Neck management in head and neck squamous cell carcinomas: where do we stand?
- 80 Downloads
Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/− followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms ‘neck management’ OR ‘cervical lymphadenopathies’ AND ‘head and neck neoplasms’. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV− or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna’s trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers’ experience, in the context of limited data, especially for N2–3 HPV− HNSCC.
KeywordsHead and neck neoplasms Neck dissection Radiotherapy Disease management Lymphadenopathy Combined modality therapy
Compliance with ethical standards
Conflict of interest
The author(s) declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Chung E-J, Kim G-W, Cho B-K, Park HS, Rho Y-S. Pattern of lymph node metastasis in hypopharyngeal squamous cell carcinoma and indications for level VI lymph node dissection: Level VI lymph node metastasis in hypopharyngeal squamous cell carcinoma. Head Neck. 2016;38:E1969–73.PubMedCrossRefGoogle Scholar
- 2.Bataini JP, Bernier J, Jaulerry C, Brunin F, Pontvert D, Lave C. Impact of neck node radio responsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy. Int J Radiat Oncol Biol Phys. 1987;13:817–24.PubMedCrossRefGoogle Scholar
- 3.Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet Lond Engl. 2000;355:949–55.CrossRefGoogle Scholar
- 8.Kharytaniuk N, Molony P, Boyle S, O’Leary G, Werner R, Heffron C, et al. Association of extracapsular spread with survival according to human papillomavirus status in oropharynx squamous cell carcinoma and carcinoma of unknown primary site. JAMA Otolaryngol-Head Neck Surg. 2016;142:683–90.PubMedCrossRefGoogle Scholar
- 10.Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27:843–50.PubMedCrossRefGoogle Scholar
- 12.Ghadjar P, Schreiber-Facklam H, Gräter R, Evers C, Simcock M, Geretschläger A, et al. Quantitative analysis of extracapsular extension of metastatic lymph nodes and its significance in radiotherapy planning in head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2010;76:1127–32.PubMedCrossRefGoogle Scholar
- 14.Robbins KT, Clayman G, Levine PA, Medina J, Sessions R, Shaha A, et al. Neck dissection classification update: revisions proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002;128:751–8.PubMedCrossRefGoogle Scholar
- 15.Hamoir M, Silver CE, Schmitz S, Takes RP, Rinaldo A, Rodrigo JP, et al. Radical neck dissection: is it still indicated? Eur Arch Oto–Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol-Head Neck Surg. 2013;270:1–4.Google Scholar
- 22.Grégoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, et al. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2014;110:172–81.CrossRefGoogle Scholar
- 26.Rivière D, Mancini J, Santini L, Giovanni A, Dessi P, Fakhry N. Lymph-node metastasis following total laryngectomy and total pharyngolaryngectomy for laryngeal and hypopharyngeal squamous cell carcinoma: frequency, distribution and risk factors. Eur Ann Otorhinolaryngol Head Neck Dis. 2018;135:163–6.PubMedCrossRefGoogle Scholar
- 29.van den Bosch S, Dijkema T, Verhoef LCG, Zwijnenburg EM, Janssens GO, Kaanders JHAM. Patterns of recurrence in electively irradiated lymph node regions after definitive accelerated intensity modulated radiation therapy for head and neck squamous cell carcinoma. Int J Radiat Oncol. 2016;94:766–74.CrossRefGoogle Scholar
- 30.Schmitz S, Machiels J-P, Weynand B, Gregoire V, Hamoir M. Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma. Eur Arch Oto–Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol-Head Neck Surg. 2009;266:437–43.Google Scholar
- 31.NCCN guidelines v2. 2018. https://www.nccn.org/professionals/physician_gls/default.aspx#head-and-neck.
- 32.Horiot JC, Le Fur R, N’Guyen T, Chenal C, Schraub S, Alfonsi S, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC Cooperative Group of Radiotherapy. Radiother Oncol J Eur Soc Ther Radiol Oncol. 1992;25:231–41.CrossRefGoogle Scholar
- 34.Adelstein DJ, Lavertu P, Saxton JP, Secic M, Wood BG, Wanamaker JR, et al. Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer. 2000;88:876–83.PubMedCrossRefPubMedCentralGoogle Scholar
- 36.Li W-F, Sun Y, Mao Y-P, Chen L, Chen Y-Y, Chen M, et al. Proposed lymph node staging system using the International Consensus Guidelines for lymph node levels is predictive for nasopharyngeal carcinoma patients from endemic areas treated with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86:249–56.PubMedCrossRefPubMedCentralGoogle Scholar
- 42.Yao M, Buatti JM, Dornfeld KJ, Graham MM, Smith RB, Funk GF, et al. Can post-RT FDG PET accurately predict the pathologic status in neck dissection after radiation for locally advanced head and neck cancer? In regard to Rogers et al. (Int J Radiat Oncol Biol Phys 2004;58:694–697). Int J Radiat Oncol Biol Phys. 2005;61:306–7; author reply 307.Google Scholar
- 46.Mehanna H, McConkey CC, Rahman JK, Wong W-L, Smith AF, Nutting C, 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 Winch Engl. 2017;21:1–122.CrossRefGoogle Scholar
- 47.Smith AF, Hall PS, Hulme CT, Dunn JA, McConkey CC, Rahman JK, et al. Cost-effectiveness analysis of PET–CT-guided management for locally advanced head and neck cancer. Eur J Cancer Oxf Engl. 1990;2017(85):6–14.Google Scholar
- 49.Schmitz S, Van Maanen A, Rousseaux L, Andry G, Temam S, Dequanter D, et al. The role of PET for predicting nodal response in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy (CRT): results of a prospective multicenter trial. J Clin Oncol. 2017;35:6013–6013.CrossRefGoogle Scholar
- 54.Noij DP, Pouwels PJW, Ljumanovic R, Knol DL, Doornaert P, de Bree R, et al. Predictive value of diffusion-weighted imaging without and with including contrast-enhanced magnetic resonance imaging in image analysis of head and neck squamous cell carcinoma. Eur J Radiol. 2015;84:108–16.PubMedCrossRefGoogle Scholar
- 70.D’cruz AK, Pantvaidya GH, Agarwal JP, Chaukar DA, Pathak KA, Deshpande MS, et al. Split therapy: planned neck dissection followed by definitive radiotherapy for a T1, T2 pharyngolaryngeal primary cancer with operable N2, N3 nodal metastases—a prospective study. J Surg Oncol. 2006;93:56–61.PubMedCrossRefGoogle Scholar
- 71.Shenoy AM, Shiva Kumar T, Prashanth V, Chavan P, Halkud R, Jacob L, et al. Neck dissection followed by definitive radiotherapy for small upper aerodigestive tract squamous cell carcinoma, with advanced neck disease: an alternative treatment strategy. Indian J Otolaryngol Head Neck Surg. 2013;65:48–52.PubMedCrossRefGoogle Scholar
- 77.Gane EM, McPhail SM, Hatton AL, Panizza BJ, O’Leary SP. Predictors of health-related quality of life in patients treated with neck dissection for head and neck cancer. Eur Arch Oto–Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol-Head Neck Surg. 2017;274:4183–93.Google Scholar
- 81.Early pharyngolaryngeal carcinomas with palpable nodes. French Head and Neck Study Group (GETTEC). Am J Surg. 1991;162:377–80.Google Scholar
- 85.Elicin O, Nisa L, Dal Pra A, Bojaxhiu B, Caversaccio M, Schmücking M, et al. Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: rationale, complications, toxicity rates, and oncological outcomes—a systematic review. Radiother Oncol. 2016;119:185–93.PubMedCrossRefGoogle Scholar
- 87.Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al. Randomized Phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 Trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014;32:3858–67.PubMedPubMedCentralCrossRefGoogle Scholar
- 94.van den Bovenkamp K, Noordhuis MG, Oosting SF, van der Laan BFAM, Roodenburg JL, Bijl HP, et al. Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors. Clin Otolaryngol. 2017;42:693–700.PubMedCrossRefGoogle Scholar
- 97.Christopoulos A, Nguyen-Tan PF, Tabet J-C, Fortin B, Souliàres D, Charpentier D, et al. Neck dissection following concurrent chemoradiation for advanced head and neck carcinoma: pathologic findings and complications. J Otolaryngol-Head Neck Surg J Oto–Rhino-Laryngol Chir Cerv.-Fac. 2008;37:452–6.Google Scholar
- 99.Robbins KT, Ferlito A, Shah JP, Hamoir M, Takes RP, Strojan P, et al. The evolving role of selective neck dissection for head and neck squamous cell carcinoma. Eur Arch Oto–Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol-Head Neck Surg. 2013;270:1195–202.Google Scholar
- 100.Troussier I, Klausner G, Blais E, Giraud P, Lahmi L, Pflumio C, et al. Advances in the management of cervical lymphadenopathies of unknown primary with intensity modulated radiotherapy: doses and target volumes. Cancer Radiother J Soc Fr Radiother Oncol. 2018. https://doi.org/10.1016/j.canrad.2017.10.008.CrossRefGoogle Scholar
- 101.Troussier I, Klausner G, Morinière S, Blais E, Faivre J-C, Champion A, et al. Advances in the management of cervical lymphadenopathies of unknown primary: advances in diagnostic imaging and surgical modalities and new international staging system. Bull Cancer (Paris). 2018;105:181–92.CrossRefGoogle Scholar