal carotid artery; 3 = internal jugular vein; 4 = sternocleidomastoid muscle; 5 = posterior belly of digastric; 6 = omohyoid muscle; 7 = lingual nerve; 8 = hypoglossal nerve; 9 = marginal mandibular nerve; 10 = accessory nerve; 11= cervical rootlets; and 12 = ansa cervicalis.
However, a retrospective study by Goguen et al did not concur. This study compared the complication rate, and relapse rate, between neck dissections performed before 12 weeks and those performed after 12 weeks of completion of treatment. Sixty-seven neck dissections were performed less than 12 weeks posttreatment, while 38 were performed 12 weeks or more after completion of radiation. There was no statistically significant difference in the rate of major or minor complications between the two groups. There was also no difference in the regional relapse rate, progression-free survival, and overall survival between the two groups, with a median follow-up time for surviving patients of 56 (range 3-136) months. This author concluded that the timing of neck dissection may not influence oncologic outcomes or risk of complications.53
Notwithstanding the above study, delaying a salvage neck dissection in the presence of suspected disease (especially if the residual disease is sizeable) may lead to regional disease progression with the development of resistant clones.1 Hence, all things considered, a common approach to imaging and potential neck dissection following (chemo)radiation therapy is to obtain cross-sectional imaging of the neck 6 to 8 weeks after treatment. Patients who have neck nodal remnants deemed as suspicious in axial imaging may undergo PET imaging no sooner than 12 weeks after completion of treatment. If the residual nodal disease is PET positive, a neck dissection is indicated, while patients with equivocal PET activity (low residual fluorodeoxyglucose activity) may either undergo ultrasound FNA, short-term observation with follow-up imaging, or proceed to salvage neck dissection.
Fig. 10.4 Superselective neck dissection of levels II and III for residual squamous cell carcinoma of the neck at 14 weeks following chemo- radiation therapy. Visible preserved structures include the internal jugular vein, sternocleidomastoid muscle, spinal accessory nerve, and hypoglossal nerve. Dense fibrotic scar tissue can be noted along the floor of the neck with accompanying cervical rootlets.
10.4.3 Intraoperative and Postoperative Salvage Surgery Considerations
Typically, neck dissection following RT/CRT is technically more challenging due to fibrotic tissue planes. This fibrosis may be more pronounced in patients treated with chemoradiation as opposed to radiation alone. Blunt-tipped instruments, such as the Cooley Mayo-tipped scissors, may be particularly useful in this setting, especially when dissecting around the carotid artery. A significant challenge in the realm of salvage surgery is delineation of disease boundaries, which can be significantly obscured by fibrosis. It is critically important to excise circumferential margins around areas of residual disease, balancing this primary goal with a very close secondary goal of preservation of critical neurovascular structures.
In a salvage setting, if disease is adherent to surrounding muscle (e.g., sternocleidomastoid, digastric), then at least a cuff of muscle should be resected en bloc with the disease. In some cases where the disease is significantly invading the muscle, a complete resection of the muscle may be required. In these cases, mobilization of nonradiated, well-vascularized tissue is usually necessary to cover the exposed carotid artery. The most commonly used alternative for this purpose is reconstruction with a pectoralis muscle pedicled flap (Fig. 10.2b,c). This flap is relatively easy to harvest, and has a robust pedicle and blood supply, making it extremely reliable tolerance and treatment-related morbidity (Fig. 10.6). It should be emphasized that the decision for brachytherapy must be determined prior to surgery (since the catheters are inserted intraoperatively) and that vascularized tissue (e.g., pectoralis with the appropriate technique. Another reconstructive option is free tissue transfer (e.g., anterolateral thigh, radial forearm free flap), although this is technically more challenging and requires appropriate recipient vessels in the neck. In lieu of other recipient vessel options, which may be compromised by disease and/or fibrosis, the transverse cervical vessels should be remembered as a potential alternative.
Fig. 10.5 (a) A 3.5-cm right retropharyngeal nodal metastasis. The right lateral neck levels II, III, and IV have been dissected, and the posterior belly of the digastric and stylohyoid muscles has been divided to expose the retropharyngeal space. The submandibular gland is preserved and retracted anteriorly. (b) Closer view of the 3.5-cm right retropharyngeal nodal metastasis. The disease underlies the glossopharyngeal nerve and internal carotid artery. The hypoglossal nerve is preserved inferiorly. (c) View of the retropharyngeal space following removal of the nodal metastasis, with preservation of glossopharyngeal nerve. The internal carotid artery is retracted laterally.
Fig.10.6 Interstitial brachycatheters have been inserted at 1-cm intervals following salvage neck dissection for recurrent squamous cell carcinoma. Metallic clips mark the tumor boundary to facilitate postoperative dosimetry planning. A pectoralis muscle flap will be rotated into the neck to cover the brachycatheters.
In general, major cranial nerves (e.g., hypoglossal nerve, spinal accessory nerve, vagus nerve) should be resected only if grossly involved or completely encased by disease, but should not otherwise be resected to achieve a surgical margin. Sacrificing the internal jugular vein, on the other hand, is significantly less morbid, and this structure should be resected en bloc with the nodal specimen if there are any concerns for tumoral invasion.
An area of particular difficulty with dissection in a salvage setting, after previous surgery and/or (chemo)radiation, is the retropharyngeal area. Retropharyngeal nodal metastases are most common with pharyngeal and thyroid cancers, and surgical excision of retropharyngeal lymph nodes can be performed transcervically or transorally, although transcervical resection is generally favored in a salvage setting (Fig. 10.5a-d). Treatment options for recurrent retropharyngeal nodal metastases include stereotactic re-irradiation, versus surgery, with or without postoperative adjuvant stereotactic reirradation.54 Since the hypoglossal and glossopharyngeal nerves often must be skeletonized and mobilized for access to the retropharyngeal area, these nerves are at particular risk for paresis in the setting of salvage surgery following radiation. Additionally, many small nerve branches innervating the upper pharyngeal constrictor must be divided when surgically removing retropharyngeal disease. In the setting of previous radiation, patients very often have temporary dysphagia, and a minority may even require temporary (or permanent) gastrostomy tube.
For patients who have recurrent neck disease beyond the initial postradiation period (i.e., after an initial negative postradiation scan), postoperative therapeutic options must be considered. Interstitial brachytherapy,55 re-irradiation with intensity-modulated RT,56 and proton therapy57 have been demonstrated to improve locoregional control with reasonable flap, free tissue flap) is generally necessary to improve tolerance and reduce morbidity and postoperative complications associated with postoperative adjuvant brachytherapy or reirradiation. Finally, the importance of multidisciplinary discussion in the evaluation of patients for salvage neck surgery cannot be overemphasized, as intraoperative strategy and decision-making will be greatly influenced by preoperative multidisciplinary discussion and planning.
 Lango MN, Myers JN, Garden AS. Controversies in surgical management of the node-positive neck after chemoradiation. Semin Radiat Oncol. 2009; 19 (1) :24-28
 Zafereo M. Surgical salvage of recurrent cancer of the head and neck. Curr Oncol Rep. 2014; 16(5):386
 Zafereo ME, Hanasono MM, Rosenthal DI, et al. The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx. Cancer. 2009; 115(24):5723-5733
 Barkley HT, Jr, Fletcher GH, Jesse RH, Lindberg RD. Management of cervical lymph node metastases in squamous cell carcinoma of the tonsillar fossa, base of tongue, supraglottic larynx, and hypopharynx. Am J Surg. 1972; 124(4):462-467
 Armstrong J, Pfister D, Strong E, et al. The management of the clinically positive neck as part of a larynx preservation approach. Int J Radiat Oncol Biol Phys. 1993; 26(5):759-765
 Wolf GT, Fisher SG. Effectiveness of salvage neck dissection for advanced regional metastases when induction chemotherapy and radiation are used for organ preservation. Laryngoscope. 1992; 102(8):934-939
 Simon C, Goepfert H, Rosenthal DI, et al. Presence of malignant tumor cells in persistent neck disease after radiotherapy for advanced squamous cell carcinoma of the oropharynx is associated with poor survival. Eur Arch Otorhino- laryngol. 2006; 263(4):313-318
 Brizel DM, Prosnitz RG, Hunter S, et al. Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004; 58(5):1418-1423
 Lavertu P, Adelstein DJ, Saxton JP, et al. Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer. Head Neck. 1997; 19(7):559-566
 Mendenhall WM, Million RR, Cassisi NJ. Squamous cell carcinoma of the head and neck treated with radiation therapy: the role of neck dissection for clinically positive neck nodes. Int J Radiat Oncol Biol Phys. 1986; 12(5):733-740
 Dubray BM, Bataini JP, Bernier J, et al. Is reseeding from the primary a plausible cause of node failure? IntJ Radiat Oncol Biol Phys. 1993; 25(1):9-15
 McHam SA, Adelstein DJ, Rybicki LA, et al. Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer? Head Neck. 2003; 25(10):791-798
 Stenson KM, Haraf DJ, Pelzer H, et al. The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection. Arch Otolaryngol Head Neck Surg. 2000; 126(8):950-956
 Kutler DI, Patel SG, Shah JP. The role of neck dissection following definitive chemoradiation. Oncology (Williston Park). 2004; 18(8):993-998, discussion 999,1003-1004,1007
 Lavertu P, Bonafede JP, Adelstein DJ, et al. Comparison of surgical complications after organ-preservation therapy in patients with stage III or IV squamous cell head and neck cancer. Arch Otolaryngol Head Neck Surg. 1998; 124(4):401-406
 Greven KM, Williams DW, III, Browne JD, McGuirt WF, Sr, White DR, D'Agostino RB, Jr. Radiographic complete response on post treatment CT imaging eliminates the need for adjuvant neck dissection after treatment for node positive head and neck cancer. Am J Clin Oncol. 2008; 31(2):169-172
 Peters LJ, Weber RS, Morrison WH, Byers RM, Garden AS, Goepfert H. Neck surgery in patients with primary oropharyngeal cancer treated by radiotherapy. Head Neck. 1996; 18(6):552-559
 Thariat J, Ang KK, Allen PK, et al. Prediction of neck dissection requirement after definitive radiotherapy for head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2012; 82(3):e367-e374
 Boyd TS, Harari PM, Tannehill SP, et al. Planned postradiotherapy neck dissection in patients with advanced head and neck cancer. Head Neck. 1998; 20 (2) :132-137
 Velâzquez RA, McGuff HS, Sycamore D, Miller FR. The role of computed tomographic scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy. Arch Otolaryngol Head Neck Surg. 2004; 130(1):74-77
 Strasser MD, Gleich LL, Miller MA, Saavedra HI, Gluckman JL. Management implications of evaluating the N2 and N3 neck after organ preservation therapy. Laryngoscope. 1999; 109(11):1776-1780
 Wee JT, Anderson BO, Corry J, et al. Asian Oncology Summit. Management of the neck after chemoradiotherapy for head and neck cancers in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009; 10 (11):1086-1092
 Goguen LA, Posner MR, Tishler RB, et al. Examining the need for neck dissection in the era of chemoradiation therapy for advanced head and neck cancer. Arch Otolaryngol Head Neck Surg. 2006; 132(5):526-531
 Clayman GL, Johnson CJ, II, Morrison W, Ginsberg L, Lippman SM. The role of neck dissection after chemoradiotherapy for oropharyngeal cancer with advanced nodal disease. Arch Otolaryngol Head Neck Surg. 2001; 127 (2) :135-139
 Paleri V, Urbano TG, Mehanna H, et al. Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016; 130 S2:S161-S169
 Hermann RM, Christiansen H, Rodel RM. Lymph node positive head and neck carcinoma after curative radiochemotherapy: a long lasting debate on elective post-therapeutic neck dissections comes to a conclusion. Cancer Radio- ther. 2013; 17(4):323-331
 Petruzzelli GJ, Benefield J, Yong S. Mechanism of lymph node metastases: current concepts. Otolaryngol Clin North Am. 1998; 31(4):585-599
 Jones AS, Tandon S, Helliwell TR, Husband DJ, Jones TM. Survival of patients with neck recurrence following radical neck dissection: utility of a second neck dissection? Head Neck. 2008; 30(11):1514-1522
 Dagan R, Morris CG, Kirwan JM, et al. Elective neck dissection during salvage surgery for locally recurrent head and neck squamous cell carcinoma after radiotherapy with elective nodal irradiation. Laryngoscope. 2010; 120(5):945-952
 Burge JS. Histological changes in cervical lymph nodes following clinical irradiation. Proc R Soc Med. 1975; 68(2):77-79
 Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008; 26(21):3582-3589
 Sandulache VC, Vandelaar LJ, Skinner HD, et al. Salvage total laryngectomy after external-beam radiotherapy: a 20-year experience. Head Neck. 2016; 38 Suppl 1:E1962-E1968
 Inohara H, Enomoto K, Tomiyama Y, et al. The role of CT and (18)F-FDG PET in managing the neck in node-positive head and neck cancer after chemora- diotherapy. Acta Otolaryngol. 2008; 7:1-7
 Tan A, Adelstein DJ, Rybicki LA, et al. Ability of positron emission tomography to detect residual neck node disease in patients with head and neck squamous cell carcinoma after definitive chemoradiotherapy. Arch Otolaryngol Head Neck Surg. 2007; 133(5):435-440
 Sumi M, Sakihama N, Sumi T, et al. Discrimination of metastatic cervical lymph nodes with diffusion-weighted MR imaging in patients with head and neck cancer. AJNR Am J Neuroradiol. 2003; 24(8):1627-1634
 King AD, Keung CK, Yu KH, et al. T2-weighted MR imaging early after chemo- radiotherapy to evaluate treatment response in head and neck squamous cell carcinoma. AJNR Am J Neuroradiol. 2013; 34(6):1237-1241
 Hermans R. Head and neck cancer: how imaging predicts treatment outcome. Cancer Imaging. 2006; 6:S145-S153
 de Bondt RB, Nelemans PJ, Hofman PA, et al. Detection of lymph node meta- stases in head and neck cancer: a meta-analysis comparing US, USgFNAC, CT and MR imaging. Eur J Radiol. 2007; 64(2):266-272
 Gupta T, Master Z, Kannan S, et al. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011; 38 (11):2083-2095
 Porceddu SV, Jarmolowski E, Hicks RJ, et al. Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck. 2005; 27 (3) :175-181
 Yao M, Graham MM, Hoffman HT, et al. The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2004; 59(4):1001-1010
 Mehanna H, McConkey CC, Rahman JK, et al. PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography-computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer. Health Technol Assess. 2017; 21(17):1-122
 Liauw SL, Mancuso AA, Morris CG, Amdur RJ, Mendenhall WM. Definitive radiotherapy for head-and-neck cancer with radiographically positive retropharyngeal nodes: incomplete radiographic response does not necessarily indicate failure. Int J Radiat Oncol Biol Phys. 2006; 66(4):1017-1021
 Davidson BJ, Newkirk KA, Harter KW, Picken CA, Cullen KJ, Sessions RB. Complications from planned, posttreatment neck dissections. Arch Otolaryngol Head Neck Surg. 1999; 125(4):401-405
 Kuntz AL, Weymuller EA, Jr. Impact of neck dissection on quality of life. Laryngoscope. 1999; 109(8):1334-1338
 Agarwal J, Kundu S. Salvage neck dissection after chemoradiation in head and neck cancer: practice and pitfalls. Int J Head Neck Surg. 2012; 3(1):15-21
 Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1972; 29 (6):1446-1449
 Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg. 1990; 160(4):405-409
 Robbins KT, Shannon K, Vieira F. Superselective neck dissection after chemo- radiation: feasibility based on clinical and pathologic comparisons. Arch Otolaryngol Head Neck Surg. 2007; 133(5):486-489
 Doweck I, Robbins KT, Mendenhall WM, Hinerman RW, Morris C, Amdur R. Neck level-specific nodal metastases in oropharyngeal cancer: is there a role for selective neck dissection after definitive radiation therapy? Head Neck. 2003; 25(11):960-967
 Yao M, Roebuck JC, Holsinger FC, Myers JN. Elective neck dissection during salvage laryngectomy. Am J Otolaryngol. 2005; 26(6):388-392
 Robbins KT, Doweck I, Samant S, Vieira F. Effectiveness of superselective and selective neck dissection for advanced nodal metastases after chemoradia- tion. Arch Otolaryngol Head Neck Surg. 2005; 131(11):965-969
 Goguen LA, Chapuy CI, Li Y, Zhao SD, Annino DJ. Neck dissection after chemo- radiotherapy: timing and complications. Arch Otolaryngol Head Neck Surg. 2010; 136(11):1071-1077
 Pollard C, III, Nguyen TP, Ng SP, et al. Clinical outcomes after local field conformal reirradiation of patients with retropharyngeal nodal metastasis. Head Neck. 2017; 39(10):2079-2087
 Kupferman ME, Morrison WH, Santillan AA, et al. The role of interstitial bra- chytherapy with salvage surgery for the management of recurrent head and neck cancers. Cancer. 2007; 109(10):2052-2057
 Takiar V, Garden AS, Ma D, et al. Reirradiation of head and neck cancers with intensity modulated radiation therapy: outcomes and analyses. Int J Radiat Oncol Biol Phys. 2016; 95(4):1117-1131
 Phan J, Sio TT, Nguyen TP, et al. Reirradiation of head and neck cancers with proton therapy: outcomes and analyses. Int J Radiat Oncol Biol Phys. 2016; 96 (1):30-41