Surgery Alone

Surgical resection of the primary lesion, either with laser or by intraoral conventional resection, is the treatment of choice for many T₁ lesions of the lip, tongue, and floor of the mouth. This is often accompanied by a neck dissection, either supraomohyoid or comprehensive. Some early T₂ tumors may also be treated by surgery alone, but a neck dissection must be added.

Radiotherapy Alone

Tumors classified as T₁ and select early T₂ tumors can be treated with radiation alone. Lesions of the lip and floor of the mouth can be treated by external-beam radiotherapy, brachytherapy, or both. Oral tongue lesions do not respond well to external-beam radiotherapy; therefore, surgery is probably the better treatment modality with brachytherapy or peroral cone plus external-beam therapy as alternatives.

Combined Radiotherapy and Surgery

For locally advanced carcinomas, radiotherapy combined with surgery achieves optimal results. Combination therapy is indicated when the primary lesions are large, deeply infiltrative, or necrotic; when there is bone invasion or deep muscle infiltration; when cervical lymph node metastases are present; when there is invasion of the soft tissues in the neck; and when there is known residual disease beyond the margins of resection. Even T₁ lesions may require postoperative treatment if tumor invasion is deep, despite the presence of negative margins. It is strongly recommended that the radiation oncologist review all slides with the pathologist to determine whether adjuvant radiotherapy is indicated. The selection of patients and the planning of the combined treatment should be done jointly by the radiation oncologist and the head and neck surgeon.

Combined Chemotherapy and Radiotherapy for Locoregionally Advanced Disease

Chemotherapy has been combined with radiotherapy in the management of patients with unresectable OCC with the goals of increasing local control and survival as well as decreasing distant metastases. The chemotherapeutic agents most commonly used include cisplatin, paclitaxel (Taxol), fluorouracil (5-FU), methotrexate, and bleomycin. Except for one randomized study reported by Lo and colleagues, which showed increased survival in patients with oral cavity lesions receiving 5-FU concurrently with radiotherapy as compared with patients receiving radiotherapy alone,¹⁴ there has been no definitive evidence for improved local control or survival in oral cancer when single-agent chemotherapy is combined with radiotherapy. Two recent randomized studies examined multiagent chemotherapy with consolidative chemoradiation in the treatment of locoregionally advanced head and neck cancer, comparing regimens of cisplatin, 5-FU, and docetaxel with cisplatin and 5-FU alone. One study found improved progression-free survival and overall survival,¹⁵ while the other study demonstrated improved locoregional control and overall survival.¹⁶ Enhanced radiation mucositis has been commonly observed with concurrent drug and radiation administration, especially when 5-FU is given concurrently with radiation.

Targeted agents are also being used to further improve outcomes. A study by Bonner and colleagues compared patients with advanced head and neck malignancies who were treated with radiation therapy alone versus radiation therapy with cetuximab, and found a median overall survival of 23 months in the control group and 49 months in the experimental arm, changing the treatment approach for patients with advanced disease and creating a pathway for the study of other targeted biologic agents in this disease.¹⁷

Postoperative Radiotherapy

The aims of postoperative radiotherapy are (1) to prevent local recurrence when there is known residual gross or microscopical disease after surgery, (2) to prevent recurrence in the neck when there are large or multiple lymph node metastases and tumor invasion of the soft tissues in the neck, and (3) to control occult disease in the cervical lymph nodes that were not resected surgically.¹⁸ When radiotherapy is given postoperatively, usually a dose of 60 to 66.6 Gy is delivered in 1.8- to 2.0-Gy daily fractions, five fractions a week, to the primary site and involved neck areas. The clinically and pathologically uninvolved neck areas receive 54 Gy.¹⁹ It is generally believed that tumor cells trapped in the surgical scars are less well oxygenated and therefore more radioresistant, and that higher radiation doses are required to eradicate them than are required preoperatively. However, this belief has not been adequately tested. Apparent differences in doses required preoperatively and postoperatively may be due to proliferation of tumor cells in the postoperative period before radiotherapy starts. The volume that is irradiated should include the entire surgical bed and the entire neck. Postoperative radiotherapy can be started as soon as wound healing is complete, usually within 2 to 3 weeks after surgery.

Postoperative Chemotherapy and Radiation

Much of the shift in treatment paradigm over the past several years in the management of OCC has arisen from multiple studies assessing when a postoperative chemoradiation approach achieves better outcomes than postoperative radiation alone. The landmark studies of the Radiation Therapy Oncology Group (RTOG) 9501 and the European Organisation for Research and Treatment of Cancer (EORTC) 22931, followed by the comparative analysis of Bernier and colleagues, demonstrated that all patients with resected head and neck cancer receiving standard fractionated postoperative radiation who are found to have positive margins or extranodal extension should be assigned to a combined chemoradiation approach using concurrent cisplatin (100 mg/m² on days 1, 22, and 43).^20–22 More recently, the German Cancer Society 95-06 trial²³ demonstrated that even with hyperfractionated accelerated treatment regimens, patients that received concurrent 5-FU and mitomycin experienced an improvement in locoregional control and overall survival. Finally, a study by Garden and colleagues examined patients with stage III and IV disease who received a concomitant boost treatment regimen and cisplatin on days 1 and 22, and found that 4-year locoregional progression-free survival was 74% and that 4-year overall survival was 54%—results which are quite promising.²⁴ Clearly, the ideal chemotherapeutic regimen in the postoperative setting has not yet been fully elucidated.

Megavoltage External-Beam Radiotherapy

Megavoltage external-beam radiotherapy in combination with surgery or interstitial brachytherapy is the most frequently used radiotherapy technique in the treatment of carcinoma of the oral cavity. Megavoltage beams with an energy range between 4 and 6 MV, having a maximum dose at about 1 to 1.5 cm below the skin surface, are most suitable. When higher energy beams (>4 MV) are used, bolus material may be necessary to bring the maximum dose closer to the skin surface to adequately treat superficial lymph nodes and surgical scars.

The treatment volume encompassing the primary tumor with adequate margins and cervical lymph nodes of concern is outlined on the treatment simulation films, the skin, or on the relevant imaging slices in the case of IMRT or in 3-D conformal therapy (CT, MRI, or PET scan). When conventional techniques are used, metallic wires, gold seeds, or silver clips placed in the tumor periphery are helpful in localizing the tumor volume on the simulation films. Normal tissues that are in the field but need not be irradiated are shielded with either mounted lead blocks or multileaf collimators. Examples of treatment of an advanced carcinoma of the tongue are shown in Figs. 29-4 to 29-6. Weekly port films are obtained with the patient on the treatment machine to verify the actual volume irradiated. All fields are treated daily. The usual dose fractionation is 1.8 to 2 Gy per day, with five daily treatments per week. The total dose depends on the extent of the disease and whether external-beam radiotherapy is used alone or in combination with interstitial radiotherapy or surgery. When definitive external-beam alone is used, the total dose is usually in the range of 70 to 74 Gy. The spinal cord is either shielded after 44 Gy or constrained in the radiation plan to a dose of 45 Gy or less.

FIGURE 29-5 • A, Simulation film of lateral port for tongue carcinoma. B, Portal film of lateral port.

FIGURE 29-6 • A, Simulation film of anterior port for supraclavicular and low neck treatment. B, Portal film of anterior port.

Peroral Cone Radiotherapy

Intraoral cone radiotherapy using 100 to 250 kVp x-rays or 6 meV electron beams is suitable for the treatment of select small lesions, less than 3 cm in diameter, in the floor of the mouth. For the proper administration of this radiotherapy modality, it is necessary that adequate coverage of the lesion is achieved with the intraoral cone and that patient immobilization be maintained during treatment. The use of a special immobilizing chair that locks the patient and applicator in a rigid unit is advised for orthovoltage treatment, as shown in Fig. 29-7. The analysis by Phillips on the time-dose relationships in peroral radiotherapy for oral cancer suggests that surface doses between 55 Gy in 18 days and 60 Gy in 26 days will result in good control rates with acceptable risk of soft-tissue or bone necrosis.¹⁹ Wang has described a technique for using peroral cones with electron beams (Fig. 29-8).²⁵

FIGURE 29-7 • Peroral cone for orthovoltage with treatment chair.

(From Phillips TL: Peroral roentgen therapy, Radiology 90:525, 1968.)

FIGURE 29-8 • Electron beam peroral cone set up at Massachusetts General Hospital.

(From Wang CC: Technical and radiotherapeutic considerations of intra-oral cone electron beam radiation therapy for head and neck cancer, Semin Radiat Oncol 2:171, 1992.)

The advantages of peroral radiotherapy over interstitial radiotherapy or external-beam radiotherapy in properly selected patients are as follows: (1) only a small volume is irradiated and salivary gland function is therefore preserved and late dental problems avoided, (2) no hospitalization or anesthetics are necessary, and (3) the risk of bone necrosis is minimal.

Peroral radiotherapy can also be used in combination with external-beam radiotherapy to deliver a boost dose to lesions that are marginally encompassed by an intraoral cone. The boost should be given before the external-beam treatment and is usually 21 to 27 Gy in 3-Gy fractions.

Brachytherapy

Interstitial radiotherapy, either alone or in combination with external-beam radiotherapy, is used for selected cases in the treatment of carcinoma of the oral tongue, floor of the mouth, and buccal mucosa.^26,27 Radioactive isotopes that have been used in the past in interstitial radiotherapy of oral carcinomas include radium-226, cesium-137, gold-198, and tantalum-182. Iridium-192 used in the form of pins (epingles), wires, or seeds preloaded in a plastic ribbon have the advantage of being suitable for afterloading techniques, and thus is used commonly for temporary implants. Iodine-125 may be substituted and is the isotope of choice for permanent implants. The use of remote afterloading of iridium sources with high-dose rate (HDR) is replacing the use of hand-loaded seeds in ribbons in most institutions. These techniques minimize exposure to personnel and allow optimization of dose distribution.²⁸

When the tumor thickness is 1 cm or less, a single-plane implant is adequate. When the tumor thickness is greater than 1 cm, then a double-plane implant or volume implant is necessary to deliver a relatively uniform dose to the tumor volume. The Patterson-Parker or Quimby tables are often used for treatment planning; however, dosimetry is best done by a computer using localization films of the actual implant.^29,30

When interstitial radiotherapy is used alone for patients who present with early-staged T₁ to T₂-N₀ disease, the usual implant dose is 60 to 70 Gy delivered over a period of 6 to 7 days.^31,32 For oral tongue lesions, if a combination of external-beam radiotherapy and interstitial implant is considered, several series have reported on the importance of adequate interstitial implant dose. The total implant dose is correlated with local control. Those patients who received an external-beam dose less than 40 Gy along with a higher brachytherapy dose achieved higher local control rates than those who received a lower brachytherapy dose.^33–36 If the patients have neck disease, surgery with or without postoperative radiotherapy is recommended over radiotherapy alone.

No adjustment of total dose is made when the dose rate of the minimum tumor dose is between 30 and 60 cGy per hour.³⁵ Examples of a single-plane iridium implant and a volume iridium implant and the isodose distributions are shown in Figs. 29-9 and 29-10.

FIGURE 29-9 • A, Carcinoma of the right oral tongue before brachytherapy. B, Double-plane implant for T₂ squamous cell cancer of oral tongue—lateral and anterior-posterior radiographs. C, Appearance of tongue 1 year after implant. Note normal saliva and intact teeth. D, Isodose plot of the double-plane implant.

FIGURE 29-10 • A, T₃ carcinoma of the floor of mouth before brachytherapy. B, Lateral view of volume implant with iridium-192. C, Anterior view of volume implant. D, Isodose plot of volume implant. E, Appearance of floor of mouth 1 year after implant.

Surface mold radiotherapy can be used as a primary treatment for select initial or recurrent superficial lesions of the hard palate, lower gingiva, and floor of the mouth. An impression is usually made of the surface to be irradiated and a mold in the form of a partial dental plate is made of dental plaster. After distribution of radioactive isotopes has been outlined, iridium seeds, wires, or tubes for HDR treatment can be inserted into the predrilled holes or grooves in the mold and sealed with dental plaster. Treatment can be carried out on an outpatient basis with the patient wearing the surface mold several hours a day, or the patient can be admitted into the hospital and wear the surface mold for most of the day except during mealtimes. HDR remote afterloading with fractionated delivery may be used with surface molds. Surface mold radiotherapy is not adequate for lesions greater than 1 cm in depth.

Clinical Presentation

Second to the skin, carcinoma of the lip is the most common cancer of the head and neck. In the United States, lip cancer accounts for 12.7 per 100,000 annually.³⁷ It is rare among blacks and Asians, and accounts for approximately 25% of all carcinomas of the oral cavity. Approximately 90% of the carcinomas of the lip arise from the lower lip. Elderly men are affected most frequently, particularly in the sixth and seventh decades. The incidence rates are generally stable or falling among men worldwide, but are rising among many female populations.³⁸ Chronic exposure to sunlight appears to be a predisposing factor, as carcinoma of the lip occurs most frequently in light-complected, fair-skinned persons who work outdoors.³⁹ Other possible causal factors are tobacco smoking and viruses.

The majority of carcinomas of the lower lip are moderately to well-differentiated squamous cell carcinomas. Basal cell carcinomas make up the majority of upper lip lesions.⁴⁰ Basal cell carcinomas arising from the skin that invade the lips secondarily should be considered carcinomas of the skin.

Carcinoma of the lower lip frequently presents as a thickening of the mucous membrane. Later, desquamation and ulceration that does not heal may develop. There may be a history of long-standing keratosis or leukoplakia.⁴¹

Routes of Spread

Carcinoma of the lip tends to be localized. It usually spreads by direct invasion of the surrounding soft tissue, skin, and bone, and infrequently metastasizes to regional lymph nodes.⁴² The incidence of lymph node metastasis varies with the extent of the primary lesion. The average incidence of regional lymph node metastasis is approximately 3% to 8% on presentation, and approximately an equal proportion of patients develop cervical lymph node metastasis subsequent to treatment of the primary lesion. There is a rare incidence of perineural spread, often into the mandibular canal.⁴³

Lymph node metastasis from carcinoma of the lower lip most frequently involves the ipsilateral prevascular submandibular nodes. Carcinoma arising near the midline of the lower lip usually metastasizes to the submental lymph nodes. Carcinoma at or near the commissure may rarely metastasize to the facial nodes within the substance of the cheek. Carcinoma of the upper lip may metastasize directly to the upper cervical, preauricular, or submandibular nodes. However, contralateral metastases are infrequent. Distant metastasis from carcinoma of the lip is extremely rare.

Treatment Approach

Carcinoma of the lip can be treated successfully with either radiotherapy or surgery.⁴⁴ The choice of treatment depends on the extent of disease, the functional and cosmetic results of the treatment, expediency, the patient’s age, and the available treatment personnel and facilities.⁴⁵ Radiotherapy is usually indicated for moderately large (>3 cm) infiltrative lesions that would otherwise require a complicated plastic surgery with less satisfactory cosmetic and functional results. Radiation is also indicated for tumors involving the commissure because surgical excision of the commissure would not yield satisfactory cosmetic and functional results.⁴⁶ Elderly patients who are at a high risk for complications from general anesthesia or who have persistent or recurrent disease after surgery should be considered for radiotherapy. Radiotherapy is also administered postoperatively when the surgical margin is inadequate, there is invasion of the soft tissues of the neck caused by cervical lymph node metastasis, and in combination with surgery for advanced resectable disease. Surgery is usually preferred for small lesions, young patients, very advanced disease with bone invasion, cervical lymph node metastases, and recurrent disease after radiotherapy.

Radiotherapy modalities commonly used for carcinoma of the lip include external-beam radiotherapy with orthovoltage x-rays or electrons,⁴⁷ and interstitial implants with radium or iridium.²⁷ The “sandwich” technique has also been used in some centers; however, fractionated external-beam radiotherapy usually yields more satisfactory cosmetic results, especially for moderately advanced disease. When interstitial radiotherapy is used, a dose of 60 to 70 Gy in 6 to 8 days is usually adequate.

When external-beam radiotherapy is used, a lead cut-out is usually made to outline the treatment volume. A lead shield can be inserted between the inner surface of the lip and the gingiva to prevent irradiation of the intraoral structures. The treatment volume should include the lesion with adequate margins. Leukoplakic changes on the lip adjacent to the lesion should also be included in the treatment volume. For small superficial tumors, a single field with 100- to 150-kV x-rays is sufficient. For deeper, more advanced tumors, 200- to 250-kV x-rays or electrons are usually used. The optimal dose-fractionation schedule depends on the volume of irradiation. For small lesions (<2 cm in diameter), a dose of 45 Gy to 50 Gy in 15 fractions over 3 weeks is usually adequate, with good cosmetic results. For larger lesions, more protracted treatments with 50 to 70 Gy in 4 to 7 weeks are often used. The base of the skull should be adequately covered in cases with perineural involvement (Fig. 29-11). The neck is usually not irradiated unless cervical lymph node metastasis is present. Acute moist skin and mucous membrane reactions are managed with frequent cleansing and saline soaks. Topical antibiotics are rarely used unless there is an infection.

FIGURE 29-11 • Isodose curves of an inverse intensity-modulated radiotherapy plan using seven coplanar gantry angles delivered with conventional multileaf collimator for a patient with recurrent carcinoma of the lip with perineural invasion displayed on the axial (A), coronal (B), and sagittal (C) planes through the centroid of the primary tumor and the dose-volume histogram for the relevant structures (D). The gross tumor volume is shown in red and the clinical target volume (including a margin for set-up errors) is shown in magenta.

Treatment Outcome

Results of radiotherapy in select series of patients treated with radiotherapy for carcinoma of the lip are shown in Table 29-2.^46,48–50 Control of the primary lesion can be achieved with external-beam irradiation or interstitial implants in the majority of patients. Those with recurrent disease after radiotherapy or cervical lymph node metastasis are usually treated surgically. Death resulting from uncontrolled carcinoma of the lip is uncommon (<10% in most series). The local control rate by interstitial implant is comparable to that achieved with external irradiation, although for larger lesions, better cosmetic results are obtained with protracted external-beam radiotherapy.

Clinical Presentation

Carcinoma of the oral tongue is the second most common malignancy of the oral cavity. It is more common in men than in women. The peak incidence occurs in the fifth through seventh decades of life. It is often associated with poor oral hygiene, alcoholism, and heavy tobacco smoking. In the past, it has been associated with syphilis. There also has been an association with Plummer-Vinson syndrome in Sweden, and chewing betel nuts mixed with slaked lime and tobacco in India.

Carcinoma of the oral tongue most frequently arises from the lateral border of the tongue, especially the posterior portions of the oral tongue. Grossly, it may be exophytic, papillary, or infiltrative, with superficial ulcerations. The majority of carcinomas of the oral tongue are moderately to well-differentiated squamous cell carcinomas. Areas of leukoplakia and carcinoma in situ associated with invasive carcinoma are not uncommon.

Carcinoma of the oral tongue commonly presents as a growth or ulcer with or without local pain. When the disease becomes more advanced, the patient may complain of ipsilateral otalgia, owing to involvement of the lingual nerve, hypersalivation, and dysphagia. When there is extreme involvement of the tongue or fixation of the tongue, swallowing and speech may become difficult. Patients usually die of uncontrolled local disease with hemorrhage, inanition, aspiration, or other complications.

Routes of Spread

Carcinoma of the oral tongue usually spreads by direct invasion into the floor of the mouth, anterior tonsillar pillar, base of tongue, and mandible. Approximately 30% to 40% of the patients have cervical lymph node metastasis on presentation. The thickness as well as the T stage of the tongue lesion is directly correlated with the incidence of lymph nodal involvement.^32,51 The subdigastric nodes are most frequently involved. The submandibular and midjugular lymph nodes are less commonly involved, and the submental, lower jugular, and posterior cervical nodes are rarely involved. Distant metastasis is seldom detected before death. The lungs, liver, and bones are the most common distant metastatic sites. Approximately 19% of patients develop a second malignant tumor. The majority of the second cancers are in the upper respiratory-digestive tract. The distribution of lymph nodes reported by Lindberg is shown in Fig. 29-12.⁵²

FIGURE 29-12 • Distribution of 105 lymph nodes in 302 patients for oral tongue.

(From Lindberg RD: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts, Cancer 29:1446, 1972.)

Treatment Approach

Surgery followed by radiotherapy for both the primary site as well as the bilateral necks is the preferred treatment modality for carcinoma of the oral tongue. Invasive pattern; T₁, T₂, T₃, or T₄ lesions; bone invasion; multiple cervical lymph node metastases; close or positive margins; and lymphovascular or perineural invasion are indications for postoperative radiotherapy. In regard to an invasive pattern, multiple studies have demonstrated that the risk of cervical lymph node metastases is much greater for tumors with a depth of invasion of 5 mm or greater.^53,54 In patients with positive margins or extranodal extension, a postoperative chemoradiation approach has been shown to be superior to radiation alone in the analysis of pooled RTOG and EORTC data by Bernier and colleagues, and now is the standard of care, albeit with increased toxicity.^20–22 Attempts to spare the parotid glands can be made to reduce xerostomia, particularly with the advent of IMRT (Figs. 29-13 and 29-14).⁵⁵ With the excellent functional outcome of the reconstructed oral tongue after hemiglossectomy, definitive radiotherapy with or without chemotherapy is reserved for selected cases (i.e., if the patient is medically inoperable or if the lesion is unresectable). It must include brachytherapy to be effective.^56,57

FIGURE 29-13 • Isodose curves of an inverse intensity-modulated radiation therapy (IMRT) plan using seven coplanar gantry angles delivered with conventional multileaf collimator for a patient receiving postoperative radiotherapy for a T₂-N_2b carcinoma of the oral tongue displayed on the axial (A), coronal (B), and sagittal (C) planes through the centroid of the primary tumor and the dose-volume histogram for the relevant structures (D). The gross tumor volume is shown in red and the clinical target volume (including a margin for set-up errors) is shown in magenta. A low neck/supraclavicular field is matched to the IMRT plan.

FIGURE 29-14 • Intensity-modulated radiation therapy contours for patient with stage T_2b-N₂-M₀ squamous cell carcinoma of the oral tongue, unresectable. The dosing levels are as follows: orange, gross tumor volume 70 Gy; yellow, planning target volume (PTV) 70 Gy; blue, PTV 59.4 Gy; purple, PTV 54 Gy.

Surgery is indicated for small lesions (<1 cm) located on the dorsum, the tip, or the lateral border of the tongue that can be excised without resulting in dysfunction, especially in young patients. Certain carcinomas of the tongue arising from syphilitic glossitis, lesions that are edematous and deeply infiltrative, lesions that have invaded the mandible, lesions that have invaded the glossopalatine sulcus, and advanced lesions with multiple lymph node metastases are best managed with combined surgery and radiation with or without chemotherapy.

Surgery is also preferred in elderly patients who tolerate partial glossectomy better than radiotherapy and in whom preservation of speech is not important. Recurrence in the primary lesion after radiotherapy is difficult to salvage by surgery, with one study quoting 5-year actuarial survival rates of 39%, and 27% for locoregional recurrence.⁵⁸ Local recurrence after treatment with glossectomy alone has a similarly dismal prognosis, with some studies reporting less than 10% of patients being successfully salvaged at 4 years after being diagnosed with recurrent disease.⁵⁹ Metastatic cervical lymph node metastases that develop after the primary lesion has been controlled can be successfully salvaged, although survival after neck recurrence has been documented to be as low as 18 months.⁶⁰

When external irradiation is used in combination with interstitial implants in selected cases of carcinoma of the oral tongue, usually 40 Gy are delivered in 2-Gy fractions, five daily fractions per week, before the implant. The implant should deliver at least 40 Gy. Although the primary lesion may shrink after the external irradiation, the treatment volume for the interstitial implant is usually determined before any treatment is initiated. The treatment volume for external irradiation should include the primary lesion as well as the regional lymph nodal areas. The lymph node areas are treated from 54 Gy, for uninvolved lymph nodes being treated electively, to 60 Gy. In patients with unilateral lymph node metastasis, the rate of contralateral occult node metastases has been found to be high in OCC, up to 35% to 40%.^61,62 Therefore, we generally advocate contralateral nodal treatment in all patients with carcinoma of the oral tongue because of its aggressive behavior and because it is not a well-lateralized structure such as the buccal mucosa. When lymph nodes are clinically involved, a neck dissection should be considered instead of radiotherapy as it offers better local control. In this clinical scenario, the preference is surgery followed by postoperative radiotherapy when indicated. Table 29-3 depicts nodal treatment guidelines that are used at our institution for oral cavity tumors. Interstitial implant is an integral part of radiotherapy for carcinoma of the oral tongue if definitive radiotherapy is the primary treatment approach.⁶³ The implant dose is directly correlated with local control.^33,34,36 External radiotherapy alone is not recommended, as it is rarely successful. Early superficial lesions can be controlled with a single-plane interstitial implant or peroral radiotherapy alone. For lesions greater than 1 cm in thickness, double-plane or volume implants in combination with external irradiation are usually used. Brachytherapy has also been used in the postoperative setting for T_1-2-N₀ squamous cell carcinomas of the oral tongue and the floor of mouth with close or positive margins. The recommended dose is 60 Gy.^64,65 High rates of locoregional control, close to 90%, with low risk of chronic sequelae have been reported.

The most important step in treatment planning for interstitial implants is the determination of the treatment volume. Sometimes the true extent of the tumor cannot be adequately determined without anesthesia because of pain. With the patient under general anesthesia, it is not uncommon to find a tumor more extensive than anticipated. For this reason, it is always a good idea to bring a surplus of needles to the operating room.

For interstitial implants of carcinoma of the tongue and floor of the mouth, dose rates in the range of 30 to 100 cGy per hour for the minimum tumor dose have been commonly used when low-dose rate (LDR) brachytherapy is the treatment approach. Although some authors recommend adjustments of the total dose according to the dose rate,^29,66 we agree with Mazeron and coworkers that for dose rates between 30 and 100 cGy per hour, no adjustment of total dose is indicated.⁶⁷ Overcorrection of dose for reduced overall treatment time may lead to a high incidence of local recurrence.^68,69

Although patients are usually able to speak and swallow with the implant in place, it is good practice to maintain adequate hydration with intravenous fluids unless the patient’s oral fluid intake is adequate. A liquid to semisolid diet is well tolerated during the implant period. We have used antibiotics routinely during the implants and for 1 week after the implant for oral cavity lesions. Patients are also encouraged to irrigate the mouth with salt and baking soda solutions or half-strength peroxide solutions during and after the implant period. Analgesics are prescribed whenever necessary. The peak reaction of mucous membranes usually does not occur until several days to 1 week after the implant.

Localization films of the implant are usually taken on the day of the procedure. Computer dosimetry provides detailed information on the dose distribution within the implant volume. The dose distribution in several parallel planes intersecting the tumor volume should be obtained. An isodose curve that encompasses the entire tumor volume on all the planes that intersect the volume should be used to calculate the minimum tumor dose. Sometimes part of the implant may be removed during the course of treatment when there is a volume of overdosage within the implant. The optimal minimum tumor doses for local control vary with the size of the primary lesions. For T₁ and select small T₂ lesions, the implant alone is used with a dose of 60 to 70 Gy. For larger T₂ lesions, a total dose between 75 to 80 Gy is delivered by using both intestitial implant and external-beam radiotherapy, with 30 to 40 Gy being a typical dose delivered by external-beam radiation, as noted previously. The incidence of soft-tissue and bone necrosis depends on the total dose as well as on tumor volume, but is independent of the dose rate.⁷⁰ It is important to separate the ribbons from the mandible by the use of dental rolls sutured in place.

HDR fractionated interstitial brachytherapy is the preferred treatment approach at our institution for patients undergoing implantation. A phase III trial of high- and low-dose interstitial radiotherapy for early oral tongue cancer showed that HDR can be an alternative to LDR, with similar rates of local control and the advantage of eliminating exposure to the medical staff.^28,71 If not using HDR, an afterloading technique using iridium seeds is preferable because of the reduced radiation exposure to the medical and paramedical personnel. The afterloading technique also allows more time for optimal placement of needles, because no radiation exposure occurs during the procedure. The dosing regimen for HDR brachytherapy is typically 54 to 60 Gy in 9 to 10 fractions.

Treatment Outcome

Definitive radiotherapy results for carcinoma of the oral tongue are given in Table 29-4.^36,72–76 Most of the patients in the series reported by Wendt and associates⁷⁵ and Mazeron and associates⁷⁴ did not have cervical lymph node metastasis at the time of treatment, whereas 50% of the patients in the series reported by Fletcher⁷⁷ presented with cervical lymph node metastasis. As noted previously, the incidence of occult metastasis in early-stage squamous cell carcinoma of the oral tongue is between 20% and 48%.⁷⁸

Because interstitial radiotherapy is an integral part of radiotherapy in patients receiving radiotherapy alone for carcinoma of the oral tongue, a small area of the mandible usually receives a dose in excess of 75 Gy. The incidence of osteonecrosis was 19% in the series reported by Delclos and coworkers.⁷⁹ Most of the necrosis healed with conservative management, although only 35% of the bone necrosis in that series required surgical treatment, for a total of 6% of patients requiring surgical management. Another series reported a 38% complication rate, such as erosive ulcerations and bone exposure, in patients who received brachytherapy for stage I and II disease.⁸⁰ The patients who also received external-beam radiotherapy in addition to brachytherapy had higher rates of complications than those treated with brachytherapy alone, but the incidence of neck metastases occurred in 31% to 51% of patients in whom the neck was not electively irradiated. Therefore, we still advocate for brachytherapy in combination with external-beam radiation for these patients. There have been multiple studies on the outcomes of patients treated with surgery in carcinoma of the oral tongue. One recent retrospective study from Japan demonstrated a superiority of surgery over brachytherapy in stage I and II tumors, with 5-year overall survival rates for the LDR, HDR, and surgery groups of 84.0%, 72.9%, and 95.4%, respectively.⁸¹ Another study by Aksu and colleagues compared definitive radiation with surgery and postoperative radiation in 80 patients with stages I through IVA disease.⁸² The patients that received surgery and postoperative radiation therapy had a 5-year overall survival advantage versus those treated with definitive radiation alone (49% versus 16%, respectively). Studies such as these confirm that when feasible, surgery should be performed as the definitive treatment modality in patients with oral tongue cancer.

Long-term survival in carcinoma of the oral tongue is directly related to the stage of disease. In a series of 204 patients treated between 1940 and 1971, reported by Fu and associates,⁷⁰ the overall 5-year actuarial survival was 32% and determinate survival was 47% for all stages. The prognosis for patients who had cervical lymph node metastasis on presentation and persistent or recurrent disease at 3 months after treatment was significantly poorer than the prognosis for patients who had no cervical lymph node metastasis on presentation and those who were free of disease at 3 months after treatment. A recent series of 370 stage T₁ and T₂ cases reported by Shibuya and associates showed that the 5-year primary tumor control was 85% for superficial lesions, 70% for exophytic lesions, and 45% for infiltrative lesions. The 5-year overall survivals for stages T₁, T_2a, and T_2b were 84%, 78%, and 72%, respectively.⁸⁰

Clinical Presentation

Carcinoma of the floor of the mouth accounts for approximately 15% of all carcinomas of the oral cavity. Similar to carcinoma of the oral tongue, carcinoma of the floor of the mouth is often associated with tobacco smoking, heavy alcohol consumption, and poor oral hygiene. It is more common in men than in women. The male-to-female ratio is approximately 2.5 : 1. Most of the patients are between 50 and 70 years old, with a peak incidence between 55 and 65 years.

The majority of the carcinomas of the floor of the mouth are moderately to well-differentiated squamous cell carcinomas. Clinically, they usually present as a growth or an ulcer, most often on one or the other side of the midline. Invasion of the tongue is common, and sometimes it may be difficult to distinguish whether a primary growth is arising from the floor of the mouth or from the oral tongue. The frenulum is frequently involved. With more advanced lesions, patients may complain of otalgia from referred pain, hypersalivation, difficulties in speech, and bleeding. A significant number of patients with carcinoma of the floor of the mouth develop a second primary cancer. In the series reported by Fu and colleagues,⁷⁰ 55 of 153 (36%) of the patients had a second primary cancer. The majority of the second primary sites are in the upper aerodigestive tracts.

Routes of Spread

Carcinomas of the floor of the mouth usually spread by direct invasion into the tongue, the lower alveolar ridge, the mandible, and the submandibular glands. Approximately 30% of the patients have cervical lymph node metastasis on presentation. The submandibular lymph nodes are most frequently involved. Metastasis to subdigastric nodes, midjugular nodes, and submental nodes are less frequent. The incidence of lymph node metastasis is directly proportional to the stage of the primary lesion; 9% for T₁ lesions, 25% for T₂ lesions, and 68% for T₃ and T₄ lesions (Fig. 29-15). Similarly, 20% of the patients without initial lymph node metastasis subsequently develop cervical lymph node metastasis. Distant metastasis occurs in approximately 9% of the patients. Lungs, liver, bone, and mediastinal lymph nodes are the most common sites of distant metastasis.

FIGURE 29-15 • Distribution of 79 of 258 positive lymph nodes in floor of mouth.

(From Lindberg RD: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts, Cancer 29:1446, 1972.)

Treatment Approach

Radiotherapy or surgery is a treatment option for early stage disease. A combination of surgery followed by postoperative radiotherapy is recommended for operable stage III and IV disease, especially when there is invasion of the mandible and the presence of large or multiple cervical lymph node metastases or extensive involvement of the musculature of the tongue. For medically inoperable patients, or unresectable stage T_4b disease, a combination of chemotherapy and radiotherapy should be considered. Surgery is used in the treatment of recurrent disease after radiotherapy.

Radiotherapy modalities for carcinoma of the floor of the mouth consist of external-beam irradiation, peroral cone irradiation, and interstitial implants. Interstitial implants alone or peroral cone irradiation may be used for superficial or exophytic T₁ lesions.

For postoperative treatment (with either IMRT or non-IMRT techniques), we recommend 66 Gy in 2-Gy fractions in the case of positive margins, 60 Gy in 2-Gy fractions to the high-risk region, and 54 Gy in 1.8-Gy fractions to the low-risk region. If definitive radiation therapy is used with non-IMRT techniques, for most carcinomas of the floor of mouth without bone invasion, we recommend external-beam irradiation with 50 to 54 Gy delivered at 2 Gy per fraction, five fractions per week, to the primary lesion with adequate margins and the upper neck, including the submandibular and subdigastric nodes, followed by a boost to the primary lesion with 10 to 20 Gy using interstitial implant, peroral cone irradiation, or external-beam irradiation. The boost portion of treatment encompasses any visible tumor plus a margin, and we prefer using 3-D conformal radiotherapy (Fig. 29-16). If IMRT is used as definitive treatment alone, the entire region can be treated using a dose-painting technique, delivering 70 Gy to the primary tumor and involved lymph nodes, 59.4 to 63 Gy in 1.8-Gy fractions or 60 Gy in 2-Gy fractions to the uninvolved but high-risk regions, and 54 Gy in 1.8-Gy fractions to the low-risk region.The lower neck is routinely irradiated when cervical lymph node metastases are present. Similar to carcinoma of the oral tongue, the floor of the mouth is not a well-lateralized structure and thus the bilateral neck is generally treated in all cases. If a LAN field is used, the standard dose is 50 Gy in 2-Gy fractions or 50.4 Gy in 1.8-Gy fractions. For advanced, unresectable lesions not amenable to implantation, patients can be treated with external-beam radiotherapy using accelerated hyperfractionation with a concomitant boost technique.

FIGURE 29-16 • Isodose curves of an inverse intensity-modulated radiotherapy plan using seven coplanar gantry angles delivered with conventional multileaf collimator of a boost plan to the gross tumor volume (GTV) with a margin for a patient with T₄-N₁ carcinoma of the floor of mouth displayed on the axial (A), coronal (B), and sagittal (C) planes through the centroid of the primary tumor and the dose-volume histogram for the relevant structures (D). The GTV is shown in red and the clinical target volume (including a margin for set-up errors) is shown in magenta.

Similar interstitial radiotherapy techniques for carcinoma of the oral tongue are used for carcinoma for the floor of the mouth, as shown in Fig. 29-10. The iridium seeds in nylon ribbons are afterloaded into nylon tubes extending from the skin of the submental region to the floor of the mouth. The nylon tubes are pulled in behind stainless steel needles, which are then removed. For large lesions, the catheters are usually placed with the use of needles inserted through the submental skin to the dorsum of the tongue, to deliver an adequate dose throughout the tumor volume. If the tubes terminate in the floor of the mouth, the iridium ribbons must protrude at least 1 cm or have double-strength seeds at the tip. Alternately, longer dwell times can be used with HDR. A report from Japan indicated that HDR can achieve high control rates for carcinoma of the floor of mouth and the advantage of HDR versus LDR was the elimination of radiation exposure for the medical staff.⁸³ The recommended HDR dose was 6000 cGy.

Treatment Outcome

Bone and soft-tissue necrosis develop in approximately 10% to 21% of the patients, usually within 2 years after treatment in patients treated with definitive radiation therapy.^79,84,85 Most of the necroses heal with conservative management, although some patients require hemimandibulectomy. The results of definitive radiotherapy of carcinoma of the floor of the mouth, as reported in several recent series, are given in Table 29-5.* Most patients were treated with a combination of external irradiation and interstitial implants. Some early lesions were treated with interstitial implants or external irradiation alone. The control of the primary lesion is directly proportionate to the stage of the disease. Control of the cervical lymph node metastasis is also related to the N staging. Approximately two thirds of cases of N₁ disease (lesion < 3 cm in diameter) can be controlled with radiation alone or in combination with surgery.

Following treatment, the most common site of failure is the site of the primary lesion, with or without simultaneous failure in the cervical lymph nodes. Approximately 80% of the recurrences appear within 2 years following treatment. Failure in the cervical lymph nodes alone or in distant metastasis alone is rare.

A relatively large series of 160 patients from France showed that brachytherapy alone offers excellent local control of 89% for T₁ and T₂ lesions with a 5-year survival of 76%.⁸⁴ In spite of the good local control rate of carcinoma of the floor of the mouth, actuarial survival of these patients is poor, owing to a significant number of deaths from intercurrent disease or a second primary cancer. In the series of 153 patients with carcinoma of the floor of the mouth reported by Fu and colleagues,⁷⁰ the 5-year actuarial and determinate survival rates were 35% and 60%, respectively, for the entire group of patients. Data from Washington University showed that in a retrospective study of 280 patients treated with surgery or radiation, the overall 5-year disease-specific survival was 56%.⁸⁶ Recurrence at the primary site (41%) was the most common site of failure followed by neck recurrence of 19%. Metastasis occurred in 30%. Second primaries occurred in 20% of patients, and 53% died of their second primary disease.

Clinical Presentation

After carcinoma of the lip, oral tongue, floor of the mouth, and lower gum, carcinoma of the buccal mucosa is the fifth most common carcinoma of the oral cavity. Squamous cell carcinoma of the buccal mucosa composes approximately 10% of all oral cancers in the United States and western Europe. It is the most common carcinoma of the oral cavity in India, Malaysia, and Taiwan. It usually occurs in the sixth and seventh decades of life, and is more prevalent in men than in women. Tobacco and betel nut chewing appear to play an important role in the cause of these tumors.^88,89

Carcinomas of the buccal mucosa often occur in association with pre-existing leukoplakia and tend to have multiple primary sites and recurrence. Excision of the oral leukoplakia may reduce the subsequent development of carcinoma.⁹⁰ These tumors usually arise in the area adjacent to the lower molars along the occlusal line of the teeth. Clinically, there are three distinct types: exophytic, ulcerative, and verrucous. The patient may present with pain or bleeding, trismus, or cervical lymphadenopathy. In advanced stages, the tumor may destroy the entire cheek and invade the adjacent bones and the neck. Infection is common and mastication becomes difficult. Death usually occurs as a result of poor nutrition and general debilitation.^91,92

Routes of Spread

Carcinomas of the buccal mucosa frequently spread by direct invasion into the gingivobuccal sulcus, the upper and lower alveolar ridges, the hard palate, the maxilla, and the mandible. Lymph node metastasis occurs in approximately 9% to 31% of the patients during the course of the disease.^91,93 The submandibular lymph nodes are most frequently involved; involvement of the upper cervical and the parotid lymph nodes is less common. The risk of subclinical disease is 16%.⁹² Distant metastases are rare, as patients often die of uncontrolled local disease before distant metastases are manifested clinically.

Treatment Approach

Radiotherapy alone can be considered in small (T₁) lesions involving the commissure or in the mid-cheek without sulcus invasion. Otherwise, surgery followed by postoperative radiotherapy is the recommended treatment modality for all buccal mucosa carcinomas, including T₁ lesions. A recent report stated that T classification and negative margins are not adequate predictors of local control, and even early buccal tumors could benefit from adjuvant therapy to enhance local control.⁹⁴ In another series, local recurrence occurred in all patients with stage I and II disease treated with wide local excision.⁹⁵ The extent of surgery depends on the degree of locoregional involvement. A marginal or segmental mandibulectomy, or a partial maxillectomy should be performed when tumor invasion to the nearby bony structures is clinically suspected. A radical neck dissection is recommended in all patients with a node-positive neck, whereas a supraomohyoid neck dissection can be considered in the node-negative neck.⁹⁶ As in other sites of the oral cavity, adjuvant treatment with chemotherapy and radiation is recommended in patients with positive margins or extranodal extension. In cases that are inoperable, radiotherapy in combination with chemotherapy can be used.^15,16 Surgery is also considered in patients who recur after radiotherapy as salvage. One series reported a 5-year actuarial disease-free survival after surgical salvage of 59.7%.⁹⁷

Either 3-D conformal therapy or IMRT should be used to spare the contralateral parotid gland. Because buccal mucosa lesions are lateralized, treatment of the contralateral buccal mucosa is not necessary in T₁ and T₂ lesions. Representative target delineation and a plan are shown in Figs. 29-17 and 29-18. Postoperative dosing regimens for buccal mucosa cancer are similar to other regions of the oral cavity. We recommend doses of 66 Gy in 2-Gy fractions for positive margins, 60 Gy in 2-Gy fractions or 59.4 to 63 Gy in 1.8-Gy fractions to high-risk regions, and 54 Gy in 1.8-Gy fractions for low-risk regions. An LAN is often used, treated to either 50 Gy in 2-Gy fractions or 50.4 Gy in 1.8-Gy fractions.

FIGURE 29-17 • A patient with a locally advanced, pT_4a-N_2b-M₀ squamous cell carcinoma of the right buccal mucosa, with negative margins. Orange, planning target volume (PTV) 60 Gy; blue, PTV 54 Gy.

FIGURE 29-18 • A, Three-dimensional (3-D) treatment plan for buccal mucosal cancer, axial plane. B, 3-D plan, coronal plane. C, 3-D plan, sagittal view. D, Dose-volume histogram.

Interstitial implants with iridium wires or seeds in nylon ribbons can be considered for treatment of early, small lesions that have not invaded the buccogingival sulcus, the gingiva, or bone. Usually a minimum tumor dose of 60 to 70 Gy in 5 to 8 days is delivered through a single-plane or double-plane implant on the thickness of the lesion.

Treatment Outcome

Reports of the select retrospective studies of carcinoma of the buccal mucosa can be found in Table 29-6.^95,98–102 A prospective, randomized trial from India examined the role of postoperative radiotherapy in stages III and IV carcinoma of the buccal mucosa. The 3-year actuarial disease-free survival was 68% versus 38%, with and without postoperative radiotherapy. The 3-year actuarial overall survival was 94% versus 84%, respectively.¹⁰³

Surgery can be used to salvage patients that failed radical radiotherapy. One series reported an overall 5-year actuarial disease-free survival after salvage surgery to be 59.7%. At recurrence, T stage and the presence or absence of skin infiltration were the factors that significantly influenced disease-free survival.⁹⁷

Multiple studies have demonstrated the superiority of multimodality treatment versus that of surgery or radiation alone. A study by Lin and colleagues examined 121 patients with M₀ disease treated with either surgery alone, radiotherapy alone, or surgery plus postoperative radiation. The rate of local recurrence in patients with T_1-2-N₀ disease who received surgery alone was 40%, and for locally advanced disease both locoregional control and overall survival were improved in those patients receiving a combined-modality approach.¹⁰⁴ Another study of combined-modality therapy was published by Fang and colleagues, and found that the 3-year locoregional control rate was 64%. Positive surgical margins and skin infiltration were found to be negative prognostic factors.⁹⁸

Clinical Presentation

Carcinomas of the upper gingiva are much less common than those of the lower gingiva. They frequently invade the maxillary antrum and are often difficult to differentiate from a primary carcinoma arising from the floor of the maxillary sinus. They usually affect men in the fifth and sixth decades of life.

Carcinomas of the upper gingiva usually arise in the region of the molar and premolar teeth. They often appear as papillary growths. The majority of cases are well-differentiated squamous cell carcinomas.

Patients usually present with a history of ill-fitting dentures, ulceration around the teeth that fails to heal, or bleeding. Trismus is present in advanced cases.

Routes of Spread

Carcinomas of the upper gingiva usually spread by direct invasion into the maxillary sinus or the upper gingivobuccal sulcus. Lymph node metastasis most frequently involves the submandibular lymph nodes. The subdigastric and upper cervical nodes are less frequently involved. At diagnosis, 18% to 52% of patients have positive lymph nodes.

Treatment Approach

Because of early bone involvement and the risk of bone exposure after the tumor is irradiated, surgery is the treatment of choice for carcinomas of the upper gingiva. Except for early superficial lesions, most tumors of the hard palate and upper gingiva are treated with surgery. The postoperative doses used are the same as outlined previously for the oral tongue and buccal mucosa, and IMRT is preferred when available. Postoperative radiotherapy is added in high-risk patients. For definitive radiotherapy, the patient is treated to a dose of 70 Gy, with doses of 59.4 to 63 Gy used for high-risk regions and 54 Gy in 1.8-Gy fractions for low-risk regions. A LAN field is used and treated to 50 to 50.4 Gy, as outlined previously. A balloon filled with water can be used to compensate for postsurgical tissue defects. Postoperative radiotherapy usually begins 2 to 3 weeks after surgery.

Treatment Outcome

In the review of the Memorial Sloan-Kettering Cancer Center experience of 61 patients with upper gingival tumor treated mostly with surgery, the 5-year survival rate was 51% (31/61). Clinical stage was the only predicator of survival.¹⁰⁵ In another series of 82 patients from Japan, the 5-year local control rate was 61% with a 5-year actuarial survival of 45%.¹⁰⁶ A third more recent series from India examined the results of 110 patients with tumors of the superior gingival-buccal complex treated with either surgery alone, radiation alone, or a combined modality approach. Five-year progression-free survival was 49% for patients treated surgically and 0% with a nonsurgical approach. T stage and extracapsular spread were predictors of disease progression.¹⁰⁷

Clinical Presentation

Carcinoma of the lower gingiva accounts for approximately 12% of carcinomas of the oral cavity. It usually occurs at an advanced age and is rare in persons younger than age 40. Men are affected more frequently than women.

Carcinomas of the lower gingiva usually arise in the region of the molar teeth. They can be ulcerative, exophytic, or verrucous in their gross appearance. They can be multicentric in origin. Leukoplakia is frequently present. The majority of carcinomas of the lower gingiva are well-differentiated or moderately well-differentiated squamous cell carcinomas.

Patients with carcinoma of the lower gingiva not infrequently present with a history of ill-fitting dentures or bleeding upon mastication. The dentist is frequently consulted first. A history of tooth extraction and surgical incision of a suspected abscess is not uncommon. Otalgia can occur because of secondary infection. Trismus and pain can result from bone invasion.

Routes of Spread

Tumor spreads mainly through the occlusal ridge alone or in combination with penetration of the buccal or lingual plates in edentulous patients.^108,109 Lymph node metastasis is present in 13% to 24% of patients with carcinoma of the lower gingiva. The submandibular lymph nodes are most frequently involved. Involvement of the subdigastric and upper cervical nodes is less common. Direct invasion of the mandible may be present in 50% of the patients on initial examination. The actual extent of bone involvement may exceed that shown on radiographs. Therefore, additional imaging is essential to accurate preoperative assessment.

Treatment Approach

Because of frequent bone involvement and lymph node metastasis, surgery has been the primary treatment modality in the management of carcinoma of the lower gingiva. Early superficial lesions can be expeditiously treated by a simple excision or marginal resection with skin graft. In patients with more advanced disease, postoperative radiotherapy can reduce the incidence of local recurrence. Clear margins should be achieved, as inadequate margins result in a high rate of local recurrence. One series showed that the 5-year local control rate in the presence of positive margins was 49% versus 100% with negative margins and survival was 11% versus 91%.¹¹⁰ In addition, patients with advanced T stage, radiologic or histologic evidence of mandibular invasion, tumors involving the symphyseal region, and decreased tumor differentiation have high propensity for regional metastases. Therefore, elective treatment of the neck should be considered.¹¹¹ One series reported that larger tumor size is more important than mandibular invasion in predicting local control—larger tumors that have a higher propensity for local recurrence require a more extensive surgical resection.¹¹²

Early superficial lesions, less than 2 cm in diameter, can be adequately treated with 60 Gy using electrons in 3 to 4 weeks using a peroral cone. Orthovoltage energies should not be used over bone. For more advanced unresectable disease, a definitive external-beam irradiation technique, preferrably with IMRT, should be used to a dose of 70 Gy. If IMRT is not available and conventional techniques are being used, oblique- or right-angle, wedged-pair field arrangements can be used to spare the contralateral salivary glands.

Treatment Outcome

Local control of carcinomas of the lower gingiva treated with radiotherapy alone was achieved in 71.5% (5/7) of T₁ lesions, 70% (7/10) of T₂ lesions, 59% (10/17) of T₃ lesions, and 29% (4/14) of T₄ lesions in the series reported by MacComb.⁹² The 5-year survival rate of 108 patients treated between 1947 and 1960 at the MD Anderson Cancer Center was 46%.⁹² Most series report excellent local control with surgery followed by postoperative radiotherapy when indicated. Results from select series are shown in Table 29-7.^110,113 In the aforementioned study at MD Anderson Cancer Center¹¹² examining prognostic factors of the disease, the authors found that advanced T stage, positive surgical margins, mandibular invasion, and cervical metastases were all associated with a worse overall survival.

Clinical Presentation

Carcinomas of the retromolar trigone are rare. Indirect extension into the anterior tonsillar pillar or the buccal mucosa occurs early. Frequently, they are indistinguishable from carcinomas arising from the anterior tonsillar pillar. They are usually moderately differentiated squamous cell carcinomas.

Routes of Spread

Carcinomas of the retromolar trigone frequently metastasize to the subdigastric lymph nodes. The submandibular and upper cervical lymph nodes are affected less often. The incidence on diagnosis is approximately 30%.

Treatment Approach

These lesions are treated in a highly selected manner similar to that of tonsillar pillar tumors. T₁ and early T₂ tumors can be treated with megavoltage external-beam irradiation. When external-beam irradiation is used alone with conventional methods, a technique using mixed electrons and photons with single lateral fields or parallel opposing fields with 2 : 1 weighting favoring the side of the disease can be used. Usually a dose of 66 to 74 Gy in 2-Gy fractions is administered. IMRT can be used when available, using a dose of 70 Gy for gross disease, 59.4 to 63 Gy for high-risk disease, and 54 Gy for low-risk disease. Prophylactic treatment of the neck is essential as lesions located in the retromolar trigone have a high propensity for metastases in the neck. We generally treat the contralateral lymph node levels I through V electively in patients with T₃, T₄, or node-positive disease, whether in definitive treatment or in the postoperative setting.

Surgical resection has been shown to be the preferred modality over definitive radiation. More advanced tumors, such as those tumors with bone involvement or those with nodal involvement, require surgery and postoperative radiotherapy (Fig. 29-19).

FIGURE 29-19 • A, Simulation film of a patient with cancer of the retromolar trigone, lateral view. B, Simulation film of the low neck and supraclavicular fossae.

Treatment Outcome

MD Anderson Cancer Center reported results of 159 patients with squamous cell carcinoma of the anterior faucial pillar and retromolar trigone region treated with radiation.¹¹⁴ Local control with radiation alone for T₁ lesions was 71% (12/17); for T₂ lesions, 70% (51/81); for T₃ lesions, 76% (19/25); and three of five T₄ lesions were controlled. Most of the failures were treated with surgery, and the ultimate control rate was 100% for T₁, 94% for T₂, and 92% for T₃. The overall N₀ neck failure rate was 11%. The authors recommend elective treatment of subdigastric and upper jugular nodes to the level of the hyoid. The 5-year determinate survival rate in the series was 83%. A more recent study at the Notre-Dame Hospital in Quebec demonstrated 5-year regional control rates of 88% after definitive radiation and 67% after salvage surgery.¹¹⁵ See Table 29-8 for select results of treatment for carcinoma of the retro molar trigone.^115–117

Although there have been no formal randomized comparisons of radiation alone versus combined surgery and radiation specifically in this setting, reports of institutional experience with the combination treatment versus radiation alone suggest that combined surgery and radiation, particularly with advanced tumors, may yield results superior to radiotherapy alone.^116,118 For example, University of Florida investigators noted in a retrospective review of their experience in 99 patients with stage I through III disease that surgery and radiation were associated with higher 5-year survival (56%) than definitive radiation alone (40%).¹¹⁸

Clinical Presentation

Primary malignancies of the hard palate are rare. In one series of 5000 cases of oral cancer, only 25 (0.5%) had squamous cell carcinoma of the hard palate.¹¹⁹ In another study, squamous cell carcinoma accounted for 3% of all oral cancers.¹²⁰ Patients often complain of ill-fitting dentures, pain, intermittent bleeding, or a sore that does not heal.

Routes of Spread

The majority of hard palate lesions originate in the minor salivary glands. Adenoid cystic carcinomas spread hematogeneously to lungs and bone and along the second branch, V2, of the fifth cranial nerve to the base of the skull. Lymph node spread is present in less than 10% of patients.

Treatment Approach

Very superficial lesions of the hard palate can be treated definitively with surface molds. If definitive external-beam radiation therapy is used with conventional techniques, the patient is treated with opposed-lateral fields or wedge pairs to 66 to 74 Gy in 2-Gy fractions. When IMRT techniques are used, a dose of 70 Gy is used for gross tumor, 59.4 to 63 Gy for high-risk regions, and 54 Gy for low-risk regions. Most tumors of the hard palate and upper gingiva are treated with surgery. Postoperative radiotherapy is added in high-risk patients (i.e., patients with close or positive margins; perineural invasion; lymphovascular invasion; stage T₃, T₄, or node-positive disease) (Fig. 29-20). In the postoperative setting, doses of 60 to 66 Gy using 1.8 to 2 Gy per fraction are administered, with a dose of 66 Gy being reserved for patients with positive margins. Similar guidelines for nodal coverage are used as has been previously described for carcinomas of the buccal mucosa and retromolar trigone. A prosthesis (i.e., obturator) can be placed over the postsurgical defect during radiotherapy. Alternatively, a balloon filled with water can be used to compensate for postsurgical tissue defects. Postoperative radiotherapy usually begins 2 to 3 weeks after surgery.

FIGURE 29-20 • A-C, Three-dimensional treatment reconstructed radiographs of a patient with hard palate adenoid cystic carcinoma, who required postoperative radiotherapy.

Treatment Outcome

Owing to the rarity of this disease, limited information is available. Evans and Shah reported their 15-year experience from the Memorial Sloan-Kettering Cancer Center. For stage I squamous cell carcinoma of the hard palate, the 5-year disease-free survival rate was 75% (6/8); all patients were treated with surgery alone. For stage II disease, 46% (6/13) were disease free at 5 years; postoperative radiotherapy was added in one patient. In stage III disease, the 5-year disease-free survival rate was 40% (4/10); one patient in the group received postoperative radiotherapy. In stage IV patients, 8% (1/12) of patients treated with surgery alone, 25% (1/4) of those treated with radiotherapy alone, and none (0/2) of those treated with the combined modality were disease-free at 5 years.¹²¹ In another series of patients with squamous cell carcinoma of the hard palate, from the University of Virginia, select early-stage lesions were equally effectively treated by radiotherapy as surgery during the supervoltage era. Patients with a clear margin after surgical resection had improved local control.¹²² See Table 29-9 for select results of definitive radiation therapy of the hard palate.^122–124

Acute and Late Effects

Acute changes occur in the oral mucosa, the salivary glands, and the taste buds during irradiation. Unless the parotid glands are blocked or constrained, xerostomia occurs after a few weeks. With 3-D conformal treatment or IMRT, the restoration of at least partial salivary function can be effectively accomplished with appropriate limits. A study from our institution examined geometric factors influencing dosimetric sparing of the parotid glands during IMRT in head and neck cancer, and found that dosimetric sparing, defined by a mean parotid dose less than or equal to 26.5 Gy, is feasible when the parotid–planning target volume (PTV) overlap is less than 20%. The authors concluded that sparing with additional overlap may lead to inadequate PTV coverage, and thus in some patients dosimetric sparing is not feasible.⁵⁵ Acute mucositis cannot be avoided. For the definitive treatment of lesions with radiotherapy, the goal is to achieve mucositis that is either patchy (grade 2) or confluent (grade 3). Simple erythema (grade 1) usually means that the protraction of the treatment is too long and tumor proliferation during radiotherapy will be too great. Excellent oral care is required, as detailed in the next section, to avoid grade 4 reactions, which require hospitalization. Nutritional support is also required, as discussed later.

Late effects are seen as bone necrosis in the mandible and the maxilla, which occurs after breakdown of the mucosa and exposure of the bone with ensuing osteomyelitis.^125,126 Teeth in poor condition should be extracted prior to radiation therapy. The teeth must be maintained in good condition to avoid extractions, which can lead to infection. Soft-tissue necrosis is frequently seen after both brachytherapy and peroral cone treatment. It is painful, but usually heals without surgery. A necrotic mandible often must be resected.

With the advent of IMRT, there appears to be a reduction in the toxicity associated with treatment of the oral cavity. A study from the University of Michigan demonstrated no cases of osteoradionecrosis in 176 patients treated with head and neck cancer from 1996 to 2005 with at least 6 months of follow-up.¹²⁷ Of these patients, 75% received greater than or equal to 65 Gy to at least 1% of the mandibular volume, and 50% had received at least 70 Gy to this volume. However, the authors found a high level of falloff across the mandible, with the average gradient being 11 Gy. In a study at Memorial Sloan-Kettering Cancer Center¹²⁸ examining our experience of patients receiving IMRT in the treatment of postoperative OCC, we found that the rates of grade 3 or higher acute dermatitis, mucositis, and xerostomia were 3%, 23%, and 0%, respectively. Furthermore, limiting the parotid mean dose to 26 Gy or less reduced the rates of grade 2 or higher xerostomia to 11%, a similar relative reduction that has been seen in other studies as well.¹²⁹ Clearly, more follow-up is needed before more definitively assessing the chronic toxicities of IMRT, but the results at this point are promising, in that local control does not appear to be compromised and short-term toxicity is improved.

Dental and Oral Care

Proper dental care is essential in the management of patients with head and neck cancer. After radiotherapy, there is increased susceptibility to infection and development of dental caries. This is due to the decreased amount and pH of the saliva, diminished vascular supply, reduced number of osteoblasts and osteoclasts, altered normal metabolism of bone, and impaired ability to heal in response to physical, chemical, and biologic injuries after head and neck irradiation. As a result, osteoradionecrosis develops in patients following head and neck irradiation, especially if proper preradiotherapy dental care was not done. The mandible is most commonly involved and the maxilla is rarely affected. The risk of osteonecrosis is directly related to the radiation dose to the bone. The incidence and severity of dental decay and osteonecrosis can be minimized with proper dental care and hygiene before, during, and after head and neck irradiation.

Before radiotherapy begins, the teeth and soft tissues of the oral cavity are carefully examined, pertinent radiographs are obtained, and the findings are recorded. We do not recommend routine extraction of all teeth included in the irradiated volume. The only teeth removed are those that are unsalvageable, likely to require extraction shortly after irradiation, or potentially damaging to the surrounding tissues. When tooth extraction is done before or after irradiation, the underlying alveolar bone must be smoothed to allow primary closure of the gingival tissues. Antibiotics are used routinely as a prophylaxis against infection. All patients are given dental prophylaxis with cleansing of their teeth and instructed on oral hygiene. Mouth irrigation with 1% sodium fluoride solution is started during radiotherapy and continued permanently after radiotherapy to minimize radiation caries.

During radiotherapy, patients are encouraged to irrigate the mouth with a salt and baking soda solution ( to 1 teaspoon of salt and to 1 teaspoon of baking soda in 1 quart of warm water) three to four times daily. Moniliasis is a common complication during irradiation of the head and neck. This can be effectively controlled with systemic antifungal agents. Once the patient has been placed on an agent, it is important to maintain its use until the completion of radiotherapy. Otherwise, moniliasis usually recurs if treatment is discontinued during the course of radiotherapy.

After radiotherapy, the patients are continued on a good oral hygiene program and topical fluoride applications (mouth rinses) as well as a fluoride-containing dentifrice. Caries are filled and there are no unusual contraindications for endodontic procedures. Extractions are performed whenever necessary and antibiotics are routinely used to minimize the risk of infection. When osteonecrosis develops, it is usually managed conservatively with topical or systemic antibiotics and analgesics initially. Good oral hygiene is imperative. Loose spicules of bone above the gingival crest are gently removed. Healing may take place over a period of several months. Partial mandibulectomy is performed only if conservative management fails and the patient continues to have persistent pain, infection, or trismus.

Nutrition

Maintenance of good nutrition is important for patients with head and neck cancer. Most patients receiving radiation therapy to the head and neck area do experience some eating problems during the treatment. This is due, in part, to the side effects of radiation therapy such as the loss of sense of taste, decreased saliva, and inflammation of the mucous membranes, resulting in soreness of the mouth and dysphagia. The postponement of dentures to avoid irritation of the mucous membranes in edentulous patients makes mastication difficult. The psychological impact, mental stress, discomfort, and pain associated with the disease may also contribute to a decreased appetite and food intake. Patients who have undergone head and neck surgery may experience difficulties in chewing and swallowing because of the loss of their normal tissues and because of injury to the nerves necessary for these functions. It is important to inform the patient and his or her family of the treatment side effects and the potential problems of eating that may arise, and to emphasize the importance of good nutrition during and after treatment. The assistance of a dietitian experienced in working with cancer patients can be very helpful in providing guidance for a well-balanced diet. Modification of the consistency and texture of the food may be necessary. Small, frequent meals of soft to semiliquid foods may be better tolerated. Dietary modifications are best worked out on an individual basis, tailored to the patient’s usual eating habits, cultural practices, and religious beliefs. Psychological and social support and the cooperation of the patient’s family may be essential in providing adequate dietary intake.

Dietary supplements such as instant breakfast, Sustagen, Ensure, or other homemade substitutes are soothing to the mucosa and easy to swallow, and provide a substantial amount of calories as well as essential vitamins.

In patients with severe pain and dysphagia or problems of mastication or excessive weight loss, tube feeding may be necessary. The aim of a dietary program during head and neck irradiation is to provide adequate nutrition and prevent weight loss. Percutaneous gastrostomy tube placement may be required for patients who lose more than 10% of their body weight. Multiple studies have shown that prophylactic gastrostomy tubes are safe and may limit weight loss in patients receiving radiation for head and neck cancer,^130,131 and we strongly consider their placement, particularly in patients receiving chemotherapy in conjunction with radiation.