Malignant Tumors of the Mobile Tongue Treatment & Management

A number of generalities predominate as philosophic tenets of tongue malignancy management. The general beliefs are that superficial lesions are treated with single-modality therapy (eg, radiation or surgery) and that large lesions are treated with multiple modalities (eg, combined surgery and radiation). Additionally, cervical nodes are treated with either surgery or radiation therapy, and survival increases if microscopically positive nodes are present. The therapeutic decision must take into consideration the patient's age, lifestyle, and willingness to participate in the therapeutic regimen. The treatments have substantially different morbidities and may result in significant differences in quality of life.

If possible, a younger patient is treated surgically to avoid radiation therapy because of the known late adverse effects of radiation. Additionally, premature use of radiation therapy eliminates this modality from future consideration if the disease recurs. In an older patient, either modality may be chosen if the lesion is superficial and small.

Avoid using a modality that preserves greatest function but places the patient at a greater risk of local or regional recurrence.

Radiation therapy

Radiation therapy may be used as a single-modality treatment for small or superficial tongue lesions. The local control rates for T1 and T2 oral tongue cancers are similar for surgery and radiation therapy. However, radiation therapy has the advantage of preserving normal anatomy and tongue function.

Three main techniques of radiation therapy administration may be used. External beam radiotherapy using a single ipsilateral portal or bilateral-opposed portals may be selected, depending on tumor size and location, nodal status, and the possible inclusion of interstitial implants. ^[12]

A second technique is brachytherapy, whereby the tumor is treated by implanting a series of hollow needles, through which radioactive seeds are injected during the length of the treatment. ^{[13, 14]} This may be used as a single modality or can be used following a partial glossectomy with controlled frozen sections. One of the advantages of this technique is the almost direct administration of the radiation to the tumor bed. Often, this technique is used after the tumor bed has been preliminarily treated with external beam radiotherapy. Brachytherapy may result in significant tongue edema, necessitating an elective tracheotomy.

A third technique is orthovoltage radiotherapy. Most successful in cooperative patients with well-marginated and exophytic lesions, cone therapy is administered prior to external beam radiation therapy. An intraoral cone is placed against the tumor bed. Either orthovoltage or electrons may be given with equal control rates.

In early or moderately advanced tumors (ie, T1, T2, early T3), postoperative radiation therapy is considered if adverse histological features are noted in the pathology specimen of the primary tumor or the specimen from elective neck dissection.

For advanced lesions, combined treatment with surgery is advisable. Most patients initially undergo surgical resection; however, many patients have recently been treated with high-dose (therapeutic) preoperative radiation therapy with either external beam radiotherapy alone or external radiation therapy plus interstitial radiotherapy followed by surgical resection of the residual tumor. The latter technique results in a less-extensive tongue resection, hopefully without compromising the prognosis.

Radiation therapy is considered a valid option for the primary management of small oral tongue cancers in patients who refuse surgery or those who are poor surgical candidates.

Chemotherapy

The role of chemotherapy in the management of cancer of the oral tongue is still unclear. Early tumors are not treated with this modality, because of the high success of either radiation therapy or surgery. Patients who present with extensive primary lesions or with distant metastases and poor prognoses are good candidates for chemotherapy. Factors to consider if contemplating chemotherapy include stage of disease, general medical status, potential efficacy, and tolerance to adverse effects.

A newer strategy for using chemotherapeutic agents is concomitant chemoradiation. With this modality, chemotherapy is administered at the same time as radiation therapy. This approach has multiple benefits, which include synergism, radiosensitization, beneficial antiproliferative effects, possible improved locoregional control, and possible improved survival.

The ideal surgical approach to oral tongue tumors depends on the tumor size and the involvement of adjacent structures. For most small T1 and T2 lesions confined to the tongue, peroral horizontal wedge excision with primary anterior-to-posterior closure may be achieved quite easily.

With larger lesions and impaired tongue mobility, implying deep tongue infiltration or floor-of-mouth extension, a more radical approach is required. The tongue may be approached through a lateral pharyngotomy. If more exposure is necessary, a mandibulotomy may be required for access if the mandible is free of tumor. When the tumor involves or extends to the gingiva, consider resection of the mandible.

Another strategy is to use the combination of a glossectomy and brachytherapy. In this setting, controlled margins of excision are obtained, followed by the use of brachytherapy needles prior to awakening from general anesthesia. The patient is then monitored postoperatively for 48 hours, during which the radiation oncologist proceeds with the brachytherapy dosimetry and implantation of radioactive seeds for periods of up to 72 hours. The needles are then removed and the patient's recovery proceeds in-hospital until the patient meets discharge goals.

The patient's preoperative evaluation is initiated by obtaining consent for the procedure. The discussion includes the goals of the procedure, the estimated operative time, and a description of the postoperative course. This often necessitates presenting the information to family members who will assist in the patient's recovery.

The surgeon presents a detailed plan of surgical management. With smaller tumors, peroral resections may impair tongue mobility, resulting in dysphagia or speech difficulties. With larger tumors for which a mandibulotomy or a mandibulectomy is required, the patient's airway may become an issue and the physician may need to consider a tracheotomy. The goal remains to excise the tumor in its entirety from a tridimensional standpoint, including a margin of normal-looking tissue. In these settings, a preoperative assessment by a speech therapist is beneficial to the patient so that expected difficulties can be discussed.

Educate patients who present with clinical lymphadenopathy or those whose surgical plan includes a neck dissection about the procedure and about the expected difficulties, depending on which neck structures must be resected.

In more extensive procedures, advise the blood bank about the potential need for a transfusion and request that the blood bank personnel type and cross-match the appropriate number of units. Obtain autologous blood from the patient preoperatively. In most cases, to expedite surgical management, usually the patient does not have enough time to build back sufficient reserves.

Use information obtained from the preoperative evaluation under anesthesia and the radiological imaging to plan the excision. Unless the tumor is very small, general anesthesia is necessary. In patients with more complex medical problems, a preoperative evaluation by the anesthesiologist provides additional information regarding potential medical issues that may arise during the surgery.

Prophylactic antibiotics at the time of surgery are a good means of limiting the risk of infection in the perioperative period. Consider agents that cover microorganisms in the oral flora, especially anaerobes. The antibiotic dosage may depend on the patient's medical status, especially kidney function.

For peroral resections, once the patient is under general anesthesia, all the edges of the tumor are carefully visualized. Palpation of the tumor helps assess the depth of infiltration and how much of the tongue substance must be resected. The area of excision includes a 5- to 10-mm margin of normal-looking soft tissue. Perform the excision with either a scalpel blade or electrocautery. The advantage of electrocautery is that bleeding is controlled as the resection is performed. Larger vessels may need to be controlled with ligatures. Once the resection is completed, samples of the wound bed are submitted to the pathologist for frozen section and tumor clearance. Because the defects are smaller, the tongue is usually closed in multiple layers on itself from posterior to anterior.

For larger tumors (ie, T3, T4 lesions) that require a mandibulotomy, perform a tracheotomy early in the resection to allow for postoperative airway protection and care. Tracheotomy also improves the visibility of the tumor and helps define the margins of excision more precisely. If the tumor approaches or involves the gingiva, perform a mandibulectomy. McGregor and MacDonald demonstrated the mechanisms of mandibular involvement. ^{[15, 16]} In nonirradiated patients, the tumor crawls up the lingual plate and enters through the occlusal surface of both dentulous and edentulous mandibles.

If the mandibular invasion is limited, the inferolateral mandible usually remains uninvolved and marginal mandibulectomy may be performed. The lingual cortex becomes the lateral margin, with local control rates similar to those achieved with a segmental mandibulectomy. The preservation of mandibular continuity markedly improves postoperative form and function. When the mandibular invasion is through the cortex, segmental mandibulectomy and appropriate glossectomy are required, followed by postoperative radiation therapy.

Surgical reconstruction for smaller defects may be accomplished by primary closure and insertion of a skin graft. Larger defects may require a free flap. ^{[17, 18]} If limited mandibular involvement is present, a radial forearm flap provides proper bulk while not tethering the tongue to the floor of the mouth. Anterior mandibular segmental defects must be reconstructed to avoid the so-called "Andy Gump" deformity, a term coined in 1978 in a dental publication referring to the appearance of a chinless cartoon character from the early 20th century. This is best accomplished by using a fibula free flap with skin paddle, if needed. The fibula free flap has excellent bone stock that can support osseointegrated implants for dental restoration. Alternatives include a scapular or iliac crest free flap. The decision to use one or multiple microvascular and/or pedicled flaps depends on the functional status of the patient and the size of the defect.

Final wound closure is accomplished with meticulous attention to the approximation of the wound edges after adequate hemostasis is completed. Place suction drains in the wound when indicated, and use irrigation to remove small clots and debris.

Following a limited glossectomy, most patients require sufficient analgesia and may require a short course of postoperative antibiotics. Carefully examine the patient's wounds, and intensively monitor patients who underwent free flap reconstruction to assess for early flap failure. In cases in which a neck dissection is part of the surgical plan, carefully evaluate the skin flaps for wound dehiscence. Monitor the drain sites for the amount and type of drainage.

Patients usually have postoperative odynophagia as a result of tongue pain and may require energy supplementation if unable to tolerate a soft diet. In cases of extensive resections, percutaneous feedings via a nasogastric or gastrostomy tube are advisable, at least until the wound edges have had sufficient time to epithelialize.

For patients dependent on a tracheostomy, proper nursing care is necessary to prevent crust accumulation and tube obstruction. The nursing team may want to teach the patient tracheotomy tube care early in the recovery, familiarizing the patient and other caregivers with long-term care.

All patients are monitored regularly following surgery to assess wound healing, the development of complications, and for recurrence of disease. If an ulcer develops in the surgical site, perform a biopsy because of the limited morbidity associated with this procedure.

For patients with larger tumors for whom radiation therapy is part of treatment, consider early referral to a radiation therapist. Radiation therapy also may be considered for patients who are not surgical candidates but who experience disease recurrence.

For excellent patient education resources, visit eMedicineHealth's Cancer Center. Also, see eMedicineHealth's patient education article Cancer of the Mouth and Throat.

Complications may be classified by type and timing of occurrence. Early postoperative complications include collection of blood or serum under the neck flaps or site(s) of reconstruction. Drains on high suction evacuate these fluids and keep the neck flaps in close apposition for faster wound healing. Wound dehiscence may result from infection, malnutrition, poor wound healing, or tissue necrosis. Gentle handling of the tissue and meticulous wound closure may prevent this.

Proper donor and recipient site selection, perioperative use of anticoagulants, and close monitoring of the site of vascular anastomosis help prevent flap failure. Monitoring the vascular anastomoses may be difficult, and subtle changes in flow characteristics also may herald early signs of flap failure. Sometimes, signs of flap failure can be detected with the use of a portable Doppler ultrasound unit. Later changes may include an alteration in the turgor or color of the skin paddle of the flap. Early intervention by wound reexploration and revision of the vascular anastomosis may allow salvage of a failing flap.

Salivary leaks or air leakage may occur when the mucosal incisions are not well approximated, potentially leading to fistulae and wound infection. Aggressive management of fluid collections minimizes the risk of fistulization, and small collections may be aspirated. Larger accumulations require reopening the wound and irrigating and cleaning the wound surfaces, followed by packing the surgical site.

Late complications include skin or mucosal slough, exposure of the mandibulotomy site, nonunion, osteonecrosis, and fistula formation. Others include poor speech and swallowing function. If exposure of the carotid artery occurs as a result of tissue sloughing, bring in regional or distant tissue when the wound is clean to prevent carotid rupture.

Management of mandibular exposure or nonunion depends on the severity of the problem. Solutions range from local wound care in limited cases to mandibular restabilization and reconstruction if hardware is exposed.

For T1 and T2 lesions, radiotherapy using interstitial implants with or without external beam radiotherapy and surgical excision have equivalent results. The 5-year disease-free survival rate ranges from 80-90% for lesions treated with either modality. The long-term complications of radiation implants, including local necrosis and bone exposure, are more frequent than those associated with surgery. Surgery also reserves the option of radiation for the treatment of second primary lesions, which occur in up to 40% of cases. The 5-year survival rates for patients in stages III and IV are 30-50%, with lymph node metastasis decreasing the survival rate 15-30%. A 2011 study by Bonnardot et al reports that concurrent or previous diagnosis of oral lichen planus significantly increased the risk of disease-specific death and disease recurrence. In this cohort of patients, the 5-year survival rate was less than 25%. ^[19]

A retrospective study by Marra et al indicated that in patients with oral tongue squamous cell carcinoma, high cure rates can be realized through treatment with radical surgery and subsequent radiotherapy or chemoradiotherapy. However, the disease-free survival rate tends to be diminished in association with perineural invasion and extranodal extension. In the study, 106 patients (none of whom had distant metastases at baseline imaging) underwent resection, with adjuvant radiotherapy or chemoradiotherapy administered to those at particular risk of relapse. The 5-year disease-free survival rate was 87.4%, while the hazard ratios for disease recurrence in patients with extranodal extension or perineural invasion were 2.87 and 3.85, respectively. ^[20]

In a study of oral tongue squamous cell carcinoma, Zhang et al reported that in patients in whom positive margins were detected intraoperatively, immediate resection of these margins led to a local recurrence–free 3-year survival rate (92%) comparable to that of patients with negative margins (91%) and superior to that of patients with positive margins who did not undergo margin resection (73%). Invasive carcinoma/high-grade dysplasia situated less than 1 mm from the inked edge was designated as a positive margin. ^[21]

Treatment failure often occurs in the cervical lymph nodes, even for patients with an N0 neck. The incidence of occult cervical metastasis in carcinoma of the tongue correlates with the T stage. In a study from Spiro and Strong, the incidence of cervical metastasis increases progressively as the T stage advances. ^[22] Of patients with T1 cancers, 20% had occult metastases, compared to 43% and 77% of patients with stages T2 and T3 disease, respectively.

Elective radiation therapy is an option for the treatment of the N0 neck. Mendenhall et al demonstrated that elective neck radiation significantly reduces the rate of neck recurrence. Others have published conflicting studies. Meoz et al reported a 16.6% neck recurrence rate for patients receiving the traditional 50 Gy dose to the upper neck. Decroix and Ghossein reported a 14% rate of neck recurrence among 50 patients with squamous cell carcinoma of the oral tongue staged N0 who received radiation therapy.

For patients with cancer of the oral tongue, elective treatment of the N0 neck is better than no treatment. This may take the form of either radiation therapy or surgery. Radiation therapy is preferable in individuals with poor health, but it has the associated adverse effects of mucositis and xerostomia and the risk of osteoradionecrosis. Surgery appears to provide better overall cure rates and allows for pathologic evaluation of the specimen for prognostication.

To better evaluate prognosis and outcome, many studies have looked at the expression of various growth factors and tumor markers. In studying the overexpression of epidermal growth factor (EGFR) and cerb-B2, these 2 growth factors have not been found useful in predicting outcome and survival.

A study by Yu et al indicated that overexpression of the cancer-associated biomarker CD147 in combination with a high Ki-67 labeling index correlates with a poor prognosis in patients with squamous cell carcinoma of the oral tongue. ^[23]

A study by Minami et al found that in patients with oral tongue cancer who underwent surgical resection as their primary treatment, a significantly better cause-specific survival rate was experienced by those whose tumors were positive for the p16 tumor-suppressor protein than by those who were p16-negative. ^[24]

A number of issues remain controversial in the management of tongue cancer. The optimal radiation therapy schedule for managing small lesions in order to limit xerostomia, mucositis, and potential late complications (eg, osteoradionecrosis, fibrosis) is an ongoing debate. The addition of new chemotherapy agents may provide increased tumor sensitization to the radiation and may allow for dose limitation.

The management of the N0 neck continues to be a source of open debate. Because of the relatively high incidence of occult disease, the preferred treatment of these patients is either of the 2 modalities. Possibly with newer imaging techniques on the horizon, physicians will be better able to identify smaller tumor foci and the number of patients staged as N0 will decrease.

Finally, the greatest challenge remains in the field of tongue reconstruction. Numerous microvascular flaps have been described to give bulk and also sensation to the neotongue. Some even use motor reinnervation as a means to give some mobility to these tissues. Because of the complexity of integration of the intrinsic and extrinsic tongue musculature and the crucial role the tongue has in speech, taste, and deglutition, the ideal flap has yet to be identified.