38

Anatomy

The oral cavity consists of the upper and lower lips, gingivobuccal
sulcus, buccal mucosa, upper and lower gingiva (including the alveolar
ridge), hard palate, floor of the mouth, and anterior two thirds of
the mobile tongue.

Although many investigators include the retromolar trigone and soft
palate in their discussions of the oral cavity, these anatomic
structures are grouped together with tumors of the faucial arch and
are discussed in Chapter 39.

Lips

The lips are composed of the orbicularis muscle, which is covered by
skin and mucous membrane on the inner surface. The transitional area
between the skin and mucous membrane is called the vermilion border.
The blood supply comes from the labial artery, a branch of the facial
artery. The motor nerve branches come from the facial nerve. The
sensory nerve to the upper lip is the infraorbital branch of the
maxillary nerve; that of the lower lip is composed of branches of the
mental nerve, which originate in the inferior alveolar nerve. The
commissure is partially innervated by the buccal branch of the
mandibular nerve.

Gingiva

The upper gingiva is formed by the alveolar ridge of the maxilla,
which is covered by mucosa and the teeth and continues medially with
the hard palate. The lower gingiva covers the mandible from the
gingivobuccal sulcus to the mucosa of the floor of the mouth. It
continues posteriorly with the retromolar trigone and above with the
maxillary tuberosity. There are no minor salivary glands in the mucous
membrane over the alveolar ridges. [ref: 41]

Buccal Mucosa

The buccal mucosa is made up of the mucous membrane covering the
internal surface of the lips and cheeks (buccinator muscle) extending
from the line of attachment of the upper and lower alveolar ridges to
the point of contact of the lips posteriorly and the orbicularis
anteriorly. The masseter muscle lies posterior and lateral to the
buccinator muscle. The blood supply of the buccal mucosa comes from
the facial artery. Sensory fibers are supplied by the buccal nerve, a
branch of the mandibular nerve. The motor nerve to the buccinator
muscle is derived from the facial nerve.

Floor of the Mouth

The floor of the mouth, bounded by the lower gingiva anteriorly and
laterally, extends to the insertion of the anterior tonsillar pillar
into the tongue posteriorly. It is divided into halves by the lingual
frenulum. The floor of the mouth is covered by a mucous membrane with
stratified squamous epithelium. The sublingual glands lie below the
mucous membrane and are separated by the mid-line genioglossus and the
geniohyoid muscles. The genial tubercles are bony protuberances that
occur at the point of insertion of these two muscle groups on the
symphysis. [ref: 41] The floor of the mouth contains several muscles,
including the mylohyoid and, under it, the digastric muscle. The
submaxillary glands are located on the external surface of the
mylohyoid muscle, between its insertion to the mandible. The
submaxillary duct (Wharton's duct) is about 5 cm long and courses
between the sublingual gland and the genioglossus muscle; its orifice
is in the anterior floor of the mouth, near the mid-line. The sensory
nerve is the lingual nerve, a branch of the submaxillary nerve. The
arterial supply is the lingual artery, a branch of the external
carotid.

Oral Tongue

The tongue is a muscular organ composed of the styloglossus,
hyoglossus, and hyoid muscles (Fig. 38-1). The tongue is covered by a
mucous membrane with stratified squamous epithelium. The circumvallate
papillae, situated posteriorly with a V-shaped configuration, separate
the base of the tongue from the mobile tongue. The oral tongue
consists of the tip, dorsum, lateral borders, and undersurface. The
blood supply is the lingual artery, a branch of the external carotid
artery. [ref: 48] The sensory nerve is the lingual nerve, a branch of
the maxillary nerve; the hypoglossal nerve is the motor nerve. The
taste buds are innervated by the chorda tympani branch of the sensory
root of the facial nerve.

Lymphatics

The lymphatics of the upper lip drain mostly to the submandibular
lymph nodes; the periauricular and parotid lymph nodes occasionally
receive lymphatic channels from the upper lip. The lower lip
lymphatics drain to the submandibular and posteriorly to the
subdigastric lymph nodes. The lymphatics of the lower gingiva drain to
the submandibular and subdigastric lymph nodes.

The first echelon of lymph node drainage of the floor of the mouth is
to the submandibular and subdigastric lymph nodes.

Primary lymphatic drainage in the oral tongue is to the subdigastric
and submandibular lymph nodes. Rouviere [ref: 62] described the
lymphatic trunks that bypass this primary lymphatic drainage and go
directly to the midjugular lymph nodes, which probably accounts for
the relative frequency of metastatic lymph nodes in these locations
(Fig. 38-2).

The lymphatic drainage of the buccal mucosa is primarily to the
submandibular and subdigastric lymph nodes.

Epidemiology

In 1997, the estimated number of oral cancers in the United States was
21,900, an incidence of 9.5 per 100,000 population; 6400 persons died
of the disease, with a mortality rate of 2.2 per 100,000. [ref: 53]
This cancer is predominantly a disease of men and of middle age and is
often associated with poor oral hygiene and abuse of tobacco and
alcohol. In recent years, there has been an increase in oral cancer
among relatively young women who apparently never drink alcohol or
smoke. The cause of this increase is unclear.

Natural History

Most early mucosal lesions are asymptomatic and present as slightly
elevated red lesions with ill-defined borders. The larger the lesion,
the more likely it is to be invasive carcinoma. Almost all lesions
over 2 cm in diameter are invasive. [ref: 42] Red lesions
(erythroplakia) are most likely to be cancerous. Often white lesions
(leukoplakia) are present. They are less likely to be malignant, but
approximately 17.5% are said to become cancerous on long follow-up.
[ref: 66]

Except for lesions arising from the tip of the tongue or extending
across the midline, metastatic disease usually occurs in the
ipsilateral cervical lymph nodes. [ref: 33] Lymph node involvement in
lesions of the lip is relatively rare, although 5% to 10% of patients
with clinically negative necks later develop lymph node metastases.
[ref: 37]

Clinical Presentation

Most patients with early disease present with a canker sore, denture
sore, or a lump in the mouth, frequently of several weeks' duration,
as the only symptom of the disease. Advanced lesions may be associated
with bleeding or pain. Sometimes fixation of the tongue results in
difficulty with speech or eating as a presenting symptom. With more
advanced lesions, trismus of the jaw with pain radiating to the ear
may occur. Occasionally an earache may be the only initial presenting
symptom.

The incidence of lymph node metastases of the upper gingiva is about
15% to 20% on admission, and there is about the same incidence of
subsequent development of clinical cervical lymph node metastasis in
initially clinically negative necks. [ref: 33] The incidence of
clinically positive nodes on admission for lower gingival tumors
depends on the stage, ranging from 15% to 50%. Clinically positive
nodes later develop in approximately 20% of patients who present with
N0 necks. Contralateral lymph node metastases are extremely rare.
[ref: 9]

Approximately 30% to 59% of patients with cancer of the floor of mouth
have positive neck nodes on presentation. Of patients with clinically
negative nodes, approximately 40% have pathologically positive nodes.
Of all of the patients with negative nodes at presentation, the
incidence of eventual development of a nodal metastasis without
treatment is about 20% to 35%. Submental lymph nodes are involved in
fewer than 5% of patients. [ref: 33] The incidence of bilateral lymph
node involvement is relatively high because many lesions are near or
cross the midline (Fig. 38-3).

About 35% to 65% of patients with tumors of the oral tongue have
clinically positive lymph nodes on admission; 5% to 10% of them are
bilateral (Fig. 38-3). Among patients with initially clinically
negative nodes, approximately 30% eventually develop metastatic
disease in the lymph nodes, with the exact incidence depending on the
initial stage of the disease [ref: 33] (Fig. 38-3).

For cancers of the buccal mucosa, the incidence of positive cervical
lymph nodes on admission is 10% to 30%. The risk of subsequent
development of clinical metastases or pathologically positive lymph
nodes in the neck that was negative for disease on examination is
about 15%.

Tumors of the oral cavity spread superficially along the mucosa and
infiltrate deeper tissues, including bone (maxilla and mandible) and
muscles of the oral tongue or floor of the mouth.

Diagnostic Workup

Careful physical examination, including examination of the head and
neck area, is the first step (Table 38-1). Inspection and bimanual
palpation of the primary tumor is mandatory to determine the
submucosal extent of the lesion, degree of the fixation of the tongue,
fixation of the floor of mouth to the mandible, and evaluation of the
submandibular duct and gland.

Radiographic examinations may not be necessary for very early
superficial lesions. However, they are an essential part of the workup
in more advanced stages of disease. Radiologic examinations are quite
helpful in three different ways [ref: 48]: evaluation of the status of
the mandible in regard to tumor invasion (Panorex, computed tomography
[CT] scan, magnetic resonance imaging [MRI]); evaluation of
extent of primary disease (CT scan, MRI); and evaluation of nodal
metastasis (CT scan, MRI, positron emission tomography).

Staging

The American Joint Committee on Cancer adopted the system for the
classification of oral squamous cell carcinomas shown in Table 38-2
[ref: 5] Invasion of the mandible or fixation of tongue places the
lesion in the T4 category.

Pathologic Classification

The majority (approximately 90%) of neoplasms of the oral cavity are
squamous cell carcinomas. Uncommon non-squamous cell cancers include
malignant tumors of the minor salivary gland, such as adenoid cystic
carcinoma, mucoepidermoid carcinoma, and adenocarcinoma, which are
found most often in the palate, cheek mucosa, and lips. Rarely,
lymphoma, melanoma, or sarcoma can arise in the oral cavity; these
lesions comprise approximately 10% of cases. Metastatic carcinomas to
the oral structures occur infrequently.

General Management

A variety of therapeutic measures are available for managing localized
carcinomas of the oral cavity, including surgery, radiation therapy,
laser excision, and combinations of these methods. [ref: 74] Radiation
therapy alone for N0 disease and surgery followed by postoperative
radiation therapy for N+ disease has been used for the management of
neck disease. Chemotherapy and immunotherapy have not shown any
efficacy. A decision on the treatment choice depends on the size and
site of the primary lesion, presence or absence of metastatic cervical
lymphadenopathy, expected morbidity associated with a given
therapeutic regimen, other medical comorbidity factors, preference,
skill, and experience of the surgeon and the radiation oncologists at
a given institution, and finally, the wishes of the patient.

Surgical Excision

Excisional biopsy, even of a small lesion, is usually inadequate.
Patients seen after excisional biopsy, especially if the surgical
margins are judged to be inadequate, should receive additional
treatment with an interstitial implant or intraoral cone. The use of
reexcisions to check the adequacy of a prior surgery is useless under
these conditions because few tumor cells are present, and the
pathologist is "looking for a needle in a haystack." [ref: 48]

Wide local excision is the treatment of choice for well-circumscribed
lesions that can be excised transorally. Wide local excision of
lesions of the posterior part of the mobile tongue is difficult and
without reconstruction can result in serious functional deficits in
swallowing and speech. External radiation therapy in combination with
interstitial implant may be selected for this group of patients.
Recently, a group of head and neck surgeons with expertise in plastic
reconstructive surgery and a group of plastic surgeons who treat head
and neck cancers have advocated larger surgical excisions followed by
reconstruction. Although anecdotal successful cases are presented at
meetings, the true success rate of this practice has not been
substantiated. The question of what is considered to be an adequate
clear surgical margin is still debated. Although a tumor margin of 1
cm is generally considered adequate for most other carcinomas, for
cancers of the oral tongue margins of 1.2 to 2 cm are generally
considered adequate. [ref: 48] The extent of surgery for larger
lesions is usually hemi- or total glossectomy. Severe functional
deficits after such surgical procedures signify the importance of
reconstructive surgery in this group of patients. Postoperative
radiation therapy is recommended for larger lesions, close or positive
margins, and perineural invasion. Postoperative irradiation also
should be recommended for patients who initially had positive surgical
margins and subsequently were found to have negative surgical margins
on reexcision. [ref: 63] Massive surgical resections, which are
occasionally associated with total glossectomy and laryngectomy, are
usually recommended for patients with good general condition.

Similar general philosophies also can be applied to carcinomas of the
floor of mouth. Wide local excision of small tumors, with
reconstruction, usually results in good functional outcome. In lesions
of the floor of mouth that are tethered or fixed to the mandible,
resection of the inner table is often recommended, which results in
reasonable speech and swallowing. Postoperative irradiation is usually
recommended because of often associated negative prognostic factors.
In patients with advanced lesions due to bone invasion, wide local
excision of tumor along with segmental resection of the mandible is
often followed by reconstruction of the floor of mouth as well as the
mandible. In patients with very advanced disease involving the floor
of the mouth, tongue, and mandible and massive neck disease, the
chance of cure with any aggressive treatment is slim and is often
associated with formidable complications. In these cases, a course of
radiation therapy should strongly be considered.

Management of Neck Nodes

In patients with small lesions resected with adequate margins,
thickness of less than 2 mm, and no negative prognostic factors, if
the neck is clinically and radiographically negative, no further
treatment is needed, and the neck can be observed. In patients with
resected primary lesions of the oral tongue or floor of mouth over 2
to 3 mm thick and/or negative prognostic factors such as perineural or
perilymphatic invasion, the neck needs to be treated. Because of the
central location of these lesions, most often bilateral neck
irradiation to moderate doses, which leaves minimal morbidity, is the
treatment of choice. Occasionally, aggressive surgeons have
recommended bilateral modified or functional neck dissection. In
general, any form of bilateral neck dissection has worse cosmetic
results than a moderate dose of radiation (45 to 50 Gy). If neck
dissection shows only one positive node with no extracapsular
extension, we have usually recommended no radiation therapy to the
neck. If neck dissection has shown more than one node and especially
metastases at more than one nodal station or extracapsular extension
of a single or multiple nodes, a course of postoperative radiation
therapy to the neck is indicated. In patients with clinically or
radiographically (CT scan with contrast) positive neck nodes, the
treatment of choice for the neck is ipsilateral neck dissection
followed by bilateral postoperative neck irradiation. Contralateral
prophylactic neck dissection is a serious disservice to the patient.

Radiation Therapy Techniques

Optimal oral hygiene and pretreatment dental care are of utmost
importance in patients in whom radiation therapy is contemplated. All
patients at our institution are regularly seen by a dentist or oral
surgeon for dental evaluation and fluoride treatment. Any potential
surgical procedures and tooth extractions should be performed before
initiation of radiation therapy. Most patients will have significant
dental problems that require total teeth extraction. Approximately 8
to 10 days lapse time is needed for complete recovery before
initiation of radiation therapy. Precaution in any surgical procedure
on the gums or tooth extraction, after a course of radiation therapy,
is a life-long commitment. Awareness of this issue by radiation
oncologists, dentists, and especially patients is an important factor
in reducing potential complications of radiation therapy.

For treatment of carcinoma of the mobile tongue, the most commonly
used technique is opposed lateral portals including the upper necks.
The tongue is depressed away from the palate with an individually
constructed tongue bite block (Fig. 38-4). At some institutions, a
cork and tongue blade is used. I prefer the former because the latter
has the possibility of pushing the tongue backward rather than
downward, and it leaves a portion of the dorsal tongue out of the
field. The portal includes the submandibular and subdigastric lymph
nodes. The submental nodes are also included in the portal film in the
volume of irradiation, and their coverage is of particular importance
when the lesion is located at the tip of the tongue, anterior floor of
the mouth, or lower lip. The upper border is shaped to give at least a
2-cm margin above the dorsum of the tongue and to spare the hard
palate and parotid glands. The posterior border is designed to be
about 2 cm behind the sternocleidomastoid muscle. The inferior part of
the field usually lies at the thyroid notch. For patients with
cervical nodal metastasis, depending on the degree of involvement of
the nodes, treatment of level 4 or level 5 nodal stations may be
indicated. If the posterior chain requires irradiation, the portals
are reduced to spare the spinal cord at 45 Gy. In the case of lower
neck (level 4) irradiation, these nodes are treated through an
anterior portal with a larynx shield.

The postoperative dose is usually 60 Gy at a rate of 1.8 to 2 Gy per
day. For close or positive margins or extracapsular extension in any
of the cervical nodal stations, an additional 6 Gy is delivered with
reduced fields. Every attempt should be made to avoid an excessive
dose of irradiation to the mandible.

In patients with very lateralized primary lesions, ipsilateral wedge
pair portals can be used to boost the primary site and the first
echelon of lymph nodes to the prescribed dose. Sparing the
contralateral salivary gland is very desirable in this situation. If
electron-beam therapy is used for occasional ipsilateral lesions, the
physical properties of a given energy of electron beam should be
considered. In patients for whom irradiation is the only treatment
modality, boosting the primary lesion with either interstitial
irradiation or an intraoral cone results in increased tumor control
and decreased complications by sparing high-dose effects to normal
tissue, especially the mandible, and thus avoiding osteoradionecrosis.

Interstitial Irradiation

Depending on the volume of the implant, single-plane, double-plane, or
volume implants have been used to cover the tumor volume with at least
a 0.5- to 1-cm margin. The most commonly used technique is
percutaneous afterloading technique with angiocaths and **192Ir. [ref:
79] The implant can be done manually or by using individually
constructed templates. Another preferred method of interstitial
implant of the oral tongue is the **192Ir hairpin technique, devised
and perfected by Pierquin. [ref: 59] The last two have resulted in
better precision and improved dosimetry. [ref: 39] Most of these
implants are done with a classic low dose rate, which delivers
approximately .45 to .5 Gy an hour to the target volume. There has
been a recent surge in the use of other dose rates such as pulsed dose
rate and high dose rate in brachytherapy, mostly because of logistics
and economic reasons. However, no trial shows the superiority of these
dose rates over conventional low dose-rate brachytherapy. Indeed, some
recent reports have shown a lower therapeutic ratio and higher
complication rate with high dose-rate brachytherapy. [ref: 43] It is
common practice to use interstitial irradiation after external-beam
radiation therapy with the rationale that after the external-beam
irradiation the tumor is smaller and the implant would be easier with
the smaller volume receiving higher doses. However, some argue that
the implant would often be easier to perform before external
irradiation because there is a better ability to outline the target
volume and the patient is free from the acute side effects of external
radiation therapy. Interstitial implant either alone (for small T1 and
T2 tumors) or after external-beam irradiation yields good results.
[ref: 80] In patients in whom surgical resection is done and
microscopic tumor is known to be present at the margin of resection,
an interstitial implant has been shown to convert their ominous
outcome in local control to that of patients with negative margins.
[ref: 12]

Intraoral Cone

Intraoral cone is a localized radiation therapy technique, with
similar indications as interstitial irradiation, but it is more
suitable for lesions located in the anterior tongue or anterior
segment of the floor of the mouth. Irradiation with intraoral cone
uses either 250 keV [ref: 48] or electron beams of 6 to 12 MeV. [ref:
74] The cone is always equipped with a device to visualize the target
volume and ensure proper coverage. When indicated and available, cone
therapy is usually preferred to interstitial therapy because of ease
of use. In general, centrally and anteriorly located tumors are
treated with intraoral cone. Lesions close to or tethered to the
mandible are usually boosted with interstitial irradiation. Either of
the techniques has resulted in better tumor control as well as reduced
complications of high-dose radiation therapy, especially in the
mandible. [ref: 7,77,80] In general, external-beam radiation therapy
followed by either boost technique is preferred over external
irradiation alone (Table 38-3). [ref: 48]

Irradiation Dose

Irradiation dose is generally determined by the tumor site, target
volume, fractionation schema, technique of delivery, and tolerance of
the surrounding normal tissue structures. The various organs
comprising the oral cavity manifest different tolerances to
irradiation. For example, the musculature of the tongue and lips
manifests a high tolerance to irradiation, whereas the alveolar ridge
and mandible have the lowest tolerance. The dose of irradiation is
also dependent on the number of clonogenic cells (tumor burden). With
conventional fractionation, a dose of 55 to 60 Gy in 5 to 6 weeks is
considered adequate for microscopic disease; 65 to 70 Gy in 6.5 to 7
weeks is recommended for small T1 and T2 tumors. Larger T3 and T4
tumors, if treated by irradiation alone, require 75 to 80 Gy or higher
doses. Because of poor tolerance of the normal structures of the oral
cavity to this dose level of radiation with resulting unacceptable
complication rates, other strategies are required for the treatment of
advanced tumors of the oral cavity, including a combination of surgery
and radiation therapy or altered fractionation irradiation for
inoperable or unresectable tumors.

Fractionation

In the past decade, based on biologic calculations, altered
fractionation irradiation has been used to treat patients with oral
cavity lesions. Altered fractionation may include hyperfractionation
(1.2 Gy per fraction, twice a day, for a total dose of 76 to 80 Gy)
[ref: 47] or accelerated hyperfractionation (1.6-Gy fractions, two per
day, with a minimum of 4 hours between fractions and a 2-week break
after 38.4 Gy, up to a total dose of 67 Gy in 6 weeks) [ref: 77] or
accelerated hyperfractionation using an in-field boost. [ref: 55]
Although significant improvements in local tumor control and survival
using these altered fractionation plans have been reported from
institutional trials, [ref: 47,55,77,78] one randomized study
comparing conventional fractionation with hyperfractionation showed
little or no improvement. [ref: 38] Currently, the efficacy of these
various altered fractionation schemas is being compared with that of
conventional fractionation in an intergroup protocol being conducted
by the Radiation Therapy Oncology Group.

Combined Surgery and Radiation Therapy

The cure rates for T1 and T2 carcinomas of the oral cavity are quite
good. [ref: 36,40] However, the cure rates for T3 and T4 tumors,
whether treated by radiation therapy or surgery alone, are less than
satisfactory. In these extensive lesions, failures from radiation
therapy are primarily caused by an inability to control the
radioresistant nidus at the primary site or the nodal disease. Because
of this, a program of combined surgery and irradiation has frequently
been performed. The planned use of combined surgery and radiation
therapy permits surgical resection of gross disease, even if the
resection margins are inadequate by previous standards, followed by
irradiation for subclinical or occult disease. This approach allows
effective palliation and some cures for many patients who are not
otherwise salvageable or are faced with functionally and cosmetically
unacceptable alternatives.

Two conceptual approaches to combined radiation therapy and surgery
have emerged: preoperative or postoperative radiation therapy. [ref:
60,71,75] Whether radiation therapy should be used preoperatively or
postoperatively has been the subject of debate. Although no major
differences have been found between these two approaches in terms of
local control of primary lesions or patient survival, in certain tumor
sites with exophytic tumors, good tumor response after preoperative
irradiation has encouraged additional irradiation to curative levels,
eliminating the need for a mutilating surgical procedure. Although
preoperative radiation therapy was preferred at our institution in the
past, postoperative irradiation has been used more frequently lately
for advanced tumors.

Conventional Preoperative Radiation Therapy

Conventional preoperative radiation therapy decreases local recurrence
and potential distant metastases. The disadvantages of preoperative
radiation therapy are that the exact tumor extent is unknown at the
time of surgery, surgery is delayed, and postoperative complications
may be increased. The dose used in conventional preoperative radiation
therapy is 45 Gy given in 4.5 to 5 weeks. This is followed 1 month
later by radical surgery encompassing all possible areas of disease as
though radiation therapy had not been given.

High-Dose Preoperative Radiation Therapy or
Sequential Postirradiation Resection

The dose used in high-dose preoperative radiation therapy is 60 to 65
Gy given in 6 to 7 weeks and delivered homogeneously to the primary
site and to the first echelon of lymph nodes. The treatment portal
must be progressively reduced after 50 Gy. In this program, unlike in
a conventional moderate-dose preoperative program, radiation therapy
is followed by limited surgical resection. Only the residual nidus of
the primary lesion, mostly in the muscles or bone, is excised, on the
assumption that the peripheral, superficial disease has been
controlled by high-dose radiation therapy. This approach is intended
to avoid excessive functional and cosmetic mutilation by radical
surgery and has been useful in managing advanced lesions arising from
the posterior oral tongue or alveolar ridge with tumor involvement of
the adjacent soft palate or base or tongue. Any attempt at radical
surgery would probably yield a high rate of postoperative
complications and is therefore ill advised.

Postoperative Radiation Therapy

The advantage of postoperative radiation therapy is that a high dose
of irradiation can be delivered to known sites of residual disease and
the extent of pathologic involvement is understood. The procedure
usually is performed approximately 3 to 4 weeks after surgery, after
the wound is healed. A dose of 55 Gy in 6 weeks should not be exceeded
if the surgery is radical. If the surgery is primarily a debulking
procedure, high-dose radiation therapy (65 Gy in 7 weeks) for gross
residual disease must be given through a shrinking-field technique to
the area of known disease.

Treatment and Results of Specific Subsites

Lip

Therapeutic Options

Small cancers of the lip (less than 2 cm) are treated equally well
with surgery or radiation therapy with excellent cosmetic and
functional results. Larger lesions (2 to 4 cm) also can be treated
with either surgery or radiation therapy. With surgery, however,
reconstruction with a flap often is necessary. The reconstructed lip,
although it may look good in a picture, has a significant problem
functionally. Postoperative irradiation is recommended for positive
margins or perineural invasion. Lesions larger than 4 cm as well as
uncommon lesions with poorly differentiated histology and tumors
involving the commissure are best treated with radiation therapy, with
surgery reserved for salvage. In these circumstances, the results of
surgery are poor both cosmetically and functionally.

Regional nodes are not treated in most of these patients. In patients
with locally extensive disease, recurrent disease, or poorly
differentiated tumors, the neck needs to be treated either by modified
neck dissection or radiation therapy. In rare patients with positive
nodes at presentation, the neck needs to be treated with surgery
followed by postoperative radiation therapy.

Radiation Therapy Techniques

The target volume includes the primary tumor with a 1.5-cm margin if
there is no indication for nodal irradiation and the lesion is well
differentiated. External-beam irradiation of 100 to 200 keV and/or
electron beam of a suitable energy (6 to 9 MeV with 1- to 1.5-cm
bolus) is used. Individually designed and constructed lead shields in
the gingivobuccal sulcus are always used to protect the underlying gum
and mandible. A dose of 50 Gy in 4 to 4.5 weeks for smaller lesions
and 60 Gy in 5 to 6 weeks for larger lesions is usually recommended.
In smaller lesions, interstitial irradiation alone has been
recommended. Some practitioners have used external-beam irradiation
(about 50 Gy) followed by an interstitial boost of 15 Gy.

Results of Therapy

Results of treatment are summarized in Table 38-4. For the majority of
patients, either surgery or radiation therapy produces equally good
results. Smaller lesions have excellent functional and cosmetic
results with either modality. For larger lesions, cosmesis and
functional results are better with radiation therapy alone. In
patients with recurrent disease, the local tumor control rate
generally is 50% with disease-specific survival of about 30%. Patients
with lip cancer who present with bony invasion have a poor outcome
regardless of the treatment.

Oral Tongue

Squamous cell carcinoma of the oral tongue (i.e., the anterior two
thirds or mobile portion of the tongue) is a common type of oral
cancer and includes lesions arising from the mobile portion of the
tongue anterior to the circumvallate papillae. Approximately 20% to
30% of T1 and T2 tongue carcinomas and 70% to 80% of T3 and T4 lesions
have nodal metastases when the initial diagnosis is made, and of
these, 15% to 20% have bilateral involvement. [ref: 4,33]

Therapeutic Options

The management of carcinoma of the oral tongue is difficult and
controversial and depends on size, location, and growth pattern of the
primary lesion and the nodal status in the neck.

T1 and T2 Tongue Lesions

Although surgery or radiation therapy is effective in controlling
small cancers, it is not unreasonable to consider transoral surgical
resection for small, well-defined lesions involving the tip and
anterolateral border of the tongue. [ref: 68] These lesions can be
cured by resection without risk of functional morbidity, particularly
in aged and feeble patients. Radiation therapy (60 to 65 Gy in 6 to 7
weeks) is preferred for small, posteriorly situated, ill-defined
lesions that are inaccessible for surgical excision through the
peroral route.

Superficial, exophytic T1 and T2 lesions with little muscle
involvement are amenable to successful treatment by radiation therapy
(65 to 70 Gy in 7 weeks). For moderately advanced, medium-sized T2
tumors involving the adjacent floor of the mouth, surgical treatment
must include partial glossectomy, partial mandibulectomy, and radical
neck dissection. For these lesions, comprehensive irradiation (70 to
75 Gy in 7 to 8 weeks) with progressively decreasing fields to the
primary site and neck nodes is preferred, and surgery is reserved for
salvage of residual or recurrent disease.

T3 and T4 Tongue Lesions

Advanced disease with deep muscle invasion often associated with
cervical lymph node metastases, is unlikely to be cured with
irradiation alone. It is best managed by planned combined irradiation
(50 to 60 Gy in 5 to 6 weeks) and surgery.

Management of Neck Nodes

With the exception of small, exophytic mucosal lesions, treatment of
carcinoma of the oral tongue must include treatment of primary lesions
and regional nodes because of the high incidence of occult metastases,
even in patients with N0 necks.

In patients with T1 and T2 lesions of the oral tongue in whom the neck
is not treated if clinically negative, approximately 25% to 30%
develop nodal metastases during the course of the disease. [ref: 76]
Therefore, if these lesions are treated by peroral excision or
irradiation alone, the neck must be considered at risk for occult
metastases and should be followed closely or irradiated electively to
prevent nodal recurrence. [ref: 31] The so-called prophylactic neck
dissection, however, has not been found to be necessary or rewarding.

Combined therapeutic neck dissection and radiation therapy is the
procedure of choice for the residual N1, N2, or N3 neck after the
primary lesion is controlled.

Radiation Therapy Management

In general, the smaller, more anteriorly situated primary lesion in an
edentulous jaw is most suitable for interstitial implant or intraoral
cone radiation therapy as a boost procedure.

When interstitial implants are used for carcinoma of the oral tongue,
single or double planes are used to irradiate a slab of tissue 1 or 2
cm thick, respectively. [ref: 17] Except in the treatment of tumor
arising from the dorsum of the tongue, a volume implant is rarely
used. To avoid high doses to the mandible and to prevent possible
osteoradionecrosis, rubber tubing or a dental roll may be sutured
between the gum and the implant. An afterloading technique using
angiocaths and administering **192Ir percutaneously through the
submental route facilitates good geometric distribution of the
implant. [ref: 80]

The edentulous jaw accommodates the intraoral cone smoothly and
easily; it may be necessary to sacrifice a few anterior teeth to
facilitate insertion of the cone, even if they are in good repair.

Peroral or intraoral cone radiation therapy generally is performed in
the early phase of the treatment program as a boost technique. For an
anteriorly situated carcinoma that does not involve the adjacent floor
of the mouth or the gingival ridge, a boost dose of 25 to 30 Gy in 10
daily fractions, five fractions a week by intraoral cone, can be
given. In addition to the comprehensive radiation therapy of 45 to 50
Gy (Fig. 38-5), this technique can deliver a high dose to the primary
lesion, producing high cure rates. [ref: 20,30,77,80] It has replaced
the interstitial implant for treatment of early carcinoma of the oral
tongue at some institutions. [ref: 80]

Radiation Therapy Results

Results of radiation therapy for carcinoma of the oral tongue are
related to the size of the primary lesion and the presence of
metastatic nodes and are comparable with those achieved with surgery.
[ref: 17,19,22,40,58] Survival rates are twice as good in patients
without metastatic nodes as in patients with nodal involvement. [ref:
70]

Small mucosal tumors can be successfully treated by radiation therapy
or surgical excision, with similar results. The reported series
indicate a 5-year survival rate of approximately 80% for T1 lesions
and 50% for T2 lesions. [ref: 17,57,69,70] Local control for advanced
T3 and T4 lesions is poor with surgery or radiation therapy, with
5-year survival rates of approximately 25% to 30%. [ref: 17,19,46,76]

Extensive nodal disease (N2 or N3 neck) is rarely salvageable by
radiation therapy or surgery and currently is managed by combined
modalities. Unfortunately, the chemotherapeutic response is usually
measured in terms of weeks or months. Chemotherapy given before
surgery does not appear to increase the morbidity of subsequent
therapies, but it may exaggerate the acute mucosal reaction during
radiation therapy.

The experience with radiation therapy for carcinoma of the oral tongue
is summarized in Table 38-5 and Table 38-6. Results are good for
patients in whom intraoral cone radiation therapy is suitable, in the
neighborhood of 90% for T1 and T2 lesions (Table 38-5). [ref: 80]
Combined radiation therapy and surgery was performed in a small group
of patients.

Floor of the Mouth

Carcinoma of the floor of the mouth is often located in the anterior
portion of the floor adjacent to Wharton's duct orifice; it often
spreads along the directional course of the submaxillary duct.
Far-advanced lesions may invade the neighboring mandible.

The incidence of lymph node metastases is less than 10% for T1
lesions. [ref: 76] In extensive T3 and T4 tumors, the incidence is
higher, ranging from 50% to 75%, and of these, 20% are bilateral.
[ref: 33]

Therapeutic Options

When the tumor is small or limited to the mucosa, it is highly curable
by surgery or irradiation alone. For moderately advanced T2 or
exophytic T3 lesions, a trial course of irradiation may be given
first, and salvage surgery is used for any residual disease at the
primary site or neck nodes. For infiltrative lesions with fixation or
tethering to the adjacent mandible, although the surface size is still
small or categorized as T1, surgical excision of the tumor with a rim
of adjacent normal inner table of the mandible should be followed by
postoperative irradiation to sterilize any microscopic disease at the
tumor site. For extensive, infiltrative T3 and T4 lesions with marked
involvement of the adjacent muscle of the tongue and mandible, radical
surgery followed by plastic closure and postoperative radiation
therapy is the procedure of choice.

Radiation Therapy Management

Because of its proximity to the gingival ridge, which is vulnerable to
high-dose radiation-induced soft tissue ulceration and
osteoradionecrosis, the floor of the mouth has a much lower radiation
tolerance than the tongue. These facts must be taken into
consideration in selecting irradiation modalities.

Very small superficial lesions can be treated with interstitial
implant (60 to 65 Gy) or intraoral cone (45 Gy over 3 weeks) alone. T1
and early T2 lesions need to be treated with external-beam irradiation
and various boost techniques such as interstitial implant (45 Gy
external plus 25 Gy with implant) or intraoral cone (45 Gy external
plus 20 Gy intraoral cone). The sequence of these two treatments has
been varied depending on the experience of the radiation oncologist.
In most instances, external-beam irradiation precedes implant. The
cone therapy is usually done first, followed by external-beam
radiation therapy. Occasionally, cone therapy is sandwiched between
two courses of external-beam irradiation. In patients for whom boost
treatment with intraoral cone or interstitial implant is not feasible,
after the initial 45 Gy is delivered through lateral portals to the
large volume, further irradiation of 20 Gy in 2 weeks may be
administered to the primary site in the form of external-beam
radiation therapy. Appropriate technique must be used to minimize the
dose of irradiation to the mandible. Figure 38-6 illustrates the
placement of the radiation therapy portal for treatment of carcinoma
of the floor of the mouth.

Advanced T3 and T4 lesions are best treated with surgery,
reconstruction, and postoperative irradiation. In patients for whom
surgery is not an option, external-beam radiation therapy is
administered through large opposing lateral portals with equal loading
covering the primary lesion and nodal areas to a dose of approximately
45 Gy in 4.5 to 5 weeks, followed by two- or three-step reduced fields
to a total dose of 74.4 to 76.8 Gy via a hyperfractionated regimen
(1.2 Gy twice a day). In patients with tongue involvement, the portal
arrangement is similar to that for oral tongue lesions (Fig. 38-4).

Management of the neck is similar to that of the oral tongue. Patients
with superficial small lesions (less than 2 mm thick) without negative
pathologic prognostic elements and with a clinically and
radiographically negative neck can be observed as long as they are
examined frequently for up to 3 years. Otherwise, most patients with
lesions of the floor of the mouth who have negative necks require a
dose of irradiation (50 Gy) to the first-echelon lymph nodes on both
sides. Prophylactic bilateral neck dissection of any kind has no
therapeutic value and is commonly associated with more side effects
than radiation therapy; this practice should seriously be discouraged.
For N1, N2, and N3 disease, comprehensive neck dissection followed by
postoperative irradiation of 55 to 60 Gy in 5.5 to 6 weeks is
recommended. As in other head and neck sites, if there is any
extracapsular extension, a small volume covering the region at high
risk should be treated with 64 to 66 Gy.

Radiation Therapy Results

The results of radiation therapy for carcinoma of the floor of the
mouth vary with the stage of the disease. In the reported series, the
3- and 5-year disease-free survival rates are approximately 80% for T1
lesions and 50% to 60% for T2 lesions [ref: 11,26,48] (Table 38-7).
Advanced disease is rarely curable by radiation therapy alone; cure
rates are less than 25%. [ref: 41,76] Contrary to elective neck
dissection for N0 necks, therapeutic neck dissection for nodal
metastases does not jeopardize survival. Results of radiation therapy
for carcinoma of the floor of the mouth are shown in Table 38-7.
Planned combined radiation therapy and surgery yields higher local
control, particularly for T3 and T4 lesions (Table 38-8).

Buccal Mucosa

Squamous cell carcinomas arising in this area are usually well
differentiated and are frequently associated with areas of
leukoplakia. Papillary, verrucous, and exophytic mucosal growths are
usually well differentiated with a low incidence of lymph node
metastases (i.e., 10% to 20% for T1 and T2 lesions). Ulcerative,
advanced tumors, which are often associated with muscle invasion, have
a higher propensity (60%) for lymph node metastases. [ref: 8,14]

Therapeutic Options

Primary surgery is effective for small, superficial T1 lesions without
involvement of commissure. The procedure removes the malignancy and
eradicates any adjacent leukoplakia. For intermediate T2 lesions and
lesions involving the commissure, radiation therapy, which produces a
high cure rate with good functional and cosmetic results, is
preferred. For T3 and T4 tumors with deep muscular invasion, cure
rates after radiation therapy are poor. These lesions are usually
treated by radical surgery, reconstruction, and postoperative
irradiation. Some investigators have recommended preoperative
radiation therapy followed by en bloc excision followed by a
reconstructive procedure if needed. [ref: 11]

The management of verrucous carcinoma of the buccal mucosa is often
controversial. The concept of potential malignant transformation after
radiation therapy as reported in the literature is debatable. It is
true that well-differentiated lesions are difficult to control with
homeopathic doses of irradiation and that recurrences may be more
aggressive and hard to manage. [ref: 50] Some cases of so-called
verrucous carcinoma that are diagnosed by small biopsy and undergo
malignant changes after radiation therapy may be diagnosed because of
sampling errors because the entire specimen was not available for
pathologic examination before radiation therapy. A few patients with
the diagnosis of verrucous carcinoma have been treated with radiation
therapy and have had no evidence of disease for 10 years or more.
[ref: 76]

Radiation Therapy Management

For T1 and most T2 lesions without nodal involvement, the results of
radiation therapy are best when photon or electron-beam therapy is
combined with an interstitial implant or intraoral cone therapy. Small
mucosal lesions can occasionally be treated with interstitial
radiation therapy alone in edentulous patients. For an interstitial
implant, the needles must be inserted percutaneously through the cheek
along the base of the lesion, rather than intraorally (Fig. 38-7A,
Fig. 38-7B, and Fig. 38-7C).

In moderately advanced lesions, with or without positive nodes,
appropriate radiation therapy must include the primary site and the
regional lymph nodes. This is best achieved with external-beam
radiation therapy through ipsilateral and anterior wedge pair fields
for a tumor dose of 55 to 60 Gy in 6 weeks. This is followed by boost
irradiation, sparing the mandible, with interstitial implant,
intraoral cone, or electron beam for an additional 20 Gy (Fig. 38-8AB
and Fig. 38-8C). Fortunately, the tissues of the buccal cheek can
tolerate high-dose radiation therapy. Elective neck irradiation
generally is not indicated for early lesions with well-differentiated
histology. Ipsilateral nodal coverage by elective radiation therapy is
advised for large tumors with or without positive nodes. Any residual
positive nodes are treated by neck dissection.

Any tumor extension to the gingiva or retromolar trigone probably
precludes the use of an interstitial implant as the major treatment
modality because of its insufficient coverage and attendant risk of
osteoradionecrosis. External-beam therapy is the main modality used
postoperatively.

Radiation Therapy Results

Results for treating carcinoma of the buccal mucosa are sparse. Three
series reported that the 5-year disease-free survival rates after
radiation therapy ranged from 50% to 66%, depending on the stage of
the primary lesion and the existence of nodal metastases. [ref:
1,8,76] For small and intermediate lesions, surgical salvage for
radiation therapy failures has generally been satisfactory. Large,
advanced carcinomas are rarely curable by radiation therapy, and
5-year disease-free rates are approximately 25%. Reported treatment
results for carcinoma of the buccal mucosa are summarized in
Table 38-9.

Gingiva

Squamous cell carcinoma of the gingiva usually arises in the posterior
portion of the lower dental arch and is associated with leukoplakia.
Most of these tumors are well-differentiated squamous cell carcinomas.
Because the mucous membrane adheres directly to the periosteum of the
mandible, tumors arising from the gingiva usually invade underlying
bone early in their development. A primary maxillary antrum tumor
involving the upper gingiva should be excluded by CT scans and other
radiographic studies.

Approximately 80% of the gingival carcinomas arise from the lower
gingiva, and of these, 60% are posterior to the bicuspid. Lymphatic
spread depends on whether the lesion arises from the buccal or lingual
surface of the alveolar ridge. From the buccal side, metastases occur
in the submandibular, submental, and subdigastric nodes. From the
lingual side, metastases occur in the subdigastric, deep superior
jugular, and retropharyngeal nodes. Upper and lower gingival lesions
follow similar patterns of spread. [ref: 48]

Because bony involvement by carcinoma compromises the results of
radiation therapy, careful radiographic examination of the mandible,
including Panorex and polytomes of the mandible, is essential as a
minimal pretreatment workup. Intraoral dental radiographs or CT scans
may better show minimal bony involvement of the mandible. Care should
be taken to differentiate the smooth, saucer-shaped pressure defect
caused by a slowly growing, pushing tumor from the "moth-eaten" type
of infiltration of an aggressive tumor (Fig. 38-9). Only the former
can be successfully treated by radiation therapy.

Therapeutic Options

Treatment of carcinoma of the gingiva depends on the extent of the
lesion, the status of the cervical lymph nodes, and especially on the
presence of bony involvement. Small T1 exophytic lesions without bony
involvement can be managed by external-beam therapy alone. Radical
surgery is preferred for advanced lesions associated with destruction
of the mandible, with or without metastases, because partial
mandibulectomy with radical neck dissection provides good survival
rates. [ref: 10] Because of the likelihood of local spread of the
disease along the subperiosteal lymphatics, radiation therapy is often
given after mandibular resection to eradicate microscopic disease at
the margins, to control micrometastases in the lymph nodes, and to
improve cure rates.

Radiation Therapy Management

Because of the eccentric location of the primary lesion and its
regional nodes, radiation therapy is delivered by external beam with
anteroposterior (AP) and lateral wedge pair or electron-beam
technique. The interstitial implant has no place in the management of
this disease because of the proximity of bone to tumors and the high
risk of osteoradionecrosis.

Radiation portals must include the entire segment of the hemimandible
from the mental symphysis to the temporomandibular joint. The
ipsilateral neck is irradiated if nodes are positive or if lesions are
advanced. A dose of 45 Gy is given in 5 weeks as a preoperative
procedure. If postoperative radiation therapy is given, the dose may
be increased to 55 to 60 Gy without risk of complications
(Fig. 38-10AB and Fig. 38-10C). If feasible, an ipsilateral electron
beam is used to boost the dose to the high-risk area. Radiation
therapy should be started approximately 3 to 4 weeks after surgery.

Radiation Therapy Results

Results with radiation therapy alone generally are not entirely
satisfactory, particularly for T3 and T4 lesions. For most reported
series, the 5-year survival rates range from 30% to 50%. [ref:
9,29,36] Patients with clinically positive nodes generally have a poor
prognosis and may benefit from surgery as part of the treatment of
nodal disease. The results of treatment for carcinoma of the gingiva
are shown in Table 38-10.

Hard Palate

The hard palate is the most common site of minor salivary gland tumors
in the oral cavity. Squamous cell carcinomas arising from the hard
palate are rare, are usually ulcerative, and invade the underlying
bone in the early stage of disease. Most carcinomas are well
differentiated with a 15% to 20% incidence of lymph node metastases;
the submandibular, upper jugular, and subdigastric nodes are commonly
involved.

Appropriate x-ray films should be obtained before making a decision
about management. Examination should include polytomes and CT scans of
the palatal bone, maxillary antrum, and floor of the nasal cavity.

Therapeutic Options

Exceptional early lesions without bony involvement can be treated
satisfactorily with radiation therapy alone; surgery is reserved for
salvage of irradiation failures. Advanced, deeply ulcerative,
infiltrative lesions with bone destruction are better treated by
combined radiation therapy and surgery; the resulting bone defect can
be corrected by an obturator. Malignant salivary gland tumors are
always treated by combined surgery and postoperative radiation
therapy. Some inoperable malignant minor salivary gland tumors have
been successfully controlled with high-dose irradiation. [ref: 18]

Radiation Therapy Management

Radiation therapy for very early carcinoma of the hard palate is
generally directed to treating the primary site. Parallel opposing
lateral portals cover the entire palate to deliver doses of
approximately 60 Gy in 6 weeks. The primary lesion should be boosted
to bring the total dose to 70 Gy in 7 weeks.

For advanced disease with bony destruction and positive nodes, primary
resection is performed, followed by postoperative radiation therapy of
approximately 60 Gy in 6 weeks.

Radiation Therapy Results

Results of radiation therapy for carcinoma of the hard palate are
sparse. Scattered case reports suggest that local control can be
achieved in approximately one third to one half of the patients
treated. [ref: 76] Patients with nodal metastases and bony destruction
are unlikely to be cured by surgery or radiation therapy alone, and
combined radiation therapy and surgery has improved results. The
radiation therapy experience of Massachusetts General Hospital for
carcinomas of the hard palate is shown in Table 38-11. [ref: 74]
Guidelines for radiation therapy are summarized in Table 38-12.

Sequelae of Treatment

Minor sequelae, such as xerostomia, loss of sense of taste, and dental
caries, may follow curative radiation therapy. Major complications
include soft tissue ulceration, orocutaneous fistula, and
osteoradionecrosis of the mandible. Osteoradionecrosis may be affected
by the proximity of growth, recent dental extractions, health and
integrity of the mucous membrane, and irradiation dose. It also may
occur in the edentulous jaw from an excessively high dose of
irradiation. [ref: 13] Once osteoradionecrosis of the mandible
develops, removal of the devitalized, infected bone by surgery,
including sequestrectomy or partial mandibulectomy, may be indicated.
Radiation-induced dental caries can be avoided with meticulous dental
care with fluoride treatment after radiation therapy.

Although complications are undesirable, they should be accepted as a
risk in the treatment of malignant tumors of the oral cavity. They may
be minimized by careful radiotherapeutic and surgical techniques.

Dental Care and Radiation Therapy

Dental care by dentists and oral surgeons should be a comprehensive
part of the overall management of carcinoma of the oral cavity. [ref:
15,27] Evaluation before irradiation should include an examination of
the soft tissues and teeth. Any tooth that cannot be restored because
of severe periodontal disease or dental caries should be extracted
before radiation therapy is begun. In general, radiation therapy
should not be started until the tooth socket has healed adequately,
which usually takes about 2 weeks. Sound teeth or teeth in good repair
need not be sacrificed if irradiation doses are kept within the
tolerance of the mandible, if the major portion of the salivary gland
is spared, or if a combined external megavoltage beams and
interstitial implant or intraoral cone approach is used. [ref: 13]

Postirradiation dental extraction may be possible. If the tooth lies
within the previous volume of high-dose irradiation, extraction must
be covered by antibiotic therapy before and after the dental
procedure.