Buccal Carcinoma Treatment & Management

Radiation therapy

A study by Giri et al indicated that in patients with buccal carcinoma who are treated with external beam radiation therapy, the disease-free and overall survival rates over time are higher in those with a greater response to treatment immediately after therapy and then 6 weeks after its completion. The study’s results also suggested that if, after 4 ½ weeks of radiation therapy (46 Gy), a patient has not experienced significant tumor size reduction, he or she will probably not benefit from a continuation of the treatment, even at higher doses. ^[5]

Radiation has a limited role as primary therapy in North America but is used as adjuvant therapy in advanced stage disease. For early T-stage disease, local-regional control and survival rates for primary radiation therapy are comparable to those for surgery. In this select group of patients, irradiation can be offered as primary treatment, particularly for those who are poor surgical candidates. The long and short-term complications associated with radiation therapy to the oral cavity, in addition to the long treatment course, make this a less desirable modality, especially when compared with the typical low complication rates and excellent treatment outcomes seen with primary surgery of small buccal cancers.

Indications for radiation or chemoradiation therapy in the postoperative setting include large or deeply invasive tumors, close or positive margins, multiple lymph nodes with metastatic cancer, lymph node extracapsular spread, and perineural invasion.

The results of using radiation therapy alone in patients with advanced buccal carcinoma have been dismal. For advanced disease, local-regional control rates and survival are highest with combined surgery and postoperative radiation or chemoradiation therapy. Radiotherapy is usually given to 50-60 Gy and begins approximately 4-6 weeks after surgery.

A dentist should be consulted before irradiation to manage any carious teeth and minimize the risk of osteoradionecrosis. Fluoride supplementation may be a useful adjunct in the prevention of dental decay.

Chemotherapy

The role of induction chemotherapy in the treatment of advanced stage head and neck squamous cell carcinoma is controversial and is often recommended for clinical trials.

Chemotherapy given concomitantly with radiation therapy for the treatment of nonoperative head and neck squamous cell carcinoma has an overall and disease-free survival rate greater than that of radiation therapy alone.

In several studies, postoperative chemoradiation offered improved loco-regional control versus postoperative radiation alone for high-risk histologic findings, including perineural invasion, close or positive surgical margins, extracapsular lymph node spread, multiple positive lymph nodes, and advanced T-stage.

Chemotherapy may also be indicated in the palliative setting for recurrent or distantly metastatic disease.

Surgery is the preferred treatment for early and advanced buccal carcinoma in North America. Patients with advanced disease should receive postoperative radiation or chemoradiation. Surgical approach depends on the size of the tumor. Small lesions can usually be treated via transoral wide local excision, whereas advanced lesions usually require excision via a cheek flap. Composite resection is indicated for mandibular invasion, while partial maxillectomy is used for superior alveolar ridge invasion. Complete resection of the tumor with negative margins confirmed by frozen section histopathology is the goal. Positive margins are associated with increased recurrence and decreased survival rates.

Metastatic neck disease (N+ disease) requires either a modified radical neck dissection or a radical neck dissection, depending on the extent of disease. Management of the clinically negative neck is controversial. Diaz et al found a 26% rate of occult nodal metastases and noted that the regional recurrence rate decreased from 25% to 10% in those receiving neck prophylaxis. ^[2] Mishra et al found that the recurrence rate in those having such prophylaxis was 29%, versus 48% for those who did not.

On the other hand, a study by Fang et al of surgically treated patients with clinical T1N0 (cT1N0) buccal squamous cell carcinoma indicated that when such individuals undergo elective neck dissection, the survival rate is no better than that for patients whose necks are managed with a wait-and-see approach. The investigators found that the 5-year disease-specific survival rates (DSS) in the study patients who underwent elective neck dissection and in those in whom the wait-and-see method was applied were both 94%. Moreover, the 5-year local-regional control rates for the dissection and wait-and-see groups were 92% and 90%, respectively. ^[6] Most authors recommend neck treatment for tumors of T2 or worse.

The goal of reconstruction is to prevent contracture in the buccal region that could interfere with function of the oral cavity. The type of reconstruction depends on the size of the surgical defect and the tissue that needs to be replaced. The tissue defect may involve the mucosa, skin, bone, or any combination of these. Reconstructive options include primary closure; healing by secondary intention; split-thickness skin graft; local flaps; regional flaps (eg, pectoralis major); or free tissue transfer (eg, radial forearm flap, anterolateral thigh flap, fibular osteocutaneous flap).

Written informed consent should be obtained after the patient is made aware of the risks and benefits of surgery. The patient should be counseled about the possible need for a tracheotomy, a nasogastric tube, or free tissue transfer for reconstruction. He or she should also be told that resection might be more extensive than the apparent size of the lesion to achieve clear margins.

Before surgery, a radiation oncologist may be consulted in anticipation of postoperative therapy. A dentist should be consulted if postoperative therapy is required so that dental extractions can be done at or before the time of surgery. An internal medicine consult may be of help if the patient has medical comorbidities. Such medical consultation is also arranged to assess the risk of a general anesthetic and surgery, as well as to optimize the patient's medical status prior to surgery. An anesthesiologist should be consulted in any case involving multiple medical issues or any concern about maintaining the patient's airway.

CT scans or MRIs should be reviewed before surgery and made available in the operating room. Small lesions may be excised with the patient under local anesthesia with sedation. However, general anesthesia is usually required.

Preoperatively, a detailed plan of securing the airway should be discussed with the anesthesiologist. For small lesions that are being treated with a transoral wide local excision, nasotracheal or orotracheal intubation may be performed. For advanced lesions, tracheotomy should be considered, especially if reconstruction is likely to cause significant intraoral swelling. The tracheotomy can usually be performed after the airway is secured with an endotracheal tube. If trismus is present, either tracheotomy under a local anesthetic or flexible fiberoptic intubation should be done.

After the airway is secured and the patient anesthetized, the oral cavity and tumor are inspected to gauge the extent of resection and plan possible reconstruction. The neck should also be examined with the patient in a relaxed state. Panendoscopy should be performed if not previously done. The patient is appropriately prepared and draped. Preoperative antibiotics should cover the flora of the upper aerodigestive tract. For long surgeries, prophylaxis against deep venous thrombosis with either subcutaneous heparin or pneumatic compression garments should be used.

Early-stage lesions

Small, easily accessible lesions of the buccal mucosa can usually be managed with a wide local excision via a transoral approach. The carcinoma can be excised with a scalpel, an electrocautery device, or a laser. Use of a general anesthetic, muscle paralysis, and a bite block or side-biting mouth gag can aid in achieving exposure.

Adequate margins of at least 1 cm should be obtained around the tumor. The depth of resection depends on the depth of tumoral invasion, which is determined by means of constant inspection and palpation during the resection. The orientation of the specimen is marked, and margins are sent for frozen section to confirm complete resection. Deep margins must also be sent for frozen section.

Small defects can be closed primarily or allowed to heal by secondary intention. A split-thickness skin graft is also an option for reconstruction; however, with large grafts, resulting contraction can interfere with function of the oral cavity. A graft obtained from the buccal fat pad, whereby the buccal fat is brought out to fill the defect, can also be an effective means of reconstructing a small-to-moderate defect.

Advanced-stage lesions

These lesions are best approached with a cheek flap and lower lip split, which provides excellent exposure of the tumor to ensure adequate resection. With mandibular invasion, composite resection can be done through a midline lip-splitting incision and segmental resection in continuity with the buccal cancer.

Free flap reconstruction with either a radial forearm flap or an anterolateral thigh flap is preferred for any mucosal defect of significant size with or without an associated skin defect. These flaps provide adequate tissue that is pliable and easily conformed to the defect, with minimal contracture. An external skin defect may be closed with a portion of the flap or with a cheek advancement flap. Bone and mucosal defects can be reconstructed with a free fibula flap.

Management of the Stensen duct

If the parotid duct is not grossly infiltrated by tumor but within the field of resection, it should be identified during resection and repositioned if possible after the procedure. The duct may be repositioned more posteriorly or incorporated into the reconstruction, whereby it is either brought out through the flap or at the junction of the flap and mucosa. A margin of the duct should be sampled and sent for analysis if any concern about tumor involvement exists. If relocation is not possible, the duct should be ligated to prevent salivary leakage. This procedure causes initial parotid swelling with eventual atrophy of the parotid gland.

Parotidectomy is usually unnecessary unless the proximal margins of the parotid duct are positive for carcinoma or unless the branches of the facial nerve branches need to be identified and preserved. If the duct or its papillae are grossly involved, tumor margins of the proximal aspect of the resected duct should be sent for frozen section. Diaz et al did not find any association among locoregional recurrence, survival, or proximity of the tumor to the Stensen duct.

Neck dissection

The N+ neck is managed with either modified radical or radical neck dissection. For the N0 neck, selective neck dissection at level I to level IV should be performed for a carcinoma of stage T2 or worse. If suspicious nodes are encountered during dissection, they should be sent for frozen section; the procedure should be changed to a more extensive neck dissection if the results are positive.

The prevascular and postvascular (facial) lymph nodes should be removed in the neck dissection. These nodes are intimately associated with the facial artery and the marginal mandibular branch of the facial nerve. The nerve must be identified and carefully dissected away from the region of the nodes to be removed.

A retrospective study by Xie et al suggested that in patients with squamous cell carcinoma of the buccal mucosa, in-continuity neck dissection leads to better disease-specific survival and regional control rates than does discontinuous neck dissection. The investigators reported that the in-continuity procedure was associated with a 5-year disease-specific survival rate of 62%, compared with 38% for discontinuous neck dissection, while the 5-year regional control rates were 81% and 54%, respectively. ^[7]

Vigilant mouth care is necessary in the postoperative period. Consultation with a speech therapist should be arranged for patients who have had extensive resection and reconstruction. Consultation with a radiation oncologist should be arranged for those in whom irradiation is indicated. For advanced disease (stage 3 or 4), postoperative radiotherapy is recommended.

Initial follow-up involves postoperative wound management. Follow-up is then scheduled as follows: every 1-3 months for the first year, every 2-4 months for the second year, every 3-6 months for the third year, then yearly after the fourth year.

Chest radiography should be performed on a yearly basis, as should thyroid function tests if the neck has been irradiated. Patients should be instructed to seek immediate care if they develop pain or have any concern of recurrence. Patients should also be encouraged to stop smoking and drinking alcohol. Routine dental follow-up is necessary in patients with dentition who received radiation as part of their treatment.

Radiation therapy

Complications of radiation therapy for buccal carcinoma are similar to those of irradiation to any site of the head and neck. Complications are best described as early/acute or late.

Early or acute complications are as follows: (1) Xerostomia may occur and be temporary or permanent. (2) Mucositis can lead to malnutrition. Appropriate pain control can aid in oral intake to maintain adequate nutrition. If malnutrition occurs, supplemental nutrition with feeding through a nasogastric or gastric tube should be considered. (3) Dysgeusia usually improves as the mucositis improves. (4) Skin reaction may be observed. (5) Wound breakdown can occur.

Late complications include xerostomia, soft tissue fibrosis, osteoradionecrosis, spinal cord myelitis, radiation-induced malignancy, and hypothyroidism.

Surgery

Surgical complications may be related to the general anesthetic or the surgical procedure. Surgical complications can be categorized as intraoperative or postoperative; the latter can be subcategorized as early or late.

Intraoperative complications include dental injury; bleeding that may require blood transfusion; injury to the facial, hypoglossal, accessory, vagus, or phrenic nerve; and chyle leak.

Early postoperative complications include medical complications, cardiopulmonary complications, wound complications, hematoma or seroma, wound infection and/or dehiscence, salivary fistula or sialocele, flap failure, sialadenitis, and airway obstruction.

Late postoperative complications include scarring (hypertrophic or keloid), poor speech and swallowing, and trismus (if scar contracture develops).

Recurrence

About 90% of recurrences occur within the first 1.5 years after treatment. Local recurrence is more common than regional recurrence. Marked heterogeneity in recurrence rates are reported in the literature due to the small number of patients in each series and the differences in the stage of tumor and the treatment studied. Reported local recurrence rates are 12-100%. In the largest published series to date, Diaz et al reported a 23% local recurrence rate and a regional recurrence rate of 11%.

Although the rates vary between studies, general similarities are observed among the factors that predict recurrence. Increased depth of invasion or tumor thickness increases the risk of locoregional recurrence. Lesions deeper than 3-4 mm are associated with a recurrence rate higher than that of tumors less than 3 mm deep. In a multivariate analysis, depth was independent risk factor and a better predictor for local recurrence than T stage, which was a poor predictor of depth. Therefore, the depth of the tumor on pathology should be considered an independent risk factor for locoregional recurrence and must be taken into account when deciding on further management such as postoperative radiation or neck management.

Other factors that increase locoregional recurrence include positive surgical margins, tumor size, and clinical stage. ^[8]  Using multivariate analysis, a retrospective study by Safi et al found evidence that lymph node ratio independently predicts whether buccal mucosa squamous cell carcinoma will recur locoregionally. ^[9]

Survival

Survival rates vary among studies. The overall reported 5-year survival rates for buccal carcinoma are between 49% and 68%. Advanced-stage diseases have higher survival rates with combined-modality therapy (surgery with postoperative radiation). Factors that decrease survival include advanced stage of disease, nodal metastases at presentation, extracapsular nodal spread, and recurrence. Nodal disease decreases survival by 50%, as it does with other cancers of the oral cavity.

Distant metastases are uncommon in buccal carcinoma. Most studies have shown low rates of distant metastases, with reports of 0-3%. When distant metastases do occur, they most commonly involve lung and bone. The incidence of a second primary lesion is similar to that of other subsites in the oral cavity, with a reported rate of 29-37%, of which more than 90% occur in the upper aerodigestive tract.

A retrospective study by Camilon et al indicated that the prognosis for buccal squamous cell carcinoma is no worse than that for other oral cavity cancers. The study, which employed a large population database, found that when unmatched data were used, the rates of overall and disease-specific survival were significantly worse for buccal squamous cell carcinoma than for other cancers of the oral cavity. However, when patients were matched according to age and tumor stage at diagnosis, treatment modality, and race, the overall and disease-specific survival rates for buccal carcinoma did not significantly differ from those for other oral cavity cancers. ^[10]