radiotherapy
Radiation therapy (also called radiotherapy ) is the medical application of ionizing radiation to humans and animals in order to cure diseases or to delay their progression. The radiation can come from devices or from radioactive preparations. Specializations for this special application of radiation are called radiation medicine and radiation oncology .
Gamma rays , X-rays and electron beams are mainly used as rays . In recent years, facilities for treatment with neutrons , protons and heavy ions (often carbon ions) have also been built. Non-ionizing rays such as microwave and heat rays, light and UV therapy and treatment with ultrasound waves are not assigned to radiation therapy.
Radiation therapy involves the treatment of benign and malignant diseases. It is practiced by specialists in radiology or radiation therapy with the assistance of medical-technical assistants and specialized medical physicists . Their activity is subject to the country-specific legislation on radiation protection and the subordinate ordinances (see Radiation Protection Ordinance ) and standards. The actual therapy is preceded by a complex planning process - radiation planning. Extensive organizational and technical quality assurance measures ensure that irradiation errors can largely be ruled out.
According to the further education regulations valid in Germany, the field of radiation therapy also includes drug and physical procedures for radiosensitization and enhancement of the radiation effect on the tumor ( radioimmunotherapy and radiochemotherapy ), taking into account protective measures for healthy tissue.
Use against cancer
Malignant tumors are very often irradiated; often in combination with other treatment methods such as surgery and chemotherapy . About every second cancer patient receives one or more radiation therapies. Palliative irradiation, for example of bone metastases , and curative , i.e. treatment series used with the intention of healing, are roughly equally frequent . Neoadjuvant radiation therapy is designed to shrink the tumor for subsequent surgery; adjuvant radiation therapy is intended to secure the result of a previous operation and to destroy microscopic tumor nests. Oncological treatment always follows the " log cell kill " law. Radiation therapy with the intention of healing is designed in such a way that it destroys the tumor, which often consists of 100 billion cells, down to the last cell. Since individual tumor cells can no longer be detected, the actual success of the treatment only becomes apparent in the months and years afterwards. If a tumor develops again in the same place within the follow-up period, a relapse must be assumed.
The decision on treatment is based, among other things, on the question of how far the tumor to be treated is suitable for a radiotherapy intervention in its location. Not all tumors are more sensitive to radiation than the normal tissue that surrounds them. One of the reasons for a lower sensitivity to radiation is a lack of oxygen ( hypoxia ) in the tumor tissue. Thanks to a combination of fractionation and radiation technology that is optimally tailored to the tumor biology and the surrounding organs at risk, it is now also possible to successfully treat problematic localized and relatively radiation-insensitive tumors. An optimal irradiation technique here delimits the tumor region that is supplied with dose by means of the steepest possible drop in dose from normal tissue. Various therapy concepts also attempt to increase the sensitivity of tumors to radiation with the help of so-called radiosensitizers (radiation sensitizers).
The healing effect requires a total dose of 20 to 80 Gray , depending on the tumor type and fractionation , which is administered in one session or over several weeks, depending on the treatment regimen. Symptom-relieving treatments for incurable patients can be shorter; For example, bone foci can be treated to relieve pain with a single 8 Gy.
Nowadays, modern radiation therapy methods can be used in stage-dependent combination with surgery and chemotherapy to cure a large number of tumor diseases, even in advanced stages. Averaged over all tumor types and stages, the chance of recovery is approx. 50%. Individual tumors such as Hodgkin's disease and seminoma of the testicle can almost always be cured. The most common indications for radiation therapy are currently prostate cancer , adjuvant after breast cancer surgery, and for rectal cancer . A particular advantage is the fact that radiation therapy can preserve organs even in situations in which the disease is relatively advanced. The combination of radiation therapy and chemotherapy for cancer of the larynx can be mentioned here. In the case of other tumor diseases, such as prostate carcinoma, surgical procedures and radiotherapy procedures are in competition with one another and can have comparable results. Here it is the task of the consulting doctor to explain to the patient all the advantages and disadvantages of the respective procedures. In this context, it is worth striving for certified tumor centers in which all specialist disciplines are represented and which enable the patient to receive comprehensive advice.
Very rarely there can be an abscopal effect in which a tumor regression up to complete remission can also be recorded in areas that have not been irradiated. This effect was first described in 1953 and has so far only been reported in individual cases, for example in leukemia, lymphoma, renal cell carcinoma and malignant melanoma.
Use against benign diseases
Numerous chronic inflammatory and degenerative diseases such as heel spurs , tennis elbows , shoulder pain , arthrosis of the various joints , vertebral body hemangiomas , induratio penis plastica and others can be treated with radiation therapy. This so-called stimulus radiation far below the tissue-killing dose has no side effects with the exception of the stochastic risk. The response rates are 50 to 70%. The total doses used are in the range from 1 to 20 Gray and are therefore significantly lower than the doses that have to be used in the treatment of cancer (20 to 80 Gy). Low-dose radiation reduces the activity of leukocytes and precursor cells of the connective tissue and reduces the release of cytokines ; thus it inhibits acute and chronic inflammatory processes. Direct inhibition of the pain receptors is also suspected. In particular, shoulder pain and heel spurs are easily accessible to radiation therapy. In Germany around 37,000 patients with non-malignant diseases are irradiated every year, and the trend is rising.
Mechanism of action
The effect of the irradiation is based on the transfer of energy to the irradiated tissue in scattering processes . Direct hits on biomolecules that are essential for cell growth are less important than the ionization of water molecules.
The resulting free radicals are highly toxic and chemically react with cell components. The resulting damage to the genetic material of the tumor cells, especially DNA double-strand breaks, are mainly responsible for the destructive effect. Damage that exceeds the repairability of the tumor cell prevents it from multiplying ( mitosis ) or even causes it to immediately apoptosis . Since several hits must occur in close spatial and temporal proximity to be effective, the dose-effect relationship of any tissue reaction is always sigmoid (S-shaped) with a first slow, then faster increase and finally saturation. The normal tissues show somewhat less effect than the tumor, i.e. their S-curve is in the higher dose range. The optimal radiation dose achieves an average of> 90% tumor destruction with <5% severe side effects.
Fractionation
Tumor cells usually have less ability to repair DNA damage than normal cells. This difference is exploited by reducing the dose rate ( protraction , is hardly used today) or by dividing the total dose into small daily individual doses (1.8–2.5 Gy ) ( fractionation ). This reduces the number of healthy cells killed with the same dose. The maximum tolerated total dose of normal tissue (approx. 10 Gy with a small volume) can thus be increased many times over; only fractionated schemes achieve tumoricidal focal doses of up to 80 Gy. The biological effect of different fractionation schemes can be calculated using the linear-square model .
Neutron beams have no significant fractionation effect; the divided dose is just as effective as the one irradiated at one time. This is due to their very high energy output over a short distance; a single particle can cause a large number of double-strand breaks within a cell nucleus and thus exceed the cell's repair capacity. Attempts have been made to use neutron beams against tumors that are relatively insensitive to radiation, such as the prostate or the salivary glands . Charged heavy particles seem to have even better physical properties (see below).
Acceleration
Since the tumor continues to grow during the treatment and selects radio-resistant cell clones, the shorter the total treatment time (2-7 weeks), the greater the chance of recovery. This is especially true for fast-growing types of tumors, such as throat cancer. The total treatment time can be shortened by irradiating two or even three fractions per day ( acceleration ). However, this increases the side effects on normal tissue considerably.
Chemoradiotherapy
Radiation therapy and chemotherapy are mutually reinforcing. Many potentially curable tumors in patients in good general condition are therefore treated with both procedures simultaneously (simultaneously) or sequentially, which is referred to as chemoradiotherapy. For lung cancer, colon cancer, cervical cancer and tumors of the neck region, it has been shown that simultaneous radiochemotherapy is superior to other therapy variants. Important cytostatics for radiation therapists are 5-fluorouracil (5-FU) and cisplatin . However, the combined schemes are also fraught with more severe side effects.
Substances that are supposed to increase the resistance of normal tissues are called radio protectors . Amifostine is the first and so far only approved radio protector.
Hyperthermia
Tumors with poor blood circulation and low oxygen levels are usually radiation resistant. Conversely, it can be observed that such tissues are particularly sensitive to therapeutic overheating. The combination of radiation therapy with hyperthermia therefore has theoretical advantages. Smaller studies confirm better chances of recovery in various tumors, such as black skin cancer , sarcomas , and relapsed cervical cancer . However, the data are still uncertain, also because of the confusing variety of hyperthermia techniques, so that the method has not yet found general acceptance.
Teletherapy
Radiation therapy knows methods of teletherapy (from the Greek tele , 'fern'), where the radiation acts on the patient's body from outside, and brachytherapy (from the Greek brachys , 'nah', 'short'), in which the radiation source is in the or located directly on the body.
In teletherapy, the target volumes can be several tens of centimeters deep. The ionizing radiation used must therefore be highly permeable and is normally generated in accelerators in which charged particles (for example electrons, protons or carbon ions) are brought to energies of 2 MeV up to several 100 MeV. As in proton and ion therapy, the charged particles can be used directly for irradiation. In order to generate penetrating photon radiation, the high-energy electrons must be converted into X-rays. To do this, the electron beam is shot at a cooled metal plate, usually made of tungsten , and thus bremsstrahlung is triggered.
The most common are compact electron linear accelerators that are mounted on a support arm and can be rotated around the patient. They can provide electrons and hard X-rays with high energy up to 23 MeV . The reason for the use of technically more complex linear accelerators lies in the fact that, for technical reasons , conventional X-ray tubes can only generate X-rays with energies of up to a few 100 keV.
Electrons have almost the same biological effectiveness as the photons of X-rays, but a different depth dose distribution in the tissue. The dose of hard X-ray radiation deposited in the tissue asymptotically approaches zero with increasing depth. The course follows a complex function, which contains the exponential attenuation but also distance and scatter terms. Charged particles such as electrons, on the other hand, have a limited average range due to their electrical charge. Electron beams are therefore suitable for superficial target volumes that are in front of organs at risk.
The maximum dose of hard X-rays or electron beams is not on the skin surface. Its depth is energy-dependent and can range from a few millimeters to several centimeters. The cause of this dose build-up is that the actual dose contribution mainly takes place through secondary electrons , which are only triggered in the irradiated material. So the skin is better protected than with radiation with lower energy. If this is not desired, for example when treating a skin tumor , a layer of tissue-equivalent material ( bolus ) is placed on the skin and the secondary emission is triggered in this material.
Choosing the right type of radiation and energy is very important for the individual therapeutic indications.
CT-based planning
An essential prerequisite for successful radiation therapy is an adequate dose supply of the tumor mass with the least possible exposure to the surrounding normal tissue. In the past, the radiation directions and field boundaries were determined based on clinical experience with the help of X-ray images directly on the radiation device or a geometrically identical therapy simulator. Today the basis of computer-assisted is irradiation planning a computed tomography in irradiation attitude, sometimes after image fusion with MR or PET data. From this, a three-dimensional density model of the patient with the irradiation region contained is created. The tumor mass, the target volumes derived from it and the organs at risk are usually segmented manually or, more recently, semi-automatically under the responsibility of the radio-oncologist .
Then the type of radiation and the geometric arrangement of the radiation directions as well as the optimal radiation technique are selected, and an individual radiation plan is created using a mathematical model of the radiation device. The radiation properties of the irradiation device are adequately parameterized and known to the system due to complex series of measurements. Summation and needle-beam algorithms, superposition and convolution algorithms or Monte Carlo simulations are used to calculate the expected dose distribution of a specific field arrangement . For the approach of modulated irradiation techniques, modern planning systems can calculate possible field arrangements and partly angle-dependent fluence distributions from a desired dose distribution using a cost function ( inverse planning ).
The resulting three-dimensional dose distribution is assessed in relation to the dose supply in the tumor region and protection of the neighboring organs at risk.
Simulation, verification, IGRT
The radiation plan calculated by the medical physicist and selected by the doctor is transferred to the patient. To do this, the geometric reference point of the radiation plan must be placed at the anatomically correct location. This is done either on an X-ray fluoroscopy system ( therapy simulator ) with similar dimensions to the radiation device , on a specially equipped CT device or directly on the radiation device , which for this purpose must be equipped with an imaging device.
During the final irradiation, the position of the patient and the geometric reference point from the irradiation planning are reproduced with millimeter precision using spatially fixed laser lines and corresponding markings. During the first irradiation session, the setting accuracy is checked again using an imaging method available on the irradiation device by performing a quantitative comparison with the virtual reference imaging from the irradiation planning. In this way, the position of the irradiated target volume can be checked again even on the irradiation table and corrected if necessary (so-called image-guided radiotherapy , IGRT). With the "hard" therapy radiation, however, only relatively low-contrast images can be generated. For this reason, a diagnostic X-ray recording system is also integrated in some accelerators, with which the soft tissue of the environment can also be displayed with the clarity of an X-ray image. Modern devices can also generate sectional images that can be compared directly with the CT images of the simulation. Another method for position control is based on optical three-dimensional surface scanning.
In addition to checking the geometric reference point in the patient, the verification of the emitted dose distribution of a complex irradiation plan is very important. For simple conformal techniques, the irradiation time per direction of irradiation is recalculated. For modulated approaches, the dose or fluence distribution is usually determined by measurement on the radiation device.
Conformal radiation technology
The standard procedure in teletherapy today is 3-dimensional conformal radiation therapy , in which the body region to be treated is placed in the intersection of the axes of several beams that act from different directions ( isocenter ) and through individually shaped lead diaphragms or adaptation of the accelerator-side screens of the multileaf collimator (MLC) are adapted to the target contour. The fields can also be modulated with wedge filters in order to compensate for different tissue thicknesses that are irradiated. If the radiation directions of all partial fields lie on a common plane (typically a cutting plane transverse to the patient's longitudinal axis), one speaks of coplanar , otherwise of non-coplanar planning. Modern treatment plans use several volume definitions (target volume first and second order), which are irradiated with different intensities. These techniques are standardized internationally, for example in ICRU Report 50.
Intensity modulation
A further development of the CT-supported, conformal, 3D-planned radiation as tomotherapy is the intensity-modulated radiation therapy (IMRT). In the 1990s, IMRT procedures were used almost exclusively in university hospitals, but are now offered in most radiation therapy centers with linear accelerators in Germany. With IMRT, not only the field limitation but also the radiation dose within the field area is modulated. The scientific name for this is fluence modulation. IMRT allows very complex shaped, even concave target volumes and is therefore suitable for tumors in the immediate vicinity of sensitive organs at risk. An IMRT is very time consuming to calculate, execute and control. The clinical advantages of IMRT over conformal 3D planned irradiation are clear for some indications. For example, the IMRT of prostate cancer made it possible to increase the dose due to fewer side effects, which in turn improved the healing rate. In the early days, the fluence modulation was carried out by means of metallic compensating bodies ( compensators ) in the beam path with individually cast profiles for each field. This technically and time-consuming process is no longer used outside of research institutions in Germany. In the FRG the following methods are currently used to generate fluence-modulated radiation fields:
- static IMRT
- dynamic IMRT
- VMAT (volumetrically modulated arc therapy)
- Tomotherapy
In all methods, the field is formed by a multileaf collimator (MLC). The tongue-shaped metal absorbers of the MLC can be moved by stepper motors so that almost any field shape can be generated remotely. The MLCs have largely replaced the previously used, heavy, individually cast lead absorbers. With static IMRT, several differently shaped fields are emitted one after the other from each planned irradiation direction. The irradiation is interrupted after each segment (= single field from one direction). In English the term "step and shoot" is used. This process is relatively slow. With dynamic IMRT, the field shape is continuously changed with the multileaf collimator for every direction of irradiation. Dynamic IMRT is faster than static IMRT. In English the dynamic IMRT is called "sliding window".
Another method of IMRT is the V olumetric Intensity M odulated A rc T herapy (VMAT). Here, the radiation field is modulated while the radiation source is rotating around the patient; the multileaf collimator is continuously adjusted when the radiation is switched on. In addition to the field shape, the rotational speed, collimator angle and dose rate can also be varied. The method allows a high degree of modulation of the radiation. The total application time is considerably shorter than with the IMRT. In the case of linear accelerators from Varian , the process is called RapidArc.
As tomotherapy a radiological method is referred to as the beams can be directed from all sides at the location to be irradiated in which like in a computer tomograph. For this purpose, the radiation source rotates in a corresponding ring (see illustration), while the patient is moved evenly through the Thomotherapy device with the table feed. The radiation field is very narrow and is only varied in length. The therapy beam is also known as a fan beam. The desired geometric precision of the irradiation is achieved by using a computer tomograph combined with the tomotherapy device in order to regularly re-determine the exact localization of a tumor to be irradiated. The result is a highly conformal irradiation that is not inferior to the other IMRT procedures and has advantages for very long target volumes (e.g. neuro-axis). The side effects often associated with the irradiation of tumor patients should thereby be reduced. The treatment method was first used clinically in 2003. It is based on developments at the University of Wisconsin (USA). The main areas of application for tomotherapy are malignant neoplasms such as prostate cancer, lung cancer, breast cancer and head and neck cancer.
Radiosurgery
If you want an extremely short treatment time and nevertheless killing doses on the tumor, this is possible in selected cases with radiosurgery (syn. Stereotactic radiosurgery ). This method is practically only possible with smaller brain tumors. The patient's head is screwed tight with a stereotactic ring during treatment. Newer devices fix the patient painlessly with a close-fitting mask. Suitable special systems for radiosurgery are the gamma knife and fully automated linear accelerators, which are similar to industrial robots, such as Cyberknife or Novalis . The dose is 12-18 Gy.
Particle therapy
With a view to protecting the surrounding tissue, irradiation with protons or even heavier particles often results in a more favorable depth dose curve compared to photons. Systems for irradiation with protons, neutrons and heavy ions are in operation. Unfortunately, the acquisition and operating costs of such systems are much higher than with conventional electron linear accelerators , in which the electron beam or the X-rays generated with it are used.
Systems with neutron and proton sources for particle therapy are available in some large research centers, in Villigen (Switzerland) and in Germany in Berlin ( Helmholtz Center Berlin for Materials and Energy , formerly Hahn-Meitner Institute, only eye irradiation). From March 2009 to the end of 2019 there was a clinical facility for proton irradiation, the Rinecker Proton Therapy Center (RPTC), in Munich , which has since become insolvent. In Essen , around 1,000 patients have been treated at the West German Proton Therapy Center Essen (WPE) since May 2013 . In April 2014, the WPE was completely taken over by the Essen University Hospital . All 4 treatment rooms have been in operation since spring 2016. Three rooms are equipped with so-called gantries, in which the beam guidance can be rotated 360 degrees, the fourth treatment room is equipped with a horizontal beam guidance (fixed beam line) and an eye therapy station. Here tumors can be fought with the "pencil beam scanning" technology. In the future, doctors want to treat up to 1,000 patients per year there.
There are heavy ion therapy facilities in three centers in Japan ( Chiba , Gunda and Kyōto ). In Germany, patients were treated at the GSI in Darmstadt from 1997 to 2008 as part of a pilot project . The Heidelberg Ion Beam Therapy Center (HIT) at Heidelberg University Hospital went into operation in 2009. There, patients can be treated with both protons and carbon ions using the raster scanning technique. Centers for particle therapy with protons and carbon ions were under construction in Kiel and Marburg . The center in Kiel should start operations in 2012. The Rhön-Klinikum AG, as the operator of the University Hospital Gießen / Marburg, and the University Hospital Kiel said goodbye to the construction and operation of ion beam therapy systems in 2011. In September 2014, the Heidelberg University Hospital finally reached an agreement with the State of Hesse, Rhön Klinikum AG, the Universities of Marburg and Heidelberg, the Marburg University Hospital and Siemens AG on the commissioning of the particle therapy system at the Marburg location. At the Marburg Ion Beam Therapy Center (MIT), the first two patients were treated with proton beams on October 27, 2015. In Austria, carbon ion therapies have also been possible at MedAustron since 2019.
Heavy electrically charged particles, d. H. Compared to conventionally used photon radiation, heavy ions and protons show a much denser energy transfer to the irradiated tissue ( linear energy transfer LET), which is referred to as the high LET effect. As a result, the damage caused to the DNA is more severe, its repair more difficult for the cell and the therapeutic effect is greater. High-LET radiation also has other biological advantages: It is also effective in slowly growing tumors with poor blood supply and which are very resistant to conventional radiation. In the case of heavy ions, however, this effect is locally limited and can be adapted to the tumor, while in the case of neutrons it appears over the entire length of the particle path, i.e. undesirably also affects the healthy tissue in front of the tumor. In the case of neutrons, the beam boundary is also blurred with increasing depth, and there is an exponential decrease in the radiation dose. Because of this depth course of the dose, the dose in healthy tissue in front of the tumor is higher than in the tumor itself. After neutron radiation, increased rates of side effects have been described.
In contrast to neutrons, heavy ions and protons have a defined, sharply limited range so that tissue behind the tumor to be irradiated can be completely spared. At first they give their energy to the matter only slightly and only after almost complete deceleration in a concentrated manner (so-called Bragg peak ); this makes it possible to protect tissue located in front of the tumor through a suitable choice of ion energy (see also particle radiation ). Proton and heavy ion radiation is indicated for tumors in which conventional radiation therapy does not achieve satisfactory results. Clinical studies are currently investigating which cancer patients will benefit from this therapy. Proton irradiation is indicated for tumors that are complicatedly localized, i.e. close to radiation-sensitive normal tissue. The use of heavy ions is advisable if the tumor is also comparatively resistant to conventional radiation. Heavy ions combine the advantages of higher biological effectiveness and greater physical selectivity with a simultaneously low rate of side effects.
Proton and heavy ion therapy is currently reserved for selected cancers, including, for example, chordomas and chondrosarcomas of the base of the skull and pelvis, (adenoid cystic) salivary gland carcinomas, prostate carcinomas and the like. a.
Brachytherapy
Modern brachytherapy procedures include afterloading procedures and implantations. Afterloading is the name of a process in which a small radioactive source of radiation (Ir-192) is remote-controlled into a body opening and removed again after a calculated time ( decorporation ). This method allows, on the one hand, direct irradiation, for example of the uterus, and, on the other hand, the best possible radiation protection for the treating staff. Compared to the older radium emitters, however, Iridium-192 has the radiobiological disadvantage of the high dose rate, which can only be compensated to a limited extent by fractionating the radiation. The dose interval between desired and undesired effects is smaller than with radium. Afterloading is particularly suitable for female abdominal tumors. There are numerous delivery systems for other target organs such as the trachea and esophagus; Hollow needles for spiking solid tissue ( interstitial afterloading ) are also available. Afterloading therapy is carried out in radiation protection structures similar to those used for teletherapy. Close cooperation with gynecologists, internists and surgeons is essential for the success of the technically complex method.
In implantation procedures, small, encapsulated radiation sources ( seeds ) with a short half-life are brought into the body and remain there permanently while their activity subsides. A typical application is seed implantation of the prostate with iodine -125. I-125 decays through electron capture to tellurium -125 with a half-life of 59.4 days . This releases gamma rays with an energy of 23 to 27 KeV, which are mainly absorbed in the immediate vicinity of the seeds and are hardly measurable on the body surface. There is therefore no need for a special operating room or quarantine.
Also, the radiation synovectomy is a form of brachytherapy (very small distance between the radiation source and the target tissue).
Therapy with radionuclides
In principle, open radionuclides fall into the field of nuclear medicine , which has extensive experience with radioiodine therapy and similar methods of radionuclide therapy . However, individual substances also complement the spectrum of therapies in the hands of the radiation therapist; For example, an injection of radioactive strontium-89 is effective against the pain of advanced bone metastasis. The approach of coupling tumor-specific antibodies with radioactive substances that emit beta radiation at close range ( radioimmunotherapy ) has not yet been conclusively assessed . However, the use of radiolabelled ibritumomab (monoclonal chimeric antibody against CD20) with an yttrium isotope ( ibritumomab-tiuxetan ) has already found its way into clinical practice.
In the meantime, the radiosynoviorthesis has also found wide application as a form of radiation therapy in nuclear medicine.
Aftercare
Radiation therapists are obliged to find out about the effects and side effects after completing radiation therapy. Usually the patient is called for follow-up visits, about six weeks and again after a year. In principle, the radiation therapist should follow up the patient for several years because of the side effects that often occur late.
Regardless of this, routine follow-up examinations at the family doctor, gynecologist, etc. are recommended after treatment for cancer.
History of radiation therapy
On December 28, 1895, Wilhelm Conrad Röntgen sent the first of his three communications about a new type of radiation . The medical profession was enthusiastic about the discovery; As recently as 1896, hundreds of X-ray machines were in operation across Europe and the United States. The first manufacturer to take up Röntgen's idea, the Erlangen-based Verein Physikalisch-Mechanischen Werkstätten Reiniger, Gebbert & Schall, merged with the Siemens group in 1925 . In the USA, General Electric became the largest relevant manufacturer.
It was quickly recognized that the rays cause skin inflammation and hair loss. It was only in the following years that users became aware of the serious radiation damage, including the death of many X-ray doctors. It was not until 1904 that the Boston dentist William Herbert Rollins wrote the world's first book on radiation effects. At first one was pleased with the effect and tried to use it therapeutically.
On March 6, 1897, the Austrian Leopold Freund published an article in the Wiener Medizinische Wochenschrift with the title An X-Ray Treated Case of Nevus pigmentosus piliferus (animal skin birthmark ). The treatment of a five-year-old girl was the first described case in which X-rays were used for healing purposes. In 1903 Freund published the first textbook on radiation therapy: Outline of the entire radiotherapy for general practitioners . Important pioneers in radiation therapy were Friedrich Dessauer and Hans Holfelder .
In addition to diagnostic devices, the engineers soon developed special therapy tubes and generators. An important milestone was the high-performance tube invented by William David Coolidge . In 1925, a system was presented in Erlangen that made it possible to pivot the X-ray tube around the patient and irradiate the target from several directions. This so-called "cross fire irradiation" was the forerunner of modern conformal therapy. After the Second World War , radioactive emitters with higher power and maximum energy replaced almost all therapy tubes. X-rays are occasionally used only for the treatment of superficial skin tumors ( boundary radiation and soft radiation devices ).
Almost simultaneously with the development of X-ray emitters, the discovery and technical use of natural radioactivity went hand in hand, building on the discovery of radium by Marie and Pierre Curie in 1898. The radiation emitted by radium is much more energetic than X-rays. The gamma rays can penetrate very deeply into the body. Radium can also be manufactured and packaged industrially. The radium emitters do not require a power source and disintegrate extremely slowly. They are particularly suitable for brachytherapy in body cavities. Many clinics therefore set up radiation therapy units based on the model of Radiumhemmet, founded in Stockholm in 1910 ( Stockholm method ), preferably within gynecology . In 1949 a demonstration film presented the “Göttingen Method” developed at the Göttingen University Women's Clinic, a small-area irradiation with radium in the “Siemens body cavity tube”. It is considered to be one of the forerunners of today's afterloading .
In 1941, under the direction of Enrico Fermi, the world's first nuclear reactor became critical and independently maintained a chain reaction. In these reactors it is possible to produce artificial radionuclides which have more suitable physical properties than radium, above all a higher dose rate per unit of mass. In teletherapy, the X-ray tubes were replaced everywhere by radiation cannons with sources made of radioactive cobalt -60 or cesium -137. Because of the associated radiation protection problems, the first attempts to modify electrically operated particle accelerators for therapy were made as early as 1954, starting with a large Van de Graaff accelerator in Berkeley, and later mainly with movable betatrons . However, these systems were very expensive and complex with a low dose rate, so that the Telecurie devices (so-called cobalt cannons ) continued to be used in most clinics. Despite strict radiation protection regulations for acquisition, use and disposal, serious accidents have occurred in the past due to the illegal disposal of disused radiation sources. Because of their superior technical properties and in view of such risks, the linear accelerators, which had been available since around 1970, finally replaced the cobalt and cesium emitters in routine therapy. In Germany, the last cobalt cannons went out of service in the early 2000s. In contrast to the X-ray and telecuri systems in Germany, linear accelerators may only be used in the presence of a medical physicist, who is also responsible for technical quality control. The dose effectively delivered to the patient is subject to many influences and possible errors, so that serious accidents such as the Therac-25 error in 1986 can only be prevented in the future by meticulous monitoring of the machine . New procedures such as IMRT result in additional risks, which are based on their complexity and lack of illustration.
Radium continued to be used in brachytherapy for a long time. The roughly bean-sized radium cartridges had to be inserted by hand, removed and cleaned after 1 to 2 days. Because of the high radiation exposure of the staff and the risk of accidental contamination, the European radium stations were gradually replaced by afterloading systems, which are equipped with the artificial and intensely radiating isotope Iridium -192.
Clarification of facts against fear
The German Cancer Aid is countering the continuing fear of radiation therapy with the free information series Die Blauen Ratgeber . This also includes the first DVD on radiation therapy . The patient information film from the series "The Blue DVD" is distributed free of charge by the German Cancer Aid and also explains that radiation therapy is a standard in modern cancer treatment.
In addition, the Cancer Information Service (KID) of the German Cancer Research Center (DKFZ) provides a great deal of information on the subject of cancer and cancer therapies on its website, by telephone or via e-mail, including detailed information on "Radiation Therapy and Nuclear Medicine".
Side effects of radiation treatment
Early reactions on normal tissue
Some side effects ( early reactions ) occur depending on the dose, depth of penetration and the number of single doses applied: reddening of the skin in the radiation field and inflammation of the mucous membranes in the oropharynx or esophagus when the head and neck region is irradiated. Feeling of fullness, nausea or diarrhea as well as bladder problems occur with radiation in the abdomen. Hair loss is only to be expected if the head is irradiated.
Side reactions are generally related to so-called risk organs . Every organ at risk has its own tolerance dose (in gray), from which side effects are to be expected. These tolerance doses must not be exceeded. These tolerance doses result from the tissue's sensitivity to radiation , as well as its ability to regenerate, and whether the entire organ or only part of it is irradiated. Serially structured organs such as the small intestine are particularly critical because the failure of a small sub-segment endangers the function of the entire organ. Tissues with a strictly hierarchical structure that constantly regenerate from a small population of divisible stem cells , such as the mucous membrane or bone marrow, are also extremely sensitive . The early damage is quantified according to the globally valid CTC classification ( common toxicity criteria ).
Late reactions
Delayed reactions after more than three months are based on vasoconstriction and fibrosis (scarring) in the connective tissue . Discoloration of the skin, hardening of the subcutaneous fatty tissue , dry mouth (xerostomia) due to damage to the salivary glands , loss of taste, bone and tooth damage, pulmonary fibrosis , and others are common. With radiation in the pelvic area, infertility is to be expected. Long-term effects are classified in the severity grades 0-5 of the LENT-SOMA classification ( late effects on normal tissues, in subjective, objective, management and analytic categories ). In order to reduce radiation damage to the oral mucosa may Radiation Protection rails are used.
The risk of coronary artery disease is significantly increased after radiation therapy as part of the therapy of breast cancer , depending on the approximate total organ dose acting on the heart by about 7.4% per gray . The risk increases continuously from five years to over twenty years, without a threshold value and regardless of other cardiological risk factors.
Cumulative Consequences
While the early radiation reactions regress completely, the late reactions remain lifelong. Pre-irradiated organs are very sensitive and tend to have serious side effects up to radiation necrosis or, in the case of the skeletal system, osteoradionecrosis , if the dose is continued . Radiation therapy rules of thumb allow a few years after a treatment to be repeated with a reduced dose.
Stochastic radiation damage
Stochastic radiation risks do not necessarily occur and have no dose-effect relationship, but a dose-dependent probability of occurrence. In contrast to the non-stochastic side effects, there is no lower threshold value. Stochastic risks are the induction of malignant tumors and germ cell damage with the risk of malformations in future generations. Naturally, these risks are largely age and condition-dependent. They are tabulated in the publications of the ICRP and UNSCEAR . Cancer induction within 10 years after radiation therapy is estimated to be up to 2% (depending on the region and volume); It must be taken into account that chemotherapies also have carcinogenic potential and that the cancer itself increases the statistical risk of further cancer. The risk of germline damage is around 1.4% in the first generation of children, 0.7% in the second, and 0.7% cumulatively in all subsequent generations. Synergistic mutagenic effects of the cytostatics can be assumed here. Men are advised to abstain from conception in the first year after radiation therapy.
Radiotherapy specialist
As a result of the technical and procedural advancement in the field of radiation therapy, it was outsourced from the field of radiology and a new specialist was created, under protection of the existing doctors for radiology. The model further training regulations of the German Medical Association serve as a template for the legally binding state regulations. The current MWBO (last revised in 2003) requires a five-year period of further training in departments authorized for further training in accordance with Section 5, of which one year in ward duty must be completed, 6 months of which in any area , for recognition as a specialist in radiation therapy. Previously, one year was required in diagnostic radiology; this is still creditable on a voluntary basis. The pure time in radiation therapy is therefore 3 to 4 years.
As of December 31, 2008, there were 1054 radiation therapists registered in Germany, 260 of whom were resident. 121 did not exercise any medical activity. The DEGRO (German Society for Radiation Oncology ) is your national specialist society. Relevant standards and research are organized by the Working Group for Radiation Oncology in the DKG . International specialist associations for radiation therapists are ESTRO and EORTC .
Radiotherapy in veterinary medicine
In veterinary medicine , radiation therapy can be used as well as in humans, yet here she plays only a minor role. The main reason is the lack of availability of appropriate facilities. The use of human medical centers for radiation therapy is limited by their high degree of utilization. Another aspect is the associated costs for the pet owner, which must be weighed against the limited survival time. In addition, the patients must be placed under a short-term anesthetic to ensure proper positioning. Curative (healing) and palliative (soothing) tumor irradiation are therefore mostly used where a surgical tumor resection is difficult for cosmetic and anatomical reasons, such as on the head and limbs. In addition, radioiodine therapy is also used, especially for the overactive thyroid in cats .
The most common indications are malignant skin tumors such as carcinomas , soft tissue sarcomas and mast cell tumors . Here, radiation therapy is mainly carried out after surgical removal to avoid recurrences. Due to the cosmetic-surgical limitations, radiation therapy is also carried out for tumors of the oral and nasal cavities such as squamous cell carcinoma , malignant melanoma , fibrosarcoma and gum swelling ( acanthomatous epulides ). For tumors in the central nervous system ( gliomas , meningiomas, and adenomas of the pituitary gland ), radiation therapy is the treatment of choice. In the case of osteosarcomas of the limbs, on the other hand, amputation with subsequent chemotherapy is preferred; radiation therapy can be used here palliatively if the owner of the animal refuses to amputate. Malignant lymphomas are mostly widely scattered in the animal and whole-body irradiation is hardly justifiable, so that here at best individual foci are irradiated, usually combined with chemotherapy.
See also
- Radiation dose / dosimetry
- Radiation protection / radiation damage / history of radiation protection
- Radiation exposure / radiation resistance / radiation sickness
literature
- M. Bamberg, M. Molls, H. Sack (Hrsg.): Radiooncology 1 - Basics . 2nd Edition. Zuckschwerdt Verlag, Munich 2009, ISBN 978-3-88603-946-3 .
- M. Bamberg, M. Molls, H. Sack (Ed.): Radiation oncology 2 - clinic . 2nd Edition. Zuckschwerdt Verlag, Munich 2009, ISBN 978-3-88603-953-1 .
- Michael Wannenmacher, Jürgen Debus, Frederik Wenz (Eds.): Radiotherapy . Springer, Berlin 2006, ISBN 3-540-22812-8 (textbook).
- Rolf Sauer: Radiation Therapy and Oncology . Urban & Fischer at Elsevier, 2002, ISBN 3-437-47500-2 (textbook).
- Alain Gerbaulet u. a. (Ed.): The GEC / ESTRO Handbook of Brachytherapy . Arnold Australia 2003. ISBN 0-340-80659-1 , full text (instruction and manual, English).
- Carlos A. Perez, Luther W. Brady, Edward C. Halperin (Eds.): Principles and Practice of Radiation Oncology . Lippincott, New York 2003, ISBN 0-7817-3525-4 ; Textbook (English).
- Jane Dobbs, Ann Barrett, Dan Ash: Practical Radiotherapy Planning . Hodder Arnold, 1999, ISBN 0-340-70631-7 ; Textbook on teletherapy treatment planning (English).
- Barbara Kaser-Hotz, Bettina Kandel: Radiotherapy . In: Suter, Kohn (ed.): Internship at the dog clinic . 10th edition. Paul Parey Verlag, 2006, ISBN 3-8304-4141-X , pp. 1115-1118.
- Eckart Richter, Thomas Feyerabend: Basics of radiation therapy . 2nd Edition. Springer, Berlin 2002. ISBN 3-540-41265-4 .
- Boris Peter Selby, Stefan Walter, Georgios Sakas, Uwe Stilla : Automatic Geometry Calibration of X-Ray Equipment for Image Guided Radiotherapy. In: Particle Therapy Co-Operative Group (PTCOG) Proceedings. Jacksonville, Vol. 47, 2008, p. 119.
Web links
- German Society for Radiation Oncology
- German Society for Medical Physics
- European Society for Therapeutic Radiology and Oncology
- Proton therapy at the Paul Scherrer Institute
- Biophysics at the GSI Helmholtz Center for Heavy Ion Research
- Heidelberg Ion Beam Therapy Center (HIT)
- Marburg Ion Beam Therapy Center (MIT)
- Biological dose equivalent calculator
- Brochure for radiation therapy patients, their relatives and anyone interested
Individual evidence
- ↑ https://en.wikibooks.org/wiki/Radiation_Oncology/Toxicity/RTOG , list of clinical RTOG studies with the associated dose limits for the organs at risk, Wikibooks, accessed on June 2, 2020
- ↑ https://en.wikibooks.org/wiki/Radiation_Oncology/Toxicity/QUANTEC , Summary of Clinically Relevant Organ Tolerances, Wikibooks, accessed on June 2, 2020
- ↑ LB Harrison, M. Chadha, RJ Hill, K. Hu, D. Shasha: Impact of tumor hypoxia and anemia on radiation therapy outcomes. In: The oncologist Volume 7, Number 6, 2002, pp. 492-508, ISSN 1083-7159 . PMID 12490737 . (Review).
- ^ W. Rhomberg, J. Dunst: Radiosensitizer. In: HJ Schmoll, K. Höffken, K. Possinger (Eds.): Compendium of internal oncology standards in diagnostics and therapy. Springer, 2005, ISBN 3-540-20657-4 , p. 619. limited preview in Google book search
- ↑ Ryan J. Sullivan, Donald P. Lawrence, Jennifer A. Wargo, Kevin S. Oh, R. Gilberto Gonzalez, Adriano Piris: Case 21-2013 - A 68-Year-Old Man with Metastatic Melanoma The New England Journal of Medicine 2013, Volume 369, Issue 2 of July 11, 2013, pages 173-183; doi: 10.1056 / NEJMcpc1302332
- ↑ Köhler: Radiation therapy for benign diseases. ( Memento of the original from August 10, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 228 kB) 2007
- ↑ Patricia J Eifel: Concurrent chemotherapy and radiation therapy as the standard of care for cervical cancer . In: Nature Clinical Practice Oncology . tape 3 , no. 5 , 2006, ISSN 1759-4782 , p. 248-255 , doi : 10.1038 / ncponc0486 ( nature.com [accessed April 2, 2018]).
- ↑ Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials . In: Journal of Clinical Oncology . tape 26 , no. 35 , December 10, 2008, ISSN 0732-183X , p. 5802–5812 , doi : 10.1200 / jco.2008.16.4368 ( ascopubs.org [accessed April 2, 2018]).
- ↑ D. Citrin, AP Cotrim, F. Hyodo, BJ Baum, MC Krishna, JB Mitchell: Radioprotectors and mitigators of radiation-induced normal tissue injury. In: The Oncologist Volume 15, Number 4, 2010, pp. 360-371, ISSN 1549-490X . doi: 10.1634 / theoncologist.2009-S104 . PMID 20413641 . PMC 3076305 (free full text). (Review)
- ↑ JR Kouvaris, VE Kouloulias, LJ Vlahos: Amifostine: the first selective-target and broad-spectrum radio protector. In: The oncologist Volume 12, Number 6, June 2007, pp. 738-747, ISSN 1083-7159 . doi: 10.1634 / theoncologist.12-6-738 . PMID 17602063 . (Review)
- ↑ MJ Zelefsky, Y. Yamada, Z Fuks and others: Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. International Journal of Radiation Oncology, Biology and Physics. 2008, Volume 71, pp. 1028-1033
- ↑ DGMP , DEGRO : Guideline on radiation therapy with fluence-modulated fields (IMRT). Version 2018: online only
- ↑ Karl Ruprechts University Heidelberg IKR Radiation Therapy Section: VMAT (Volumetric Intensity Modulated Arc Therapy)
- ^ West German Proton Therapy Center Essen | 500th patient. In: www.wpe-uk.de. Retrieved October 26, 2016 .
- ↑ Press release: Essen University Hospital takes over West German proton therapy center completely.
- ^ West German Proton Therapy Center Essen | Fourth treatment room opened - Essen facility is now the largest proton therapy center at a university hospital in Germany. In: www.wpe-uk.de. Retrieved October 26, 2016 .
- ↑ Westdeutsche Allgemeine Zeitung (WAZ) of April 29, 2014: The difficult history of a radiation clinic
- ↑ J. Dunst, R. Kampf: University Hospital Schleswig-Holstein, Campus Kiel: Particle Therapy Center from 2012. ( Memento of the original from March 12, 2014 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 212 kB) In: Schleswig-Holsteinisches Ärzteblatt. 10, 2008, pp. 63-68.
- ↑ Press release from the Philipps University of Marburg: "Marburg Ion Beam Therapy Center: The first patients are to be irradiated in autumn 2015" from October 23, 2014
- ↑ Press release from Heidelberg University Hospital of October 27, 2015.
- ↑ A Gerbaulet, R Pötter, JJ Mazeron, H Meertens, EV Limbergen (editor): The GEC ESTRO Handbook of Brachytherapy. ACCO-Verlag, Leuven Belgium 2002, ISBN 90-804532-6
- ↑ Sarah C. Darby, Marianne Ewertz, Paul McGale, Anna M. Bennet, Ulla Blom-Goldman, Dorthe Brønnum, Candace Correa, David Cutter, Giovanna Gagliardi, Bruna Gigante, Maj-Britt Jensen, Andrew Nisbet, Richard Peto, Kazem Rahimi , Carolyn Taylor, Per Hall: Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer . New England Journal of Medicine 2013, Volume 368, Issue 11 March 14, 2013, pages 987-998, doi: 10.1056 / NEJMoa1209825
- ↑ Doctors by designation and medical field of activity. (PDF) Table of the German Medical Association, 2008
- ^ D Hirschfeld et al .: Radiation Therapy in Small Animal Medicine . (PDF; 29 kB) In: Praktischer Tierarzt , 82, 2001, pp. 1, 16–21
