Radiation Oncology and Medical Devices ( Part 1)

Ning J. Yue, PhD, Professor Ting Chen, PhD, Assistant Professor Wei Zou, PhD, Assistant Professor

Department of Radiation Oncology, Rutgers Cancer Institute of NewJersey, Rutgers University - Robert Wood Johnson Medical School

Radiation Oncology and Medical Devices ( Part 1)

Ning J． Yue (岳寧) received his Bachelor Degree in physics fromUniversity of Science and Technology of China (中國科技大學) in 1987． He was admitted to University of Pennsylvania through the CUSPEA programto further his study in physics． He completed post-doctoral fellowship and medical physics residency training programin Thomas Jefferson University after being awarded a Ph．D． in physics fromUniversity of Pennsylvania． Dr． Yue is currently a professor in Department of Radiation Oncology, Rutgers University - Cancer Institute of NewJersey, Rutgers University - Robert Wood Johnson Medical School． Dr． Yue has served on many committees of the American Association of Physicists in Medicine (AAPM) and American Society for Radiation Oncology (ASTRO)． Dr． Yue is a Fellowof American Association of Physicists in Medicine (AAPM) and serves on the Board of Directors of AAPM(2014～2016)． Dr． Yue is a board certified medical physicist by the American Board of Radiology．

Wei J． Zou (鄒薇) received her Bachelor Degree in physics fromNanjing University (南京大學) in 1993． She received her Ph．D． fromCornell University． After completing her medical physics residency training fromUniversity of Pennsylvania, Dr． Zou joined Rutgers University． Currently, Dr． Zou is an assistant professor in Department of Radiation Oncology, Rutgers University - Cancer Institute of NewJersey, Rutgers University - Robert Wood Johnson Medical School． Dr． Zou is a board certified medical physicist by the American Board of Radiology．

Ting Chen (陳霆) received his Bachelor Degree in Biomedical Engineering fromTsinghua University （清華大學） in 1998． He received his Ph．D． in Bioengineering fromUniversity of Pennsylvania． After completing his medical physics residency training in Department of Radiation Oncology of Rutgers University - Cancer Institute of NewJersey and Rutgers University - Robert Wood Johnson Medical School, he joined the department and is currently an assistant professor in the department． Dr．Chen is a board certified medical physicist by the American Board of Radiology．

Ning J. Yue, PhD, Professor Ting Chen, PhD, Assistant Professor Wei Zou, PhD, Assistant Professor

Department of Radiation Oncology, Rutgers Cancer Institute of NewJersey, Rutgers University - Robert Wood Johnson Medical School

Modern radiation treatments have become fairly complex and involve in utilizing a variety of medical devices to achieve the goal of providing conformal radiation dose coverage to the tumor target(s) while maximizing the sparing of normal organ structures. Recently, different forms of linear accelerators/radioactive source based machines have been invented and developed with the aimof providing improved treatments and more treatment options. Besides linear accelerators (Linac) that have been undergoing constant improvement and advancement and can deliver fairly complicated dose distribution patterns, imaging systems, computer information and calculation systems have been more and more integrated into radiotherapy processes. To bring radiotherapy to a potentially higher level, many institutions have either acquired or started to consider particle therapy, especially proton therapy. The complexity of modern radiotherapy demands in-depth understanding of radiation physics and machine engineering as well as computer information systems. This paper is intended to provide an introductory description of radiation oncology and related procedures, and to provide an overviewof the current status of medical devices in radiotherapy in the United States of America. This paper covers the radiation delivery systems, imaging systems, treatment planning systems, record and verify systems, and QA systems.

radiation oncology; radiotherapy; external beamradiotherapy; brachytherapy; intensity modulated radiotherapy; SRS; SBRT; linac; treatment planning system; record and verify system; 3DCRT; simulator

1 Introduction

Radiation oncology is the clinical and scientific discipline that is specialized in treating and managing cancer patients by using ionizing radiation. Radiotherapy, along with surgery and systematic chemotherapy (including immunotherapy), is one of the three major treatment modalities for malignant diseases. It is also frequently used to treat certain benign diseases. The primary mechanismof radiotherapy in killing cancer cells is radiation producing ionizations and free radicals that lead to DNA damages and other biological changes to the cells. As it is almost impossible to confine the damages to only cancer cells, certain amount of normal cells are also unavoidably destroyed during radiotherapy. Thus, one of the major goals in radiation oncology throughout history is to advance treatment equipment and technologies to maximize cancer cell killings while limiting and minimizing normal cell damages.

The use of radiation in the management of cancer can be traced back to more than 100years ago, soon after the discovery of X-rays in 1895. Since then, radiotherapy has undergone revolutionary changes in the aspects of technologies, medical practice, and basic understanding. Its application in medicine has evolved fromremoving a hairy mole in 1896 to treating almost all types of cancer nowadays. It is estimated that 60%～70% of cancer patients receive radiation treatment during their courses of treatment in industrialized countries and about 50% of the cured cancer patients benefit fromthe radiation treatments[1].

In general, radiation treatments can be divided into two major categories: external beamtherapy and brachytherapy. In the external beamradiotherapy, radiation sources are positioned at certain distances away frompatient body and the radiation beams are shaped and aimed at the target volumes fromvarious directions to achieve conformal dose coverage to the tumor while avoiding normal structures. In brachytherapy, radiation sources are placed either directly inside or adjacent to the target volumes so that the radiation doses are relatively locally confined and the dose distribution drops quickly beyond certain region. Regardless of treatment modality, a typical radiotherapy procedure consists of three major steps: treatment simulation, treatment planning, and treatment delivery. In the treatment simulation, patient anatomy information is acquired with patient immobilized in treatment position. Treatment target volumes and critical normal structures are determined based on the acquired anatomic information and treatment delivery is then designed and dose distribution is calculated with the goal of achieving adequate dose coverage of the target volume and sparing the critical organs. Finally, the designed treatment plan is implemented with radiation delivery device.

Although active research has been continued and significant amount of knowledge has been accumulated in understanding the biological mechanisms of radiation in cell killings, the biggest contributions to the improvement of radiotherapy efficacy have come fromthe advancements of technologies and physics research, in the aspects of radiation delivery methods, radiation dose quantification and treatment planning, and the integrations of various imaging systems and computer technologies into radiotherapy. Compared to the treatment systems of decades ago that consisted of simple components such as X-ray tube and that required manual dose and output calculations, modern radiotherapy systems are comprehensively complex with most of the functionalities controlled by computer systems. These machines are able to deliver precise doses to tumor volumes almost anywhere inside patient. Especially in the past two decades, radiation delivery and treatment planning devices have undergone dramatic advancement in both external beamand brachytherapy. Radiotherapy has evolved fromsimple twodimensional treatment to complex four-dimensional treatment. Radiation beams can be manipulated and modulated to provide precise coverage of the target volumes while sparing normal tissues, improving the treatment efficacies in terms of both tumor control and toxicity reduction. One of the major contributions to this advancement is the incorporation of various imaging devices into each of treatment steps. CT scanners are routinely used in treatment simulation to acquire three or four-dimensional patient anatomy while diagnostic imaging modalities such as MR, PET and Ultrasound are often fused with the simulation CT images for more accurate target volume identification and delineation. Cone beamCT (CBCT), kV imaging, optical imaging, and even MR are nowequipped to radiation delivery devices in order to improve patient treatment positioning and to minimize the negative impacts caused by inter- and intra-fractional organ motion.

Another important aspect of modern radiotherapy systemis the integration of computerized automatic Record & Verify System(RVS) that documents various parameters of treatment simulation, planning and treatment preparation, and verifies and records those parameters before and after treatment. The utilization of RVS systemoffers the opportunities to streamline and simplify the radiation treatment process and the opportunities to significantly reduce potential errors and safety hazards.

As radiotherapy procedures and equipment becomemore and more advanced, a key component is to establish and maintain a comprehensive quality assurance (QA) program. The QA programincludes periodic checks and evaluations of simulation devices, treatment planning systems, and treatment delivery devices, as well as patient specific QA measurements, to ensure that the procedures and equipment meet the desired requirements, precision and accuracy.It involves using a variety of medical devices, such as ionization chambers, diodes, and electrometers. Traditionally, due to the lack of development of QA tools for radiotherapy, many of the QA measurements were performed and analyzed manually, leading to some extremely time consuming and labor intensive QA processes. Fortunately, many of these QA devices have been integrated and computerized to improve the efficiency.

This paper reviews the current status of various radiotherapy medical devices in the United States of America. In addition to the external beamand brachy radiotherapy, this paper also briefly covers the medical devices employed in a radiation oncology department.

2 External Beam Radiotherapy

2.1 Photon based radiotherapy

2.1.1 EquipmentTypes

Most of tumors are situated inside patient body. Radiation treatment of tumor in certain depth of the patient requires highenergy photon beams with sufficient penetrating power. The Linear Accelerator (linac) is the most popular device for such application. Historically external beamradiotherapy uses X-ray with energy up to 300kV that are produced with conventional X-ray tubes. In X-ray tubes, after being accelerated with the voltage between the anode and cathode, electrons bombard a target, normally made of high atomic number materials, to produce X-rays. This type of machines can normally produce X-rays with energy up to 300kV. Although these beams do not have adequate penetration power and do not provide skin sparing for treating deeply situated tumors, the machines are still active in skin cancer treatment with superficial beams (up to 150kV) and for palliative treatment with orthovoltage beams (up to 300kV)[2].

High energy radiotherapy usually refers to X-ray beamtreatment with energy larger than or equal to that of the Cobalt-60at 1.25 MeV. The generation of the photon beamwith energy higher than that of the Cobalt usually involves a linac where the electrons are generated by thermionic process in the electron gun and then accelerated through a vacuumed accelerating waveguide. As a high frequency microwave supplies power into the waveguide, the alternating electromagnetic field accelerates the electrons in bunches as the electrons travel through the waveguide. Most linacs adopt the standing waveguide design with side cavities[3].The waveguide medical linac can accelerate the electrons to more than 20MeV. The apparatus that supplies the microwave can be magnetron or klystron where magnetron generates the microwave while Klystron only amplifies the microwave. When the electron beamis accelerated to the desired energy, it is guided to hit a target. The photons are then emitted with various energies due to Bremsstralung process. The photons can then be flattened by a flattening filter to achieve uniformfield intensity (In some of newLinacs, the flattening filter is not used in certain modes). Jaws, Multi-leaf Collimator (MLC) and physical wedges are used to collimate and modify the beams and deliver the photon beams to patient with desired dose distribution. The MLC can be used to not only shape the beams but also modulate the beamintensities across the fields. Modulating the beamintensities significantly increases the degrees of freedomin radiation delivery and it becomes possible to provide a very conformal dose distribution to the target while sparing adjacent critical structures. This technology is called intensity modulated radiotherapy (IMRT) and has been widely applied in radiotherapy.

In the United States of America, there used to three major Linac vendors: Varian Medical System, Elekta and Siemens. Recently, Siemens decided to phase out of the Linac market. The Linac machines fromthese three vendors have some similar designs. These machines usually offer 6 MV to 15 or 18 MV beams. The beams can be delivered through the gantry with 360degree rotation in a vertical plane. The collimators are mounted at the end of the gantry. The patient couch rotates in a horizontal plane and travels in vertical and lateral directions. In principle, the three rotational axes should intersect at a single point called isocenter, making the linacs isocentric. These rotations enable the beams being delivered to patient with quite large range of entrance angles.

The machines manufactured by the three vendors differ slightly in the ways the electron beams are guided to hit the target and howthe MLC and jaws are constructed and positioned. Bending magnets are used when the waveguide is too long to enable straight patient treatment. Varian linac has a 270-degree bending magnets that can bend as well as focusing the electron beams that has spectral spread after leaving the accelerating waveguide. An energy slit built in the bending magnets is tofinely select the energy of the electron beams. Elekta design uses magnets to deflect electrons by small angles within its travelling waveguide and the final deflection is slightly more than 90degrees. This is known as a slalomwaveguide that bends the beamby 112.5 degrees. The Varian linac retains two sets of jaws and the MLC is a tertiary collimator.The clearance fromthe bottomof the leaves to isocenter is 42 cm. Varian’s Millennium120MLC has 60pairs of leaves with rounded end design. The leaf width at the projected isocenter level is0.5 cmfromthe isocenter to 20cmfield size, and then 1 cmleaves to 40cmfield size. The Siemens design retains the upper jawand replaces the lower jawwith the MLC leaves. This provides good patient to treatment head clearance. The Siemens MLC is with double-focused leaf design where the leaf end aligns with beamdivergence as well as the side. It employs a spur drive to enable the leaf ends to tilt during motion. The leaf width is 1 cmfor inner leaves. Traditionally, the Elekta MLC is mounted close to the target above the two sets of jaws and the leaves are narrower. One jawis thinner and attenuates MLC end leaf leakage. The leaf width is 1 cmat the projected isocenter level and is a single-focused design with rounded leaf end. As a matter of fact, both Varian and Elekta are offering more types of MLC designs for various specialized treatment goals. For example, Varian nowoffers high definition MLC (HDMLC) with 28 peripheral pairs of leaves in 5 mmwidth and 32 central pairs of leaves in 2.5 mmwidth at the projected isocenter level; Agility and Apex MLC systems offered by Elekta provide similar level of special resolution and functionality.

Volumetric Modulated Arc Therapy (VMAT) is newer treatment modality that delivers an optimized plan comprising of one or several arcs with continuous gantry rotation while changing the photon fluence with moving MLC leaves. It was commercially implemented by Varian linac as RapidArc and Elekta as VMAT. The arc approach of VMAT further increases the degrees of freedomof radiation delivery, and is able to provide more conformal dose coverage to tumors. In addition, VMAT shortens the delivery time by two or three folds. To further reduce the delivery time, the vendors start to offer linacs with the flattening filter free (FFF) photon mode. In the FFF mode, no flattening filter is inserted into the photon beampath and the field has a higher intensity in the center. While satisfactory dose distribution can still be planned with MLC modulation and gantry angle selections, the photon beamdose rate can be significantly increased. For example, In TrueBeamlinacs developed by Varian, 6 MV and 10MV photon beams can be delivered in FFF mode, and dose rates can reach 1400MU/min in 6 MV and 2400MU/min in 10MV to enable faster treatment delivery.

Vendors may offer multiple models of linac. Varian Medical Systems nowoffers TrueBeam(Figure 1), Triology, and Clinac (visithttp://www.varian.com/us/oncology/radiation_oncology/formoreinformation); Elekat offers Versa HD, Axesse, Infinity, Synergy, and Compact (visit http://www.elekta.com/healthcare-professionals/products/elekta-oncology.html for more information). The primary functionalities of these models are usually very similar. Different models may be equipped with different peripheral devices (e.g., imaging devices, MLC, energy modes, SRS devices, etc) for different treatment goal and purpose, and may be targeted for different price range group or design size.

Figure 1. TrueBeamLinear Accelerator. Courtesy of Varian Medical Systems

Another kind of intensity modulated arc therapy is offered by Tomotherapy (an Accuray company) (visithttp://www.tomotherapy.comformoreinformation).Tomotherapy machines consist of a 6 MV linear accelerator, MLCs and other ancillary components mounted on a ring gantry. The binary MLC has 64 leaves in0.625 cmwidth at the projected isocenter level (85 cmfromthe source). Tomotherapy delivers fan beamto patient in helical mode, that is, couch is translating through the gantry with continuous gantry rotation while the beamis delivered slice by slice. The fan beamarc length is 40cmand is with field width of 1.0, 2.5 and 5.0cm. Tomotherapy systemis equipped with MV CT image capabilities.

Modern linacs generally come with imaging devices for patient setup and target identification before and/or during treatment. An electronic portal imaging device (EPID) consists of a flat-plate detector array opposite to the gantry head. The EPID is capable of imaging the MV beamthat penetrates the patient. The source of EPID imaging radiation is the same one for patient treatment. The modern EPID detector design has an amorphous silicon (a-Si) array overlaid with a gadoliniumoxysulphide (GdOS) or cesiumiodine (CsI) fluorescent layer. EPID can be used to image patient position as well as capture beamfield shapes withrespect to patient anatomy. Another common imaging device is on-board imaging (OBI) device capable of kV imaging with an X-ray tube source and an a-Si detector at the opposite sides of the patient. The OBI device is positioned 90degree to the linac gantry head. The OBI kV imaging can have X-rays with peak energy up to 140KV and can performcone-beamCT (CBCT) at patient treatment. Both Varian and Elekta offer EPID and OBI. Siemens linac uses existing MV beamfor MV cone-beamimages. Since photo-electric interaction is more dominant in kV photon energy range, kV imaging systems provide better tissue differentiating imaging qualities than MV imaging systems.

Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiotheray (SBRT) refer to deliver high doses to a focused volume in one or a fewfractions.Due to the high doses, SRS and SBRT demand careful treatment planning and precise target setup. SRS and SBRT can be treated on linacs with sufficient image guidance under 3D-conformal, IMRT, or VMAT modalities. It can also be treated on other specially designed machines, such as Gammaknife (visithttp://www.gammaknife.comformoreinformation) and Cyberknife (visithttp://www.cyberknife.comformoreinformation). One SRS platformis Novalis Tx linear accelerator jointly developed by Brainlab (visithttp://www.brainlab.comformoreinformation) and Varian. It is equipped with ExacTrac systemthat includes an optical image guidance systemconsisting of two infrared IR cameral, dual kV imagers and a robotic couch. It is also equipped with a high-definition MLC with 2.5 mmcentral leaves and a six-degree of freedomcouch to provide precise stereotactic radiation delivery.

Gammaknife (Elekta) is primarily used to deliver SRS to intra-cranial brain patient, although the treatments can be extended to head and neck region with a specially designed extension board. It utilizes60Cobalt sources. It has excellent isocentric precision less than0.5 mm. The newest Gammaknife Perfexion model has 192 sources and features a newsectorbased collimator design. This model has 4 mm, 8 mmand 16 mmcollimations which are partitioned into 8 independently moveable sections. Each of these sections can deliver 24 beams of radiation with its own selected collimation or be individually blocked. Through single shot, multi-shots and multiple targets, highly conformed dose can be delivered to the target with reduced procedure time compared with previous models. This model also features a newcouch design and an enlarged opening to facilitate extended anatomical reach. The treatment plan can be developed based on MRI or CT of patient brain with a rigid stereotactic frame attached to patient’s head.

Another addition in the medical devices to the steorotactic radiotherapy is Cyberknife (Accuray). Cyberknife amounts a linac accelerator on a robotic armthat delivers 6MV photon beam. It uses a X band microwave to accelerate the electron beam. The robotic armcan move the beamsource with six degrees of freedomduring the treatment. Image guidance is carried out through two X-ray imaging sources mounted on the treatment roomceiling and two corresponding flat panel detectors installed on the floor. The X-ray sources deliver the imaging beams to the patients during treatment and the detected target volume motion can be compensated for by moving the robotic armduring treatment. The largest aperture of the Cyberknife beamis 60mmand the smallest is 5 mmat 80cmfromthe source. The tumor target is treated with many beamlets fromdifferent directions to conformto its shape. With patient positioned supine on the treatment couch, no posterior beamlets are permissible due to the way the robotic armis designed and constructed. The Cyberknife is equipped with a robotic couch with six degrees of freedom.

One of the newdevices in image guided radiotherapy is the Vero machine jointly developed by Brainlab and Mitsubishi Heavy Industries. It has a 6 MV linac with attached MLC mounted on an O-ring gantry that rotates around the central axis by ± 180degrees. The ring itself can also rotate ± 60degree with respect to the vertical direction. Such design enables beamentry into the patient in virtually any angle.The orthogonal gimbals allowpan and tilt motions of the linac. The MLC consists of 605-mm-leafs and produces a maximumfield size of 15 cm× 15 cm.This set-up enables compensation for any gantry distortions during rotation and guarantees an isocenter accuracy of0.1 mm. Vero also boasts two orthogonal kV imaging systems that are attached to the O-ring together with a megavoltage EPID. There is also an integrated ExacTrac infrared marker-based positioning system. All the hardware in combination with motion management software provide precise patient set-up and realtime monitoring for target motion. Such systemcan be used for high precision image guided radiotherapy, for example, SBRT treatments.

ViewRay system(Figure 2) is an effort to improve both accuracy and precision in radiotherapy with real-time image guidance during the beamdeliveries. Instead of CT/CBCT imaging system, ViewRay systememploys an MRI systemfor better tissue imaging. The systemfeatures60Cobalt as the radiation source and MRI for continuous soft-tissue imaging. It is an integrated systemthat includes treatment planning, treatment management and treatment delivery. The cobalt sources aremounted in three treatment heads splitting 120degree apart and installed on a rotation gantry. With the current design, the treatment heads are equipped with MLC that has 1 cmleave width. The maximumtreatment field size is 30cm× 40cm. The MR field is0.35T with split coil design. The systemis capable of gated delivery under MR image guidance.

Figure 2. ViewRay System. Courtesy of ViewRay Inc.

2.1.2 Dosimetry Characteristics

The energy spectra of linac photon beams are not monoenergetic due to the physical Bremsstralung process. The energy levels of these photon beams are in megavoltage range. The penetration powers of the MV photon beams are significantly higher than those of kV photon beams. On the other hand, as an MV photon beamis incident into patient, unlike the kV photon beams for which the maximumdeposited dose is at patient skin surface, there is an initial dose built-up region before the deposited dose reaching maximum. Beyond this region, the deposited dose would exhibit an almost exponential decrease with depth. This is because the electrons liberated by the MV photon beamalso possess high energies and would travel for quite a distance into patient before stopping. This skin sparing quality of MV photon beams is advantageous in protecting superficial normal tissues of patient when treating deeply situated tumors.

2.2 Electron based radiotherapy

2.2.1 EquipmentTypes

The clinically useful electron beams can also be produced in linac machines under electron mode. The accelerated relativistic electron beamis not directed onto a target but instead strikes a scattering foil to spread out prior to exiting the linac. Therefore the electron beamproduction efficiency is much higher than for photons. Typically electron beaminvolves less electron gun current and the power of magnetron and klystron may also be reduced. There are typically five or more electron energies available for the linacs ranging from4 MeV to 20MeV. Due to the scattering nature of the electron beams, the collimation of the beamis generally performed close to the patient body surface with electron applicators. These electron applicators come with various sizes. Several planes of collimation are built in the applicator. The last plane allows the insert of an aperture in a lowmeltingpoint alloy that is cut out to the shape of the patient target.

2.2.2 Dosimetry Characteristics

At the exit of the linac gantry, the electron beamis almost monoenergetic of the peak energy. Due to its small mass and charge, the electrons interact with air with large angular scattering. When they reach patient body surface, the electron spectrumis quite wide. After entry into the patient, the average energy of the electron beamreduces with depth in tissue through collisions, ionization and excitation. Once the electron loses all of its initial energy, the electron stops and almost no dose is delivered beyond the electron track except for the contributions fromthe Bremsstralung. Two parameters, the mean energy and the most probable energy, are used to characterize the electron beam. These two parameters have certain relationships with the depth in patient. Due to its small mass, electrons has quite significant lateral dose scattering. Therefore the dose at the central axis reduces when the field size is smaller than the lateral equilibriumdistance.

2.3 Particle Radiotherapy

The termof particle radiation means the energy is propagated by traveling hadrons and heavy ions that have definite rest mass and definite momentum. Physical interactions such as electromagnetic and nuclear processes happen between the particles and human tissues. Particle therapy includes charged particle therapy such as proton therapy and heavy ion therapy and uncharged neutron therapy. Protons have excellent depthdose distributions but have similar （slightly higher） Radiobiology Effects (RBEs) to photons. Neutrons have no dose distribution advantage over photons but are likely to have very high RBEs. The heavy ions have better dose distribution and higher RBEs than photons. Currently particles heavier than carbon are not well investigated for clinical use because a tail in dose distribution downstreamof the Bragg peak increases with Z which may increase dose to normal tissues. Charged particle beamtherapy has many potential advantages for cancer treatment without increasing severe side effects in normal tissue. These kinds of radiation, in theory, have different biologic characteristics and have advantages over using conventional photon beamradiation during treatment.

The different modes of particle interactions with the matter determine their unique dosimetric characteristics. The depth dose profile of neutron is similar to that of photons. Travelling throughtissue, protons and carbon ions lose energy continuously and at an increasing rate. The rate of the energy loss reaches maximumright before the particles stop. Such peak dose to the tissue is termed Bragg Peak. To deliver dose to tumor at a range of depth in the tissue, a spread-out Bragg peak is utilized. It consists of a series of pristine Bragg peaks with successively lower energies and lower intensities fromthe initial Bragg peak. It results in a dose entrance build up region, a near uniformdose region followed by a rapid fall off distal region.

Proton therapy becomes possible in clinical applications when the accelerator technologies have advanced so that the beamenergy is high enough to reach the target at any depth in the human body. It is becoming the most popular alternative to linac X-ray in radiotherapy[4-6]The idea of treating target with proton beamthat has finite range and Bragg peak was first introduced by Wilson at 1954. Before early 1990s, the proton therapy was restricted mainly to the research institutions and to modest number of patients due to the beamtime availability. Since the first hospital based proton therapy was started in 1990at Loma Linda University of Medical Center (LLUMC), many proton therapy facilities have since opened worldwide.

Currently there are two types of accelerators, cyclotron and synchrotron, to accelerate charged particles. Both machines are offered commercially and have proven to be reliable treatment machines. The cyclotron accelerates charged particles fromhigh-voltage, high frequency electric field applied between two D-shaped hollowelectrodes. Powerful electromagnets generate magnetic fields to keep protons travelling in semicircular arcs. The isochronous cyclotron design has increasing radius in order to preserve the orbital period. Popular venders include IBA (visithttp://www.iba-protontherapy.com/why-ibaformoreinformation) and Varian ProBeam(visithttp://www.varian.com/us/oncology/protonformoreinformation).The synchrocyclotron design has decreasing oscillatory frequency of the electric field while maintaining a constant magnetic field. Currently the gantry mounted single roomMevion proton machine (visithttp://www.mevion.comformoreinformation) uses synchrocyclotron. The cyclotron accelerators deliver fixed energy with large current of protons produced in isochronous cyclotron and pulsed beamproduced in synchrocyclotron. Another type is synchrotron accelerator that delivers variable energy and pulsed proton beamat one time. Their trajectories followorbits of fixed radius. The electromagnetic resonant cavities at the straight sections between dipole magnets accelerate the particles. The accelerating frequency increases with the proton speed. The synchrotrons are typically about two times the diameter of cyclotrons for the same maximumenergy. Popular venders include Hitachi (visithttp://www.hitachi-america.us/products/business/protonbeamformoreinformation). Synchrotrons can also be used to deliver heavier particles such as carbon-12. There exist synchrotron designs to combine carbon-12 and proton treatments with the same facility.

The beamtransport systemthat transports the charged particles fromthe accelerators to the treatment roomcomprises a sequence of dipole and quadruple magnets. These magnets are to bend, steer and focus the beamalong the transport path. They can also be used to deflect the beamto be delivered to different treatment rooms. In the treatment room, the particle beamis either delivered horizontally or froma rotation gantry. A nozzle is equipped at the beamline to spread and shape the beam. To deliver the beamto the patient, two methods can be used. One is passive scattering beam. The other one is active scanning beam.The passive scattering method broadens the proton beamby a set of thin foil or plates that aligns with the incident proton beamdelivered fromthe beamtransport system. In the nozzle, to achieve the SOBP dose distribution along the penetration depth in patient, various energies needs to be modulated fromthe transported proton beam. A range modulator wheel that comprises of steps with various thickness and arc length can rotate into the beamline and controls the energy modulation. The broadened beamis then collimated laterally with a cutout block or a proton MLC to track the shape of the tumor. A range compensator made of plastic or wax material is milled out to compensate for the range differences at the distal shape of the tumor target. In this system, the neutron generated fromthe proton interactions with collimators should be evaluated. The proton utilization efficiency for passive scattering treatment is usually around 50%.

The other beamdelivery systemis the beamscanning system. It utilizes the fast-steering magnet to deflect the beamand sweep along the target cross-section. The change between the target cross-section layers is performed either by changing the beamenergy or with a range shifter. This technique provides the possibility to shape the dose to be conformal to the target both distally and proximally. This would be the delivery of intensity modulated proton therapy (IMPT) where the beamscanning spots are optimized to achieve desired dose distribution. The absence of scatters and apertures in this beamdelivery systemreduces secondary radiation concerns. It also saves time and effort frommaking compensators and apertures and increases the beamutilization efficiencies. The interplay effects between tumor motion and the scanning beamare currently addressed by eitherbeamgating or beamrepainting.

The major disadvantage of particle therapy is its high cost. Efforts in particle therapy research and development include reducing the proton facility costs such as developing gantry mounted single roomsuperconducting synchrocyclotron, developing high gradient proton linear accelerator and laserplasma particle acceleration. As the accuracy and robustness of the particle therapy systemcontinue to improve, the advantages of the particle therapy will be harnessed to benefit the radiotherapy community.

3 Radiotherapy Treatment Planning Systems

Treatment planning in radiotherapy is the process to plan and determine treatment modality, beamtype, beamenergy, beamconfiguration, amounts of beamoutput, and so forth, to achieve the treatment goal of cancer cell killings while preserving normal tissues. A typical treatment planning process consists of three major steps: ① patient positioning and immobilization and image acquisition,② target and organs at risk (OAR) localization, treatment plan design, dose calculations and evaluations, ③patient setup and verification according to the approved plan. The first step involves the use of various immobilization devices to optimally position and immobilize patient to simulate patient treatment and image acquisition of positioned patient anatomy with simulators. The simulators can be linac-look type of machines that provide 2D fluoroscopic and planar images or CT/MRI type of machines that can be used to acquire three dimensional anatomic information. In the second step, treatment target volumes and OARs are identified and delineated (if necessary) fromthe simulation images, treatment plan is designed based on the available treatment machines in the department to achieve desired dose coverage of the target volumes while sparing OARs as much as possible. During this process, radiation dose distributions are computed. It demands accurate dose calculation algorithms and the accuracy is critical to the dose coverage evaluation. The evaluated and approved treatment plan is then transferred to the Record and Verify Systemand the plan is checked again with patient in the treatment position to ensure the plan is feasible for delivery on the treatment machine (e.g., no collisions). Patient and beamsetups are further confirmed by taking portal images and setup images.

The key medical devices in the treatment planning process are the simulators and treatment planning systems.

3.1 Simulators

The traditional 2D simulators are being used less and less. Although some of the 2D simulators are equipped with CBCT capabilities and can be used to assess patient organ motion before treatment, in general, the 2D images acquired with this type of simulators are not ideal for modern treatment planning purpose. Currently, the most common type of simulators is computed tomography (CT) scanner, which provides detailed 3D information of patient anatomy, including both the target volumes and normal structures. This type of CT scanner is very similar to the type used in a diagnostic department, except for flat table top and generally larger bore size.As a matter of fact, many of diagnostic CT scanners can be used as radiotherapy CT simulators if the machine table top is flat and bore size is large enough to allowpatient (in desired treatment position) passing through. MR scanner can also be used for the purpose of treatment planning simulation. CT simulator has the advantages of relatively lower price tag, better tissue and bone differentiation, and less geometric distortion. CT images can be used directly for tissue inhomogeneity correction in dose calculations. MR simulator is better in producing soft tissue differentiating images, but it is more expensive and prone to geometric distortion.MR images most likely cannot be directly used for tissue inhomogeneity dose correction although some work has been pursued to conduct tissue inhomogeneity dose correction with MR images.

There are three major manufacturers of CT simulators in USA: GE Healthcare, Phillips, and Siemens. The CT simulator models offered by the manufactures have evolved rapidly. Currently, GE Healthcare offers two models of CT simulators: Discovery CT590RT and Optima CT580RT (visithttp://www3.gehealthcare.com/en/Products/Categories/Computed_Tomography/Radiation_Therapy_Planningformoreinformation), and Philips offers Brilliance CT - Big Bore Oncology (visithttp://www.healthcare.philips.com/main/products/ct/products/ct_brilliance_big_bore_oncology/index.wpdformoreinformation). Siemens also offers various types of CT scanners (visithttp://usa.healthcare.siemens.com/computed-tomographyformoreinformation).

3.2 Treatment PlanningSystems

Thanks to the advancement of computer technologies, a typical radiotherapy treatment planning systemhas become very sophisticated and possesses many varieties of capabilities and features. It can generate complex plans and has moved beyond dose distribution calculation and optimization. It can be used to performimage rendering, multi-image modality registration, virtual simulation, motion analysis, and so forth. Thedose calculation accuracy has also been significantly improved with the implementation of dose calculation algorithms such as convolution/superposition and Monte Carlo method. Most of treatment planning systems can be directly interfaced (via computer network) with other systems to import and export patient information (e.g., images, plan parameters).

However, treatment planning systems can be machine specific. Not all treatment planning systems can be used to model and design plans for any type of radiation treatment machine. As a matter of fact, for certain newtypes/models of treatment machines, only specific type(s) of treatment planning systems are usable. For example, Cyberknife and Tomotherapy machines all have their own dedicated treatment planning systems.

Correct use of a treatment planning systemrequires good understanding of the dose algorithm(s) in the systemand other features. It also requires rigorous acceptance testing and commissioning processes prior to clinical use[7]. The main purpose of acceptance testing is to ensure the systemmeets the required specifications. The commissioning process is to measure beamdata of a treatment machine for the treatment planning systemso that the treatment machine is accurately modeled in the treatment planning systemand the calculated dose distributions are in agreement with the machine delivery.

There are quite a fewtypes of treatment planning systems in the USA market: Eclipse (Varian Medical Systems), Pinnacle (Philips), Xio, Focal and Monaco/Oncentra (Elekta), RayStation (RayResearch Laboratories), etc. Most of these treatment planning systems offer advanced dose calculation and optimization algorithms, as well as image rendering and registration tools. The following is a list of some major features an external beamtreatment planning systemshould have:

(1) 2D/3D/4D virtual simulation and field setup

(2) Comprehensive contouring and segmentation tools

(3) Multi-image modality registrations

(4) Advanced dose calculation algorithms that accurately account for tissue inhomogeneities for photon and electron beams (proton beams if needed).

(5) 2D/3D conformal radiotherapy planning, Intensity Modulated Radiotherapy planning, and Volumetric Modulated Arc Radiotherapy planning

(6) Comprehensive dose evaluation tools, including 2D/3D isodose distribution display, Dose Volume Histogram(DVH), dose comparison, composite plan generation, etc.

(7) DICOMRT compatibility

For Brachytherapy, the treatment planning systemmust be able to model the radioactive sources used in the treatment and generate plans that are deliverable in the specially designed delivery systems (section IV). (To be continued)

[1] IAEA Technical Report 461

[2] Khan FM． The Physics of Radiation Therapy[M]． 4th Edition, Lippincott Williams & Wilkins, 2010．

[3] Metcalf P,Kron T,Hoban P． The Physics of Radiotheray X-rays and Electrons[M]．Medical Physics Publishing Corporation, 2007．

[4] DeLaney TF,Kooy HM．Proton and Charged Particle Radiotherapy[M]．Lippincott Williams & Wilkins,2008．

[5] Metz,JM．Proton Therapy[M]．Demos Medical Publishing, 2010．

[6] Harald Paganetti．Proton Therapy Physics[M]．CRC Press Inc,2012．

[7] Das IJ,Cheng CW,Watts RJ,et al．Accelerator beamdata commissioning equipment and procedures:Report of the TG-106 of the Therapy Physics Committee of the AAPM[J/OL]． Med．Phys．2008,35(9): 4186-4215．

R197.39；TH774

B

1674-1633(2014)01-0001-09

10.3969/j.issn.1674-1633.2014.01.001

Received November 5, 2013; Revision received December 3, 2013

Address correspondence to NJ Yue．(e-mail: yuenj@cinj．rutgers．edu)．