Hokkaido University Graduate School of Medicine
Department of Radiation Medicine Professor Hiroki Shirato
Gated radiotherapy, tumor tracking, organ motion, respiratory movement, pattern matching technology, 4DRT, four dimensional radiotherapy.
We have studied and developed stereotactic radiotherapy using the linear accelerator to a head and neck cancers and intracranial lesions from 1989. Accuracy of the stereotactic radiotherapy (SRT) improved by direct fixation of the skull bone, with giving a retainer the coordinate center in intracranial diseases. However, in stereotactic body radiotherapy (SBRT) which the movement is accompanied with softly, we cannot expect improvement of the treatment accuracy by the anchorage from the outside of the body. Analysis on the effect of the internal organ movement has been giving us so much information. According to that knowledge, the organ is accompanied with the movement or existence of the difficulty in localization of the tumor itself, we should keep the coordinate center in tumor itself and grasped the position in real time and were found to be necessary to develop the irradiation system that we can do them. We started fundamental experiment in 1995 in this purpose and developed real time tumor tracking radiotherapy system (RTRT) with support of the Education Ministry Grant-in-Aid for Scientific Research in 1998. In the following, we describe the summary and initial treatment results.
(However, we are describing about here is only almost a level of the three-dimensional position recognition of the degree with +/- 1mm 30 times a second to be highly precise. It is impossible that we irradiate one another one cancer cell stereotactically. It is totally a-big-picture treatment for the communication of the intracellular millimeters second unit. How should we deal with an in vivo unpredictable event? It is necessary to be able to subtilize the sensitivity for words called “stereotactic” more and more. And that leads to making future insight of the frontier in the filed of radiotherapy.
2.Method and Material
2.1.Real time Tumor tracking radiotherapy (RTRT) system.
The RTRT system was intended that we can performe the radiation to the internal lesion with movement in +/- 1mm accuracy while possessing all the performance of the normal X-rays linear accelerator. The linear accelerator has 60 pairs of multi-leaf collimator (MLC) ; central part 10cm around beam axis is consisted of 5mm leaf and equipped with 4MV and 10MV (EXL-20DP, Mitsubishi Electric Corporation) beam energy.
Before radiotherapy, we implant the Au marker (diameter 1.5-2mm) to be concrete in the tumor inside or the periphery. After an insertion procedure, we perform computed tomography and conduct a three-dimensional treatment plan. We send the coordinates data of the each structure position; tumor, marker(s) to the RTRT sysytem. The Real time Tumor tracking system is equipped with four pairs of fluoroscope around a linear accelerator, and all those X-ray beam passes an X-ray isocenter for treatment (Fig 1).
Fig. 1 A Linear acceralator synchronized with and controlled by Real time Tumor tracking sysytem
(15; Gantry of the Linac 21,22: X-ray imager）
Fig. 2 Room view of real time tumor tracking radiotherpy and Au marker 2mm in diameter
2.2.Synchronized radiotherapy using RTRT system
A 2mm in diameter Au marker to be implanted around the target in a Real time Tumor tracking radiotherapy is shown in Fig 2. At first we set up the patients using a skin mark like a normal treatment. Using two sets of four pairs of fluoroscope, we calculate the three-dimensional position of the internal marker. Because there are four pairs of fluoroscope, we can see the internal marker without interference of a liniac gantry.
The RTRT system can superimpose on to the fluoroscopic images and the 3d cordinate information of the tumor and the marker transfered in advance from 3D-RTP. Precise patient setup becomes possible by repeating an actual marker position to coincide with a planned marker position. During radiation therapy, the shape of the marker is stored as a template for the 0.1mm image matrix. At 30 times per second real-time pattern recognition techniques are used continuously, RTRT system compared and calculated the location of the maker from the fluoroscopic image. Only at the moment when a marker comes to the planned three-dimensional position, treatment beam is disposed. (Fig 4).
Fig. 3 Images of the Au marker inserted around the tumor
Template data sets of the Au marker view are stored before treatment.
Fig. 4 Concept of the synchronized radiotherapy with RTRT sysytem
The delay from position recognition to radiation is 0.09 seconds. As for his delay, revision is possible in speed and acceleration and we predict a position after 0.09 seconds and can irradiate it.
This method is presented as “Real-time Tumor-tracking Radiotherapy”, and this way of radiation method is called “Wait and Shoot” radiation method.
We put a marker in a human body phantom. This phantom was designed to move so as to represent the simulated respiratory movement. And then we performed irradiation with RTRT system trigered by the marker in the phantom. As a result, an unnecessary irradiatiated lesion decreased sharply with RTRT system, and we found that accurate irradiation was realized to the moving target (Fig 5).
Without RTRT With RTRT
Fig. 5 RTRT system can dramatically redusing the desposed area
We can record the movement of the marker which was inserted near the tumor, the trace of the interal tumor movement was determined in real time precisely for the first time in the world (Fig 6). Irradiation was enabled only at the moment when a tumor come to the planned correct position (Fig 7).
Fig. 6 Traces of the movement of the lung cancer on the tracheal schematic picture according to its presence location
A left upper line is 1cm, and the size of the trace is magnified. The movement of the tumor in the lower lung field is larger than that of upper.
Fig. 7 The trace of the marker which moved of a certain lung cancer The Radiation beam for treatment was irradiated only when a tumor was present in a gray part. We find that the volumes that the normal lungs irradiated are decreased greatly.
When we pursue the treatment results improvement of the radiotherapy, it is im-portant to study precision of the dose distribution to a moving target not only to a static tumor. With the radiotherapy that is less harmfull to the surrounding normal tissue, we can achieve further high treatment results.
In near the future, with the level of lower than mili-meter order, a diagnosis and the stereotactic irradiation at the micrometer level will be established.
1. Harada T, Shirato H, Ogura S, Oizumi S, Yamazaki K, Shimizu S, Onimaru R, Miyasaka K, Nishimura M, Dosaka-Akita H. Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy. Cancer. 2002;95(8):1720-7.
2. Seppenwoolde Y, Shirato H, Kitamura K, Shimizu S, van Herk M, Lebesque JV, Miyasaka Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy. Int J Radiat Oncol Biol Phys. 2002;53(4):822-34.
3. Shimizu S, Shirato H, Ogura S, Akita-Dosaka H, Kitamura K, Nishioka T, Kagei K, Nishimura M, Miyasaka K. Detection of lung tumor movement in real-time tumor-tracking radiotherapy. Int J Radiat Oncol Biol Phys 2001 ;51(2):304-10.
4. Shirato H, Shimizu S, Kunieda T, Kitamura K, van Herk M, Kagei K, Nishioka T, Hashimoto S, Fujita K, Aoyama H, Tsuchiya K, Kudo K, Miyasaka K. Physical aspects of a real-time tumor-tracking system for gated radiotherapy. Int J Radiat Oncol Biol Phys 2000;48(4):1187-95.
5. Shirato H, Shimizu S, Kitamura K,et al. Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor. Int J Radiat Oncol Biol Phys 2000;48(2):435-42.
6. Shirato H, Shimizu S, Shimizu T, et al. Real-time Tumor-tracking radiotherapy. Lancet 1999; 353: 1331-1332.