Oral and Maxillofacial surgery/Fifth year

‫ سلوان يوسف‬.‫د‬.‫م‬.‫أ‬

Oral Cancer

O
ral cancer accounts for less than 3% of all cancers. It is the
eleventh most common cancer worldwide. Squamous cell
carcinoma (SCC) is the predominant form of oral cancer and
accounts for greater than 90% of malignant pathology. Other forms
include salivary gland tumors, mesenchymal tumors, lymphoma, and
melanoma. Oral cancer is predominantly a disease of older age. More
than 92% of oral and pharyngeal cancers occur in individuals older than
40 years, with the average age being 63. Oral cancer is predominantly
male disease, but females have experienced a steady rise in the incidence
of oral cancer since the increase in female smokers began in the 1950s.

The natural history of oral SCC

Oral carcinogenesis appears to evolve through a complex, multistage
process involving biomolecular changes that precede premalignant
lesions, which in turn precede invasive cancer. The genetic changes
caused by exposure to carcinogens like tobacco and alcohol tend to
accumulate over time in the entire mucosa exposed to this insult.

The fundamental regulatory mechanism in carcinogenesis is thought to

be the cellular balance between oncogenes and tumor suppressor
genes. The proto-oncogenes stimulate cell growth and proliferation and
are under negative control of the tumor suppressor genes, which prevent
overgrowth.

A cancer may therefore arise either from activation of a proto-oncogene

or due to loss of a tumor suppressor gene. Numerous genetic events
are required to cause a cancer, but the most frequently observed
molecular abnormality is mutation of the 'p53 tumor suppressor gene'
which is seen in 40-70% of malignant lesions and 20% of premalignant
lesions. Several other oncogenes and tumor suppressor genes have been
studied, but no clear relationship has been demonstrated with
phenotypic behavior or survival.

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Etiology
The cause of oral SCC is multifactorial. No single causative agent or
factor (carcinogen) has been clearly defined or accepted, but both
extrinsic and intrinsic factors may be at work.

1. Tobacco smoking & Smokeless tobacco use: studies revealed that

the proportion of smokers among patients with oral carcinoma is 2-3
times greater than the general population. Also pipe and cigar
smoking carries a greater oral cancer risk than does cigarette
smoking. The risk of oral SCC is dose and time dependent. The
practice of reverse smoking is popular in India and South America
considerably elevates one’s risk for oral cancer. Chronic Smokeless
tobacco use increases the risk of oral SCC 2-26 times. Approximately
50% of all oral cancers in smokeless tobacco users occur at the site
where the tobacco is habitually placed.

2. Betel quid: is a compound of natural substances chewed for their

psychostimulating effects. Among betel quid users in Asia, the lifetime
risk of developing oral cancer is a remarkable 8%.

3. Alcohol: It is uncertain whether excessive alcohol consumption alone

can initiate carcinogenesis, although it is well established that alcohol
in combination with tobacco is a significant risk factor for oral cancer
development (the risk increases 15 times).

4. Chronic irritation: including poor oral hygiene, ill-fitting prostheses,

chronic use of mouth washes or Marijuana smoking.

5. Phenolic agents: there is increased risk of oral cancer for workers in

the wood products industry chronically exposed to certain chemicals,
such as phenoxyacetic acids.

6. Radiation: this includes ultraviolet radiation and X-irradiation, which

reduces immune reactivity and produces chromosomal abnormalities.

7. Iron deficiency: especially severe chronic form known as Plummer-

Vinson syndrome. People who are deficient in iron tend to have
impaired cell-mediated immunity, and iron is essential to the normal
functioning of epithelial cells of the upper digestive tract. In deficiency
states, these epithelial cells turn over more rapidly and produce an
atrophic or immature mucosa.

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8. Vitamin A deficiency: producing excessive keratinization of the skin
and mucous membrane.

9. Syphilis (tertiary stage): has long been accepted as having a strong

association with the development of dorsal tongue carcinoma. Also
the arsenical agents and heavy metals that were used to treat syphilis
before the advent of modern antibiotic therapy have carcinogenic
properties themselves and may have been responsible for some of the
earlier cancer development in this disease. Today syphilis associated
oral malignancies are rare because the infection is typically diagnosed
and treated before the onset of the tertiary stage.

10. Candidal infection: hyperplastic candidiasis also called candidal

leukoplakia is considered a precancerous condition. Some strains of
candida albicans produce certain chemicals that are implicated in
carcinogenesis. But the role of candidal infection in oral cancer
development is debated.

11. Oncogenic viruses: human papilloma virus is implicated in oral

cancer development especially subtypes 16, 18, 31 and 33. The
mechanism involves 2 virally encoded proteins; E6 which promotes
degradation of p53 tumor suppressor gene products and E7 which
promote degradation of pRb gene products.

12. Immunosuppression

13. Oncogenes and Tumor suppressor genes: which are

chromosomal components capable of being acted on by a variety of
causative agents.

Site distribution
The importance of the "cancer-prone crescent" and its significance is
related to the postulate that most oral cancers should occur in mucosa
where saliva pools due to gravity exposing it to salivary carcinogens. The
site distribution of oral SCC is varied but the general trend is as follows:

 Tongue → 35% (31% lateral border, 2% tip and 2% dorsum).

 Floor of mouth → 30% (25% anterior and 5% posterior).

 Lower alveolus → 15%.

 Buccal mucosa→ 10%.

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 Upper alveolus →5%.

 Hard palate → 3%.

 Retromolar trigon → 2%.

The distribution of oral cancer in developing countries is, however, very

different and may be explained by certain habits peculiar to that
population, for example, betel quid chewing that contributes to the high
incidence of buccal cancer in the Indian subcontinent.

Clinical presentation
Despite the fact that the oral cavity is an easily accessible site for the
patient and the clinician, a surprisingly large number of oral tumors
present late because of the painless and rather vague nature of the
symptoms.

The clinical manifestation of oral cancer is varied including:

 Exophytic or mass forming lesion which typically has a surface that

is irregular, fungating, papillary, or verruciform, and its color may
vary from normal to red to white, depending on the amount of keratin
and vascularity. The surface is often ulcerated, and the tumor is
indurated on palpation.

 Endophytic growth pattern which has a depressed, irregularly

shaped, ulcerated, central area with a surrounding rolled border of
normal, red or white mucosa. The rolled border results from invasion
of the tumor downward and laterally under adjacent epithelium with
induration of the underlying tissues.

 Leukoplakic, Erythroplakic or combined Erythroleukoplakic

lesions (speckled leukoplakia) which has a high incidence of
malignant transformation.

A thorough examination of the upper aerodigestive tract mucosa should

be performed in every case since synchronous multiple primary cancers
occur in approximately in 4% of patients with oral cancers.

Symptoms
 Lesions in the floor of mouth or tongue may be painful, infiltrative
lesions of the floor of mouth also may extend to invade bone

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 anteriorly, muscles of the floor of mouth deeply, or tongue posteriorly.
Patients may complain of difficulty in swallowing or speaking, which
becomes even more pronounced when the tumor spreads to the floor
of the mouth.

 Early spread to the alveolus and periosteum of the mandible is

common; clinical fixation of the tumor to the mandible indicates
periosteal involvement, and direct bone invasion may be present in a
high number of cases. Patients may report pain while chewing,
intermittent bleeding, loose teeth or ill-fitting dentures in gingival or
alveolar ridge lesions.

 Some symptoms like trismus or altered sensation or anesthesia of the

lower lip may signify locally advanced disease.

Clinical staging
The purpose of staging is to group patients into statistical classifications
that:

1. Provide useful information on treatment (appropriate therapy for a

given tumor can be selected) and prognosis.

2. This standardized format facilitates research, assessment of

outcomes, and communication among clinicians by establishing
uniform reporting parameters.

As a general rule, more advanced stage implies a worse prognosis.

Initial staging is performed by using all available clinical and

radiographic data (cTNM). Final staging incorporates histopathologic
data if surgery is performed (pTNM).

The TNM system stages cancer purely on the anatomic extent of disease
and does not account for the many biologic, molecular, or host
characteristics that are known to influence prognosis.

TNM system
T= Tumor size.

N=Nodal status in the cervical region.

M=Metastatic disease beyond the cervical lymph nodes.

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Definition of Primary Tumor (T)

T CATEGORY T CRITERIA
TX Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor<2 cm , < 5 mm depth of invasion (DOI)
DOI is depth of invasion and not tumor thickness.
T2 Tumor < 2 cm, DOI > 5 mm and < 1 0 mm
or tumor > 2 cm but < 4 cm, and < 10 mm DOI
T3 Tumor>4 cm
or any tumor> 10 mm DOI
T4a Moderately advanced local disease
(Lip) Tumor invades through cortical bone or
involves the inferior alveolar nerve, floor of mouth,
or skin of face (i.e., chin or nose)
(Oral cavity) Tumor invades adjacent structures only
(e.g., through cortical bone of the mandible or maxilla, or
involves the maxillary sinus or skin of the face)
Note: Superficial erosion of bone/tooth socket (alone) by
a gingival primary is not sufficient to classify a tumor as
T4.
T4b Very advanced local disease
Tumor invades masticator space, pterygoid plates, or
skull base and/or encases the internal carotid artery

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Definition of Regional Lymph Node (N)

Clinical N (cN)

N Category N Criteria
NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in a single ipsilateral lymph node, 3 cm or

smaller in greatest dimension ENE(-)
N2a Metastasis in a single ipsilateral node larger than 3 cm but
not larger than 6 cm in greatest dimension, and ENE(-)
N2b Metastasis in multiple ipsilateral nodes, none larger than 6
cm in greatest dimension, and ENE(-)
N2c Metastasis in bilateral or contralateral lymph nodes, none
larger than 6 cm in greatest dimension, and ENE(-)
N3a Metastasis in a lymph node larger than 6 cm in greatest
dimension and ENE(-)
N3b Metastasis in any node(s) and clinically overt ENE(+)

ENE (-): Without Extranodal Extension

ENE (+): With Extranodal Extension

Definition of distant metastasis (M)

M Category M Criteria

M0 No distant metastasis

M1 Distant metastasis

AJCC prognostic stage groups

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When T is… And N is… And M is… Then the
stage group
is…
T1 N0 M0 I
T2 N0 M0 II
T3 N0 M0 III
T1, T2, T3 N1 M0 III
T4a N0, N1 M0 IVA
T1, T2, T3 T4a N2 M0 IVA
Any T N3 M0 IVB
T4b Any N M0 IVB
Any T Any N M1 IVC

Grading
Histopathologic grading of SCC is based upon the degree of
differentiation and resemblance to normal squamous epithelium and the
amount of keratin production. It consists of 3 grades:

 Grade 1 (well differentiated)

 Grade 2 (moderately differentiated)

 Grade 3 (poorly differentiated)

The histopathologic grade of a tumor is related to its biologic behavior;

grade 1 (well differentiated) tumor is a low-grade tumor and it grows at a
slightly slower pace and metastasizes later in its course whereas high-
grade tumor (poorly differentiated) enlarges rapidly and metastasizes
early. A tumor with a microscopic appearance somewhere between these
two extremes is called moderately differentiated.

Physical examination
During examination the following points should be considered:

 Tumor’s location, size, and relationship to adjacent anatomic

structures.

 Fixation to the mandible.

 Proximity to the midline often guides the decision for unilateral

versus bilateral neck dissection when indicated.

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 Trismus or decreased tongue mobility may be an indication of
invasion into deeper structures.

 Cranial nerve deficits suggest tumor involvement, which may

increase suspicion for perineural spread.

 The status of the dentition should be assessed in patients in whom

radiation therapy may be indicated because of the risk for
xerostomia-related caries and osteoradionecrosis. Plans should be
made for non-viable teeth to be removed at the time of surgery or
before radiation therapy.

 Biopsy of the primary tumor is required for histologic diagnosis and

treatment planning.

 Lymph nodes in the neck must be palpated carefully to assess for

cervical metastasis or other abnormalities. Palpable nodes should be
evaluated for size, location, and fixation to skin or deeper
structures.

 Identify distant sites that may be used for reconstructive purposes.

Radiographic assessment
Pretreatment imaging is important to evaluate:

 The tumor size and extent.

 Involvement of adjacent anatomic structures.

 Staging the cervical lymph nodes.

 Tumor invasion for the bone especially the mandible.

The modalities used include:

 Conventional Radiographs

 Computed Tomography

The most common imaging modality used. The main advantages are:
excellent bone detail, adequate soft tissue enhancement, and relatively
low cost and availability. While the main disadvantages include; ionizing
radiation, artifacts created by metallic dental restorations and irregular

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teeth sockets and periapical lesions that may be confused as bony
invasion.

 Magnetic Resonance Imaging

Advantages are superior soft tissue details and lack of ionizing

radiation. MRI is superior to CT when there is suspicion of perineural
invasion, skull base invasion or intracranial involvement. The main
disadvantages are; more sensitive to motion artifacts, expensive, difficult
for patients who suffer from claustrophobia, and it is contraindicated in
case of presence of ferromagnetic implants.

 Ultrasound

Advantages: quick, inexpensive, non-invasive, lymph nodes can be

sampled under ultrasound guidance. The main disadvantages include;
limited utility in the oral cavity, bone does not transmit sound, it is
highly technique sensitive, and operator dependent with steep learning
curve.

 Positron Emission Tomography (PET)

Functional imaging with 18F-fluorodeoxyglucose PET has been shown to

be an effective tool in the diagnosis of head and neck cancer. PET has
shown promise in the evaluation of metastatic disease, tumor
recurrence, and treatment response after chemotherapy or radiation
therapy. The integration of PET and CT technology is more accurate than
either modality alone in the depiction of head and neck malignancies.

Treatment
The goals of the treatment of cancer of the oral cavity are:

1. Cure of the cancer.

2. Preservation or restoration of speech, mastication, swallowing, and

external appearance.

3. Minimization of the sequelae of treatment such as dental decay,

osteonecrosis of the mandible, and trismus.

4. Awareness of the risk of subsequent primary tumors and their

management.

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The main modalities of treatment are surgery, radiotherapy and
chemotherapy (others: immunotherapy, photodynamic therapy, and
laser).

In general, small and superficial tumors of the oral cavity are equally
amenable to being cured by surgical resection or radiotherapy.

Therefore use of a single modality is preferred as the definitive treatment

in early stage (T1 and T2) tumors of the oral cavity. When the end point
of treatment, that is, cure of cancer, is comparable, other factors must
play a role in the selection of initial treatment. These factors include
complications, cost, convenience, compliance, and long-term sequelae of
treatment. Considering these factors, surgery is the preferred treatment
for T1 and T2 tumors of the oral cavity.

In advanced stage (T3 and T4) oral cancer combining surgery with
adjuvant postoperative radiotherapy offers improved locoregional control
but does not improve survival.

The most important high-risk features for combining surgery and

radiotherapy are:

 Positive margins.

 Extranodal spread.

 Multiple positive nodes.

 Perineural or vascular invasion.

 Metastasis to lymph node levels IV and V.

Surgical treatment
Surgical excision is one of the two mainstays of loco-regional treatment
of oral cancer. It allows histopathological assessment of the clearance
margins of the tumor together with further information regarding tumor
spread and dynamics.

Factors that influence the choice of surgical treatment for a primary

tumor of the oral cavity are:

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Tumor Factors

 Site.

 Size.

 Location (anterior versus posterior).

 Proximity to bone.

 Previous treatment.

 Depth of invasion.

 The histological characteristics of the primary tumor (i.e., type and

grade).

 Status of cervical lymph nodes.

Patient Factors

 Age.

 General medical condition.

 Occupation.

 Lifestyle (smoking and drinking).

 Socio-economic considerations.

 Previous treatment.

Physician Factors

 Surgery.

 Radiotherapy.

 Chemotherapy.

 Nursing & rehabilitation services.

 Dental.

 Prosthetics.

 Support services.

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The excision of the lesions should include at least 1 cm of adjacent
normal tissues as safe margin. Superficial lesions of the floor of mouth,
buccal mucosa and soft palate can be excised through peroral approach,
also T1 and most T2 lesions of the anterior two thirds of the tongue (oral
tongue) where the mobility of the tongue is not restricted, and the tumor
does not extend to involve the adjacent floor of the mouth or cross the
midline are amenable for partial glossectomy through peroral approach.

Access to the oral cavity

The main surgical approaches are peroral (transoral), mandibulotomy,
lower cheek flap approach, visor flap approach, and upper cheek flap
approach.

 Peroral or Transoral approach

It can be safely used for small, anteriorly located, and easily accessible
tumors of the oral tongue, floor of mouth, gum, cheek mucosa, and hard
or soft palate.

 Lower cheek flap

It requires a midline lip–splitting incision that is continued laterally into

the neck for exposure and neck dissection. This approach provides
excellent exposure for tumors of the oral cavity that are posteriorly
situated and not accessible for peroral approach except those of the
upper gum and hard palate.

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 Upper cheek flap

The upper cheek flap approach (the Weber-Ferguson incision and its
modifications) is raised using a median upper lip split and carrying the
incision around the nose with the corresponding mucosal incision in the
upper gingivobuccal sulcus. It is required for resection of larger tumors
of the hard palate and upper alveolus, particularly if they are posteriorly
located.

 Visor Flap

It provides sufficient exposure for anteriorly located lesions but is not

satisfactory for tumors located in the posterior oral cavity. The benefit of
this approach is that it avoids a lower lip–splitting incision but
produces permanent numbness of the chin because the mental nerves
need to be transected for adequate mobilization of the flap. It also may
cause sagging of the lower lip and drooling because of a loss of support
and sensation. Thus its usefulness is limited.

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 Midfacial degloving flap

Through bilateral gingivobuccal incisions is preferable in appropriate

cases as this avoids midfacial scars.

 Mandibulotomy

Adequate surgical exposure of tumors located in the posterior oral cavity

may be obtained using a lip-splitting mandibulotomy.

Maxillary resection procedures

 Partial Maxillectomy in malignant tumors of the floor of the

maxillary sinus with spread toward the oral cavity or in the early
malignant tumors of the maxilla, the procedure is done through the
mouth and it requires removal of the lower half of the maxilla.

 Medial Maxillectomy indicated for tumors of limited extent on the

lateral wall of the nasal cavity or medial wall of the maxillary sinus.

 Subtotal Maxillectomy for larger tumors of the maxilla with Weber-

Fergusson approach

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 Total Maxillectomy complete removal of the maxilla is necessary
when the entire antrum is involved with the tumor and when the
tumor extends to the walls of the maxillary sinus.

 Radical Maxillectomy with Orbital Exentration when the tumor

extends into the orbit through the orbital periosteum, removal of a
functioning eye should only be considered when the chance for
curative treatment exists.

 Anterior Craniofacial Resection for tumors that have spread to the

anterior cranial fossa.

Management of the Neck

The status of the cervical lymph nodes is the most important
prognostic factor in SCC of the head and neck. The overall survival
rate decreases by approximately 50% in patients with metastases to the
cervical lymph nodes. Approximately 40% of patients will initially be
found to have evidence of regional nodal metastasis. Therefore,
management of the cervical lymph nodes is an important component of
the overall treatment of patients with head and neck cancer.

The head and neck drain into an extensive network of cervical

lymphatics, and this drainage pattern usually occurs in a predictable
manner for each site. Knowledge of the anatomy of the regional
lymphatic system is therefore important for clinicians treating patients
with head and neck cancer.

Anatomy and biology of lymphatic metastasis

Cervical lymph nodes are categorized into five nodal levels, and
additionally levels VI and VII encompassing central compartment and
superior mediastinal nodes. Levels I, II, and V are further subdivided into
sublevels A and B.

For primary tumors in the oral cavity, the regional lymph nodes at
highest risk for early dissemination by metastatic cancer are limited to
levels I, II, and III.

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Clinical evaluation and diagnostic imaging
Imaging modalities currently available in routine clinical practice include
ultrasonography, CT, and MRI scans, and PET scans.

Although the presence of metastatic involvement of a lymph node is a

histologic, not a radiologic diagnosis, there are characteristic changes
apparent on CT and MRI suggestive of metastatic SCC including:

 Enhancement.

 Poorly circumscribed margins.

 Central necrosis.

 Nodal size in excess of 1 cm in diameter.

Note: Cervical lymph node size does not always correlate with the
presence of tumor involvement. Although larger metastatic lymph
nodes indicate greater tumor volume, a small lymph node less than 1 cm
in diameter may still harbor foci of tumor cells. Conversely, lymph node
size greater than 1 cm in diameter does not automatically herald
metastatic cancer, because reactive lymphadenopathy following infection,
inflammation, or surgical intervention may result in lymph nodes of such
size.

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Classification of Neck Dissection
 Radical Neck Dissection (RND) involves the en bloc removal of all
ipsilateral lymph nodes from levels I through V, along with the
ipsilateral spinal accessory nerve (SAN), internal jugular vein (IJV),
and sternocleidomastoid muscle (SCM).

 Modified Radical Neck Dissection (MRND) When one or more non-

lymphatic structures are preserved during the dissection. The basis
for this modification is that the lymph node–containing tissues lie
within the cervical fascial planes surrounding the SCM, IJV, and SAN
and that these structures can be preserved if they are not involved
with tumor by skeletonizing them during the dissection. MRND can be
subclassified as follows:

1. Type I MRND preserves the SAN

2. Type II MRND preserves the SAN and IJV

3. Type III MRND preserves the SAN, IJV, and SCM. This modification
is also termed functional neck dissection.

 Selective Neck Dissection (SND) when one or more lymph node

groups are preserved during cervical lymphadenectomy that are
routinely removed with RND. The lymph node groups that are
removed are dependent on the predictable patterns of metastases
from the primary site. The levels of lymph nodes removed are
identified (e.g., SND levels I to III).

 Extended Neck Dissection when one or more lymph node groups or

non-lymphatic structures, or both, that are not usually involved in
RND are removed. Examples of lymph node groups include the
parapharyngeal, paratracheal, and superior mediastinal nodes.
Examples of non-lymphatic structures include the carotid artery,
hypoglossal nerve, and paraspinal muscles.

Subclassification into ‘‘therapeutic’’ and ‘‘elective’’ neck dissection

refers to the indication for surgery, but does not specify the extent of the
dissection.

 ‘‘Therapeutic’’ neck dissection is used when cervical metastases are

detected preoperatively.

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 ‘‘Prophylactic’’ or preferably ‘‘elective’’ neck dissection is used
when neck dissection is done for potential subclinical cervical
metastases.

Studies have demonstrated that occult metastasis occurs in

approximately 20-45% of patients who were clinically staged as N0. One
option is performing elective neck dissection (END) in patients with no
clinical evidence of nodal metastases. However, this may lead to 55-80%
of patients undergoing unnecessary neck dissections, along with the
associated morbidity, particularly postoperative shoulder dysfunction.
Various techniques have been used to detect cervical occult metastasis of
the clinically negative neck like ultrasound, CT, MRI scans, PET, PET/CT
and sentinel lymph node biopsy.

Prognostic variables of nodal metastasis

 Primary site.

 Perineural invasion.

 Lymphovascular invasion.

 Histopathologic grading.

 T stage.

Radiation versus Surgery in treatment of Oral SCC

 Surgery allows histopathologic analysis of the nodes, thus leading to
more accurate staging of the cancer and determination of potential
further treatment requirements.

 The choice of treatment of the primary tumor.

 If radiation therapy is used as the initial primary treatment modality

for early SCC of the oral cavity, this will exhaust its use in the event of
future recurrence.

 Surgical salvage for recurrent cancer in an irradiated field can be very

challenging.

 Radiation therapy also has potentially significant morbidity associated

with the treatment, including osteoradionecrosis, mucositis,
xerostomia, dysphagia, subcutaneous fibrosis, and poor wound

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 healing. This can lead to a more prolonged and difficult recovery than
occurs with END

Postoperative follow up

Postoperative visit Examination schedule

0-3 months Biweekly examination

3-12 months Monthly examination

1-2 years Examination every 2 months

2-4 years Examination every 4 months

4-5 years Examination every 6 months

Radiotherapy
It uses ionizing radiation; it is locoregional treatment and should be
considered as complementary to surgery rather than competitive. The
rationale of radiotherapy:

 Cells are killed in mitosis (mitotic death).

 Cancer cells divide more frequently.

 Malignant cells repair less efficiently.

 It preserves function

The basic principle is to achieve high dose in the tumor while minimizing
the dose to the normal tissues, this is difficult in the head and neck
because:

1. SCC is less sensitive to radiation than other types of malignancies

requiring higher dose.

2. Better technique precision is required due to the juxtaposition of

critically radiosensitive organs like the eyes and the brainstem.

So the therapeutic ratio, defined as the relationship between the dose

that is required for cure and the dose that causes unacceptable changes,
is low.

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Radiotherapy can be used as a definitive treatment or combined with
other modalities, surgery or chemotherapy. It is best at eradicating small
volumes of disease but it is more likely to fail if there is a large bulky
tumor.

Types of radiotherapy

1. External beam radiotherapy (Teletherapy).

2. Brachytherapy.

3. Unsealed radionuclide radiotherapy.

Preoperative radiotherapy

Preoperative radiotherapy is infrequently used and should not be

considered to be a standard of care. It can be considered in some
situations such as:

1. Fixed, inoperable neck nodes.

2. In situations where the initiation of postoperative radiotherapy is

likely to be delayed by more than 6–8 weeks due to the need for
extensive surgical reconstruction.

3. In patients who have undergone an open, incisional biopsy of a

positive neck node.

Postoperative radiotherapy

It should start no later than 6 weeks after surgery.

 Absolute indications for postoperative irradiation are; involved

(positive) margins at the primary tumor resection site and
extracapsular spread of involved lymph nodes.

 Near absolute indications include close (less than 5 mm) margins,

two or more involved cervical lymph nodes and invasion of the soft
tissues of the neck.

 The relative indications include; the presence of lymphovascular

space invasion and perineural invasion.

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Techniques of radiotherapy
 Brachytherapy (internal radiotherapy)

Brachytherapy describes the situation in which radioactive sources are

brought close to the tumor mass (or even implanted within it) to deliver a
highly localized radiation dose, it uses radioactive isotopes e.g., Radium,
Iridium or Radon. Its approaches include:

1. Interstitial brachytherapy: in which radioactive sources are inserted

directly in to tumor-bearing tissues (e.g., the tongue).

2. Intraluminal brachytherapy: in which the radioactive source is placed

within a hollow viscus (e.g., the nasopharynx).

3. Surface molds: in which the radioactive source is placed close to

disease on the skin surface or lip.

 Conventional (external beam or teletherapy) radiotherapy

In which a beam of radiation is directed toward the tumor bearing part of

the patient who is a distance away. It uses photons (like X-rays or
Gamma rays) or particles like protons.

 3-Dimensional conformal radiotherapy

In this planning technique a CT scan is taken with the patient

immobilized in the radiotherapy treatment position. Data from these
scans provide the radiation oncologist with precise anatomical and
electron density data on tumor and normal tissues.

 Intensity modulated radiotherapy (IMRT)

This is an advanced approach to three-dimensional conformal

radiotherapy. It optimizes the delivery of irradiation to irregularly shaped
volumes and has the ability to treat concave volumes. IMRT uses
sophisticated computer software and hardware to vary the shape and
intensity of radiation delivered to different parts of the treatment volume.

Fractionation of radiotherapy

Since the maximum radiation in a single dose is limited by the normal

tissue tolerance, the total dose is divided into a number of small doses
(fractions):

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 Conventional: 65 Gy (Gray) is given in protracted treatment course of
2 Gy× 30 fractions for 42 days (conventional).

 Hyperfractionation: when the number of fractions is increased

beyond the conventional levels, so the ratio of dose/fraction is
reduced. The treatment should be given 2-3 times/day with 6 hours
interval.

 Acceleration: is reduction in overall treatment time.

 Continuous hyperfractionated accelerated radiation therapy

(CHART): 12 days, 3 fractions/ day, 7 days/week. This is given to
prevent repopulation of malignant cells.

 Split courses: designed to reduce the severity of mucosal reaction, so

the radiotherapy course is divided into 2 halves separated by 2 weeks,
but this may lead to repopulation of tumor cells so it is condemned.

Chemotherapy
In SCC of the head and neck chemotherapy is used in combination with
radiotherapy and/or surgery in radical treatment or alone in palliative
treatment. Failure of cancer treatment is due to inherent or acquired
resistance of malignant cells.

Classes of chemotherapeutic agents:

In general, they are grouped as:

 Antimetabolites; this group predominantly interferes with synthesis

and metabolism of DNA and, to some extent, RNA. It includes:
methotrexate, 5-fluorouracil (5-FU), cytarabine, gemcitabine and 6
mercaptopurine (6MP).

 DNA damaging agents; these include:

 Alkylating agents like cyclophosphamide and ifosfamide and

melphalan.

 Antibiotics like adriamycin, mitomycin, actinomycin D and

bleomycin; nitrosoureas (such as BCNU and CCNU).

 Platinum derivatives like cisplatin and carboplatin.

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 Mitosis inhibitors; this group includes vinca alkaloids (like
vincristine and vinblastine) and taxanes (Taxol).

 Cancer cell enzyme inactivators; e.g., Tyrosine kinase inhibitors

(generic name Imatinib Mesylate, other name STI 571) (trade name
Gleevec). Tyrosine kinase is an essential for malignant cell
reproduction.

Scheduling of Chemotherapy

 Before radiotherapy (Neoadjuvant or Induction).

 During radiotherapy (Synchronous or Concomitant).

 After radiotherapy (Adjuvant or Subsequent).

Chemotherapy can be given as a single agent with reported response rate

of 40% or in combination with response rate of 75%. The main outcome
measures are:

 Local control.

 Survival rate.

The main benefit is improved local control. Adjuvant chemotherapy is not

a routine management in head and neck SCC. Chemotherapy is also
considered in patients with significant symptoms due to advanced or
recurrent tumors only to improve symptoms with short lived benefit.
Any costly treatment of questionable benefit must be given only after
careful considerations.

Concomitant Chemoradiation

Use of concomitant chemoradiotherapy is based on a belief that

chemotherapy synergistically acts with radiotherapy by:

 Inhibiting repair of DNA damage caused by radiotherapy, arresting

cells in radiosensitive phases and possibly preventing regrowth
between radiotherapy treatments.

 In addition it is thought that chemotherapy may treat radio-resistant

tumor lineages such as hypoxic cells.

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The addition of concomitant chemotherapy to radiotherapy has been
shown to be superior to radiotherapy alone for locoregional control and
survival in head and neck SCC

Palliative treatment and terminal care

Treatment is usually radical in intent; also any salvage treatment is

aimed to cure the patient. The treatment may progress to palliative and
finally to terminal care which is a right to every patient and duty of every
health professional. The aim of terminal care is to:

1. Make the patient free of pain.

2. Mobile.

3. Sufficiently alert.

It is usually home care, in a hospice or in the same hospital.

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