- Open Access
The Hannover experience: Surgical treatment of tongue cancer - A clinical retrospective evaluation over a 30 years period
- Horst Kokemueller†1,
- Majeed Rana†1Email author,
- Jennifer Rublack1,
- Andre Eckardt1,
- Frank Tavassol1,
- Paul Schumann1,
- Daniel Lindhorst1,
- Martin Ruecker1 and
- Nils-Claudius Gellrich1
© Kokemueller et al; licensee BioMed Central Ltd. 2011
- Received: 11 April 2011
- Accepted: 21 May 2011
- Published: 21 May 2011
In this retrospective study, we present a clinical review of our experience with tongue cancer in order to obtain valid criteria for therapeutic decision-making.
Materials and methods
Between 1980 and 2009, a total of 341 patients with squamous cell carcinoma of the tongue were treated at our Department. The average follow-up was 5.2 years. 309 patients received surgical treatment, which was combined in nearly 10% with neoadjuvant and in nearly 20% with postoperative radio(chemo)therapy. 32 patients were excluded from surgery and received primary radiation.
Local and regional failure occurred in 23.9% and 20.4%, leading to a total failure rate of 37.2% after an average duration of 1,6 years. N-Status, extracapsular spread and clear margins were identified as the dominant factors for survival, which was calculated with 54.5% after 5 years.
We recommend categorical bilateral neck dissection in order to reliably remove occult lymph node metastases. Adjuvant treatment modalities should be applied more frequently in controlled clinical trials and should generally be implemented in cases with unclear margins and lymphatic spread.
This study provides new treatment strategies for primary tumour disease and for tumour recurrence.
- tongue cancer
- squamous cell carcinoma
- prognostic factors
Tongue cancer is the most common malignancy diagnosed within the oral cavity, which accounts between 25 and 40% of oral squamous cell carcinomas . Despite the development of multimodal treatment options, the prognosis remains relatively poor. Manifest and occult lymph node metastasis are observed more often than in any other cancer of the oral cavity . The tongue seems to be predisposed for malignant invasion due to its highly muscularized structure and its rich lymphatic network . Extensive resection with implementation of elective neck dissection especially in early stages of tongue cancer has therefore been a source of debate in recent years [4–6].
Only a limited number of studies have examined larger series of tongue cancer. Spiro and Strong evaluated 314 patients (1957-1963) with tongue cancer and found an overall 5-year survival rate of only 42% . In a later study from the same institution with 412 patients (1969-1978), Callery et al. noted an increased proportion of female patients and an increased involvement of the base of tongue compared to the earlier decade . More patients received primary and adjuvant radiotherapy, and elective neck dissection was performed more frequently. Age, sex, and adjuvant therapy did not affect survival, which remained stable compared to the earlier decade. However, lower stages of tongue cancer had a better prognosis when the tumour was located in the mobile tongue instead of the base of the tongue. In a further study from the same institution with 297 patients (1978-1987), Franceschi et al. demonstrated an improved overall 5-year survival rate of 65%, although the distribution of tumour stages was about the same compared to the preceding 10-year period . Better survival was related to a more aggressive treatment of the neck even in early tumour stages and to adjuvant radiotherapy in advanced tumour stages. A considerable number of patients had to be upstaged after elective neck dissection due to occult lymph node metastases. The number of lymph node metastases turned out to be of prognostic value.
Since surgical treatment of tongue cancer strongly affects quality of life, many attempts have been made during the last decades towards organ preservation, leading to different treatment strategies with various combinations of surgery, radiation and chemotherapy . Pernot et al. reviewed the medical records of 448 patients with tongue cancer who exclusively received radiation based therapy either as a combination of brachytherapy and external beam radiation or as a combination of brachytherapy and neck dissection . The size of the lesion turned out to be the most important factor for prognosis with an overall 5-year survival rate of 44%.
The purpose of the present study was to give a precise description of our experience with surgical based therapy of tongue cancer during the last three decades. Furthermore, prognostic factors for survival were analyzed in order to obtain valid criteria for therapeutic decision-making in clinical routine.
Between January 1980 and December 2009, a total of 341 patients with squamous cell carcinoma of the tongue were treated at the Department of Oral and Maxillofacial Surgery, Hannover Medical School. Data concerning patient characteristics, clinical and pathologic tumour characteristics and treatment strategies and their results were obtained from a retrospective review of medical records. Informations regarding patient survival and local, regional and distant control were available for all patients. The average follow-up was 5.2 years. Statistical analysis for survival was calculated by the method of Kaplan and Meier. The relationship between the clinicopathologic variables and survival was assessed in univariate analysis using the log rank test. For multivariate analysis, the Cox proportional hazard model was used. A value of p ≤ 0.05 was considered to be statistically significant.
Histopathological and clinical staging results (pT-/cT-status) of patients with surgical treatment and patients with radiotherapy
(n = 309)
treatment (n = 32)
Histopathological and clinical staging results (pN-/cN-status) of patients with surgical treatment and patients with radiotherapy
(n = 309)
(n = 32)
9.7% of the operated patients received neoadjuvant radiochemotherapy (30Gy/Cisplatin) prior to surgery, which was performed via a transoral (55.7%) or transmandibular approach (32.6%) or in pull-through technique (10.4%). 4 patients (1.3%) only received bilateral neck dissection, while the tumour at the primary site was radiated without surgery. Clear margins were achieved in 91.3% of the operated patients. On the ipsilateral neck, 44% of the operated patients received a comprehensive neck dissection, while 38.2% only received lymphadenectomy of level I-III and 17.8% no surgical therapy. On the contralateral neck, only 1.3% of these patients received a comprehensive neck dissection, while 36.6% still received lymphadenectomy of level I-III and the majority of 62.1% no surgical therapy. 19.5% of patients in the surgical group received postoperative radiation due to unclear margins, extensive tumour growth at the primary site, massive lymph node involvement or extracapsular spread, reflecting the scope of changing indications for radiotherapy during the past 30 years.
Local recurrence and regional recurrence were observed in 74 patients (23.9%) and 63 patients (20.4%) of the operated group, leading to total locoregional recurrence in 115 patients (37.2%) after surgical based therapy. In patients with regional recurrence, secondary lymph node metastases were located on the ipsilateral neck in 73.8%, on the contralateral neck in 18.0% and on both sides of the neck in 8.2%. Locoregional recurrence occurred after an average duration of 1.6 years after initial treatment. 10.9% of all patients (surgical plus non-surgical group) developed a second malignant disease during follow-up.
Survival rates of patients with different pT-stages (surgical group)
Survival rates of patients with different pN-stages (surgical group)
For many head and neck cancer patients, treatment consists of both chemotherapy and radiation therapy given simultaneously. This type of treatment is intensive and often results in serious and sometimes permanent damage to a patient's ability to swallow and hence, ability to eat a normal diet for the remainder of their lives. The locoregional recurrence rate of our patients lies within the range of locoregional recurrence rates decribed by other authors, which are quoted between 16 and 42% [12–17]. According to the literature, adjuvant treatment modalities seem to improve locoregional control. Patients undergoing a targeted chemora- diation protocol for head and neck cancer lost about 10% of their pretreatment weight and had a decline in eating ability [16, 18]. In our study, almost 10% of the operated patients received neoadjuvant radiochemotherapy prior to surgery and almost 20% of patients in the surgical group received postoperative radiation due to unclear margins, extensive tumour growth at the primary site, massive lymph node involvement or extracapsular spread, reflecting the scope of changing indications for radiotherapy during a period of three decades. Since patient selection for (neo) adjuvant treatment was not randomized, the impact of radio(chemo)therapy could not be determined in our study.
Local failure at the primary site occurred in almost a quarter of our patients with surgical treatment, although clear margins were described for more than 90% of these patients. It is generally accepted that clear margins reduce local failure, although local control is not guaranteed. Byers et al. decribes local failure rates between 15 and 30% in patients with clear margins (> 5 mm distance to the tumour) and between 50 and 80% in patients with unclear margins . In oncologic regard, it also remains unclear how much distance to the tumour should be maintained in tongue cancer.
The dimension of lymphatic involvement seems to reflect the degree of malignancy in tongue cancer [19–23]. In multivariate analysis, pN-status and extracapsular spread directly influenced survival besides clear margins. In univariate analysis, further factors showed prognostic value on the first sight. However, better survival of patients with tumours of the mobile tongue were attributed to the higher proportion of advanced tumour stages in patients with tumours of the base of the tongue, since these tumours were usually detected later [24, 25]. The size of the tumour alone seemed not to be of relevance for prognosis as long clear margins were obtained. This also explains why tumour extension across the midline alone did not affect survival [26, 27]. Furthermore, the statistical distribution of tumour grade and number of lymph nodes were also associated with prognostic factors which were later identified in multivariate analysis. Age and gender - as described by other authors - did not influence prognosis in our study .
In the literature, the prognostic value of tumour grade is controversially discussed. Whereas some authors consider tumour grade as a prognostic factor [24, 26–29], other authors doubt the prognostic value of tumour grade [12, 14, 30–32]. It seems reasonable that there are further prognostic factors, which are still unknown and currently not detectable by modern imaging and histopathological techniques . Therefore, a clear definition of high risk groups remains incomplete up to the present. In current literature, serum and saliva are considered very useful in the fields of genomics, proteomics, transcriptomics and metabolomics for generation of diagnostic and prognostic biomarker signatures [34–36]. However, first studies for oral cancer show that these techniques seem to have greater potential as a tumor diagnostic tool for follow-up than for prognostication . Further validation by multi-institutional studies and randomized clinical trials are recommended before these techniques can be translated into clinical practice for oral cancer .
In general, treatment strategies for tumour recurrence follow the same principles than for primary tumour disease. As already described by Eckardt et al., surgical intervention seems to be associated with better survival for patients with recurrent floor of mouth carcinoma, which was also confirmed by our study for patients with tongue cancer . Therefore, curative total resection should be aimed if survival is clearly defined as highest preference. However, functional impairment with dramatic loss of life quality needs to be discussed individually with every patient. If recurrent tumour disease seems to be unresectable, subtotal tumour reduction can be discussed in order to improve the starting position for adjuvant treatment modalities in an interdisciplinary treatment concept. In general, however, mutilations caused by surgical interventions should be minimized in these cases in order to preserve the greatest amount of life quality as long as possible.
Funding: The article processing charges are funded by the Deutsche Forschungsgemeinschaft (DFG), "Open Acess Publizieren".
- Regezi JA, Sciubba JJ, Jordan RCK: Oral pathology: clinical, pathologic correlations. Edited by: St Louis (MO). 2008, Saunders Elsevier, 12-24. 5Google Scholar
- Byers RM, El-Naggar AK, Lee YY, et al: Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?. Head Neck. 1998, 20: 138-44. 10.1002/(SICI)1097-0347(199803)20:2<138::AID-HED7>3.0.CO;2-3.View ArticlePubMedGoogle Scholar
- Lim MSRE: Correlational of oral tongue cancer inversion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression, by. J Surg Oncol. Edited by: Kim S-H, Cho NH, Kim K. 2006, 93: 253-54. 10.1002/jso.20462.Google Scholar
- Huang SF, Kang CJ, Lin CY, et al: Neck treatment of patients with early stage oral tongue cancer: comparison between observation, supraomohyoid dissection, and extended dissection. Cancer. 2008, 112: 1066-75. 10.1002/cncr.23278.View ArticlePubMedGoogle Scholar
- D'Cruz AK, Siddachari RC, Walvekar RR, et al: Elective neck dissection for the management of the N0 neck in early cancer of the oral tongue: need for a randomized controlled trial. Head Neck. 2009, 31: 618-24. 10.1002/hed.20988.View ArticlePubMedGoogle Scholar
- Hsu MY, Wang CC: Elective radiotherapy or neck dissection for CT-staged T1-2N0 oral tongue cancer. Head Neck. 2010, 32 (2): 191-8.Google Scholar
- Spiro RH, Strong EW: Surgical treatment of cancer of the tongue. Surg Clin North Am. 1974, 54: 759-65.PubMedGoogle Scholar
- Callery CD, Spiro RH, Strong EW: Changing trends in the management of squamous carcinoma of the tongue. Am J Surg. 1984, 148: 449-54. 10.1016/0002-9610(84)90368-4.View ArticlePubMedGoogle Scholar
- Franceschi D, Gupta R, Spiro RH, Shah JP: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg. 1993, 166: 360-65. 10.1016/S0002-9610(05)80333-2.View ArticlePubMedGoogle Scholar
- Khalilur RM, Hayashi K, Shibuya H: Brachytherapy for tongue cancer in the very elderly is an alternative to external beam radiation. Br J Radiol. 2010,Google Scholar
- Pernot M, Malissard L, Hoffstetter S, et al: The study of tumoral, radiobiological and general health factors that influence results and complications in a series of 448 oral tongue carcinomas treated exclusively by irradiation. Int J Radiat Oncol Biol Phys. 1994, 29: 673-79. 10.1016/0360-3016(94)90553-3.View ArticlePubMedGoogle Scholar
- El-Husseiny G, Kandil A, Jamshed A, et al: Squamous cell carcinoma of the oral tongue: An analysis of prognostic factors. Br J Oral Maxillofac Surg. 2000, 38: 193-99. 10.1054/bjom.1999.0235.View ArticlePubMedGoogle Scholar
- Hosal AS, Unal OF, Ayhan A: Possible prognostic value of histopathologic parameters in patients with carcinoma of the oral tongue. Eur Arch Otorhinolaryngol. 1998, 225: 216-19.Google Scholar
- Kantola S, Parikka M, Jokinen K, et al: Prognostic factors in tongue cancer: Relative importance of demographic clinical and histopathological factors. Br J Cancer. 2000, 83: 614-19. 10.1054/bjoc.2000.1323.PubMed CentralView ArticlePubMedGoogle Scholar
- Ünal OF, Ayhan A, Hosal AS: Prognostic value of p53 expression and histopathological parameters in squamous cell carcinoma of oral tongue. J Laryngol Otol. 1999, 113: 446-50.View ArticlePubMedGoogle Scholar
- Wang YH, Chen YF, Guo ZM, Zhang Q, Liu TR, Chen FJ: Reasons for recurrence and prognostic analysis of early stage squamous cell carcinoma of the oral tongue. Chinese Journal of Cancer. 2009, 28: 1-5.PubMedGoogle Scholar
- Zwetyenga N, Majoufre-Lefebvre C, Siberchicot F, Demeaux H, Pinsolle J: Squamous cell carcinoma of the tongue: treatment results and prognosis. Rev Stomatol Chir Maxillofac. 2003, 104: 10-17.PubMedGoogle Scholar
- Hua H, Zeng ZY, Xu GP: Multivariate analysis of prognosis of patients with clinical stage I and II carcinoma of mobile tongue. Ai Zheng. 2003, 22: 210-13.PubMedGoogle Scholar
- Daisuke S, Myers JN: Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev. 2007, 26: 645-62. 10.1007/s10555-007-9082-y.View ArticleGoogle Scholar
- Greenberg JS, Fowler R, Gomez J, et al: Extent of extracapsular spread: A critical prognosticator in oral tongue cancer. Cancer. 2003, 97: 1464-70. 10.1002/cncr.11202.View ArticlePubMedGoogle Scholar
- Okamoto M, Nishimine M, Kishi M, et al: Prediction of delayed neck metastasis in patients with stage I/II squamous cell carcinoma of the tongue. J Oral Pathol Med. 2002, 31: 227-33. 10.1034/j.1600-0714.2002.310406.x.View ArticlePubMedGoogle Scholar
- Myers JN, Greenberg JS, Mo V, Roberts D: Extracapsular spread. A significant predictor of treatment failure in patients with squamous cell carcinoma of the tongue. Cancer. 2001, 92: 3030-36. 10.1002/1097-0142(20011215)92:12<3030::AID-CNCR10148>3.0.CO;2-P.View ArticlePubMedGoogle Scholar
- Shingaki S, Takada M, Sasai K, et al: Impact of lymph node metastasis on the pattern of failure and survival in oral carcinoma. Am J Surg. 2003, 185: 278-84. 10.1016/S0002-9610(02)01378-8.View ArticlePubMedGoogle Scholar
- Gorsky M, Epstein JB, Oakley C, Le ND, Hay J, Stevenson-Moore P: Carcinoma of the tongue: A case series analysis of clinical presentation, risk factors, staging, and outcome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004, 98: 546-52. 10.1016/j.tripleo.2003.12.041.View ArticlePubMedGoogle Scholar
- Malone JP, Stephens JA, Grecula JC, Rhoades CA, Ghaheri BA, Schuller DE: Disease control, survival, and functional outcome after multimodal treatment for advanced-stage tongue base cancer. Head Neck. 2004, 26: 561-72. 10.1002/hed.20012.View ArticlePubMedGoogle Scholar
- Korpi JT, Kervinen V, Maklin H, et al: Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer. Br J Cancer. 2008, 98: 766-75. 10.1038/sj.bjc.6604239.PubMed CentralView ArticlePubMedGoogle Scholar
- Teixeira G, Antonangelo L, Kowalski L, Saldiva P, Ferraz A, Silva Filho G: Argyrophilic nucleolar organizer regions staining is useful in predicting recurrence-free interval in oral tongue and floor of mouth squamous cell carcinoma. Am J Surg. 1996, 172: 684-88. 10.1016/S0002-9610(96)00306-6.View ArticlePubMedGoogle Scholar
- Arduino PG, Carrozzo M, Chiecchio A, et al: Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases. J Oral Maxillofac Surg. 2008, 66: 1570-79. 10.1016/j.joms.2007.12.024.View ArticlePubMedGoogle Scholar
- Fan KH, Lin CY, Kang CJ: Combined-modality treatment for advanced oral tongue squamous cell carci-noma. Int J Radiat Oncol Biol Phys. 2007, 67: 453-61. 10.1016/j.ijrobp.2006.06.026.View ArticlePubMedGoogle Scholar
- Kademani D, Bell RB, Bagheri S, et al: Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg. 2005, 63: 1599-605. 10.1016/j.joms.2005.07.011.View ArticlePubMedGoogle Scholar
- Al-Rajhi N, Khafaga Y, El-Husseiny J, et al: Early stage carcinoma of oral tongue: prognostic factors for local control and survival. Oral Oncol. 2000, 36: 508-14. 10.1016/S1368-8375(00)00042-7.View ArticlePubMedGoogle Scholar
- O-charoenrat P, Pillai G, Patel S, et al: Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer. Oral Oncol. 2003, 39: 386-90. 10.1016/S1368-8375(02)00142-2.View ArticlePubMedGoogle Scholar
- Woolgar JA: Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncol. 2006, 42: 229-39. 10.1016/j.oraloncology.2005.05.008.View ArticlePubMedGoogle Scholar
- Nagler RM: Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol. 2009, 45: 1006-10. 10.1016/j.oraloncology.2009.07.005.View ArticlePubMedGoogle Scholar
- Matharoo-Ball B, Miles AK, Creaser CS, Ball G, Rees R: Serum biomarker profiling in cancer studies: a question of standardisation?. Vet Comp Oncol. 2008, 6: 224-47. 10.1111/j.1476-5829.2008.00171.x.View ArticlePubMedGoogle Scholar
- Zhang L, Farrell JJ, Zhou H, et al: Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010, 138: 949-57. 10.1053/j.gastro.2009.11.010.PubMed CentralView ArticlePubMedGoogle Scholar
- Bello IO, Soini Y, Salo T: Prognostic evaluation of oral tongue cancer: Means, markers and perspectives (I). Oral Oncology. 2010, 46: 630-635. 10.1016/j.oraloncology.2010.06.006.View ArticlePubMedGoogle Scholar
- Bello IO, Soini Y, Salo T: Prognostic evaluation of oral tongue cancer: Means, markers and perspectives (II). Oral Oncology. 2010, 46: 636-643. 10.1016/j.oraloncology.2010.06.008.View ArticlePubMedGoogle Scholar
- Brugere JM, Mosseri VF, Mamelle G, et al: Nodal failures in patients with N0, N+ oral squamous cell carcinoma without capsular rupture. Head Neck. 1996, 18: 133-37. 10.1002/(SICI)1097-0347(199603/04)18:2<133::AID-HED4>3.0.CO;2-2.View ArticlePubMedGoogle Scholar
- Kowalski LP, Sanabria A: Elective neck dissection in oral carcinoma: a critical review of the evidence. Acta Otorhinolaryngol Ital. 2007, 27: 113-17.PubMed CentralPubMedGoogle Scholar
- Manni JJ, van der Hoogen FJ: Supraomohyoid neck dissection with frozen section biopsy as a staging pro-cedure in the clinically node-negative neck in carcinoma of the oral cavity. Am J Surg. 1991, 162: 373-76. 10.1016/0002-9610(91)90151-3.View ArticlePubMedGoogle Scholar
- Capote-Moreno A, Naval L, Munoz-Guerra MF, Sastre J, Rodríguez-Campo FJ: Prognostic factors influencing contralateral neck lymph node metastases in oral and oropharyngeal carcinoma. J Oral Maxillofac Surg. 2010, 68: 268-75. 10.1016/j.joms.2009.09.071.View ArticlePubMedGoogle Scholar
- Ho CM, Lam KH, Wei WI, Lau SK, Lam LK: Occult lymph node metastasis in small oral tongue cancers. Head Neck. 1992, 14: 359-63. 10.1002/hed.2880140504.View ArticlePubMedGoogle Scholar
- Lydiatt DD, Robbins KT, Byers RM, Wolf PF: Treatment of stage I and II oral tongue cancer. Head Neck. 1993, 15: 308-12. 10.1002/hed.2880150407.View ArticlePubMedGoogle Scholar
- Persky MS, Lagmay VM: Treatment of the clinically negative neck in oral squamous cell carcinoma. Laryngoscope. 1999, 109: 1160-64. 10.1097/00005537-199907000-00029.View ArticlePubMedGoogle Scholar
- Kokemüller H, Brachvogel P, Eckardt A, Hausamen JE: Neck dissection in oral cancer - clinical review and analysis of prognostic factors. Int J Oral Maxillofac Surg. 2002, 31: 608-614. 10.1054/ijom.2002.0265.View ArticleGoogle Scholar
- Yun IS, Lee DW, Lee WJ, Lew DH, Choi EC, Rah DK: Correlation of neotongue volume changes with functional outcomes after long-term follow-up of total glossectomy. J Craniofac Surg. 2010, 21: 111-16. 10.1097/SCS.0b013e3181c46692.View ArticlePubMedGoogle Scholar
- Eckardt A, Barth EL, Kokemueller H, Wegener G: Recurrent carcinoma of the head and neck: treatment strategies and survival analysis in a 20-year period. Oral Oncology. 2004, 40: 427-432. 10.1016/j.oraloncology.2003.09.019.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.