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Advances and residual knowledge gaps in the neck management of head and neck squamous cell carcinoma patients with advanced nodal disease undergoing definitive (chemo)radiotherapy for their primary

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Abstract

Purpose

Substantial changes have been made in the neck management of patients with head and neck squamous cell carcinomas (HNSCC) in the past century. These have been fostered by changes in cancer epidemiology and technological progress in imaging, surgery, or radiotherapy, as well as disruptive concepts in oncology. We aimed to review changes in nodal management, with a focus on HNSCC patients with nodal involvement (cN+) undergoing (chemo)radiotherapy.

Methods

A narrative review was conducted to review current advances and address knowledge gaps in the multidisciplinary management of the cN+ neck in the context of (chemo)radiotherapy.

Results

Metastatic neck nodes are associated with poorer prognosis and poorer response to radiotherapy, and have therefore been systematically treated by surgery. Radical neck dissection (ND) has gradually evolved toward more personalized and less morbid approaches, i.e., from functional to selective ND. Omission of ND has been made feasible by use of positron-emission tomography/computed tomography to monitor the radiation response in cN+ patients. Human papillomavirus-driven oropharyngeal cancers and their cystic nodes have shown dramatically better prognosis than tobacco-related cancers, justifying a specific prognostic classification (AJCC) creation. Finally, considering the role of lymph nodes in anti-tumor immunity, de-escalation of ND and prophylactic nodal irradiation in combination are intense areas of investigation. However, the management of bulky cN3 disease remains an issue, as aggressive multidisciplinary strategies or innovative combined treatments have not yet significantly improved their prognosis.

Conclusion

Personalized neck management is an increasingly important aspect of the overall therapeutic strategies in cN+ HNSCC.

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References

  1. Paleri V, Urbano TG, Mehanna H, Repanos C, Lancaster J, Roques T et al (2016) Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 130(S2):S161–9 (May)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lindberg R (1972) Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 29(6):1446–1449 (Jun)

    Article  CAS  PubMed  Google Scholar 

  3. Robbins KT, Shaha AR, Medina JE, Califano JA, Wolf GT, Ferlito A et al (2008) Consensus Statement on the Classification and Terminology of Neck Dissection. Arch Otolaryngol Head Neck Surg 1;134(5):536 (May)

    Article  Google Scholar 

  4. Huang SH, O’Sullivan B, Xu W, Zhao H, Chen D duo, Ringash J, et al. Temporal Nodal Regression and Regional Control After Primary Radiation Therapy for N2–N3 Head-and-Neck Cancer Stratified by HPV Status. International Journal of Radiation Oncology*Biology*Physics. 2013 Dec;87(5):1078–85.

  5. Wong ET, Huang SH, O’Sullivan B, Persaud V, Su J, Waldron J et al (2021) Head and neck imaging surveillance strategy for HPV-positive oropharyngeal carcinoma following definitive (chemo)radiotherapy. Radiother Oncol 157:255–262 (Apr)

    Article  PubMed  Google Scholar 

  6. Koyfman SA, Ismaila N, Crook D, D’Cruz A, Rodriguez CP, Sher DJ et al (2019) Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. J Clin Oncol 10;37(20):1753–1774 (Jul)

    Article  Google Scholar 

  7. Mehanna H, Wong WL, McConkey CC, Rahman JK, Robinson M, Hartley AGJ et al (2016) PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 14;374(15):1444–1454 (Apr)

    Article  Google Scholar 

  8. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 20;26(21):3582–3589 (Jul)

    Article  Google Scholar 

  9. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 10;29(32):4294–4301 (Nov)

    Article  PubMed  Google Scholar 

  10. Lydiatt WM, Patel SG, O’Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, et al. Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA: a cancer journal for clinicians. 2017;67(2):122–37.

  11. Sharabi AB, Lim M, DeWeese TL, Drake CG (2015) Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16(13):e498–509 (Oct)

    Article  PubMed  Google Scholar 

  12. Paterson C, Hargreaves S, Rumley CN (2020) Functional Imaging to Predict Treatment Response in Head and Neck Cancer: How Close are We to Biologically Adaptive Radiotherapy? Clin Oncol (r Coll Radiol) 32(12):861–873 (Dec)

    Article  CAS  PubMed  Google Scholar 

  13. Abdel-Halim CN, Rosenberg T, Dyrvig AK, Høilund-Carlsen PF, Sørensen JA, Rohde M et al (2021) Diagnostic accuracy of imaging modalities in detection of histopathological extranodal extension: A systematic review and meta-analysis. Oral Oncol 114:105169 (Mar)

    Article  PubMed  Google Scholar 

  14. Li WF, Zhang Y, Liu X, Tang LL, Tian L, Guo R et al (2017) Delayed clinical complete response to intensity-modulated radiotherapy in nasopharyngeal carcinoma. Oral Oncol 75:120–126 (Dec)

    Article  PubMed  Google Scholar 

  15. Garibaldi C, Ronchi S, Cremonesi M, Gilardi L, Travaini L, Ferrari M et al (2017) Interim 18F-FDG PET/CT During Chemoradiation Therapy in the Management of Head and Neck Cancer Patients: A Systematic Review. Int J Radiat Oncol Biol Phys 1;98(3):555–573 (Jul)

    Article  Google Scholar 

  16. Martens RM, Noij DP, Koopman T, Zwezerijnen B, Heymans M, de Jong MC et al (2019) Predictive value of quantitative diffusion-weighted imaging and 18-F-FDG-PET in head and neck squamous cell carcinoma treated by (chemo)radiotherapy. Eur J Radiol 113:39–50 (Apr)

    Article  PubMed  Google Scholar 

  17. Katirtzidou E, Rager O, Varoquaux AD, Poncet A, Lenoir V, Dulguerov N et al (2022) Detection of distant metastases and distant second primary cancers in head and neck squamous cell carcinoma: comparison of [18F]FDG PET/MRI and [18F]FDG PET/CT. Insights Imaging 28;13(1):121 (Jul)

    Article  Google Scholar 

  18. Wreesmann VB, Katabi N, Palmer FL, Montero PH, Migliacci JC, Gönen M et al (2016) Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma: Extent of Extranodal Spread. Head Neck 38(S1):E1192–9 (Apr)

    Article  PubMed  Google Scholar 

  19. Mermod M, Tolstonog G, Simon C, Monnier Y (2016) Extracapsular spread in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol 62:60–71 (Nov)

    Article  PubMed  Google Scholar 

  20. Hurel C, Carsuzaa F, Salleron J, Gorphe P, Righini C, Rogé M, et al. Impact of HPV status in T1–2 oropharyngeal squamous cell carcinoma with bulky N3 nodes: a multicenter GETTEC study. Eur Arch Otorhinolaryngol [Internet]. 2022 Sep 6 [cited 2022 Nov 16]; Available from: https://doi.org/10.1007/s00405-022-07637-8

  21. Lewis JS, Carpenter DH, Thorstad WL, Zhang Q, Haughey BH (2011) Extracapsular extension is a poor predictor of disease recurrence in surgically treated oropharyngeal squamous cell carcinoma. Mod Pathol 24(11):1413–1420 (Nov)

    Article  PubMed  PubMed Central  Google Scholar 

  22. Billfalk-Kelly A, Yu E, Su J, O’Sullivan B, Waldron J, Ringash J et al (2019) Radiologic Extranodal Extension Portends Worse Outcome in cN+ TNM‑8 Stage I Human Papillomavirus-Mediated Oropharyngeal Cancer. Int J Radiat Oncol Biol Phys 1;104(5):1017–1027 (Aug)

    Article  PubMed  Google Scholar 

  23. Matos LL, Dedivitis RA, Kulcsar MAV, de Mello ES, Alves VAF, Cernea CR (2017) External validation of the AJCC Cancer Staging Manual, 8th edn. Aug, vol 71. ition, in an independent cohort of oral cancer patients. Oral Oncology, pp 47–53

    Google Scholar 

  24. Deschuymer S, Dok R, Laenen A, Hauben E, Nuyts S (2018) Patient Selection in Human Papillomavirus Related Oropharyngeal Cancer: The Added Value of Prognostic Models in the New TNM 8th Edition Era. Front Oncol 8:273

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nauta IH, Rietbergen MM, van Bokhoven A a. JD, Bloemena E, Lissenberg-Witte BI, Heideman D a. M, et al. Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing. Ann Oncol. 2018 May 1;29(5):1273–9.

  26. Würdemann N, Wagner S, Sharma SJ, Prigge ES, Reuschenbach M, Gattenlöhner S et al (2017) Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma. Front Oncol 7:129

    Article  PubMed  PubMed Central  Google Scholar 

  27. Divi V, Harris J, Harari PM, Cooper JS, McHugh J, Bell D et al (2016) Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234). Cancer 15;122(22):3464–3471 (Nov)

    Article  Google Scholar 

  28. Farrokhian N, Holcomb AJ, Dimon E, Karadaghy O, Ward C, Whiteford E et al (2022) Assessing Prognostic Value of Quantitative Neck Dissection Quality Measures in Patients With Clinically Node-Negative Oral Cavity Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg 1;148(10):947–955 (Oct)

    Article  PubMed  Google Scholar 

  29. Bullock MJ, Beitler JJ, Carlson DL, Fonseca I, Hunt JL, Katabi N et al (2019) Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting. Arch Pathol Lab Med 143(4):452–462 (Apr)

    Article  CAS  PubMed  Google Scholar 

  30. Hamoir M, Silver CE, Schmitz S, Takes RP, Rinaldo A, Rodrigo JP et al (2013) Radical neck dissection: is it still indicated? Eur Arch Otorhinolaryngol 270(1):1–4 (Jan)

    Article  PubMed  Google Scholar 

  31. Garrel R, Poissonnet G, Plana MA, Fakhry N, Dolivet G, Lallemant B et al (2020) Equivalence Randomized Trial to Compare Treatment on the Basis of Sentinel Node Biopsy Versus Neck Node Dissection in Operable T1–T2N0 Oral and Oropharyngeal Cancer. JCO 1;38(34):4010–4018 (Dec)

    Article  Google Scholar 

  32. Patel RS, Clark JR, Gao K, O’Brien CJ (2008) Effectiveness of selective neck dissection in the treatment of the clinically positive neck. Head Neck 30(9):1231–1236 (Sep)

    Article  PubMed  Google Scholar 

  33. Schmitz S, Machiels JP, Weynand B, Gregoire V, Hamoir M (2009) Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 266(3):437–443 (Mar)

    Article  PubMed  Google Scholar 

  34. Binmadi NO, Basile JR (2011) Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature. Oral Oncol 47(11):1005–1010 (Nov)

    Article  PubMed  Google Scholar 

  35. Böttcher A, Olze H, Thieme N, Stromberger C, Sander S, Münscher A et al (2017) A novel classification scheme for advanced laryngeal cancer midline involvement: implications for the contralateral neck. J Cancer Res Clin Oncol 143(8):1605–1612 (Aug)

    Article  PubMed  Google Scholar 

  36. Mattei P, Dghayem D, Dupret-Bories A, Sarini J, Vairel B, Rivière LD, et al. Should an elective contralateral neck dissection be performed in midline-reaching squamous cell carcinomas of the oral cavity and oropharynx? Eur J Surg Oncol. 2023 Apr 5;S0748–7983(23)00421–3.

  37. Robbins KT (2000) Indications for selective neck dissection: when, how, and why. Oncology (Williston Park). Oct 14(10):1455–1464 (discussion 1467–1469)

    CAS  Google Scholar 

  38. Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP et al (2014) The origin of regional failure in oral cavity squamous cell carcinoma with pathologically negative neck metastases. JAMA Otolaryngol Head Neck Surg 140(12):1130–1137 (Dec)

    Article  PubMed  Google Scholar 

  39. So YK, Oh D, Choi N, Baek CH, Ahn YC, Chung MK (2018) Efficacy of postoperative neck irradiation for regional control in patients with pN0 oral tongue cancer: Propensity analysis. Head Neck 40(1):163–169 (Jan)

    Article  PubMed  Google Scholar 

  40. Lang P, Contreras J, Kalman N, Paterson C, Bahig H, Billfalk-Kelly A et al (2020) Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial. Radiat Oncol 14;15(1):196 (Aug)

    Article  Google Scholar 

  41. Rosenthal DI, Mohamed ASR, Garden AS, Morrison WH, El-Naggar AK, Kamal M et al (2017) Final Report of a Prospective Randomized Trial to Evaluate the Dose-Response Relationship for Postoperative Radiation Therapy and Pathologic Risk Groups in Patients With Head and Neck Cancer. Int J Radiat Oncol Biol Phys 1;98(5):1002–1011 (Aug)

    Article  PubMed  Google Scholar 

  42. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB et al (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 6;350(19):1937–1944 (May)

    Article  PubMed  Google Scholar 

  43. Avkshtol V, Handorf EA, Ridge JA, Leachman BK, Liu JC, Bauman J et al (2019) Examining adjuvant radiation dose in head and neck squamous cell carcinoma. Head Neck 41(7):2133–2142 (Jul)

    Article  PubMed  PubMed Central  Google Scholar 

  44. Grégoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA et al (2014) 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 110(1):172–181 (Jan)

    Article  PubMed  Google Scholar 

  45. van der Veen J, Gulyban A, Nuyts S (2019) Interobserver variability in delineation of target volumes in head and neck cancer. Radiother Oncol 137:9–15 (Aug)

    Article  PubMed  Google Scholar 

  46. Biau J, Lapeyre M, Troussier I, Budach W, Giralt J, Grau C et al (2019) Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 Update. Radiother Oncol 134:1–9 (May)

    Article  PubMed  Google Scholar 

  47. Nevens D, Duprez F, Daisne JF, Dok R, Belmans A, Voordeckers M et al (2017) Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control. Radiother Oncol 122(2):171–177 (Feb)

    Article  PubMed  Google Scholar 

  48. Hietanen T, Pitkänen M, Kapanen M, Kellokumpu-Lehtinen PL (2015) Effects of Single and Fractionated Irradiation on Natural Killer Cell Populations: Radiobiological Characteristics of Viability and Cytotoxicity In Vitro. Anticancer Res 35(10):5193–5200 (Oct)

    CAS  PubMed  Google Scholar 

  49. Leeman JE, Li J gao, Pei X, Venigalla P, Zumsteg ZS, Katsoulakis E, et al. Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques. JAMA Oncol. 2017 Nov 1;3(11):1487.

  50. Sykes AJ, Slevin NJ, Gupta NK, Brewster AE (2000) 331 cases of clinically node-negative supraglottic carcinoma of the larynx: a study of a modest size fixed field radiotherapy approach. Int J Radiat Oncol 46(5):1109–1115 (Mar)

    Article  CAS  Google Scholar 

  51. Elicin O, Albrecht T, Haynes AG, Bojaxhiu B, Nisa L, Caversaccio M et al (2016) Outcomes in Advanced Head and Neck Cancer Treated with Up-front Neck Dissection prior to (Chemo)Radiotherapy. Otolaryngol Head Neck Surg 154(2):300–308 (Feb)

    Article  PubMed  Google Scholar 

  52. Nevens D, Duprez F, Bonte K, Deron P, Huvenne W, Laenen A et al (2017) Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Tumor control and late toxicity. Radiother Oncol 124(2):220–224 (Aug)

    Article  PubMed  Google Scholar 

  53. Lambrecht M, Dirix P, Van den Bogaert W, Nuyts S (2009) Incidence of isolated regional recurrence after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma. Radiother Oncol 93(3):498–502 (Dec)

    Article  PubMed  Google Scholar 

  54. Thariat J, Ang KK, Allen PK, Ahamad A, Williams MD, Myers JN et al (2012) Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head and Neck Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys 1;82(3):e367–74 (Mar)

    Article  Google Scholar 

  55. Elicin O, Nisa L, Dal Pra A, Bojaxhiu B, Caversaccio M, Schmücking M et al (2016) 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 119(2):185–193 (May)

    Article  PubMed  Google Scholar 

  56. Byers RM, Clayman GL, Guillamondequi OM, Peters LJ, Goepfert H (1992) Resection of advanced cervical metastasis prior to definitive radiotherapy for primary squamous carcinomas of the upper aerodigestive tract. Head Neck 14(2):133–138 (Apr)

    Article  CAS  PubMed  Google Scholar 

  57. Samant S, Robbins KT (2003) Evolution of neck dissection for improved functional outcome. World J Surg 27(7):805–810 (Jul)

    Article  PubMed  Google Scholar 

  58. Carsuzaa F, Gorphe P, Vergez S, Malard O, Fakhry N, Righini C et al (2020) Consensus on resectability in N3 head and neck squamous cell carcinomas: GETTEC recommendations. Oral Oncol 106:104733 (Jul)

    Article  PubMed  Google Scholar 

  59. Dunlap Q, Gardner JR, Ederle A, King D, Merriweather M, Vural E et al (2022) Comparative Morbidity Profile of Elective vs Therapeutic Neck Dissection. Otolaryngol Head Neck Surg 166(2):327–333 (Feb)

    Article  PubMed  Google Scholar 

  60. Molteni G, Comini L, Le Pera B, Bassani S, Ghirelli M, Martone A et al (2021) Salvage neck dissection for isolated neck recurrences in head and neck tumors: Intra and postoperative complications. J Surg Oncol 124(5):740–750 (Oct)

    Article  PubMed  Google Scholar 

  61. Klausner G, Troussier I, Kreps S, Fabiano E, Laccourreye O, Giraud P (2021) Impact of neck dissection in N2–3 oropharyngeal squamous cell carcinomas treated with definitive chemoradiotherapy: An observational real-life study. Cancer Radiother 25(8):771–778 (Dec)

    Article  CAS  PubMed  Google Scholar 

  62. Al-Mamgani A, Meeuwis CA, van Rooij PH, Mehilal R, Basdew H, Sewnaik A et al (2013) Node-positive hypopharyngeal cancer treated by (chemo)radiotherapy: impact of up-front neck dissection on outcome, toxicity, and quality of life. Head Neck 35(9):1278–1286 (Sep)

    Article  PubMed  Google Scholar 

  63. van der Putten L, van den Broek GB, de Bree R, van den Brekel MWM, Balm AJM, Hoebers FJP et al (2009) Effectiveness of salvage selective and modified radical neck dissection for regional pathologic lymphadenopathy after chemoradiation. Head Neck 31(5):593–603 (May)

    Article  PubMed  Google Scholar 

  64. Sato MP, Otsuki N, Kitano M, Ishikawa K, Tanaka K, Kimura T et al (2021) Up-front neck dissection followed by chemoradiotherapy for T1–T3 hypopharyngeal cancer with advanced nodal involvement. Head Neck 43(12):3810–3819 (Dec)

    Article  PubMed  PubMed Central  Google Scholar 

  65. Liu XK, Li Q, Zhang Q, Su Y, Shi YX, Li H et al (2012) Planned neck dissection before combined chemoradiation in organ preservation protocol for N2–N3 of supraglottic or hypopharyngeal carcinoma. Orl J Otorhinolaryngol Relat Spec 74(2):64–69

    Article  PubMed  Google Scholar 

  66. Carinci F, Cassano L, Farina A, Pelucchi S, Calearo C, Modugno V et al (2001) Unresectable primary tumor of head and neck: does neck dissection combined with chemoradiotherapy improve survival? J Craniofac Surg 12(5):438–443 (Sep)

    Article  CAS  PubMed  Google Scholar 

  67. Li F, Hsueh C, Gong H, Zhu Y, Tao L, Zhou L et al (2022) The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma. Head Neck 44(9):2009–2017 (Sep)

    Article  PubMed  Google Scholar 

  68. Cohen EEW, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH et al (2014) Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol 1;32(25):2735–2743 (Sep)

    Article  PubMed  Google Scholar 

  69. Haddad R, O’Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D et al (2013) Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14(3):257–264 (Mar)

    Article  CAS  PubMed  Google Scholar 

  70. Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P et al (2018) Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. J Clin Oncol 1;36(31):3077–3083 (Nov)

    Article  PubMed  Google Scholar 

  71. Carsuzaa F, Dufour X, Gorphe P, Righini C, Cosmidis A, Rogé M et al (2020) Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study. Clin Otolaryngol 45(6):877–884 (Nov)

    Article  PubMed  Google Scholar 

  72. Tao Y, Aupérin A, Graff P, Lapeyre M, Grégoire V, Maingon P et al (2017) Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials. Oral Oncol 71:61–66 (Aug)

    Article  PubMed  Google Scholar 

  73. Seidler M, Forghani B, Reinhold C, Pérez-Lara A, Romero-Sanchez G, Muthukrishnan N et al (2019) Dual-Energy CT Texture Analysis With Machine Learning for the Evaluation and Characterization of Cervical Lymphadenopathy. Comput Struct Biotechnol J 17:1009–1015

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hoffmann C, Shen C, Le Tourneau C (2022) Nanoparticle therapy for head and neck cancers. Curr Opin Oncol 1;34(3):177–184 (May)

    Article  Google Scholar 

  75. Lekanne Dit Deprez LW, Morand GB, Thüring C, Pazahr S, Hüllner MW, Broglie MA (2022) SUVmax for predicting regional control in oropharyngeal cancer. Eur Arch Otorhinolaryngol 279(6):3167–3177 (Jun)

    Article  PubMed  Google Scholar 

  76. Mahajan A, Chand A, Agarwal U, Patil V, Vaish R, Noronha V et al (2022) Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy. Front Oncol 12:814895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bonomo P, Merlotti A, Olmetto E, Bianchi A, Desideri I, Bacigalupo A et al (2018) What is the prognostic impact of FDG PET in locally advanced head and neck squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 45(12):2122–2138 (Nov)

    Article  PubMed  PubMed Central  Google Scholar 

  78. Castelli J, De Bari B, Depeursinge A, Simon A, Devillers A, Jimenez RG et al (2016) Overview of the predictive value of quantitative 18 FDG PET in head and neck cancer treated with chemoradiotherapy. Crit Rev Oncol Hematol 108:40–51 (Dec)

    Article  CAS  PubMed  Google Scholar 

  79. Schwartz DL, Harris J, Yao M, Rosenthal DI, Opanowski A, Levering A et al (2015) Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522. Int J Radiat Oncol Biol Phys 15;91(4):721–729 (Mar)

    Article  Google Scholar 

  80. Inokuchi H, Kodaira T, Tachibana H, Nakamura T, Tomita N, Nakahara R et al (2011) Clinical usefulness of [18F] fluoro-2-deoxy-D-glucose uptake in 178 head-and-neck cancer patients with nodal metastasis treated with definitive chemoradiotherapy: consideration of its prognostic value and ability to provide guidance for optimal selection of patients for planned neck dissection. Int J Radiat Oncol Biol Phys 1;79(3):747–755 (Mar)

    Article  PubMed  Google Scholar 

  81. Göttgens EL, Ostheimer C, Span PN, Bussink J, Hammond EM (2019) HPV, hypoxia and radiation response in head and neck cancer. Br J Radiol 92(1093):20180047 (Jan)

    PubMed  Google Scholar 

  82. Rüegg P, Morand GB, Kudura K, Rupp NJ, Hüllner MW, Broglie MA (2020) Tumor cell viability in salvage neck dissections: Poor prognosis predicted by high postradiation nodal SUVmax, p16-negativity, and low nodal shrinkage. Head Neck 42(4):660–669 (Apr)

    Article  PubMed  Google Scholar 

  83. van den Bovenkamp K, Dorgelo B, Noordhuis MG, van der Laan BFAM, van der Vegt B, Bijl HP et al (2018) Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus. Oral Oncol 77:131–136 (Feb)

    Article  PubMed  Google Scholar 

  84. Sjövall J, Bitzén U, Kjellén E, Nilsson P, Wahlberg P, Brun E (2016) Qualitative interpretation of PET scans using a Likert scale to assess neck node response to radiotherapy in head and neck cancer. Eur J Nucl Med Mol Imaging 43(4):609–616 (Apr)

    Article  PubMed  Google Scholar 

  85. Billingsley S, Iyizoba Z, Frood R, Vaidyanathan S, Prestwich R, Scarsbrook A (2023) Clinical Utility of Second-Look FDG PET-CT to Stratify Incomplete Metabolic Response Post (Chemo) Radiotherapy in Oropharyngeal Squamous Cell Carcinoma. Cancers 11;15(2):464 (Jan)

    Article  Google Scholar 

  86. Costantino A, Mercante G, D’Ascoli E, Ferreli F, Di Tommaso L, Franzese C et al (2021) Accuracy of fine-needle aspiration cytology in detecting cervical node metastasis after radiotherapy: Systematic review and meta-analysis. Head Neck 43(3):987–996 (Mar)

    Article  PubMed  Google Scholar 

  87. Pfeiffer J, Kayser L, Ridder GJ (2009) Minimal-invasive core needle biopsy of head and neck malignancies: clinical evaluation for radiation oncology. Radiother Oncol 90(2):202–207 (Feb)

    Article  PubMed  Google Scholar 

  88. Zhu VL, Rand DR, Arnold KE, Pagedar NA, Bayon R, Buchakjian MR (2023) Association of Core Biopsy With Extranodal Extension in Surgically Treated Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg 1;149(11):955–960 (Nov)

    Article  PubMed  Google Scholar 

  89. Cao Y, Aryal M, Li P, Lee C, Schipper M, Hawkins PG et al (2019) Predictive Values of MRI and PET Derived Quantitative Parameters for Patterns of Failure in Both p16+ and p16-High Risk Head and Neck Cancer. Front Oncol 9:1118

    Article  PubMed  PubMed Central  Google Scholar 

  90. Surov A, Meyer HJ, Wienke A (2017) Associations between apparent diffusion coefficient (ADC) and KI 67 in different tumors: a meta-analysis. Part 1: ADCmean. Oncotarget 26;8(43):75434–75444 (Sep)

    Article  Google Scholar 

  91. Meyer HJ, Purz S, Sabri O, Surov A (2018) Relationships between histogram analysis of ADC values and complex 18F-FDG-PET parameters in head and neck squamous cell carcinoma. PLoS ONE 13(9):e202897

    Article  PubMed  PubMed Central  Google Scholar 

  92. Matoba M, Tuji H, Shimode Y, Toyoda I, Kuginuki Y, Miwa K et al (2014) Fractional change in apparent diffusion coefficient as an imaging biomarker for predicting treatment response in head and neck cancer treated with chemoradiotherapy. Ajnr Am J Neuroradiol 35(2):379–385 (Feb)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Post CM, Ohaegbulam KC, Mitin T (2023) From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer. J Med Radiat Sci 15:

  94. Lee JY, Garcia-Murillas I, Cutts RJ, De Castro DG, Grove L, Hurley T et al (2017) Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma. Br J Cancer 5;117(6):876–883 (Sep)

    Article  Google Scholar 

  95. Verma T, Kumari S, Mishra S, Rastogi M, Tiwari V, Agarwal GR et al (2020) Circulating free DNA as a marker of response to chemoradiation in locally advanced head and neck squamous cell carcinoma. Indian J Pathol Microbiol 63(4):521–526

    Article  PubMed  Google Scholar 

  96. Deist TM, Dankers FJWM, Valdes G, Wijsman R, Hsu IC, Oberije C et al (2018) Machine learning algorithms for outcome prediction in (chemo)radiotherapy: An empirical comparison of classifiers. Med Phys 45(7):3449–3459 (Jul)

    Article  PubMed  PubMed Central  Google Scholar 

  97. Zhang MH, Cao D, Ginat DT (2021) Radiomic Model Predicts Lymph Node Response to Induction Chemotherapy in Locally Advanced Head and Neck Cancer. Diagnostics (basel) 25;11(4):588 (Mar)

    Article  Google Scholar 

  98. Zhai TT, Langendijk JA, van Dijk LV, van der Schaaf A, Sommers L, Vemer-van den Hoek JGM, et al. Pre-treatment radiomic features predict individual lymph node failure for head and neck cancer patients. Radiother Oncol. 2020 May;146:58–65.

  99. Zhai TT, Wesseling F, Langendijk JA, Shi Z, Kalendralis P, van Dijk LV et al (2021) External validation of nodal failure prediction models including radiomics in head and neck cancer. Oral Oncol 112:105083 (Jan)

    Article  CAS  PubMed  Google Scholar 

  100. Iancu RI, Zara AD, Mirestean CC, Iancu DPT (2021) Radiomics in Head and Neck Cancers Radiotherapy. Promises Challenges Maedica (bucur) 16(3):482–488 (Sep)

    PubMed  Google Scholar 

  101. van der Heijden M, Essers PBM, de Jong MC, de Roest RH, Sanduleanu S, Verhagen CVM et al (2019) Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation. Front Oncol 9:1470

    Article  PubMed  Google Scholar 

  102. Balermpas P, Michel Y, Wagenblast J, Seitz O, Weiss C, Rödel F et al (2014) Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. Br J Cancer 21;110(2):501–509 (Jan)

    Article  Google Scholar 

  103. Swartz JE, Pothen AJ, van Kempen PMW, Stegeman I, Formsma FK, Cann EMV et al (2016) Poor prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinomas that overexpress hypoxia inducible factor-1α. Head Neck 38(9):1338–1346 (Sep)

    Article  PubMed  Google Scholar 

  104. Kaanders JHAM, Wijffels KIEM, Marres HAM, Ljungkvist ASE, Pop LAM, van den Hoogen FJA et al (2002) Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer. Cancer Res 1;62(23):7066–7074 (Dec)

    PubMed  Google Scholar 

  105. Hohenstein NA, Chan JW, Wu SY, Tahir P, Yom SS (2020) Diagnosis, Staging, Radiation Treatment Response Assessment, and Outcome Prognostication of Head and Neck Cancers Using PET Imaging: A Systematic Review. PET Clin 15(1):65–75 (Jan)

    Article  PubMed  Google Scholar 

  106. Song IH, Noh Y, Kwon J, Jung JH, Lee BC, Kim KI et al (2017) Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model. Oncotarget 3;8(54):92090–92105 (Nov)

    Article  PubMed  Google Scholar 

  107. Choi W, Lee S wook, Park SH, Ryu JS, Oh SJ, Im KC, et al. Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer. Radiother Oncol. 2010 Nov;97(2):176–82.

  108. Toustrup K, Sørensen BS, Lassen P, Wiuf C, Alsner J, Overgaard J et al (2012) Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck. Radiother Oncol 102(1):122–129 (Jan)

    Article  CAS  PubMed  Google Scholar 

  109. Eschrich SA, Pramana J, Zhang H, Zhao H, Boulware D, Lee JH et al (2009) A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys 1;75(2):489–496 (Oct)

    Article  Google Scholar 

  110. Scott JG, Berglund A, Schell MJ, Mihaylov I, Fulp WJ, Yue B et al (2017) A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol 18(2):202–211 (Feb)

    Article  PubMed  Google Scholar 

  111. Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D et al (2014) 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. JCO 1;32(34):3858–3867 (Dec)

    Article  Google Scholar 

  112. López L, García-Cabo P, Llorente JL, López F, Rodrigo JP. Results of salvage neck dissection after chemoradiation in locally advanced head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol [Internet]. 2023 Oct 28 [cited 2023 Nov 16]; Available from: https://doi.org/10.1007/s00405-023-08315-z

  113. Yao M, Hoffman HT, Chang K, Funk GF, Smith RB, Tan H et al (2007) Is planned neck dissection necessary for head and neck cancer after intensity-modulated radiotherapy? Int J Radiat Oncol Biol Phys 1;68(3):707–713 (Jul)

    Article  PubMed  Google Scholar 

  114. Rengan R, Pfister DG, Lee NY, Kraus DH, Shah JP, Shaha AR et al (2008) Long-term neck control rates after complete response to chemoradiation in patients with advanced head and neck cancer. Am J Clin Oncol 31(5):465–469 (Oct)

    Article  PubMed  Google Scholar 

  115. Peters LJ, Weber RS, Morrison WH, Byers RM, Garden AS, Goepfert H (1996) Neck surgery in patients with primary oropharyngeal cancer treated by radiotherapy. Head Neck 18(6):552–559 (Dec)

    Article  CAS  PubMed  Google Scholar 

  116. Johnson CR, Silverman LN, Clay LB, Schmidt-Ullrich R (1998) Radiotherapeutic management of bulky cervical lymphadenopathy in squamous cell carcinoma of the head and neck: is postradiotherapy neck dissection necessary? Radiat Oncol Investig 6(1):52–57

    Article  CAS  PubMed  Google Scholar 

  117. Vedrine PO, Thariat J, Hitier M, Janot F, Kaminsky MC, Makeieff M et al (2008) Need for neck dissection after radiochemotherapy? A study of the French GETTEC Group. Laryngoscope 118(10):1775–1780 (Oct)

    Article  PubMed  Google Scholar 

  118. Canning CA, Gubbels S, Chinn C, Wax M, Holland JM (2005) Positron emission tomography scan to determine the need for neck dissection after chemoradiation for head and neck cancer: timing is everything. Laryngoscope 115(12):2206–2208 (Dec)

    Article  PubMed  Google Scholar 

  119. 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 Jan 1;61(1):306–7; author reply 307.

  120. Yao M, Graham MM, Hoffman HT, Smith RB, Funk GF, Graham SM et al (2004) 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 15;59(4):1001–1010 (Jul)

    Article  Google Scholar 

  121. Golliez A, Morand GB, Broglie MA, Balermpas P, Rupp NJ (2023) Histopathological Analysis of Nodal Disease After Chemoradiation Reveals Viable Tumor Cells as the most Important Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Head and Neck Pathol 17;17(3):599–606 (May)

    Article  Google Scholar 

  122. Adams G, Porceddu SV, Pryor DI, Panizza B, Foote M, Rowan A et al (2014) Outcomes after primary chemoradiotherapy for N3 (〉 6 cm) head and neck squamous cell carcinoma after an FDG-PET-guided neck management policy. Head Neck 36(8):1200–1206 (Aug)

    Article  PubMed  Google Scholar 

  123. Malone J, Robbins KT (2010) Neck dissection after chemoradiation for carcinoma of the upper aerodigestive tract: indications and complications. Curr Opin Otolaryngol Head Neck Surg 18(2):89–94 (Apr)

    Article  PubMed  Google Scholar 

  124. Wolf GT, Fisher SG (1992) Effectiveness of salvage neck dissection for advanced regional metastases when induction chemotherapy and radiation are used for organ preservation. Laryngoscope 102(8):934–939 (Aug)

    Article  CAS  PubMed  Google Scholar 

  125. van den Bovenkamp K, Noordhuis MG, Oosting SF, van der Laan BFAM, Roodenburg JL, Bijl HP et al (2017) Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors. Clin Otolaryngol 42(3):693–700 (Jun)

    Article  PubMed  Google Scholar 

  126. Robbins KT, Wong FS, Kumar P, Hartsell WF, Vieira F, Mullins B et al (1999) Efficacy of targeted chemoradiation and planned selective neck dissection to control bulky nodal disease in advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 125(6):670–675 (Jun)

    Article  CAS  PubMed  Google Scholar 

  127. Hamoir M, Ferlito A, Schmitz S, Hanin FX, Thariat J, Weynand B et al (2012) The role of neck dissection in the setting of chemoradiation therapy for head and neck squamous cell carcinoma with advanced neck disease. Oral Oncol 48(3):203–210 (Mar)

    Article  PubMed  Google Scholar 

  128. Hillel AT, Fakhry C, Pai SI, Williams MF, Blanco RGF, Zinreich ES et al (2009) Selective versus comprehensive neck dissection after chemoradiation for advanced oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg 141(6):737–742 (Dec)

    Article  PubMed  Google Scholar 

  129. Chung EJ, Lee SH, Baek SH, Bae WJ, Chang YJ, Rho YS (2015) Clinical outcome and prognostic factors after salvage surgery for isolated regional squamous cell carcinoma recurrences. Head Neck 37(11):1612–1617 (Nov)

    Article  PubMed  Google Scholar 

  130. Robbins KT, Ferlito A, Shah JP, Hamoir M, Takes RP, Strojan P et al (2013) The evolving role of selective neck dissection for head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 270(4):1195–1202 (Mar)

    Article  PubMed  Google Scholar 

  131. Tirelli G, Tofanelli M, Sacchet E, Bussani R, Shafiei V, Gatto A et al (2021) Extranodal extension in head and neck squamous cell cancer: is there a role for further stratification? Br J Oral Maxillofac Surg 59(5):567–572

    Article  CAS  PubMed  Google Scholar 

  132. Teudt IU, Kovàcs G, Ritter M, Melchert C, Soror T, Wollenberg B et al (2016) Intensity modulated perioperative HDR brachytherapy for recurrent and/or advanced head and neck metastases. Eur Arch Otorhinolaryngol 273(9):2707–2715 (Sep)

    Article  PubMed  Google Scholar 

  133. Huynh M, Kempson I, Bezak E, Phillips W (2021) Predictive modeling of hypoxic head and neck cancers during fractionated radiotherapy with gold nanoparticle radiosensitization. Med Phys 48(6):3120–3133 (Jun)

    Article  CAS  PubMed  Google Scholar 

  134. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 1;363(1):24–35 (Jul)

    Article  PubMed  Google Scholar 

  135. Spiro RH, Gallo O, Shah JP. Selective jugular node dissection in patients with squamous carcinoma of the larynx or pharynx. The American journal of surgery. 1993 Oct 1;166(4):399–402.

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Authors and Affiliations

  1. Department of Oto-Rhino-Laryngology & Head and Neck Surgery, Poitiers University Hospital, Poitiers, France

    Florent Carsuzaa MD

  2. Department of Surgery, University Cancer Institute of Toulouse—Oncopole, Toulouse, France

    Emilien Chabrillac MD

  3. Department of Radiology, Clinique du Cap d’Or, La Seyne-sur-mer, France

    Pierre Yves Marcy MD

  4. Institute for Head and Neck Studies and Education (InHANSE), University of Birmingham, Birmingham, UK

    Hisham Mehanna MD PhD

  5. Department of radiotherapy, Centre François Baclesse, Caen, France

    Juliette Thariat MD PhD

  6. Laboratoire de physique Corpusculaire, IN2P3/ENSICAEN/CNRS, UMR 6534, Normandie Université, Caen, France

    Juliette Thariat MD PhD

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Carsuzaa, F., Chabrillac, E., Marcy, P.Y. et al. Advances and residual knowledge gaps in the neck management of head and neck squamous cell carcinoma patients with advanced nodal disease undergoing definitive (chemo)radiotherapy for their primary. Strahlenther Onkol (2024). https://doi.org/10.1007/s00066-024-02228-4

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