Early Buccal Mucosa Cancer

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Early Buccal Mucosa Cancer JONATHAN SHUM, ANGEL BLANCO, SHAN GUO, JOANN MARRUFFO, JAMES C. MELVILLE

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uccal squamous cell carcinoma is an aggressive cancer requiring multimodal treatment due to its high rate of reoccurrence.1,2 It is relatively uncommon in North America and Western Europe, accounting for only 10% of all carcinomas of the oral cavity3 (Fig. 25.1). However, it is one of the most common forms of oral cancer in central and Southeast Asia (30%), primarily related to the popularity of chewing tobacco and betel quid (betel nut and slaked lime) in this geographic region.4 In contrast, tobacco and alcohol use are considered to be the major risk factors for buccal squamous cell carcinoma in the United States.5 Buccal carcinoma in the United States and Europe is most frequently diagnosed in individuals older than 60 years of age, whereas in studies from India and Taiwan the average age is younger than 50 years.6

Relevant Anatomy The buccal mucosa is defined by the epithelium lining the inner surface of the cheeks and lips from the line of contact of the opposing lips to the line of attachment between the alveolar ridge (upper and lower) and the pterygomandibular raphe. The buccinator muscle provides the main structural and functional component of the cheek. This muscle originates from the pterygomandibular raphe as well as from the lateral aspect of the maxillary and mandibular alveolus. The ligamentous raphe separates the buccinator from the superior constrictor muscle, and extends from the hamulus of the pterygoid to the mylohyoid ridge of the mandible. Anteriorly, the buccinator muscle extends to contribute to the orbicularis oris. Lateral to the ­buccinator is the buccal fat pad, which also extends between the masseter and temporalis muscles. The parotid duct pierces the buccinator muscle and enters the oral cavity adjacent to the second maxillary molar. The buccal mucosa contains approximately 40 cm2 of mucosal surface on each side of the oral ­vestibule. Fig. 25.2 illustrates the location of the buccal mucosa within the oral cavity. This intimate anatomic relationship between the buccal mucosa, buccinators, and buccal space allows for the potential for cancer to progress unimpeded by any anatomic 532

barriers once it penetrates the buccinator muscle. Once into the buccal space, cancer may spread to neighboring intraoral subsites and structures, such as the infratemporal fossae, external skin, and adjacent maxilla and mandible. Involvement of the maxilla, mandible, cheek skin, parotid gland, and lips leads to varied and morbid resections including through-and-through resection of the skin and composite resections of the mandible and/or maxilla resulting in complex defects. Also, tumors of the buccal mucosa may involve multiple subsites, which may lead to ambiguity of the site of origin.7

Presentation Almost half of all leukoplakias are identified on the buccal mucosa, 80.1% of which are microscopically benign and approximately 3.1% are squamous cell carcinoma.8 Due to the likelihood of benign etiology, leukoplakia of the buccal mucosa can often be ignored by dentists and attributed to trauma such as denture irritation. Buccal carcinoma often presents as an asymptomatic leukoplakia or erythroplakia, often adjacent to the retromolar trigone and third molar region. The common chief complaint for a suspected buccal carcinoma is of an intraoral mass (55%), a non-healing oral ulcer (39%), or intractable pain (28%)4

Tongue

Lip

Floor of mouth

Hard palate

Cheek

Retromolar trigone

Gum

• Fig. 25.1  Distribution of primary oral cancer sites in the mouth. (From Shah JP, Patel SJ, Singh B: Jatin Shah’s head and neck surgery and oncology. 4th ed. Philadelphia; Elsevier Mosby, 2012, p 233.)

CHAPTER 25  Early Buccal Mucosa Cancer

(Fig. 25.3). Other signs and symptoms include lymphadenopathy and trismus. Facial paralysis and skin ulceration have been reported more commonly in advanced stages, that is, T3 and T4 lesions. Dysfunction of the facial nerve indicates deep invasion through both the buccinator muscle and buccal space, and suggests perineural invasion, an adverse prognostic factor.

Lip (upper and lower) Tongue (anterior 2/3rds) Floor of mouth Gingiva (upper and lower) Buccal mucosa Retromolar trigone Hard palate

• Fig. 25.2  Regional anatomy of the oral cavity. (From Shah JP, Patel SJ, Singh B: Jatin Shah’s head and neck surgery and oncology. 4th ed. Philadelphia; Elsevier Mosby, 2012, p 232.)

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Staging The National Comprehensive Cancer Network (NCCN) outlines the criteria for tumor staging of the buccal squamous carcinoma within the section for oral cavity tumors. The identification of a biopsy proven squamous cell carcinoma should prompt a thorough head and neck examination with care to obtain the necessary information to complete an accurate staging of the cancer. The clinical examination includes a detailed description of the lesion in terms of location, dimension, texture, and associated symptoms. In terms of staging for buccal carcinoma, the T category requires the greatest dimension of the tumor and is also dependent upon the structures involved by the lesion; for example, the invasion of bone or of adjacent structures such as the external skin would upstage a tumor to T4 regardless of size. The only feature that defines T1 and T2 lesions is based on the lesion’s greatest dimension. T1 lesions are less than 2 cm in greatest dimension, and T2 lesions are greater than 2 cm but less than 4 cm in greatest dimension. Fiber-optic evaluation of the larynx and hypopharynx should be considered in the work-up of the patient with traditional risk factors such as tobacco and alcohol use. Imaging studies further enhance the accuracy of staging due to the ability to evaluate a lesion and their respective lymphatic drainage basins in the neck. Computed tomography (CT) and magnetic resonance imaging (MRI) are ideal

B • Fig. 25.3  A, Various patterns of presentation. T2 exophytic squamous cell carcinoma of the buccal mucosa. Note the raised, granular lesion arising from the buccal mucosa. B, T2 ulcerative squamous cell carcinoma of the buccal mucosa. On examination this lesion demonstrates ulceration, necrosis, and induration.

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for the work-up of T1 and T2 lesions of the buccal mucosa. These two modalities, CT and MRI, provide good soft tissue definition to interpret the dimensions and proximity to vital structures at the primary and regional sites (Fig. 25.4). Image clarity and resolution can be affected by dental hardware and restorations and in some cases can be modified by patient positioning or by the gantry tilt angle to reposition metal artifacts away from the area of interest. The imaging studies should also assess the possibility of bony invasion. Current techniques with CT, MRI, cone beam CT, and positron emission tomography/CT, have high diagnostic accuracy for detection of mandibular bone tissue invasion by squamous cell carcinoma: 83% to 94% sensitivity and 91% to 100% specificity.9 MRI is the modality of choice if no bony invasion is suspected. It allows for superior soft tissue resolution and can detect the presence of perineural spread.10 Nodal evaluation is completed by the combination of the physical examination and radiographic findings to determine the number, greatest dimension, and laterality of any suspected nodal disease.

Management Principles and Known Outcomes Squamous cell carcinoma of the buccal mucosa has traditionally been treated surgically, with postoperative therapy in the forms of radiation and/or chemotherapy reserved for high risk features such as positive or close margins, bone invasion, and late T stage, and if a neck dissection is performed, the identification of nodal disease and extracapsular extension.

• Fig. 25.4  Axial CT image of a T2 ulcerative squamous cell carcinoma of the buccal mucosa.

A review of the literature on buccal carcinoma demonstrated a predominance of studies from areas of the world where betel nut habits are endemic. These areas include Southeast Asia, with India being a predominant contributor to the current studies. Although buccal carcinoma associated with betel nut usage and cancers occurring in North America are clinically similar, they have been described to have a different molecular pathogenesis. A high-frequency of HRAS mutation is detected in Asian populations associated with betel nut chewing.11,12 Only less than 6% of HRAS mutations are identified in samples in North America.13 The tumor suppressor gene, p53, is the predominant mutation identified in the tobacco-associated oral squamous cell carcinomas in North America.14 A comparison between patients at Cancer Care Manitoba, Canada, and Tata Memorial Hospital, India, treated for buccal carcinoma revealed significant differences in 5-year overall survival and disease-free survival of 57.4% versus 80.1% and 42.9% versus 66.4%, respectively.15 Although the oncogenic pathways may differ between the two types of buccal carcinomas, Pathak and colleagues15 concluded that the significant discrepancy in the survival outcomes was due to the difference in the age of presentation and not to different biologic behavior. With regard to NCCN management of buccal squamous cell carcinoma, the initial step is the work-up and clinical staging. Following completion of the medical history and physical examination, the dimensions of the primary tumor are evaluated to determine the T stage of the lesion. T1 lesions are less than 2 cm, whereas T2 lesions are 2 to 4 cm in greatest dimension. Nodal status of N0 denotes no clinical or radiographic concern for regional metastasis. Management strategies for stages I and II include resection of the primary lesion with consideration for ipsilateral neck dissection. If contralateral nodal disease is present, a bilateral neck dissection is indicated. In an N0 scenario, T2 to T4 lesions warrant an elective neck dissection due to the increased risk for occult metastasis. Tumor thickness is the main determinant for an elective neck dissection in T1 lesions. Sentinel lymph node biopsy is an alternative to elective neck dissection for the evaluation of occult cervical metastasis, for which the reported sensitivity is 0.93 and the negative predictive values range from 0.88 to 1.16-18 The identification of tumor invasion of the buccinator muscle, Stensen’s duct involvement, skin involvement, perineural invasion, lymph node involvement, and extracapsular extension are poor prognostic features for which to consider addition of adjuvant therapy. For patients who are not candidates for initial surgical therapy, definitive radiation therapy is a viable option. Surgical intervention is the preferred initial therapy for T1 and T2 lesions at our institution. In multiple studies examining stage I and II buccal carcinoma, all cases were treated primarily with surgical intervention, with 60% to 80% undergoing a unilateral elective neck dissection and 10% to 35% receiving adjuvant radiotherapy.3,19,20 Despite aggressive initial therapy, T1 and T2 buccal carcinomas carry a poor local recurrence rate. Despite aggressive initial therapy, T1 and TE buccal carcinomas carry a poor local recurrence rate ranging from 38% to 45%.3,20,21 Five-year overall survival for T1- and T2-sized tumors was 78% and 66%, respectively.21

CHAPTER 25  Early Buccal Mucosa Cancer

Surgical Management In preparation for surgery, wide exposure is essential to avoid unnecessary contamination of the wound by unintentional dislodgment of surgical towels that outline the field. If a neck dissection is performed, landmarks of the ipsilateral mastoid tip, clavicle, and midline are necessary. Placement of a nasal endotracheal tube avoids inadvertent damage to the airway circuit and increases the working room for excision of an oral lesion. Care should be taken to ensure there is no pressure over the alar cartilage, eyes are protected, and the anesthesia circuit is padded to prevent pressure sores. Whether to use neuromuscular blockade is surgeon preference. Perioperative antibiotics are administered routinely because access is gained via a combination of transoral and transcervical approaches.22 Single and combination antibiotic regimens have been studied and recommended for head and neck oncologic surgery.22,23 Clindamycin and ampicillin-sulbactam are commonly used as sole agents; whereas, cefazolin and metronidazole are administered as a combination.24,25 Duration for antibiotic coverage is generally 24 to 48 hours after surgery.26

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a chin crease incision (McGregor), which attempts to conceal the wound around the contours of the chin. In either approach, it is beneficial to create a superficial hash mark along the vermillion border of the lip to facilitate accurate closure. A full-thickness incision through the lower lip is performed and can be extended to the mandible depending on the location of the surgical margins. Closure of the wound is in a layered fashion with care to ensure approximation of the vermillion border.

Management of the Primary Evaluation of the primary tumor includes both the clinical examination and review of imaging studies. The lesion is first outlined followed by the delineation of the resection margin

Approach Depending on the extent of the lesion, the approach to surgical resection of squamous cell carcinoma of the buccal mucosa varies. The majority of T1 and T2 lesions of the buccal mucosa can be removed via a transoral access (Fig. 25.5). Common instrumentation to augment this approach is a bite block and mouth prop to maintain the mouth open during the procedure. For buccal lesions above the occlusal plane, a WeberFerguson approach may facilitate the removal of a lesion that encroaches onto the maxillary gingiva or bony substructure. A mandibular lip split/cheek flap may also facilitate removal of a buccal lesion that incorporates the inferior half of the buccal mucosa (Figs. 25.5 and 25.6). A lip split incision may be performed for larger lesions that prevent adequate transoral visualization of the tumor. Factors such as trismus, microstomia, or posterior buccal location are indications for lip split access. The more common lip split incisions include a midline incision (Roux-Trotter) and

• Fig. 25.5  Access procedures. Left: Transoral approach. Right: Lip split exposure. (Redrawn from Hao S-P, Cheng M-H: Cancer of the buccal mucosa and retromolar trigone, Oper Tech Otolaryngol-Head Neck Surg 15:239-251, 2004.)

• Fig. 25.6  Clinical photograph of a lip split with preservation of chin pad and exposure of left squamous cell carcinoma of the buccal mucosa.

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approximately 1.5 to 2 cm around the primary tumor with care to avoid stretching the mucosa while marking the tissue. An adjunct technique for identifying the extent of lesion is the application of Lugol’s iodine. The predominant lining of the oral cavity is non-keratinizing stratified squamous epithelium, which allows for the use of Lugol’s iodine to aid in the identification of dysplastic mucosa. In the normal epithelium, the intermediate and superficial layer cells contain glycogen in their cytoplasm. Cancer and dysplastic cells contain little or no glycogen due to the increased glycolysis consequent to a dysfunctional cellular cycle.27 This observed effect of a higher rate of glycolysis relative to most normal cells is called the Warburg effect.28 Iodine is glycophilic and forms tri-iodide molecules within glycogen molecules, resulting in a brown staining of normal nonkeratinized oral mucosa. A lack of stain is observed in areas of dysplasia and carcinoma. The margins surrounding the planned resection are sent for frozen margin analysis. Care is taken to obtain a frozen margin specimen of adequate size, approximately 3 mm in width along the remaining mucosal margin surrounding the resection specimen. The tissue margin is placed on a non-adherent dressing and sent for pathology review with the mucosal surface facing upward for frozen section analysis. This assists the pathologist in the orientation of the specimen. To facilitate the removal of the mucosal margins for frozen section, the posterior margin is obtained first, followed by the anterior margins. When specimens are obtained from the anterior wound margins before the posterior margins, bleeding can be a nuisance. Several anatomic landmarks should be considered in the resection of T1 and T2 lesions, including the dentoalveolar complex of the mandible and maxilla, Stensen’s duct, buccinator, and external skin. The proximity of the tumor to adjacent bony structures, such as the dentoalveolar complex of the mandible and/or maxilla, should be examined for the presence of erosions in the cortices, which would suggest bony involvement by tumor. Of note, the erosion of the alveolar bone or tooth socket is not sufficient to classify the lesion as a T4 lesion. Medullary involvement of the mandible or erosion into the sinus is an indication for a segmental resection and/or maxillectomy. If the projected resection margin incorporated the mandible/maxillary complex, without identified gross bony involvement, it is possible to consider a marginal resection in order to maintain a 1.5- to 2-cm clear margin. Use of a marginal resection depends on the viability of residual basal bone, with mandibular bone less than 10 mm being an indication for reinforcement with a reconstruction plate. Plate thickness of 2.5 mm and greater are standard for the reconstruction and reinforcement of mandibular defects. The nerves located in this area are generally removed as part of the specimen. These can include the inferior alveolar nerve, buccal nerve, and infraorbital nerve. For lesions with erosion into the maxillary sinus, the sinus lining should be sent as a specimen. The design of a marginal resection should incorporate smooth lines, with an effort to avoid the placement of acute angles that could act as potential sites for stress/strain fractures to occur. The marginal resection will have an anterior boundary commonly requiring the extraction of teeth at the

planned osteotomy site. A horizontal osteotomy is performed below the roots of the teeth with special consideration to the amount of residual bone on the mandible. For the mandible, the posterior osteotomy generally travels through the sigmoid notch in a gentle curve. A maxillectomy may require separation of or osteotomy through the pterygoid plates to clear the posterior margin. Osteotomies can be created with a saw blade or fissure burr under copious irrigation. Following the marginal resection, sharp edges are smoothed with a burnishing burr or bone rasp to facilitate healing and closure. The extent of Stensen’s duct involvement should be considered in the tumor resection. If the resection margin violates the duct orifice without significant involvement of the length of the duct, it is possible to truncate Stensen’s duct at the resection margin and to perform a sialodochoplasty following frozen margin analysis. Sialodochoplasty allows one to reposition the duct into uninvolved mucosa. The duct can be spatulated and secured to the mucosa with a non-resorbable suture, such as 6-0 nylon. The alternative is to clip the duct and to chemo-denervate the parotid gland, for example, with Botox injections.29 Without ligation of Stensen’s duct, it is common for sialoceles to develop, which may compromise reconstruction of the resection defect and result in a salivary fistula. The buccinator muscle is a significant landmark for lesions of the buccal mucosa, in that 60% of superficial cancers that do not clinically appear to involve the muscle actually do have muscle involvement.30 T1 lesions identified as superficially invasive squamous cell carcinoma, that is, those thinner than 3 mm, have a low potential for violation of the buccinator muscle, and generally the deep surgical margin will spare the muscle. Studies have demonstrated no significant reduction in survival by preserving the buccinator when the tumor thickness does not grossly violate the submucosal layers.31 In contrast, T1 lesions more than 3 mm thick and T2 lesions should be resected to include the buccinator muscle as a deep surgical margin. It is believed that the buccinator is an anatomic barrier for the containment of cancerous cells, and the risk of local recurrence is increased when the buccinator demonstrates signs of invasion by cancer. Penetration of the buccinator potentially places cancer cells into the buccal fat pad, enabling spread via unpredictable patterns in this area that has no significant anatomic barriers. This aspect of buccal carcinoma is believed to contribute to the increased risks of local and regional recurrence. The external skin should be examined for the possibility of tumor involvement, which would manifest as induration and lack of mobility of the subcutaneous and skin layers. These features indicate the necessity for a full-thickness resection of the buccal mucosa and cheek. Lesions that encroach on 1 cm of the oral commissure risk development of microstomia because involvement of the lip results in contracture and immobility of the lip and mouth movements. The buccal artery is generally encountered for lesions of the buccal mucosa and should be ligated to prevent postoperative bleeding. Branches of the facial nerve are situated along the lateral aspect of the buccinator and effort to salvage the nerve

CHAPTER 25  Early Buccal Mucosa Cancer

may be considered if there is no dysfunction of the nerve or no suggestion of clinical tumor invasion.

Management of the Neck Management of the neck is based on the likelihood of occult metastasis in lesions staged T1 and T2. Patients with a clinically negative N0 neck are indicated for neck dissection if the primary buccal lesion is of T2 to T4 size. With T1 lesions that are less than 2 cm in greatest dimension, the most accessible predictor of occult metastasis is tumor thickness.21,32 Current literature has defined this feature to be an established predictor for occult metastasis in the oral cavity for the tongue and floor of mouth. Due to limited data on cancers of the buccal mucosa, recommendations are generally extrapolated from studies of more common subsites such as the tongue. Debate exists regarding the threshold for an elective neck dissection: lesions less than 2 mm thick are commonly observed, and lesions thicker than 4 mm are generally indicated for elective neck dissection. These thresholds vary among institutions and range from greater than 3 mm to 5 mm.21,32 Additional features with a strong association to tumor aggressiveness and propensity for occult metastatic spread include the identification of tumor budding, presence of perineural invasion, pattern of the infiltrating front, and poorly differentiated tumors.21,32-34 Patterns of lymphatic drainage that commonly filter to levels I, II, and III of the neck are well described for the oral cavity.35,36 Lesions of the buccal mucosa adhere to these described general patterns, with the addition of having predictable ipsilateral drainage and being less likely than cancers of the tongue

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to develop skip metastasis.37,38 In an N0 neck with T1 or T2 lesions, the supraomohyoid neck dissection at levels I, II, and III are commonly completed and sufficient for node sampling. The presence of nodal disease by clinical or radiographic examination would indicate the need for a selective neck dissection or modified radical neck dissection whereby structures that are not adjacent to or involved in the nodal disease are preserved. Fig. 25.7 highlights the identification of nodal disease in level Ib from an ipsilateral T2 squamous cell carcinoma. In bulky nodal disease, a radical neck dissection may be needed to remove gross disease when the internal jugular vein, spinal accessory nerve, or sternocleidomastoid muscle cannot be separated without disruption of the nodal disease.

Reconstruction Reconstruction for T1 and T2 buccal carcinoma resection defects falls into three categories that include primary closure via local flap advancement, non-vascularized grafts, and microvascular free tissue transfer. Lesions of T1 size are generally amenable to primary closure. Local regional flaps can be raised or mucosal margins undermined to obtain tension-free closure. Buccal fat pad advancement is commonly obtained because resection alone can draw out the buccal fat pad lobules. Gentle dissection and guidance can delivery the fat pad to cover areas of the buccal mucosa for wound coverage. The buccal fat pad has five lobes with a rich vascular supply for a reliable source for wound coverage. It is a delicate structure and meticulous care is required to ensure the blood supply is not disrupted or fat lobules and septae are not separated when

B • Fig. 25.7  A, Axial CT image of nodal disease associated with a T2 squamous cell carcinoma of the buccal mucosa. Arrowhead points to the level Ib regional metastasis. B, Coronal CT image of nodal disease associated with a T2 squamous cell carcinoma of the buccal mucosa. Arrowhead points to the level Ib regional metastasis.

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manipulating the tissue into the desired location. The use of the buccal fat pad as an oncologically viable reconstruction platform for buccal mucosal defects has not demonstrated an increase in local recurrence compared with alternative means of reconstruction.3 Skin grafts can be used to reline the resection wound, most commonly for superficially invasive carcinomas. Even with the loss of the buccinator muscle, the underlying buccal fat pad and/or subcutaneous tissues of the face are rich in vascular supply and collaterals and can support a graft. Common practice is to obtain a split-thickness skin graft of 0.015 to 0.018 inches, ideally from the upper thigh. This graft would be applied directly onto the wound bed and secured with chromic gut suture to eliminate dead space. A bolster is placed to ensure direct contact of the graft to underlying tissue. Microvascular free flap reconstruction is also a viable option in areas of the buccal mucosa. For T2 lesions, resections involving only soft tissue are reconstructed with fasciocutaneous or myocutaneous flaps. The radial forearm fasciocutaneous free flap would serve this purpose well in that it is a relatively thin and pliable soft tissue reconstruction that can reline the buccal mucosal defect if the buccinator muscle is removed. In reconstruction of the anterior buccal mucosa in which the commissure of the mouth is compromised, the radial forearm flap can include the harvest of the palmaris longus tendon to suspend the corner of the mouth for improved lip competence and symmetry. Alternative donor sites include lateral arm, ulnar, and anterior lateral thigh free flaps. In a mandibular discontinuity defect, the fibula osteocutaneous flap would provide bony and soft tissue reconstruction. Vascular anastomosis is commonly completed between the facial artery and vein, with the vascular pedicle delivered into the neck on the medial or lateral aspect of the mandible.

Complications Complications encountered in the resection of T1 and T2 buccal carcinomas include collateral injuries that occur as a result of cancer resection or that occur secondary to wound healing. Collateral damage can include injury to the terminal branches of the facial nerve, specifically the marginal mandibular branches, and the buccal branches. Marginal mandibular branch weakness manifests as a lack of animation for the depressor muscles of the lower lip, depressor anguli oris, depressor labii inferioris, and mentalis. The buccal branch of the facial nerve innervates the buccinator, levator labii, anguli oris, and orbicularis oris. Resection margins can also affect drainage of saliva from Stensen’s duct, accessory ducts, and the parotid gland, which may create salivary leaks, fistulae, and sialoceles. Late complications such as wound contracture of the buccal mucosa can lead to trismus if portions of the posterior buccal mucosa are resected and become fibrotic. Trismus induced by surgical fibrosis can be improved with vigorous jaw stretching and physiotherapy. Oral appliances can be used to help facilitate mouth opening. Oral incompetence and microstomia may result if the lesion involves the anterior buccal mucosa or oral commissure.

Fracture of the residual mandible may result after marginal resection if insufficient bone remains without adequate support. A reconstruction plate can reinforce residual mandible bone if the bone is less than 10 mm in height. Care is taken to design a marginal resection with curved osteotomies to avoid sharp angles in the native mandible because these are areas of stress and tension, and can propagate a fracture more readily than with curved line angles.

Radiation Therapy General Principles Radiation therapy is the therapeutic application of ionizing radiation to treat cancer by damaging the DNA necessary for cellular functions. It is an effective modality for the treatment of oral cavity carcinomas such as the location on the buccal mucosa and can be used as a single definitive treatment alone or more commonly after surgery with or without the addition of chemotherapy. With respect to T1 and T2 lesions of the buccal mucosa, radiation treatment is reserved as additional treatment following surgical resection. Indications for postoperative radiation include positive margins, bone involvement, perineural invasion, poor histologic differentiation, multiple nodal involvement, and extracapsular spread. Application of radiation therapy as initial treatment for T1 and T2 buccal cancer is reserved for patients who choose the treatment or for those who would not be able to tolerate surgical intervention because of medical comorbidities or instability. Although radiation therapy is effective, it is associated with a significant acute and late toxicity profile, including dehydration, dermatitis, fatigue, osteoradionecrosis, fibrosis, xerostomia, mucositis, dysphagia, weakness, and relative prolonged treatment time. Treatment strategies correspond to guidelines defined by the NCCN. Surgery is generally indicated as initial therapy for T1 and T2 buccal carcinomas. Indications for adjuvant therapy are dictated by the final pathologic analysis, and in the absence of adverse histopathologic features there is no requirement for radiation therapy. Adjuvant treatment in the form of postoperative radiation therapy alone is the identification of additional high-risk features, such as one positive lymph node in the absence of extracapsular spread. The presence of multiple adverse features such as extracapsular spread, positive margin, and perineural invasion would be considered for the combination of radiation therapy and chemotherapy. Re-resection is attempted if a positive margin is resectable. An ipsilateral neck dissection is completed as part of the resection in all T2 lesions and in select T1 lesions based on tumor depth. Radiation is typically completed bilaterally with a decreased dose to the contralateral site, although unilateral radiation therapy is sometimes offered. After receipt of final pathology results, it is prudent to facilitate the recovery of the patient from surgery and to ensure the wounds are adequately healed for adjuvant therapy. The overall treatment time—surgery plus indicated adjuvant treatment—should be completed in less than 100 days. Studies have demonstrated improved tumor control and survival when radiation therapy begins within 6 weeks of surgery.39,40

CHAPTER 25  Early Buccal Mucosa Cancer

Imaging for Treatment Planning and Setup Intensity modulated radiation therapy is used at the authors’ institution and in preparation for radiation therapy; mouth guards are fabricated to protect areas of the jaw or non-target tissues from collateral radiation. Planning and treatment are done with the patient in a consistent supine position; a

• Fig. 25.8  Three-dimensional representation of target volume for a primary buccal carcinoma and regional sites. Red shading outlines target zone of primary surgical bed and area of detected nodal disease.

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custom thermoplastic mask and the aforementioned mouth guard help with immobilization. The planning CT scan is conducted with intravenous contrast and using a multislice CT scanner and 2.5-mm slices. Information gathered from the final pathology report, surgeon, and preoperative and postoperative imaging is considered when the radiation oncologist completes the target volume delineation. Targeting is completed through axial CT images and three-dimensional reconstruction, and care is taken to protect vital structures in the field to limit complications associated with radiation treatment (Figs. 25.8 and 25.9). The indication for radiation therapy in T1 and T2 buccal cancers is based on the identification of high-risk factors of the primary tumor; these include close and/or positive margins, perineural invasion, lymphovascular invasion, and cellular differentiation. Following discussion by the multidisciplinary tumor board, the decision for adjuvant therapy is commonly made because buccal carcinoma is notorious for increased risk for local regional recurrence. The typical radiation dose prescribed for the postoperative bed and the dissected neck is 60 Gy (2 Gy/fraction) in 30 fractions. Low-risk sites, such as the contralateral neck, receive a minimum of 54 Gy in 30 fractions. High-risk sites, such as extracapsular spread and/or focally positive surgical margin, would receive 66 Gy in 33 fractures.41 Fig. 25.10 outlines the dose-volume histogram that summarizes radiation dose at vital structures of the head and neck. Adaptive radiotherapy is used in treatment of buccal carcinomas to provide accurate and optimal treatment delivery, in addition to limiting collateral injury during the course

• Fig. 25.9  Radiation therapy treatment planning with CT imaging. Post-resection CT images in the axial (top left), coronal (bottom left), and sagittal (bottom right) planes with outline demonstrating planned treatment dosage. Red areas will be treated with approximately 66 Gy; included is the area of the primary buccal carcinoma and associated regional lymphatic basin with nodal disease. Top right window demonstrates three-dimensional reconstruction of planned target volumes.

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of adjuvant treatment. Multiple factors can alter the anatomy upon which an initial radiotherapy plan is established. These factors include postoperative edema and fluctuations in weight. Following surgery, the surgical bed can undergo significant changes, generally involving postoperative edema followed by a reduction in edema as tissues recover. Microvascular reconstructions can place a combination of tissues into the recipient site, and the properties of those tissues dictate the amount of contraction and volume loss to be expected. For example, bone and adipose tissue generally demonstrate less significant volume loss compared with muscle. Fluctuations in weight are also a significant factor in postoperative anatomic changes because one’s diet is generally limited by access via the oral cavity and/or dependence on a percutaneous gastrostomy tube. Also, tumor response to radiotherapy leads to deviations from the initial treatment plan. These concepts have led to the practice of adaptive radiotherapy, which is generally applied to all sites of the head and neck, including buccal mucosa. Indications for replanning include greater than 10% weight loss from initial planning and immobilization issues, such as an ill-fitting radiation mask. Replanning is scheduled about halfway through treatment, in the 20- to 30-fraction period. Treatment response specifically in buccal carcinoma sites has demonstrated an apparent anterior migration of the parotid gland toward the high-dose radiation field. With adaptive radiotherapy, the amount of excess radiation to the parotid glands can be controlled and thereby reduce the effects of xerostomia.42 Without replanning, treatment sequences have been shown to significantly reduce doses to target volumes and increase doses to critical structures.43

Complications General complications associated with radiation therapy to the oral cavity include mucositis, radiation-induced fibrosis, radiation caries, osteoradionecrosis, xerostomia, radiation dermatitis, fatigue, and delayed wound healing. Radiation-induced complications more common to the buccal carcinoma include radiation-induced fibrosis leading to trismus, osteoradionecrosis, and xerostomia. A thorough oral examination should be done by a dentist and all questionable dentition should be extracted due to the significant dose of external beam radiation (>60 Gy) and associated risk for osteorradionecrosis. Patients are also fitted for fluoride trays and consulted on effects of radiation mucositis, xerostomia, and overall oral health. Radiation-induced trismus is another morbidity associated with the treatment of buccal squamous cell carcinoma. If the trismus is due to tight and resilient mucosal fibrosis in the tonsillar and/or retromolar areas (typically the pterygoid musculature), a significant increase in opening may be achieved by excising this tissue and replacing it with a viable skin paddle from either a myocutaneous or a free microvascular flap. Modest gains can be achieved with bilateral coronoidectomies or partial excisions of the fibrosis in the masseter or medial pterygoid muscles.44 An alterative to excision is the use of CO2 laser ablation of the fibrotic cicatrix. Scar bands are released and the post-laser ablation wound is manipulated with extensive physical therapy to avoid the recurrence of dense scar. Success of the procedure appears to be closely associated with compliance with physical therapy and mouth-opening exercises and less so with the type of procedure for scar lysis. Positive results have been achieved using physical therapy rehabilitation devices such as TheraBite and Dynasplint systems. At our institution we have developed a protocol of

• Fig. 25.10  Dose-volume histogram. Summary of treatment dosage to vital structures in the vicinity of a right T2 squamous cell carcinoma of the buccal mucosa.

CHAPTER 25  Early Buccal Mucosa Cancer

prophylactically performing coronoidectomies at the time of pre-radiation extractions or at initial surgery. Patients who will undergo radiation therapy are examined to have teeth with questionable prognosis extracted with particular attention given to posterior mandibular dentition. The first and second molars are commonly the site of trauma and initial osteoradionecrosis. Coronoidectomies are also performed in patients who have undergone surgery in the area of the coronoid and who will undergo radiation on the premise that the release of the temporalis attachment will reduce the amount of scarification that can occur on the temporalis.

Chemotherapy Systemic therapy can be integrated in the management of buccal mucosa squamous cell carcinoma in adjuvant, neoadjuvant, and palliative settings. In the adjuvant or postoperative setting, chemotherapy is administered with radiation after surgical resection. The survival benefit of adjuvant chemotherapy when used with radiation was demonstrated in two prospective randomized studies (RTOG 9501 and EORTC 22931).45-47 For patients with early-stage (T1/2N0M0) buccal mucosa cancer after R0 resection, the benefit of chemotherapy is not established; however, it should be considered for T2 disease with positive margins. For those patients with node-positive T1/2 buccal mucosa cancer, chemotherapy can be considered for those with adverse features that include N2/3 disease, nodal disease at level IV or V, lymphovascular invasion, perineural invasion, extracapsular extension of nodal disease, and positive margins after resection. The two subsets of patients who benefit most from the addition of chemotherapy are those with positive margins and those with evidence of extracapsular spread.46 Various chemotherapy agents with radiosensitizing properties have been used in the management of buccal mucosa squamous cell carcinoma. Among them, cisplatin is the most established and most commonly used agent. Cisplatin crosslinks DNA, which makes DNA more susceptible to radiation damage and blocks cellular DNA repair after sublethal or lethal damage. The most common potential side effects of cisplatin include nausea, tinnitus, hearing impairment, cytopenia, electrolyte imbalance, and renal insufficiency, which can all be well managed with supportive care. Carboplatin and taxanes can be used as alternatives for those who cannot tolerate cisplatin. Cetuximab, an EGFR (epidermal growth factor receptor) inhibitor, has demonstrated survival benefit when used with radiation treatment in oropharyngeal and laryngeal squamous cell carcinoma. The benefit of cetuximab in the adjuvant setting for oral cavity cancer is not well established despite its use in clinical practice due to its favorable tolerability.

Rehabilitation Prosthetic dental rehabilitation options should be addressed with the patient before surgical treatment to establish realistic patient expectations. Depending on the oral health status of each patient, the restorative dentist and the surgeon can create

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the foundation for the final prosthesis. The size of tumor and location would determine the amount of resection and type of reconstruction needed. Implants are a valuable tool that are used to aid in the retention and stability of the final restoration. Ideally, implants should be placed at the time of surgical removal of the tumor and extraction of nonrestorable teeth. However, this is not always possible because tumor removal, reconstruction, and control of disease take priority. Implant placement after radiation treatment has been linked to a reduction in functional osseointegration, which in turn increases the risk of osteoradionecrosis and the need for prophylactic treatments such as hyperbaric oxygen and pentoxifylline and vitamin E.44,48,49 Studies have shown that implants placed in bone irradiated at doses lower than 45 Gy have a higher implant success rate.50 Despite the risks associated with surgery on irradiated bone, some would consider implant placement 2 years after the completion of radiation treatment.51 Like for other carcinomas of the oral cavity, treatment of buccal carcinoma should be aimed at restoring function, esthetics, and quality of life. Maintenance of masticatory and swallowing functions, prevention of trismus, and establishing the groundwork for a prosthetic rehabilitation should be the main goals of the reconstructive surgeon. A microvascular free flap, such as a radial forearm flap or an anterolateral thigh flap, is ideal for such reconstruction, except such flaps provide too much bulk, which impedes the patient’s functions. In some cases, this is a minor problem for patients who undergo external beam radiation because the flap frequently has fibrosis and diminution of this tissue. Patients who are not candidates for external beam radiation, however, can undergo modification procedures as early as 6 months without compromising viability of the reconstruction. The use of an osteocutaneous flap, such as a fibula flap, allows the surgeon to place endosseous dental implants immediately or at a later stage. The use of traditional avascular bone grafting is another option but requires a secondary procedure and the presence of adequate well-vascularized soft tissue. The management of bulky soft tissue reconstructions, scar tissue, and decreased mouth opening encompass the most challenging issues for the restorative dentist.49 Debulking of skin paddles is necessary when excess tissue encroaches into the interarch space, which should be reserved for the final dental prosthesis. Ideally, a minimum of 8.5 mm of vertical space and 9 mm of horizontal space of denture base is required for an implant-supported overdenture with Locator attachments. An implant bar restoration requires approximately 13 to 14 mm of vertical space.52,53 The type of implant restoration should be determined before implant placement if possible. Vertical soft tissue excess overlying the native mandible or bony reconstruction also needs to be reduced to obtain a fixed keratinized tissue interface for implant placement and maintenance. It is common for soft tissue reconstructions of the buccal mucosa to obliterate the vestibule. Through a process of soft tissue ­debulking, vestibuloplasty, and placement of a split thickness skin graft or AlloDerm the area can be prepped for a dental prosthesis. Generally, the soft tissue overlying the mandible and/or fibula should be thinned to the level of the periosteum.

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PA RT I I     Site-Specific Multidisciplinary Treatment

If a bony microvascular reconstruction is placed, care is taken to be aware of the side of the vascular pedicle and to prevent inadvertent injury to the periosteum. An acrylic splint can be used to bolster a graft along an open surgical wound to guide soft tissue healing and create a vestibule. Scar release should also be considered if inadequate mouth opening is caused by scar formation. Areas of dense scar bands are located in the region of the ascending ramus and coincide with the fibers of the temporalis muscle. Palpation of the buccal soft tissues generally identifies locations of the restrictive soft tissue scars. Following scar release, aggressive postoperative jaw opening exercises facilitate the maintenance of a functional mouth opening greater than 30 mm. Devices such as the TheraBite and Dynasplint have demonstrated increased patient compliance and maintenance of functional mouth opening following the identification of postsurgical and radiation-induced trismus. Dental implants in patients who underwent resection of mandible, maxilla, or both aid in the retention and stabilization of the prosthesis. If possible the use of tools such as virtual implant planning should be used to improve the outcome of the final prosthesis. Due to the high reoccurrence rate of buccal squamous cell carcinoma, the authors advocate a prosthesis that allows for accessible visualization of the site, such as a removable implant retained denture. Also, the use of a removable prosthesis is considered most cost effective, provides for better oral hygiene, requires fewer implants, and creates better distribution of forces between implants and tissue.49 Patients with remaining dentition who receive radiation therapy should have fluoride carriers fabricated for daily fluoride treatment and be informed of overall oral health care as well as the side effects of irradiation, such as mucositis, xerostomia, increased risk for dental caries, loss of taste, trismus, and osteoradionecrosis. It is important for the patient to have frequent dental visits, at least every 4 to 6 months, after cancer treatment to address any complications that may arise due to the side effects of radiation and to reinforce the importance of oral health care. After the first year of treatment, it is common for patients to move forward with their lives and become noncompliant with oral hygiene and fluoride treatments that are vital to the overall success of treatment and quality of life.

Surveillance Among oral cavity subsites of carcinoma, the buccal carcinoma is understood to have an aggressive tendency for local and regional recurrence. Multiple studies have demonstrated a pattern for tumor recurrence within 2 years, with the majority recurring in less than 1 year of surgery.20,21,54 Furthermore, the identification of recurrence is a poor prognostic feature associated with a 50% salvage rate, which is similar to that of other sites in the oral cavity. Close surveillance is essential to the overall success. Follow-up recommendations vary by year following treatment and are defined in the NCCN guidelines. Generally, follow-up is recommended every 2 to 4 months for the first 2 years and every 6 months during the third to fifth years. Annual examinations are suggested after 5 years.

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