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Der Onkologe

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Behandlungsstrategien beim Oropharynxkarzinom

  • Andreas DietzEmail author
Leitthema
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Abstract

Hintergrund

Das Oropharynxkarzinom (OPSCC) stellt aufgrund seiner weltweiten Inzidenzzunahme und der Assoziation mit dem humanen Papillomavirus HPV-16, aber auch chronischem Tabak‑/Alkoholkonsum eine genetisch heterogene Tumorgruppe mit hoher prognostischer Diversität dar.

Ziel

Die Übersichtsarbeit versucht, die aktuelle Sicht der Therapie und Prävention des OPSCC in Hinblick auf die Assoziation mit HPV16 darzustellen.

Material und Methoden

Die Übersicht erfolgt auf der Basis der aktuellen relevanten Literatur sowie der derzeit laufenden Studien.

Ergebnisse und Diskussion

Das OPSCC stellt sich als sehr komplexe, genetisch heterogene und daher detailliert anzusehende Gruppe von Kopf-Hals-Tumoren dar. Die derzeit widersprüchliche Studienlage, die auf dem Boden retrospektiver Daten aktuelle TNM-Klassifikation („8th Edition“) und die abzuwartenden prospektiven Daten zur Therapiedeintensivierung ermahnen aktuell eher zu einer konservativen Therapiebetrachtung. Durch die aktuellen Impfempfehlungen ist jetzt auch die HPV-Impfung für Jungen analog zu den Mädchen in Deutschland zugelassen.

Schlüsselwörter

Tabak‑/Alkoholkonsum Papillomavirus HPV-16 Therapiedeintensivierung Transorale Roboterchirurgie HPV-Impfung 

Treatment strategies for oropharyngeal carcinoma

Abstract

Background

Oropharyngeal squamous cell carcinoma (OPSCC) is a genetically heterogeneous group of tumors with high prognostic diversity due to the worldwide increase in incidence and the association with the human papillomavirus HPV-16 and also chronic tobacco and alcohol consumption.

Objective

The review presents the current view on treatment and prevention of OPSCC with respect to the association with HPV16.

Material and methods

This overview is based on the relevant available literature as well as currently running studies.

Results and discussion

The OPSCC is manifested as a very complex, genetically heterogeneous group of head and neck tumors, which should therefore be considered in detail. The currently contradictory study situation, the current TNM classification (8th edition) on the basis of retrospective data and the expected prospective patient data on the deintensification of treatment are currently more likely to encourage conservative treatment. Due to the current recommendations, the HPV vaccination for boys is now also approved in Germany analogously to girls.

Keywords

Tobacco and alcohol consumption Papillomavirus HPV16 Treatment intensification Transoral robotic surgery HPV vaccination 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

A. Dietz gibt folgende Interessenkonflikte an: Honorar für wissenschaftliche Vorträge und beratende Gremien: Merck Serono, Roche, Astra Zeneca, MSD, BMS, Sanofi; Forschungsförderung: Roche, Merck Serono, MSD.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

Verwendete Literatur

  1. 1.
    Dietz A, Pirlich M, Wiegand S (2018) Current Status of therapy and prophylaxis of oropharyngeal carcinoma. Laryngorhinootologie 97(2):123–137CrossRefGoogle Scholar
  2. 2.
    Becker N, Wahrendorf J (1998) Krebsatlas der Bundesrepublik Deutschland 1981–1990. Springer, Berlin, Heidelberg, New York (Fortschreibung im Internet: www.krebsatlas.de)Google Scholar
  3. 3.
    Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX (1998) Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res 58(1):5–13PubMedGoogle Scholar
  4. 4.
    Wichmann G (2017) Variation of HPV subtypes with focus on HPV-infection and cancer in the head and neck region. Recent Results Cancer Res 206:113–122CrossRefGoogle Scholar
  5. 5.
    Wagner S, Würdemann N, Hübbers C, Reuschenbach M, Prigge ES, Wichmann G, Hess J, Dietz A, Dürst M, Tinhofer I, von Knebel-Döberitz M, Wittekindt C, Klussmann JP (2015) HPV-associated head and neck cancer : mutational signature and genomic aberrations. HNO 63(11):758–767CrossRefGoogle Scholar
  6. 6.
    Wichmann G, Rosolowski M, Krohn K, Kreuz M, Boehm A, Reiche A, Scharrer U, Halama D, Bertolini J, Bauer U, Holzinger D, Pawlita M, Hess J, Engel C, Hasenclever D, Scholz M, Ahnert P, Kirsten H, Hemprich A, Wittekind C, Herbarth O, Horn F, Dietz A, Loeffler M, Leipzig Head and Neck Group (LHNG) (2015) The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer. Int J Cancer 137(12):2846–2857CrossRefGoogle Scholar
  7. 7.
    8th Edition of the UICC TNM Classification of Malignant Tumours, 1 January 2017.Google Scholar
  8. 8.
    Boscolo-Rizzo P, Dietz A (2017) The AJCC/UICC eighth edition for staging head and neck cancers: Is it wise to de-escalate treatment regimens in p16-positive oropharyngeal cancer patients? Int J Cancer 141(7):1490–1491CrossRefGoogle Scholar
  9. 9.
    Golusinski W, Leemans R, Dietz A (2017) HPV infection on head and neck cancer. Springer, Berlin Heidelberg. ISBN 978-3319435800CrossRefGoogle Scholar
  10. 10.
    Robinson M, Schache A, Sloan P, Thavaraj S (2012) HPV specific testing: a requirement for oropharyngeal squamous cell carcinoma patients. Head Neck Pathol 6:83–90CrossRefGoogle Scholar
  11. 11.
    Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ, Pawlita M, Meijer CJ, Braakhuis BJ, Leemans CR, Brakenhoff RH (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472CrossRefGoogle Scholar
  12. 12.
    Lewis JS Jr. (2012) p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol 6:75–82CrossRefGoogle Scholar
  13. 13.
    Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, Solomon B, Choi J, O’Sullivan B, Kenny LM, McArthur GA (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 28:4142–4148CrossRefGoogle Scholar
  14. 14.
    Wasylyk B, Abecassis J, Jung AC (2013) Identification of clinically relevant HPV-related HNSCC: in p16 should we trust? Oral Oncol 49:e33–e37CrossRefGoogle Scholar
  15. 15.
    Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, D’Souza G, Gravitt PE, Westra W, Psyrri A, Kast WM, Koutsky LA, Giuliano A, Krosnick S, Trotti A, Schuller DE, Forastiere A, Ullmann CD (2009) Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head Neck 31:1393–1422CrossRefGoogle Scholar
  16. 16.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35CrossRefGoogle Scholar
  17. 17.
    Brotherston IP, Le T, Leung M, Kiss A, Ringash J, Balogh J, Lee J, Wright JR (2013) Patient preferences for oropharyngeal cancer treatment de-escalation. Head Neck 35(2):151–159CrossRefGoogle Scholar
  18. 18.
    Mehanna H, Kong A, Hartley A, Mistry P, Dalby M, Fulton-Lieuw T, Robinson M, Gray A, Foran B, Sen M, O’Toole L, Dyker K, Al Booz H, Moleron R, Brennan S, Aynsley E, Chan A, Srinivasan D, Buter J, Dunn J (2018) Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy. Ann Oncol 29(suppl_8).  https://doi.org/10.1093/annonc/mdy424.046 CrossRefGoogle Scholar
  19. 19.
    National Institutes of Health (2018) Cetuximab with radiation found to be inferior to standard treatment in HPV-positive oropharyngeal cancerGoogle Scholar
  20. 20.
    Haughey BH, Haughey BH, Hinni ML, Salassa JR, Hayden RE, Grant DG, Rich JT, Milov S, Lewis JS Jr, Krishna M (2011) Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: a United States multicenter study. Head Neck 33(12):1683–1694CrossRefGoogle Scholar
  21. 21.
    Sinha P, Lewis JS Jr, Piccirillo JF, Kallogjeri D, Haughey BH (2012) Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma. Cancer 118(14):3519–3530CrossRefGoogle Scholar
  22. 22.
    Mattheis S, Hasskamp P, Holtmann L, Schäfer C, Geisthoff U, Dominas N, Lang S (2017) Flex robotic system in transoral robotic surgery: the first 40 patients. Head Neck 39(3):471–475CrossRefGoogle Scholar
  23. 23.
    Kwok P, Gleich O, Hübner G, Strutz J (2010) Prognostic importance of „clear versus revised margins“ in oral and pharyngeal cancer. Head Neck 32(11):1479–1484CrossRefGoogle Scholar
  24. 24.
    Wittekind C, Compton CC, Greene FL, Sobin LH (2002) TNM residual tumor classification revisited. Cancer 94:2511–2516CrossRefGoogle Scholar
  25. 25.
    Meier JD, Oliver DA, Varvares MA (2005) Surgical margin determination in head and neck oncology: current clinical practice. The results of an international american head and neck society member survey. Head Neck 27:952–958CrossRefGoogle Scholar
  26. 26.
    Slootweg PJ, Hordijk GJ, Schade Y, van Es RJJ, Koole R (2002) Treatment failure and margin status in head and neck cancer. A critical view on the potential value of molecular pathology. Oral Oncol 38:500–503CrossRefGoogle Scholar
  27. 27.
    Wittekind C (2006) Residualtumorklassifikation in der Onkologie. Anwendungen und Probleme. Onkologe 12:803–814CrossRefGoogle Scholar
  28. 28.
    Wittekind C, Meyer HJ (2010) TNM-Klassifikation maligner Tumoren, 7. Aufl. Wiley-Blackwell, WeinheimGoogle Scholar
  29. 29.
    Dietz A, Fischer M, Magill C, Haughey BH (2016) In: Bernier J (Hrsg) Head and neck cancer. Springer, Berlin, Heidelberg  https://doi.org/10.1007/978-3-319-27601-4_32 CrossRefGoogle Scholar
  30. 30.
    Laccourreye O, Malinvaud D, Garcia D, Ménard M, Hans S, Cauchois R, Bonfils P (2015) Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. Ann Otol Rhinol Laryngol 124(5):361–367CrossRefGoogle Scholar
  31. 31.
    Salassa JR, Hinni ML, Grant DG, Hayden RE (2008) Postoperative bleeding in transoral laser microsurgery for upper aerodigestive tract tumors. Otolaryngol Head Neck Surg 139(3):453–459CrossRefGoogle Scholar
  32. 32.
    Pollei TR, Hinni ML, Moore EJ, Hayden RE, Olsen KD, Casler JD, Walter LC (2013) Analysis of postoperative bleeding and risk factors in transoral surgery of the oropharynx. Jama Otolaryngol Head Neck Surg 139(11):1212–1218CrossRefGoogle Scholar
  33. 33.
    Robbins KT, Shaha AR, Medina JE et al (2008) Consensus statement on the classification and terminology of neck dissection. Arch Otolaryngol Head Neck Surg 134:536–538CrossRefGoogle Scholar
  34. 34.
    Mehanna H, Wong WL, McConkey CC, Rahman JK, Robinson M, Hartley AG, Nutting C, Powell N, Al-Booz H, Robinson M, Junor E, Rizwanullah M, von Zeidler SV, Wieshmann H, Hulme C, Smith AF, Hall P, Dunn J, PET-NECK Trial Management Group (2016) PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med 374(15):1444–1454CrossRefGoogle Scholar
  35. 35.
    Licitra L, Grandi C, Guzzo M, Mariani L, Lo Vullo S, Valvo F, Quattrone P, Valagussa P, Bonadonna G, Molinari R, Cantù G (2003) Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 21(2):327–333CrossRefGoogle Scholar
  36. 36.
    Inhestern J, Schmalenberg H, Dietz A, Rotter N, Maschmeyer G, Jungehülsing M, Grosse-Thie C, Kuhnt T, Görner M, Sudhoff H, Wittekindt C, Guntinas-Lichius O (2017) A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5‑fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol 28(8):1917–1922CrossRefGoogle Scholar
  37. 37.
    Wichmann G, Krüger A, Boehm A, Kolb M, Hofer M, Fischer M, Müller S, Purz S, Stumpp P, Sabri O, Dietz A, Kluge R (2017) Induction chemotherapy followed by radiotherapy for larynx preservation in advanced laryngeal and hypopharyngeal cancer: Outcome prediction after one cycle induction chemotherapy by a score based on clinical evaluation, computed tomography-based volumetry and 18F-FDG-PET/CT. Eur J Cancer 72:144–155CrossRefGoogle Scholar
  38. 38.
    Seiwert TY, Clement PM, Cupissol D, Del Campo J, de Mont-Serrat H, Thurm HC, Blackman AS, Cohen EE (2010) BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study. J Clin Oncol 28:15s (suppl; abstr 5501)CrossRefGoogle Scholar
  39. 39.
    Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK (2004) Postoperative concurrent radiotherapy and chemotherapy for high risk squamous-cell carcinoma of the head and neck. N Engl J Med 350(19):1937–1944CrossRefGoogle Scholar
  40. 40.
    Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK (2012) Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84(5):1198–1205CrossRefGoogle Scholar
  41. 41.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabecke M (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350(19):1945–1952CrossRefGoogle Scholar
  42. 42.
    Fietkau R, Lautenschläger C, Sauer R, Dunst J, Becker A, Baumann M, Wendt T, Grüschow K, Hess C, Budach V, Iro H (2006) Postoperative concurrent radiochemotherapy versus radiotherapy in high risk SCCA of head and neck: results of the German phase III trial ARO 96-3. J Clin Oncol 24(18_suppl):5507 (ASCO Annual Meeting Proceedings Part I)Google Scholar
  43. 43.
    Pignon JP, Le Maitre A, Maillard E, Bourhis J (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NH): an update on 93 randomised trials and 17346 patients. Radiother Oncol 92:4–14CrossRefGoogle Scholar
  44. 44.
    Budach W, Hehr T, Budach V, Belka C, Dietz K (2006) A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer 6:28CrossRefGoogle Scholar
  45. 45.
    Nichols AC, Kneuertz PJ, Deschler DG, Lin DT, Emerick KS, Clark JR, Busse PW, Rocco JW (2011) Surgical salvage of the oropharynx after failure of organ-sparing therapy. Head Neck 33(4):516–524.  https://doi.org/10.1002/hed.21480 CrossRefPubMedGoogle Scholar
  46. 46.
    Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, Soulieres D, Trotti A, Avizonis V, Ridge JA, Harris J, Le QT, Gillison M (2014) Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol 32(30):3365–3373CrossRefGoogle Scholar
  47. 47.
    Goodwin WJ Jr. (2000) Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? Laryngoscope 110(3 Pt 2 Suppl 93):1–18CrossRefGoogle Scholar
  48. 48.
    Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359(11):1116–1127CrossRefGoogle Scholar
  49. 49.
    Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867CrossRefGoogle Scholar
  50. 50.
    Soulières D, Cohen EEW, Le Tourneau C, Didis J, Licitra L, Ahn M, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby R, Harrington KJ (2018) Updated survival results of the KEYNOTE-040 study of pembrolizumab vs standard-of-care chemotherapy for recurrent or metastatic head and neck squamous carcinoma. Abstract AACR 2018CrossRefGoogle Scholar
  51. 51.
    Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, De Castro G Jr, Psyrri A, Baste Rotllan N, Neupane PC, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Roy A, Cheng J, Jin F, Rischin D (2018) KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) LBA8_PR. Ann Oncol 29:8CrossRefGoogle Scholar
  52. 52.
    SIKO (2017) Empfehlungen der Sächsischen Impfkommission zur Durchführung von Schutzimpfungen im Freistaat Sachsen (Stand Januar 2017. Impfempfehlungen E1: 1–30.)Google Scholar
  53. 53.
    Hartwig S, Syrjänen S, Dominiak-Felden G, Brotons M, Castellsagué X (2012) Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review. BMC Cancer 12:30CrossRefGoogle Scholar
  54. 54.
    D’Souza G, Cullen K, Bowie J, Thorpe R, Fakhry C (2014) Differences in oral sexual behaviors by gender, age, and race explain observed differences in prevalence of oral human papillomavirus infection. PLoS ONE 9(1):e86023CrossRefGoogle Scholar
  55. 55.
    D’Souza G, Gross ND, Pai SI, Haddad R, Anderson KS, Rajan S, Gerber J, Gillison ML, Posner MR (2014) Oral human papillomavirus (HPV) infection in HPV-positive patients with oropharyngeal cancer and their partners. J Clin Oncol 32(23):2408–2415CrossRefGoogle Scholar
  56. 56.
    Kreimer AR, Johansson M, Waterboer T, Kaaks R, Chang-Claude J, Drogen D, Tjønneland A, Overvad K, Quirós JR, González CA, Sánchez MJ, Larrañaga N, Navarro C, Barricarte A, Travis RC, Khaw KT, Wareham N, Trichopoulou A, Lagiou P, Trichopoulos D, Peeters PH, Panico S, Masala G, Grioni S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Laurell G, Hallmans G, Manjer J, Ekström J, Skeie G, Lund E, Weiderpass E, Ferrari P, Byrnes G, Romieu I, Riboli E, Hildesheim A, Boeing H, Pawlita M, Brennan P (2013) Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. Clin Oncol 31(21):2708–2715CrossRefGoogle Scholar
  57. 57.
    Holzinger D, Wichmann G, Baboci L, Michel A, Höfler D, Wiesenfarth M, Schroeder L, Boscolo-Rizzo P, Herold-Mende C, Dyckhoff G, Boehm A, Del Mistro A, Bosch FX, Dietz A, Pawlita M, Waterboer T (2017) Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma. Int J Cancer 140(12):2748–2757CrossRefGoogle Scholar

Weiterführende Literatur

  1. 58.
    O’Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B, Weinreb I, Kim J, Ringash J, Bayley A, Dawson LA, Hope A, Cho J, Irish J, Gilbert R, Gullane P, Hui A, Liu FF, Chen E, Xu W (2013) Deintensification candidate subgroups in human papillomavirus–related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol 31(5):543–550CrossRefGoogle Scholar
  2. 59.
    Weinstein GS, O’Malley BW Jr, Magnuson JS, Carroll WR, Olsen KD, Daio L, Moore EJ, Holsinger FC (2012) Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins. Laryngoscope 122(8):1701–1707CrossRefGoogle Scholar
  3. 60.
    Crespo AN, Chone CT, Gripp FM, Spina AL, Altemani A (2006) Role of margin status in recurrence after CO2 laser endoscopic resection of early glottic cancer. Acta Otolaryngol 126:306–310CrossRefGoogle Scholar
  4. 61.
    Domenge C, Hill C, Lefebvre JL, De Raucourt D, Rhein B, Wibault P, Marandas P, Coche-Dequeant B, Stromboni-Luboinski M, Sancho-Garnier H, Luboinski B, French Groupe d’Etude des Tumeurs de la Tête et du Cou (GETTEC) (2000) Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. Br J Cancer 83(12):1594–1598CrossRefGoogle Scholar
  5. 62.
    Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr, Sun J, Zhu HG, Tu WY, Li J, Cai YL, Wang LZ, Fan XD, Wang ZH, Hu YJ, Ji T, Yang WJ, Ye WM, Li J, He Y, Wang YA, Xu LQ, Wang BS, Kies MS, Lee JJ, Myers JN, Zhang ZY (2013) Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol 31(6):744–751CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.HNO-Universitätsklinik LeipzigLeipzigDeutschland

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