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Detection of Distant Metastases in Head and Neck Cancer: Changing Landscape

Advances in Therapy volume 35, pages 161–172 (2018)Cite this article

Abstract

As head and neck squamous cell carcinoma (HNSCC) patients with distant metastases (DM) were generally treated only palliatively, the value of screening for DM was usually limited to attempts to avoid extensive locoregional treatment when DM were present pretreatment. Recently, the concept of treating oligometastases, e.g., by metastatectomy or stereotactic body radiotherapy, has been reintroduced for HNSCC and may cause a change in the treatment paradigm. Although whole body 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) combined with computed tomography (CT; WB-FDG-PET/CT) is still the mainstay diagnostic technique, there is a growing body of evidence supporting implementation of whole body magnetic resonance imaging (WB-MRI) as an important diagnostic technique for screening for DM. Also, FDG-PET/MRI may become a valuable technique for the detection of DM in HNSCC patients. Because the yield of examinations for detection of DM is too low to warrant routine screening of all HNSCC patients, only patients with high risk factors should be selected for intense screening for DM. Clinical and histopathological risk factors are mainly related to the extent of lymph node metastases. Risk for development of DM may also be assessed by molecular characterization of the primary tumor using genomic and proteomic technologies and radiomics. More research is needed to develop a new protocol for screening for DM after introduction of the concept of treating oligometastases in HNSCC.

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References

  1. Takes RP, Rinaldo A, Silver CE, et al. Distant metastases from head and neck squamous cell carcinoma. Part I. Basic aspects. Oral Oncol. 2012;48:775–9.

    Article  PubMed  Google Scholar 

  2. Haigentz M Jr, Hartl DM, Silver CE, et al. Distant metastases from head and neck squamous cell carcinoma. Part III. Treatment. Oral Oncol. 2012;48:787–93.

    Article  PubMed  Google Scholar 

  3. De Bree R, Haigentz M Jr, Silver CE, et al. Distant metastases from head and neck squamous cell carcinoma. Part II. Diagnosis. Oral Oncol. 2012;48:780–6.

    Article  PubMed  Google Scholar 

  4. Florescu C, Thariat J. Local ablative treatments of oligometastases from head and neck carcinomas. Crit Rev Oncol Hematol. 2014;91:47–63.

    Article  CAS  PubMed  Google Scholar 

  5. Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence. Cancer. 2007;110:1429–35.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. De Bree R, Deurloo EE, Snow GB, Leemans CR. Screening for distant metastases in patients with head and neck cancer. Laryngoscope. 2000;110:397–400.

    Article  PubMed  Google Scholar 

  8. Uyl-de Groot CA, Senft A, de Bree R, Leemans CR, Hoekstra OS. Chest CT and whole-body 18F-FDG PET are cost-effective in screening for distant metastases in head and neck cancer patients. J Nucl Med. 2010;51:176–82.

    Article  PubMed  Google Scholar 

  9. Senft A, de Bree R, Hoekstra OS, et al. Screening for distant metastases in head and neck cancer patients by chest CT or whole body FDG-PET: a prospective multicenter trial study. Radiother Oncol. 2008;87:221–9.

    Article  PubMed  Google Scholar 

  10. Peters TT, Senft A, Hoekstra OS, et al. Pretreatment screening on distant metastases and head and neck cancer patients: validation of risk factors and influence on survival. Oral Oncol. 2015;51:267–71.

    Article  PubMed  Google Scholar 

  11. Ng SH, Chan SC, Liao CT, et al. Distant metastases and synchronous second primary tumors in patients with newly diagnosed oropharyngeal and hypopharyngeal carcinomas: evaluation of (18)F-FDG PET and extended-field multi-detector row CT. Neuroradiology. 2008;50:969–79.

    Article  PubMed  Google Scholar 

  12. Rohde M, Nielsen AL, Johansen J, et al. Head-to-head comparison of chest X-ray/head and neck MRI, chest CT/head and neck MRI, and 18F-FDG-PET/CT for detection of distant metastases and synchronous cancer in oral, pharyngeal, and laryngeal cancer. J Nucl Med. 2017;58:1919–24.

    Article  PubMed  Google Scholar 

  13. Yankevich U, Hughes MA, Rath TJ, et al. PET/CT for head and neck squamous cell carcinoma: should we routinely include the head and abdomen? AJR Am J Roentgenol. 2017;208:844–8.

    Article  PubMed  Google Scholar 

  14. Xu GZ, Guan DJ, He ZY. (18)FDG-PET/CT for detecting distant metastases and second primary cancers in patients with head and neck cancer. A meta-analysis. Oral Oncol. 2011;47:560–5.

    Article  PubMed  Google Scholar 

  15. Senft A, Yildirim G, Hoekstra OS, Castelijns JA, Leemans CR, de Bree R. The adverse impact of surveillance intervals on the sensitivity of FDG-PET/CT for the detection of distant metastases in head and neck cancer patients. Eur Arch Otorhinolaryngol. 2017;274:1113–20.

    Article  PubMed  Google Scholar 

  16. Suenaga Y, Kitajima K, Ishihara T, et al. FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT. Eur Radiol. 2016;26:1018–30.

    Article  PubMed  Google Scholar 

  17. Brouwer J, Bree R, Hoekstra OS, Langendijk JA, Castelijns JA, Leemans CR. Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice? Clin Otolaryngol. 2005;30:438–43.

    Article  CAS  PubMed  Google Scholar 

  18. Cheng G, Torigian DA, Zhuang H, Alavi A. When should we recommend use of dual time-point and delayed time-point imaging techniques in FDG PET? Eur J Nucl Med Mol Imaging. 2013;40:779–87.

    Article  CAS  PubMed  Google Scholar 

  19. Cheng G, Alavi A, Lim E, Werner TJ, Del Bello CV, Akers SR. Dynamic changes of FDG uptake and clearance in normal tissues. Mol Imaging Biol. 2013;15:345–52.

    Article  PubMed  Google Scholar 

  20. Uesaka D, Demura Y, Ishizaki T, et al. Evaluation of dual-time-point 18F-FDG PET for staging in patients with lung cancer. J Nucl Med. 2008;49:1606–12.

    Article  PubMed  Google Scholar 

  21. Heuveling DA, de Bree R, van Dongen GA. The potential role of non-FDG-PET in the management of head and neck cancer. Oral Oncol. 2011;47:2–7.

    Article  CAS  PubMed  Google Scholar 

  22. Hoshikawa H, Kishino T, Mori T, Nishiyama Y, Yamamoto Y, Mori N. The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients. Clin Nucl Med. 2013;38:e318–23.

    Article  PubMed  Google Scholar 

  23. Kwee TC, Takahara T, Ochiai R, Nievelstein RA, Luijten PR. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS): features and potential applications in oncology. Eur Radiol. 2008;18:1937–52.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Huang B, Law MW, Khong PL. Whole-body PET/CT scanning: estimation of radiation dose and cancer risk. Radiology. 2009;251:166–74.

    Article  PubMed  Google Scholar 

  25. Quinn B, Dauer Z, Pandit-Taskar N, Schoder H, Dauer LT. Radiation dosimetry of 18F-FDG PET/CT: incorporating exam-specific parameters in dose estimates. BMC Med Imaging. 2016;16:41.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Li B, Li Q, Nie W, Liu S. Diagnostic value of whole-body diffusion-weighted magnetic resonance imaging for detection of primary and metastatic malignancies: a meta-analysis. Eur J Radiol. 2014;83:338–44.

    Article  PubMed  Google Scholar 

  27. Noij DP, Boerhout EJ, Pieters-van den Bos IC, et al. Whole-body-MR imaging including DWIBS in the work-up of patients with head and neck squamous cell carcinoma: a feasibility study. Eur J Radiol. 2014;83:1144–51.

    Article  PubMed  Google Scholar 

  28. Ng SH, Chan SC, Yen TC, et al. Pretreatment evaluation of distant-site status in patients with nasopharyngeal carcinoma: accuracy of whole-body MRI at 3-Tesla and FDG-PET-CT. Eur Radiol. 2009;19:2965–76.

    Article  PubMed  Google Scholar 

  29. Chan SC, Wang HM, Yen TC, et al. 18F-FDG PET/CT and 3.0-T whole-body MRI for the detection of distant metastases and second primary tumours in patients with untreated oropharyngeal/hypopharyngeal carcinoma: a comparative study. Eur J Nucl Med Mol Imaging. 2011;38:1607–19.

    Article  PubMed  Google Scholar 

  30. Castelijns JA. PET-MRI in the head and neck area: challenges and new directions. Eur Radiol. 2011;21:2425–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Heusch P, Nensa F, Schaarschmidt B, et al. Diagnostic accuracy of whole-body PET/MRI and whole-body PET/CT for TNM staging in oncology. Eur J Nucl Med Mol Imaging. 2015;42:42–8.

    Article  CAS  PubMed  Google Scholar 

  32. Partovi S, Kohan A, Vercher-Conejero JL, et al. Qualitative and quantitative performance of 18F-FDG-PET/MRI versus 18F-FDG-PET/CT in patients with head and neck cancer. AJNR Am J Neuroradiol. 2014;35:1970–5.

    Article  CAS  PubMed  Google Scholar 

  33. Schaarschmidt BM, Gomez B, Buchbender C, et al. Is integrated 18F-FDG PET/MRI superior to 18F-FDG PET/CT in the differentiation of incidental tracer uptake in the head and neck area? Diagn Interv Radiol. 2017;23:127–32.

    Article  PubMed  PubMed Central  Google Scholar 

  34. de Bree R, Ljumanovic R, Hazewinkel MJ, Witte BI, Castelijns JA. Radiologic extranodal spread and matted nodes: important predictive factors for development of distant metastases in patients with high-risk head and neck cancer. Head Neck. 2016;38(Suppl 1):E1452–8.

    Article  PubMed  Google Scholar 

  35. Meeuwis J, Hoekstra OS, Witte BI, Boellaard R, Leemans CR, de Bree R. 18FDG SUV in the primary tumor and lymph node metastases is not predictive for development of distant metastases in high risk head and neck cancer patients. Oral Oncol. 2015;51:536–40.

    Article  PubMed  Google Scholar 

  36. Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer. 1993;71:452–6.

    Article  CAS  PubMed  Google Scholar 

  37. Coca-Pelaz A, Rodrigo JP, Suárez C. Clinicopathologic analysis and predictive factors for distant metastases in patients with head and neck squamous cell carcinomas. Head Neck. 2012;34:771–5.

    Article  PubMed  Google Scholar 

  38. Duprez F, Berwouts D, De Neve W, et al. Distant metastases in head and neck cancer. Head Neck. 2017;39:1733–43.

    Article  PubMed  Google Scholar 

  39. León X, Quer M, Orús C, Venegas MP, Montoro V. Distant metastases in head and neck cancer patients who achieved loco-regional control. Head Neck. 2000;22:680–6.

    Article  PubMed  Google Scholar 

  40. Ren YY, Li YC, Wu HB, et al. Whole-body 18F-FDG PET/CT for M staging in the patient with newly diagnosed nasopharyngeal carcinoma: who needs? Eur J Radiol. 2017;89:200–7.

    Article  PubMed  Google Scholar 

  41. Loh KS, Brown DH, Baker JT, Gilbert RW, Gullane PJ, Irish JC. A rational approach to pulmonary screening in newly diagnosed head and neck cancer. Head Neck. 2005;27:990–4.

    Article  PubMed  Google Scholar 

  42. Haerle SK, Schmid DT, Ahmad N, Hany TF, Stoeckli SJ. The value of (18)F-FDG PET/CT for the detection of distant metastases in high-risk patients with head and neck squamous cell carcinoma. Oral Oncol. 2011;47:653–9.

    Article  PubMed  Google Scholar 

  43. Ljumanovic R, Langendijk JA, Hoekstra OS, Leemans CR, Castelijns JA. Distant metastases in head and neck carcinoma: identification of prognostic groups with MR imaging. Eur J Radiol. 2006;60:58–66.

    Article  PubMed  Google Scholar 

  44. Khwaja SS, Baker C, Haynes W, et al. High E6 gene expression predicts for distant metastasis and poor survival in patients with HPV-positive oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2016;95:1132–41.

    Article  CAS  PubMed  Google Scholar 

  45. Kumar B, Brown NV, Swanson BJ, et al. High expression of myoferlin is associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with HPV-status. Oncotarget. 2016;7:18665–77.

    PubMed  PubMed Central  Google Scholar 

  46. Zhuo X, Luo H, Chang A, Li D, Zhao H, Zhou Q. Is overexpression of TWIST, a transcriptional factor, a prognostic biomarker ofhead and neck carcinoma? Evidence from fifteen studies. Sci Rep. 2015;5:18073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lin YM, Sung WW, Hsieh MJ, et al. High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. PLoS One. 2015;10:e0142656.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Pickhard A, Gröber S, Haug AK, et al. Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:733–42.

    Article  PubMed  Google Scholar 

  49. Rodrigo JP, Martínez P, Allonca E, et al. Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas. Clin Exp Metastasis. 2014;31:317–25.

    Article  CAS  PubMed  Google Scholar 

  50. Nijkamp MM, Span PN, Hoogsteen IJ, van der Kogel AJ, Kaanders JH, Bussink J. Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients. Radiother Oncol. 2011;99:344–8.

    Article  CAS  PubMed  Google Scholar 

  51. Rasmussen GB, Håkansson KE, Vogelius IR, et al. Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma. Acta Oncol. 2017:56:1562–70.

  52. Aerts HJ, Velazquez ER, Leijenaar RT, et al. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat Commun. 2014;5:4006.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Vallières M, Kay-Rivest E, Perrin LJ, et al. Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer. Sci Rep. 2017;7:10117.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Sol N, Wurdinger T. Platelet RNA signatures for the detection of cancer. Cancer Metastasis Rev. 2017;36:263–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Möckelmann N, Laban S, Pantel K, Knecht R. Circulating tumor cells in head and neck cancer: clinical impact in diagnosis and follow-up. Eur Arch Otorhinolaryngol. 2014;271:15–22.

    Article  PubMed  Google Scholar 

  56. Colnot DR, Nieuwenhuis EJ, Kuik DJ, et al. Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients. Clin Cancer Res. 2004;10:7827–33.

    Article  CAS  PubMed  Google Scholar 

  57. van Ginkel JH, Huibers MMH, Noorlag R, de Bree R, van Es RJJ, Willems SM. Liquid biopsy: a future tool for posttreatment surveillance in head and neck cancer? Pathobiology. 2017;84:115–20.

    Article  PubMed  Google Scholar 

  58. van Ginkel JH, Huibers MMH, van Es RJJ, de Bree R, Willems SM. Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. BMC Cancer. 2017;17:428.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Digonnet A, Hamoir M, Andry G, et al. Post-therapeutic surveillance strategies in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2013;270:1569–80.

    Article  PubMed  Google Scholar 

  60. Brouwer J, de Bree R, Hoekstra OS, et al. Screening for distant metastases in patients with head and neck cancer: is chest computed tomography sufficient? Laryngoscope. 2005;115:1813–7.

    Article  PubMed  Google Scholar 

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Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. This article was written by members and invitees of the International Head and Neck Scientific Group (www.IHNSG.com).

Disclosures

Remco de Bree, Asaf Senft, Andrés Coca-Pelaz, Luiz Kowalski, Fernando Lopez, William Mendenhall, Miquel Quer, Alessandra Rinaldo, Ashok R. Shaha, Primož Strojan, Robert P. Takes, Carl E. Silver, C. René Leemans, and Alfio Ferlito have nothing to disclose.

Compliance with Ethics Guidelines

This article is based on previously conducted and reported studies and does contain studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands

    Remco de Bree

  2. Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands

    Remco de Bree, Asaf Senft & C. René Leemans

  3. Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Andrés Coca-Pelaz & Fernando Lopez

  4. Department of Otorhinolaryngology-Head and Neck Surgery, Centro de Tratamento e Pesquisa Hospital do Cancer A.C. Camargo, São Paulo, Brazil

    Luiz Kowalski

  5. Instituto Universitario de Oncología del Principado de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias and CIBERONC, ISCIII, University of Oviedo, Oviedo, Spain

    Fernando Lopez

  6. Department of Radiation Oncology, University of Florida, Gainesville, FL, USA

    William Mendenhall

  7. Department of Otolaryngology, Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Miquel Quer

  8. University of Udine School of Medicine, Udine, Italy

    Alessandra Rinaldo

  9. Head and Neck Service, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    Ashok R. Shaha

  10. Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia

    Primož Strojan

  11. Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands

    Robert P. Takes

  12. Department of Surgery, University of Arizona College of Medicine, Phoenix, AZ, USA

    Carl E. Silver

  13. Coordinator of the International Head and Neck Scientific Group, Padua, Italy

    Alfio Ferlito

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  1. Remco de Bree
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  2. Asaf Senft
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  12. Carl E. Silver
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Correspondence to Remco de Bree.

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de Bree, R., Senft, A., Coca-Pelaz, A. et al. Detection of Distant Metastases in Head and Neck Cancer: Changing Landscape. Adv Ther 35, 161–172 (2018). https://doi.org/10.1007/s12325-018-0662-8

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Keywords

  • Distant metastases
  • Oligometastases
  • Positron emission tomography
  • Risk factors
  • Whole body magnetic resonance imaging