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pN status predicts outcomes in surgically treated pT1–pT2 patients of various disease stages with squamous cell carcinoma of the head and neck: a 17-year retrospective single center cohort study

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Abstract

Objectives

The optimal treatment for a substantial proportion of patients with pT1–pT2 squamous cell carcinomas of the head and neck (SCCHN) remains to be refined. The extent of surgery, role and potential benefit of adjuvant treatment are to be balanced against therapy-induced side effects. We compared the outcomes of surgery with or without adjuvant radiotherapy (RT) or chemotherapy (CRT) and investigated the prognostic value of established clinicopathological parameters.

Methods

Data were retrospectively collected for 227 patients who were treated by surgery alone (n = 31), RT (n = 87) and CRT (n = 109) in a single center.

Results

Patients with stage I/II disease who had received adjuvant RT showed a better disease-free survival (DFS) (P = 0.04) than those who had received adjuvant CRT treatment. Conversely, patients with stage III/IV disease who had received CRT showed a better overall survival (OS) (P = 0.003) and DFS (P = 0.03) than those who had received surgery alone or adjuvant RT without chemotherapy. Survival analysis demonstrated that patients with pN0 to pN1 had better OS (P = 0.02), disease-specific survival (DSS) (P = 0.003), DFS (P = 0.02) and metastases free survival (MFS) (P = 0.002) compared to patients with pN2 to pN3. Multivariate analysis showed that the pN status was an independent factor for OS (P = 0.03), DSS (P = 0.04), relapse-free survival (P = 0.03), DFS (P = 0.03).

Conclusion

The pN status is the most important prognostic factor for pT1 to pT2 SCCHN. Adjuvant CRT was associated with significantly better survival outcomes in patients with pN1 and pN2-3 or more advanced stage, while adjuvant RT showed significantly better outcomes in patients with pN0.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29. https://doi.org/10.3322/caac.21208

    Article  PubMed  Google Scholar 

  2. Gregoire V, Lefebvre JL, Licitra L, Felip E, Group E-E-EGW (2010) Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v184–186. https://doi.org/10.1093/annonc/mdq185

    Article  PubMed  Google Scholar 

  3. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer J Int Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210

    Article  CAS  Google Scholar 

  4. 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 Glabbeke M (2004) European organization for R, treatment of cancer. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N. Engl J Med 350(19):1945–1952. https://doi.org/10.1056/NEJMoa032641

    Article  CAS  PubMed  Google Scholar 

  5. Tschudi D, Stoeckli S, Schmid S (2003) Quality of life after different treatment modalities for carcinoma of the oropharynx. Laryngoscope 113(11):1949–1954

    Article  PubMed  Google Scholar 

  6. Roosli C, Tschudi DC, Studer G, Braun J, Stoeckli SJ (2009) Outcome of patients after treatment for a squamous cell carcinoma of the oropharynx. Laryngoscope 119(3):534–540. https://doi.org/10.1002/lary.20033

    Article  PubMed  Google Scholar 

  7. Kass JI, Giraldez L, Gooding W, Choby G, Kim S, Miles B, Teng M, Sikora AG, Johnson JT, Myers EN, Duvvuri U, Genden EM, Ferris RL (2016) Oncologic outcomes of surgically treated early-stage oropharyngeal squamous cell carcinoma. Head Neck 38(10):1467–1471. https://doi.org/10.1002/hed.24456

    Article  PubMed  PubMed Central  Google Scholar 

  8. Roman BR, Baxi SS, Cracchiolo JR, Blackwell TJ, Pfister DG, McBride S, Ganly I, Shah JP, Patel SG, Morris LG, Cohen MA (2017) Variation in use of postoperative chemoradiation following surgery for T1 and T2 oropharyngeal squamous cell carcinoma; National Cancer Database. J Surg Oncol 116(3):351–358. https://doi.org/10.1002/jso.24674

    Article  PubMed  PubMed Central  Google Scholar 

  9. Galati LT, Myers EN, Johnson JT (2000) Primary surgery as treatment for early squamous cell carcinoma of the tonsil. Head Neck 22(3):294–296

    Article  CAS  PubMed  Google Scholar 

  10. 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, Radiation Therapy Oncology Group I (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350(19):1937–1944. https://doi.org/10.1056/NEJMoa032646

    Article  PubMed  Google Scholar 

  11. Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92(1):4–14. https://doi.org/10.1016/j.radonc.2009.04.014

    Article  PubMed  Google Scholar 

  12. 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):1198–1205. https://doi.org/10.1016/j.ijrobp.2012.05.008

    Article  PubMed  PubMed Central  Google Scholar 

  13. Harrington K, Temam S, Mehanna H, D’Cruz A, Jain M, D’Onofrio I, Manikhas G, Horvath Z, Sun Y, Dietzsch S, Dubinsky P, Holeckova P, El-Hariry I, Franklin N, Biswas-Baldwin N, Legenne P, Wissel P, Netherway T, Farrell J, Ellis C, Wang-Silvanto J, Amonkar M, Ahmed N, Santillana S, Bourhis J (2015) postoperative adjuvant lapatinib and concurrent chemoradiotherapy followed by maintenance lapatinib monotherapy in high-risk patients with resected squamous cell carcinoma of the head and neck: a phase III, randomized, double-blind, Placebo-Controlled Study. J Clin Oncol 33(35):4202–4209. https://doi.org/10.1200/JCO.2015.61.4370

    Article  CAS  PubMed  Google Scholar 

  14. Qian X, Coordes A, Kaufmann AM, Albers AE (2016) Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time. Oncol Lett 12(5):3429–3434. https://doi.org/10.3892/ol.2016.5100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1993) Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer 71(2):452–456

    Article  CAS  PubMed  Google Scholar 

  16. Sagheb K, Blatt S, Rahimi-Nedjat RK, Eigenbrodt S, Al-Nawas B, Walter C (2017) Cervical metastases behavior of T1-2 squamous cell cancer of the oral mucosa. Clin Oral Investig 21(3):931–935. https://doi.org/10.1007/s00784-016-1845-9

    Article  PubMed  Google Scholar 

  17. Jang JY, Kim MJ, Ryu G, Choi N, Ko YH, Jeong HS (2016) Prediction of lymph node metastasis by tumor dimension versus tumor biological properties in head and neck squamous cell carcinomas. Cancer Res Treat 48(1):54–62. https://doi.org/10.4143/crt.2014.332

    Article  CAS  PubMed  Google Scholar 

  18. Mair M, Nair D, Nair S, Malik A, Mishra A, Kannan S, Bobdey S, Singhvi H, Chaturvedi P (2018) Comparison of tumor volume, thickness, and T classification as predictors of outcomes in surgically treated squamous cell carcinoma of the oral tongue. Head Neck. https://doi.org/10.1002/hed.25161

    Article  PubMed  Google Scholar 

  19. Lydiatt WM, Patel SG, O’Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP (2017) Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67(2):122–137. https://doi.org/10.3322/caac.21389

    Article  PubMed  Google Scholar 

  20. Hurtuk AM, Marcinow A, Agrawal A, Old M, Teknos TN, Ozer E (2012) Quality-of-life outcomes in transoral robotic surgery. Otolaryngol Head Neck Surg 146(1):68–73. https://doi.org/10.1177/0194599811421298

    Article  PubMed  Google Scholar 

  21. Ling DC, Chapman BV, Kim J, Choby GW, Kabolizadeh P, Clump DA, Ferris RL, Kim S, Beriwal S, Heron DE, Duvvuri U (2016) Oncologic outcomes and patient-reported quality of life in patients with oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation. Oral Oncol 61:41–46. https://doi.org/10.1016/j.oraloncology.2016.08.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gildener-Leapman N, Kim J, Abberbock S, Choby GW, Mandal R, Duvvuri U, Ferris RL, Kim S (2016) Utility of up-front transoral robotic surgery in tailoring adjuvant therapy. Head Neck 38(8):1201–1207. https://doi.org/10.1002/hed.24390

    Article  PubMed  PubMed Central  Google Scholar 

  23. Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25(16):2171–2177. https://doi.org/10.1200/JCO.2006.06.7447

    Article  CAS  PubMed  Google Scholar 

  24. Albers AE, Grabow R, Qian X, Jumah MD, Hofmann VM, Krannich A, Pecher G (2017) Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck. Mol Clin Oncol 7(1):151–157. https://doi.org/10.3892/mco.2017.1281

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kemmer JD, Johnson DE, Grandis JR (2018) Leveraging genomics for head and neck cancer treatment. J Dent Res 97(6):603–613. https://doi.org/10.1177/0022034518756352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rodrigues M, Xavier FCA, Andrade NP, Lopes C, Miguita Luiz L, Sedassari BT, Ibarra AMC, Lopez RVM, Kliemann Schmerling C, Moyses RA, da Tajara Silva EE, Nunes FD (2018) Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma. Head Neck. https://doi.org/10.1002/hed.25158

    Article  PubMed  Google Scholar 

  27. Balermpas P, Rodel F, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Sak A, Stuschke M, Gkika E, Grosu AL, Abdollahi A, Debus J, Stangl S, Ganswindt U, Belka C, Pigorsch S, Multhoff G, Combs SE, Welz S, Zips D, Lim SY, Rodel C, Fokas E, Dktk ROG (2017) The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: a multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Int J Cancer J Int Cancer 141(3):594–603. https://doi.org/10.1002/ijc.30770

    Article  CAS  Google Scholar 

  28. Schmidt S, Linge A, Zwanenburg A, Leger S, Lohaus F, Krenn C, Appold S, Gudziol V, Nowak A, von Neubeck C, Tinhofer I, Budach V, Sak A, Stuschke M, Balermpas P, Rodel C, Bunea H, Grosu AL, Abdollahi A, Debus J, Ganswindt U, Belka C, Pigorsch S, Combs SE, Monnich D, Zips D, Baretton GB, Buchholz F, Baumann M, Krause M, Lock S, Dktk ROG (2018) Development and validation of a gene signature for patients with head and neck carcinomas treated by postoperative radio(chemo)therapy. Clin Cancer Res 24(6):1364–1374. https://doi.org/10.1158/1078-0432.CCR-17-2345

    Article  CAS  PubMed  Google Scholar 

  29. Suarez C, Rodrigo JP, Robbins KT, Paleri V, Silver CE, Rinaldo A, Medina JE, Hamoir M, Sanabria A, Mondin V, Takes RP, Ferlito A (2013) Superselective neck dissection: rationale, indications, and results. Eur Arch Oto-Rhino-Laryngol 270 (11):2815–2821. https://doi.org/10.1007/s00405-012-2344-5

    Article  Google Scholar 

  30. Coskun HH, Medina JE, Robbins KT, Silver CE, Strojan P, Teymoortash A, Pellitteri PK, Rodrigo JP, Stoeckli SJ, Shaha AR, Suarez C, Hartl DM, de Bree R, Takes RP, Hamoir M, Pitman KT, Rinaldo A, Ferlito A (2015) Current philosophy in the surgical management of neck metastases for head and neck squamous cell carcinoma. Head neck 37(6):915–926. https://doi.org/10.1002/hed.23689

    Article  PubMed  Google Scholar 

  31. Bottcher A, Dommerich S, Sander S, Olze H, Stromberger C, Coordes A, Jowett N, Knopke S (2016) Nodal yield of neck dissections and influence on outcome in laryngectomized patients. Eur Arch Oto-Rhino-Laryngol 273 (10):3321–3329. https://doi.org/10.1007/s00405-016-3928-2

    Article  Google Scholar 

  32. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan 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):24–35. https://doi.org/10.1056/NEJMoa0912217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ward MJ, Mellows T, Harris S, Webb A, Patel NN, Cox HJ, Piper K, Ottensmeier CH, Thomas GJ, King EV (2015) Staging and treatment of oropharyngeal cancer in the human papillomavirus era. Head Neck 37(7):1002–1013. https://doi.org/10.1002/hed.23697

    Article  PubMed  Google Scholar 

  34. Liederbach E, Kyrillos A, Wang CH, Liu JC, Sturgis EM, Bhayani MK (2017) The national landscape of human papillomavirus-associated oropharynx squamous cell carcinoma. Int J Cancer J Int Cancer 140(3):504–512. https://doi.org/10.1002/ijc.30442

    Article  CAS  Google Scholar 

  35. Albers AE, Qian X, Kaufmann AM, Coordes A (2017) Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype. Sci Rep 7(1):16715. https://doi.org/10.1038/s41598-017-16918-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Coordes A, Lenz K, Qian X, Lenarz M, Kaufmann AM, Albers AE (2016) Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status. Eur Arch Oto-rhino-Laryngol 273 (8):2157–2169. https://doi.org/10.1007/s00405-015-3728-0

    Article  Google Scholar 

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Author notes

  1. Xu Qian and Branko Sinikovic contributed equally.

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, 12200, Berlin, Germany

    Xu Qian & Andreas E. Albers

  2. Department of Craniomaxillofacial, Oral and Plastic Surgery, Klinikum Ernst von Bergmann, Potsdam, Germany

    Branko Sinikovic

  3. KU64, Practice for Dental Care, Implantology and Prophylaxis, 10707, Berlin, Germany

    Frank Schreiber

  4. Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, 12200, Berlin, Germany

    Sebastian Ochsenreither

  5. Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, 12200, Berlin, Germany

    Konrad Klinghammer

  6. Department of Otorhinolaryngology, Head and Neck Surgery, University of Schleswig Holstein, Campus Lübeck, 23538, Lübeck, Germany

    Barbara Wollenberg

  7. Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, 12200, Berlin, Germany

    Andreas M. Kaufmann

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  1. Xu Qian
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Correspondence to Andreas E. Albers.

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Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval for this study was obtained from the Institutional Review Board of the Charité-Universitätsmedizin Berlin, Germany (EA4/035/08).

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Qian, X., Sinikovic, B., Schreiber, F. et al. pN status predicts outcomes in surgically treated pT1–pT2 patients of various disease stages with squamous cell carcinoma of the head and neck: a 17-year retrospective single center cohort study. Eur Arch Otorhinolaryngol 275, 2787–2795 (2018). https://doi.org/10.1007/s00405-018-5108-z

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