Role of Radiotherapy in Head & Neck cancer

Introduction:

Treatment of patients with head and neck cancer requires multidisciplinary approach. Radiotherapy is employed as a primary treatment, or as an adjuvant to surgery. Each of the subsite involved in head and neck malignancy need appropriate techniques, fields, dose and fractionation radiotherapy scheme. Quality of life is another important factor in the management of head and neck cancer. The radiation induced complications have a great impact on the quality of life. Modern radiotherapy techniques hence focuses on the quality of life of the patient. Techniques like intensity-modulated radiotherapy and image guided radiotherapy offers precise radiation delivery and thereby reduces the dose to surrounding normal tissues. This happens without compromising the tumoricidal effect of irradiation.

Head and neck malignancies comprises of a diverse group of tumors arising from upper aerodigestive tract, paranasal sinuses, salivary glands and thyroid glands. The optimal management of head and neck cancer needs a multidisciplinary approach. Surgery and radiotherapy happens to be the primary treatment modalities.

In patients with locally advanced head and neck cancers, surgery and post op irradiation are complementary, a combination of two modalities achieve optimal result. Surgical removal of gross tumor may eliminate the major source of irradiation failure, and radiotherapy may sterilize microscopic tumor spread beyond surgical margins. Recently a combination of chemotherapy and radiotherapy have been introduced to increase tumor control and to preserve organ integrity.

Types of radiation beams:

External beam radiation therapy:

During external beam radiation therapy, a beam (or multiple beams) of radiation is directed through the skin to the cancer site and the immediate surrounding area to destroy the tumor and any nearby cancer cells. To minimize side effects, the treatments are typically given for 5 days a week for 36 weeks. This allows enough radiation to get into the body to kill the cancer while giving healthy cells time to recover. The radiation beam is usually generated by a machine called linear accelerator. The linear accelerator produces high energy x-rays or electrons for the treatment of cancer. Planning computers controls the size and shape of the beam, it all controls how the beam is directed at the body.

The following forms of radiation are used:

Photon beams:

These are the most common forms of radiation. Both X-rays and gamma rays fall in this category. A "photon" is considered as a "packet" of electromagenetic radiations. X-rays are produced by X-ray machines when high energy electrons bombard a metallic target. Gamma rays are emitted by radioactive sources (cobalt 60).

Electron beams:

This is the second most common form of radiation. Their main beneficial characteristic is a rapid dose build up which is followed by a sharp dose fall off with very little scatter. Hence they are used to boost up the radiation dose to the target area avoiding radiation to adjoining vital structures like the spinal cord. They are produced by linear accelerator, betatron and microtron.

Particle radiation:

Electrons, protons or pions belong to this category. This modality is very much under investigation. Neutron radiation is currently being used in malignant salivary gland tumors.

Three-Dimensional Conformal Radiation Therapy:

It is also known as the 3-D CRT. Tumors are not always the same. They come in different shapes and sizes. Three dimensional conformal radiation therapy uses computers and special imaging techniques like CT, MR, or PET scans to show the size, shape and location of the tumor as well as surrounding organs. Since radiation beams are carefully and accurately targettted, nearby normal tissue receives less radiation and hence heals better.

Image guided radiation therapy (IGRT):

Radiation oncologists use image guided radiation therapy to accurately deliver radiation dose to the cancer cells. This involves conformal radiation treatment guided by imaging like CT, Ultrasound or X-rays taken in the treatment room just before administration of radiation dose. Since tumors can move and change in size between treatment, differences in organ filling and movements whilee breathing allows for better targeting of cancer cells. The team compares these images and change the treatment accordingly. In some patients a tiny marker may be implanted near the tumor to help localize the treatment area.

Stereotactic Radiation Therapy:

This technique allows the radiation oncologist to used extremely focused beams of radiation to destroy certain types of tukors using higher doses than with daily radiation treatments. Since the beam is very precise, more healthy tissue may be spared from the effects of radiation.

This was first developed to treat brain tumors in a single dose. This is also known as stereotactic radiosurgery (SRS). In addition to treatment of cancers, radiosurgery can be used to treat benign tumors and certain noncancerous neurologic conditions. In some cases using more than a single dose may help to decrease the risk of side effects.

Intraoperative radiation therapy:

Radiation therapy given during surgery is known as intraoperative radiation therapy. This is helpful when vital normal organs are very close to the tumor. During surgery the surgeon temporarily moves the normal organs out of the way so that radiation can be applied directly to the tumor. This allows the oncologist to avoid exposing those organs to radiation.

Neutron beam therapy:

Like proton therapy, neutron beam therapy is a specialized form of external beam radiation therapy. It involves using neutrons rather than electrons or x-rays to treat certain types of cancer. It is used to treat radioresistant tumors. Neutorns have a greater biologic impact on cells than other types of radiation.

Brachytherapy:

It uses radioactive materials close to the target area. Its major advantages include:

1. Delivery of high dose to the target area

2. Provides continuous radiation rather than intermittent

Continuous low dose radiation is found to be more effective than intermediate or high dose treatment to slowly proliferating or hypoxic cells. Brachytherapy can be delivered in three ways:

a. Interstitial brachytherapy:

Radioactive material is implanted into the tumor

b. Intracavitary brachitherapy:

Here the radiation source is placed into the cavity (nasopharynx/maxillary antrum)

c. Surface moulds:

Here the radioactive material is applied directly to the surface of the tumor with the help of a mould.

Two types of radioactive materials are used for brachytherapy:

Permanent ones: Radium 226 needles (half life 1620 years), Cesium 137 (tubes and needles) half life 30 years

They have a long half life and need to be removed after the period of exposure is over.

Temporary ones: Gold seeds 198 (half life 2.7 days), iodine seeds 125 (half life 60 days)

They have a short half life and need not be removed.

Brachytherapy can be used to deliver full dosee of radiation / to boost radiation after external beam radiation.

Radiation sources:

Higher the energy of radiation, deeper it penetrates. X-rays produced energy in kilovolts (kV) and could be used for superficial tumors of the skin / lip. The currently available machines produce radiations of high energy in MV. They have greater penetrating power and can be used for deep seated tumors sparing untoward effects on the skin and bone. Various machines used for radiations include:

Kilovoltage machines:

These machines produce X-rays of 50-400 kV. They were the earliest machines useed and can be divided into superficial 5-15kV or orthovoltage 200-400 kV x-ray machines.

Cobalt 60 machines:

This is the most commonly used radiation source for head and neck tumors. It uses radiactive cobalt source, which produces gamma rays of 1.17 and 1.33 MeV (fixed). The source has its natural decay time and needs replacement after 5 years.

Linear accelerator:

These are mega voltage machines which work on electricity and produce radiation of 4-25 MV. They are capable of producing both photon / electron beams depending on whether an intervening metallic target is used in machine or not. Most of the currently available machines can produce low energy megavoltage x-rays (4-6MV), high energy megavoltage (15-25 MV) and also electrom beams.

Advantages of megavotage beam therapy:

1. Skin sparing effect

2. Penetration depth is rather deep. Deeper the location of tumor higher is the megavoltage beam used

3. Dose distribution is isodose providing uniform dose distribution.

Units of radiation:

During earliers years RAD (Radiation absorbed dose) was considered to be the unit of radiation. Now currently it has been replaced by Gray. One Gray is equivalent to one joule of energy deposited per kilogram of material.

One Gray = 100 rads / 100 centigray

Curative dose delivered to the tumor:

If radiation is used as a single modality of treatment then:

It is delivered by teletherapy, brachytherapy, or by a combination of both. The dose used will depend on the extent of the tumor and its lymphatic field and tolerance of normal tissue in the adjoining area. The usual delivered dose is:

6000-6500 cGy for small tumors

6500 - 7000 cGy for large tumors

7000 - 7500 cGy for massive tumors

Shrinking field radiation is used i.e. the initial dose covers cancer area and its lymphatic field, and subsequently the portals are reduced to cover the tumor area only. This technique is used when different volumes within the patient are thoought to contain different quantities of tumor cells. This is done in an effort to reudce the volume or normal tissue being treated with a higher radiation dosage.

Types of radiation treatment for cancer:

1. Radiation alone is effectinve in early cases and it preserves the function of the organ.

2. In combination with surgery:

It can be used as preop radiation or post op radiation

In advanced cases:

In combination with chemotherapy

Concurrent chemoradiation

Palliative radiation is used in massive inoperable tumors, poor patient general condition and presence of distant metastasis.

Advantages of preop radiation:

a. It reduces the bulk of the tumor making a borderline unresectable tumor to the one that can definitely be resectable

b. Since there are no operative scar tissue, the response of tumor cells to irradiation is that much better

c. Lymphatic tissue gets fibrosed and blocked after irradiation, and hence tumor dissemination during surgery via lymphatics is rare

d. Pre op irradiation eliminates microscopic disease and occult metastasis to lymph nodes

e. Treatment portals in preop irradiation are smaller that that would be required for post op irradiation

Disadvantages of Preop irradiation:

a. It reduces the vascularity to normal tissues also there by interfers with post operative wound healing. These patients commonly have post op wound infection, dehiscence, fistula etc.

b. If the post op margins are positive for malignancy then irradiation cannot be given again

Dose of preop radiation:

Preop radiation dose is usually 4500cGy delivered in 4-5 weeks. This dose is sufficient to eradicate nearly 90% of micrometastasis. Higher than this dose would interfere with wound healing.

Postop irradiation:

Dose used in postop irradiation is 60-66 Gy delivered at 2 Gy per fraction, one fraction per day, for 5 days a week in a continuous manner.

Advantages of postop radiation:

a. It becomes more effective as the bulk of the disease has been removed by surgery

b. Extent of the disease can be precisely assessed and radiation can be given to suspected areas of residual disease / to areas that show positive margins

c. Surgical resection is technically easy as the tissue is a virgin one

d. Post op healing is very good

e. Greater dose of radiation can be delivered to the target area adjusted on the basis of residual disease and presence of positive margins

f. Postop complications are fewer

Disadvantages of postop irradiation:

1. Blood supply to tissues is interfered due to fibrosis following surgery and the cancer cells are hypoxic and dont respond well to irradiation

2. If surgical complications occur postop irradiation is delayed allowing time for residual malignant cells to regrow. Results of post of radiation are poor if it gets delayed beyond a period of 6 weeks

3. Distant metastasis due to tumor dissemination via blood circulation and lymphatics is a distinct possibility

Indications for postop radiation:

1. When the resected margins are postive or too close

2. When there is involvement of bone / cartilage

3. If nodes show extracapsular invasion

4. When there is involvementof multiple nodes and their size exceeds 3 cm.

Combination of radiation & chemotherapy:

Aim of combining radiation with chemotherapy is to

i. Create a synergistic effect to kill malignant cells

ii. To eliminate micrometastasis that could cause distant metastasis

Combination of these two modalities has resulted in better tumor response and longer periods of remission.

Palliative radiotherapy:

This is indicated when the tumor is in a very advanced state and has distant metastasis.

Complications of radiotherapy:

Early complications:

1. Radiation sickness (loss of appetitie/nausea)

2. Mucositis

3. Xerostomia

4. Skin reactions (erythema / desquamations)

5. Laryngeal oedema

6. Candida infections

7. Suppression of Hemopoiesis

8. Acute transverse myelitis

Late complications include:

1. Permanent xerostomia

2. Skin changes (atrophy of skin, subcutaenous fibrosis)

3. Dental decay secondary to xerostomia

4. Osteoradionecrosis of mandible

5. Cartilage necrosis

6. Trismus due to fibrosis of TM joint and muscles

7. Transverse myelitis (Lhermitte syndrome)

8. Cataract

9. Radiation retinopathy

10. Cataract formation

11. Endocrinal deficit (thyroid, pituitary)

12. Serous otitis media, SN loss, vestibular symptoms

13. Radiation induced malignancy of thyroid

14. Brain injury

Patient care during radiotherapy:

1. Nutrition: Patient should be fed with nutritional diet with vitamin supplements. Nasogastric feeding can also be resorted to to improve intake.

2. Blood transfusion in patients who are anaemic

3. Dental care

4. Skin care. The skin should be kept dry and soap should not be used. Exposure to sunlight should be avoided. Wet shaving should also be avoided. Adhesive plasters should not be used over the skin. Dressing worn should be soft and loose.

5. Oral cavity care. Prevention of mucositis and xerostomia.

6. Infection prevention and maintanance of hygiene.