Radiotherapy – Radiation Treatment

Radiotherapy (RT), also called ray treatment, beam treatment and radiation treatment, was first used to treat cancer approximately 1 century ago. Since then, major technological progress has improved its effectiveness and minimized side effects.

Radiotherapy is increasingly combined with surgery and systemic treatments to improve tumor control and quality of life while reducing side effects. The best outcomes are achieved by having each patient evaluated by a multidisciplinary cancer treatment team, including a radiation oncologist, medical oncologist, surgeon and other specialists.

Radiotherapy has many different applications and purposes:

• as the sole treatment,
• together with systemic agents,
• before or after surgery to minimize the possibility of microscopic tumor remaining,
• for support when disease is advanced

Treatment duration can range from a single session to daily treatment for 8 weeks. For each patient, the technique, dose, expected benefits and side effects vary according to diagnosis and the treatment area.

Protecting healthy organs outside the tumor has become an important oncology issue (organ-preserving treatments). In certain cancers, such as breast and laryngeal cancer, long-term outcomes are equivalent between radical operations removing the whole organ and removal of only the tumor with some surrounding normal tissue followed by adjuvant (protective) radiotherapy. As expected, organ-preserving procedures even offer fewer side effects.

How Does Radiotherapy Work?

This treatment uses radiation energy to kill cancer cells in a specific area targeted by the clinician.

Radiotherapy damages cancer cell DNA by ionizing atoms (breaks in the DNA double helix).

Both cancerous and normal cells in the treated area are exposed to radiation's ionizing effects. However, normal cells detect and repair radiation-induced DNA damage more quickly. Cancer cells are focused on multiplication, growing and multiplying faster, which puts them at a disadvantage in repairing DNA damage compared with normal cells. Nevertheless, normal tissues have maximum total radiation dose limits. This balance must be carefully managed. Dividing the total radiation dose into small daily doses (fractions) allows normal tissues to repair themselves.

Radiotherapy techniques fall under 3 main headings:

1. External radiotherapy
2. Brachytherapy (internal radiotherapy)
3. Intraoperative radiotherapy (during surgery)

External radiotherapy

This is the most frequently used radiotherapy method. A radiation source outside the patient (external beam) is used.

Charged particles such as electrons or protons are accelerated, or Cobalt-60 is used, to produce ionizing radiation. Linear accelerator: this device accelerates electrons to achieve higher energy and become X-rays (photons , as they are also known). It can produce photon or electron beams at various energies, with output managed through advanced computer controls.

Photons Versus Electrons: photons can reach deeper tissues and are preferred in cancers of internal organs. Electrons are often preferred for superficial tumors such as breast and skin cancers, also preventing damage to internal organs. Photons and electrons are frequently combined to achieve the best dose distribution in tumors and normal tissues.

Treatment planning:

The treatment plan includes;

• careful immobilization of the patient,
• identifying the radiation treatment area with imaging such as computed tomography (CT) or magnetic resonance imaging (MRI), and
• calculating dose and treatment frequency.

Different tumors have different sensitivities to radiotherapy. For example, lymphoma and seminoma, a type of testicular cancer, are highly sensitive (radiosensitive) and can be completely treated with radiotherapy; malignant melanoma skin cancer and soft tissue sarcomas are resistant (radioresistant) and require higher radiation doses to have an effect.

Conformal Therapy

This term describes delivering high doses to the tumor area while exposing normal tissues to as little radiation as possible. Using advanced imaging such as CT and MRI, radiation oncologists can calculate and adjust doses to tumors and neighboring normal tissues separately with 3-dimensional conformal RT (3D-CRT). This minimizes side effects. It also allows a previously irradiated area to be irradiated again later if necessary.

3D-CRT applications fall into two categories:

1. Intensity-modulated RT (IMRT)
2. Image-guided RT (IGRT)

Intensity-Modulated Radiotherapy (IMRT)

An advanced form of 3-dimensional conformal radiotherapy, IMRT allows radiation from a single source to be delivered to different parts of the target at different intensitiesas part of treatment delivery.

Image-Guided Radiotherapy (IGRT)

The exact area requiring high-intensity irradiation is debated in radiation oncology practice. Small organ movements during breathing are also considered.

During each treatment, real-time imaging allows more accurate target identification. These technologies are generally called image-guided radiotherapy (IGRT).

Proton Therapy

A special form of external radiotherapy, proton therapy allows more precise irradiation of the tumor with less damage to normal tissues because of the distinctive physical properties of heavy particles. Protons can penetrate tissues at different depths; on reaching the target tissue, they release their energy sharply, called the Bragg peak.

Although studies are investigating whether protons have advantages over photons in many cancers, superiority has not been shown outside disease groups such as certain childhood cancers and uveal melanoma. Results of proton therapy, extensively tested particularly in prostate cancer, have been equivalent to 3-dimensional conformal techniques.

Stereotactic Radiotherapy Techniques (SBRT and Radiosurgery SRS)

These deliver the calculated total radiation dose in a single or a few sessions (fractions).

Stereotactic radiosurgery (SRS) is used for brain tumors, while stereotactic body radiation therapy (SBRT) irradiates organs outside the brain, such as the lungs, spine or liver.

SBRT treatment of an early-stage lung tumor in the left lung

Stereotactic methods require high-resolution imaging. They are particularly preferred for well-defined small tumors, such as lung cancer metastasizing to a single vertebra.

Because a high radiation dose is delivered to a specific point, patient immobilization is especially important with this method.

Total Body Irradiation

This is part of treatment preparing patients with leukemia and lymphoma for hematopoietic cell transplantation.

Total body irradiation has 2 aims: weakening the immune system (immunosuppression) to prevent rejection of donor stem cells, and eliminating cancer cells.

Brachytherapy (internal radiotherapy)

In brachytherapy, a radiation source is placed beside or inside the treatment area. It is particularly preferred in prostate cancers and gynecological malignancies such as cervical cancer.

For example, in localized (early-stage) prostate cancer, brachytherapy is a treatment option. A low-dose-rate (LDR) system is applied to the patient in a single procedure. Radioactive sources are permanently placed in the prostate gland under ultrasound guidance. These sources slowly release radiation over months.

Intraoperative Radiotherapy (IORT)

This means delivering radiation during surgery. It has advantages regarding certain limitations of external radiotherapy, such as damage to normal tissues. It is administered in a single session during surgery, and the dose is limited by structures that cannot be visualized at that moment (nerves, fixed organs).

If the risk of local recurrence is high (if an intraoperative pathology sample, or frozen section, shows tumor at surgical margins, or the tumor cannot be completely removed), the decision to use IORT may be made during surgery.

It is mostly used for cancers of the groin and abdominal cavity. However, a single IORT dose often cannot provide adequate tumor control, and external radiotherapy must complement it.

Possible Side Effects of Radiotherapy

Side effects during or after radiotherapy largely depend on the anatomical area treated. They also relate to total dose, dose per fraction, tissue radiosensitivity and other cancer treatments such as chemotherapy and surgery.

As a general rule, tissues swell during radiotherapy, producing edema in target tissues. Most acute (sudden-onset) side effects are anticipated and limited to the irradiated region. Abdominal radiation causes effects such as nausea and vomiting. Head and neck radiotherapy causes mouth and throat sores, while thoracic radiotherapy can inflame the esophagus. These conditions lead respectively to dysphagia (difficulty swallowing), reduced oral food intake and dehydration (water loss). Pelvic radiotherapy causes urinary tract and bowel changes. Edema and tissue irritation diminish after treatment, and acute side effects largely disappear.

The long-term effect of radiation therapy is largely fibrosis in exposed tissues. These side effects can be balanced against treatment benefits. Late toxicities specific to radiotherapy relate to the treated tissue and radiation dose. For example;

The ovaries and testes are highly radiosensitive, and reproductive organs can be damaged after radiotherapy. Infertility is therefore a serious issue for pediatric and young adult cancer patients.

Cardiac toxicity (heart damage) occurs as a late complication in treatment of breast cancer, Hodgkin lymphoma and other cancers in which the heart area is exposed to radiation.

A strong association has been established between secondary cancers and earlier radiotherapy. A large study reported that among cancer patients receiving radiotherapy between 1973 and 2002, the risk of secondary cancer was 8 percent.

However, this analysis did not control for cancer development in a population not exposed to radiation. Many of the cancers may therefore be unrelated to radiation exposure. This issue is particularly important and critical in pediatric and young adult patients. Secondary cancers may take 10-15 years to become clinically diagnosable.

The side effects of radiotherapy, used in cancer treatment for over 100 years, are well defined, and one major advantage of new technological equipment is minimizing them. An experienced radiation oncology team can take precautions against these potential side effects through close communication with patients and treat emerging side effects effectively.

Further Reading: The Discovery of Radiotherapy in Cancer Treatment

Toward the end of 1895, Wilhelm Conrad Röntgen noticed a strange leakage while working with an electron tube. This radiant energy was powerful and invisible; it passed through black cardboard sheets and produced a white, phosphorescent glow on a barium plate in the room. Röntgen then placed his wife's hand between the radiation source and a photographic plate. The rays passed through her hand, leaving the outlines of finger bones and a metal wedding ring on the plate. The hand's internal anatomy appeared as though through a magical lens. He named this form of energy and light, powerful enough to pass through most living tissues, X-rays.

In 1896, less than 1 year after Röntgen discovered X-rays, Emil Grubbe, a 21-year-old medical student in Chicago, thought of using them to treat cancer. Brilliant, adventurous and extraordinarily creative, Grubbe had worked in a Chicago factory making vacuum X-ray tubes and built a simple version for his own experiments. Having witnessed skin and nails peeling from factory workers exposed to X-rays, and having cracks and swelling on his own hands for the same reason, he quickly applied this “cell death” principle to tumors.

On 29 March 1896, in a tube factory on Chicago's Halsted Street, Grubbe bombarded Rose Lee, an older woman with breast cancer, with rays from an adapted X-ray tube. Lee's cancer had recurred after mastectomy, and both tumor and breast had become a large, painful mass. Seeing Grubbe had been suggested as a last resort. Hoping to find something to cover the rest of the breast, he looked around, but finding no metal sheet, wrapped Lee's chest with metal foil found at the bottom of a Chinese tea box. The cancerous tissue was thus exposed to radiation for 18 consecutive days. Although painful, the treatment was successful in one sense. The breast tumor first ulcerated, then contracted and shrank. This represented the first documented local response in X-ray treatment history. However, a few months after the first treatment period, Lee became dizzy and nauseated. The cancer had spread to the spinal cord, brain and liver. She died soon afterward. Grubbe had made another important observation: X-rays could only treat cancer locally; they had almost no effect on tumors that had spread.

Encouraged by the response despite its temporary nature, Grubbe began using X-rays to treat many other patients with localized tumors. A new medical field, radiation oncology, was born. X-ray clinics quickly sprang up across Europe and America. By the early 1900s, less than a decade after Röntgen's discovery, doctors were already exhilarated by the possibility of treating cancer with radiation. The Curies' discovery of radium in 1902 allowed surgeons to irradiate tumors with energy bursts thousands of times stronger. This excitement prompted conferences and associations devoted to high-dose radiation treatment. Gold wires filled with radium were sewn directly onto tumors, increasing the local X-ray dose further. Vacuum tube technology was advancing in parallel. By the mid-1950s, various types of these tubes could deliver extraordinarily high X-ray energy doses to cancerous tissue.

Over time, radiation oncology technology developed and became more precise. After the X-rays used in early history, high-energy photons, electrons, protons and neutrons also came into use. Advances in computing and electronics also brought treatment planning and delivery to a nearly perfect level.