Introduction

Cancer in its basic sense is an uncontrolled, unrestricted excessive growth of cells and is very clearly differentiated from other forms of illness. With the mortality rates of cancer raging high a thorough knowledge of its causes and a precautionary measure to decrease its occurrence risk can be beneficial. But what about a scenario where your body has already submitted to cancerous growth and you are already suffering with the ill effects?

The knowledge about the treatment options available can come as a great advantage. Whether it is you, a family member, or an acquaintance this knowledge can be beneficial in giving you a heads up on what’s next, what to expect from a therapy and some basic do’s and don’ts that can aid during therapy. Because cancer comprises many diseases, doctors use many different treatments. The course of treatment depends on the type of cancer, its location, and its state of advancement. Once the diagnosis has been formulated, the doctor and the patient are faced with the decision as to which treatment can offer the patient a complete relief as well as quality of life. Choosing the appropriate treatment relies on many factors, including the patient’s medical condition as well as the modalities available to the clinician. Certain therapeutic modalities, such as neutron beam radiotherapy, may hold promise for certain tumours, but are limited in their availability.

Types of treatment modalities

The treatment of cancer falls into these basic categories:

1. Surgery
2. Chemotherapy
3. Radiotherapy,
4. Combination therapy
5. Hormonal therapy
6. Biologic therapy
7. Targeted therapy
8. Bone marrow transplantation
9. Palliative therapy

Objective of treatment

The principle objective of treatment is to cure the patient of cancer and in cases where the cancer is significantly untreatable the aim is to provide palliative treatment to increase the patient’s quality of life.

Which treatment to choose is a crucial decision

The choice of treatment depends on various factors like:

1. Type of cancer
2. Extent of cell differentiation
3. Site /size and location of the primary lesion
4. Lymph node status, presence of bone involvement
5. Physical and mental status of the patient
6. Thorough assessment of the complications involved in each therapy
7. The experience and skill of the surgeon and radiotherapist
8. The personal preferences and co-operation of the patient
9. State of nutrition, general health & age of the patient
10. Tobacco use, alcohol intake

Surgery

Surgery is used

• To remove solid tumours
• Early stage cancers and benign tumours.
• Cases where Side effects of surgery are expected to be less than those for radiation therapy
• Tumours that lack any sensitivity to radiation.
• Tumours that recur and areas that have already previously received the maximum limit of radiation exposure by therapy.
• To remove the bulk of a tumour and promote drainage from a blocked cavity.

Advantages of getting the tumour mass removed surgically

• Surgery remains the cornerstone of most treatment regimens for cancer.
• It offers the advantage of harvesting of specimen for further analysis
• The possibility of removing the complete cancer in one treatment session
• Surgical removal offers a lesser chance of recurrence than the other treatment options.
• For most Stage 1 and stage 2 cancers of oral cavity, surgical resection with frozen section analysis of the margins is advocated by most clinicians.
• Surgical removal offers a lesser spectrum of side effects than a radiation therapy and is hence an obvious choice over radiotherapy when the option is available.

It is agreed by most that surgeons should strive for clear margins while resecting a cancer tissue surgically. Excision with 1 to 1.5 centimetres of normal tissue beyond the obvious tumour edge is generally sufficient. Combining surgery and radiation is widely advocated for advanced stage disease to improve survival and decrease the likelihood of recurrence. Radiation therapy can be employed both prior and post the surgical therapy.

Complications of surgery and its disadvantages

Complications of surgical resection are many and vary directly with the patient’s other health diseases, such as ischemic cardiac disease, chronic pulmonary disease and alcoholism.

• Medical manifestations of pre-existing chronic disease states, such as myocardial infarction, stroke and pneumonia, can be precipitated by major surgery, a long general anaesthetic and a prolonged intensive care unit stay.
• Significant morbidity or death can be the result.
• Technical surgical complications, such as failure of reconstructive flaps, development of fistulas, and the other myriad problems that may require return to surgery for management, which is still a lesser issue when compared to the greatest complication— recurrence of the cancer
• Recurrence of the cancerous growth can occur due to incomplete removal or a failure in removing the adjoining normal tissue, as we already know; even a single malignant cell can pose a threat to developing cancer.
• Surgery cannot be applied in cases of advanced cancer lesions where the tumour mass has shown the property of a malignancy and has invaded distant organs (metastatic).

Chemotherapy

A chemical war with the cancerous cells

Chemotherapy is mostly employed for patients with recurrent or highly metastatic forms of the disease. As in such cases surgery and radiation therapy cannot be employed without serious complications. Mostly chemotherapy is used along with either radiation therapy or surgery and in such cases it is reported to decrease distant metastasis, increase local-control and also increase survival rates and overall prognosis. For e.g. chemotherapy used as an only treatment modality has been shown to be curative in majority of cases with advanced testicular cancer and in young children with acute lymphoblastic leukaemia (ALL).

Where it is used

• Patients who have relapsed after extensive surgery and radiation therapy.
• Debilitated patients with excessive weight loss and pain.
• Patients with adequate physiologic functions to tolerate the toxicity induced by these chemotherapeutic drugs.

Chemotherapeutic drugs are toxic compounds that target the rapidly growing cells in the body. These act by interfering with DNA replication and hence they disturb the cell which fails to complete S phase of the cell cycle. They cause extensive DNA damage and hence stop the cell division. Because most adult normal cells do not divide much they are less sensitive to these drugs and then the aggressively dividing cancer cells. These four drugs have been used commonly as single agents in patients with recurrent and metastatic cancers of head and neck region:

1. Methotrexate
2. Bleomycin
3. Cisplatin and its analogue carboplatin
4. 5-fluorouracil

Other, less commonly used single agents are: Cyclophosphamide, ifosfamide and hydroxyurea.

Complications of chemotherapy

• Patient’s poor tolerance to combination chemotherapy.
• Overall poor compliance.
• Chemotherapeutic drugs can prove harmful to some normal adult cells that divide rapidly such as those that line the Gastrointestinal Tract, bone marrow and hair follicles. Therefore causing the significant side effects like: Gastrointestinal distress, low WBC count, and hair loss.
• About 40 percent patients receiving chemotherapy will experience oral complications.
  • Mucositis and ulcerations.
  • Pain
  • Xerostomia or salivary gland dysfunction.
  • Taste alteration
  • Dental Developmental Abnormalities.
• Many of these drugs can cause bone marrow suppression and hence leukaemia, which will further put the patient at a higher risks of frequent infections.
• The usual clinical signs of inflammation (redness, pain, swelling and heat) can be almost absent in such cases of immunosuppression.
• Administration of drugs like vincristine and vinblastine can cause neurotoxicity.

Radiation therapy

Radiation may be administered with intent to cure, as part of a combined radiation - surgery and/or chemotherapy management, or for palliation. Radical radiotherapy is intended to cure; Palliative therapy provides symptomatic relief from pain, bleeding, ulceration and oropharyngeal obstruction. Radiation kills the cancer cells by targeting the tumour cell’s DNA with high energy photons. This causes DNA damage and hence prevents replication by these cells. It preferentially kills the cancer cells as they are rapidly dividing and have a higher growth fraction. Although it may cause harm to some normal adult cells too that are dividing. The affected cells may die or may be rendered incapable of division. The differential effect of radiation in normal versus cancerous cells is achieved due to the greater capability of the normal cells to undergo repair which is almost absent in cancer cells.

Choosing between radiation therapy and surgery

Radiation therapy has the advantage of treating the disease in situ and avoiding the need for unnecessary removal of sound normal tissue as well. But When faced with the question of whether to opt for surgery or for radiotherapy, it is important to understand how exactly radiation works in such cases of therapies. Following factors should be weighed and compared:

• The relative cure that can obtained in that case when radiation therapy is employed as compared to other modalities.
• The Relative morbidity and complications that is associated with radiation therapy when compared to surgery.
• The cosmetic and functional results of radiation versus surgery.
• Improved local control and survival that can be achieved if the combination of radiation and surgery is done.

Options for radiation therapy

• Lesions that are small (under 3 cm in size) and superficial (exophytic and without necrotic areas)
• The more differentiated a tumour the lesser will its response be to radiation therapy.
• Superficial lesions where the functional and cosmetic results of radiation are better than surgery.
• When the lesion is potentially extremely radiosensitive, radiotherapy becomes the treatment of choice E.g. Lymphomas.
• If a lesion when tested clinically, histological and otherwise shows lymphatic involvement, radiotherapy is useful as it covers a wide range of lymphatic.
• Patient’s medical condition.
• Patients in whom radical surgery and prolonged anaesthesia are absolutely contraindicated.
• Availability of equipment and expertise

Planning the treatment

The treatment plan for radiation therapy is dependent upon certain factors like:

• Where the tumour is located?
• How large or small the tumour is?
• What is the total volume of area that will receive the radiations?
• How many treatment fractions will be required?
• How long will this treatment last?
• Is the patient tolerant to such a treatment?

Treatment planning requires localization of tumour and radiation planning.

Brachytherapy

Brachytherapy may be the primary treatment modality for:

• Localized tumours
• Boosted doses of radiation to a specific site
• Following recurrence

Directly implanted sources may be used to deliver the radiation doses or an after loading technique may be used in which radiation source is placed by using previously inserted guide tubes. These implants deliver radiation in immediate vicinity to the implanted isotope and at a relatively low dose rate which has an added biologic advantage in sparing the normal tissues.

Interstitial and intracavitary implants may be used for brachytherapy. Interstitial technique involves placing the radiation source in the tissue mass of the tumour growth while intracavitary technique employs placing the source in a close proximity to the tumour in the nearest body cavity. Commonly used isotopes are cesium, iridium and gold. Cesium-137 is directly inserted around cervix delivers a high dose of radiation to locally advanced cervical cancer.

External beam technique

Radiation therapy is primarily given by external beam using electro-magnetic radiations. Low energy external beam sources are referred to as orthovoltage. These orthovoltage beams are more damaging to bone and hence require shielding of bone. Megavoltage beams from Cobalt-60 or linear accelerators of 4 million electron volts or higher are used for external beam treatment. It is beneficial in treating superficial lesions.

Peroral cones or applicators

Peroral irradiation or direct applicators may be delivered with electrons using special cones or applicator instruments. This approach is useful alone or combined with external beam x-rays for lesions under 3 cm in diameter. This therapy can produce effects which are parallel to brachytherapy. It is clearly superior to external beam for T2 tumours of the Floor of mouth.

Complications of radiation therapy

When delivering ionizing radiations to an area to kill the cancer cells some collateral damage is unavoidable and many complications are frequently observed, these include:

• Acute skin reactions or radiation dermatitis causing loss of hair, dryness of skin by damage to sweat glands, redness, frequent ulcerations.
• Delayed skin and subcutaneous damage including Telangiectasia, edema and fibrosis.
• Radiation damage to chromosomes may predispose a cell to malignant behaviour.
• Damage to bone marrow may result in leukaemia, anaemia, lymphopenia.
• Cataract of lens can be induced by high doses of radiation.
• Brittleness of nails.
• Radiation otitis media and even deafness due to rupture of eardrums.
• Alterations in fertility when area subjected to radiations includes gonads.
• A specific late effect of radiotherapy is the development of secondary malignancies noticed in cases of Hodgkin’s Lymphoma and breast cancer which received radiation therapy.

Intraoral changes include:

• Acute mucositis (redness, pain, ulcers covered by a pseudo membrane) which may become so severe that a break in treatment may be required.
• Radiation caries can be seen altered anatomy of developing teeth.
• Damage to bone can lead to osteonecrosis and sequestration or progressive osteonecrosis.
• Damage to salivary glands can cause hyposalivation and xerostomia.
• Damage to taste buds may cause temporary or permanent (rare) alteration of taste.

Combination therapy

Surgery and radiotherapy

Surgery has the ability to remove the major bulk of tumour including the potentially resistant central portion, and radiation then helps to sterilize the routes of spread in the lymphatic and other tissue planes that cannot be excised completely by surgery. Combination of surgery and irradiation are used in at least one half of all cancer treatments. Radiation can be used pre-operatively, post-operatively or in a planned split-course approach. Preoperative radiation therapy can prove beneficial by reducing the size of large tumours and hence making them easier to remove by surgery. If proper fractionation of dose and techniques are employed postoperative complications are significantly reduced. Postoperative irradiation is used more extensively.

Why it is helpful?

Preoperative Radiation:

• Destruction of peripheral tumour cells.
• Potential control of subclinical disease.
• Converting inoperable lesions into operable ones.

Postoperative Radiation:

• Treat cells remaining at the margins after removal of central tumor mass.
• Control subclinical disease

Chemotherapy and Radiation

There is enhanced effect when chemotherapy is given prior to radiotherapy or in rapidly alternating sequences to radiation therapy. This combination enhances local disease control and is useful in cases where surgery is not an option. Combined chemoradiotherapy has generally utilized single agents along with radiation. Multiagent chemotherapy when combined with radiotherapy can have higher incidences of mucositis and hence a rapidly alternating schedule is employed to decrease the toxicity of the agents used as well as to make the treatment possible without interruptions.

Chemotherapy, Radiation therapy and Surgery

Combination of all the three that is Chemotherapy, radiation as well as surgery in any sequence of treatment plan can be useful in many difficult-to-treat cases of cancer. With all three of these working in their individual mechanism they can provide a combined rapid effect in the curative process.

Hormonal therapy

Cancer originating from the tissues that are under the influence of hormones like breast, prostate and endometrium often respond to agents that can inhibit the hormonal secretions by blocking the respective hormone receptor. For e.g. Progesterone therapy is given in cases with endometrial cancer. Luteinizing Hormone- Releasing Hormone (LHRH) agonist is useful in cases with prostate cancer; Tamoxifen is useful in metastatic breast cancer.

Biologic therapy

Interferon, interleukin-2, and monoclonal antibodies are examples of biologic therapies. For e.g. interferon therapy is used commonly for treating Chronic Myelogenous Leukaemia (CML), Interleukin-2 is used in patients with metastatic renal cell carcinoma.

Targeted therapy

Targeted therapy is the use of drugs and antibodies that target receptors specific to a cancer or critical for cancer cellular growth. For e.g. Monoclonal antibodies are used in treatment of patients with low grade lymphoma and breast cancer

Bone marrow transplantation

Cancer involving Bone marrow can prove to be very difficult to treat by conventional therapy as bone marrow is extremely susceptible to complications produced by radiation and chemotherapy. For e.g. Bone Marrow transplantation can improve survival rates of patients with Chronic Myelogenous Leukaemia (CML), relapsed Hodgkin’s and non-Hodgkin’s Lymphoma and acute leukaemia.

Palliative therapy

Cancer Care in an advanced stage requires every skill of the clinician to provide the patient a better and more comfortable life by decreasing the symptoms. In patients with advanced stage cancer where complete cure is not possible due to multiple organ involvement, palliative therapy comes into play. This therapy is intended to minimize the discomfort of the patient and to provide comfort and care to the patient as well as his family when they are going through the most difficult time of their lives. Palliative therapy may be delivered in any of the already mentioned ways of - radiation therapy, chemotherapy, surgery or combination therapy, delivered at a lower intensity than the conventional treatment regime so as to provide a palliative effect. For e.g. Palliative Chemotherapy in 5-10% of unresectable lung cancer has long term disease-free survival.

Conclusion

Although science has advanced to a level where most cancers are treatable if diagnosed at an early stage, Cancer remains to be an unpredictable form of disease with sky-high incidences of recurrence or even complete resistance to therapeutic radiation and chemotherapeutic drugs hence placing the patient at high mortality risk. The best chance of winning against cancer is by avoiding the battle altogether. Therefore certain preventive changes to your lifestyle can make you less susceptible to this disease. These include abstinence from alcohol abuse, smoking, any other forms of tobacco (including smokeless tobacco forms) , consuming a healthy balanced diet, maintaining a strong body immunity and taking necessary protection against the carcinogenic substances that might be present in your work/home environment.

References

1. SILVERMAN’S ORAL CANCER - 4th Edition, Chapter 6: Treatment Chapter 7: Complications of Treatment
2. BURKET’s ORAL MEDICINE,DIAGNOSIS AND TREATMENT- 11th Edition, Chapter- Oral Cancer: Treatment
3. REDISCOVERING BIOLOGY - Molecular to Global Perspectives: Cell Biology and Cancer
4. FACT SHEET ON CANCER-WORLD HEALTH ORGANISATION
5. CANCER- Malcolm R.Alison, Imperial College School of Medicine, LONDON,UK
6. ORAL MANAGEMENT OF CANCER PATIENT- Gerry J. Barker, Bruce F. Barker, Ronald E.Gier : Introduction to treatment.
7. TEXTBOOK OF DENTAL AND MAXILLOFACIAL RADIOLOGY - Freny R. Karjodkar, 1st Edition, Chapter- Radiation Biology
8. PETERSON's PRINCIPLES OF ORAL AND MAXILLOFACIAL SURGERY - 2nd edition Part 5- Maxillofacial Pathology Chapter- 33: Oral Cancer Treatment
9. CECIL’s- ESSENTIALS OF MEDICINE- 6th Edition, ANDREOLI