Radiotherapy

Radiatiotherapy or radiation therapy is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells by linear accelerator (Pic. 1). Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body (Pic. 2). It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer; Pic. 3). Variations in the indication for treatment, as adjuvant, radical or palliative radiotherapy, also define different variables in the influence. 

Radiation therapy is commonly applied to the cancerous tumor because of its ability to control cell growth. Ionizing radiation works by damaging the DNA of cancerous tissue leading to cellular death. This DNA damage is caused by one of two types of energy, photon or charged particle. This damage is either direct or indirect ionization of the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming free radicals (hydroxyl radicals), which then damage the DNA.

Before treatment, a CT (computered tomography) scan is often performed to identify the tumor and surrounding normal structures. The patient receives small skin marks to guide the placement of treatment fields. Patient positioning is crucial at this stage as the patient will have to be set-up in the identical position during treatment. Many patient positioning devices have been developed for this purpose, including masks and cushions which can be molded to the patient.

Most of times, conventional treatments with radiotherapy are delivered in five weekly fractions (Pic. 4) throughout an uninterrupted variable period of two-eight weeks, depending on the disease to be treated; however, alterations in the therapeutic scheme may occur.

Radiotherapy, especially when administered in limited fractions of high dose, positively influences tumorspecific immunity. Current fertility preserving strategies before chemotherapy/radiotherapy such as cryoconservation (using freeze) of oocytes or ovarian tissue and limitation of the dose applied to the ovaries, ultimately were depending on the use a surrogate mother, as uterine dysfunction after pelvic radiation therapy was assumed to preclude to carry a pregnancy to term.

During the first two weeks after fertilization, radiation therapy is lethal (causing death) but not teratogenic (causing developmental malformations). High doses of radiation during pregnancy induce anomalies, impaired growth and intellectual disability, and there may be an increased risk of childhood leukemia and other tumours in the offspring.

In males previously having undergone radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. However, the use of assisted reproductive technologies (ART) and micromanipulation techniques might increase this risk.

Radiotherapy is an important therapeutic option for the treatment of cancer. Growing evidence indicates that, besides inducing an irreversible DNA damage, radiotherapy promotes tumor-specific immune response, which significantly contribute to therapeutic efficacy.

Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology.

The combination of early diagnosis and current therapeutic methods (radiotherapy, chemotherapy, surgery and bone marrow transplant) has allowed the achievement of increasing survival rates and better quality of life for patients considered as incurable.

The response of a tumor to radiation therapy is related to its size. Due to complex radiobiology, very large tumors respond less well to radiation than smaller tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection prior to radiation therapy. This is most commonly seen in the treatment of breast cancer with wide local excision or mastectomy followed by adjuvant radiation therapy. Another method is to shrink the tumor with neoadjuvant chemotherapy prior to radical radiation therapy. A third technique is to enhance the radiosensitivity of the cancer by giving certain drugs during a course of radiation therapy. 

Besides the tumour itself, the radiation fields may also include the draining lymph nodes if they are clinically or radiologically involved with tumor, or if there is thought to be a risk of subclinical malignant spread. 

The degree of irreversible uterus damage has been shown to be dependent on the total radiation dose and it was shown that the pre-pubertal uterus is more vulnerable than the adult uterus to the effect of pelvic radiation therapy.

Radiation therapy is in itself painless. Many low-dose palliative treatments (for example, radiation therapy to bony metastases) cause minimal or no side effects, although short-term pain flare-up can be experienced in the days following treatment due to oedema compressing nerves in the treated area. Higher doses can cause varying side effects during treatment (acute side effects), in the months or years following treatment (long-term side effects), or after re-treatment (cumulative side effects). The nature, severity, and longevity of side effects depends on the organs that receive the radiation, the treatment itself (type of radiation, dose, fractionation, concurrent chemotherapy), and the patient.

Most side effects are predictable and expected. Side effects from radiation are usually limited to the area of the patient's body that is under treatment. Side effects are dose-dependent; for example higher doses of head and neck radiation can be associated with cardiovascular complications, thyroid dysfunction, and pituitary axis dysfunction. Modern radiation therapy aims to reduce side effects to a minimum and to help the patient understand and deal with side effects that are unavoidable.

The main side effects reported are fatigue and skin irritation, like a mild to moderate sun burn. The fatigue often sets in during the middle of a course of treatment and can last for weeks after treatment ends. The irritated skin will heal, but may not be as elastic as it was before.

Irritated skin

A great number of patients are submitted to adjuvant radiotherapy after surgery with or without chemotherapy. In the course of radiotherapy, skin toxicity remains an important clinical problem for many patients. The severity of the acute toxicity is related to several factors: dose per fraction, total delivered dose, location and volume of the treated area, radiating energy, other treatments received concomitantly or before. The literature shows individual variations depending on age, chronic diseases, skin types, genetic predisposition, skin damage from the previous and concomitant drug therapy (cytotoxic chemotherapy).

Currently, radiotherapy is considered as the most effective curative treatment after surgery for cancer. About one third of the population will develop the disease, and will require this therapeutic modality, and 60% of the patients will be submitted to radiotherapy for curative purposes, often combined with surgery and chemotherapy.

The effect of radiotherapy on control of cancer has been shown to be limited to the first five years after surgery, particularly for breast cancer. The difference between breast cancer recurrence in patients who receive radiotherapy vs. those who don't is seen mostly in the first 2–3 years and no difference is seen after 5 years.

The gonads (ovaries and testicles) are very sensitive to radiation. They may be unable to produce gametes following direct exposure to most normal treatment doses of radiation. Treatment planning for all body sites is designed to minimize, if not completely exclude dose to the gonads if they are not the primary area of treatment.

After abdomino-pelvic radiation therapy, the likelihood to have low-birth-weight infants, premature low-birth-weight infants and the perinatal infant mortality is increased as compared to patients without radiation therapy. However, these associations are dose dependent