41 03

Eligibility criteria included patients with pathologic T3 or T4 disease (except T3/N0), or patients with any T-stage disease with two or more involved lymph nodes, or patients with T1-2 and N0-1 disease with unfavorable pathologic findings (extranodal spread, positive margins, perineural involvement, or vascular embolism). Local control, progression-free survival, and overall survival were superior for patients on the chemoradiation arm. These studies suggest that the addition of chemoradiation following surgery may be beneficial in selected patients with high-risk head and neck cancer, although with increased toxicity profiles.

Dental Care

Prior to the initiation of head and neck radiation a careful oral and dental evaluation, including a panoramic radiograph, should be performed. Dentition in poor condition should be identified and considered for extraction to minimize the subsequent risk of osteoradionecrosis. Specifically, those teeth that will reside within the high-dose radiation volume that demonstrate significant periodontal disease, advanced caries, abscess formation, or are otherwise in a state of disrepair should be extracted. In addition, impacted teeth, unopposed teeth, and teeth that could potentially oppose a segment of a resected jawbone should be considered for extraction if they are anticipated to reside within the high-dose radiation treatment volume. Extraction of marginal teeth should also be considered in patients who are deemed unable to maintain adequate oral hygiene.
Radiation can induce several chronic effects in the oral cavity that warrant routine surveillance. Radiation can impair bone healing and diminish the capacity for successful recovery following trauma or oral surgery. For this reason, elective oral surgical procedures including extractions must be very carefully considered after radiation. Escalation of dental caries deriving from xerostomia following radiation is well recognized (Fig. 41.21). Radiation of the major salivary glands changes the nature of salivary secretions (121), which can increase the


accumulation of plaque and debris, reduce salivary pH, and reduce the buffering ability of saliva (55). This creates an environment in the oral cavity, which predisposes patients to caries. During a course of radiation to the oral cavity, simple techniques such as the use of custom molds to absorb electron backscatter can diminish hot-spot mucositis from dental fillings and improve treatment tolerance (Fig. 41.22). Attention to oral hygiene with frequent dental follow-up examinations and cleanings, daily fluoride therapy (Fig. 41.23), flossing, and brushing should be an integral component of the education and postradiation care of patients who undergo radiation to the oral cavity.

Prognostic and Predictive Factors
The most significant prognostic factor for outcome in oral cavity carcinoma is the presence of cervical metastases (81). In patients with positive cervical metastases the 5-year survival is reduced by approximately 50% from that in the absence of metastases (53). The prognosis diminishes further when patients harbor multiple levels of nodal involvement or extracapsular extension (ECE). In a retrospective review, Myers et al. (81) found that 5-year disease-specific and overall survival rates for pathologically N0 patients were 88% and 75%, respectively; these decreased to 65% and 50%, respectively, if patients were node positive but without evidence of ECE. Patients who were node positive with evidence of ECE had 5-year disease-specific and overall survival rates of 48% and 30%, respec-tively.
Several histopathologic factors in the primary lesion are associated with adverse prognosis. Tumor thickness and depth of invasion have been shown to confer a higher risk of regional metastases (18). Perineural invasion has been correlated with cervical lymph node metastases, extracapsular extension, and diminished survival (8,35,105). Microvascular invasion has also been correlated significantly with cervical lymph node metastases (19,67). However, lymphatic invasion has not been correlated significantly with cervical lymph node invasion (18). L '


prognostic significance of grade has also been evaluated (3). Because of the wide variation in pathologic interpretation, it is difficult to discern the independent value of histologic grading as a prognostic or predictive value (18).

Subsite-Specific Treatment and Results
Labbro
Early stage carcinoma of the lip can be managed with surgery or radiation therapy. However, surgery is generally preferred for small tumors (<2 cm). Although the local control of T1 and T2 squamous cancers of the lip is excellent with surgical resection, disruption of the oral sphincter provided by the orbicularis muscle can lead to oral incompetence if not properly reconstructed. Therefore, a number of reconstructive methods have been developed to help preserve oral sphincteric function even following large excisions for T3 and T4 lesions. For these larger lesions, surgery followed by radiotherapy remains a standard therapy.
When primary radiotherapy is used to treat lip cancer, the target volume should include the primary tumor plus a 1.5- to 2-cm margin. For early stage lesions, photons in the orthovoltage range (100 to 200 keV) or electrons may be used. The electron energy should be chosen based on the thickness of the lesion (commonly 6 to 9 MeV). Effort should be made to shield the underlying gum, dentition, and mandible as appropriate. This can be accomplished with the use of oral shields or cerrobend stents. The recommended dose is 50 Gy in 4.5 to 5 weeks for smaller lesions and 60 Gy in 5 to 6 weeks for larger lesions. Some institutions have used an approach where external beam radiation is given to approximately 40 to 50 Gy followed by a brachytherapy boost, or smaller lesions are treated by primary brachytherapy alone. An important consideration in managing lip cancer is the risk of regional metastatic disease. Generally, the risk of regional lymph node metastatic disease for T1 and T2 cancers of the lip is lower than for stage-matched tumors of other oral cavity sites. Thus, elective neck dissection is recommended for patients with T3 and T4 carcinomas of the lip; however, it may not be warranted for all T1 and T2 lesions. Some institutions have used a “moustache field” for elective irradiation of the perifacial lymphatics (approximately 50 Gy) for more advanced upper lip lesions (2). Sentinel lymph node biopsy may prove to be useful in the management of patients of node-negative lip cancers, but further clinical investigation in this area is needed.
Oral Tongue
Although primary radiation therapy and surgery are potential treatment options for carcinoma of the oral tongue, most oral tongue cancers in the United States are treated surgically (18). Surgical resection and reconstruction as appropriate is generally preferred for medically operable patients. Postoperative radiation therapy is recommended for patients with large primary tumors (T3, T4), close or positive surgical margins, evidence of perineural spread, multiple positive nodes, or extracapsular extension (2). Postoperative chemoradiation should be considered for patients with adverse risk factors who are able to tolerate combined modality treatment (7,21). Primary radiotherapy techniques can be used for patients who refuse or are unable to tolerate surgery.
Superficial T1 lesions can be treated with brachytherapy alone. Commonly, 192Ir temporary implants are used to deliver 50 to 60 Gy with dose rates of 40 to 60 cGy per hour. For infiltrating T1 or T2 lesions, a combined approach using external beam and a brachytherapy or intraoral cone boost should be considered. More advanced lesions should be treated with an approach combining surgery and radiation therapy. Postoperative treatment should include the site of primary tumor, dissected neck, and draining lymphatics. Opposing lateral fields are used to encompass the tongue and upper neck bilaterally, and this volume should be treated to 50 to 54 Gy (see Fig. 41.12A and Table 41.1). High-risk areas (primary surgical bed, positive/close margins, extracapsular extension, perineural spread) should receive additional boost treatment up to 60 to 66 Gy.
Surgical approaches to oral tongue cancers can either be transoral, transcervical, or alternatively via mandibulectomy to obtain the exposure necessary to achieve adequate margins. Partial glossectomy is the most common procedure performed for oral tongue cancers, and the extent of resection depends on the size and growth pattern of the tumor, as some lesions are relatively infiltrative while others may be more exophytic. Since the tongue is essentially comprised of skeletal muscle covered by mucosa, the tissue is extremely elastic, and wide margins are encouraged at the onset of resection to avoid retraction of muscle fibers with microscopic tumor cells that could serve as a source of local recurrence.
Total glossectomy may be indicated for extensive tumors or those that involve the intrinsic tongue musculature. Total glossectomy, even with reconstruction, can result in difficulty with deglutition and maintenance of an adequate airway. Aspiration may be a chronic problem, and, thus, laryngectomy may be necessary in some cases. However, properly selected patients with adequate postoperative rehabilitation can be treated with total glossectomy without laryngectomy. If the larynx is preserved, laryngeal suspension and palatal augmentation may help with the rehabilitative efforts.
Tumor size and depth of invasion are currently the most reliable indicators for predicting cervical metastases in patients with oral tongue squamous-cell carcinoma. Because of the high risk of nodal metastases the neck should be addressed either with surgery or radiation in all but the earliest tumors of the oral tongue. Patients with small oral tongue cancers should be considered for neck therapy, particularly if the primary tumor exhibits extension onto the floor of mouth or there is increased tumor thickness. Treatment of the clinically negative neck is most often accomplished by supraomohyoid neck dissection. Elective neck dissection appears to result in better overall cancer outcome than observation. Potential pitfalls of observation include a salvage rate of only one-third for patients who do not undergo elective neck dissection along with resection of the oral cavity primary. For patients with a clinically and radiographically N0 neck, with well-lateralized disease, or those who do not undergo neck dissection, 50 to 54 Gy should be considered to the ipsilateral neck as elective nodal irradiation (Fig. 41.16).


Patients with advanced lesions and high-risk disease (particularly with multiple positive nodes) should receive radiation treatment to the bilateral neck.
Pavimento della bocca
Early stage floor of the mouth cancer can be treated effectively by radiation therapy or surgery. However, surgery is usually preferred in patients who are medically operable because proximity of the tumor to the mandible confers a significant risk of radiation-induced ulceration and osteoradionecrosis. Small lesions of the floor of the mouth are most commonly resected transorally. The surgical defect can be left to heal by granulation or reconstructed with a split thickness skin graft or local flap. Advanced stage floor of the mouth cancers are usually managed by a combination of surgery and radiation or chemoradiation.
Small (T1 and T2) lesions may be treated with a combination of external beam radiation and boost with interstitial implant or intraoral cone. For lesions that are very close to the mandible, brachytherapy is contraindicated because of the risk of osteoradionecrosis. Infiltrative lesions that are tethered to the mandible and advanced lesions following surgical resection should receive postoperative radiation. Portals for postoperative treatment are similar to that for oral tongue carcinoma. Opposing lateral fields are used to encompass the oral cavity tumor bed and upper neck bilaterally, and this volume is commonly treated to 50 to 54 Gy. High-risk areas (primary surgical bed, positive/close margins, extracapsular extension, perineural spread) may receive additional boost treatment up to 60 to 66 Gy.
In the surgical management of floor of the mouth cancer, special attention should be paid to mandibular invasion. A cancer that appears to involve only the periosteum or that only superficially invades the mandible can be removed via a transoral or transcervical approach in which a marginal mandibulectomy is performed. However, segmental mandibulectomy may be necessary for patients with a limited mandibular height when there is no direct bone invasion, because marginal mandibulectomy may leave these patients with insufficient bone, placing them at high risk for radionecrosis or pathologic fracture. A full thickness segmental resection may be necessary if there is frank bone invasion. For advanced cancers, resection of the anterior arch of the mandible may be necessary. Defects of the anterior segment of the mandible require reconstruction with bone, usually with a free fibular or iliac crest graft.
Management of the neck is similar to that for other tumors of the oral cavity. Patients with lesions <2-mm thick with no adverse pathologic factors and a clinically and radiographically negative neck may be observed after primary resection and observation. Otherwise most N0 patients should receive either selective neck dissection or radiation therapy. Patients with advanced lesions and high-risk disease (particularly with multiple positive nodes) should receive radiation treatment to bilateral necks.
Hard Palate and Upper Alveolar Ridge
Tumors of the hard palate are quite rare, accounting for only 0.5% of all oral cancers in the United States. Most carcinomas manifest as a granular superficial ulceration of the hard palate. Initial growth tends to be superficial, although these tumors can extend through the periosteum of bone into regions adjacent to the oral cavity, such as the paranasal sinuses and floor of the nose. Although radiation can be used to treat carcinomas of this site, surgery is preferred. Postoperative radiation therapy should be delivered when there are adverse features; that is, close/positive margins, perineural extension, vascular invasion, high-grade histology, multiple positive nodes, or extracapsular extension. The radiation field should encompass the entire surgical bed. In most cases it is necessary to treat with opposed lateral fields to cover the volume at risk. However, for well-lateralized lesions of the upper alveolar ridge, ipsilateral radiation with a wedge pair may be adequate. Conformal treatment techniques can also be used to tailor the radiation coverage to the high-risk tissue bed and draining lymphatics as appropriate.
Wide local excision may be adequate to obtain surgical margins. However, infrastructure maxillectomy may in some cases be necessary. For tumors that extensively involve the adjacent bony and soft tissue structures a total maxillectomy, with or without orbital exenteration, may be required. A defect in the maxilla results in lack of oral/nasal separation that can impair the ability to speak and swallow effectively. An obturator with or without a skin graft is the most common method used to restore oral/nasal separation. The obturator is commonly fabricated from a synthetic polymer and provides oronasal separation that can yield improved speech and swallowing function. Regional pedicled flaps and free-tissue transfers may provide alternatives to obturation. However, their use is somewhat controversial for reconstruction of palatal defects since these nonremovable flaps may mask local recurrences that can be more readily identified in patients whose defects are obturated.
Elective treatment of the neck is controversial for hard palate region tumors. Although some series have shown lower rates of occult metastases for palatal tumors when compared to other oral cavity sites, preoperative imaging should be performed to evaluate for the presence of metastases to the retropharyngeal nodes since these are difficult to evaluate on clinical examination and are at some risk for spread from primary palatal tumors.
Retromolare trigono
Squamous-cell carcinoma of the retromolar trigone is uncommon, and the true incidence is difficult to determine since these cancers often involve both the retromolar trigone and adjacent sites, thereby making it difficult in some cases to identify the original tumor epicenter. Cancers of the retromolar trigone may be advanced at presentation because only a thin layer of soft tissue overlies the bone in this region and invasion of the underlying bone may occur early. In addition, there are multiple pathways for spread from this site including the buccal mucosa, tonsillar fossa, glossopharyngeal sulcus, floor of the mouth, base of the tongue, hard and soft palate, masticator space, and maxillary tuberosity. As patients tend to present with advanced disease of the retromolar trigone, many have regional metastases at the time of presentation.
Early stage T1 and T2 cancers can be treated equally effectively with surgery or radiation with primary control rates for T1 and T2 tumors of 92% and 88%, respectively. For more extensive superficial lesions that extend to involve the soft palate or tonsillar complex but do not invade bone, radiotherapy may be a better treatment option, since broad resection of the palate can result in poor speech and swallow outcomes. Well-lateralized lesions of the retromolar trigone can be treated by ipsilateral mixed beam techniques or angled wedge techniques.
Stage III and IV lesions commonly require combined surgery and radiation. The resection of advanced cancer of the retromolar trigone usually requires a composite resection of soft tissue and bone. A limiting factor for the achievement of adequate surgical resection margins for tumors in this area includes extension of tumor posterosuperiorly into the pterygopalatine fossa and into the base of skull.
Mucosa buccale
Verrucous carcinoma accounts for <5% of all oral cavity carcinomas, occurs most often in the buccal mucosa, has a more


favorable prognosis, and is considered a low-grade malignancy. Surgical resection remains the preferred mode of treatment for primary lesions of the buccal mucosa. Adjuvant radiation treatment is usually not indicated. Since verrucous carcinomas rarely metastasize, elective neck dissection is often not indicated for patients with this disease. Careful pathology review with clinical correlation is important in the categorization of verrucous carcinomas, as this diagnosis can influence subsequent treatment recommendations.
Squamous-cell carcinoma of the buccal mucosa can be an especially aggressive cancer of the oral cavity, as buccal cancers have multiple potential routes of spread to adjacent areas in the head and neck. Posteriorly, they can extend to involve the pterygoid muscles, and superiorly, they can grow to involve the alveolar ridge, palate, or maxillary sinus. The majority of patients have cancer that extends beyond the buccal mucosa. Metastasis to the cervical lymph nodes most commonly affects the submandibular nodes.
T1 and T2 tumors of the buccal mucosa can be managed with equal effectiveness by either surgery or radiation. Transoral resection is preferred and is most convenient for small lesions. Tumors approximating the gingiva should be resected with the gingiva and periosteum as an additional deep margin, while those that involve the periosteum should be resected with an additional deep margin of bone. Cancers that directly invade bone should be resected with a segment of bone. Larger tumors (T3 or T4) may require surgery combined with radiation therapy.
Management of Recurrent Disease
The appropriate management of recurrent oral cavity cancer depends largely on the extent of disease, the prior therapy administered, and whether the recurrences are local, regional, or both. Obviously, if there is distant disease recurrence, systemic therapy approaches will likely assume primary importance. In the case of small recurrences at the primary site for patients treated with primary excision only, further excision with or without postoperative radiotherapy is often recommended. For larger recurrences in patients who received radiation as part of their initial management, the rate of surgical salvage is quite low. In some cases, further resection may be considered for palliation or curative treatment attempt, particularly in the setting of a clinical trial. Systemic therapy, reirradiation, and palliative care are other options for this group of patients, and the risks and benefits of each should be discussed with the individual patient.