Stage III Lip and Oral Cavity Cancer
Advanced Lesions of the Lip
Moderately Advanced (Late T2, Small T3) Lesions of the AnteriorTongue
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
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
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 thereby 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 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. Such
patients are appropriate candidates for clinical trials.
Standard treatment options:
- Surgery: A variety of surgical approaches can be used depending on the size
and location of the lesion and the needs for reconstruction.
- Radiation therapy: A variety of radiation therapy techniques can be used as
dictated by the size and location of the lesion. Options include external-beam
radiation therapy (EBRT) with or without brachytherapy.
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]
- Superfractionated radiation therapy.[11]
Moderately Advanced (Late T2, Small T3) Lesions of the AnteriorTongue
Standard treatment options:
- Minimally infiltrative lesions may be treated with external-beam radiation therapy with or
without interstitial implant.
- Deeply infiltrative lesions may be treated with surgery with postoperative radiation
therapy.[2]
Advanced Lesions of the Buccal Mucosa
Standard treatment options:
- Radical surgical resection alone.
- Radiation therapy alone.
- 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:
- Surgery: Rim resection plus neck dissection or partial mandibulectomy with
neck dissection as appropriate.
- Radiation therapy: EBRT alone or EBRT plus an interstitial implant.
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]
- Clinical trials using novel radiation therapy fractionation schemas.[13]
Moderately Advanced Lesions of the Lower Gingiva
Standard treatment options:
- Extensive lesions with moderate bone destruction and/or nodal metastases should
be treated by combined radiation therapy and radical resection or by radical
resection alone. Radiation therapy may be either preoperative or
postoperative.
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:
- 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]
- Clinical trials using novel radiation therapy fractionation schemas.[13]
Moderately Advanced Lesions of the Upper Gingiva
Standard treatment options:
- Superficial lesions with extensive involvement of the gingiva, hard palate,
or soft palate may be treated by radiation therapy alone.
- Deeply invasive lesions involving bone should be treated by a combination of
surgery and radiation therapy.
Moderately Advanced Lesions of the Hard Palate
Standard treatment options:
- Superficial lesions with extensive involvement of the gingiva, hard palate,
or soft palate may be treated by radiation therapy alone.
- Deeply invasive lesions involving bone should be treated by a combination of
surgery and radiation therapy or by surgery alone.
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:
- 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.)
- Radiation therapy and neck dissection:
- 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 neck, as appropriate, >2 cm).
- Radiation therapy prior to surgery:
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 PDQ Cancer Clinical Trials Registry 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
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Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.
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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]
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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.
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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.
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Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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