Pathology & Oncology Research

, Volume 19, Issue 4, pp 795–803 | Cite as

Predictors of Locoregional Recurrence in T1-2N0 Tongue Cancer Patients

  • Souichi Yanamoto
  • Shin-ichi Yamada
  • Hidenori Takahashi
  • Goro Kawasaki
  • Hisazumi Ikeda
  • Takeshi Shiraishi
  • Shuichi Fujita
  • Tohru Ikeda
  • Izumi Asahina
  • Masahiro Umeda


Locoregional recurrence of oral tongue squamous cell carcinoma (OTSCC) has been considered a poor prognostic entity in terms of survival rate. The purpose of this study was to evaluate the incidence of locoregional recurrence and to identify significant risk factors for locoregional recurrence in early-stage OTSCC. We retrospectively reviewed the records of 58 patients who underwent radical surgery for T1-2N0 OTSCC. The local recurrence and regional recurrence rates were 10.3 % (6/58 patients) and 15.5 % (9/58 patients) in this study, respectively. The survival rate of patients with local recurrence was 66.7 %, which was significantly lower than that (96.2 %) of patients without local recurrence, whereas the survival rates of patients with or without regional recurrence were not significantly difference. Pattern of invasion (POI), neoadjuvant chemotherapy (NAC) and the status of the surgical margin were identified as factors influencing local recurrence. In particular, the status of the deep surgical margin was a high potential independent risk factor. The deep surgical margin was resected closely in many NAC-treated cases, suggesting that NAC may lead to local recurrence and a poor outcome. No efficacy of NAC was observed, suggesting that the standard treatment for early OTSCC is surgery alone.


Tongue cancer Recurrence Neoadjuvant chemotherapy Surgical margin 



Oral tongue squamous cell carcinoma


Pattern of invasion


Neoadjuvant chemotherapy


Depth of invasion


Local recurrence


Regional recurrence


Locoregional recurrence


Disease specific survival


Recurrence free survival


Harzard ratio


Confidence interval


  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global Cancer Statistics 2011. CA Cancer J Clin 61:69–90PubMedCrossRefGoogle Scholar
  2. 2.
    Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:309–316PubMedCrossRefGoogle Scholar
  3. 3.
    National Cancer Institute (2012). Surveillance, Epidemiology, and End Results (SEER) web site. Accessed 15 March 2012
  4. 4.
    Rusthoven KE, Raben D, Song JI, Kane M, Altoos TA, Chen C (2010) Survival and patterns of relapse in patients with oral tongue cancer. J Oral Maxillofac Surg 68:584–589PubMedCrossRefGoogle Scholar
  5. 5.
    Ganly I, Patel S, Shah J (2012) Early stage squamous cell cancer of the oral tongue-clinicopathologic features affecting outcome. Cancer 118:101–111PubMedCrossRefGoogle Scholar
  6. 6.
    Spiro RH, Guillamondegui O, Paulino AF, Huvos AG (1999) Pattern of invasion and margin assessment in patients with oral tongue cancer. Head Neck 21:408–413PubMedCrossRefGoogle Scholar
  7. 7.
    Goto M, Hasegawa Y, Terada A, Hyodo I, Hanai N, Ijichi K, Yamada H, Fujimoto Y, Ogawa T (2005) Prognostic significance of late cervical metastasis and distant failure in patients with stage I and II oral tongue cancers. Oral Oncol 41:62–69PubMedCrossRefGoogle Scholar
  8. 8.
    Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY (2005) Oral squamous cell carcinoma. Histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol 29:167–178PubMedCrossRefGoogle Scholar
  9. 9.
    Pentenero M, Gandolfo S, Carrozzo M (2005) Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma a review of the literature. Head Neck 27:1080–1091PubMedCrossRefGoogle Scholar
  10. 10.
    Vered M, Dayan D, Dobriyan A, Yahalom R, Shalmon B, Barshack I, Bedrin L, Talmi YP, Taicher S (2010) Oral tongue squamous cell carcinoma: recurrent disease is associated with histopathologic risk score and young age. J Cancer Res Clin Oncol 136:1039–1048PubMedCrossRefGoogle Scholar
  11. 11.
    El-Naaj IA, Leiser Y, Shveis M, Sabo E, Peled M (2011) Incidence of oral cancer occult metastasis and survival of T1-T2N0 oral cancer patients. J Oral Maxillofac Surg 69:2674–2679PubMedCrossRefGoogle Scholar
  12. 12.
    Shah JP, Gil Z (2009) Current concepts in management of oral cancer. Oral Oncol 45:394–401PubMedCrossRefGoogle Scholar
  13. 13.
    Brennan S, Corry J, Kleid S, Porceddu S, Yuen K, Rischin D, Peters LJ (2010) Prospective trial to evaluate staged neck dissection or elective neck radiotherapy in patients with ct-staged T1-2 N0 squamous cell carcinoma of the oral tongue. Head Neck 32:191–198PubMedCrossRefGoogle Scholar
  14. 14.
    Nag S, Cano ER, Demanes J, Puthawala AA, Vikram B (2001) The American brachytherapy society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma. Int J Radia Oncol Biol Phys 50:1190–1198CrossRefGoogle Scholar
  15. 15.
    Mazeron JJ, Ardiet JM, Haie-Meder C, Kovacs G, Levendag P, Peiffert D, Polo A, Rovirosa A, Strnad V (2009) GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas. Radiother Oncol 91:150–156PubMedCrossRefGoogle Scholar
  16. 16.
    Umeda M, Komatsubara H, Ojima Y, Minamikawa T, Shibuya Y, Yokoo S, Ishii J, Komori T (2005) A comparison of brachytherapy and surgery for the treatment of stage I-II squamous cell carcinoma of the tongue. Int J Oral Maxillofac Surg 34:739–744Google Scholar
  17. 17.
    Sobin LH, Wittekind C (2002) UICC TNM classification of malignant tumours, 6th edn. Wiley, New YorkGoogle Scholar
  18. 18.
    Pindborg JJ, Reichart PA, Smith CJ, van der Waal I (eds) (1997) World Health Organization histological typing of cancer and precancer of the oral mucosa, 2nd edn. Springer, New YorkGoogle Scholar
  19. 19.
    Bryne M, Boysen M, Alfsen CG, Abeler VM, Sudbø J, Nesland JM, Kristensen GB, Piffko J, Bankfalvi A (1998) The invasive front of carcinomas. The most important area for tumor prognosis? Anticancer Res 18:4757–4764PubMedGoogle Scholar
  20. 20.
    Asakage T, Yokose T, Mukai K, Tsugane S, Tsubono Y, Asai M, Ebihara S (1998) Tumor thickness predicts cervical metastasis in patients with stage I/II carcinoma of the tongue. Cancer 82:1443–1448PubMedCrossRefGoogle Scholar
  21. 21.
    Kurokawa H, Yamashita Y, Takeda S, Zhang M, Fukuyama H, Takahashi T (2002) Risk factors for late cervical lymph node metastases in patients with stage I or II carcinoma of the tongue. Head Neck 24:731–736PubMedCrossRefGoogle Scholar
  22. 22.
    Lim SC, Zhang S, Ishii G, Endoh Y, Kodama K, Miyamoto S, Hayashi R, Ebihara S, Cho JS, Ochiai A (2004) Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue. Clin Cancer Res 10:166–172PubMedCrossRefGoogle Scholar
  23. 23.
    Sparano A, Weinstein G, Chalian A, Yodul M, Weber R (2004) Multivariate predictors of occult neck metastasis in early oral tongue cancer. Otolaryngol Head Neck Surg 131:472–476PubMedCrossRefGoogle Scholar
  24. 24.
    Huang SH, Hwang D, Lockwood G, Goldstein DP, O’Sullivan B (2009) Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity. A meta-analysis of reported studies. Cancer 115:1489–1497PubMedCrossRefGoogle Scholar
  25. 25.
    Fan KH, Wang HM, Kang CJ, Lee LY, Huang SF, Lin CY, Chen EYC, Chen IH, Liao CT, Chang JTC (2010) Treatment results of postoperative radiotherapy on squamous cell carcinoma of the oral cavity: coexistence of multiple minor risk factors results in higher recurrence rates. Int J Radiation Oncology Biol Phys 77:1024–1029CrossRefGoogle Scholar
  26. 26.
    Kernohan MD, Clark JR, Gao K, Ebrahimi A, Milross CG (2010) Predicting the prognosis of oral squamous cell carcinoma after first recurrence. Arch Otolaryngol Head Neck Surg 136:1235–1239PubMedCrossRefGoogle Scholar
  27. 27.
    Huang TY, Hsu LP, Wen YH, Huang TT, Chou YF, Lee CF, Yang MC, Chang YK, Chen PR (2010) Predictors of locoregional recurrence in early stage oral cavity cancer with free surgical margins. Oral Oncol 45:49–55CrossRefGoogle Scholar
  28. 28.
    O-charoenrat PO, Pillai G, Patel S, Fisher C, Archer D, Eccles S, Rhys-Evans P (2003) Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer. Oral Oncol 39:386–390PubMedCrossRefGoogle Scholar
  29. 29.
    Al-Rajhi N, Khafaga Y, El-Husseiny J, Saleem M, Mourad W, Al-Otieschan A, Al-Amro A (2000) Early stage carcinoma of oral tongue: prognostic factors for local control and survival. Oral Oncol 36:508–514PubMedCrossRefGoogle Scholar
  30. 30.
    Yuen APW, Lam KY, Lam LK, Ho CM, Wong A, Chow TL, Yuen WF, Wei WI (2002) Prognostic factors of clinically stage I and II oral tongue carcinoma-a comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martines-Gimen score, and pathologic features. Head Neck 24:513–520PubMedCrossRefGoogle Scholar
  31. 31.
    Keski-Säntti H, Atula T, Tikka J, Hollmén J, Mäkitie AA, Leivo I (2007) Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue. Oral Oncol 43:1007–1013PubMedCrossRefGoogle Scholar
  32. 32.
    Pignon JP, Bourhis J, Domenge C, Designe L (2000) Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Lancet 355:949–955PubMedGoogle Scholar
  33. 33.
    Kirita T, Ohgi K, Kawakami M, Miyawaki S, Okamoto M, Yamanaka Y, Sugimura M (2002) Primary tumour resection of tongue carcinoma based on response to preoperative therapy. Int J Oral Maxillofac Surg 31:267–272PubMedCrossRefGoogle Scholar
  34. 34.
    Licitra L, Grandi C, Guzzo M, Mariani L, Lo Vullo S, Valvo F, Quattrone P, Valagussa P, Bonadonna G, Molinari R, Cantu G (2003) Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 21:327–333PubMedCrossRefGoogle Scholar
  35. 35.
    Olasz L, Szalma J, Orsi E, Tornoczky T, Marko T, Nyarady Z (2010) Neoadjuvant chemotherapy: does it have benefits for surgeon in the treatment of advanced squamous cell cancer of the oral cavity? Pathol Oncol Res 16:207–212PubMedCrossRefGoogle Scholar
  36. 36.
    Lore JM, Diaz-Ordaz E, Spaulding M, Chary K, Kaufman S, Lawrence W, Hong F, Gerold T, Sundquist N, Barrali RA (1995) Improved survival with preoperative chemotherapy followed by tumor response for advanced squamous cell carcinoma of the head and neck. Am J Surg 170:506–511PubMedCrossRefGoogle Scholar
  37. 37.
    Okura M, Hiranuma T, Adachi T, Ogura T, Aikawa T, Yoshioka H, Hayashido Y, Kogo M, Matsuya T (1998) Induction chemotherapy is associated with an increase in the incidence of locoregional recurrence in patients with carcinoma of the oral cavity: results from a single institution. Cancer 82:804–815PubMedCrossRefGoogle Scholar
  38. 38.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Michel B, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Eng J Med 350:1945–1952CrossRefGoogle Scholar
  39. 39.
    Kurita H, Nakanishi Y, Nishizawa R, Xiao T, Kamata T, Koike T, Kobayashi H (2010) Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol 46:814–817PubMedCrossRefGoogle Scholar
  40. 40.
    Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA (2003) The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 32:30–34PubMedCrossRefGoogle Scholar
  41. 41.
    Upile T, Fisher C, Jerjes W, El Maaytah M, Searle A, Archer D, Michaels L, Rhys-Evans P, Hopper C, Howard D, Wright A (2007) The uncertainty of the surgical margin in the treatment of head and neck cancer. Oral Oncol 43:321–326PubMedCrossRefGoogle Scholar
  42. 42.
    Umeda M, Shigeta T, Takahashi H, Minamikawa T, Komatsubara H, Oguni A, Shibuya Y, Komori T (2011) Cinical evaluation of Lugol’s iodine staining in the treatment of stage I-II squamous cell carcinoma of the tongue. Int J Oral Maxillofac Surg 40:593–596PubMedCrossRefGoogle Scholar
  43. 43.
    Kim JJ, Tannock IF (2005) Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer 5:516–525PubMedCrossRefGoogle Scholar
  44. 44.
    Bourhis J, Wilson G, Wibault P, Janot F, Bosq J, Armand JP, Luboinski B, Malaise EP, Eschwege F (1994) Rapid tumor cell proliferation after induction chemotherapy in oropharyngeal cancer. Laryngoscope 104:468–472PubMedCrossRefGoogle Scholar
  45. 45.
    Penel N, Fournier C, Lefebvre D, Roussel-Delvallez M, Sarini J, Kar A, Mallet Y, Lefebvre JL (2004) Previous chemotherapy as a predictor of wound infections in nonmajor head and neck surgery: results of a prospective study. Head Neck 26:513–517PubMedCrossRefGoogle Scholar
  46. 46.
    Penel N, Fournier C, Lefebvre D, Lefebvre JL (2005) Multivariate analysis of risk factors for wound infection in head and neck squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical procedures. Oral Oncol 41:294–303PubMedCrossRefGoogle Scholar
  47. 47.
    Rahima B, Shingaki S, Nagata M, Saito C (2004) Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:423–431PubMedCrossRefGoogle Scholar
  48. 48.
    Gonzalez-Garcia R, Naval-Gias L, Roman-Romero L, Sastre-Perez J, Rodriguez-Campo FJ (2009) Local recurrences and second primary tumors from squamous cell carcinoma of the oral cavity: a retrospective analytic study of 500 patients. Head Neck 31:1168–1180PubMedCrossRefGoogle Scholar
  49. 49.
    Ord RA, Kolokythas A, Reynolds MA (2006) Surgical salvage for local and regional recurrence in oral cancer. J Oral Maxillofac Surg 64:1409–1414PubMedCrossRefGoogle Scholar
  50. 50.
    Schwartz GJ, Mehta RH, Wenig BL, Shaligram C, Portugal LG (2000) Salvage treatment for recurrent squamous cell carcinoma of the oral cavity. Head Neck 22:34–41PubMedCrossRefGoogle Scholar
  51. 51.
    Sklenicka S, Gardiner S, Dierks EJ, Potter BE, Bell RB (2010) Survival analysis and risk factors for recurrence in oral squamous cell carcinoma: Does surgical salvage affect outcome? J Oral Maxillofac Surg 68:1270–1275PubMedCrossRefGoogle Scholar
  52. 52.
    Kaya S, Yilmaz T, Gürsel B, Saraç S, Sennaroğlu L (2001) The value of elective neck dissection in treatment of cancer of the tongue. Am J Otolaryngol 22:59–64PubMedCrossRefGoogle Scholar
  53. 53.
    Lim YC, Lee JS, Koo BS, Kim SH, Kim YH, Choi EC (2006) Treatment of contralateral N0 neck in early squamous cell carcinoma of the oral tongue: elective neck dissection versus observation. Laryngoscope 116:461–465PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2013

Authors and Affiliations

  • Souichi Yanamoto
    • 1
  • Shin-ichi Yamada
    • 1
  • Hidenori Takahashi
    • 1
  • Goro Kawasaki
    • 1
  • Hisazumi Ikeda
    • 2
  • Takeshi Shiraishi
    • 2
  • Shuichi Fujita
    • 3
  • Tohru Ikeda
    • 3
  • Izumi Asahina
    • 2
  • Masahiro Umeda
    • 1
  1. 1.Department of Clinical Oral OncologyUnit of Translational Medicine, Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of Regenerative Oral SurgeryUnit of Translational Medicine, Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  3. 3.Department of Oral Pathology and Bone MetabolismUnit of Basic Medical Sciences Nagasaki University Graduate School of Biomedical SciencesNagasakiJapan

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