Treatment
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:
  • 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 are altered.
  • Dentist/ Prosthodontist: Replaces teeth and parts of jaw to maintain good oral hygiene.
  • 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.
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 problems.
Treatment
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 nerve.

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.

Treatment Options
Surgery
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:

  • 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.
  • Curative 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 therapy).
  • 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.
  • Palliative 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.
  • Supportive 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 cancers.
Various techniques are employed to treat specific types of oral tumours, which include:
  • Primary tumour resection - entire tumour is removed along with surrounding area of tissue.
  • 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.
Radiation
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 grow.

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
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:
  • 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 two cells.
Current chemotherapy drugs will act in one of these ways to achieve the ultimate goal of killing the cancer cells in the body.

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, Cisplatin (Platinol).
  • 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.
  • Anti-tumor 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.

Recent methods
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 to accomplish.

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 similar names.

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 treatments.

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 cells.
  • 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 of tumours.
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.
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