Biological Effect of Radiation – Radiation therapy uses high-energy ionizing radiation to kill cancer cells. It is considered a local therapy because the cancer cells are destroyed only in the anatomical area being treated. The radiation causes a breakage of one or both strands of the DNA molecule inside the cells, thereby preventing their ability to grow and divide. While cells in all phases of the cell cycle can be damaged by radiation, the lethal effect of radiation may not be apparent until after one or more cell divisions have occurred. Although normal cells can also be affected by ionizing radiation, they are usually better able to repair their DNA damage.
Principles of Treatment – The dose of radiation administered is determined by a number of factors, including the radiosensitivity of the tumour, the normal tissue tolerance, and the volume of the tissue irradiated. The Gray, the Systeme Internationale Unit, has now replaced the “rad” (radiation absorbed dose) as the accepted term of radiation dosage. One Gray (Gy) = 100 rads; therefore, 1cGy = 1 rad.
A radiosensitive tumour is one that can be eradicated by a dose of radiation and is well tolerated by the surrounding normal tissues
Table of Radiosensitivity
| Tumours or Tissues | Relative Radiosensitivity |
|---|---|
| Lymphoma, leukaemia, seminoma, dysgerminoma |
high |
| Squamous cell cancer of the oropharynx; Glottis, bladder, skin, and uterine cervix; Adenocarcinomas of the alimentary tract |
fairly high |
| Vascular and connective tissue elements of all tumours; Secondary neurovascularization, astrocytomas |
medium |
| Salivary gland tumours, hepatoma, renal cancer, pancreatic cancer, chondrosarcoma, osteogenic sarcomas |
fairly low |
| Rhabdomyosarcoma, leiomyosarcoma and ganglioneurofibrosarcoma |
low |
The sensitivity of tumour cells to the effects of radiation are also dependent on the presence of oxygen. Killing hypoxic cells requires 2-3 times the dose of radiation required to achieve the same therapeutic effect on well-oxygenated cells. Hypoxic cells occur when tumour growth exceeds the blood supply and the central core of the tumour becomes necrotic. Strategies are being developed to increase the radiosensitivity of these hypoxic, resistant cells with chemicals to mimic the presence of oxygen or with hyperthermia (use of heat).
The dose of radiation that can be delivered to a tumour is also limited by the radiation tolerance of the adjacent normal tissues. This limit is the point at which normal tissues are irreparably damaged. The maximum dose of radiation that can be administered to parts of the body varies with the tissues involved.
Administration of a tumour-lethal dose of radiation in a single treatment would result in an unacceptable toxicity or even death. Thus, the total prescribed dose is administered over a course of smaller divided doses, called fractions. Treatments are usually given on a daily basis, five days per week, for an average of 25 to 30 treatments. Hyperfractionation usually involves the delivery of radiation twice a day, as early as possible in the day and then late in the afternoon. With fractionation, a tumouricidal dose can be delivered while minimizing the damage to normal tissues. In addition, gradual shrinkage of the tumour during treatment bring hypoxic cells closer to the vascular supply, where they become oxygenated and more susceptible to the effects of radiation.
For some tumours, a “boost” or “reduced field” of radiation is administered to complete the course of therapy. These treatments are delivered to limited areas within the treatment field that are at highest risk for recurrence. In this way, the tumour can be treated with a higher dose than the normal surrounding tissues would tolerate or need. The “boost” may be administered externally or internally.
Primary Therapy – Radiation therapy is a primary therapy for basal cell carcinomas of the skin, early-stage laryngeal cancers and other head and neck cancers, early stage Hodgkin’s disease, non-Hodgkin’s lymphomas, early stage breast cancer following lumpectomy, certain lung cancers, seminomas, carcinomas of the cervix, prostate cancers, bladder cancers, certain pediatric tumours, and some brain tumours.
Radiation and surgery, both of which are local therapies, may achieve comparable responses and cure rates in some diseases; however, radiation may have some treatment advantages in certain cases. For example, the functional and cosmetic outcomes of radiation therapy may be superior to the surgically obtained results. Individuals may be unable to undergo surgery due to pre-existing medical conditions, thus making radiation therapy a better choice.
Combined Modality Therapy – Radiation therapy may be used in addition to other primary treatment modalities. Postoperative radiation therapy is frequently used to decrease the risk of local recurrences following surgery to the breast, lung, high-risk rectal cancers, and brain tumours. Preoperative radiation to shrink the size of a tumour to allow a less radical or disfiguring surgical procedure is used less frequently at present.
Radiation therapy and chemotherapy are frequently combined to increase tumour destruction. Certain chemotherapeutic agents increase the radiosensitivity of cancer cells. However, combination approaches may exacerbate known side effects of these therapies. For example, concurrent radiation of patients receiving cyclophosphamide (which is known to damage the bladder mucosa) often have a higher incidence of cystitis.
Tumour cells appear to be especially sensitive to heat. Hyperthermia is used in some treatment centers in conjunction with radiation therapy to potentiate the effects of the radiation therapy.
Prophylaxis – Radiation therapy may also be used to prophylactically treat tissues or organs before disease is clinically evident. The central nervous system is frequently treated with radiation to prevent relapse of certain forms of leukemia in the brain.
Palliative Treatment – Radiation therapy may be used to palliate the symptoms of metastases in patients with widespread disease. Pain, bleeding, compression of vital structures such as the brain, ulcerating skin lesions, and metastases in weight-bearing bones susceptible to fracture can be managed with palliative radiation.
Oncologic Emergencies – Radiation therapy is used to manage spinal cord compression and superior vena cava syndrome.
Administration of Radiation Therapy
Radiation treatments can be administered externally or internally, depending on the type and extent of the tumour. X-rays, radioactive elements, and radioactive isotopes are most often used.
External Beam Radiation – External radiation treatment are administered by machines that deliver high-energy radiation. These machines vary according to the amount and type (electromagnetic or particulate) of energy produced. The Cobalt-60 machine was the first megavoltage machine, and is still workhorse used in institutions throughout the world. Linear accelerators, using high-energy x-ray beams, are now frequently used machines. Technological advances have permitted the development of machines with increased energy, allowing for precise treatments of deep seated tumours with less damage to superficial tissues (skin sparing).
Simulation and Treatment Planning – The purpose of treatment planning is to determine the best way to deliver the radiation treatment and to limit the radiation dose to normal tissues. X-ray machine which “simulates” is used to visualize and define the exact treatment area.
Customized shielding devices (blocks) protect healthy tissues from the radiation beam. Temporary dye or permanent tattoos about the size of a small freckle may be used to mark reference points on the skin to allow exactly the same area to be treated each day. In order to deliver treatments precisely, immobilization devices may be used to support and assist the patient in maintaining an exact position during treatment.
Internal Radiation – Internal radiation, or brachytherapy, is the use of radioactive isotopes for either temporary or permanent implants. Methods of delivering brachytherapy include intracavitary or interstitial placement of sources, instillation of colloidal solutions, and parenteral or oral administration. Sealed sources are encapsulated in a metal seed, wire, tube or needle. Unsealed radioactive sources are prepared in a suspension or solution.
Encapsulated radioactive elements are placed in body cavities or inserted directly into tissues with suitable applicators. The applicator is usually placed into the body cavity or tissue surgically or using fluoroscopy. The applicators, usually plastic or metal tubes, may be sutured into or near the tumour to hold them in place. When the patient is returned to his hospital room, the radioactive isotope is placed into the applicator. This “after loading” technique is used to reduce the radiation exposure to hospital personnel. These implants provide radiation to a limited area. Radiative implants are used in the treatment of cancers of the tongue, lip, breast, vagina, cervix, endometrium, rectum, bladder, and brain.
Encapsulated sources may also be left within a patient as permanent implants. “Seeding” with small beads of radioactive material is an approach used for the treatment of localized prostate cancers, and localized but inoperable lung cancers. The patient’s body attenuates (blocks) most of the radiation, requiring minimum precautions. Radioactive isotopes can be administered orally, parenterally, or instilled into pleural or peritoneal spaces. Thyroid cancer, for example, is frequently treated by oral administration of radioactive iodine (I-131). The period of greatest radioactivity of I-131 is 8 days.
Patients receiving internal radiation via either sealed or unsealed sources eminate some radioactivity and thus should be physically isolated. People under the age of 18 and pregnant women should not be permitted in the room. With sealed sources, body fluids and waste from the patient are not radioactive. Bed rest may be required to prevent dislodging the radioactive source. Once the implant is removed and returned to the lead-lined container, the patient is no longer radioactive.
Secretions from patient treated with unsealed radioactive isotopes should be treated as radioactive waste. These patients may be discharged from the hospital when it is determined that the total body retention of the isotope is at a safe level.
Patients receiving external beam therapy have no internal radioactivity during or after their therapy.
Newer ways are being investigated to increase the effectiveness of radiation therapy. Two types of investigational drugs are being studied for their effect on cells undergoing radiation. Radiosensitizers make the tumour cells more sensitive to be damaged, and radioprotectors protect normal tissues from the effects of radiation. Hyperthermia, the use of heat, is also being studied for its effectiveness in sensitizing tissue to radiation
