What's the Buzz About Radiation?

Oncology Nursing Society 42nd Annual CongressMay 4–7, 2017 • Denver, CO 1Clinical Practice

Annette Quinn, MSNProgram Manager, Stereotactic Radiosurgery Uni-versity of Pittsburgh Cancer CentersUPMC [email protected]

Key Session Takeaways1. Radiation therapy delivery continues to become more

precise, resulting in less damage to normal surround-ing tissues and thus decreasing the number of frac-tions delivered.

2. Radiation planning is a very complex, tedious process that requires anywhere from one day to several weeks to be completed. It is not simply giving an x-ray treat-ment.

3. With more conformal techniques of delivering radi-ation therapy, we continue to improve quality of life with a decrease in toxicity and number of fractions needing to be delivered.

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What’s the Buzz About Radiation?

What’s the Buzz About Radiation Therapy

Annette Quinn, RN, MSN

Program Manager, Radiation Oncology

University of Pittsburgh Cancer Center

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I have no disclosures

Oncology Nursing Society 42nd Annual CongressMay 4–7, 2017 • Denver, CO2 Clinical Practice

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Overview

What is the physical and biological basis for radiation What are the clinical applications of radiation in the

management of cancer What is the process for treatment Simulation Treatment planning Delivery of radiation

What types of radiation are available Summary

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

What is Radiation Therapy?

The use of ionizing radiation in the treatment of disease, especially cancer.


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Radiation: A Brief History

Marie Curie (1867-1934)

1895 – Röntgen discovers x-rays (Nobel Prize 1901)1896 – Becquerel discovers natural radioactive decay

Marie and Pierre Curie further characterize radioactive compounds. (All three win Nobel Prize in 1903)

1896 – First patients with cancer treated with x-rays by Emil Grubbe in Chicago

1901 – Thomas Edison is displaying X-ray machine at the World’s Fair when President McKinley is assassinated.

1952 – first “linear accelerator” used for treatment (USA in 1957)

1968 – Radiosurgery1970 – CT1975 – PET1980 – Multi-leaf collimators, Proton therapy1988 – Intensity modulated radiation treatment (IMRT)2000’s – Image-guided RT (IGRT)

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 (xrays, gamma rays) or a particulate form such as an electron, proton or neutron.

Ionizing Radiation

Ionizing radiation is so named because its reaction with neutral atoms or molecules causes those atoms or groups of atoms to become ions, or electrically charged entities.

Ionizing radiation includes both electromagnetic waves and particle radiation. Electromagnetic waves are the broad spectrum of waves that includes radio waves, microwaves, visible light, X-rays, and gamma rays.


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Ionizing Radiation (cont.) Many types of Radiation:

Light that comes from the sun Heat that is constantly coming off our bodies.

Cancer Treatment deals mostly with X-rays and Gamma Rays X-rays and gamma rays can come from natural sources:

radon gas radioactive elements in the earth cosmic rays that hit the earth from outer space.

Can also be man-made. X-rays and gamma rays are created in power plants for nuclear

energy, and are also used in smaller amounts for medical imaging tests, cancer treatment, food irradiation, and airport security scanners.

Ionizing Radiation (cont.)

X-rays and gamma rays are both types of high energy (high frequency) electromagnetic radiation. They are packets of energy that have no charge or mass (weight). These packets of energy are known as photons.

They are forms of ionizing radiation, which means they have enough energy to remove an electron from (ionize) an atom or molecule. Ionized molecules are unstable and quickly undergo chemical changes.

Ionizing Radiation (cont.)

If ionizing radiation passes through a cell in the body, it can lead to mutations in the cell’s DNA Sometimes this causes the cell to die, but

sometimes it can lead to cancer later on. The amount of damage caused in the cell is related to the dose of radiation it receives.


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Major Differences Between Gamma Rays and X-Rays

Gamma rays are produced during nuclear decay by nuclei of atoms, whereas X-rays are produced by electrons. X-rays are produced by accelerating some

electrons and then making them collide with a metal target.

Differences (cont.)

We can control the maximum energy of the resulting x-ray spectrum, and we can control, like an on-off switch, when the x-rays are produced.

Since gamma rays come from the nuclei of an radioactive atoms, we can't turn the gamma radiation on or off. We can only shield the radiation. In addition, beyond selecting which radioactive materials we use, we can't control the energies of the gamma radiations.

What Is the Biologic Basis for 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


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Directly/Indirectly Ionizing

Directly ionizing radiation: This process occurs when charged particles such as electrons (e-) with sufficient kinetic energy interact with atoms and molecules to liberate electrons and create free radicals.

Protons Electrons

Directly/Indirectly Ionizing (cont.)

Indirectly ionizing radiation: When non-charged particles pass through tissues, and

interact with atoms and molecules. Interactions result in the release of charged particles (such

as electrons) that then go on to interact with atoms and molecules.

The term "indirect" refers to the fact that the uncharged particles themselves do not create the free radicals that ultimately cause biological damage.


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Thus…

Photons are indirectly ionizing. To damage DNA they must first create a free radical to ionize and cause damage. Electrons are directly ionizing can also interact

with tissue through “Bremsstrahlung” (braking radiation) and create photons that will then further interact with tissue.

Radiation Units

Absorbed Dose Conventional Units = Rads Standard International Units = Gray 1 Gray (Gy) = 100 Rads 1 cGy = 1 Rad

Incident x-ray photon

Fast Electron

Free Radical

Cellular DNA Damage

Biologic Effects of Radiation


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Radiation Biology

Single-strand breaks: Easily repaired

Normal cells complete repair in 6 hours

This time interval is relevant to fractionation

If another fraction is given and another single-strand break occurs in the right place before repair of the first is complete, a double-strand break can occur

Fractionation: A Basic RadiobiologicPrinciple

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 repairand repopulation while increasing damage to tumor cells through redistribution and reoxygenation

Single-Strand DNA Break

Repaired in ~6 hours


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2 Single-Strand DNA Breaks Close in Time Lead to a Double-Strand

Break

~2 hours

The Four R’s of Radiobiology

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

1. Repair of sublethal damage to cells between fractions caused by radiation

2. Repopulation or regrowth of cells between fractions3. Redistribution of cells into radiosensitive phases of cell

cycle4. Reoxygenation of hypoxic cells to make them more

sensitive to radiation

Repair Repair is the one of the primary reasons to fractionate

radiotherapy. By splitting radiation dose into small parts, cells are allowed

to repair sublethal damage. Amount of damage that is repaired depends on the ability

of the cell to recognize the damage and activatea) repair pathways b) cell cycle arrest

Malignant cells have often suppressed these pathways, often through mutation or inhibition of TP53, preventing them from undergoing efficient repair. Normal tissue cells with intact repair pathways are able to repair the sublethaldamage by the time the next fraction is delivered.


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Repair

Repair half life is an important consideration when fractionating radiotherapy. Some tissues, notably the spinal cord, appear

to have a slow repair mechanism with a half life of about 4 hours. It is important to separate dose by at least 6

hours and preferably 8 hours if two fractions are given on the same day.

Repopulation Repopulation is the increase in cell division that is seen

in normal and malignant cells at some point after radiation is delivered

Some tumors exhibit accelerated repopulation, a marked increase in their growth fraction and doubling time, at 4 - 5 weeks.

Seen most notably in squamous cell carcinoma of the head and neck as well as the cervix. Accelerated repopulation is a dangerous phenomenon that must be countered if treatment time extends over five weeks. Methods to do this include accelerated treatment with hyperfractionation to minimize late effects.

Redistribution When radiotherapy is given to a population of cells, they

may be in different parts of the cell cycle. Cells in S-phase are typically radioresistant, whereas those

in late G2 and M phase are relatively sensitive. A small dose of radiation delivered over a short time period

(external beam or high dose brachytherapy) will kill a lot of the sensitive cells and less of the resistant cells.

Over time, the surviving cells will continue to cycle. If a second dose of radiation is delivered some time later, some of these cells will have left the resistant phase and be in a more sensitive phase, allowing them to be killed more easily.


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Cell-Cycle Effect

Radiosensitivity varies with positions in the cell cycle

Mitotic cells are most susceptible (G2 & M phase)

Cells in S phase are least susceptible

Reoxygenation

Chronic hypoxia is due to the poor vasculature of tumors and the distance oxygen must travel to reach cells that are far from the capillaries.

These chronically hypoxic cells are also resistant to radiation.

Fractionated radiotherapy kills cells that lie close to the capillary more effectively.

As these cells are removed, the chronically hypoxic cells are able to move closer to their nutrient source, and therefore become relatively oxic.

Oxic cells can be killed.

Fractionation Regaud and The French Ram

A single dose of radiation that is sufficient to sterilize a ram also causes significant skin toxicity

If the same dose is delivered in several fractions, the ram is sterilized, but there is no skin toxicity

1920’s – 1930’s Regaud – extended treatment

time for uterine cancer improved outcomes

Coutard – fractionated treatment for head and neck cancer reduced toxicity with better outcomes


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Treatment planning

Dosimetry Originally done using hand calculations, graph

paper Computer planning revolutionized our ability to

deliver radiation accurately and precisely Modern treatment planning systems use CT data

to accurately calculate dose to entire target volume (3D-CRT) and computers to determine optimum dose delivery from multiple beams (IMRT)

Volumes defined prior to treatment planning :

Gross Tumor Volume (GTV) Clinical Target Volume (CTV)

Volumes defined during the treatment planning :

Planning Target Volume (PTV) Organs at Risk Treated Volume Irradiated Volume

ICRU 50

GROSS TUMOR VOLUME ( GTV )

Gross palpable or visible/demonstrable extent and location of the malignant growth.

It consists of:1. Primary tumor2. Metastatic lymphadenopathy3. Other metastasis

Corresponds to those parts of the malignant growth where the tumor density is largest.

If the tumor has been removed prior to radiotherapy then no GTV can be defined.


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GTV can be determined by using either clinical examination (inspection, palpation) and by various imaging techniques (X-rays, CT, MRI etc.)

Method used for determination of GTV should meet the requirements for staging the tumor according to the clinical TNM (UICC and AJCCS).

GROSS TUMOR VOLUME (cont.)

Reasons for identification of GTV :

1. An adequate dose should be delivered to the whole of GTV to obtain local tumor control in radical treatments.

2. To allow for recording of tumor response in relation to dose and its variation, and to other relevant factors.

GROSS TUMOR VOLUME (cont.)

GTV


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CLINICAL TARGET VOLUME ( CTV )

It is a tissue volume that contains a GTV and/or subclinical microscopic disease, which has to be eliminated.

This volume has to be treated adequately in order to achieve the aim of therapy : cure or palliation.

The delineation of this volume requires consideration of factors like local invasive capacity of the tumor and its potential to spread to different regions (eg: regional lymph nodes).

CTV

The delineation of GTV and CTV are based on purely anatomic-topographic and biological considerations without regard to technical factors of treatment.

GTV versus CTV


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PLANNING TARGET VOLUME ( PTV )

It is a geometrical concept, and is defined to select appropriate beam sizes and arrangements, taking into consideration the net effect of all possible geometrical variations, in order to ensure that the prescribed dose is actually absorbed in the CTV.

PTV

TREATED VOLUME

It is a volume enclosed by an isodose surface, selected and specified by the radiation oncologist as being appropriate to achieve the purpose of treatment ( tumor eradication or palliation ).

It may closely match to the PTV or may be larger than the PTV.

If, however, it is smaller than the PTV, or not wholly enclosing the PTV, then the probability of tumor control is reduced and the treatment plan has to be reevaluated or the aim of the therapy has to be reconsidered.


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IRRADIATED VOLUME ( IrV )

It is that tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance.

It depends on the treatment technique used.

ORGANS AT RISK ( OR )

These are normal tissues whose radiation sensitivity may significantly influence the treatment planning and/or prescribed dose.

They may be divided into 3 classes : Class I : Radiation lesions are fatal or result in severe

morbidity. Class II : Radiation lesions result in mild to moderate

morbidity. Class III : Radiation lesions are mild, transient, and

reversible, or result in no significant morbidity.

ICRU 50

Irradiated Volume

Treated Volume

Planning Target Volume (PTV)

Clinical Target Volume (CTV)Gross Tumor Volume(GTV)


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Treatment PlanningPlan Evaluation: Early stage breast cancer (supine)

Treatment Planning Plan Evaluation: Intermediate-risk prostate cancer

Treatment PlanningPlan Evaluation: Intermediate-risk prostate cancer


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Treatment Planning

How can we modulate dose? Adjust number,

intensity, angle of beams

Treatment Planning Examples

How Can We Modulate Dose?

Use computer planning to modulate dose from multiple beams (IMRT)


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Types of External Beam Radiation Therapy

Two-dimensional radiation therapy Three-dimensional conformal radiation therapy (3-D CRT) Intensity modulated radiation therapy (IMRT) Image Guided Radiation Therapy (IGRT) Intraoperative Radiation Therapy (IORT) Stereotactic Radiotherapy (SRS/SBRT) Particle Beam Therapy

2D Treatment Planning

Anatomical landmark Simple radiation principles

Intensity falls off by distance squared

Simple beam arrangement With or without custom blocks

Still very useful for some routine rudimentary cases Simple bone mets where there

is little critical tissue in field

CT simulator most common PET/CT simulator CT/MR and CT/PET fusion

programs available Multiple treatment fields converge Most frequently utilizes a trial &

error process called forward planning

Coplanar or non-coplanar Minimizes radiation to normal

tissue. Allows calculation of a “Dose-

Volume Histogram” (DVH)

3D Conformal Treatment Planning


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3-D CRT Uses CT, PET or MRI scans

to create a 3-D picture of the tumor and surrounding anatomy Improved precision,

decreased normal tissue damage

Breast cancers, lung cancers

3D Conformal Radiation Therapy

What is IMRT???

IMRT = Intensity Modulated Radiation Treatment

Inverse planning MD denotes what tissues will receive what dose The planning computer decides how to deliver it “Blocks” are not used The beam is modified as it leaves the accelerator

The target receives the minimum dose. The nature of the beam modification results in

inhomogeneity of dose within the target Multiple treatment beams with dynamic multileaf Arcs (Rapid Arc) Static fields (IMRT)


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IMRT A highly sophisticated form of 3-D

CRT allowing radiation to be shaped more exactly to fit the tumor Radiation is broken into many

“beamlets,” the intensity of each can be adjusted individually

IMRT allows higher doses of radiation to be delivered to the tumor while sparing more healthy surrounding tissue

Head and neck cancers, esophageal and prostate cancers

3D CRT vs. IMRT

Definition of Targets & Normal Tissues


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Delivery of Radiation Therapy

External beam radiation therapy typically delivers radiation using a linear accelerator

Internal radiation therapy, called brachytherapy, involves placing radioactive sources into or near the tumor

The modern unit of radiation is the Gray (Gy), traditionally called the rad 1Gy = 100 centigray (cGy) 1cGy = 1 rad

Image Guidance

For patients treated with 3-D CRT or IMRT

Physicians use frequent imaging of the tumor, bony anatomy or implanted fiducial markers for daily set-up accuracy Imaging performed using CT

scans, high quality X-rays, MRI or ultrasound

Motion of tumors can be tracked to maximize tumor coverage and minimize dose to normal tissues

Fiducial markers in prostate visualized and aligned.

4-Dimensional Radiation Therapy

Treatment for the New Millennium—the addition of the TIME dimension


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Stereotactic RadiationRadiosurgery (1 treatment fraction) Gamma Knife or Linac (TruBeam) Minimally invasive procedure (head frame) Sub-millimeter accuracy

Radiotherapy (Up to 5 treatment fractions) Linac Arc therapy Framed (re-locatable) or frameless

Cyber Knife Compact linear accelerator mounted on a robotic arm Frameless

The Gamma Knife

Metastasis


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The CyberKnifeOrthogonal diagnostic x-ray

imaging system

6 MV Linear Accelerator

– compact

– 280 pounds

Robot manipulator

– 0.5 mm accuracy

Clinical Uses for Radiation TherapyTwo major functions:1. To cure cancer Destroy tumors that have not spread Kill residual microscopic disease left

after surgery or chemotherapy

2. 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

External beam radiation treatments are usually scheduled five days a week and continue for one to ten weeks

Stereotactic Body Radiotherapy (SBRT)SBRT refers to stereotactic radiation treatments in 1-5 fractions on specialized linear accelerators Uses sophisticated imaging,

treatment planning and immobilization techniques Respiratory gating may be

necessary for motions management, e.g., lung tumors

SBRT is used for a number of sites: spine, lung, liver, brain, adrenals, pancreas

Data maturing for sites such as prostate


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Proton Beam Therapy Protons are charged particles that

deposit most of their energy at a given depth, minimizing risk to tissues beyond that point

Allows for highly specific targeting of tumors located near critical structures

Increasingly available in the U.S. Most commonly used in treatment

of pediatric, CNS and intraocular malignancies Data maturing for use in other tumor

sites

Types of Internal Radiation Therapy

Intracavitary implants Radioactive sources are placed in a cavity near

the tumor (breast, cervix, uterine) Interstitial implants Sources placed directly into the tissue (prostate,

vagina) Intra-operative implants Surface applicator is in direct contact with the

surgical tumor bed

Brachytherapy Dose Rate

Low-Dose-Rate (LDR) Radiation delivered over days and

months Prostate, breast, head and neck,

and gynecologic cancers may be treated with LDR brachytherapy

High-Dose-Rate (HDR) High energy source delivers the dose

in a matter of minutes rather than days

Gynecologic, breast, head and neck, lung, skin and some prostate implants may use HDR brachytherapy

LDR prostate implant


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Brachytherapy

Radioactive sources are implanted into the tumor or surrounding tissue 125I, 103Pd, 192Ir, 137Cs

Purpose is to deliver high doses of radiation to the desired target while minimizing the dose to surrounding normal tissues

Radioactive seeds for a permanent prostate implant, an example of low-dose-rate brachytherapy.

Permanent vs. Temporary Implants

Permanent Implants Release small amounts of

radiation over a period of several months

Examples include low-dose-rate prostate implants (“seeds”)

Patients receiving permanent implants may be minimally radioactive and should avoid close contact with children or pregnant women

Temporary Implants Temporary implants are left

in the body for several hours to several days

Examples include low-dose-rate GYN implants and high-dose-rate prostate or breast implants

Patient may require hospitalization during the implant depending on the treatment site

Intraoperative Radiation Therapy (IORT)

IORT delivers a concentrated dose of radiation therapy to a tumor bed during surgery Advantages

Decrease volume of tissue in boost field

Ability to exclude part or all of dose-limiting normal structures

Increase the effective dose

Multiple sites Pancreas, stomach, lung, esophagus,

colorectal, sarcomas, pediatric tumors, bladder, kidney, gyn

Several recent trials have shown efficacy for breast cancer


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Radiation Therapy in Multidisciplinary Care

Radiation therapy plays a major role in the management of many common cancers either alone or as an adjuvant therapy with surgery and chemotherapy Sites commonly treated include

breast, prostate, lung, colorectal, pancreas, esophagus, head and neck, brain, skin, gynecologic, lymphomas, bladder cancers and sarcomas

Radiation is also frequently used to treat brain and bone metastases as well as cord compression

Radiation Therapy Basics The delivery of external beam

radiation treatments is painless and usually scheduled five days a week for one to ten weeks

The effects of radiation therapy are cumulative with most significant side effects occurring near the end of the treatment course. Side effects usually resolve over the

course of a few weeks There is a slight risk that radiation

may cause a secondary cancer many years after treatment, but the risk is outweighed by the potential for curative treatment with radiation therapy

{Sabin Motwani will send us image of mild skin redness after RT in a treatment field}.

Example of erythroderma after several weeks of radiotherapy with moist desquamation

Common Radiation Side Effects Vary depending on site of the treatment and affect the tissues in

radiation field: Breast – swelling, skin redness Abdomen – nausea, vomiting, diarrhea Chest – cough, shortness of breath, esophageal irritation Head and neck – taste alterations, dry mouth, mucositis, skin redness Brain – hair loss, scalp redness Pelvis – diarrhea, cramping, urinary frequency, vaginal irritation Prostate – impotence, urinary symptoms, diarrhea Fatigue is often seen when large areas are irradiated

Modern radiation therapy techniques have decreased these side effects significantly

Unlike the systemic side effects from chemotherapy, radiation therapy usually only impacts the area that received radiation


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Palliative Radiation Therapy Commonly used to relieve pain from bone

cancers ~ 50 percent of patients receive total relief

from their pain 80 to 90 percent of patients will derive some

relief Other palliative uses:

Spinal cord compression Vascular compression, e.g., superior vena

cava syndrome Bronchial obstruction Bleeding from gastrointestinal or gynecologic

tumors Esophageal obstruction

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

1. Referral2. Consultation3. Simulation4. Treatment Planning5. Quality Assurance


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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

It is important for a referring physician to discuss all possible treatment options available to the patient

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

The radiation oncologist will discuss with the patient which type of radiation therapy treatment is best for their type of cancer

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 or “tattoos” may be placed on patient

CT simulation images are often fused with PET or MRI scans for treatment planning


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Treatment Planning

Physician outlines the target and organs at risk Sophisticated software is used

to carefully derive an appropriate treatment plan Computerized algorithms enable the

treatment plan to spare as much healthy tissue as possible

Medical physicist checks the chart and dose calculations

Radiation oncologist reviews and approves final plan

Radiation oncologists work with medical physicists and dosimetrists to create the optimal treatment plan for each individualized patient

Safety and Quality Assurance

Each radiation therapy treatment plan goes through many safety checks The medical physicist checks the calibration of the linear

accelerator on a regular basis to assure the correct dose is being delivered

The radiation oncologist, along with the dosimetrist and medical physicist go through a rigorous multi-step QA process to be sure the plan can be safely delivered

QA checks are done by the radiation therapist daily to ensure that each patient is receiving the treatment that was prescribed for them

Systemic Radiation Therapy

Radiation can also be delivered by an injection: Metastron (89Strontium), Quadramet (153Samarium)

and Xofigo (223Radium) are radioactive isotopes absorbed primarily by cancer cells Used for treating bone metastases

Radioactive isotopes may be attached to an antibody targeted at tumor cells Zevalin, Bexxar for Lymphomas

Radioactive “beads” may be used to treat primary or metastatic liver cancer Y90-Microspheres


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Public Awareness of Radiation Therapy

Patients report going to friends and family and their referring physician to get cancer treatment information

Take Away Points

Radiation therapy delivery continues to become more precise resulting in less damage to normal surrounding tissues and thus decreasing number of fractions delivered. Radiation planning is a very complex, tedious

process that requires anywhere from one day to several weeks. With more conformal techniques, side effects

from radiation therapy are diminishing.

For More Information…

The American Society for Radiation Oncology (ASTRO) can provide information on radiation therapy

Visit www.rtanswers.org to view information on how radiation therapy works to treat various cancers

Documents

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