Physics of Radiotherapy MSc Hemn A. Rahman Salahaddin University-Erbil

Covered in Module 2

Recommended Reading 3

Assumed Knowledge  Basic human anatomy and physiology  Radioactivity  Interaction of radiation with matter  Basic dosimetric units 4

Outline  Human cell and cell-cycle  Cancer and its risks and risk factors  Cancer treatment options  Definition of radiotherapy  Tissue irradiation  Cell damage  TCP and NTCP  Therapeutic ratio  Fractionation in radiotherapy  Radiotherapy treatment  Brachytherapy  Some side effects of radiotherapy 5

The Human Cell NOTE: JUST HAVE A LOOK. 6

The Cell Cycle NOTE: STUDENTS SHOULD KNOW THE PHASES OF THE CELL CYCLE.  Phases of the cell cycle: For more: Human cell-cycle videoHuman cell-cycle video Second Gap Phase Synthesis Phase First Gap Phase Mitosis Phase 7

Cancer Cancer is characterized by a disorderly proliferation of cells that can invade adjacent tissues and spread via the lymphatic system or blood vessels to other parts of the body (metastases). 8

Cancers  Tumours: benign or malignant  Secondary cancer or metastasis  >200 different cancers  85% carcinomas – originate in epithelium –common forms breast, lung, prostate and bowel  Carcinomas are named after the type of epithelial cell that they originate in and the part of the body 9

Risk of Cancer  250,000 are diagnosed with cancer in the UK per year  1 in 3 people will develop cancer during their lifetime.  64% of all newly diagnosed cancers occur in people aged 65 years or more  The most recent statistics for the UK (from 2003) show that for men the most common cancer is prostate(23%), followed by lung (16%) large bowel(14%) and bladder (5%).  For women the figures are breast(31%), large bowel(11%), lung(11%) and ovary (5%). 10

Cancer Risk Factors  Old age  Tobacco  Sunlight  Ionizing radiation  Some chemicals and substances  Some viruses and bacteria  Certain hormones  Family history  Alcohol  Poor diet, lack of physical activity, overweight 11

Effect of Tobacco  50% of smokers will die from smoking related illnesses  Accounts for 30% of all cancer deaths, 87% of lung cancers  Risk of developing lung cancers 23% higher in male smokers than male non-smokers 12

Treatment options of Cancer  Surgery often used if the cancer is only in one area of the body and has not spread. It may be used to remove lymph nodes if these are also affected by the cancer.  Chemotherapy cytotoxic drugs.> 50 different chemotherapy drugs. Tablets or capsules but most by infusion into a vein. The drugs go into the bloodstream and travel throughout the body to treat the cancer cells wherever they are. often a combination of two, three or more drugs is given.  Hormonal therapy 13

Treatment options of Cancer (Cont.)  Biological therapy – Monoclonal antibodies are drugs that can 'recognise' and find specific cells in the body. They can be designed to find a particular type of cancer cell, attach itself to them and destroy them. They can also carry a radioactive molecule, which then delivers radiation directly to the cancer cells. – Cancer growth inhibitors: interfere with the way cancer cells use 'chemical messengers' to help the cell to develop and divide. – Vaccines and gene therapy: research is in the very early stages.  Radiation Therapy – External Beam Radiotherapy – Brachytherapy 14

What is Radiotherapy ?  Treatment of disease with radiation. 15

What is Radiotherapy ? (cont.)  Electromagnetic radiation, such as x-rays, gamma rays, electron beams or protons, used to kill or damage cancer cells to stop/slow them from growing or multiplying.  Radiotherapy can take place before, during or after treatment and in conjunction with other treatments such as chemotherapy or surgery.  About 50% of all cancer patients receive some form of radiation therapy during the course of their treatment. 16

Cancer & Radiotherapy  Cancer is characterized by a disorderly proliferation of cells that can invade adjacent tissues and spread via the lymphatic system or blood vessels to other parts of the body (metastases).  The aim of radiotherapy is to deliver enough radiation to the tumour to destroy it without irradiating normal tissue to a dose that will lead to serious complications (morbidity).  Treatment either radical or palliative 17

Tissue irradiation  When ionizing radiation is absorbed in biological material, the damage to the cell may occur in one of two ways: direct or indirect.  In direct action, charged particles with sufficient energy directly interact with the critical target in the cell (DNA or Cell membrane). The atoms of the target itself may be ionized or excited through Coulomb interactions, leading to the chain of physical and chemical events that eventually produce the biological damage.  In indirect action, photons interact with other molecules and atoms (mainly water) within the cell to produce free radicals, which can, eventually, damage the critical target within the cell. 18

Cell damage  Radiation damage to mammalian cells is divided into three categories: – Lethal damage (irreversible, cell death) – Sublethal damage (reversible unless additional damage is added) – Potentially lethal damage (can be manipulated by repair when cells are allowed to remain in a non-dividing state) 19

Fate of irradiated cells  No effect.  Division delay  Apoptosis  Reproductive failure  Genomic instability  Mutation  Transformation  Bystander effects  Adaptive responses 20

TCP & NTCP  The principle of radiotherapy is usually illustrated by plotting two sigmoid curves. – For tumour control probability (TCP) – For normal tissue complication probability (NTCP) 21

Therapeutic ratio  The concept of the therapeutic ratio is often used to represent the optimal radiotherapy treatment.  Therapeutic ratio generally refers to the ratio of the TCP and NTCP at a specified level of response (usually 0.05) for normal tissue 22

Therapeutic ratio (cont.)  The further the NTCP curve is to the right of the TCP curve: – the easier it is to achieve the radiotherapeutic goal – the larger is the therapeutic ratio – the less likely are treatment complications 23

Fractionation  Fractionation of radiation treatment so that it is given over a period of weeks rather than in a single session results in a better therapeutic ratio ( better tumour control with less severe side effects).  To achieve the desired level of biological damage the total dose in a fractionated treatment must be much larger than that in a single treatment. 24

Fractionation  The basis of fractionation is rooted in 5 primary biological factors called the five R’s of radiotherapy: – Radiosensitivity: Mammalian cells have different radio-sensitivities. – Repair: Mammalian cells can repair radiation damage. – Repopulation: During a 4- to 6-week course of radiotherapy, tumour cells that survive irradiation may proliferate and thus increase the number of cells which must be killed. – Redistribution: Cell-cycle progression effects. Cells that survive a first dose of radiation will tend to be in a resistant phase of the cell cycle, and within a few hours, they may progress into a more radiosensitive phase (G1 & Mitosis phase ) – Reoxygenation of hypoxic cells occurs during a fractionated course of treatment, making them more radiosensitive to subsequent doses of radiation. 25

Fractionation  Conventional fractionation is explained as follows: – Division of dose into multiple fractions spares normal tissues through repair of sublethal damage between dose fractions and repopulation of cells. – The repair of sublethal damage is greater for late responding tissues, the repopulation of cells is greater for early responding tissues. 26

Fractionation (cont.)  Conventional fractionation is explained as follows (cont.): – Fractionation increases tumour damage through reoxygenation and redistribution of tumour cells – A balance is achieved between the response of tumour and early and late responding normal tissues, so that small doses per fraction spare late reacting tissues preferentially, and a reasonable schedule duration allows regeneration of early responding tissues and tumour reoxygenation likely to occur. 27

Fractionation  The current standard fractionation is based on: – 5 daily treatments per week (Monday to Friday) – 1.8 to 2.0 Gy/fraction – a total treatment time of several weeks  This regimen reflects: – the practical aspects of dose delivery to a patient – Successful outcome of patient’s treatments – Convenience to staff delivering the treatment 28

Fractionation  In addition to the standard fractionation regimens, other fractionation schemes are being studied with the aim of improving the therapeutic ratio: – Hyperfractionation uses more than one fraction per day with a smaller dose per fraction (<1.8 Gy) to reduce long term complications and to allow delivery of higher total tumour dose. – Accelerated fractionation reduces the overall treatment time, minimizing tumour cell repopulation during the course of treatment. – Continuous hyperfractionated accelerated radiation therapy (CHART) is an experimental programme used with three fractions per day for 12 continuous days. 29

Purpose of Radiotherapy (RECAP)  Deliver radiation dose accurately  Increase radiation dose to tumour to improve local control  Minimise radiation dose to critical structures to reduce radiation toxicity 30

Radiotherapy Process  Diagnosis  Therapeutic Decisions  Target Volume Localisation  Fabrication of Treatment Aids  Treatment Planning  Simulation  Treatment  Patient Evaluation during treatment  Patient Follow up 31

Radiotherapy Treatment Planning process 1. CT scanning 2. Tumour localization 3. Skin reference marks 4. Treatment planning 5. Virtual simulation 6. Radiotherapy treatment 32

Brachytherapy  Method of radiation treatment in which sealed radioactive source is used to deliver the dose to a short distance by – Interstitial (direct insertion into tissue) – intracavitary(placement within a cavity) – surface application (molds)  Radiation sources may be form of needles, narrow tubes, wires or small beads.  Most commonly used radioisotope in head and neck regions are iridium 192, cesium137 and radium

Brachytherapy (cont.) US probe Afterloader Brachy seeds Supporting unit and stepping system Template 34

Brachytherapy (cont.) Infatable balloon Radioactive source port pathway Needle injection site Catheter line to the balloon 35

Advantages and disadvantages of Brachytherapy  Advantages – Rapid decrease in dose with distance from radiation source (inverse square law). – Thus a high radiation dose can be given to the tumor while sparing surrounding normal tissues. – Thus continuous low dose irradiation tends to synchronize the cell cycle and allows sublethal damage repair.  Disadvantages – Inhomogeneity – Needs a skilful operator to achieve good dose distribution – Exposure to the therapist the room personnel 36

Possible side effects of RT Side effects of radiation depend on the area is being treated:  Hair loss  mouth dryness or mouth sores  Skin changes, itching, skin dryness  Diarrhea  Swelling of the area being treated  Nausea and vomiting  Bladder dysfunction 37