Radiotherapy Lecture Notes PDF

RADIOTHERAPY I Dr. Anastasia Hadjiconstanti Acknowledgements: Dr. Constantinos Zervides LECTURE LOB’S 52. DEFINE RADIOTHERAPY. 53. EXPLAIN HOW RADIOTHERAPY CAN TREAT CANCER. 55. EXPLAIN THE CRITERIA FOR SELECTING SUITABLE ISOTOPE SOURCES FOR RADIOTHERAPY. RADIOTHERAPY I Radiation therapy, is using i...

RADIOTHERAPY I Dr. Anastasia Hadjiconstanti Acknowledgements: Dr. Constantinos Zervides LECTURE LOB’S 52. DEFINE RADIOTHERAPY. 53. EXPLAIN HOW RADIOTHERAPY CAN TREAT CANCER. 55. EXPLAIN THE CRITERIA FOR SELECTING SUITABLE ISOTOPE SOURCES FOR RADIOTHERAPY. RADIOTHERAPY I Radiation therapy, is using ionizing radiation to kill tumors. Lethal doses of radiation are rapidly delivered to malignant tumor cells. Because the doses are in the deterministic regime, a predictable fraction of the tumor cells die. Unfortunately, healthy tissues are also exposed to high doses, along with the tumors. As a result, the treatments deliver a stochastic dose to the rest of the body. However, in cancer therapy this small future risk is weighed against an existing life-threatening disease. RADIOTHERAPY II Most malignant tumor cells fall into the class of rapidly reproducing cells, easily affected by radiation. However, destroying enough of a tumor to prevent its regrowth is still a difficult task. Radiation therapy strives to achieve total extinction of tumor cells. This is because if one cell is left behind the tumor will reseed. Cancer cells are not necessarily confined in separate, compact masses. They can be spread throughout the body and infiltrate vital organs. RADIOTHERAPY III Thus, treating a cancer often involves treating an entire region surrounded by healthy tissue. This infers that a compromise is made between effectiveness in tumor killing and in sparing nearby healthy tissue. Plot shows that even small variations in this treatment dose lead to undesirable consequences: too high a dose kills too many healthy cells, while too low a dose spares tumor cells. There is an appreciable overlap between the two curves, making the choice of dose size difficult. In this case, killing appreciable numbers of tumor cells necessarily inflicts great damage on the normal population. RADIOTHERAPY IV The significant features of these curves are:  there is a threshold dose for cell killing,  the fraction of cells killed increases with dose via a characteristic S-shaped curve, and  there is a dose at which 100% of the cells are killed thus no effect is seen if dose is increased. If the threshold for the healthy tissue exceeds that for the tumor, treatments can use a dose that:  kills most of the tumor cells and  affects relatively few of the healthy cells. RADIOTHERAPY V However, even small variations in the treatment dose will lead to undesirable consequences. Too high a dose kills too many healthy cells. Too low a dose spares tumor cells. Unfortunately, there are situations where there is an appreciable overlap between the two curves. This makes the choice of dose size difficult. In this case, killing appreciable numbers of tumor cells necessarily inflicts great damage on healthy tissue. RADIOTHERAPY VI In general, the form of the dose-response curve depends on:  the tissue from which the cells originate,  the type of ionizing radiation used and  its energy. The dose-response curve also depends on the rate at which the radiation dose is delivered. More rapidly delivered doses causing more damage with a lower threshold. Since healthy cells tend to have better DNA repair mechanisms the above effect can be taken advantage of. RADIOTHERAPY VII This is done by dividing the high dose required to kill tumor cells into many fractions (fractionation). Smaller doses are delivered with a pause of a day or so between fractions. This gives time to healthy cells to recover and repopulate. Using fractions also damages tumor cells by changing the point in the cell cycle at which the tumor cells are irradiated. For some regions of the body, radiation is especially effective (superficial skin cancers). For others the responsiveness of tumor cells can differ little from that of neighboring healthy tissues. RADIOTHERAPY VIII The cure rate and effectiveness of radiation greatly depends on:  cancer type and  specifics of individual cases. Radiation therapy may be used as a palliative measure if a cure is unlikely. THE 4 R’S OF FRACTIONATION Repair (few hours). Cells are allowed to repair sub lethal damage. Redistribution (few hours-days). The cell is given time to move to a more radiation sensitive phase of the cell cycle. Re-oxygenetion (few hours-days). Tumour hypoxia and greater radiation resistance is seen. Repopulation (few weeks). Healthy and malignant cells repopulate after irradiation. FRACTIONATION SCHEMES I Conventional.  Dose/fraction: 1.8 -2.2 Gy.  Total dose: 45.0 – 50.4 Gy.  Fractions/week: 5.  Issues: Can be too slow for fast growing tumours. Dose too low for resistant cancers. Example: 𝟓 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏 𝟐. 𝟐 𝑮𝒚 𝑮𝒚 𝒙 = 𝟏𝟏 𝒘𝒆𝒆𝒌 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏 𝒘𝒆𝒆𝒌 𝟓𝟎. 𝟒 𝑮𝒚 = 𝟒. 𝟔 𝒘𝒆𝒆𝒌𝒔 𝟏𝟏 𝑮𝒚/𝒘𝒆𝒆𝒌 FRACTIONATION SCHEMES II Hyper-fractionation (avoid late normal tissue complication).  Dose/fraction: 1.1 - 1.3 Gy.  Total dose: 70 - 80 Gy.  Fractions/week: 10.  Issues: Burden on patients, staff and equipment. No clear benefit has been demonstrated. Accelerated fractionation (for fast growing tumours). Dose/fraction: 1.4 – 2.5 Gy. Total dose: 40 – 50 Gy. Fractions/week: 10. Issues: Burden on patients, staff and equipment. Acute reactions. FRACTIONATION SCHEMES III Accelerated fractionation (for fast growing tumours). Dose/fraction: 1.4 – 2.5 Gy. Total dose: 40 – 50 Gy. Fractions/week: 10. Issues: Burden on patients, staff and equipment. Acute reactions. Example: 𝟏𝟎 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏 𝟐. 𝟓 𝑮𝒚 𝑮𝒚 𝒙 = 𝟐𝟓 𝒘𝒆𝒆𝒌 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏 𝒘𝒆𝒆𝒌 𝟓𝟎 𝑮𝒚 = 𝟐 𝒘𝒆𝒆𝒌𝒔 𝟐𝟓 𝑮𝒚/𝒘𝒆𝒆𝒌 FRACTIONATION SCHEMES IV Hypo-fractionation Dose/fraction: above 2.5 Gy Total dose: 20 – 55 Gy. Fractions/week: 1-5; Issues: Acute reactions. RADIOTHERAPY IX Factors that can be controlled in radiotherapy include: i. means of delivering the radiation, ii. radiation type, iii. total dose, iv. fractions into which the total dose is divided and v. time between fractions. The type of particle used and its energy are essential issues in radiation therapy. RADIOTHERAPY X Because the main goal of radiotherapy is to have tumors absorb energy from radiation, particles are an obvious choice. However, the very short range of alpha particles prevents them from reaching the diseased region. Neutrons require a nearby nuclear reactor for their production. Currently, most therapy is performed with high-energy photons or β- particles. RADIOTHERAPY XI Three alternative approaches for delivering ionizing radiation for therapy exist: beam sources external to the body. They produce a beam of ionizing radiation aimed at the tumor(s) during treatment sessions; brachytherapy sources. Sealed radioactive sources are placed in proximity with the tumor; unsealed sources. Radionuclides are taken into the body in liquid form, either by injection or swallowing. RADIOTHERAPY XII Beam sources are the most widely used type. The beam source delivers a :  uniform,  well-defined, and  stable beam. The particles are pre-selected for correct penetration depth as per the needs of each individual case. This ensures that the beam reaches only the regions intended and delivers the desired dose. TREATMENT MACHINES FOR EXTERNAL BEAM RADIOTHERAPY I Since the beginning of radiotherapy, the aim was to produce ever higher photon and electron beam energies and intensities. In the last 25 years, computerization and intensity modulated beam delivery has become important. During the first 50 years of radiotherapy the technological progress was relatively slow. The invention of the 60Co teletherapy unit in the early 1950s provided a tremendous boost. This placed the cobalt unit at the forefront of radiotherapy for a number of years. The parallel developed medical LINACS, soon eclipsed cobalt units and became the most widely used radiation source. TREATMENT MACHINES FOR EXTERNAL BEAM RADIOTHERAPY I LINAC stands for Linear Accelerator. With a compact and efficient design, LINACs offer excellent versatility and provides either electron or megavoltage X ray therapy with a wide range of energies. In addition to LINACs, electron and X ray radiotherapy is also carried out with other types of accelerator such as: betatrons and microtrons. TREATMENT MACHINES FOR EXTERNAL BEAM RADIOTHERAPY II TREATMENT MACHINES FOR EXTERNAL BEAM RADIOTHERAPY III More exotic particles, like protons, neutrons and heavy ions are produced by special accelerators. They are also sometimes used for radiotherapy, however, most contemporary radiotherapy is carried out with LINACS or teletherapy cobalt units. X-RAY MACHINES FOR RADIOTHERAPY Superficial (50 to 150 kV) and orthovoltage (150 to 500 kV) X rays used in radiotherapy are produced with X ray machines. The main components of a radiotherapeutic X ray machine are: an X ray tube, a ceiling or floor mount for the X ray tube, a target cooling system, a control console, and an X ray power generator. TELETHERAPY MACHINES I Treatment machines incorporating gamma ray sources for use in external beam radiotherapy are called teletherapy machines. The main components of a teletherapy machine are:  a radioactive source,  a source housing with beam collimator and source movement mechanism,  a gantry and stand or a housing support assembly in stand-alone machines,  a patient support assembly and  a machine console. TELETHERAPY SOURCES I The most widely used teletherapy source uses 60Co radionuclides. They are contained inside a cylindrical stainless steel capsule and sealed by welding. A double welded seal is used to prevent any leakage of the radioactive material. To enable swapping of sources from one teletherapy machine to another and from one isotope production facility to another, standard source capsules have been developed. The typical diameter of the cylindrical teletherapy source is between 1 and 2 cm with a height of about 2.5 cm. TELETHERAPY SOURCES II The smaller the source diameter, the smaller is its physical penumbra and the more expensive is the source. The rapid decrease at the edges of the radiation beam is called the penumbra region. TELETHERAPY SOURCES III Often a diameter of 1.5 cm is chosen as a compromise between the cost and penumbra. Typical source activities are of the order of 5000–10 000 Ci (185–370 TBq). They provide a typical dose rate at 80 cm from the teletherapy source of the order of 1–2 Gy/min. Teletherapy sources are usually replaced within one half-life after they are installed. However, financial considerations often result in longer source usage. The 60Co radionuclides in a teletherapy source decay with a half-life of 5.26 years into 60Ni with the emission of electrons. TELETHERAPY SOURCES IV The maximum energy of the electrons is 320 keV. Two gamma rays are also released with energies of 1.17 MeV and 1.33 MeV. The emitted gamma rays constitute the therapy beam. The electrons are absorbed in the cobalt source or the source capsule. TELETHERAPY SOURCES V SUMMARY I Radiation therapy, is using ionizing radiation to kill tumors. Lethal doses of radiation are rapidly delivered to malignant tumor cells. Because the doses are in the deterministic regime, a predictable fraction of the tumor cells die. Unfortunately, healthy tissues are also exposed to high doses, along with the tumors. Treating a cancer often involves treating an entire region surrounded by healthy tissue. This infers that a compromise is made between effectiveness in tumor killing and in sparing nearby healthy tissue. SUMMARY II Using fractions damages tumor cells and allows sufficient time to healthy tissue to recover. There are three alternative approaches for delivering ionizing radiation for therapy: beam sources external to the body. brachytherapy sources. unsealed sources. SUMMARY III Superficial (50 to 150 kV) and orthovoltage (150 to 500 kV) X rays used in radiotherapy are produced with X ray machines. Treatment machines incorporating gamma ray sources for use in external beam radiotherapy are called teletherapy machines. The most widely used teletherapy source uses 60Co radionuclides. When selecting a suitable source for teletherapy devices the following need to be considered: half-life, specific activity, decay into a more stable daughter nucleus, photon energy. REFERENCES Authors T. Pawlicki, D.J. Scanderbeg and G. Starkschall E.B. Podgorsak Title Edition Hendee’s Radiotherapy Physics 4th Edition Radiation Physics for Medical Physicists Intermediate Physics for Medicine and Biology 3rd Edition Springer 2016 9783319253824 5th Edition Springer 2015 9783319126814 1st Edition Springer 2014 9783319068404 2nd Edition CRC Press 2009 9781584889434 IAEA 2005 9201073046 R. K. Hobbie and B. J. Roth D.S. Chang, F. D. Lasley, I.J. Das, M. S. Basic Radiotherapy Physics and Mendonca and J. R. Biology Dynlacht Introduction to Physics in Suzanne Amador Kane Modern Medicine Radiation Oncology Physics: A E. B. Podgorsak handbook for teachers and students 1st Edition Publisher Year Wiley-Blackwell 2016 ISBN 9780470376515