- Open Access
Planned neck dissection following chemo-radiotherapy in advanced HNSCC
© Gupta and Agarwal; licensee BioMed Central Ltd. 2004
- Received: 30 June 2004
- Accepted: 17 September 2004
- Published: 17 September 2004
Neck dissection has traditionally played an important role in the management of patients with regionally advanced head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy alone. However, with the incorporation of chemotherapy in the therapeutic strategy for advanced HNSCC and resultant improvement in outcome the routine use of post chemo-radiotherapy neck dissection is being questioned.
Published data for this review was identified by systematically searching MEDLINE, CANCERLIT & EMBASE databases from 1995 until date with restriction to the English language.
There is lack of high quality evidence on the role of planned neck dissection in advanced HNSCC treated with chemo-radiotherapy. A systematic literature search could identify only one small randomized controlled trial (Level I evidence) addressing this issue, albeit with major limitations. Upfront neck dissection followed by chemo-radiotherapy resulted in better disease-specific survival as compared to chemoradiation only. Several single arm prospective and retrospective reports were also identified with significant heterogeneity and often-contradictory conclusions.
Planned neck dissection after radical chemo-radiotherapy achieves a high level of regional control, but its ultimate benefit is limited to a small subset of patients only. Unless there are better non-invasive ways to identify residual viable disease, the role of such neck dissection shall remain debatable. A large randomized controlled trial addressing this issue is needed to clarify its role and provide evidence-based answers.
- and neck dissection
Literature search strategy
Published data for this review was identified by systematically searching the MEDLINE, CANCERLIT & EMBASE databases from 1995 until date with restriction to the English language. "Head & Neck cancer" OR "HNSCC" was combined with "chemo-radiotherapy" OR "chemo-radiation" as Medical Subject Heading (MeSH) terms and each of the following phrase used as text words: "adjuvant neck dissection"; "planned neck dissection"; and "neck management". Relevant cross-references were also considered.
There is only one small randomized control trial (American Society of Clinical Oncology  Level I evidence) evaluating the role of planned neck dissection in advanced HNSCC treated with primary chemo-radiotherapy. Carinci  et al randomly assigned patients with advanced unresectable HNSCC to either elective neck dissection followed by chemo-radiotherapy (Group I, n = 23) or chemo-radiotherapy alone (Group II, n = 31). The two groups were reasonably well balanced for known prognostic factors. The 2-and 5-year disease-specific survival rates significantly favored the surgical arm (52% and 26% for Group I versus 29% and 0% for Group II respectively). A Cox regression analysis adjusted for T-stage, N-stage, age and gender showed that only therapy (Group I versus II) reached a positive and significant odds ratio in association with the probability of death (p = 0.0366 in favor of neck dissection). This study however suffers from major limitations. Firstly, the trial methodology was not detailed adequately to assess the validity of the interpretations. The investigators neither specified the method of randomization (why was the distribution unequal in the two arms) nor about stratification on known prognostic factors. Secondly, the numbers of patients in each arm were too small to draw any definite conclusions without ruling out an element of bias. Thirdly, the radiotherapy delivery was suboptimal (only 60–65 Gy with conventional fractionation) for sterilizing advanced HNSCC, in which case the addition of neck dissection was expected to improve outcome. Finally, since neck dissection was done upfront rather than after chemo-radiotherapy, the results of this trial cannot be directly extrapolated to the issue under consideration.
In absence of high quality evidence, the best available evidence tempered with clinical judgment often guides decision-making. Two of the recently published reports [11, 12] somewhat at contradiction with each other are briefly discussed to illustrate the dilemma.
Argiris  et al evaluated 131 patients with HNSCC having N2–N3 disease treated on concurrent chemo-radiotherapy protocols. Neck dissection was performed in 92 (70%) patients, either before (n = 31) or after chemo-radiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year loco-regional progression-free-survival (PFS) was significantly better in patients with planned neck dissection as compared to those without neck dissection (88% versus 74% respectively, p = 0.02) The addition of neck dissection to chemo-radiotherapy resulted in only one neck failure in 92 patients (neck PFS 99%) versus six neck failures in 39 patients (neck PFS 82%) not undergoing neck dissection (p = 0.0007). Neck dissection was however, not beneficial in patients with a complete clinical response (CCR). Of the 92 patients with a CCR, 62 underwent neck dissection, of which only 1 relapsed in the neck (neck PFS 98%). The neck PFS of 92% (2 neck failures) in the 30 patients in CCR who did not undergo neck dissection was not significantly different (p = 0.21). On subset analysis, in patients with N3 disease (n = 27), there was either a trend or a statistically significant advantage in all the survival parameters for the neck dissection arm. In contrast, in patients with N2 disease (n = 104), only the neck control improved with neck dissection. The local PFS, distant PFS, and the overall survival were similar irrespective of neck dissection. The authors concluded that in patients with N3 stage and less than CCR it was necessary to add neck dissection for optimal disease control, whereas in patients with N2 disease in CCR, neck dissection could safely be omitted without compromising outcome.
Brizel  et al identified 108 patients with nodal disease from a cohort of 154 patients on concurrent chemo-radiation protocols. A modified neck dissection was performed in 65 (60%) of 108 patients. With a median follow up of 4 years for surviving patients, the neck control rate was 100% for N1 patients irrespective of neck dissection being performed or not. Their disease-free-survival (DFS) was 70% with no differences relative to neck dissection. In N2–N3 patients, a CCR was achieved in 43 (55%) patients. Ten patients with local progression or systemic dissemination were excluded from analysis. Of the 52 patients undergoing neck dissection in N2–N3 group, only 1 regional relapse was seen, in contrast to 3 neck failures out of 16 in those not undergoing dissection (p = 0.05). The 4-year DFS was 75% for N2–N3 patients with a CCR and neck dissection versus 53% for those with CCR but no neck dissection (p = 0.08). The 4-year overall survival was also better for the dissection arm (77% versus 50% respectively, p = 0.04). The authors concluded that the policy of neck dissection in patients with N2–N3 disease even in CCR is justified to optimize loco-regional control and survival.
Neck failure in selected series of chemo-radiotherapy for HNSCC treated with or without ND
No of pts (n)
Pts in CCR
Neck failures (overall)
Neck failure (pts in CCR)
ND not done
ND not done
ND needed for all N2–N3 patients
Only patients with CCR offered ND
No clear benefit of ND after CCR
ND not needed for patients in CCR
All 69 pts had ND; needed for N2–N3
N2–N3: 52 (56 heminecks)
Good control with ND for N2–N3
8/78 neck failures in all
ND done for all pts with N2–N3
ND needed for all N2–N3 patients even in CCR
The potential benefit of planned neck dissection after a course of intensive chemo-radiotherapy in terms of improved regional control with or without an impact on survival needs to be weighed against the expected morbidity associated with the surgical procedure [12, 14, 25]. One argument put forward in favor of planned neck dissection even for patients in CCR is the high rate of pathological positivity (30%–50%) depending upon the meticulousness of sectioning by the pathologist [14, 17]. However, a significant majority of them actually may represent microscopic non-viable residual disease only, as has been demonstrated by Strasser using Ki-67 proliferating index , unlikely to relapse later. Proponents of neck dissection also argue that the ultimate success rate of salvage neck dissection after a relapse in the neck treated with full dose chemo-radiotherapy is small, whereas the morbidity is high [10, 25]. In contrast, the morbidity of a planned neck dissection is at best modest, when scheduled between 6–12 weeks from end of chemo-radiotherapy [7, 14, 17], which is supposed to be the time window between acute and chronic radiation injury.
Planned neck dissection after radical chemo-radiotherapy achieves a high level of regional control, but its ultimate benefit is limited to a small subset of patients only. The morbidity of such dissection is small, but significant. Its impact on survival is yet to be completely realized. In the majority of patients it is either unnecessary because there is no residual disease in the neck or futile because of unsalvageable primary recurrence or distant metastases. Nevertheless, it is recommended that planned neck dissection be performed for patients with less than a complete response in the neck after combined modality therapy to optimize regional control, provided the primary is controlled and there is no evidence of distant metastases. It should also be performed as part of salvage surgery for locally persistent or residual disease at primary site. The criterion for planned neck dissection for patients with advanced nodal disease with a CCR in the neck following chemo-radiotherapy should incorporate not only the nodal staging but also the actual size of the involved lymph nodes. Unless there are better non-invasive ways to identify residual viable disease, which could include functional imaging like Positron Emission Tomography and biological assays like hypoxia markers, the role of such neck dissection shall remain debatable. A large randomized controlled trial across several institutions addressing these issues is needed to clarify the role of planned neck dissection in advanced HNSCC treated with primary chemo-radiotherapy and provide evidence-based answers.
No source of funding involved in this review
- Garg M, Beitler JJ: Controversies in Management of the Neck in Head and Neck Cancer. Curr Treat Options Oncol. 2004, 5: 35-40.View ArticlePubMedGoogle Scholar
- McHam SA, Adelstein DJ, Rybicki LA, Lavertu P, Esclamado RM, Wood BG, Strome M, Carroll MA: Who merits a neck dissection after definitive chemoradiotherapy for N2–N3 squamous cell head and neck cancer. Head Neck. 2003, 25: 791-798. 10.1002/hed.10293.View ArticlePubMedGoogle Scholar
- Parsons JT, Mendenhall WM, Cassisi NJ, Stringer SP, Million RR: Neckdissection after twice-a-day radiotherapy: Morbidity and recurrence rates. Head Neck. 1989, 11: 400-404.View ArticlePubMedGoogle Scholar
- Mendenhall WM, Villaret DB, Amdur RJ, Hinerman RW, Mancuso AA: Planned neck dissection after definitive radiotherapy for squamous cell carcinoma ofthe head and neck. Head Neck. 2002, 24: 1012-1018. 10.1002/hed.10187.View ArticlePubMedGoogle Scholar
- Pignon JP, Bourhis J, Domenge C, Designe L: Chemotherapy added to loco-regional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data (for the Meta-Analysis of Chemotherapy on Head and Neck Cancer (MACH-NC) Collaborative group. Lancet. 2000, 355: 949-955. 10.1016/S0140-6736(00)90011-0.View ArticlePubMedGoogle Scholar
- Browman GP, Hodson DI, Mackenzie RJ, Bestic N, Zuraw L, Cancer Care Ontario Practice Guideline Initiative Head and Neck Cancer Disease Site Group: Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis. Head Neck. 2001, 23: 579-589. 10.1002/hed.1081.View ArticlePubMedGoogle Scholar
- Grabenbauer GG, Rodel C, Ernst-Stecken A, Brunner T, Hornung J, Kittel K, Steinhart H, Iro H, Sauer R, Schultze-Mosgau S: Neck dissection following radiochemotherapy of advanced head and neck cancer-for selected cases only?. Radiother Oncol. 2003, 66: 57-63. 10.1016/S0167-8140(02)00193-7.View ArticlePubMedGoogle Scholar
- Corry J, Smith JG, Peters LJ: The concept of a planned neck dissection is obsolete. Cancer J. 2001, 7: 472-474.PubMedGoogle Scholar
- American Society of Clinical Oncology (ASCO): Clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol. 1999, 17: 3333-3355.Google Scholar
- Carinci F, Cassano L, Farina A, Pelucchi S, Calearo C, Modugno V, Nielsen I, Api P, Pastore A: Unresectable primary tumor of head and neck: does neck dissection combined with chemoradiotherapy improve survival. J Craniofac Surg. 2001, 12: 438-443. 10.1097/00001665-200109000-00007.View ArticlePubMedGoogle Scholar
- Argiris A, Stenson KM, Brockstein BE, Mittal BB, Pelzer H, Kies MS, Jayaram P, Portugal L, Weing BL, Rosen FR, Haraf DJ, Vokes EE: Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer. Head Neck. 2004, 26: 447-455. 10.1002/hed.10394.View ArticlePubMedGoogle Scholar
- Brizel DM, Prosnitz RG, Hunter S, Fisher SR, Clough RL, Downey MA, Scher RL: Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004, 58: 1418-1423. 10.1016/j.ijrobp.2003.09.004.View ArticlePubMedGoogle Scholar
- 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: 135-139.View ArticlePubMedGoogle Scholar
- Stenson KM, Haraf DJ, Pelzer H, Recant W, Kies MS, Weichselbaum RR, Vokes EE: The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: The feasibility of selective neck dissection. Arch Otolaryngol Head Neck Surg. 2000, 126: 950-956.View ArticlePubMedGoogle Scholar
- Robbins KT, Wong FSH, Kumar P, Hartsell WF, Vieira F, Mullins B, Barry Niell H: Efficacy of targeted chemoradiation and planned selective neckdissection to control bulky nodal disease in advanced head and neck cancer. Arch Otolaryngol Head Neck Surg. 1999, 125: 670-675.View ArticlePubMedGoogle Scholar
- Lavertu P, Adelstein DJ, Saxton JP, Sesic M, Eliachar I, Strome M, Larto MA, Wood BG: Aggressive concurrent chemo-radiotherapy for squamous cell head and neck cancer: An 8-year single-institution experience. Arch Otolaryngol Head Neck Surg. 1999, 125: 142-148.View ArticlePubMedGoogle Scholar
- Lavertu P, Adelstein DJ, Saxton JP, Secic M, Wanamaker JR, Eliachar I, Wood BG, Strome M: 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: 559-566. 10.1002/(SICI)1097-0347(199710)19:7<559::AID-HED1>3.3.CO;2-L.View ArticlePubMedGoogle Scholar
- Wanebo H, Chougule P, Ready N, Safran H, Ackerley W, Koness RJ, McRae R, Nigri P, Leone L, Radie-Keane K, Reiss P, Kennedy T: Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV). Ann Surg Oncol. 2001, 8: 644-650. 10.1245/aso.2001.8.8.644.View ArticlePubMedGoogle Scholar
- Newkirk KA, Cullen KJ, William Harter K, Picken CA, Sessions RB, Davidson BJ: Planned neck dissection for advanced primary head and neckmalignancy treated with organ preservation therapy: disease control and survival outcomes. Head Neck. 2001, 23: 73-79. 10.1002/1097-0347(200102)23:2<73::AID-HED1001>3.0.CO;2-6.View ArticlePubMedGoogle Scholar
- Ahmed KA, Robbins KT, Wong F, Salazar JE: Efficacy of concomitant chemoradiation and surgical salvage for N3 nodal disease associated with upper aero-digestive tract carcinoma. Laryngoscope. 2000, 110: 1789-1793. 10.1097/00005537-200011000-00002.View ArticlePubMedGoogle Scholar
- Sanguineti G, Corvo R, Benasso M, Margarino G, Sormani MP, Roncallo F, Mereu P, Bacigalupo A, Vitale V: Management of the neck after alternating chemoradiotherapy for advanced head and neck cancer. Head Neck. 1999, 21: 223-228. 10.1002/(SICI)1097-0347(199905)21:3<223::AID-HED7>3.3.CO;2-R.View ArticlePubMedGoogle Scholar
- Weisman RA, Christen RD, Jones VE, Kerber CW, Seagren SL, Orloff LA, Glassmeyer SL, Howell SB, Robbins KT: Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation. Laryngoscope. 1998, 108: 800-805. 10.1097/00005537-199806000-00005.View ArticlePubMedGoogle Scholar
- Dagum P, Pinto HA, Newman JP, Higgins JP, Terris DJ, Goffinet DR, Fee WE: Management of the clinically positive neck in organ preservation for advanced head and neck cancer. Am J Surg. 1998, 176: 448-452. 10.1016/S0002-9610(98)00240-2.View ArticlePubMedGoogle Scholar
- Koch WM, Lee DJ, Eisele DW, Miller D, Poole M, Cummings CW, Forastiere AA: Chemo-radiotherapy for organ preservation in oral and pharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 1995, 121: 974-980.View ArticlePubMedGoogle Scholar
- Narayan K, Crane CH, Kleid S, Hughes PG, Peters LJ: Planned neck dissection as an adjunct to the management of patients with advanced neck disease treated with definitive radiotherapy: For some or for all?. Head Neck. 1999, 21: 606-613. 10.1002/(SICI)1097-0347(199910)21:7<606::AID-HED4>3.3.CO;2-7.View ArticlePubMedGoogle Scholar
- 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: 1776-1780. 10.1097/00005537-199911000-00010.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.