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NCI/PDQ^® Health professionals: Lip and Oral Cavity Cancer Treatment (PDQ®)

National Cancer Institute
Last Modified: July 16, 2012

TABLE OF CONTENTS

• General Information About Lip and Oral Cavity Cancer
  • Related Summaries

• Cellular Classification of Lip and Oral Cavity Cancer

• Stage Information for Lip and Oral Cavity Cancer
  • Definitions of TNM

• Treatment Option Overview

• Stage I Lip and Oral Cavity Cancer
  • Small Lesions of the Lip
  • Small Anterior Tongue Lesions
  • Small Lesions of the Buccal Mucosa
  • Small Lesions of the Floor of the Mouth
  • Small Lesions of the Lower Gingiva
  • Small Tumors of the Retromolar Trigone
  • Small Lesions of the Upper Gingiva and Hard Palate
  • Current Clinical Trials

• Stage II Lip and Oral Cavity Cancer
  • Small Lesions of the Lip
  • Small Anterior Tongue Lesions
  • Small Lesions of the Buccal Mucosa
  • Small Lesions of the Floor of the Mouth
  • Small Lesions of the Lower Gingiva
  • Small Tumors of the Retromolar Trigone
  • Small Lesions of the Upper Gingiva and Hard Palate
  • Current Clinical Trials

• 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

• Stage IV Lip and Oral Cavity Cancer
  • Advanced Lesions of the Lip
  • Advanced Lesions of the Anterior Tongue
  • Advanced Lesions of the Buccal Mucosa
  • Advanced Lesions of the Floor of the Mouth
  • Advanced Lesions of the Lower Gingiva
  • Advanced Lesions of the Retromolar Trigone
  • Advanced Lesions of the Upper Gingiva
  • Advanced Lesions of the Hard Palate
  • Current Clinical Trials

• Recurrent Lip and Oral Cavity Cancer
  • Current Clinical Trials

• Changes to This Summary (07/16/2012)

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
  • Disclaimer
  • Contact Us

• Get More Information From NCI

General Information About Lip and Oral Cavity Cancer

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Related Summaries

Note: Other PDQ® summaries containing information related to lip and oral cavity cancer include the following:

• Oral Cancer Prevention
• Oral Cancer Screening

The oral cavity extends from the skin-vermilion junctions of the anterior lips to the junction of the hard and soft palates above and to the line of circumvallate papillae below and is divided into the following specific areas:

• Lip.
• Anterior two thirds of tongue.
• Buccal mucosa.
• Floor of mouth.
• Lower gingiva.
• Retromolar trigone.
• Upper gingiva.
• Hard palate.

The main routes of lymph node drainage are into the first station nodes (i.e., buccinator, jugulodigastric, submandibular, and submental). Sites close to the midline often drain bilaterally. Second station nodes include the parotid, jugular, and the upper and lower posterior cervical nodes.

Early cancers (stage I and stage II) of the lip and oral cavity are highly curable by surgery or by radiation therapy, and the choice of treatment is dictated by the anticipated functional and cosmetic results of treatment and by the availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient. 1 2 3 The presence of a positive margin or a tumor depth of more than 5 mm significantly increases the risk of local recurrence and suggests that combined modality treatment may be beneficial. 4 5

Advanced cancers (stage III and stage IV) of the lip and oral cavity represent a wide spectrum of challenges for the surgeon and radiation oncologist. Except for patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes larger than 2 cm in diameter, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. 2 Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials. Such trials evaluate the potential role of radiation modifiers or combination chemotherapy combined with surgery and/or radiation therapy.

Patients with head and neck cancers have an increased chance of developing a second primary tumor of the upper aerodigestive tract. 6 7 A study has shown that daily treatment of these patients with moderate doses of isotretinoin (13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors. No survival advantage has yet been demonstrated, however, in part due to recurrence and death from the primary malignancy. An additional trial has shown no benefit of retinyl palmitate or retinyl palmitate plus beta-carotene when compared to retinoic acid alone. 8[Level of evidence: 1iiDii]

The rate of curability of cancers of the lip and oral cavity varies depending on the stage and specific site. Most patients present with early cancers of the lip, which are highly curable by surgery or by radiation therapy with cure rates of 90% to 100%. Small cancers of the retromolar trigone, hard palate, and upper gingiva are highly curable by either radiation therapy or surgery with survival rates of as much as 100%. Local control rates of as much as 90% can be achieved with either radiation therapy or surgery in small cancers of the anterior tongue, the floor of the mouth, and buccal mucosa. 9

Moderately advanced and advanced cancers of the lip also can be controlled effectively by surgery or radiation therapy or a combination of these. The choice of treatment is generally dictated by the anticipated functional and cosmetic results of the treatment. Moderately advanced lesions of the retromolar trigone without evidence of spread to cervical lymph nodes are usually curable and have shown local control rates of as much as 90%; such lesions of the hard palate, upper gingiva, and buccal mucosa have a local control rate of as much as 80%. In the absence of clinical evidence of spread to cervical lymph nodes, moderately advanced lesions of the floor of the mouth and anterior tongue are generally curable with survival rates of as much as 70% and 65%, respectively. 9 10

References:

1. Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology - Head and Neck Surgery. Saint Louis, Mo: Mosby-Year Book, Inc., 1998. [PUBMED Abstract]
2. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009. [PUBMED Abstract]
3. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
4. Jones KR, Lodge-Rigal RD, Reddick RL, et al.: Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity. Arch Otolaryngol Head Neck Surg 118 (5): 483-5, 1992. [PUBMED Abstract]
5. Po Wing Yuen A, Lam KY, Lam LK, et al.: Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck 24 (6): 513-20, 2002. [PUBMED Abstract]
6. Day GL, Blot WJ: Second primary tumors in patients with oral cancer. Cancer 70 (1): 14-9, 1992. [PUBMED Abstract]
7. van der Tol IG, de Visscher JG, Jovanovic A, et al.: Risk of second primary cancer following treatment of squamous cell carcinoma of the lower lip. Oral Oncol 35 (6): 571-4, 1999. [PUBMED Abstract]
8. Papadimitrakopoulou VA, Lee JJ, William WN Jr, et al.: Randomized trial of 13-cis retinoic acid compared with retinyl palmitate with or without beta-carotene in oral premalignancy. J Clin Oncol 27 (4): 599-604, 2009. [PUBMED Abstract]
9. Wallner PE, Hanks GE, Kramer S, et al.: Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth. Am J Clin Oncol 9 (1): 50-7, 1986. [PUBMED Abstract]
10. Takagi M, Kayano T, Yamamoto H, et al.: Causes of oral tongue cancer treatment failures. Analysis of autopsy cases. Cancer 69 (5): 1081-7, 1992. [PUBMED Abstract]

Cellular Classification of Lip and Oral Cavity Cancer

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Most head and neck cancers are of the squamous cell variety and may be preceded by various precancerous lesions. Minor salivary gland tumors are not uncommon in these sites. Specimens removed from the lesions may show the carcinomas to be noninvasive, in which case the term carcinoma in situ is applied. An invasive carcinoma will be well differentiated, moderately well-differentiated, poorly differentiated or undifferentiated.

Tumor grading is recommended using Broder classification (Tumor Grade [G]):

• G1: well differentiated.
• G2: moderately well differentiated.
• G3: poorly differentiated.
• G4: undifferentiated. 1

No statistically significant correlation between degree of differentiation and the biologic behavior of the cancer exists; however, vascular invasion is a negative prognostic factor. 2

Other tumors of glandular epithelium, odontogenic apparatus, lymphoid tissue, soft tissue, and bone and cartilage origin require special consideration and are not included in this section of PDQ®. Reference to the World Health Organization nomenclature is recommended.

The term leukoplakia should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may only represent a fungal infection, lichen planus, or other benign oral disease.

References:

1. Bansberg SF, Olsen KD, Gaffey TA: High-grade carcinoma of the oral cavity. Otolaryngol Head Neck Surg 100 (1): 41-8, 1989. [PUBMED Abstract]
2. Close LG, Brown PM, Vuitch MF, et al.: Microvascular invasion and survival in cancer of the oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg 115 (11): 1304-9, 1989. [PUBMED Abstract]

Stage Information for Lip and Oral Cavity Cancer

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The staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging offers an advantage over computed tomographic scans in the detection and localization of head and neck tumors and in the distinction of lymph nodes from blood vessels. 1 If a patient relapses, complete restaging must be done to select the appropriate additional therapy. 2 3

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define lip and oral cavity cancer. 4

Table 1. Primary Tumor (T)^a

^aReprinted with permission from AJCC: Lip and oral cavity. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 29-40.^bSuperficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4.

TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
Tis	Carcinoma in situ.
T1	Tumor 2 cm in greatest dimension.
T2	Tumor >2 cm but 4 cm in greatest dimension.
T3	Tumor >4 cm in greatest dimension.
T4a	Moderately advanced local disease.b
	(Lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, that is, chin or nose.
	(Oral cavity) Tumor invades adjacent structures only (e.g., through cortical bone [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, or skin of face).
T4b	Very advanced local disease.
	Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery.

Table 2. Regional Lymph Nodes (N)^a

^aReprinted with permission from AJCC: Lip and oral cavity. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 29-40.

NX	Regional lymph nodes cannot be assessed.
N0	No regional lymph node metastasis.
N1	Metastasis in a single ipsilateral lymph node, 3 cm in greatest dimension.
N2	Metastasis in a single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension.
	Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.
	Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
N2a	Metastasis in single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension.
N2b	Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.
N2c	Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
N3	Metastasis in a lymph node >6 cm in greatest dimension.

Table 3. Distant Metastasis^a

^aReprinted with permission from AJCC: Lip and oral cavity. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 29-40.

M0	No distant metastasis.
M1	Distant metastasis.

Table 4. Anatomic Stage/Prognostic Groups^a

^aReprinted with permission from AJCC: Lip and oral cavity. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 29-40.

Stage	T	N	M
0	Tis	N0	M0
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1	N1	M0
	T2	N1	M0
	T3	N1	M0
IVA	T4a	N0	M0
	T4a	N1	M0
	T1	N2	M0
	T2	N2	M0
	T3	N2	M0
	T4a	N2	M0
IVB	Any T	N3	M0
	T4b	Any N	M0
IVC	Any T	Any N	M1

References:

1. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988. [PUBMED Abstract]
2. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009. [PUBMED Abstract]
3. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
4. Lip and oral cavity. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 29-35. [PUBMED Abstract]

Treatment Option Overview

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Depending on the site and extent of the primary tumor and the status of the lymph nodes, some general considerations for the treatment of lip and oral cavity cancer include the following: 1 2 3 4 5

• Surgery alone.
• Radiation therapy alone.
• A combination of the above.

For lesions of the oral cavity, surgery must adequately encompass all of the gross as well as the presumed microscopic extent of the disease. If regional nodes are positive, cervical node dissection is usually done in continuity. With modern approaches, the surgeon can successfully ablate large posterior oral cavity tumors and with reconstructive methods can achieve satisfactory functional results. Prosthodontic rehabilitation is important, particularly in early-stage cancers, to assure the best quality of life.

Radiation therapy for lip and oral cavity cancers can be administered by external-beam radiation therapy (EBRT) or interstitial implantation alone, but for many sites the use of both modalities produces better control and functional results. Small superficial cancers can be very successfully treated by local implantation using any one of several radioactive sources, by intraoral cone radiation therapy, or by electrons. Larger lesions are frequently managed using EBRT to include the primary site and regional lymph nodes, even if they are not clinically involved. Supplementation with interstitial radiation sources may be necessary to achieve adequate doses to large primary tumors and/or bulky nodal metastases. A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible. 6 7

Early cancers (stage I and stage II) of the lip, floor of the mouth, and retromolar trigone are highly curable by surgery or radiation therapy. The choice of treatment is dictated by the anticipated functional and cosmetic results. Availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient is also a factor in treatment choice.

Advanced cancers (stage III and stage IV) of the lip, floor of the mouth, and retromolar trigone represent a wide spectrum of challenges for the surgeon and radiation oncologists. Most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. Patients with small T3 lesions and no regional lymph nodes, and no distant metastases or patients who have no lymph nodes larger than 2 cm in diameter, for whom treatment by radiation therapy alone or surgery alone might be appropriate, are the exceptions. Because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials that are evaluating the following:

• The potential role of radiation modifiers to improve local control or decrease morbidity.
• The role of combinations of chemotherapy with surgery and/or radiation therapy both to improve local control and to decrease the frequency of distant metastases.

Early cancers of the buccal mucosa are equally curable by radiation therapy or by adequate excision. Patient factors and local expertise influence the choice of treatment. Larger cancers require composite resection with reconstruction of the defect by pedicle flaps.

Early lesions (T1 and T2) of the anterior tongue may be managed by surgery or by radiation therapy alone. Both modalities produce 70% to 85% cure rates in early lesions. Moderate excisions of tongue, even hemiglossectomy, can often result in little speech disability provided the wound closure is such that the tongue is not bound down. If, however, the resection is more extensive, problems may include aspiration of liquids and solids and difficulty in swallowing in addition to speech difficulties. Occasionally, patients with tumor of the tongue require almost total glossectomy. Large lesions generally require combined surgical and radiation treatment. The control rates for larger lesions are about 30% to 40%. According to clinical and radiological evidence of involvement, cancers of the lower gingiva that are exophytic and amenable to adequate local excision may be excised to include portions of bone. More advanced lesions require segmental bone resection, hemimandibulectomy, or maxillectomy, depending on the extent of the lesion and its location.

Early lesions of the upper gingiva or hard palate without bone involvement can be treated with equal effectiveness by surgery or by radiation therapy alone. Advanced infiltrative and ulcerating lesions should be treated by a combination of radiation therapy and surgery. Most primary cancers of the hard palate are of minor salivary gland origin. Primary squamous cell carcinoma of the hard palate is uncommon, and these tumors generally represent invasion of squamous cell carcinoma arising on the upper gingiva, which is much more common. Management of squamous cell carcinoma of the upper gingiva and hard palate are usually considered together. Surgical treatment of cancer of the hard palate usually requires excision of underlying bone producing an opening into the antrum. This defect can be filled and covered with a dental prosthesis, which is a maneuver that restores satisfactory swallowing and speech.

Patients who smoke while on radiation therapy appear to have lower response rates and shorter survival durations than those who do not; 8 therefore, patients should be counseled to stop smoking before beginning radiation therapy. Dental status evaluation should be performed prior to therapy to prevent late sequelae.

References:

1. Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA: Lippincott, William & Wilkins, 2009. [PUBMED Abstract]
2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
3. Myers EN, Suen MD, Myers J, eds.: Cancer of the Head and Neck. 4th ed. Philadelphia, Pa: Saunders, 2003. [PUBMED Abstract]
4. Freund HR: Principles of Head and Neck Surgery. 2nd ed. New York, NY: Appleton-Century-Crofts, 1979. [PUBMED Abstract]
5. Lore JM: An Atlas of Head and Neck Surgery. 3rd ed. Philadelphia, Pa: Saunders, 1988. [PUBMED Abstract]
6. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
7. Langendijk JA, de Jong MA, Leemans ChR, et al.: Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time. Int J Radiat Oncol Biol Phys 57 (3): 693-700, 2003. [PUBMED Abstract]
8. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993. [PUBMED Abstract]

Stage I Lip and Oral Cavity Cancer

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Surgery and/or radiation therapy may be used, depending on the exact site. 1 2

Small Lesions of the Lip

Standard treatment options:

1. Surgery.
2. Radiation therapy.

Surgery and radiation therapy produce similar cure rates, and the method of treatment is dictated by the anticipated cosmetic and functional results.

Small Anterior Tongue Lesions

Standard treatment options:

1. Wide local excision is often used for small lesions that can be resected transorally.
2. For patients with larger T1 lesions, the following standard treatments are used:
   1. Surgery.
   2. Radiation therapy.
   3. Interstitial implantation alone or with external-beam radiation therapy.
   4. Irradiation of the neck.

Small Lesions of the Buccal Mucosa

Standard treatment options:

1. Surgery alone for patients with lesions smaller than 1 cm in diameter, if the commissure is not involved.
2. Radiation therapy, including brachytherapy, should be considered to treat lesions smaller than 1 cm in diameter, if the commissure is involved.
3. Surgical excision with a split-thickness skin graft or radiation therapy is used to treat larger T1 lesions.

Small Lesions of the Floor of the Mouth

Standard treatment options:

1. Surgery for patients with T1 lesions.
2. Radiation therapy is used to treat T1 lesions.
3. Excision alone is generally adequate to treat lesions smaller than 0.5 cm, if there is a margin of normal mucosa between the lesion and the gingiva.
4. Surgery is often used, if the lesion is attached to the periosteum.
5. Radiation therapy is often used, if the lesion encroaches on the tongue.

Small Lesions of the Lower Gingiva

Standard treatment options:

1. Intraoral resection with or without a rim resection of bone and repair with a split-thickness skin graft are used to treat small lesions.
2. Radiation therapy may be used for small lesions, but results are generally better after surgery alone.

Small Tumors of the Retromolar Trigone

Standard treatment options:

1. Limited resection of the mandible is performed for early lesions without detectable bone invasion.
2. Radiation therapy may be used initially, if limited resection is not feasible, with surgery reserved for radiation failure.

Small Lesions of the Upper Gingiva and Hard Palate

Standard treatment options:

1. Surgical resection is used to treat most small lesions.
2. Postoperative radiation therapy may be used, if appropriate.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I 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. [PUBMED Abstract]
2. Guerry TL, Silverman S Jr, Dedo HH: Carbon dioxide laser resection of superficial oral carcinoma: indications, technique, and results. Ann Otol Rhinol Laryngol 95 (6 Pt 1): 547-55, 1986 Nov-Dec. [PUBMED Abstract]

Stage II Lip and Oral Cavity Cancer

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Surgery and/or radiation therapy may be used, depending on the exact site. 1

Small Lesions of the Lip

Standard treatment options:

1. Surgery is used for patients with smaller T2 lesions on the lower lip, if simple closure produces an acceptable cosmetic result.
2. Radiation therapy, which may include external-beam and/or interstitial techniques, as appropriate, has the advantage of producing a relatively better functional and cosmetic result with intact skin and muscle innervation, if a reconstructive surgical procedure is required.

Small Anterior Tongue Lesions

Standard treatment options:

1. Radiation therapy is usually selected for patients with T2 lesions that have minimal infiltration to preserve speech and swallowing. 2
2. Surgery is reserved for patients for whom radiation treatment failed. 2
3. Neck dissection may be considered when primary brachytherapy is used. 2
4. Surgery, radiation therapy, or a combination of both are used for deeply infiltrative lesions.

Small Lesions of the Buccal Mucosa

Standard treatment options:

1. Radiation therapy is the usual treatment for patients with small T2 lesions (3 cm).
2. Surgery, radiation therapy, or a combination of these are used, if indicated to treat large T2 lesions (>3 cm). Radiation therapy is often used, if the lesion involves the commissure. Surgery is often used, if tumor invades the mandible or maxilla.

Small Lesions of the Floor of the Mouth

Standard treatment options:

1. Surgery is often used for patients with small T2 lesions (3 cm), if the lesion is attached to the periosteum.
2. Radiation therapy is often used to treat patients with small T2 lesions (3 cm), if the lesion encroaches on the tongue.
3. Surgery and radiation therapy are alternative methods of treatment for patients with large T2 lesions (>3 cm), the choice of which depends primarily on the expected extent of disability from surgery.
4. External-beam radiation therapy with or without interstitial radiation therapy should be considered postoperatively for larger lesions.

Small Lesions of the Lower Gingiva

Standard treatment options:

1. Intraoral resection with or without a rim resection of bone and repair with a split-thickness skin graft are used to treat patients with small lesions.
2. Radiation therapy may be used to treat patients with small lesions, but results are generally better after surgery alone.

Small Tumors of the Retromolar Trigone

Standard treatment options:

1. Limited resection of the mandible is performed to treat patients with early lesions that are without detectable bone invasion.
2. Radiation therapy may be used initially, if limited resection is not feasible.
3. Surgery is reserved for radiation failure.

Small Lesions of the Upper Gingiva and Hard Palate

Standard treatment options:

• Surgical resection with postoperative radiation therapy, as appropriate, is used to treat most lesions. A small study showed that radiation therapy may be used effectively as the sole treatment modality. 3

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II 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. [PUBMED Abstract]
2. Pernot M, Malissard L, Aletti P, et al.: Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques. Radiother Oncol 23 (4): 223-8, 1992. [PUBMED Abstract]
3. Yorozu A, Sykes AJ, Slevin NJ: Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases. Oral Oncol 37 (6): 493-7, 2001. [PUBMED Abstract]

Stage III Lip and Oral Cavity Cancer

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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 4 5 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 4 5 6 8 9 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 4 5 6 8 9 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 4 5 6 8 9 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 4 5 6 8 9 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 (02 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 (23 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. [PUBMED Abstract]
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, Corví 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]

Stage IV Lip and Oral Cavity Cancer

Back Up

Randomized, prospective trials have yet to demonstrate a benefit in either disease-free survival or overall survival for patients receiving neoadjuvant chemotherapy. 1 The use of isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primaries is under clinical evaluation. 2

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,