Basics of Radiation Oncology

Radiation oncology is a medical speciality that involves the use of high-energy radiation to treat cancer.

 Overview

Radiation oncology is one of the three main cancer treatment modalities, alongside surgery and chemotherapy. It uses ionizing radiation to destroy cancer cells by damaging their DNA, ultimately leading to cell death. Radiation therapy either used alone or in combination with surgery and/or chemotherapeutic modalities has become an important aspect in the treatment of head and neck cancer.  A basic understanding of the principles of radiotherapy will benefit the otolaryngologist in planning treatment strategies for these patients.  The following discussion outlines the basic principles of radiation oncology and is intended to provide a clear understanding of the biological basis for the use of ionizing radiation in treating head and neck cancer.

 Types of Radiation Therapy

External Beam Radiation Therapy (EBRT)The most common form, where radiation is delivered from outside the body using machines like linear accelerators.

Internal Radiation Therapy (Brachytherapy): Involves placing radioactive sources inside or near(close) the tumor.

Systemic Radiation Therapy: Involves swallowing or injecting radioactive substances that travel through the bloodstream to target cancer cells.

Radiation Physics

The basis of radiation therapy is the interaction of ionizing particles (x-rays, gamma rays or electrons) with tissues at the molecular level.  This interaction depends on the energy created by the production of secondary charged particles, usually electrons, which can break chemical bonds and inflict cellular injury.  Radiation therapy is delivered by an external beam, an interstitial implant, or a combination of the two.  External beam radiation therapy entails the generation of energy particles at some distance from the patient.  Interstitial implants, or brachytherapy, entail the placement of radioactive sources near or within the tumor.  Radiant energy is deposited in biological material in a discrete yet random fashion, and the biological effects occur as a result of the transfer of energy to atoms or molecules within the cell.

 Techniques in EBRT

Dual-energy linear accelerators allow for the generation of either low-energy megavoltage x-rays (4-6 MeV), high-energy megavoltage x-rays (15-20 MeV) or electrons.  Most patients are treated with X-rays or gamma rays (photons) because of the skin-sparing properties, penetration and beam uniformity.  Due to the typical location of head and neck cancers (7 to 8 cm deep) and regional lymph nodes (superficial), 4 to 6 MeV x-rays or cobalt 60 gamma rays are typically used.  Additional treatment (a boost) with 15 to 20 MeV x-rays can be used for the base of the tongue or nasopharynx.  Electron beams are useful for managing superficial lesions, because of their finite range and deep tissue sparing properties.

3D Conformal Radiation Therapy (3D-CRT): Uses imaging to shape the radiation beams to match the tumor.

Intensity-modulated radiation Therapy (IMRT): Allows the radiation dose to conform more precisely to the 3D shape of the tumor by modulating the intensity of the radiation beams.

Image-guided radiation Therapy (IGRT): Uses imaging during treatment to improve precision.

Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotherapy (SBRT): Deliver very high doses of radiation to small, well-defined tumors.

Brachytherapy

This is a technique in which radioactive sources are placed directly into the tumor and surrounding tissues (interstitial implants), within body cavities (intracavitary therapy), or onto epithelial surfaces (surface moulds).  The advantages of this therapy over an external beam are that a greater dose can be delivered to the tumor at a continuously low dose rate.  This allows for a theoretical advantage in the treatment of hypoxic or slowly proliferating tumors and potentially, shorter treatment times.  The tumor must be accessible and well-demarcated.  It should not be the only treatment modality for tumors with a high risk of regional lymph node metastasis.

Radiobiology

The energy of therapeutic radiation is high enough to eject an electron from a target molecule, thus, the term ionizing irradiation.  Ionizing energy is distributed randomly within the cell so that the X-rays hit a wide array of molecules.  A DNA double-strand break is generally believed to be responsible for cell death, which is determined by cells that are no longer able to undergo cell division.  The injury responsible for cell death can occur directly or indirectly, via free radicals (molecules with an unpaired electron, e.g., DNA à DNA·).  Free radicals are highly reactive and can either be reduced by cellular mechanisms (repaired DNA) or stabilized by oxygen (permanent DNA-OO· damage).  Inadequate repair of DNA lesions, either nucleotide base damage or single/double-strand breaks, can lead to cell death    ( lethal damage) or mutation.

Dose-Response Relations

The probability of controlling cancerous lesions with radiotherapy depends on the size of the tumor and the dose of radiation given.  The dose-response relation for small, well-vascularized neoplasms is steep, because they are relatively homogeneous, are well-oxygenated and have approximately the same number of cells.  Bulky tumors, however, are more heterogeneous with considerable variability in the number of cells and oxygenation.  Therefore, the dose-response curve is much shallower.  The dose-response relation for normal tissue injury is the limiting factor in the amount of irradiation that can be given.  As the size of the tumor increases, and the dose needed for local control likewise increases, the risk of injury to normal tissue becomes greater.

Fractionation Schedules

Conventional fractionation schedules are typically in increments of 1.8 to 2.0 Gy given five times per week for 6 to 8 weeks.  Altered fractionation schedules have been developed in an attempt to optimize treatment results under various clinical circumstances.  In essence, the objective of altered fractionation is to improve the therapeutic ratio through an alteration of time, dose, and/or fractionation based on the differential response of tumors and normal tissues to these altered schedules.  Accelerated fractionation involves two or more dose fractions of the conventional size per day in an attempt to shorten overall treatment time.  In theory, this may minimize tumor repopulation during treatment and, therefore, increase the probability of tumor control for the same total dose.  Hypofractionation involves the administration of two or more smaller dose fractions per day for a conventional or slightly longer treatment time.  Theoretically, with hyperfractionation it is possible to increase the total dose, thereby increasing the probability of tumor control without increasing late complications.

Treatment

The treatment strategy for an individual patient with head and neck cancer is based on the size and location of the primary lesion, the presence or absence and extent of regional or distant metastatic disease, and the general condition of the patient.  Early-stage head and neck cancer usually is effectively managed with either surgery or radiation therapy alone.  The choice between these two modalities of treatment is often determined by the functional deficit that would result from the proposed treatment.  Larger cancers are generally managed with a combination of surgery and radiation.  Radiation therapy alone is sometimes attempted, and in this case, surgery is reserved for the salvage of tumor recurrence.  Surgical salvage of radiation failures is generally more effective than radiation salvage of surgical failures.

A course of radiotherapy is usually delivered using a shrinking field technique.  This is based on the concept that tumor cell killing by radiation is an exponential function of dose and that the dose required for a particular tumor control probability is proportional to the logarithm of the number of viable cells in the tumor.  For example, the initial tumor dose of 45 to 50 Gy usually is delivered in 4.5 to 5 weeks through large portals that cover the clinically involved region and areas of possible regional lymph node metastasis.  The field is then reduced to encompass only gross tumor with a small margin (boost fields) and an additional 15 to 25 Gy is delivered over the next 1.5 to 2.5 weeks to bring the total dose to 60 to 75 Gy in 6 to 7.5 weeks.  With massive tumors, a second field reduction at 60 to 65 Gy is performed.  An additional 10 to 15 Gy is given through small fields for a total dose of 70 to 75 Gy in 7 to 8 weeks.  The spinal cord should not receive more than 45 Gy to avoid the risk or radiation myelitis.

 When used appropriately, combining surgery and radiotherapy complement one another very well.  Surgery is ideal for the removal of gross tumor, and most radiation failures are the result of an inability to control bulky masses.  Radiotherapy is very effective in controlling microscopic disease, and often surgical failures occur as a result of leaving subclinical tumor extensions, or microscopic disease, behind.  Intuitively, combining the two modalities effectively counteract the limitations of the other.  Radiation can be administered either pre- or post-operatively.

Preoperative radiotherapy may decrease tumor bulk to facilitate dissection.  Also, microscopic disease may be more effectively controlled prior to disturbing its blood supply.  Tumor cell seed may be diminished, and it may be possible to use smaller treatment portals preoperatively.  A typical preoperative dose is 45 Gy in 4.5 weeks.  This dose is sufficient to eradicate subclinical disease among 85% to 90% of patients.

Postoperative radiotherapy, on the other hand, enables more accurate surgical staging.  The dissection is much less difficult in tissues that have not been previously irradiated, and surgical complications are often reduced because healing is generally better.  Finally, a larger dose of radiation may be given postoperatively than preoperatively.  The typical postoperative dose is 60 to 65 Gy over 6 to 7 weeks.  Postoperative radiotherapy markedly reduces the risk of recurrence in the surgical field, however, the results are poorer is delayed more than 6 weeks.

 Treatment Planning

Simulation: A planning session where the patient's anatomy is mapped using imaging techniques like CT, MRI, or PET scans.

Dosimetry: The calculation and assessment of the radiation dose delivered to the tumor and surrounding tissues.

Treatment Planning Systems (TPS): Software used to design the radiation treatment plan, optimizing the dose distribution.

 Side Effects

Acute Side Effects: Occur during or shortly after treatment, such as skin irritation, fatigue, and localized inflammation.

Chronic Side Effects: Develop months or years after treatment, potentially including fibrosis, memory loss, or secondary cancers.

 Radiation Safety

Radiation Protection: Ensuring that the radiation dose to normal tissues and medical staff is minimized using shielding, proper equipment, and safety protocols.

Quality Assurance: Regular checks and maintenance of radiation equipment to ensure accurate delivery of treatment.

 Multidisciplinary Approach

Radiation oncologists work closely with medical oncologists, surgical oncologists, radiologists, pathologists, and other healthcare professionals to develop and execute comprehensive cancer treatment plans.

 Advances in Radiation Oncology

Proton Therapy: Uses protons instead of X-rays for more precise tumor targeting.

Adaptive Radiation Therapy: Adjusts the treatment plan based on changes in the patient’s anatomy and size of tumor over the course of treatment.

Artificial Intelligence and Machine Learning: Enhancing treatment planning, prediction of side effects, and overall patient management.

 Radiation oncology continues to evolve with advancements in technology, imaging, and treatment methodologies, aiming to increase the efficacy of cancer treatment while minimizing side effects

 Conclusions

Radiation therapy plays a key role in the treatment of head and neck cancer as it is often used as in a primary or combined fashion.  The basic concepts of radiation physics and radiobiology help to explain the rationale for radiation treatment schedules and the reasons for associated complications.  An understanding of these fundamentals is essential to the otolaryngologist in order to adequately counsel head and neck cancer patients regarding their treatment options and the possibility of serious side effects after radiation therapy.

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