Three-dimensional conformal radiotherapy
The growth mode and location of tumor are complex, and the irradiation field of radiotherapy should include all tumor tissues, lymphatic drainage area and a certain range of peripheral edge, also known as safe edge. In order to meet the requirement of keeping the irradiation volume consistent with the target volume and avoid 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 usually used to implement the radiotherapy of irregular irradiation field. In the 1940s, 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 realize the most primitive conformal radiotherapy for 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 gratings instead of hand-made lead blocks to shape rays. Computer-controlled multi-leaf grating shaping can adjust the shape of the irradiation field according to the shape of the target 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 makes it possible to reconstruct the target area of radiotherapy and the 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 in the clinical practice of radiation tumor by more and more hospitals and cancer treatment centers in the world, and gradually incorporated into routine application.
The localization technology of three-dimensional conformal radiotherapy for trunk tumors is complicated. Compared with radiotherapy for head and neck tumors, the physiological movement of chest and abdomen affects the accuracy of three-dimensional image reconstruction and radiotherapy plan. In addition, the trunk tumor is large, and the treatment amount is also large. In addition, the volume and shape of radiotherapy targets for trunk tumors are usually irregular. Therefore, three-dimensional conformal radiotherapy has higher requirements for trunk tumors. The ICRU50 report describes in detail the standardization of tumor volume, clinical target volume, planned target volume and treatment prescription. Broadly speaking, radiotherapy guided by three-dimensional treatment plan based on three-dimensional image reconstruction should be called three-dimensional conformal radiotherapy. However, stereotactic radiosurgery (SRS) is different from trunk tumor in terms of equipment and accessories, and there are also some differences in operation technology. In many literature reports, three-dimensional conformal radiotherapy for head tumors using SRS system is generally called stereotactic radiotherapy (SRT), while radiotherapy for trunk tumors 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:
[1] There are many kinds of multi-leaf grating systems MLC, including manual, semi-automatic and full-automatic. Its leaves are different in size and number. The purpose of MLC system is to replace lead blocks; Simplify the shaping process of irregular irradiation fields, thereby increasing the number of irradiation fields to improve the shielding of normal organ structures; The static illumination field and single frame angle of multi-leaf grating can be used to adjust the flatness of the beam. When the gantry rotates, the blade can move to adapt to the dynamic adjustment of irregular tumor shape.
[2] Three-dimensional radiotherapy planning system, whose main feature is the treatment display based on three-dimensional reconstruction of CT images. For example, BEV function can show 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, and it is the key function to realize conformal irradiation. [Room View] (RV) function can display the treatment in any position in the treatment room. This function makes up for the deficiency of BEV from the perspective of beams, especially when the isocenter depth of rays is set, multiple beams can be displayed 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] Computer-controlled radiotherapy machine, new generation linear accelerator, some high-gear cobalt 60 therapeutic machines and afterloading therapeutic machines are all controlled by computers.
(4) Positioning, fixing and verifying. The system mainly includes a body fixing frame, a head and neck fixing frame, a thermoplastic mask, a vacuum pad and a device for limiting visceral activity to improve the accuracy of repeated positioning. Confirmation images of 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, it also minimizes the exposure to normal tissues. Theoretically, it can greatly improve the local control rate of tumor, but an important problem encountered in clinic is: how to determine the range of treatment volume? The understanding and determination of the edge of the treatment volume largely depends on the imaging technology and the operator's image reading level, so the accuracy of the determination of the treatment volume is closely related to the understanding of the tumor range in three-dimensional conformal radiotherapy. Obviously, modern imaging diagnosis technology plays a vital role in the implementation of three-dimensional conformal radiotherapy.
Intensity modulated radiation therapy (IMRT〕)
Intensity modulated radiotherapy (IMRT) is short for three-dimensional conformal intensity modulated radiotherapy. Compared with conventional radiotherapy, IMRT has the following advantages:
[1] Adopt precise posture fixing and stereotactic techniques; The positioning accuracy, positioning accuracy and irradiation accuracy of radiotherapy are improved.
(2) Adopt accurate treatment plan: [reverse plan], that is, the doctor first determines the maximum optimization 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 optimization of the treatment plan.
(3) Adopt precise irradiation: the weights of each beam in the radiation field can be optimally configured, so that the distribution of three-dimensional high-dose area can realize Ohno irradiation and Xiao Ye supplementary dose irradiation (SIB) in one plan. IMRT can meet the "four most" wishes of radiotherapy doctors, that is, the maximum radiation dose in the target area, the minimum radiation dose in the normal tissues around the target area, the most accurate target location and irradiation, and the most uniform dose distribution in the target area. The clinical results show that the local control rate of tumor is obviously improved and the radiation damage of normal tissue is reduced.
The main implementation methods of IMRT include:
[1] intensity modulation of two-dimensional physical compensator,
(2) multi-leaf collimator static intensity modulation (step &; Shoot]
(3) multi-leaf collimator dynamic intensity modulation (sliding window),
(4) intensity modulated radiation therapy,
(5) Intensity modulated electromagnetic scanning radiotherapy.
At present, the intensity modulation technology of electric multi-leaf grating is widely used in clinic. The study of IMRT in the treatment of head and neck, brain, chest, abdomen, pelvic cavity and breast tumors has reached positive conclusions. Zelefsky et al. used IMRT and 3D-CRT to treat patients with prostate cancer respectively. Under the same prescription dose [8 1Gy], the target dose distribution of IMRT is obviously better than that of 3D-CRT. The incidence of early and late radiation injury of rectal cancer in IMRT group was also significantly lower than that in 3D-CRT group. IMRT in the treatment of head and neck tumors can not only protect parotid gland and brain stem better, but also further improve the curative effect if combined with lobular supplementary dose (〔SIB) technology. Radiotherapy with IMRT technology after breast-conserving surgery for breast cancer can improve the dose distribution in the target area and better protect the lung and heart. 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. There is no doubt that IMRT will become the mainstream of radiotherapy in the future.
Image-guided radiotherapy [IGRT]
Increasing the dose of radiotherapy in target area is the key to improve the local control rate of tumor. Because the spatial position of the tumor and its surrounding normal tissues is constantly changing during and during the treatment, if we don't pay enough attention to these changes and errors, it may cause the tumor to miss the target and/or increase the damage of normal tissues, thus reducing the curative effect. The influencing factors of position uncertainty in radiotherapy are mainly summarized in two aspects: first, the integral error of irradiation field position refers to the error of data transmission in image positioning, planning and treatment stage and the position error of compensator, diaphragm and other design, marking or treatment auxiliary equipment; The second is the random error of irradiation field position: it refers to the position difference caused by the change of technician's posture and patient's anatomical position in different treatment processes, such as respiratory movement, bladder filling, small intestine peristalsis, pleural effusion, tumor enlargement or shrinkage, etc. Clinical practice and experimental research have confirmed that the above errors will have a significant impact on the dose distribution of normal tissues around the total 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 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 calculate and verify the dose distribution while verifying the position. At present, there are CT- electronic linear accelerator and respiratory control system, such as image-guided radiotherapy (IGRT), which combines the therapeutic machine with imaging equipment, collects relevant image information in the daily treatment process, determines the treatment target area, and realizes one target position every day.
Bioconformal radiotherapy [〔BCRT〕]
In the traditional concept, the irradiation field in the external irradiation plan should completely cover the tumor volume marked by anatomical images CT and MRI, and use uniform dose irradiation. For example, due to the limitation of traditional imaging technology, we can't completely 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 gross tumor volume is uneven, and the radiosensitivity of different cancer cells varies greatly due to different blood supply and cell heterogeneity. If the whole target area 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 BTV theory, BTV can be defined as a region with different radiosensitivity in the therapeutic target area determined by a series of tumor biological factors. These biological factors include:
[1] Hypoxia and blood supply;
(2) Proliferation, apoptosis and cell cycle regulation;
(3) Changes of oncogenes and tumor suppressor genes;
(4) Permeability and transfer characteristics. These factors include the sensitivity difference between tumor cells and normal tissues in the total 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, images such as magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPECT) are fused with images such as X-ray and CT, which mainly reflect the changes of morphological anatomical structure and belong to the category of anatomical images. These image fusion technologies have been 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 1 1C- methionine. Tumor nucleic acid metabolism can be detected by 18F- thymidine. Studies have shown that the application of PET can change the radiotherapy scheme of at least 30% 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, predict and evaluate curative effect.
At present, with the development of IMRT, the physical fitness of radiation therapy dose distribution has reached a quite ideal level, and biological and functional imaging has opened a new era of biological fitness. Multidimensional conformal therapy, which combines physical conformal therapy with biological conformal therapy, will surely become the development direction of tumor radiotherapy in the new century. Chao et al. used Cu-ATSM as a tracer of hypoxia in PET, and conducted phantom and human studies on head and neck tumors. The results show that when GTV receives 80Gy of PET with Cu-ATSM PET and reverse planning system, the dose of hypoxic target area can reach 80Gy, while the dose of parotid gland is mostly lower than 30Gy. The results of this study confirmed the possibility of biological intensity modulated radiotherapy. Researchers at the University of California use proton magnetic resonance imaging to plan and evaluate radiotherapy for prostate cancer. The relative concentration of choline is higher in swollen cancer area, while the concentration of citric acid is higher in normal prostate tissue and benign hyperplasia area. Based on this difference, they are using IMRT plan to carry out higher dose radiation in areas with high choline/citric acid, which is also derived from the treatment mode of biological conformal intensity modulated radiotherapy.
Three-dimensional stereotactic radiotherapy developed rapidly in the last two decades of the 20th century. Although there are still many problems to be overcome, its advantages are beyond doubt. Its establishment, development and perfection indicate that the era of tumor radiotherapy has entered the characteristics of "accurate positioning, accurate planning and accurate treatment". Three-dimensional stereotactic radiotherapy has also built a new high-tech platform for our radiation tumor clinicians, radiation physicists and radiation biologists, and put forward higher technical requirements.