Introduction to Radiation Oncology

Question 1

<p>What is the role of radiation oncology and cancer treatment?</p>

Answer 1

<ul>
<li><span>At a multidisciplinary tumor board, the patient&rsquo;s case, diagnostic and staging procedures, and pathology is discussed, and in coordination with the other oncologist the <strong>best treatment strategy chosen</strong></span></li>
<li>The role of the radiation oncologist (RO) is to:
<ul>
<li>provide an oncologic opinion at tumor board</li>
<li>discuss with the patient the rationale for treatment</li>
<li>the time frame of therapy</li>
<li>the potential acute and late side effects of treatment</li>
<li>assess the patient weekly during their treatments to manage acute side effects</li>
<li>follow them over the long-term to assess outcomes and address potential late side effects</li>
</ul>
</li>
<li>The goal of radiation therapy is to <strong>precisely deliver a measured dose of radiation</strong> to the target volume while minimizing damage to adjacent healthy tissue</li>
<li><strong>The aims are to</strong>:
<ul>
<li>eradicate tumor</li>
<li>minimize side effects</li>
<li>provide the patient with a high quality of life</li>
<li>prolong survival (depending on site and tumor)</li>
<li>and provide effective palliation from symptoms of cancer (in patients with metastatic and/or incurable disease)</li>
</ul>
</li>
</ul>

Question 2

<p>Whats the difference between definitive, adjuvant, curative, and pallative uses of radiation in cancer treatment?</p>

Answer 2

<ul>
<li><strong>Definitive</strong>: RT may be the sole or major treatment modality

<ul>
<li>It can be given concurrently with chemotherapy therapy or alone</li>
</ul>
</li>
<li><strong>Adjuvant</strong>: RT may precede or follow surgical intervention (multi-modality therapy)
<ul>
<li>The goal of therapy is <u>determined at the onset of treatment</u></li>
</ul>
</li>
<li>Treatment is given with either <strong>curative or palliative intent</strong>.</li>
<li><strong>Curative</strong>: There is loco-regionally confined disease with a probability of <strong>long-term survival</strong> after adequate therapy
<ul>
<li>Some side effects of therapy, although undesirable, are accepted in light of a chance of cure</li>
<li><u>Examples include</u>:
<ul>
<li>A patient will early stage localized prostate cancer treated with radioactive seeds (Low Dose Rate (LDR) brachytherapy)</li>
<li>A patient with <u>locally-advanced</u> lung cancer that is un-resectable and treated with concurrent chemo-radiation</li>
<li>A patient with a large <u>oral tongue cancer</u> undergoes surgical resection of his tumor and neck nodes followed by <u>concurrent chemo-radiation</u></li>
</ul>
</li>
</ul>
</li>
<li><strong>Palliation</strong>: Disease is considered incurable and patients have symptoms that are <strong>causing discomfort</strong> or an impending condition that could lead to <strong>symptoms and affect quality of life</strong>
<ul>
<li>Lower tolerance for toxicity in this setting</li>
<li><u>Examples include</u>:
<ul>
<li>Bone metastases that is causing pain in a patient with breast cancer</li>
<li>Invasion of the bladder by a prostate tumor that is causing hematuria</li>
<li>An asymptomatic patient with epidural disease in the spinal canal that could lead to spinal cord compression and cause paralysis</li>
</ul>
</li>
</ul>
</li>
</ul>

Question 3

<p>What are the major steps of radiotherapy?</p>

Answer 3

<ul>
<li><strong>Consultation</strong>:

<ul>
<li>The patient is seen by a radiation oncologist; a history is taken, a physical examination is performed, and laboratory and imaging studies are reviewed</li>
<li>The radiation oncologist and patient have a discussion about treatment options, radiotherapy, its process, benefits and toxicities</li>
</ul>
</li>
<li><strong>CT Simulation</strong>:
<ul>
<li>An immobilization device is crafted and patient positioning is optimized</li>
<li>Sometimes, radio-opaque markers or contrast are used</li>
<li>A CT scan is obtained</li>
<li>Motion management or 4D simulation may be added</li>
<li>Tattoos are placed</li>
</ul>
</li>
<li><strong>Planning and quality assurance</strong>:
<ul>
<li>The radiation oncologist delineates both target structures and normal tissues for avoidance</li>
<li>Constraints are set concerning optimal target coverage and normal tissue sparing</li>
<li>A radiation plan is created</li>
<li>This plan then undergoes a series of quality assurance checks by the physics team</li>
</ul>
</li>
<li><strong>Initiation of treatment</strong>:
<ul>
<li>The patient begins radiation therapy</li>
<li>The radiation oncologist checks all details before initiation</li>
</ul>
</li>
<li><strong>Monitoring on treatment</strong>:
<ul>
<li>Each patient is seen at least weekly in order to monitor and manage acute toxicity</li>
</ul>
</li>
<li><strong>Follow-up</strong>:
<ul>
<li>The patient is followed at regular intervals for years in order to monitor for recurrence and/or treatment-related toxicity</li>
<li>Surveillance imaging may be ordered</li>
</ul>
</li>
</ul>

Question 4

<p>Describe the radiation physics employed in cancer treatment.</p>

Answer 4

<ul>
<li>When radiation interacts with biologic material, the absorption of energy can lead to <strong>excitation</strong> (raising of an electron in at atom or molecule to a higher energy level without ejection of the electron) or <strong>ionization</strong> (sufficient energy is present to eject an electron)

<ul>
<li>Ionizing radiation releases enough energy to break strong chemical bonds, alter DNA and cause a biologic event</li>
</ul>
</li>
<li>Radiation is administered to cells either in the form of <strong>photons</strong> (x-rays and gamma rays) or <strong>particles</strong> (protons, neutrons, and electrons).</li>
<li><strong>X-rays</strong> (produced artificially by a machine and most commonly used for treatments) and <strong>gamma rays</strong> (produced by decay of radioactive isotopes) are ionizing radiation that have <strong>short wavelengths</strong> and thus higher frequency or large photon energy and are able to <strong>break chemical bonds and cause biologic effects</strong></li>
<li>Radiation can be classified as <strong>directly or indirectly ionizing</strong>
<ul>
<li><u>Charged particles</u> in general are directly ionizing</li>
<li>There is <u>direct interaction</u> with subcellular structures to produce chemical and biologic changes</li>
<li><u>Electromagnetic radiation</u> is indirectly ionizing - radiation interacts with H20 and generates free radicals that then interact with subcellular structures</li>
</ul>
</li>
</ul>

Question 5

<p>How does radiation kill cancer cells?</p>

Answer 5

<ul>
<li><strong>DNA is the principal target</strong> for the biologic effects of radiation</li>
<li><strong>Ionizing radiation</strong> results in events such as:
<ul>
<li>base and sugar damage</li>
<li>single strand (SSB) breaks</li>
<li>double strand (DSB) breaks</li>
</ul>
</li>
<li><strong>Single strand breaks</strong> are repaired easily by using the opposite strand as a template</li>
<li>The generation of <strong>DSB causes important biologic endpoints</strong> such as cell death</li>
</ul>

Question 6

<p>How is radiation dose quantified and determined for cancer treatment?</p>

Answer 6

<ul>
<li>The amount of radiation given is measured in <strong>gray (Gy)</strong>

<ul>
<li>One Gy is defined as the absorption of <strong>one joule of energy </strong>in the form of ionizing radiation, per kg of matter</li>
</ul>
</li>
<li>The amount of radiation given depends on the <strong>intent</strong> of treatment and <strong>type</strong> and <strong>stage</strong> of cancer.
<ul>
<li>Generally doses in conventional fractionation are given at <u>1.8Gy to 2Gy per day</u></li>
<li>For curative cases of epithelial tumors, doses range from <u>60 to 80 Gy over 7 to 9 weeks</u></li>
<li>For radiosensitive tumors like seminomas and lymphomas, doses of <u>20 to 45Gy are given over 3 to 5 weeks</u></li>
<li>Palliative doses vary widely but in general are <u>delivered over 1 to 4 weeks</u> (20 to 40Gy) and can be given in conventional fractionation of 1.8Gy to 2Gy or larger fractions of 3Gy to 5Gy or in a single fraction</li>
<li>Some <u>common palliative doses</u> are 30Gy in 10 fractions over 2 weeks, 20Gy 5 fractions over 1 week, and 8Gy in a single fraction</li>
</ul>
</li>
</ul>

Question 7

<p>What is fractionation, and why is it necessary?</p>

Answer 7

<ul>
<li><strong>Sparing of normal tissue</strong>:

<ul>
<li>Both malignant and normal cells are <u>subject to the effects of ionizing radiation</u></li>
<li>Normal cells have the intact mechanism to <u>detect and repair DNA breaks and mutations</u> (repair of sublethal damage) between fractions and repopulate if sufficient time between fractions is present</li>
<li>Many malignant cells <u>lack these molecular mechanisms</u> and are <u>preferentially targeted by the radiation</u></li>
<li>There is a <u>tolerance to the dose</u> that normal tissue can tolerate and this determines the maximum dose that be given during a course of treatment</li>
</ul>
</li>
<li><strong>Better efficacy of cell kill</strong>:
<ul>
<li>Dividing the dose into <u>small fractions</u> allows for tumors that are in a relatively <u>radio-resistant phase</u> of the cell cycle during treatment to cycle into a <u>sensitive phase</u> prior to delivery of the next fraction (reassortment)</li>
<li>Tumor cells that are <u>acutely or chronically hypoxic </u>(which renders them more radioresistant) may reoxygenate between fractions allowing for better cell kill</li>
</ul>
</li>
</ul>

Question 8

<p>What are the pros and cons of extending treatment time with radiation in cancer treatment?</p>

Answer 8

<ul>
<li>The advantages of prolonging treatment time are to <strong>spare early reactions</strong> for normal tissue and to allow for reoxygenation of tumors</li>
<li>Prolonging treatment time, however, can <strong>allow surviving tumor cells to proliferate</strong> during treatment
<ul>
<li>It is preferred to finish the RT course as prescribed within a <u>set time frame</u> once treatment has commenced</li>
</ul>
</li>
</ul>

Question 9

<p>What is external beam radiotherapy (EBRT)? What is its clinical use?</p>

Answer 9

<ul>
<li>The most common RT approach is to deliver RT from a <strong>source outside the patient</strong> (external beam RT).</li>
<li>Radiation is <strong>generated by Linear accelerators</strong> (LINACS), which, are found in all RT centers, or <strong>Cobalt-60 machines</strong> (via radioactive decay of Cobalt), which, are mostly obsolete in the US
<ul>
<li>In LINACS, electrons are accelerated and can exit the machine as an <u>electron beam</u> or strike a target to produce <u>x-rays</u> (photons), which are then directed at the target volume</li>
<li>The energies generated by LINACS range from 4 MV to 20 MV (megavolts)
<ul>
<li><em>Photons</em> are most commonly used to treat cancers as they can penetrate deep into tissue</li>
</ul>
</li>
</ul>
</li>
<li>Electrons are used in the <strong>treatment of superficial lesions</strong> (ie. skin cancers) as they have a limited range</li>
<li><strong>Examples of EBRT include</strong>:
<ul>
<li><u>3D CRT</u> (Three dimensional conformal RT):
<ul>
<li>allows for simple 2 field plans to more complex 5 to 6 field plans</li>
</ul>
</li>
<li><u>IMRT</u> (Intensity Modulated RT):
<ul>
<li>used&nbsp;in more complex scenarios such as treatment of brain tumors, head and neck cancers, prostate cancer</li>
<li>Allows for dose escalation and better sparing of adjacent critical structure than 3D-CRT</li>
</ul>
</li>
<li><u>SRS/SBRT</u> (Stereotactic Radiosurgery/Stereotactic Body Radiotherapy)
<ul>
<li>used to treat small well defined lesions</li>
<li>genrally&nbsp;delivered in large fractions and given in a single fraction and up to 5 fractions</li>
</ul>
</li>
<li><u>Particle therapy</u> (proton therapy and neutron therapy)
<ul>
<li>requires special equipment to generate high-energy particles and have limited availability</li>
</ul>
</li>
</ul>
</li>
</ul>

Question 10

<p>What is brachytherapy and what are its clinical applications?</p>

Answer 10

<ul>
<li>The radiation source is <strong>placed inside the patient</strong> or next to the area of interest

<ul>
<li><u>Emission is active over a relatively short distance</u> (deliver high doses to target volume while minimizing dose to adjacent tissue)</li>
<li><u>It can be given alone or after EBRT</u> to increase dose to target volume.</li>
</ul>
</li>
<li>Can be delivered with a <strong>low-dose-rate system (LDR)</strong> or a <strong>high-dose-rate system (HDR)</strong>
<ul>
<li><u>LDR</u>: dose is generally 0.4 to 2Gy per hour, common sources used are <u>Iodine-125 and Palladium-103</u> in prostate cancer and <u>Cesium-137</u> in the treatment of cervical cancer
<ul>
<li>Sources may be placed in <em>tumor permanently</em> (prostate) or <em>temporarily</em> (cervix) until desired dose is reached</li>
</ul>
</li>
<li><u>HDR</u>: dose is delivered at <u>>12Gy per hour</u>, common source used is Iridium-192&nbsp;in the treatment of prostate cancers and gynecological malignancies
<ul>
<li>Sources are <em>placed in the tumors temporarily</em> and radiation is delivered over several fractions</li>
</ul>
</li>
</ul>
</li>
</ul>

Question 11

<p>What is intraoperative radiation therapy?</p>

Answer 11

<ul>
<li>Radiation is given at the <strong>time of surgery</strong> in a single fraction</li>
<li>Decision to give RT is made at time of surgery based on presence of <strong>adverse features</strong> (example: + margin)</li>
<li>Can be delivered with <strong>linac or brachytherapy</strong></li>
<li>Used in breast, pelvic, and abdominal malignancies</li>
<li><strong>May precede or follow EBRT</strong></li>
</ul>

Question 12

<p>What is targeted radionucleotide therapy/unsealed sources?</p>

Answer 12

<ul>
<li>Targeted therapy with the use of <strong>radionuclides that decay in the body in specific locations</strong></li>
<li><strong>Some examples include</strong>:
<ul>
<li><u>Strontium, Samarium, and Radium 223</u> for metastatic prostate cancer: Radioisotopes can accumulate in bone and can be used in <u>treatment of extensive metastatic bone disease</u></li>
<li><u>Iodine-131</u>: thyroid cells selectively accumulate 1-131 &ndash; the release of radiation can be used to <u>treat thyroid malignancies</u></li>
</ul>
</li>
</ul>

Question 13

<p>What are some acute side effects of radiotherapy?</p>

Answer 13

<ul>
<li>Side effects can be divided into <strong>acute</strong> (occur during treatment) and <strong>late</strong> (occur after 90 days)

<ul>
<li>Side effects depend on:
<ul>
<li>the anatomic site</li>
<li>proximity of critical organs to target volume</li>
<li>dose per fraction</li>
<li>cumulative dose and concurrent treatment</li>
</ul>
</li>
</ul>
</li>
<li><strong>Acute Side Effects</strong> are generally temporary and start during the <strong>2nd week</strong> of RT and can <strong>persist for weeks to months</strong> after RT is completed
<ul>
<li>Most acute side effects are predictable</li>
<li>They can be exacerbated by:
<ul>
<li>previous surgeries</li>
<li>concurrent treatments (chemotherapy)</li>
<li>patient&rsquo;s underlying symptoms prior to starting treatment</li>
<li>use of irritants during treatment (smoking)</li>
<li>noncompliance with recommended symptom management therapies during treatment</li>
</ul>
</li>
<li>Typically related to:
<ul>
<li>denuding of epithelial surfaces</li>
<li>inflammatory cascade</li>
<li>hematocytopenia</li>
</ul>
</li>
</ul>
</li>
</ul>

Question 14

<p>What are som eof the late side effects of radiation therapy?</p>

Answer 14

<ul>
<li><strong>Late Side Effects</strong> can be permanent and can manifest months to decades after completion of treatment

<ul>
<li>Examples include:
<ul>
<li>cardiac toxicity in young patients treated for lymphoma</li>
<li>xerostomia in patient&rsquo;s treated for head and neck cancers</li>
<li>radiation induced secondary malignancy in a pediatric patient that occurs when they are an adult</li>
</ul>
</li>
<li>Typically related to vascular structures, fibrosis and parenchymal cell death</li>
</ul>
</li>
<li><strong>Close follow up</strong> with the oncology team to address potential late side effects and serial imaging as indicated are important aspects of patient care after treatment</li>
</ul>