MODULE I : PRACTICES OF RADIATION ONCOLOGY

 

PRACTICES OF RADIATION ONCOLOGY

LEARNING OBJECTIVES:

At the end of  this module the staff will be able to:

👉describe the principles of radiation oncology

👉list down the sources of ionizing radiations

👉describe the factors that influence radiation sensitivity

INTRODUCTION:

Radiation has been an effective tool for treating cancer for more than 100 years.More than 60 percent of patients diagnosed with cancer will receive radiation therapy as part of their treatment.
Radiation oncologists are cancer specialists who manage the care of cancer patients with radiation for either cure or palliation.
Main  goal of radiation therapy is to determine the optimal dose of radiation to the pathological focus with minimal damage to normal tissues located in the area of exposure.

BIOLOGIC BASIS OF RADIATION THERAPY:

Radiation therapy works by damaging the DNA of cells and destroys their ability to reproduce,
Both normal and cancer cells can be affected by radiation, but cancer cells have generally impaired ability to repair this damage, leading to cell death.
All tissues have a tolerance level, or maximum dose, beyond which irreparable damage may occur. 

FRACTIONATION: A BASIC RADIO-BIOLOGIC PRINCIPLE:

Fractionation, or dividing the total dose into small daily fractions over several weeks, takes advantage of differential repair abilities of normal and malignant tissues
Fractionation spares normal tissue through repair and repopulation while increasing damage to tumor cells through redistribution and reoxygenation.

THE FOUR R’S OF RADIOBIOLOGY:

Four major factors are believed to affect tissue’s response to fractionated radiation: 

• Repair of sublethal damage to cells between fractions caused by radiation
• Repopulation or regrowth of cells between fractions
• Redistribution of cells into radiosensitive phases of cell cycle
• Reoxygenation of hypoxic cells to make them more sensitive to radiation

SOURCES OF IONIZING RADIATION:

Photons: 

 💥Gamma Rays

• Emitted from a nucleus of a radioactive atom
• Cobalt treatment machine

 💥Radioisotopes used in brachytherapy

• X-rays
• Generated by a linear accelerator when accelerated electrons hit a target

Particle Beams

• Protons
• Neutrons
• Electrons

HOW RADIATION WORKS:

IONIZING RADIATION:

Ionizing radiation is energy sufficiently strong to remove an orbital electron from an atom. This radiation can have an electromagnetic form, such as a high-energy photon, or a particulate form, such as an electron, proton, neutron, or alpha particle.

High-energy photons:

🌠 The most common form of radiation used in practice today is the high-energy photon

🌠Photons that are released from the nucleus of a radioactive atom are known as gamma rays.

🌠 When photons are created electronically, such as in a clinical linear accelerator, they are known as x-rays. Thus,  the only difference between the two terms is the origin of the photon.

Inverse square law :

The intensity of an x-ray beam is governed by the inverse square law. This law states that the radiation intensity from a point source is inversely proportional to the square of the distance away from the radiation source. In other words, the dose at 2 cm will be one-fourth of the dose at 1 cm.

Electron volt :

Photon absorption in human tissue is determined by the energy of the radiation, as well as the atomic structure of the tissue in question. The basic unit of energy used in radiation oncology is the electron volt. 

PHOTON-TISSUE INTERACTIONS

Photoelectric effect: 

An incoming photon undergoes a collision with a tightly bound electron. The photon transfers practically all of its energy to the electron and ceases to exist. The electron departs with most of the energy from the photon and begins to ionize surrounding molecules. This interaction depends on the energy of the incoming photon, as well as the atomic number of the tissue; the lower the energy and the higher the atomic number, the more likely that a photoelectric effect will take place.

Compton effect : 

The Compton effect is the most important photon-tissue interaction for the treatment of cancer. In this case, a photon collides with a “free electron,” ie, one that is not tightly bound to the atom. Unlike the photoelectric effect, in the Compton interaction both the photon and electron are scattered. The photon can then continue to undergo additional interactions, albeit with a lower energy. The electron begins to ionize with the energy given to it by the photon.

Pair production :

A photon interacts with the nucleus of an atom, not an orbital electron. The photon gives up its energy to the nucleus and creates a pair of positively and negatively charged electrons. The positive electron (positron) ionizes until it combines with a free electron. This generates two photons that scatter in opposite directions.

CLINICAL  USES OF RADIATION THERAPY:

Therapeutic radiation serves two major functions

🔎 To cure cancer:

☝Destroy tumors that have not spread 

☝Kill  residual microscopic disease left after surgery or chemotherapy

🔎To reduce or palliate symptoms:

☝Shrink tumors affecting quality of life, e.g., a lung tumor causing shortness of breath  

☝Alleviate pain or neurologic symptoms by reducing the size of a tumor

MEASURING RADIATION ABSORPTION:

The dose of radiation absorbed correlates directly with the energy of the beam. An accurate measurement of absorbed dose is critical in radiation treatment. 

Gray : The basic unit of radiation absorbed dose is the amount of energy (joules) absorbed per unit mass (kg) known as the gray (Gy), has replaced the unit of rad used in the past (100 rads = 1 Gy; 1 rad = 1 cGy).

Exposure:  To measure dose in a patient, one must first measure the ionization produced in air by a beam of radiation. This quantity is known as exposure. 

Percentage depth dose:  The dose absorbed by tissues due to these interactions can be measured and plotted to form a percentage depth dose curve. As energy increases, the penetrative ability of the beam increases and the skin dose decreases.

RADIOSENSITIVITY:

Radiosensitivity is the innate sensitivity of cells, tissues or tumours to radiation. Both normal and cancer cells,are affected by radiation.Cells vary in their expressed sensitivity to radiation. Rapid dividing cells (e.g:mucosa)  are most sensitive and are referred to as radiosensitive.Nondividing or slowly dividing cells (e.g: muscle cells, neurons) generally are less radiosensitive , or are radioresistant . Exceptions include small lymphocytes and salivary gland cells , which are non dividing but very radiosensitive.These may experience an interphase death(death prior to mitosis). 

FACTORS THAT INFLUENCE RADIATION SENSITIVITY:

Cell Cycle Phase: Cells in the late G2  and mitosis phase are more sensitive, late synthesis cells are more resistant.

Oxygen: The presence of oxygen enhances radiation damage , when oxygen is not present , chemical damage in DNA may be repaired . Reoxygenation occurs as the tumour shrinks during RT. Hypoxia may contribute to radio resistance.

Differentiation: Poorly differentiated tumors generally are more sensitive . Far more radiation is required to destroy the function of a differentiated cell than to destroy.

Proliferative Capacity: Rapidly dividing cells generally are more sensitive to the effects of radiation. Non dividing or slowly dividing cells usually are less sensitive  or radio resistant 

Repair of radiation damage: The greater the repair capability of the normal tissue , the greater the effectiveness of the treatment. DNA damage can be repaired to its original state or repaired with errors(mutation). Most repairs are believed to occur within six hours after a treatment. 

Tumour size: Tumour size is a major factor in dose –response outcomes or RT. Large tumours are more difficult to control than small tumours of the same type. Control of large tumours may require a radiation dose that would result in unacceptable damage to normal tissue. 

Fractionation: This is division of total prescribed dose into smaller daily doses or fractions. Fraction size is dominant factor in determining late effects on tissue , with large fractions causing an increase in late effects. Fractionation varies depending on goal of therapy.

💎Hyperfractionation: Multiple daily fractions are delivered generally separated at least 6 hours to allow for repair of damage to the normal tissues from the first dose of administration.

💎Hypofractionation: The total dose of radiation is divided into large doses and treatment may be given less than once a day.

Quality of Radiation: Energy of various types of radiation is distributed differently in tissues . Heavy Particles (e.g. neutrons and alpha particles) ionize quickly and densely.. Light particles (e.g. electrons) ionize sparsely in tissues.

EFFECTS OF RADIATION ON NORMAL CELLS VERSUS CANCER CELLS:

🌋Although both normal cells and cancer cells are affected by radiation and respond similarly to RT. only cancer cells are believed to undergo reoxygenation.

🌋Malignant tumors differ greatly in radiosensitivity because of innate sensitivity , mitotic activity, hypoxic component, and blood supply.

🌋 Dividing a dose into multiple daily fractions spares normal tissues because of damage repair between fractions and repopulation of cells if overall time is sufficient. Dose fractionation increases damage to cancer cells because of reoxygenation of the tumor and reassortment of cancer cells into more sensitive phases of the cell cycle.

🌋 Side effects are the result of radiation damage to normal cells

BIOMARKERS FOR RT:

A biomarker, or biologic marker, is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes or radiobiologic responses to RT treatments. Research is being conduct on biomarkers for tumor /tissue response and treatment assessment in predictive radiation oncology.

THE RADIATION ONCOLOGY TEAM:

Radiation Oncologist:

The doctor who prescribes and oversees the radiation therapy treatments

Medical Physicist:

Ensures that treatment plans are properly tailored for each patient, and is responsible for the calibration and accuracy of treatment equipment

Dosimetrist:

Works with the radiation oncologist and medical physicist to calculate the proper dose of radiation given to the tumor

Radiation Therapist:

Administers the daily radiation under the doctor’s prescription and supervision

Radiation Oncology Nurse:

Interacts with the patient and family at the time of consultation, throughout the treatment process and during follow-up care

THE TREATMENT PROCESS:

💉Referral

💉Consultation

💉Simulation

💉Treatment Planning

💉Quality Assurance

Referral:

👉Tissue diagnosis has been established

👉Referring physician reviews potential treatment options with patient

👉Treatment options may include  radiation therapy, surgery, chemotherapy or a combination.

Consultation:

📎Radiation oncologist determines whether radiation therapy is appropriate

📎  A treatment plan is developed

📎Care is coordinated with other members of patient’s oncology team

Simulation:

💡Patient is set up in treatment position on a dedicated CT  scanner
💡Immobilization devices may be created to assure patient comfort and daily reproducibility
💡Reference marks may be placed on patient
💡CT simulation images are often fused with PET or MRI scans for treatment planning

DOSE PRESCRIPTION, TREATMENT PLANNING AND SIMULATION 

DOSE PRESCRIPTION:

Specification of dose and volume:

a)The international commission on radiation units and measurements definition of the treatment volume is separated into three distinct boundaries:

1. Visible tumor
2. A region to  account for uncertainties in microscopic tumor spread 
3. A region  to account for positional uncertainties.

These boundaries create three volumes 

⛔Gross Target Volume(GTV): This is the gross extent of the malignant growth as determined by palpation or an imaging study.

⛔Clinical Target Volume(CTV): This is the tissue volume that contains the GTV and/or subclinical microscopic malignant disease.

⛔Planning  Target Volume(CTV):This is the volume is defined by specifying by specifying the margins that must be added around the CTV to compensate for the effects of organ, tumor and patient movements and inaccuracies  in beam and patient setup.

ICRU also defined two other dose volumes.

Treated Volume: This is the volume enclosed by an isodose surface that is selected and specified by the radiation oncologist as being appropriate to achieve the purpose of treatment.

Irradiated Volume: This is the volume that receives a dose significant in relation to normal tissue tolerance. 

TREATMENT PLANNING:

RT is a complex procedure that requires comprehensive treatment planning and quality assurance. Treatment planning entails interactions among the radiation physicists, dosimetrists, radiation oncologist, radiation therapist & nurses.  

RT also requires  the use of large number of software programs and hardware devices for geometric and dosimetric planning and QA.

The following are the steps in the treatment planning process.  

• Patient positioning and immobilization to ensure a consistent position during the course of imaging and treatment.
• Patient data acquisition (computed tomography, magnetic resonance imaging, positron-emission tomography;manual contouring).
• Data transfer to treatment planning system
• Definition of treatment volumes and OARs
• Treatment design (modality, beam arrangements, modifiers)
• Computation of dose distributions 
• Plan evaluation (review of isodose distributions, DVHs, or other physical or biologic dosimetric parameters)
• Computation of monitor units or minutes based on the prescribed dose.
• Production of blocks and beam modifiers
• Plan implementation (treatment simulation, data transfer to record and verify system)
• Patient specific treatment planning QA (review the plan, chart, monitor unit calculation, and port film and perform additional calculations or measurements to verify the dose.

SIMULATION:

This is the process of aiming and defining the radiations beams to meet the goals of the prescribed therapy.

Patient is set up in treatment position on a dedicated CT scanner.Immobilization devices may be created to assure patient comfort and daily reproducibility.Reference marks or “tattoos” may be placed on patient.CT simulation images are often fused with PET or MRI scans for treatment planning.`

Unforeseeable problems with a patient set up or treatment technique also can be solved during simulation. 

🅰 A treatment simulator is an apparatus that uses a diagnostic x-ray tube but duplicates a radiation treatment unit in terms of its geometrical, mechanical and optical properties.

🅰  By radiographic visualization of internal organs, correct positioning of fields and shielding blocks can be obtained in relation to external landmarks.

🅰 A virtual simulator is a piece of software that performs treatment simulation based on a digital representation of the patient derived from serial CT or other tomographic images.

THREE DIMENSIONAL CONFORMAL RT (3DCRT):

The goal of 3DCRT is to conform the spatial distribution of the prescribed radiation dose to the precise three dimensional configuration of the treatment volume while at the same time minimizing the dose to the surrounding normal tissues.

A three dimensional treatment planning system is needed to plan a radiation treatment based on the three dimensional treatment volume. A 3DTPS generally is characterized by acquisition of three dimensional patient data, delineation of treatment portals based on a beam's eye view projection of the PTV, calculation of dose in three dimensional patient geometry , and display of dosimetric information in volumes.

3DCRT is commonly delivered with megavoltage photon and electron beams using multileaf collimators or custom designed blocks to shape uniform open fields or using wedges or custom designed compensators to account for the effect of surface irregularities and internal heterogeneities.

INTENSITY MODULATED RT: 

IMRT is an advanced form of 3DCRT in which varying intensities of small subdivisions of beams are used to custom design optimal radiation dose distributions. Because of the conformal dose distributions and steep dose gradients that can be achieved with IMRT, requirements for patient immobilization , target and structure delineation, treatment planning , beam delivery, and dose verification are more stringent.

🔑Special treatment planning software is needed to optimize the weights of individual beamlets via inverse planning (Inverse planning is a technique using a computer program to automatically achieve a treatment plan which has an optimal merit) or forward planning ( planner places beams into a radiotherapy treatment planning system that can deliver sufficient radiation to a tumour while both sparing critical organs and minimising the dose to healthy tissue) to achieve superior target coverage and normal tissue sparing based on the specified dose requirements for the treatment volumes and dose constraints on the OARs( Organs at Risk).

🔑IMRT is time and resource intensive . Adequate time to perform reviews and quality checks is essential . 

🔑IMRT fields are commonly delivered using a computer controlled multileaf collimator, however beam intensity modulation also can be achieved using complex physical compensators.

   

IMAGE GUIDED RADIATION THERAPY:

IGRT is and advanced radiation radiation treatment technique that uses imaging technology during treatment technique that uses imaging technology during treatment to ensure tumor location and beam delivery accuracy . The goal of IGRt is to decrease radiation dose to normal tissue or improve local control and quality of life by dose escalation or hypofractionation. IGRT systems allow for frequent two or three dimensional imaging correlate the actual tumor position with the radiation treatment plan to ensure accurate target dose delivery.

PURPOSE OF RADIATION THERAPY:

Radiation therapy is used to treat local or regional disease and rarely, systemic disease . The aim is to destroy malignant cells in the treated volume of tissue while minimizing damage to normal tissues.RT can be selected for various purposes.

Definitive treatment: RT is prescribed as the primary treatment modality, with or without chemotherapy, for the treatment of cancer. Examples can include cancers of the head and neck, lung, prostate, or bladder or Hodgkin lymphoma.  

Neoadjuvant Treatment: RT is prescribed prior to definitive treatment, usually surgery , to improve the chance of successful resection. Examples include esophageal or colon cancers. 

Adjuvant treatment: RT is given after definitive treatment (either surgery or chemotherapy to improve local control, examples may include breast , lung or high risk rectal cancers.

Prophylaxis therapy:  RT is delivered to asymptomatic, high risk areas to prevent growth of cancer. Examples are prophylactic cranial irradiation in lung cancer or  central nervous system (CNS) cancers to prevent growth of cancer.Examples are prophylactic cranial irradiation in lung cancer or central nervous system cancers to prevent relapse of certain forms of leukemia.

Control:RT is given to limit the growth of cancer cells to extend the symptom free interval for the patient. Examples may include pancreatic or lung cancers.

Palliation: RT is given to manage symptoms of bleeding, pain,airway obstruction or neurologic compromise to alleviate life threatening problems in incurable illness or to improve the patient quality of life. Examples may include relieving spinal cord compression , opening airways in patient with pneumonia, or relieving pain from bone metastases.

TISSUE TOLERANCE DOSE

The radiation dose to which a normal tissue can be irradiated and continue to function.

➗Organs vary in their ability to tolerate radiation injury. Normal tissue tolerance to radiation depends on the ability of the dividing cells to produce enough mature cells to maintain function of the organ. The tolerance dose is the dose of radiation that results in an acceptable probability of a treatment complication.

➗The dose prescribed to eradicate a cancer ultimately is dependent on the normal tissue tolerance of the dose. 

FACTORS RELATED TO RADIATION INDUCED INJURY OF NORMAL TISSUE

📌Patient-related factors

🎎Age: Growth related factors like growth retardation, endocrine changes in children.

🎎Hemoglobin level: Low hemoglobin has been found to decrease local control probability in cancers such as squamous cell carcinoma of the head and neck and transitional carcinoma of the bladder 

🎎Smoking: Can enhance some early and late side effects 

🎎Tumor invasion: May interfere with normal tissue reactions

🎎 Infections: May interfere with normal tissue injury , especially when the immune system is compromised. 

 📌Intrinsic radiosensitivity

🎎Genetic syndromes: Some are associated with increased sensitivity to RT

🎎Autoimmune diseases for e.g:  Systemic lupus erythematous.

CONSIDERATIONS FOR RADIATION THERAPY:

🔖 Diagnosis and staging: tumor histology and extent of disease.

🔖General condition of the patient and comorbid conditions

🔖Tumor site: Whether normal tissues are included in treatment fields

🔖Combination therapy(Chemotherapy, immunotherapy, biotherapy) the goal is to improve the therapeutic ration relative to the use of a single modality of treatment.

🔖 Available treatment facilities

 

RADIORESPONSIVENSS OF NORMAL TISSUE:

⚡ Expression of normal tissue injury varies greatly from patient to patient

⚡ Response of a tissue or organ primarily depends on the radio-sensitivity of the cells and the kinetics of the population in which the cells are functioning

⚡Treatment characteristics include total dose , dose per fraction or dose rate and overall treatment time

⚡With combined -modality therapy (sequential or concomitant chemotherapy)interactions may substantially influence side-effects of RT.

SIDE EFFECTS

Early side-effects:

🌊Occur during or immediately after RT

🌊Depend on total dose,dose per fraction and overall treatment time.

Late side-effects:

🌊Occurs months to years after RT usually are the result of damage to the microcirculation 

🌊Depend highly on dose per fraction. High dose per fraction results in more severe late effects 

🌊The time from RT to specific late effects is a latent period.

🌊Late injury expression is time dependent. The severity and percentage of patients expressing the injury increase over time  

REFERENCES

1. Ryan. R; Marilyn.L; Tracy.K; (2015) Manual for Radiation Oncology Nursing Practice and Education , 4^th edition , 

ONS publications 

2. An Overview of Radiation Therapy for Health Care Professionals;American Society for Radiation Oncology;

https://www.astro.org/ASTRO/media/ASTRO/Patient%20Care%20and%20Research/PDFs/RTforHealthCareProfessionals.ppt