With the strong support of computer technology, radiation physics, radiation biology, molecular biology, imaging and functional imaging, as well as the organic combination of multi-edge disciplines, radiotherapy technology has made revolutionary progress. According to WHO statistics at the end of 1998, 45% of tumor patients can be cured, of which 22% are cured by surgery, 18% by radiotherapy and 5% by chemotherapy. Radiotherapy also has the advantage of preserving organ function and beauty. Three-dimensional stereotactic radiotherapy technology will further strengthen this advantage. In recent ten years, China's three-dimensional stereotactic radiotherapy technology has developed very rapidly, from ordinary radiotherapy to three-dimensional high-precision stereotactic radiotherapy. Three-dimensional stereotactic combination, additional beam limiting device and posture fixing device have been adopted, so that the dose gradient at the edge of the target area has dropped sharply and a sharp "knife" shape has been formed between gross tumor volume and normal tissues at the edge. Its purpose is to give high-dose irradiation in the target area and protect normal tissues and important sensitive organs around the target area from damage.
〔Three dimensional conformal RT (3D-CRT)
The growth mode and location of tumor are complex, and the irradiation field of radiotherapy should include all tumor tissues, lymphatic drainage areas and a certain range of peripheral edges, also known as safe edges. In order to meet the requirements of keeping the radiation volume consistent with the target volume and avoiding unnecessary irradiation on normal tissues, the shapes of most irradiation fields are irregular. In the past clinical radiotherapy practice, low melting point lead block technology was generally used to implement radiotherapy of irregular irradiation fields. In the 194s, under the guidance of two-dimensional radiotherapy plan, some people used semi-automatic primitive multi-leaf grating (MLC) technology or low melting point lead block to implement the most primitive conformal radiotherapy with multiple irregular irradiation fields. This technology has been used in clinic for half a century. Due to the progress of computer technology, radiation physicists use more advanced multi-leaf grating instead of hand-made lead block to achieve the purpose of shaping rays. The computer controls the shaping of multi-leaf grating, and can adjust the shape of irradiation field according to the shape of target volume at different viewing angles when the accelerator frame rotates, making it completely automatic. The conformal radiotherapy technology is improved to a new level. In recent years, the computer processing of image diagnosis images has enabled the three-dimensional reconstruction of radiotherapy target and adjacent important tissues and organs in human body, thus realizing three-dimensional conformal radiotherapy under the guidance of three-dimensional radiotherapy plan in clinic. At present, it has been used by more and more hospitals and cancer treatment centers in the world for clinical practice of radiation tumor, and it has been gradually incorporated into routine application.
It is more complicated to realize the positioning technology of three-dimensional conformal radiotherapy for trunk tumors. Compared with radiotherapy technology for head and neck tumors, the physiological movement of chest and abdomen affects the accuracy of three-dimensional reconstruction of images and radiotherapy planning. In addition, the trunk tumors are larger and the treatment volume is larger. Furthermore, the volume and shape of radiotherapy target for trunk tumors are generally irregular. Therefore, the requirements of three-dimensional conformal radiotherapy for trunk tumors are relatively high. Report ICRU5 gives a detailed description of the standardization of tumor volume, clinical target volume, planned target volume and treatment prescription. Broadly speaking, radiotherapy based on three-dimensional image reconstruction and guided by three-dimensional treatment plan should be called three-dimensional conformal radiotherapy. However, the three-dimensional conformal radiotherapy of head tumor by using stereotactic radiosurgery (SRS) is different from that of trunk tumor in terms of equipment and accessories, and there are also some differences in operation technology. In many literature reports, the three-dimensional conformal radiotherapy of head tumor by using SRS system is generally called 〔Stereotactic radiotherapy (SRT〕), while the radiotherapy of trunk tumor by using body fixator, MLC or low melting point lead block is called three-dimensional conformal radiotherapy. In fact, SRS, FSRT, SRT, 3D-CRT and stereotactic brachytherapy (STB〕) all belong to the category of stereotactic brachytherapy. The implementation of three-dimensional conformal radiotherapy mainly depends on the following four aspects of technical support: < P > [1] Multi-leaf grating system MLC, which has many types, including manual, semi-automatic and automatic. The size and number of its leaves are also different. The purpose of MLC system is to replace the lead block; Simplify the shaping process of irregular irradiation fields, thus increasing the number of irradiation fields to improve the shielding of normal organ structures; The static irradiation field and single frame angle of multi-leaf grating can be used to adjust the flatness of wire harness. The blades can move when the gantry rotates to adapt to the dynamic adjustment of irregular tumor shape.
[2] Three-dimensional radiotherapy planning system, its main feature is the treatment display based on three-dimensional reconstruction of CT images. For example, 〔Beameye view (BEV〕) function can display the coincidence degree between the shape of irradiation field and the shape of tumor and the shielding of adjacent key structures at any incident angle of rays, which is the key function to realize conformal irradiation. The function of 〔Room-view (RV) can display the treatment in any position in the treatment room. This function makes up for the deficiency of BEV from the perspective of the beam, especially when setting the isocenter depth of the ray, it can display multiple beams at the same time, so that the treatment technology can be properly adjusted geometrically. The function of 〔Dose-volume histogram (DVH〕) can show the rationality of the treatment plan, and the isodose curve includes the treatment volume state and the evaluation of the whole plan.
[3] The computer-controlled radiotherapy machine, the new generation linear accelerator, some high-gear cobalt 6 therapeutic machines and afterloading therapeutic machines are controlled by computers.
[4] Positioning, fixing and verifying the system mainly include a body fixing frame, a head and neck fixing frame, a thermoplastic mask, a vacuum pad and a device for limiting visceral activity for increasing the accuracy of repeated positioning; Confirmed images of the irradiation field and some verification equipment. Although the clinical application of three-dimensional conformal radiotherapy technology has obtained the uniform distribution of high-dose rays in the target area, at the same time, it has minimized the irradiation to normal tissues; Theoretically, it can greatly improve the local control rate of tumor, but an important problem encountered in clinical practice is: how to determine the range of treatment volume? The understanding and determination of the edge of the treatment volume depends to a great extent on the imaging technology and the operator's level of image reading, so in three-dimensional conformal radiotherapy, the accuracy of the determination of the treatment volume is closely related to the understanding of the tumor range. Obviously, modern imaging diagnosis technology plays a vital role in the implementation of three-dimensional conformal radiotherapy.
Intensity modulated radiotherapy (IMRT)
Intensity modulated radiotherapy (IMRT) is the abbreviation of three-dimensional conformal intensity modulated radiotherapy, which has the following advantages compared with conventional radiotherapy:
[1] accurate posture fixation and stereotactic techniques are adopted; The positioning accuracy, positioning accuracy and irradiation accuracy of radiotherapy are improved.
[2] An accurate treatment plan is adopted: 〔Inverse Planning〕, that is, the doctor first determines the maximum optimized plan result, including the irradiation dose of the target area and the tolerance dose of sensitive tissues around the target area, and then the computer gives the method and parameters to realize the result, thus realizing the automatic optimal optimization of the treatment plan.
[3] Precise irradiation is adopted: the weight of each beam in the radiation field can be optimized, so that the distribution of high-dose areas in three dimensions can realize outdoor irradiation and Xiao Ye's supplementary dose irradiation (SIB〕) in one plan. IMRT can meet the "four most" wishes of radiotherapy doctors, namely, the maximum radiation dose of the target area, the minimum radiation dose of normal tissues around the target area, the most accurate positioning and irradiation of the target area and the most uniform dose distribution of the target area. The clinical results are: obviously improving the local control rate of tumors and reducing the radiation damage of normal tissues.
the main implementation methods of p>IMRT include:
[1] two-dimensional physical compensator intensity modulation,
[2] multi-leaf collimator static intensity modulation [step &; Shoot〕,
[3] multi-leaf collimator dynamic intensity-modulated (〔Sliding Window〕),
[4] intensity-modulated radiotherapy for fault,
[5] intensity-modulated radiotherapy for electromagnetic scanning, etc.
At present, the electric multi-leaf grating intensity modulation technology is widely used in clinic. The study of IMRT in the treatment of tumors in head and neck, brain, chest, abdomen, pelvic cavity and breast has reached positive conclusions. Zelefsky et al. used IMRT and 3D-CRT to treat patients with prostate cancer, respectively. Under the condition of the same prescription dose [〔81Gy〕], IMRT was obviously better than 3D-CRT in target dose distribution. The incidence of early and late radiation injury to rectal cancer in IMRT group was also significantly lower than that in 3D-CRT group. Using IMRT to treat head and neck tumors can not only better protect parotid gland and brain stem, but also further improve the curative effect if using Xiao Ye Supplementary Dose (〔SIB〕) technology. Using IMRT technology for radiotherapy after breast-conserving surgery for breast cancer can improve the dose distribution in the target area and protect the lung and heart better. Many units in China have used IMRT technology to treat nasopharyngeal carcinoma, breast cancer, esophageal cancer and lung cancer, and all of them have positive preliminary conclusions. Undoubtedly, IMRT will become the mainstream of radiotherapy in the future.
〔Imaging Guided RT (igrt)
increasing the target dose of radiotherapy is the key to improve the local control rate of tumor. because the spatial position of tumor and surrounding normal tissues is constantly changing during treatment and during treatment, if we do not pay enough attention to these changes and errors, it may lead to tumor off-target and/or normal tissue damage, which may reduce the curative effect. The influencing factors of position uncertainty in radiotherapy are mainly summarized in two aspects: first, the integration error of irradiation field position, which refers to the error of data transmission in the image positioning, planning and treatment stages and the position error of design, marking or treatment AIDS such as compensators and stops; The second is the random error of irradiation field position: it refers to the position difference caused by the technician's posture during each treatment and the change of the patient's anatomical position during different treatments, such as respiratory movement, bladder filling, small intestine peristalsis, pleural effusion and tumor enlargement or contraction. Clinical practice and experimental research have confirmed that the above errors will have a significant impact on the dose distribution of normal tissues around gross tumor volume, especially in conformal and intensity modulated radiotherapy. In recent years, electronic portal imaging system (〔EPID〕), CT and other equipment have been able to study the uncertainty of the target area more accurately, including the verification of position and dose, and correct it by off-line and on-line methods. The new EPID is installed on the accelerator, which can be used to calculate and verify the dose distribution while verifying the position. At present, there are CT- electron linear accelerator and respiratory control systems, such as combining the therapeutic machine with imaging equipment, collecting relevant imaging information during daily treatment, and determining the treatment target area to achieve one target per day, which is called imaging-guided radiotherapy [〔IGRT〕].
Biologically conformal radiotherapy (BCRT)
In the traditional concept, the irradiation field in the external irradiation plan should completely cover the gross tumor volume marked by anatomical images CT and MRI, and be irradiated with uniform dose. For example, due to the limitation of traditional imaging technology, we can't fully show the difference between cancer tissue and normal prostate tissue, but bring the whole prostate into the target area, which is inconsistent with the theory of radiotherapy. More importantly, the distribution of cancer cells in the tumor target volume is uneven, and the radiosensitivity of different cancer cell nuclei is very different due to the difference of blood supply and cell heterogeneity. If the whole target volume is irradiated with uniform dose, some cancer cells may survive due to insufficient dose and become the source of recurrence and metastasis. If the dose of the whole target area is too high, it will cause serious damage to the surrounding sensitive tissues. In addition, the dose response and tolerance of normal tissue structures in and around the target area are different; Even with the same structure, the tolerance of its substructure may be different, which is bound to have an impact on the expected goal of radiotherapy.
according to the theory of biological target area (〔BTV〕), biological target area can be defined as the area with different radiosensitivity in the treatment target area determined by a series of tumor biological factors. These biological factors include: < P > [1] hypoxia and blood supply;
[2] proliferation, apoptosis and cell cycle regulation;
[3] changes in oncogenes and tumor suppressor genes;
[4] infiltration and transfer characteristics, etc. These factors include the sensitivity difference between tumor cells and normal tissues in gross tumor volume, and these biological targets can be displayed by modern advanced comprehensive imaging technology, which lays a solid foundation for conformal radiotherapy and expands a broad space. For example, 〔Magnetic resonance spectroscopy (MRS〕), positron emission tomography (Positron emission tomography), PET), single photon emission computed tomography (SPECT) and other images are fused with X-ray, CT and other images, which mainly reflect the changes of morphological anatomical structure and belong to the category of anatomical images. These image fusion technologies are applied to radiotherapy planning system and become the basis of biological conformal treatment planning. In recent years, functional imaging technologies such as PET, SPECT and MRS have developed rapidly. FDG-PET can reflect the metabolism of tissues. Tumor hypoxia can be detected in vitro by hypoxia imaging agent such as fluoronitroimidazole [〔18-FMISO〕]. Protein metabolism of tumor can be detected by 11C- methionine. The metabolism of tumor nucleic acid can be detected by 18F- thymidine. Studies have shown that the application of PET can change the radiotherapy scheme of at least 3% tumors. Moreover, with the application of CT-PET, the performance and quality of images have been greatly improved. The application of functional magnetic resonance imaging (fMRI) technology is also exciting. fmri can display brain function and reflect the state of oxygen supply and angiogenesis, thus providing important information for brain surgery and brain radiotherapy, and protecting important functional areas of the brain to the greatest extent. Using special pulse echo dynamic imaging technology, we can scan tissue blood perfusion and blood-brain barrier permeability, not only distinguish normal and tumor tissues, but also evaluate tumor types and grades, and predict and evaluate curative effect.
At present, the development of IMRT makes the physical conformal of radiation therapy dose distribution reach a quite ideal level, while biological and functional imaging has opened a new era of biological conformal. Multidimensional conformal therapy with close combination of physical conformal and biological conformal will surely become the development direction of tumor radiotherapy in the new century. Chao et al. used Cu-ATSM as a tracer for PET hypoxia.