Current Oncology Reports

, 21:102 | Cite as

Treatment Strategy for Distant Synchronous Metastatic Head and Neck Squamous Cell Carcinoma

  • Eliane TangEmail author
  • Lucien Lahmi
  • Nicolas Meillan
  • Gianandrea Pietta
  • Sébastien Albert
  • Philippe Maingon
Head and Neck Cancers (EY Hanna, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Head and Neck Cancers


Purpose of Review

Management of metastatic head and neck squamous cell cancers (HNSCC) can be challenging. This review gives an insight of current treatment options for patients with synchronous metastatic HNSCC and suggests a therapeutic algorithm.

Recent Findings

With the rise of novel therapeutic techniques and medications, many treatment options for both locoregional and distant metastatic disease have become available. The evolving paradigm of metastatic disease now integrates the concept of oligometastatic disease. On top of systemic treatments, patients with low metastatic burden can benefit from curative approaches such as local therapies (surgery, radiotherapy) directed to either primary tumour and distant metastasis. However, data integrating these considerations in the management of metastatic HNSCC is still lacking.


Based on this algorithm, we can provide a tailored treatment to each patient with synchronous metastatic HNSCC, according to their age, general condition and metastatic burden.


Squamous cell cancer Head and neck cancer Metastases Chemotherapy Radiotherapy Treatment algorithm 


Compliance with Ethical Standards

Conflict of Interest

Eliane Tang, Lucien Lahmi, Nicolas Meillan, Gianandrea Pietta, Sébastien Albert, and Philippe Maingon declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ferlito A, Shaha AR, Silver CE, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. ORL. 2001;63:202–7.PubMedGoogle Scholar
  2. 2.
    Vermorken J, Mesia R, Rivera F, Remenar E. Platinum-based chemotherapy plus Cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.PubMedGoogle Scholar
  3. 3.
    Kotwall C, Sako K, Razack MS, Rao U, Bakamjian V, Shedd DP. Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg. 1987;154:439–42.PubMedGoogle Scholar
  4. 4.
    Garavello W, Ciardo A, Spreafico R, Gaini RM. Risk factors for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol Neck Surg. 2006;132:762–6.Google Scholar
  5. 5.
    Kuperman DI, Auethavekiat V, Adkins DR, Nussenbaum B, Collins S, Boonchalermvichian C, et al. Squamous cell cancer of the head and neck with distant metastasis at presentation. Head Neck. 2011;33:714–8.PubMedGoogle Scholar
  6. 6.
    Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol. 2006;24:2606–11.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Taberna M, Mena M, Pavón MA, Alemany L, Gillison ML, Mesía R. Human papillomavirus-related oropharyngeal cancer. Ann Oncol. 2017;28:2386–98.PubMedGoogle Scholar
  8. 8.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014;32:3365–73.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Huang SH, Perez-Ordonez B, Liu F-F, Waldron J, Ringash J, Irish J, et al. Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Int J Radiat Oncol. 2012;82:276–83.Google Scholar
  11. 11.
    Müller S, Khuri FR, Kono SA, Beitler JJ, Shin DM, Saba NF. HPV positive squamous cell carcinoma of the oropharynx. Are we observing an unusual pattern of metastases? Head Neck Pathol. 2012;6:336–44.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.Google Scholar
  13. 13.
    Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011;8:378–82.PubMedGoogle Scholar
  14. 14.
    Lee DH, Kim MJ, Roh J-L, Kim S-B, Choi S-H, Nam SY, et al. Distant metastases and survival prediction in head and neck squamous cell carcinoma. Otolaryngol-Head Neck Surg. 2012;147:870–5.PubMedGoogle Scholar
  15. 15.
    Guigay J, Fayette J, Dillies AF, Sire C, Kerger JN, Tennevet I, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol. 2015;26:1941–7.PubMedGoogle Scholar
  16. 16.
    Boisdron-Celle M, Capitain O, Faroux R, Borg C, Metges JP, Galais MP, et al. Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: assessment of a multiparametric approach. Cancer Screen Still Work Prog. 2017;44:13–23.Google Scholar
  17. 17.
    Tahara M, Kiyota N, Yokota T, Hasegawa Y, Muro K, Takahashi S, et al. Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). Ann Oncol. 2018;mdy040–mdy040.Google Scholar
  18. 18.
    Pfister DG, Foote RL, Gilbert J, Gillison ML, Ridge JA, Rocco J. NCCN Guidelines Index Table of Contents Discussion 2018;227.Google Scholar
  19. 19.
    Gregoire V, Lefebvre J-L, Licitra L, Felip E. On behalf of the EHNS-ESMO-ESTRO guidelines working group. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:v184–6.PubMedGoogle Scholar
  20. 20.
    Economopoulou P, Agelaki S, Perisanidis C, Giotakis EI, Psyrri A. The promise of immunotherapy in head and neck squamous cell carcinoma. Ann Oncol. 2016;27:1675–85.PubMedGoogle Scholar
  21. 21.
    Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 17:956–65.PubMedGoogle Scholar
  22. 22.
    Harrington KJ, Ferris RL, Blumenschein G, Colevas AD, Fayette J, Licitra L, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017;18:1104–15.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kaifi JT, Gusani NJ, Deshaies I, Kimchi ET, Reed MF, Mahraj RP, et al. Indications and approach to surgical resection of lung metastases. J Surg Oncol. 2010;102:187–95.PubMedGoogle Scholar
  24. 24.
    Young ER, Diakos E, Khalid-Raja M, Mehanna H. Resection of subsequent pulmonary metastases from treated head and neck squamous cell carcinoma: systematic review and meta-analysis. Clin Otolaryngol. 2015;40:208–18.PubMedGoogle Scholar
  25. 25.
    Liu D, Labow DM, Dang N, Martini N, Bains M, Burt M, et al. Pulmonary metastasectomy for head and neck cancers. Ann Surg Oncol. 1999;6:572–8.PubMedGoogle Scholar
  26. 26.
    Haro A, Yano T, Yoshida T, Ito K, Morodomi Y, Shoji F, et al. Results of a surgical resection of pulmonary metastasis from malignant head and neck tumor. Interact Cardiovasc Thorac Surg. 2010;10:700–3.PubMedGoogle Scholar
  27. 27.
    Shiono S, Kawamura M, Sato T, Okumura S, Nakajima J, Yoshino I, et al. Pulmonary metastasectomy for pulmonary metastases of head and neck squamous cell carcinomas. Ann Thorac Surg. 2009;88:856–60.PubMedGoogle Scholar
  28. 28.
    Ricco A, Davis J, Rate W, Yang J, Perry D, Pablo J, et al. Lung metastases treated with stereotactic body radiotherapy: the RSSearch® patient Registry’s experience. Radiat Oncol. 2017;12.Google Scholar
  29. 29.
    Bhattacharya IS, Hoskin PJ. Stereotactic body radiotherapy for spinal and bone metastases. Clin Oncol. 2015;27:298–306.Google Scholar
  30. 30.
    Adam R, Chiche L, Aloia T, Elias D, Salmon R, Rivoire M, et al. Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1452 patients and development of a prognostic model. Trans Meet Am Surg Assoc. 2006;124:189–200.Google Scholar
  31. 31.
    Pawlik TM, Gleisner AL, Bauer TW, Adams RB, Reddy SK, Clary BM, et al. Liver-directed surgery for metastatic squamous cell carcinoma to the liver: results of a multi-center analysis. Ann Surg Oncol. 2007;14:2807–16.PubMedGoogle Scholar
  32. 32.
    Adam R, Wicherts DA, de Haas RJ, Ciacio O, Lévi F, Paule B, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009;27:1829–35.PubMedGoogle Scholar
  33. 33.
    Scorsetti M, Clerici E, Comito T. Stereotactic body radiation therapy for liver metastases. J Gastrointest Oncol. 2014;5:190.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases. JAMA. 2006;295:2483–91.PubMedGoogle Scholar
  35. 35.
    Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10:1037–44.PubMedGoogle Scholar
  36. 36.
    Patel RA, Bell JB, Kim T, Agulnik M, Chandler JP, Mittal BB, et al. Stereotactic radiosurgery for brain metastases from primary head and neck carcinomas: a retrospective analysis. J Neuro-Oncol. 2017;134:197–203.Google Scholar
  37. 37.
    Roland NJ, Bradley PJ. The role of surgery in the palliation of head and neck cancer. Curr Opin Otolaryngol Head Neck Surg. 2014;22:101–8.PubMedGoogle Scholar
  38. 38.
    •• Kabarriti R, Baliga S, Ohri N, Guha C, Kalnicki S, Garg MK. Radiation therapy for patients with newly diagnosed metastatic head and neck squamous cell carcinoma. Head Neck. 2018;41(1):130–8 First clinical study to demonstrate a survival benefit for the use of radiotherapy in the initial management of metastatic HNSCC. PubMedGoogle Scholar
  39. 39.
    • Patel TD, Marchiano E, Chin OY, Kilic S, Eloy JA, Baredes S, et al. Utility of surgery/radiotherapy in distant metastatic head and neck squamous cell carcinoma: a population-based approach. Otolaryngol-Head Neck Surg. 2016;154:868–74 Study reporting longer survival in metastatic HNSCC patients treated with radiotherapy and/or surgery compared to patients who did not undergo any therapy. PubMedGoogle Scholar
  40. 40.
    •• Zumsteg ZS, Luu M, Yoshida EJ, Kim S, Tighiouart M, David JM, et al. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: an analysis of the National Cancer Data Base: local treatment in metastatic HNSCC. Cancer. 2017;123:4583–93 Study reporting an association between prolonged OS and the addition of high-intensity local treatment (radiotherapy delivered at curative dose or surgery) to systemic therapy in metastatic HNSCC patients. PubMedPubMedCentralGoogle Scholar
  41. 41.
    Chen AM, Vaughan A, Narayan S, Vijayakumar S. Palliative radiation therapy for head and neck cancer: toward an optimal fractionation scheme. Head Neck. 2008;30:1586–91.PubMedGoogle Scholar
  42. 42.
    Corry J, Peters LJ, Costa ID, Milner AD, Fawns H, Rischin D, et al. The ‘QUAD SHOT’—a phase II study of palliative radiotherapy for incurable head and neck cancer. Radiother Oncol. 2005;77:137–42.PubMedGoogle Scholar
  43. 43.
    Porceddu SV, Rosser B, Burmeister BH, Jones M, Hickey B, Baumann K, et al. Hypofractionated radiotherapy for the palliation of advanced head and neck cancer in patients unsuitable for curative treatment – “Hypo Trial.”. Radiother Oncol. 2007;85:456–62.PubMedGoogle Scholar
  44. 44.
    Mertens C, Le Caer H, Ortholan C, Blot E, Even C, Rousselot H, et al. The ELAN-ONCOVAL (ELderly heAd and neck cancer-oncology eValuation) study: evaluation of the feasibility of a suited geriatric assessment for use by oncologists to classify patients as fit or unfit. Ann Oncol. 2017;28.Google Scholar
  45. 45.
    Adelstein DJ, Li Y, Adams GL, Wagner H, Kish JA, Ensley JF, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003;21:92–8.PubMedGoogle Scholar
  46. 46.
    Leclerc M, Maingon P, Hamoir M, Dalban C, Calais G, Nuyts S, et al. A dose escalation study with intensity modulated radiation therapy (IMRT) in T2N0, T2N1, T3N0 squamous cell carcinomas (SCC) of the oropharynx, larynx and hypopharynx using a simultaneous integrated boost (SIB) approach. Radiother Oncol. 2013;106:333–40.PubMedGoogle Scholar
  47. 47.
    Vermorken JB, Psyrri A, Mesía R, Peyrade F, Beier F, de Blas B, et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol. 2014;25:801–7.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14:697–710.PubMedGoogle Scholar
  49. 49.
    Mehra R, Egloff AM, Li S, Yang D, Wang L, Zhu F, et al. Analysis of HPV and ERCC1 in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). J Clin Oncol. 2013;31:6006.Google Scholar
  50. 50.
    Spreafico A, Amir E, Siu LL. Demystifying the role of tumor HPV status in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2014;25:760–2.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Eliane Tang
    • 1
    Email author
  • Lucien Lahmi
    • 1
  • Nicolas Meillan
    • 1
  • Gianandrea Pietta
    • 1
  • Sébastien Albert
    • 2
  • Philippe Maingon
    • 1
  1. 1.Department of Radiation Oncology, groupe Pitié-SalpêtrièreAssistance Publique-Hôpitaux de Paris, Sorbonne UniversitéParisFrance
  2. 2.Department of Head and Neck SurgeryHôpital Bichat, Assistance Publique-Hôpitaux de ParisParisFrance

Personalised recommendations