Post-therapeutic detection of local tumor persistence of head and neck cancer: the value of routine control endoscopy with biopsy and medical imaging


  • Tobias Engert Department of Otorhinolaryngology, Head and Neck Surgery, Kantonsspital Aarau, Aarau, Switzerland
  • Leyla Acu Department of Neuroradiology, Kantonsspital Aarau, Aarau, Switzerland
  • Johann Schoenhofer Department of Neuroradiology, Kantonsspital Aarau, Aarau, Switzerland
  • Nikki Rommers Department of Clinical Research, University Hospital Basel, Basel, Switzerland
  • Nader Ahmad Department of Otorhinolaryngology, Head and Neck Surgery, Kantonsspital Aarau, Aarau, Switzerland



Follow-up, HNC, Imaging, Re-staging


Background: Insufficient local tumor control is the main cause of treatment failure in head and neck cancer (HNC). Re-staging HNC is challenging because of post-therapeutic tissue distortion. We investigate whether medical imaging and biopsy is more sensitive in identifying tumor persistence.

Methods: In our clinic a re-staging with a control endoscopy and medical imaging is performed 3 months after therapy for some HNC patients. In this retrospective study, we compare the accuracy of imaging to the histology (gold standard). Imaging reports were classified according to 3 scales and re-assessed by 2 neuroradiologists. Furthermore, we evaluate recurrence rates and disease-free survival.  

Results: 100 cases were evaluated. 14 patients presented with positive histology at the re-staging. Biopsy detected malignancy in 7 patients with inconspicuous imaging. Disease-free survival during the first 2 years was generally low (n=55). The accuracy of the RECIST scale was 0.74 with a sensitivity of 0.50 and a specificity of 0.78. Imaging reports reviewed according to the Lee-scale and a self-developed scale presented an accuracy of 0.47 and 0.51. Re-assessment of imaging by 2 neuroradiologists showed an accuracy of 0.87.

Conclusions: Medical imaging alone serves as a moderate diagnostic tool to diagnose local persistence of HNC 3 months after therapy. Radiologic misdiagnosing can be addressed by control endoscopy. Our results indicate a benefit of routine biopsies since reliance on imaging may fail to notice tumor persistence. A binary classification of imaging showed a higher accuracy than conventional imaging scales and may help to predict tumor recurrence within 24 months after re-staging.


Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.

Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471-4.

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 Cancer J Clin. 2017;67(2):122-37.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-47.

Lee JY, Cheng KL, Lee JH, Choi YJ, Kim HW, Sung YS, et al. Detection of Local Recurrence in Patients with Head and Neck Squamous Cell Carcinoma Using Voxel-Based Color Maps of Initial and Final Area under the Curve Values Derived from DCE-MRI. AJNR Am J Neuroradiol. 2019;40(8):1392-401.

Manikantan K, Khode S, Dwivedi RC, Palav R, Nutting CM, Rhys-Evans P, et al. Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up. Cancer Treat Rev. 2009;35(8):744-53.

Ritoe SC, Krabbe PF, Kaanders JH, van den Hoogen FJ, Verbeek AL, Marres HA. Value of routine follow-up for patients cured of laryngeal carcinoma. Cancer. 2004;101(6):1382-9.

Quon H, Vapiwala N, Forastiere A, Kennedy EB, Adelstein DJ, Boykin H, et al. Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol. 2017;35(36):4078-90.

Preda L, Chiesa F, Calabrese L, Latronico A, Bruschini R, Leon ME, et al. Relationship between histologic thickness of tongue carcinoma and thickness estimated from preoperative MRI. Eur Radiol. 2006;16(10):2242-8.

Abgral R, Querellou S, Potard G, Le Roux PY, Le Duc-Pennec A, Marianovski R, et al. Does 18F-FDG PET/CT improve the detection of posttreatment recurrence of head and neck squamous cell carcinoma in patients negative for disease on clinical follow-up? J Nucl Med. 2009;50(1):24-9.

Denaro N, Merlano MC, Russi EG. Follow-up in Head and Neck Cancer: Do More Does It Mean Do Better? A Systematic Review and Our Proposal Based on Our Experience. Clin Exp Otorhinolaryngol. 2016;9(4):287-97.

Cohen EE, LaMonte SJ, Erb NL, Beckman KL, Sadeghi N, Hutcheson KA, et al. American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016;66(3):203-39.

Kyto E, Haapio E, Minn H, Irjala H. Critical review of the follow-up protocol for head and neck cancer patients. J Laryngol Otol. 2019;133(5):424-9.

Spector JG, Sessions DG, Haughey BH, Chao KS, Simpson J, El Mofty S, et al. Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope. 2001;111(6):1079-87.

Brands MT, Brennan PA, Verbeek ALM, Merkx MAW, Geurts SME. Follow-up after curative treatment for oral squamous cell carcinoma. A critical appraisal of the guidelines and a review of the literature. Eur J Surg Oncol. 2018;44(5):559-65.

Agrawal A, Hammond TH, Young GS, Avon AL, Ozer E, Schuller DE. Factors affecting long-term survival in patients with recurrent head and neck cancer may help define the role of post-treatment surveillance. Laryngoscope. 2009;119(11):2135-40.

Sandro V Porceddu RSW. Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma. Uptodate. 2020. Available at: Accessed on 18 January 2024.

Roman BR, Goldenberg D, Givi B. AHNS Series--Do you know your guidelines? Guideline recommended follow-up and surveillance of head and neck cancer survivors. Head Neck. 2016;38(2):168-74.

Sullivan BP, Parks KA, Dean NR, Rosenthal EL, Carroll WR, Magnuson JS. Utility of CT surveillance for primary site recurrence of squamous cell carcinoma of the head and neck. Head Neck. 2011;33(11):1547-50.

Hwang HS, Perez DA, Orloff LA. Comparison of positron emission tomography/computed tomography imaging and ultrasound in staging and surveillance of head and neck and thyroid cancer. Laryngoscope. 2009;119(10):1958-65.

Ahuja A, Leung SF, Ying M, Metreweli C. Echography of metastatic nodes treated by radiotherapy. J Laryngol Otol. 1999;113(11):993-8.

Mehanna H, Wong W-L, McConkey CC, Rahman JK, Robinson M, Hartley AGJ, et al. PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med. 2016;374(15):1444-54.

Porceddu SV, Pryor DI, Burmeister E, Burmeister BH, Poulsen MG, Foote MC, et al. Results of a prospective study of positron emission tomography-directed management of residual nodal abnormalities in node-positive head and neck cancer after definitive radiotherapy with or without systemic therapy. Head Neck. 2011;33(12):1675-82.

Meerwein CM, Queiroz M, Kollias S, Hullner M, Veit-Haibach P, Huber GF. Post-treatment surveillance of head and neck cancer: pitfalls in the interpretation of FDG PET-CT/MRI. Swiss Med Wkly. 2015;145:w14116.

Diagnostik, Therapie und Nachsorge des Larynxkarzinoms. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). AWMF-Registernummer: 017/076OL. 2019.

Haughey BH, Gates GA, Arfken CL, Harvey J. Meta-analysis of second malignant tumors in head and neck cancer: the case for an endoscopic screening protocol. Ann Otol Rhinol Laryngol. 1992;101(2 Pt 1):105-12.

Zbaren P, de Bree R, Takes RP, Rinaldo A, Ferlito A. Which is the most reliable diagnostic modality for detecting locally residual or recurrent laryngeal squamous cell carcinoma after (chemo)radiotherapy? Eur Arch Otorhinolaryngol. 2013;270(11):2787-91.

Glynn F, Brennan S, O'Leary G. CT staging and surveillance of the thorax in patients with newly diagnosed and recurrent squamous cell carcinoma of the head and neck: is it necessary? Eur Arch Otorhinolaryngol. 2006;263(10):943-5.

Patrucco MS, Aramendi MV. Prognostic impact of second primary tumors in head and neck cancer. Eur Arch Otorhinolaryngol. 2016;273(7):1871-7.

Tiwana MS, Hay J, Wu J, Wong F, Cheung W, Olson RA. Incidence of second metachronous head and neck cancers: population-based outcomes over 25 years. Laryngoscope. 2014;124(10):2287-91.

Murphy CT, Galloway TJ, Handorf EA, Egleston BL, Wang LS, Mehra R, et al. Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States. J Clin Oncol. 2016;34(2):169-78.

Yom SS, Machtay M, Biel MA, Sinard RJ, El-Naggar AK, Weber RS, et al. Survival impact of planned restaging and early surgical salvage following definitive chemoradiation for locally advanced squamous cell carcinomas of the oropharynx and hypopharynx. Am J Clin Oncol. 2005;28(4):385-92.

Cao H, Banh A, Kwok S, Shi X, Wu S, Krakow T, et al. Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys. 2012;82(3):e351-8.

Colevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, et al. NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018. J Natl Compr Canc Netw. 2018;16(5):479-90.

Ebnoether E, Muller L. Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC). Int J Mol Sci. 2020;21(12).

Kristina P, Laura B, Laurent M. Exosomes as a promising diagnostic tool in head and neck squamous cell carcinoma? Journal of Cancer Metastasis and Treatment. 2020;6:39.

Szturz P, Van Laer C, Simon C, Van Gestel D, Bourhis J, Vermorken JB. Follow-Up of Head and Neck Cancer Survivors: Tipping the Balance of Intensity. Front Oncol. 2020 2020;10:688.

Francis DO, Yueh B, Weymuller EA, Merati AL. Impact of surveillance on survival after laryngeal cancer in the medicare population. Laryngoscope. 2009;119(12):2337-44.

Flynn CJ, Khaouam N, Gardner S, Higgins K, Enepekides D, Balogh J, et al. The value of periodic follow-up in the detection of recurrences after radical treatment in locally advanced head and neck cancer. Clin Oncol (R Coll Radiol). 2010;22(10):868-73.

Zätterström U, Boysen M, Evensen JF. Significance of self-reported symptoms as part of follow-up routines in patients treated for oral squamous cell carcinoma. Anticancer Res. 2014;34(11):6593-9.






Original Research Articles