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Lip and Oral Cavity Cancer Treatment (PDQ®)

Health Professional Version
Last Modified: 11/20/2014

Stage III Lip and Oral Cavity Cancer

Advanced Lesions of the Lip
Moderately Advanced (Late T2, Small T3) Lesions of the Anterior Tongue
Advanced Lesions of the Buccal Mucosa
Moderately Advanced Lesions of the Floor of the Mouth
Moderately Advanced Lesions of the Lower Gingiva
Advanced Lesions of the Retromolar Trigone
Moderately Advanced Lesions of the Upper Gingiva
Moderately Advanced Lesions of the Hard Palate
Current Clinical Trials

Surgery and/or radiation therapy are used, depending on the exact tumor site.[1,2] Neoadjuvant chemotherapy, as given in clinical trials, has been used to shrink tumors and render them more definitively treatable with either surgery or radiation. Neoadjuvant chemotherapy is given prior to the other modalities, as opposed to standard adjuvant chemotherapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used as neoadjuvant chemotherapy.[3-6] Randomized, prospective trials, however, have yet to demonstrate a benefit in either disease-free survival or overall survival for patients receiving neoadjuvant chemotherapy.[7]

Advanced Lesions of the Lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy.

Standard treatment options:

  1. Surgery using a variety of surgical approaches, the choice of which is dependent on the size and location of the lesion and the needs for reconstruction.

  2. Radiation therapy using a variety of therapy techniques, including external-beam radiation therapy (EBRT) with or without brachytherapy, the choice of which is dictated by the size and location of the lesion.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.[3-6,8-10]
  2. Superfractionated radiation therapy.[11]
Moderately Advanced (Late T2, Small T3) Lesions of the Anterior Tongue

Standard treatment options:

  1. EBRT with or without interstitial implant is used to treat minimally infiltrative lesions.

  2. Surgery with postoperative radiation therapy is used to treat deeply infiltrative lesions.[2]

Advanced Lesions of the Buccal Mucosa

Standard treatment options:

  1. Radical surgical resection alone.
  2. Radiation therapy alone.
  3. Surgical resection plus radiation therapy, generally postoperative.

Treatment options under clinical evaluation:

  • Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.[3-6,8-10,12]
Moderately Advanced Lesions of the Floor of the Mouth

Standard treatment options:

  1. Surgery using rim resection plus neck dissection or partial mandibulectomy with neck dissection, as appropriate.

  2. Radiation therapy using EBRT alone or EBRT plus an interstitial implant.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.[3-6,8-10,12]

  2. Clinical trials using novel radiation therapy fractionation schemas.[13]

Moderately Advanced Lesions of the Lower Gingiva

Standard treatment options:

  • Combined radiation therapy and radical resection or radical resection alone are used to treat extensive lesions with moderate bone destruction and/or nodal metastases; radiation therapy may be administered either preoperatively or postoperatively.
Advanced Lesions of the Retromolar Trigone

Standard treatment options:

  • Surgical composite resection that may be followed by postoperative radiation therapy.

Treatment options under clinical evaluation:

  1. Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate.[3-6,8-10,12]
  2. Clinical trials using novel radiation therapy fractionation schemas.[13]
Moderately Advanced Lesions of the Upper Gingiva

Standard treatment options:

  1. Radiation therapy alone is used to treat superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate.

  2. A combination of surgery and radiation therapy is used to treat deeply invasive lesions involving bone.

Moderately Advanced Lesions of the Hard Palate

Standard treatment options:

  1. Radiation therapy alone is used to treat superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate.

  2. A combination of surgery and radiation therapy or surgery alone is used to treat deeply invasive lesions involving bone.

Treatment options for management of lymph nodes:[1]

  • Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread to involve the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle (i.e., orbicularis oris).

Standard treatment options:

  1. Radiation therapy alone or neck dissection:
    • N1 (0–2 cm).
    • N2b or N3; all nodes smaller than 2 cm. (A combined surgical and radiation therapy approach should also be considered.)
  2. Radiation therapy and neck dissection:
    • N1 (2–3 cm), N2a, N3.
  3. Surgery followed by radiation therapy, indications for which are as follows:
    • Multiple positive nodes.
    • Contralateral subclinical metastases.
    • Invasion of tumor through the capsule of the lymph node.
    • N2b or N3 (one or more nodes in each side of the neck, as appropriate, >2 cm).
  4. Radiation therapy prior to surgery:
    • Large fixed nodes.

Treatment options under clinical evaluation (all stage III lesions):

  • Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[8,10,14,15]

A meta-analysis of 63 randomized, prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy.[16][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data were not available; no standard regimen existed; and the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oral cavity cancer.

The best chemotherapy to use and the appropriate way to integrate the two modalities is still unresolved.[17]

Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

Novel fractionation radiation therapy clinical trials are under clinical evaluation.[13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III lip and oral cavity cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009. 

  2. Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.  [PUBMED Abstract]

  3. Ervin TJ, Clark JR, Weichselbaum RR, et al.: An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol 5 (1): 10-20, 1987.  [PUBMED Abstract]

  4. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.  [PUBMED Abstract]

  5. Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.  [PUBMED Abstract]

  6. Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.  [PUBMED Abstract]

  7. Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.  [PUBMED Abstract]

  8. Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.  [PUBMED Abstract]

  9. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.  [PUBMED Abstract]

  10. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.  [PUBMED Abstract]

  11. Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.  [PUBMED Abstract]

  12. Licitra L, Grandi C, Guzzo M, et al.: Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 21 (2): 327-33, 2003.  [PUBMED Abstract]

  13. Stuschke M, Thames HD: Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys 37 (2): 259-67, 1997.  [PUBMED Abstract]

  14. Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.  [PUBMED Abstract]

  15. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.  [PUBMED Abstract]

  16. Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.  [PUBMED Abstract]

  17. Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.  [PUBMED Abstract]