A oral cancer patient's treatment can include surgery, radiation therapy, chemotherapy
and immunotherapy. Some patients have a combination of treatments consisting a multidisciplinary
approach involving the following:
Next oral cancer patients need symptom management, supportive or palliative care
to help patients maintain independence and increase comfort by managing the symptoms
of cancer and side effects of treatment. The patients need to control of pain and
other symptoms to relieve side effects of therapy, ease emotional and practical
- Oral and maxillofacial surgeon: Diagnoses and surgically excises the tumour.
- Plastic surgeon: Improves appearance and function of the patient.
Radiation oncologist: Treats cancer with radiation.
- Medical oncologist: Treats cancer with chemotherapy.
- Speech therapist: Helps improve the ability to talk and swallow, if they
- Dentist/ Prosthodontist: Replaces teeth and parts of jaw to maintain good
- Dietician: Makes sure that diet is adequate.
- Physiotherapist: Ensures that the muscles of the head and neck which are
affected by surgery continue to function properly.
- Psychologist: Deals with the emotional aspects of cancer.
A. Primary Cancer
Surgical excision is the treatment of choice for most oral cancers. Cancers of the
vermilion surface of the lip are best treated with full-thickness excision of the
lip. Lateral margins of 5 mm of uninvolved lip are taken with the cancer. The defect
is closed primarily when one-third or less of the lip is excised. When excision
of more than one-third of the lip is required, closure is achieved by transposition
of a segment of the opposite lip on a vascular pedicle (Abbe flap). When the entire
vermilion of the lip has been damaged, vermilionectomy (lip shave) can be performed
along with excision of the cancer and a new vermilion surface created by advancing
the labial mucosa.
Within the oral cavity, small cancers can usually be excised through the open mouth
taking a margin of 1 cm of normal-appearing tissue. Small defects are closed by
direct suture or split-thickness skin grafts. Larger cancers (> 2 cm) require more
extensive exposure (ie, cheek flap), resection and subsequent reconstruction. For
cancers involving bone, marginal or segmental resection of the mandible is performed.
A composite resection involves resection of an oral cancer, resection of a portion
of the mandible and a neck dissection.
Radiation therapy is an alternative to surgery for oral cancers smaller than 4 cm
in diameter (T1 and T2 cancers). The side effects of mucositis, xerostomia and osteoradionecrosis
of the mandible must be balanced against potential advantages. T3 and T4 cancers
are usually treated with combined surgery and radiation therapy to improve the rate
of local control.
B. Management of Neck Metastases
Clinically apparent cervical lymph node metastases can be treated by radical neck
dissection, which involves removal of all the lymphatic tissue of the neck along
with the sternocleidomastoid muscle, internal jugular vein and spinal accessory
nerve. To save structures not directly involved by cancer, modified neck dissection
is performed. A modified radical neck dissection always preserves the spinal accessory
nerve, while a functional neck dissection always preserves the sternocleidomastoid
muscle, the internal jugular vein and the spinal accessory nerve. Selective neck
dissections involve only certain cervical lymph node levels. For example, levels
I, II and III cervical lymph nodes and cervical lymph nodes in the upper portion
of level V are removed with a supraomohyoid neck dissection while preserving the
sternocleidomastoid muscle, the internal jugular vein, and the spinal accessory
When modified neck dissections are performed, adjuvant radiation therapy to the
neck is frequently required. It is recommended when more than two cervical lymph
nodes contain metastases, when more than one level of cervical lymph nodes are involved
or when there is extension of metastases through the capsule of a cervical lymph
node. Occult cervical lymph node metastases are present in 20-30% of patients with
oral cancers (other than lip, buccal mucosa or hard palate cancers) who present
with a clinically negative neck. Elective neck dissections have been advocated for
these patients to more accurately stage the cancer and to prevent the need for a
later and probably more radical neck dissection when the cervical lymph node metastases
becomes clinically apparent. A supraomohyoid neck dissection is the dissection of
choice in the elective situation.
Surgery is the oldest form of treatment for cancer. It also has an important role
in diagnosing and staging (finding the extent) of cancer. Advances in surgical techniques
have allowed surgeons to successfully operate on a growing number of patients. Today,
less invasive operations are often done to remove tumours and to try to preserve
as much normal oral cavity structure and function as possible. Surgery offers the
greatest chance for cure for many types of cancer, especially those that have not
yet spread to other parts of the body. When the disease is localized, a surgical
procedure may be able to remove the cancer in its entirety.
Surgery can be done for any of several reasons. It is often done to achieve more
than one of these goals:
Various techniques are employed to treat specific types of oral tumours, which include:
- Preventive (or prophylactic) surgery is done to remove body tissue that is not malignant
but is likely to become malignant
- Diagnostic surgery is used to get a tissue sample to identify your specific cancer
and make a diagnosis. The diagnosis of cancer often can be confirmed only by looking
at the cells under a microscope. Several surgical techniques can be used to obtain
a sample. These are surgical biopsies.
- Staging surgery helps determine the extent
and the amount of disease. While your physical exam and the results of lab and imaging
tests can help determine the clinical stage of your cancer, surgical staging is
usually a more accurate assessment of how far the cancer has spread.
surgery is the removal of a tumour when it appears to be confined to one area. It
is done when there is hope of taking out all of the cancerous tissue. Curative surgery
is thought of as a primary treatment of the cancer. It may be used along with chemotherapy
or radiation therapy, which can be given before or after the operation. In some
cases, radiation therapy is actually used during an operation (intraoperative radiation
- Debulking (or cytoreductive) surgery is done in some cases when removing
a tumour entirely would cause too much damage to an organ or surrounding areas.
In these cases, the doctor may remove as much of the tumour as possible and then
try to treat what’s left with radiation therapy or chemotherapy.
surgery is used to treat complications of advanced disease. It is not intended to
cure the cancer. It can also be used to correct a problem that is causing discomfort
or disability. This may require surgery for effective relief. Palliative surgery
may also be used to treat pain when it is hard to control by other means.
surgery is used to help with other types of treatment. For example, a vascular access
device such as a catheter port can be placed into a vein to help deliver chemotherapy
treatments reducing the number of needle sticks needed.
- Restorative (or reconstructive)
surgery is used to restore a person’s appearance or the function of an organ or
body part after primary surgery. Examples include the use of tissue flaps, bone
grafts or prosthetic (metal or plastic) materials after surgery for oral cavity
- Primary tumour resection - entire tumour is removed along with surrounding area
- Mandible resection - all or part of the jawbone is removed.
- Maxillectomy - removal of the tumour, along with part or all of the hard palate
(roof of the mouth), if bone is involved.
- Mohs' micrographic surgery - the tumour is removed in "slices" to minimize amount
of healthy tissue removed (may be taken into account when the lip is involved).
- Laryngectomy - removal of a huge tumour of the tongue or oropharynx, that might
include removal of the larynx (voice box).
- Neck dissection - spreading of cancer to the lymph nodes in the neck, is an indication
for their removal.
Radiotherapy, also called radiation therapy, is the treatment of cancer and other
diseases with ionizing radiation. Ionizing radiation deposits energy that injures
or destroys cells in the area being treated (the target tissue) by damaging the
genetic material (DNA) in the individual cells, making it impossible for them to
Although radiation damages both cancer cells and normal cells, normal healthy cells
are able to repair themselves and return to proper functioning. The total dose of
radiation therapy prescribed by the radiation oncologist is broken down into small
amounts (fractions) which are given on a daily basis, usually five days in a row
with a two day break each week. It has been found that patients tolerate the smaller
daily doses better, while still receiving the maximum benefit of the treatments.
The reason that the treatment course for some cancers is so relatively long (2-8
weeks) is to allow for normal tissue repair after each exposure to radiation and
to minimize permanent injury. Tissue repair can also be helped by proper nutrition
and a positive mental state. The daily dose must also be great enough to destroy
the cancer cell while sparing the normal tissues of excessive levels of radiation.
This balancing act forms the basis of modern radiation therapy.
Types of radiation therapy
One type of radiation therapy commonly used involves photons, "packets" of energy.
X- rays were the first form of photon radiation to be used to treat cancer.
Gamma rays are another form of photons used in radiotherapy.
Another technique for delivering radiation to cancer cells is to place radioactive
implants directly into a tumour or body cavity. This is called internal radiotherapy.
(Brachytherapy, interstitial irradiation and intracavitary irradiation are types
of internal radiotherapy). In this treatment, the radiation dose is concentrated
in a small area. Internal radiotherapy is sometimes used for cancers of the tongue,
uterus, prostate and cervix. One of the advantages of this type of therapy is there
is less radiation exposure to other parts of the body.
Several new approaches to radiation therapy are being evaluated to determine their
effectiveness in treating cancer. One such technique is intraoperative irradiation,
in which a large dose of external radiation is directed at the tumour and surrounding
tissue during surgery. Another investigational approach is particle beam radiation
therapy. This type of therapy differs from photon radiotherapy in that it involves
the use of fast-moving subatomic particles to treat localized cancers.
Other recent radiotherapy research has focused on the use of radiolabeled antibodies
to deliver doses of radiation directly to the cancer site (radioimmunotherapy).
Antibodies are highly specific proteins that are made by the body in response to
the presence of antigens (substances recognized as foreign by the immune system).
Some tumour cells contain specific antigens that trigger the body's immune system
to produce tumour- specific antibodies. Large quantities of these antibodies can
be made in the laboratory and attached to radioactive substances (a process known
as radiolabeling). Once injected into the body, the antibodies actively seek out
the cancer cells, which are destroyed by the cell-killing (cytotoxic) action of
the radiation. The benefit to this approach is that it can minimize the risk of
radiation damage to the body's healthy cells. The success of this technique will
depend upon both the identification of appropriate radioactive substances and determination
of the safe and effective dose of radiation that can be delivered in this way.
Chemotherapy is the use of chemicals to destroy cancer cells. Chemotherapy works
by interfering with the cancer cell's ability to grow. What makes chemotherapy very
effective, is that it has the ability to treat widespread (metastatic) cancer, that
is in more than one location in your body. This ability makes chemotherapy very
important in a patient's fight to overcome cancer, because radiation therapy and
surgery are only suitable for treating cancer in localized areas. When these three
treatments are used in conjunction, their complimentary avenues of attacking the
disease frequently offer the patient the best chance to beat cancer.
Depending on the drug chosen, chemotherapy will affect malignant cells in one of
the following three ways:
Current chemotherapy drugs will act in one of these ways to achieve the ultimate
goal of killing the cancer cells in the body.
- Damage the DNA of the cancer cells so they can no longer reproduce. This is done
by altering the DNA structure in the nucleus of the cell preventing replication.
- During the S phase of cell life, inhibit the synthesis of new DNA strands so that
no cell replication is possible.
- Stop the mitotic processes of the cell so that the cancer cell cannot divide into
The drugs are classified into a specific category depending on what part of the
cell cycle the drug interrupts. The categories are alkylating agents, nitrosoureas,
antimetabolites, antitumor antibiotics, plant alkaloids and steroid hormones.
- Alkylating agents are drugs that work by directly attacking the
DNA of a cell. These drugs can work at any time of the cell cycle, but are most
effective during DNA synthesis.Alkylating agents are administered either orally
or intravenously. Examples of drugs in this category are Cyclophosphamide and Mechlorethamine,
- Nitrosoureas are similar to alkylating agents and work by inhibiting
the changes necessary for DNA repair. A very important feature of this class of
drugs is that they can cross the blood- brain barrier which makes them very useful
for treating brain tumors. Nitrosoureas are administered either orally or intravenously.
Examples of drugs in this category are Carmustine and Lomustine.
- Anti-metabolites block cell growth by interfering with DNA synthesis.
These drugs work by mimicking a substance involved in DNA synthesis, inhibiting
production of an acid necessary for DNA to be synthesized. These drugs affect the
"S" phase of the cell cycle. They are administered either orally or intravenously.
Examples of these drugs are 6- mercaptopurine and 5- fluorouracil.
antibiotics work by binding with DNA to prevent RNA synthesis. These also
prevent cell growth by preventing DNA replication. Antitumor antibiotics prevent
the DNA from reattaching itself together which causes the cell to die. Antitumor
antibiotic drugs are administered intravenously. Some examples of this category
are Doxorubicin and Mitomycin-C.
- Plant (Vinca) alkaloids work
by preventing cell division. During metaphase, mitotic spindles hold the two sets
of DNA the cell needs to divide. The spindles are formed using a protein called
tubulin. Plant alkaloids bind to tubulin, which prevents the formation of mitotic
spindles. Without mitotic spindles, the cell cannot divide. Plant alkaloids are
administered intravenously. Some examples of this category are Vincristine and Vinblastine.
Steroid hormones modify the growth of hormone dependant cancers.
They induce a change in the three dimensional shape of the receptor on a cell preventing
the cell's binding to the needed oestrogen response element on the DNA. The hormones
are administered orally. Some examples of this category are Tamoxifen and Flutamide.
The administration of chemotherapy can be accomplished in several ways. The most
common means are oral and intravenous, but chemotherapy may also be administered
intramuscularly or through catheters.
The oral form is when the drug is in capsule or pill and is taken through the mouth.
Oral administration is very convenient, since all that is required is for the patient
to swallow a pill.
The intravenous form or IV, is when the drug, in liquid form, is introduced directly
into the bloodstream through a small needle that is usually inserted in the arm.
Intramuscular administration of chemotherapy is administered through an injection
directly into the muscle tissue. It is much like receiving a common shot. Chemotherapy
agents injected into the muscle tissue disperse more slowly into the body than if
they are given by an intravenous method.
Catheters are also used in chemotherapy. A catheter is a thin plastic tube that
is inserted into one of the central veins and usually left in place during the course
of treatment. The benefit of a catheter is that the patient always has a device
to receive the chemotherapy and eliminates the need for multiple needle insertions
every time treatment is needed. Catheters may be chosen for patients who have small
veins or have few easily accessible veins.
Though the conventional therapies used to treat cancers have been successfully used
since decades, but they definitely do have some side effects. Healthy surrounding
tissues and even parts of our bodies remote from the area of the cancer are affected
by these treatments. Ideally science would like to find methods of treatment that
are more specific to killing just the cancer cells and not affecting healthy tissues
at the same time.
As we learn more about the mechanisms by which our cells operate, the means by which
they replicate, become malignant or even just their methods of obtaining the nutrients
that allow them to survive, we are finding that using these paths of normal cellular
activity, we may be able to stop the growth of or even kill, very specific cells
such as those that have become cancerous. This is what targeted therapies endeavour
These very specific methods which interfere with some aspect of cellular life without
harming healthy cells in the process are referred to as targeted therapies. They
interfere with specific molecules involved in carcinogenesis (the process by which
normal cells become cancer cells) and tumour growth. Since these biological molecules
are called “molecular targets,” these therapies are sometimes called “molecular-
targeted drugs,” “molecularly targeted therapies,” “targeted drug therapy” or other
Biological therapies for cancer
Biological therapy (sometimes called immunotherapy, biotherapy or biological response
modifier therapy) is a relatively new addition to the family of cancer treatments.
Biological therapies use the body’s immune system, either directly or indirectly,
to fight cancer or to lessen the side effects that may be caused by some cancer
Biological response modifiers: Some antibodies, cytokines and other immune
system substances can be produced in the laboratory for use in cancer treatment.
These substances are often called biological response modifiers (BRMs). They alter
the interaction between the body’s immune defences and cancer cells to boost, direct
or restore the body’s ability to fight the disease. BRMs include interferons, interleukins,
colony- stimulating factors, monoclonal antibodies, vaccines, gene therapy and nonspecific
immunomodulating agents. They work by many different mechanisms:
- Stop, control or suppress the processes that permit cancer growth.
- Make cancer cells more recognizable and, therefore, more susceptible to destruction
by the immune system.
- Boost the killing power of immune system cells, such as T cells, NK cells and macrophages.
- Alter the growth patterns of cancer cells to promote behaviour like that of healthy
- Block or reverse the process that changes a normal cell or a pre- cancerous cell
into a cancerous cell.
- Enhance the body’s ability to repair or replace normal cells damaged or destroyed
by other forms of cancer treatment, such as chemotherapy or radiation.
- Prevent cancer cells from spreading to other parts of the body.
Cancer vaccines: Cancer vaccines are a form of biological therapy currently
under study. Vaccines for infectious diseases, such as measles, mumps and tetanus,
are injected into a person before the disease develops. These vaccines are effective
because they expose the body’s immune cells to weakened forms of the disease antigens
that are present on the surface of the infectious agent. This exposure causes the
immune system to increase production of plasma cells that make antibodies specific
to that particular infectious agent. The immune system also increases production
of T cells, which are designed to destroy abnormal cells. This small amount of disease
antigen that was introduced via the vaccine, programmes them on what to look for
and makes it possible for the T cells to recognize the infectious agent. Now activated
and programmed, the next time the agent enters the body, the immune system is already
prepared to respond and stop the infection.
Gene therapy: Gene therapy is an experimental treatment that involves introducing
genetic material into a person’s cells to fight disease. Researchers are studying
gene therapy methods that can improve a patient’s immune response to cancer. For
example, a gene may be inserted into an immune system cell to enhance its ability
to recognize and attack cancer cells. In another approach, scientists inject cancer
cells with genes that cause the cancer cells to produce cytokines and stimulate
the immune system. A number of clinical trials are currently studying gene therapy
and its potential application to the biological treatment of cancer.
Cancer Immunotherapy: Cancer Immunotherapy is the use of the immune system
to reject cancer. The main premise is stimulating the patient's immune system to
attack the malignant tumour cells that are responsible for the disease. This can
be either through immunization of the patient, in which case the patient's own immune
system is trained to recognize tumour cells as targets to be destroyed or through
the administration of therapeutic antibodies as drugs, in which case the patient's
immune system is recruited to destroy tumour cells by the therapeutic antibodies.
Monoclonal antibody therapy: Antibodies are a key component of the adaptive
immune response, playing a central role in both, the recognition of foreign antigens
and the stimulation of an immune response to them. It is not surprising therefore,
that many immunotherapeutic approaches involve the use of antibodies. The advent
of monoclonal antibody technology has made it possible to raise antibodies against
specific antigens such as the unusual antigens that are presented on the surfaces
Tumour growth factors and targeted therapy: Researchers have discovered naturally
occurring substances in the body that promote cell growth. These hormone- like substances
are called growth factors. Growth factors activate cells by attaching to their specific
receptors, which are present on the outer surface of the cells. One of the growth
factors that have been linked to oral and oropharyngeal cancers is called epidermal
growth factor or EGF. Oral and oropharyngeal cancers with too many EGF receptors
tend to be especially aggressive. New drugs that specifically target and block EGF
receptors have been tested in clinical trials. These drugs work by preventing EGF
from causing cancer cells to grow and divide or by reducing the efficiency of cancer
cells to repair injury to their DNA.
A drug called cetuximab (Erbitux) which blocks the growth receptor, has been successful
in shrinking and eliminating oral cancers when it was given along with radiation.
It has recently been approved by the Food and Drug Administration (FDA) to use along
with radiation in people with advanced oral cancer. Since the FDA approval for this
drug was granted for head and neck use in 2006, we may see this drug used in other
combinations as an adjunct to conventional chemotherapy and radiation or in combination
with other drugs in the future.
Cetuximab is also used alone (a mono- therapy) in people with widespread cancer
that can’t be treated with radiation and no longer respond to chemotherapy. This
drug is given intravenously and can cause rash, fever and chills and nausea. Another
drug called erlotinib (Tarceva), also blocks the growth receptor. This drug, which
is given as a pill, seems to have helped some patients with oral cancer. Further
studies with this class of agents are being undertaken.
The potential impact of targeted and biological therapies: Targeted and biological
cancer therapies may give doctors a better way to custom tailor cancer treatment
for a specific patient. Eventually, treatments may even be individualized based
on the unique set of molecular targets produced by an individual patient’s tumour
biology. These cancer therapies also hold the promise of being more selective, thus
harming fewer normal cells, reducing side effects and improving the quality of life.