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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:
Early cancers (stages I and 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 therapist for the individual patient.[1-3] The presence of a positive margin or a tumor depth greater than 5 millimeters significantly increases the risk of local recurrence and suggests that combined modality treatment may be beneficial.[4]
Advanced cancers (stages III and IV) of the lip and oral cavity represent a wide spectrum of challenges for the surgeon and radiation therapist. 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 centimeters, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or 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.[5,6] 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. Additional trials are ongoing.[7]
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 up to 100%. Local control rates of up to 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.[8]
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, with local control rates of up to 90%; such lesions of the hard palate, upper gingiva, and buccal mucosa have a local control rate of up to 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 up to 70% and 65% respectively.[8,9]
Tumor grading is recommended using Broder's classification (Tumor Grade (G)):
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.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[4]
Distant metastasis (M)
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 by external-beam therapy 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 external-beam radiation therapy 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]
Early cancers (stages I and II) of the lip, floor of 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 and by the availability of the particular expertise required of the surgeon or radiation therapist for the individual patient. Advanced cancers (stages III and IV) of the lip, floor of mouth, and retromolar trigone represent a wide spectrum of challenges for the surgeon and radiation therapists. 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 centimeters, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or IV tumors are candidates for treatment by a combination of surgery and radiation therapy. Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials evaluating the following: the potential role of radiation modifiers to improve local control or decrease morbidity or 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 surprisingly 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. Thus, 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, 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;[7] 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.
The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.
Surgery and radiation therapy produce similar cure rates, and the method of treatment is dictated by the anticipated cosmetic and functional results.
1. Wide local excision is preferred for small lesions that can be resected
transorally.
2. For larger T1 lesions, either surgery or radiation therapy is an acceptable
treatment. Interstitial implantation alone or with external-beam radiation
therapy should be considered. Consideration should be given to irradiating the
neck.
1. Lesions less than 1 centimeter in diameter may be managed by surgery alone
if the commissure is not involved. If the commissure is involved, radiation
therapy (including brachytherapy) should be considered.
2. Larger T1 lesions may be treated by surgical excision with split thickness
skin graft or radiation therapy.
1. Surgery and radiation therapy produce similar cure rates for T1 lesions.
2. In general for lesions less than 0.5 centimeters, excision alone is adequate
if there is a margin of normal mucosa between the lesion and the gingiva.
3. For larger lesions, surgery is preferred if the lesion is attached to the
periosteum, whereas radiation therapy is preferred if the lesion encroaches on
the tongue.
1. Small lesions may be treated by intraoral resection with or without a rim
resection of bone and repaired with a split thickness skin graft.
2. Radiation therapy may be used for small lesions but results are generally
better after surgery alone.
1. For early lesions without detectable bone invasion, limited resection of the
mandible is performed.
2. If limited resection is not feasible, radiation therapy may be used
initially with surgery reserved for radiation failure.
1. Most small lesions are treated by surgical resection.
2. Postoperative radiation therapy may be used if appropriate.
1. Surgery is used for smaller T2 lesions on the lower lip if simple closure
produces an acceptable cosmetic result.
2. If a reconstructive surgical procedure is required, radiation therapy has
the advantage of producing a relatively better functional and cosmetic result
with intact skin and muscle innervation.
3. Radiation therapy may include external-beam and/or interstitial techniques
as appropriate.
1. Radiation therapy is usually selected for T2 lesions that have minimal
infiltration to preserve speech and swallowing. Surgery is reserved for
patients for whom radiation treatment failed. Neck dissection may be
considered when primary brachytherapy is used.[2]
2. Deeply infiltrative lesions are best treated by surgery, radiation therapy,
or a combination of both.
1. Small T2 lesions (</= 3 centimeters) are usually treated by radiation
therapy.
2. Large T2 lesions (> 3 centimeters) may be treated by surgery, radiation
therapy, or a combination of these, if indicated. Radiation therapy is
preferred if the lesion involves the commissure. Surgery is preferred if tumor
invades the mandible or maxilla.
1. For small T2 lesions (</= 3 centimeters), surgery is preferred if the lesion
is attached to the periosteum, whereas radiation therapy is preferred if the
lesion encroaches on the tongue.
2. For large T2 lesions (> 3 centimeters), surgery and radiation therapy are
alternative methods of treatment, the choice of which depends primarily on the
expected extent of disability from surgery.
3. External-beam with or without interstitial radiation therapy should be
considered postoperatively for larger lesions.
1. Small lesions may be treated by intraoral resection with or without a rim
resection of bone and repaired with a split thickness skin graft.
2. Radiation therapy may be used for small lesions but results are generally
better after surgery alone.
1. For early lesions without detectable bone invasion, limited resection of the
mandible is performed.
2. If limited resection is not feasible, radiation therapy may be used
initially with surgery reserved for radiation failure.
Most lesions are treated by surgical resection with postoperative radiation therapy as appropriate.
Standard treatment options:
1. Surgery: a variety of surgical approaches can be used depending on the size
and location of the lesion and the needs for reconstruction.
2. 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
irradiation with or without brachytherapy.
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]
1. Minimally infiltrative lesions: external-beam radiation therapy with or
without interstitial implant.
2. Deeply infiltrative lesions: surgery with postoperative radiation
therapy.[2]
1. Radical surgical resection alone.
2. Radiation therapy alone.
3. Surgical resection + 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]
1. Surgery: rim resection plus neck dissection or partial mandibulectomy with
neck dissection as appropriate.
2. Radiation therapy: external-beam radiation therapy alone or external-beam
radiation therapy 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]
2. Clinical trials using novel radiation therapy fractionation schemas.[12]
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.
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]
2. Clinical trials using novel radiation therapy fractionation schemas.[12]
1. Superficial lesions with extensive involvement of the gingiva, hard palate,
or soft palate may be treated by radiation therapy alone.
2. Deeply invasive lesions involving bone should be treated by a combination of
surgery and radiation therapy.
1. Superficial lesions with extensive involvement of the gingiva, hard palate,
or soft palate may be treated by radiation therapy alone.
2. 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 (orbicularis oris).
Standard treatment options:
1. Radiation therapy alone or neck dissection:
1. Chemotherapy has been combined with radiation therapy in patients who have
locally advanced disease that is surgically unresectable.[8,10,13,14]
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.[15][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. However, cost, quality of life, and morbidity data were not available; there was no standard regimen; 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 2 modalities is still unresolved.[16]
Similar approaches in the patient with resectable disease, where 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.[12]
Standard treatment options for primary tumors:
1. Surgery: a variety of surgical approaches can be used depending on the size
and location of the lesion and the need for reconstruction. Treatment of both
sides of the neck is indicated for selected patients.
2. 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
irradiation with or without brachytherapy.
Treatment options under clinical evaluation:
Superfractionated radiation therapy [3]
1. Selected patients: combined surgery (total glossectomy, sometimes requiring
laryngectomy) that may be combined with postoperative radiation therapy.[4]
2. Patients with very advanced lesions: palliative radiation therapy.
1. Radical surgical resection alone.
2. Radiation therapy alone.
3. Surgical resection + radiation therapy, generally postoperative.
1. A combination of surgery and radiation therapy, generally postoperative, is
preferred.
2. For fixed nodes (equal to or >5 centimeters) preoperative radiation therapy
is preferred.
Far-advanced tumors with extensive destruction of the mandible and with nodal metastases are poorly controlled by surgery, radiation therapy, or a combination of both.
Surgical composite resection followed by postoperative radiation therapy.
Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.
Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.
Treatment options for management of lymph nodes:[5] 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 involving the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle (orbicularis oris).
Standard treatment options:
1. Radiation therapy alone or neck dissection:
1. Chemotherapy has been combined with radiation therapy in patients who
have locally advanced disease that is surgically unresectable.[6-9]
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.[10][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. However, cost, quality of life, and morbidity data were not available; there was no standard regimen; 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 2 modalities is still unresolved.[11]
Similar approaches in the patient with resectable disease, where resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.
2. Clinical trials for advanced tumors evaluating the use of chemotherapy
preoperatively, before radiation therapy, or as adjuvant therapy after surgery
are appropriate.[6,12-19]
3. Novel fractionation radiation therapy clinical trials are under clinical
evaluation.[20]
Standard treatment options:
1. If radiation therapy was used initially, surgery is the preferred treatment.
2. If surgery was used to treat the lesion initially, surgery, radiation
therapy, or a combination of these may be considered.
3. Although chemotherapy has been shown to induce responses, no increase in
survival has been demonstrated.[3]
Treatment options under clinical evaluation:
Because surgical salvage after primary treatment by radiation therapy and radiation therapy after primary surgery give poor results, clinical trials evaluating new chemotherapy drugs, chemotherapy and re-irradiation, or hyperthermia should be considered.[4,5]
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