\r\n\tIt is a relatively simple process and a standard tool in any industry. Because of the versatility of the titration techniques, nearly all aspects of society depend on various forms of titration to analyze key chemical compounds. \r\n\tThe aims of this book is to provide the reader with an up-to-date coverage of experimental and theoretical aspects related to titration techniques used in environmental, pharmaceutical, biomedical and food sciences.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"5278b500d19d2508a7c933276167d82c",bookSignature:"Associate Prof. Vu Dang Hoang",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9212.jpg",keywords:"Acid-Base, Redox, Complexometric, Potentiometric, Voltammetric, Biomedical, Amperometric, Spectrophotometric, Isothermal Titration Calorimetry, Food Applications, Conductometric, Environmental Applications",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 20th 2019",dateEndSecondStepPublish:"March 16th 2020",dateEndThirdStepPublish:"May 15th 2020",dateEndFourthStepPublish:"August 3rd 2020",dateEndFifthStepPublish:"October 2nd 2020",remainingDaysToSecondStep:"10 months",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"199907",title:"Associate Prof.",name:"Vu Dang",middleName:null,surname:"Hoang",slug:"vu-dang-hoang",fullName:"Vu Dang Hoang",profilePictureURL:"https://mts.intechopen.com/storage/users/199907/images/system/199907.jpg",biography:"Vu Dang Hoang completed his doctorate in pharmaceutics at the University of Strathclyde, UK, in 2005 and conducted a postdoctoral research at the Ecole Nationale d'Ingénieurs des Techniques des Industries Agricoles et Alimentaires, France, in 2006. He has been lecturing at the Department of Analytical Chemistry and Toxicology, Hanoi University of Pharmacy, Vietnam, since 2007. He became an associate professor in the field of drug quality control in 2015. 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1. Introduction
This chapter presents a comprehensive review of RFID technology concerning the antennas and propagation for multi-band operation. The technical considerations of antenna parameters are also discussed in details in order to provide a complete realization of the parameters in pragmatic approach to the antenna designing process, which primarily includes scattering parameters and radiation characteristics. The antenna literature is also critically overviewed to identify the possible solutions of the multi-band microstrip antennas to utilize in multi-band RFID reader operation. In the literature dual-band antennas are principally discussed since they are ideal to realize and describe multi-band antenna mechanism. However, it has been seen that these techniques can be combined to enhance multi-band antennas with wider bandwidths. Last but not least, the high gain dual-band antennas and limitations have been described and it is realized that the conventional feeding technique might limit the performance of multi-band antennas to only one frequency.
2. Radio frequency identification
The idea of early radio frequency identification (RFID) system was invented by Scottish physicist Sir Robert Alexander Watson-Watt in 1935. With the supervision of Watson-Watt, the British government developed the first active identify friend or foe (IFF) system. This prototype of RFID concept was modified in 1950s and 60s by using radio frequency (RF) energy for commercialization purpose. The first US patent in this field was published on January 23, 1973 for the invention of an active RFID tag with rewritable memory by M. W. Cardullo (Cardullo 1973). That same year, C. Walton received another RFID patent for a passive transponder used to unlock a door without a key. In the recent days, the low power ultra high frequency (UHF) RFID system research has gained a lot of importance after some of the biggest retailers in the world, e.g., Albertsons, Metro, Target, Tesco, Wal-Mart and the US Department of Defense, have said they plan to use electronic product code (EPC) technology to track goods in their supply chain (Mitra 2008).
RFID is an emerging technology for the identification of objects and/or personnel. RFID is recognized as one of the technologies capable of realizing a complete ubiquitous computing network due to its strong benefits and advantages over traditional means of identification such as the optical bar code systems. Comparing with barcode, RFID has some advantages of rapid identifying, flexible method and high intelligent degree (Wang et al. 2007; Xiao et al. 2008). Furthermore, it can function under a variety of environmental conditions (Intermec Technologies Corporation 2006). It has recently found a tremendous demand due to emerging as well as already existing applications requiring more and more automatic identification techniques that facilitate management, increase security levels, enhance access control and tracking, and reduce labor force. A brief listing of RFID applications that find use on a daily basis is:
Warehouse Management Systems
Retail Inventory Management
Toll Roads
Automatic Payment Transactions
High Value Asset Tracking and Management
Public Transportation
Automotive Industry
Livestock Ranching
Healthcare and Hospitals
Pharmaceutical Management Systems
Military
Marine Terminal Operation
Manufacturing
Anti-counterfeit
2.1. RFID system
Basically RFID is a contact-free non-line-of-sight type identification technology using radio frequency consisting of a RFID transponder (tag), a RFID interrogator (reader) with an antenna and data processing unit (host computer). In case of the handheld RFID reader, the reader itself contains the feature of data processing unit. The typical block diagram of RFID system is shown in Fig. 1.
Figure 1.
Block diagram of RFID system
The interrogation signal coming from the reader antenna must have enough power to activate the transponder microchip by energizing the tag antenna, perform data processing and transmit back the data stored in the chip up to the required reading range (typically 0.3–1m). The reader antenna receives the modulated backscattered signal from the tags in field of antenna and examines the data.
2.1.1. RFID tags
The tag is the basic building block of RFID. Each tag consists of an antenna and a small silicon chip that contains a radio receiver, a radio modulator for sending a response back to the reader, control logic, some amount of memory, and a power system. Tags contain a unique identification number called an Electronic Product Code (EPC), and potentially additional information of interest to manufacturers, healthcare organizations, military organizations, logistics providers, and retailers, or others that need to track the physical location of goods or equipment. All information on RFID tags, such as product attributes, physical dimensions, prices, or laundering requirements, can be scanned wirelessly by a reader at high speed and from a distance of several meters. According to the energizing power system, the tags can be classified into three types:
Figure 2.
Communication between (a) reader and passive tag, (b) reader and active tag, (c) reader and semi-passive tag (Khan et al. 2009)
Passive tag - These tags (shown in Fig. 2 (a)) use the signal received from the reader to power the IC, and vary their reflection of this signal to transmit information back to the reader. Passive tags are the most common in cost-sensitive applications, because, having no battery and no transmitter, they are very inexpensive (Dobkin 2007). In this research we will consider only passive tags, the most commonly-encountered, and range-challenged, of the three types.
Active tags - These tags are full-featured radios with their own transmitting capability independent of the reader. The primary advantages of active tags are their reading range and reliability. The typical communication between the reader and an active tag is shown in Fig. 2 (b). The tags also tend to be more reliable because they do not need a continuous radio signal to power their electronics. But due to the decay of battery life, the active tags have the disadvantage of shorter shelf life than passive tags, normally a few years after manufacturing (Garfinkel & Holtzman 2005).
Semi-passive tags - These tags, sometimes known as battery-assisted passive tags, (as shown in Fig. 2 (c)) have a battery, like active tags, but still use the reader’s power to transmit a message back to the RFID reader using a technique known as backscatter. These tags thus have the read reliability of an active tag but the read range of a passive tag. They also have a longer shelf life than a tag that is fully active.
2.1.2. RFID reader
The RFID reader sends a pulse of radio energy to the tag and listens for the tag’s response. The tag detects this energy and sends back a response that contains the tag’s serial number and possibly other information as well. In simple RFID systems, the reader’s pulse of energy functioned as an on-off switch; in more sophisticated systems, the reader’s RF signal can contain commands to the tag, instructions to read or write memory that the tag contains, and even passwords (Garfinkel & Holtzman 2005).
RFID readers are usually on, continually transmitting radio energy and awaiting any tags that enter their field of operation. However, for some applications, this is unnecessary and could be undesirable in battery-powered devices that need to conserve energy. Thus, it is possible to configure an RFID reader so that it sends the radio pulse only in response to an external event. For example, most electronic toll collection systems have the reader constantly powered up so that every passing car will be recorded. On the other hand, RFID scanners used in veterinarian’s offices are frequently equipped with triggers and power up the only when the trigger is pulled.
Like the tags themselves, RFID readers come in many sizes. The largest readers might consist of a desktop personal computer with a special card and multiple antennas connected to the card through shielded cable. Such a reader would typically have a network connection as well so that it could report tags that it reads to other computers. The smallest readers are the size of a postage stamp and are designed to be embedded in mobile telephones.
2.2. Near & far field concept & the selection of RFID operating bands
There are only two possible physics concepts used by RFID technology for the detection of RF tags as depicted in Fig. 3: near field concept (magnetic coupling) and far field concept. In the far field, electric and magnetic fields propagate outward as an electromagnetic wave and are perpendicular to each other and to the direction of propagation. The fields are uniquely related to each other via free-space impedance and decay as 1/r. In the near field, the field components have different angular and radial dependence (e.g. 1/r3). The near field region includes two sub-regions: radiating and reactive. In radiating region, the angular field distribution is dependent on the distance. And in the reactive near field, energy is stored in the electric and magnetic fields very close to the source but not radiated from them. Instead, energy is exchanged between the signal source and the fields (Lecklider 2005).
Figure 3.
Antenna near and far field region (Nikitin et al. 2007)
Figure 4.
Frequency-ranges used for RFID-systems
As shown in Fig. 4, several frequency bands have been assigned to RFID applications: 125/134 KHz, 13.56 MHz, 860-960 MHz, 2.450 (2.400–2.483) GHz and 5.800 (5.725–5.875) GHz. Several issues are involved in choosing a frequency of operation (Dobkin 2007).
Figure 5.
Inductive coupling or near field detection of RFID reader
The most fundamental, as indicated in the diagram, is whether inductive or radiative coupling will be employed. The distinction is closely related to the side of the antennas to be used relative to the wavelength. When the antennas are very small compared to the wavelength, the effects of the currents flowing in the antenna cancel when viewed from a great distance, so there is no radiation. Only objects so close to the antenna that one part of the antenna appears significantly closer than another part can feel the presence of the current. As depicted in Fig. 5, in case of inductive coupling, the antennas act like transformers and the propagation time from reader to tag is fraction of cycle time. Thus, these systems, which are known as inductively-coupled systems, are limited to short ranges comparable to the size of the antenna. In practice, inductive RFID systems usually use antenna sizes from a few cm to a meter or so, and frequencies of 125/134 KHz (LF) or 13.56 MHz (HF). Thus the wavelength (respectively about 2000 or 20 meters) is much longer than the antenna.
Figure 6.
Radiative coupling or far field detection of RFID reader
Radiative systems use antennas comparable in size to the wavelength. The very common 900 MHz range has wavelengths around 33 cm. Reader antennas vary in size from around 10 to >30 cm, and tags are typically 10-18 cm long. These systems use radiative coupling, and are not limited by reader antenna size but by signal propagation issues. In these systems, the reader antenna launches an electromagnetic wave (exhibited in Fig. 6) and use backscattering from tag to reader. However, the propagation time from reader to tag is longer than a single RF cycle
A second key issue in selection of frequency bands is the allocation of frequencies by regulatory authorities. In essentially every country in the world, the government either directly regulates the use of the radio spectrum, or delegates that authority to related organizations.
RFID systems are typically operated in unlicensed bands. In the US, unlicensed operation is available in the Industrial, Scientific, and Medical (ISM) band at 902-928 MHz, among others. However, for Malaysia the UHF RFID band is 919-923MHz. The UHF RFID frequency allocation statuses are pictured in Fig. 7, where it is realized that, the 900-MHz ISM band is a very common frequency range for UHF RFID readers and tags in all over the world. That’s why in this research, the frequency band of 902-928 MHz is aimed for the operation of UHF RFID band.
The practical consequence of UHF band being in proximity to other bands of different wireless applications is the possibility of interference: for example, a nearby cell phone transmitting tower may interfere with the operation of RFID readers, due to the finite ability of the reader receiver to reject the powerful cell signal. (Cellular base stations may sometimes use transmit powers of 10\'s to hundreds of watts.) Other users of the ISM band may also interfere with RFID readers, or encounter interference due to them: examples are cordless phones and older wireless local area networks.
Figure 7.
UHF RFID frequency allocation statuses from 2004 (www.mapquest.com)
Finally, changes in operating frequency affect the propagation characteristics of the resulting radiated fields. Lower frequencies diffract more readily around obstacles, but couple less well to small antennas. Radiated fields are absorbed by many common materials in buildings and the environment, particularly those containing water. The degree of absorption due to water increases gradually with increasing frequency. Tags immersed in water-containing materials (i.e. injected into or swallowed by animals or people) must use very low frequencies to minimize absorption: this is a typical 125 KHz application. For locating large objects or people outdoors, a relatively low frequency may be desirable to avoid obstacle blockage; when a clear line of sight from the antenna to the tag can be assured, a higher frequency may be useful to reduce the size of the antennas.
3. Antenna characteristics
Antennas are the key components of any wireless communication system (Balanis 1996; Kraus 1988). According to The IEEE Standard Definitions of terms for Antennas, an antenna is defined as “a means for radiating or receiving radio waves" (IEEE Std 145-1993 1993). In other words, they are the devices that allow for the transfer of a signal (in a wired system) to waves that, in turn, propagate through space and can be received by another antenna. The receiving antenna is responsible for the reciprocal process, i.e., that of turning an electromagnetic wave into a signal or voltage at its terminals that can subsequently be processed by the receiver.
In the following sections, some of the antenna parameters are described that necessary to fully characterize an antenna and determine whether an antenna is optimized for a certain application.
3.1. Impedance bandwidth, reflection coefficient, VSWR & return loss
Figure 8.
Transmission line model
Impedance bandwidth indicates the bandwidth for which the antenna is sufficiently matched to its input transmission line such that 10% or less of the incident signal is lost due to reflections. Impedance bandwidth measurements include the characterization of the Voltage Standing Wave Ratio (VSWR) and return loss throughout the band of interest. VSWR and return loss are both dependent on the measurement of the reflection coefficient Γ. Γ is defined as ratio of the reflected wave Vo- to the incident wave Vo+ at a transmission line load as shown in Fig. 8. Transmission Line Model, and can be calculated by equation 2.1 (Balanis 1996; Stutzman 1998; Pozar 2001):
Γ=V0−V0+=Zline−ZloadZline+ZloadE1
Zline and Zload are the transmission line impedance and the load (antenna) impedance, respectively. The voltage and current through the transmission line as a function of the distance from the load, z, are given as follows:
V(z)=V0+e−jβz+V0−ejβz=V0+(e−jβz+Γejβz)E2
I(z)=1/Z0(V0+e−jβz−V0−ejβz)=V0+/Z0(e−jβz−Γejβz)E3
where β = 2π/λ.
The reflection coefficient Γ is equivalent to the S11 parameter of the scattering matrix. A perfect impedance match would be indicated by Γ = 0. The worst impedance match is given by Γ = -1 or 1, corresponding to a load impedance of a short or an open.
Power reflected at the terminals of the antenna is the main concern related to impedance matching. Time-average power flow is usually measured along a transmission line to determine the net average power delivered to the load. The average incident power is given by:
Piave=|V0+|22Z0E4
The reflected power is proportional to the incident power by a multiplicative factor of|Γ|2, as follows:
Prave=−|Γ|2|V0+|22Z0E5
The net average power delivered to the load, then, is the sum of the average incident and average reflected power:
Pave=|V0+|22Z0[1−|Γ|2]E6
Since power delivered to the load is proportional to(1−|Γ|2), an acceptable value of Γ that enables only 10% reflected power can be calculated. This result is Γ= 0.3162.
When a load is not perfectly matched to the transmission line, reflections at the load cause a negative traveling wave to propagate down the transmission line. Ultimately, this creates unwanted standing waves in the transmission line. VSWR measures the ratio of the amplitudes of the maximum standing wave to the minimum standing wave, and can be calculated by the equation below:
VSWR=VmaxVmin=1+|Γ|1−|Γ|E7
The typically desired value of VSWR to indicate a good impedance match is 2.0 or less. This VSWR limit is derived from the value of Γ calculated above.
Return loss is another measure of impedance match quality, also dependent on the value of Γ, or S11. Antenna return loss is calculated by the following equation:
Return Loss =−10log|S11|2, or−20log(|Γ|)E8
A good impedance match is indicated by a return loss greater than 10 dB. A summary of desired antenna impedance parameters include Γ<0.3162, VSWR<2, and Return Loss > 10 dB.
3.2. Radiation pattern
One of the most common descriptors of an antenna is its radiation pattern. Radiation pattern can easily indicate an application for which an antenna will be used. For example, fixed indoor RFID reader applications, such as a ware-house, would necessitate a nearly omni-directional antenna which could be hung in the ceiling, since the position of the detectable object might not be known. Therefore, radiation power should be spread out uniformly around the user for optimal reception. However, for high range RFID detection applications, a highly directive antenna would be desired such that the majority of radiated power is directed to a specific, known location. According to the IEEE Standard Definitions of Terms for Antennas, an antenna radiation pattern (or antenna pattern) is defined as: “a mathematical function or a graphical representation of the radiation properties of the antenna as a function of space coordinates. In most cases, the radiation pattern is determined in the far-field region and is represented as a function of the directional coordinates. Radiation properties include power flux density, radiation intensity, field strength, directivity phase or polarization (IEEE Std 145-1993 1993).
In most cases, it is determined in the far-field region where the spatial (angular) distribution of the radiated power does not depend on the distance. Usually, the pattern describes the normalized field (power) values with respect to the maximum values. The radiation property of most concern is the two-or three-dimensional (2D or 3D) spatial distribution of radiated energy as a function of the observer\'s position along a path or surface of constant radius. In practice, the three-dimensional pattern is some-times required and can be constructed in a series of two-dimensional patterns. For most practical applications, a few plots of the pattern as a function of ϕ for some particular values of frequency, plus a few plots as a function of frequency for some particular values of θ will provide most of the useful information needed, where ϕ and θ are the two axes in a spherical coordinate.
There are two common portions used to describe the characteristic of a radiation pattern of an antenna:
Co-polar pattern: diagram representing the radiation pattern of a test antenna when the reference antenna is similarly polarized, scaled in dBi or dB relative to the measured antenna gain
Cross-polar pattern: diagram representing the radiation pattern of a test antenna when the reference antenna is orthogonally polarized, scaled in dBi, or dB relative to the measured antenna gain
3.3. Antenna polarization
Polarization is a property of a single-frequency electromagnetic wave; it describes the shape and orientation of the locus of the extremity of the field vectors as a function of time. In antenna engineering, the polarization properties of plane waves or waves that can be considered to be planar over the local region of observation are of interest. For plane waves, it is sufficient to specify the polarization properties of the electric field vector since the magnetic field vector is simply related to the electric field vector. The plane containing the electric and magnetic fields is called the plane of polarization and is orthogonal to the direction of propagation (Volakis 2007).
The polarization of an electromagnetic wave may be linear, circular, or elliptical (Kumar & Ray 2003). The instantaneous field of a plane wave, traveling in the negative z -direction, is given by
E(z,t)=Ex(z,t)x⌢+Ey(z,t)y⌢E9
The instantaneous components are related to their complex counter-parts by
Ex(z,t)=Excos(ωt+βz+ϕx)E10
and
Ey(z,t)=Eycos(ωt+βz+ϕy)E11
where Ex and Ey are the maximum magnitudes and ϕx and ϕy are the phase angles of the x and y components, respectively, ωis the angular frequency, and b is the propagation constant. For the wave to be linearly polarized, the phase difference between the two components must be
Δϕ=ϕy−ϕx=nπ, where n=0, 1, 2,…E12
The wave is circularly polarized when the magnitudes of the two components are equal (i.e., Ex = Ey) and the phase difference Δϕ is an odd multiple ofπ/2; in other words,
Δϕ=ϕy−ϕx={+(2n+1/2)πforRHCPor−(2n+1/2)πforLHCPE13
Figure 9.
Elliptically polarized wave
If Ex ≠ Ey or Δϕ does not satisfy (11) and (12), then the resulting polarization is of elliptical shape as shown in Fig. 9. The performance of a circularly polarized antenna is characterized by its AR. The AR is defined as the ratio of the major axis to the minor axis; in other words,
AR=major axisminor axis=OAOBE14
where
OA=[12{Ex2+Ey2+[Ex4+Ey4+2Ex2Ey2cos(2Δϕ)]12}]12E15
and
OB=[12{Ex2+Ey2−[Ex4+Ey4+2Ex2Ey2cos(2Δϕ)]12}]12E16
The tilt angle τof the ellipse is given by
τ=π2−12tan−1[2ExEyEx2−Ey2cos(Δϕ)]E17
For CP, OA = OB (i.e., AR = 1), whereas for linear polarization, AR → ∞. The deviation of AR from unity puts a limit on the operating frequency range of the circularly polarized antennas. Generally, AR = 3–6 dB (numerical value 1.414 to 2) is acceptable for most of the practical applications.
3.4. Directivity & gain
Directivity of an antenna, D is defined as the ratio of the radiation intensity U in a given direction from the antenna to the radiation intensity averaged over all directions, i.e. an isotropic source. It is introduced to describe the directional properties of antenna radiation pattern. For an isotropic source, the radiation intensity U0 is equal to the total radiated power Prad divided by 4π. So the directivity can be calculated by:
D=UU0=4πUPradE18
If not specified, antenna directivity implies its maximum value, i.e. D0.
D0=U|maxU0−UmaxU0=4πUmaxPradE19
Antenna gain G is closely related to the directivity, but it takes into account the radiation efficiency erad of the antenna as well as its directional properties, as given by:
G=eradDE20
Figure 10.
Equivalent circuit of antenna
Fig. 10 shows the equivalent circuit of the antenna, where Rr, RL, L and C represent the radiation resistance, loss resistance, inductor and capacitor, respectively. The radiation efficiency erad is defined as the ratio of the power delivered to the radiation resistance Rr to the power delivered to Rr and RL. So the radiation efficiency erad can be written as:
erad=12|I|2Rr12|I|2Rr+12|I|2RL=RrRr+RLE21
According to the IEEE Standard Definitions of Terms for Antennas (IEEE Std 145-1993 1993), the antenna absolute gain is “the ratio of the intensity, in a given direction, to the radiation intensity that would be obtained if the power accepted by the antenna were radiated isotropically” (IEEE Std 145-1993 1993). The maximum gain G0 is related the maximum directivity D0 mathematically as follows:
G0=eradD0(Dimensionless)E22
Also, if the direction of the gain measurement is not indicated, the direction of maximum gain is assumed. The gain measurement is referred to the power at the input terminals rather than the radiated power, so it tends to be a more thorough measurement, which reflects the losses in the antenna structure.
Gain measurement is typically misunderstood in terms of determining the quality of an antenna. A common misconception is that the higher the gain, the better the antenna. This is only true if the application requires a highly directive antenna. Since gain is linearly proportional to directivity, the gain measurement is a direct indication of how directive the antenna is (provided the antenna has adequate radiation efficiency).
4. Multi-band antenna techniques: review
When the antenna operates only at more than one spot frequency, then it is known as a multi-frequency antenna. When it operates over a finite BW at all of the frequencies, it is known as multi-band antenna. When two or more resonance frequencies of a MSA are close to each other, one gets broadband characteristics. When these are significantly separated, dual-band or multi-band operations are obtained. In literature, numerous multi-band antennas are available. However, in order to understand the technique of multi-band operation, it is worthy to understand the mechanism of dual-band antennas which could be extended to more than two bands employing the same or combination of other techniques.
For dual-band operations, various single and multilayer microstrip antennas configurations are possible. In the single-layer microstrip antenna, dual-band operation can be achieved by utilizing the multi-resonance characteristics of a single patch, by reactively loading the patch with quarter-wavelength stubs, by using shorting posts, by cutting slots, and by adding lumped elements, among other techniques. Multi-resonators in both planar and stacked configurations yield dual-band operations. Both electromagnetic as well as aperture coupling mechanisms are used in multilayer configurations (Kumar & Ray 2003).
4.1. Higher order or orthogonal mode microstrip antennas
As is well-known, a simple rectangular patch can be regarded as a cavity with magnetic walls on the radiating edges. The first three modes with the same polarization can be indicated by TM100, TM200, and TM300, where TM denotes the magnetic field transverse with respect to the interface normal. TM100 is the mode typically used in practical applications; TM200 and TM300 are associated with a frequency approximately twice and triple of that of the TM100 mode. This provides, in principle, the possibility to operate at multiple frequencies. In practice, the TM200 and the TM300 modes cannot be used. Indeed, owing to the behavior of the radiating currents, the TM200 pattern has a broadside null, and the TM300 pattern has grating lobes.
The simplest way to operate at dual frequencies is to use the first resonance of the two orthogonal dimensions of the rectangular patch, i.e., the TM100 and the TM101 modes. In this case, the frequency ratio is approximately equal to the ratio between the two orthogonal sides of the patch. The obvious limitation of this approach is that the two different frequencies excite two orthogonal polarizations. This simple method is very useful in low-cost short-range applications, where polarization requirements are not pressing (Maci & Gentili 1997).
4.1.1. Single feed dual-band microstrip antenna
Figure 11.
a) Rectangular microstrip antenna with a single feed for orthogonal dual-band operation and its and (b) VSWR plots (Chen & Wong 1996)
Figure 12.
Aperture coupled RMSA with an inclined slot
An interesting feature of these antennas is their capability of simultaneous matching of the input impedance at the two frequencies with a single feed structure (denoted by “single-point” in Fig. 11). This may be obtained with a probe-fed configuration, which is displaced from the two principal axes of the patch. As demonstrated in literature (Chen & Wong 1996), the performance of this approach in terms of matching level and bandwidth is almost equal to that of the same patch fed separately on the two orthogonal principal axes. This provides the possibility of using the well-known design formula for standard feeds. It is also worth noting that the simultaneous matching level for structures that provide the same polarizations at the two frequencies is, in general, worse with respect to the case relevant to orthogonal polarization.
Instead of using a single coaxial feed, similar results are obtained by using an aperture coupled rectangular microstrip antenna, in which an inclined slot is cut in the ground plane with respect to the microstrip feed line as shown in Fig. 12 to give proper matching at both the frequencies (Antar et al. 1995). The required slot length and inclination angle can be approximately obtained by projecting the slot onto the two orthogonal directions. The two projections can be thought of as the length of two equivalent slots that excite the patch at the two separate polarizations. The inclination of the slots may also be adjusted, in order to compensate for error introduced by the matching stub, which is designed to be a quarter of a wavelength for only one frequency.
4.1.2. Dual feed microstrip antennas
The use of a circulator or diplexer that should be used in single fed dual-band microstrip antenna to isolate reception from transmission may be avoided by feeding the RMSA at two orthogonal points as shown in Fig. 13(a) (Srinivasan et al. 2000a). Since these feed points are at null locations of the respective orthogonal modes, the loading of one feed point does not affect the input impedance at the other feed point. The isolation between the two modes using orthogonal feeds is nearly 30 dB and 40 dB at the lower and higher resonance frequencies, respectively.
Figure 13.
a) Rectangular microstrip antenna with two orthogonal feeds for dual-band operation, (b) Elliptical microstrip antenna with two orthogonal feeds, (c) Circular microstrip antenna with two orthogonal slots (Kumar & Ray 2003)
Similar results are obtained for an ellipse with two orthogonal feed points. This configuration is fed with two orthogonal electromagnetically coupled microstrip lines (Deepukumar et al. 1996). As before, the frequency ratio of dual-band operation is approximately equal to the ratio of the orthogonal dimensions in the two planes. The isolation between the two ports is 27 dB.
Another variation using a circular patch is shown in Fig. 13 (c). It is excited by two orthogonal microstrip lines through the two orthogonal slots cut in the ground plane. By changing the slot dimensions, the two orthogonal resonance frequencies can be changed (Murakami et al. 1993).
4.2. Multi-patch antenna design approach
It is also a common practice to utilize two or more patches to accomplish multi-band. This section describes two main multi-patch techniques for dual-band or multi-band antennas.
4.2.1. Multi-patch stacked antennas
The dual-frequency behavior of these antennas is obtained by means of multiple radiating elements, each of them supporting strong currents and radiation at the resonance. This category includes multi-layer stacked patches (Fig. 14) that can use circular (Long & Walton 1979; Dahele & Lee 1982; Bennegueouche et al. 1993; Iwasaki & Suzuki 1995), annular (Dahele et al. 1987; Tagle & Christodoulous 1997), rectangular (Wang, et al. 1990; Yazidi et al. 1993), and triangular (Bhatnagar et al. 1986) patches. These antennas operate with the same polarization at the two frequencies, as well as with a dual polarization.
Figure 14.
A dual-frequency stacked circular-disc antenna (Long & Walton 1979)
The same multilayer structures can also be used to broaden the bandwidth of a single-frequency antenna, when the two frequencies are forced to be closely spaced. In this latter case, the lower patch can be fed by a conventional arrangement and the upper patch by proximity coupling with the lower patch (Wang et al. 1990). In order to avoid disappearance of the upper resonance, the sizes of the two patches should be close, so that only a frequency ratio close to unity may be obtained. A direct probe feed for the upper patch may also be used (Long & Walton 1979; Dahele et al. 1987). In this case, the probe passes through a clearance hole in the lower patch, and is electrically connected to the upper patch. This kind of configuration insures one more degree of freedom (the hole radius) in designing the optimum matching at the two frequencies, and allows a wider range of the frequency ratio with respect to the structure in which the upper patch is electromagnetically coupled. In comparison with the resonant frequencies of the two isolated patches, the frequency of the upper (smaller) patch increases, and the frequency of the lower (larger) patch decreases. In any case, due to the strong coupling between the two elements, simple design formulas cannot be found, so that a full-wave analysis is, in general, required in the first phase of the design.
Figure 15.
An aperture-coupled rectangular microstrip antenna with two slots: (a) top and (b) side views (Yazidi et al. 1993)
Coplanar parallel dipoles fed by aperture coupling could be used to obtain multi-frequency operation. The dipoles of different lengths are fed by a microstrip line through a rectangular slot cut in the ground plane. In general, this antenna consists of 2N dipoles of N different lengths, which are symmetrically excited through the aperture at N frequencies (Croq & Pozar 1992). Either the longest identical pair of dipoles could be placed in the center of the slot and smallest identical pair close to the edges of the slot, or the smallest dipoles could be placed in the center and the longest at the edge. For the latter case, six symmetrical dipoles are shown in Fig. 16. Since there are three pairs of dipoles, there will be three resonance frequencies. The radiation pattern is in the broadside direction at all the three frequencies, and the antenna is attractive for its simplicity.
Figure 17.
Dual frequency sub-array microstrip antenna (Salvador et al. 1995)
Many radar and communication systems often require a large separation between the two frequencies, so the multi-resonator configuration requires patches of very different resonant lengths. A simple example of this concept is shown in Fig. 17 (Salvador et al. 1995). It consists of a cross-shaped patch at the S-band and a sub-array of four patches at the X-band. The resonance frequency of the cross-patch is only slightly perturbed by the addition of four square patches, since the radiating edges of the cross patch are away from the four square patches. However, the resonance frequency of the square patches is affected by the presence of the cross patch, which causes a reactive loading to the square patch. Therefore, the upper resonance frequency corresponding to the four square patches is slightly lower than that of the isolated square patches. The decrease of this upper frequency is noticeable when the spacing is less than the substrate thickness because of increased gap coupling. In designing the antenna, one should carefully choose the distance between the square patches, which should be less than 0.7l λ0 to avoid scan blindness at the upper frequency.
4.3. Loaded multi-band antennas
The patch can be loaded for multi-band operation of microstrip antennas. The loading could be primarily stubs, notches, pins, lumped elements like resistors or capacitors and slots. Nevertheless, combination of these loading is also possible. In the following section the load antenna techniques are described in brief.
4.3.1. Stub loaded microstrip antennas
The reactive-loading approach was first used in Richards et al. (1985), where an adjustable coaxial stub was employed. This structure may provide both tuning and design of the frequency ratio in a simple manner; on the other hand, it is encumbering and not well-suited for high frequencies. In Davidson et al. (1985), a more practical configuration is presented, in which the stub is constituted by a microstrip. The tuning of the two frequencies was obtained by changing the length of the short-circuited coaxial line. Instead of short circuited coaxial line, a λ/2 short-circuited microstrip line is used as shown in Fig. 18(b), which can be etched on the same substrate along with the patch. Antennas with a single stub have slightly higher cross-polar level because it is asymmetrical configuration. To make the configuration symmetrical, not harming dual frequency operation, a λ /4 open-circuited stub is placed along both the radiating edges of the rectangular patch.
Figure 18.
Various dual-band stub-loaded RMSA configurations: (a) short-circuited coaxial line, (b) short-circuited λ/2 stub (Kumar & Ray 2003)
Loading the radiating edge with an inset (Nakano & Vichien 1989; Palit et al. 1998) or a spur-line (Hernandez & Robertson 1995; Hernandez & Robertson 1993; Vaello & Hernandez 1998) (“notch loading”) is an alterative way to introduce a dual-frequency behavior that creates the same effect as the microstrip-loading effect, with the advantage of reduced size. However, both with stubs and notches, the frequency ratio cannot be designed to be higher than 1.2 without introducing strong cross-polarization levels or pattern distortion at the additional frequency.
4.3.3. Pins and lumped elements loaded dual-band antenna
Figure 20.
a) A rectangular microstrip antenna with shorting posts for dual-band operation, (b) top view of dual-band antenna mounted on the conducting telephone case, (c) Edge-Jed rectangular microstrip patch with double stub matching network and symmetrically loaded with two varactor diodes (Zhong & Lo 1983; Gao et al. 2002; Waterhouse & Shuley 1992)
A rectangular microstrip antenna operating in the TM10 and TM30 modes has a broadside radiation pattern with the same polarization at the two frequencies. The ratio of their resonance frequencies is approximately three. A shorting post placed at the null position of the TM30 mode will not change its corresponding resonance frequency but will have a strong effect on the TM10 mode frequency (Zhong & Lo 1983). An RMSA with six shorting posts is shown in Fig. 20 (a). Since all these posts are located at the nulls of the TM30 mode, f2 remains constant at around 1,865 MHz, while f1 varies from 613 MHz to 891 MHz. The ratio f2/f1 varies from 3.0 to 2.1, which could be lowered by using more shorting posts. However similar principle might be seen in other antennas in literature (Gao et al. 2002; Pan & Wong 1998; Liu et al. 1997; Srinivasan et al. 1998). The structure of the antenna might be circular (Tang et al. 1997; Pan & Wong 1997) or triangular. Very high values of the frequency ratio (4-5) can be obtained by means of lumped loaded elements like resistors (Srinivasan et al. 2000b), varactors (Waterhouse & Shuley 1992), connected from the patch to the ground plane.
4.3.4. Slot antenna technique
Another kind of reactive loading can be introduced by etching slots on the patch. The slot loading allows for a strong modification of the resonant mode of a rectangular patch, particularly when the slots are oriented to cut the current lines of the unperturbed mode. In particular, as shown in (Wang & Lo 1984), the simultaneous use of slots and short-circuit vias allows a frequency ratio of from 1.3 to 3, depending on the number of vias. Other kinds of slot-loaded patches have been independently introduced in (Maci et al. 1993) and (Yazidi et al. 1993), and consist of a rectangular patch with two narrow slots etched close to and parallel to the radiating edge. The same configuration has been investigated in ([58] Maci, S., 1995), and extended to dual polarization in (Piazzesi et al. 1995).
Figure 21.
a) The microstrip antenna with shorting pins and slot, (b) Aperture coupled microstrip antenna for dual frequency operation (Wang & Lo 1984; Yazidi et al. 1993)
5. Dual-band high gain antennas & limitations
Many dual band antennas are developed and reported in the literature, especially for 2.4/5.8GHz. In order to achieve good radiation characteristics especially high gain, there are a lot of approaches taken. Printed dipoles (Kim et al. 2005; Lin et al. 2003), printed monopole (Wu et al. 2003; Jianhui et al. 2008; Wu et al. 2005), planar (Raj et al. 2005), slot (Wong et al. 2007) antennas are popularly used to provide dual frequency operation. But these antennas have complicated patch structures. Dielectric resonators (Chen et al. 2009; Ding & Leung 2009) and chip antennas (Moon & Park 2003) also provide dual band coverage which are very hard to fabricate. Rectenna (Suh & Chang 2002; Heikkinen & Kivikoski 2003), stacked patch (Yang et al. 2005), aperture coupled antenna (Yang et al. 2008), even though offer these two bands, occupy large space and difficult to integrate with handheld applications. However, the gain of these reported antennas are very low; lower than 7dBi, even printed simple element arrays (Lin et al. 2003; Wu et al. 2003) could not boost the gain higher.
Figure 22.
Geometry of the dual-band bidirectional high gain antenna (Zhang et al. 2009)
Figure 23.
Configuration of novel high-gain dual-band antenna (He et al. 2009)
Lately, to have high gain in these two bands a four-element printed dipole array antenna with balanced twin transmission line is reported (Zhang et al. 2009). Here the use of vertical patch increases the antenna volume. But still the gains for the 2.4 and 5.8 GHz bands are between 4.8–6 and 6–8.8 dBi, respectively.
Another novel high-gain dual band antenna is reported (He et al. 2009) shortly. The radiator is composed of three parts: the fork-like monopole, the rectangular ring, and the rectangular patch. A metal reflector with the same dimensions as the substrate is used behind the designed antenna, so the directivity/gain of the presented antenna is enhanced for both bands by suppressing the backside radiation. This antenna came up with a good peak gain; but still the antenna is inadequate to achieve desired bandwidth for lower frequencies and gain variation is severe over both the bands with an unlike radiation pattern in frequency bands. However taking the metal reflector into account requires bigger space for the antenna profile.
Figure 24.
a) Configuration of the proposed, high-gain, dual-loop antennas for MIMO access-point applications (b) Top view of the proposed, three-antenna MIMO system (Su 2010)
Another novel, high-gain, dual-loop antenna design applied to a three-antenna system for MIMO access point (AP) applications is presented in Fig. 24 (Su 2010). The metal shape of the dual-loop antenna is configured to be affixed to the surfaces of a foam base occupying a moderate size, which allows the antenna to be surface-mountable on the ground plane and to be concealed in the casing of the AP at the height of 10 mm. The proposed design comprises two loop antennas of uniform width, namely a large 2.4-GHz outer loop and a small 5-GHz inner loop, both attached onto the rectangular foam base and operating at 1.0-wavelength resonant mode. Both loops also share common antenna feeding and grounding portions. However, the antenna shows peak gain of 7dBi over the operating bands.
From the literature review, it is realized that previously reported antennas limit good performances only to one frequency band or sometimes lack in consideration of compactness. This can be attributed to the conventional feeding techniques that the antennas are being fed. So it is necessitated to introduce a new feeding technique to have the best performances in the operating bands.
6. Conclusion
A review of RFID technology from the point of antenna specifications in presented in this chapter. The antenna theory is also described for proper convenience of antenna characterization. The parameters are mainly related to scattering parameters including return loss and VSWR as well as radiation characteristics like radiation patterns, antenna gain, polarization and so on. Moreover, a wide literature review has been done in order to identify the techniques to design multi-band microstrip antennas. Mostly dual-frequency operation is discussed since they mean the basics of multi-band operation. However, it has been seen that these techniques can be combined to enhance multi-band antennas with wider bandwidths. Finally, the high gain antennas and limitations have been described and it is realized that the conventional feeding technique might limit the performance of multi-band antennas to only one frequency.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16518.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16518.xml",downloadPdfUrl:"/chapter/pdf-download/16518",previewPdfUrl:"/chapter/pdf-preview/16518",totalDownloads:3736,totalViews:571,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:1,dateSubmitted:"October 16th 2010",dateReviewed:"April 16th 2011",datePrePublished:null,datePublished:"July 20th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16518",risUrl:"/chapter/ris/16518",book:{slug:"current-trends-and-challenges-in-rfid"},signatures:"Ahmed Toaha Mobashsher, Mohammad Tariqul Islam and Norbahiah Misran",authors:[{id:"26661",title:"Mr",name:"Ahmed Toaha",middleName:null,surname:"Mobashsher",fullName:"Ahmed Toaha Mobashsher",slug:"ahmed-toaha-mobashsher",email:"i_toaha@yahoo.com",position:null,institution:null},{id:"39359",title:"Dr.",name:"Mohammad Tariqul",middleName:null,surname:"Islam",fullName:"Mohammad Tariqul Islam",slug:"mohammad-tariqul-islam",email:"tariqul@ukm.my",position:null,institution:null},{id:"39360",title:"Dr.",name:"Norbahiah",middleName:null,surname:"Misran",fullName:"Norbahiah Misran",slug:"norbahiah-misran",email:"bahiah@vlsi.eng.ukm.my",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction ",level:"1"},{id:"sec_2",title:"2. Radio frequency identification",level:"1"},{id:"sec_2_2",title:"2.1. RFID system",level:"2"},{id:"sec_2_3",title:"2.1.1. RFID tags",level:"3"},{id:"sec_3_3",title:"2.1.2. RFID reader",level:"3"},{id:"sec_5_2",title:"2.2. Near & far field concept & the selection of RFID operating bands",level:"2"},{id:"sec_7",title:"3. Antenna characteristics",level:"1"},{id:"sec_7_2",title:"3.1. Impedance bandwidth, reflection coefficient, VSWR & return loss",level:"2"},{id:"sec_8_2",title:"3.2. Radiation pattern",level:"2"},{id:"sec_9_2",title:"3.3. Antenna polarization",level:"2"},{id:"sec_10_2",title:"3.4. Directivity & gain",level:"2"},{id:"sec_12",title:"4. Multi-band antenna techniques: review",level:"1"},{id:"sec_12_2",title:"4.1. Higher order or orthogonal mode microstrip antennas",level:"2"},{id:"sec_12_3",title:"4.1.1. Single feed dual-band microstrip antenna",level:"3"},{id:"sec_13_3",title:"4.1.2. Dual feed microstrip antennas",level:"3"},{id:"sec_15_2",title:"4.2. Multi-patch antenna design approach",level:"2"},{id:"sec_15_3",title:"4.2.1. Multi-patch stacked antennas",level:"3"},{id:"sec_16_3",title:"4.2.2. Multi-patch co-planar antennas",level:"3"},{id:"sec_18_2",title:"4.3. Loaded multi-band antennas",level:"2"},{id:"sec_18_3",title:"4.3.1. Stub loaded microstrip antennas",level:"3"},{id:"sec_19_3",title:"4.3.2. Notch-loaded dual-band microstrip antennas",level:"3"},{id:"sec_20_3",title:"4.3.3. Pins and lumped elements loaded dual-band antenna",level:"3"},{id:"sec_21_3",title:"4.3.4. Slot antenna technique",level:"3"},{id:"sec_24",title:"5. Dual-band high gain antennas & limitations",level:"1"},{id:"sec_25",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'ChenH.M.WangY.K.LinY.F.LinS.C.PanS.C.\n\t\t\t\t\t2009\n\t\t\t\t\tA compact dual-band dielectric resonator antenna using a parasitic slot. 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1Institute of Space Science (ANGKASA), Universiti Kebangsaan
1Institute of Space Science (ANGKASA), Universiti Kebangsaan
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C. Nascimento and J. C. da S. Lacava",authors:[{id:"17182",title:"Dr.",name:"José Carlos",middleName:"Da Silva",surname:"Lacava",fullName:"José Carlos Lacava",slug:"jose-carlos-lacava"},{id:"21173",title:"PhD.",name:"Daniel",middleName:null,surname:"Nascimento",fullName:"Daniel Nascimento",slug:"daniel-nascimento"}]},{id:"14707",title:"Analysis of a Rectangular Microstrip Antenna on a Uniaxial Substrate",slug:"analysis-of-a-rectangular-microstrip-antenna-on-a-uniaxial-substrate",signatures:"Amel Boufrioua",authors:[{id:"18041",title:"Prof.",name:"Amel",middleName:null,surname:"Boufrioua",fullName:"Amel Boufrioua",slug:"amel-boufrioua"}]},{id:"14708",title:"Artificial Materials based Microstrip Antenna Design",slug:"artificial-materials-based-microstrip-antenna-design",signatures:"Merih Palandöken",authors:[{id:"19051",title:"Dr.Ing.",name:"Merih",middleName:null,surname:"Palandöken",fullName:"Merih Palandöken",slug:"merih-palandoken"}]},{id:"14709",title:"Particle-Swarm-Optimization-Based Selective Neural Network Ensemble and Its Application to Modeling Resonant Frequency of Microstrip Antenna",slug:"particle-swarm-optimization-based-selective-neural-network-ensemble-and-its-application-to-modeling-",signatures:"Tian Yu-Bo and Xie Zhi-Bin",authors:[{id:"21523",title:"Dr.",name:"Yu-Bo",middleName:null,surname:"Tian",fullName:"Yu-Bo Tian",slug:"yu-bo-tian"}]},{id:"14710",title:"Microstrip Antennas Conformed onto Spherical Surfaces",slug:"microstrip-antennas-conformed-onto-spherical-surfaces",signatures:"Daniel B. Ferreira and J. C. da S. Lacava",authors:[{id:"17182",title:"Dr.",name:"José Carlos",middleName:"Da Silva",surname:"Lacava",fullName:"José Carlos Lacava",slug:"jose-carlos-lacava"},{id:"21171",title:"Dr.",name:"Daniel",middleName:null,surname:"Ferreira",fullName:"Daniel Ferreira",slug:"daniel-ferreira"}]},{id:"14711",title:"Mathematical Modeling of Spherical Microstrip Antennas and Applications",slug:"mathematical-modeling-of-spherical-microstrip-antennas-and-applications",signatures:"Nikolaos L. Tsitsas and Constantinos A. Valagiannopoulos",authors:[{id:"20921",title:"Dr.",name:"Nikolaos L.",middleName:null,surname:"Tsitsas",fullName:"Nikolaos L. Tsitsas",slug:"nikolaos-l.-tsitsas"},{id:"20922",title:"PhD.",name:"Constantinos A.",middleName:null,surname:"Valagiannopoulos",fullName:"Constantinos A. Valagiannopoulos",slug:"constantinos-a.-valagiannopoulos"}]},{id:"14712",title:"Cavity-Backed Cylindrical Wraparound Antennas",slug:"cavity-backed-cylindrical-wraparound-antennas",signatures:"O. M. C. Pereira-Filho, T. B. Ventura, C. G. Rego, A. F. Tinoco-S., and J. C. da S. Lacava",authors:[{id:"17182",title:"Dr.",name:"José Carlos",middleName:"Da Silva",surname:"Lacava",fullName:"José Carlos Lacava",slug:"jose-carlos-lacava"},{id:"19227",title:"PhD.",name:"Odilon",middleName:null,surname:"Pereira Filho",fullName:"Odilon Pereira Filho",slug:"odilon-pereira-filho"},{id:"19450",title:"Mr.",name:"Thiago",middleName:null,surname:"Ventura",fullName:"Thiago Ventura",slug:"thiago-ventura"},{id:"19451",title:"PhD.",name:"Cassio",middleName:null,surname:"Rego",fullName:"Cassio Rego",slug:"cassio-rego"},{id:"19452",title:"Prof.",name:"Alexis F.",middleName:null,surname:"Tinoco Salazar",fullName:"Alexis F. Tinoco Salazar",slug:"alexis-f.-tinoco-salazar"}]},{id:"14713",title:"Analysis into Proximity-Coupled Microstrip Antenna on Dielectric Lens",slug:"analysis-into-proximity-coupled-microstrip-antenna-on-dielectric-lens",signatures:"Lawrence Mall",authors:[{id:"18397",title:"Dr.",name:"Lawrence",middleName:null,surname:"Mall",fullName:"Lawrence Mall",slug:"lawrence-mall"}]},{id:"14714",title:"Methods to Design Microstrip Antennas for Modern Applications",slug:"methods-to-design-microstrip-antennas-for-modern-applications",signatures:"K. Siakavara",authors:[{id:"18497",title:"PhD.",name:"Katherine",middleName:null,surname:"Siakavara",fullName:"Katherine Siakavara",slug:"katherine-siakavara"}]},{id:"14715",title:"Fractal-Shaped Reconfigurable Antennas",slug:"fractal-shaped-reconfigurable-antennas",signatures:"Ali Ramadan, Mohammed Al-Husseini, Karim Y. Kabalan and Ali El-Hajj",authors:[{id:"17558",title:"Dr.",name:"Mohammed",middleName:null,surname:"Al-Husseini",fullName:"Mohammed Al-Husseini",slug:"mohammed-al-husseini"},{id:"21637",title:"Mr.",name:"Ali",middleName:null,surname:"Ramadan",fullName:"Ali Ramadan",slug:"ali-ramadan"},{id:"21638",title:"Prof.",name:"Karim",middleName:null,surname:"Kabalan",fullName:"Karim Kabalan",slug:"karim-kabalan"},{id:"21639",title:"Prof.",name:"Ali",middleName:null,surname:"El-Hajj",fullName:"Ali El-Hajj",slug:"ali-el-hajj"}]},{id:"14716",title:"A Microstrip Antenna Shape Grammar",slug:"a-microstrip-antenna-shape-grammar",signatures:"Adrian Muscat and Joseph A. Zammit",authors:[{id:"19668",title:"Dr.",name:"Adrian",middleName:null,surname:"Muscat",fullName:"Adrian Muscat",slug:"adrian-muscat"},{id:"19669",title:"Dr.",name:"Joseph A.",middleName:null,surname:"Zammit",fullName:"Joseph A. Zammit",slug:"joseph-a.-zammit"}]},{id:"14717",title:"Electrically Small Microstrip Antennas Targeting Miniaturized Satellites: the CubeSat Paradigm",slug:"electrically-small-microstrip-antennas-targeting-miniaturized-satellites-the-cubesat-paradigm",signatures:"Constantine Kakoyiannis and Philip Constantinou",authors:[{id:"19252",title:"Dr.Ing.",name:"Constantine",middleName:"G.",surname:"Kakoyiannis",fullName:"Constantine Kakoyiannis",slug:"constantine-kakoyiannis"},{id:"21863",title:"Prof.",name:"Philip",middleName:null,surname:"Constantinou",fullName:"Philip Constantinou",slug:"philip-constantinou"}]},{id:"14718",title:"Circularly Polarized Microstrip Antennas with Proximity Coupled Feed for Circularly Polarized Synthetic Aperture Radar",slug:"circularly-polarized-microstrip-antennas-with-proximity-coupled-feed-for-circularly-polarized-synthe",signatures:"Merna Baharuddin and Josaphat Tetuko Sri Sumantyo",authors:[{id:"18521",title:"PhD.",name:"Merna",middleName:null,surname:"Baharuddin",fullName:"Merna Baharuddin",slug:"merna-baharuddin"},{id:"21582",title:"Prof.",name:"Josaphat",middleName:null,surname:"Tetuko Sri Sumantyo",fullName:"Josaphat Tetuko Sri Sumantyo",slug:"josaphat-tetuko-sri-sumantyo"}]},{id:"14719",title:"Circularly Polarized Slotted/Slit-Microstrip Patch Antennas",slug:"circularly-polarized-slotted-slit-microstrip-patch-antennas",signatures:"Nasimuddin, Zhi-Ning Chen and Xianming Qing",authors:[{id:"21459",title:"Dr.",name:"N",middleName:null,surname:"Nasimuddin",fullName:"N Nasimuddin",slug:"n-nasimuddin"}]},{id:"14720",title:"Microstrip Antenna Arrays",slug:"microstrip-antenna-arrays",signatures:"Albert Sabban",authors:[{id:"16889",title:"Dr.",name:"Albert",middleName:null,surname:"Sabban",fullName:"Albert Sabban",slug:"albert-sabban"}]},{id:"14721",title:"Microstrip Antennas for Indoor Wireless Dynamic Environments",slug:"microstrip-antennas-for-indoor-wireless-dynamic-environments",signatures:"Mohamed Elhefnawy and Widad Ismail",authors:[{id:"17004",title:"Dr.",name:"Widad",middleName:null,surname:"Ismail",fullName:"Widad Ismail",slug:"widad-ismail"},{id:"17005",title:"Dr.",name:"Mohamed",middleName:null,surname:"Elhefnawy",fullName:"Mohamed Elhefnawy",slug:"mohamed-elhefnawy"}]},{id:"14722",title:"DBDP SAR Microstrip Array Technology",slug:"dbdp-sar-microstrip-array-technology",signatures:"Shun-Shi Zhong",authors:[{id:"4123",title:"Prof.",name:"Shun-Shi",middleName:null,surname:"Zhong",fullName:"Shun-Shi Zhong",slug:"shun-shi-zhong"}]},{id:"14723",title:"Microwave Properties of Dielectric Materials",slug:"microwave-properties-of-dielectric-materials",signatures:"JS Mandeep and Loke Ngai Kin",authors:[{id:"21035",title:"Prof.",name:"Mandeep",middleName:null,surname:"Singh Jit",fullName:"Mandeep Singh Jit",slug:"mandeep-singh-jit"},{id:"135784",title:"Prof.",name:"Ngai Kin",middleName:null,surname:"Loke",fullName:"Ngai Kin Loke",slug:"ngai-kin-loke"}]},{id:"14724",title:"Hybrid Microstrip Antennas",slug:"hybrid-microstrip-antennas",signatures:"Alexandre Perron, Tayeb A. Denidni and Abdel R. Sebak",authors:[{id:"11473",title:"Prof.",name:"Tayeb A.",middleName:null,surname:"Denidni",fullName:"Tayeb A. Denidni",slug:"tayeb-a.-denidni"},{id:"21901",title:"Prof.",name:"Alexandre",middleName:null,surname:"Perron",fullName:"Alexandre Perron",slug:"alexandre-perron"},{id:"21902",title:"Prof.",name:"Abdel R.",middleName:null,surname:"Sebak",fullName:"Abdel R. Sebak",slug:"abdel-r.-sebak"}]},{id:"14725",title:"Integration of 60-GHz Microstrip Antennas with CMOS Chip",slug:"integration-of-60-ghz-microstrip-antennas-with-cmos-chip",signatures:"Gordana Klaric Felic and Efstratios Skafidas",authors:[{id:"18389",title:"Prof.",name:"Gordana Klaric",middleName:null,surname:"Felic",fullName:"Gordana Klaric Felic",slug:"gordana-klaric-felic"},{id:"21215",title:"PhD.",name:"Efstratios",middleName:null,surname:"Skafidas",fullName:"Efstratios Skafidas",slug:"efstratios-skafidas"}]},{id:"14726",title:"A Practical Guide to 3D Electromagnetic Software Tools",slug:"a-practical-guide-to-3d-electromagnetic-software-tools",signatures:"Guy A. E. Vandenbosch and Alexander Vasylchenko",authors:[{id:"18667",title:"PhD.",name:"Alexander",middleName:null,surname:"Vasylchenko",fullName:"Alexander Vasylchenko",slug:"alexander-vasylchenko"},{id:"20908",title:"Prof.",name:"Guy A. E.",middleName:null,surname:"Vandenbosch",fullName:"Guy A. E. Vandenbosch",slug:"guy-a.-e.-vandenbosch"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"74496",title:"Proton Cancer Therapy: Synchrotron-Based Clinical Experiences 2020 Update",doi:"10.5772/intechopen.94937",slug:"proton-cancer-therapy-synchrotron-based-clinical-experiences-2020-update",body:'\n
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1. Background
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1.1 Cancer medicine: precision, interdisciplinary and personalization
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Proton beam therapy (PBT) is developing in the context of a substantial increase in the incidence of cancer, the enormous advances made in our understanding of the biological basis and clinical implications of the disease, and the need to improve the therapeutic index: tumor control promotion and minimal clinically relevant toxicity. PBT is an accessible precision high-energy particle radiation technology, adapted to the therapeutic demands tendencies in health care and health budget of modern clinical practice [1]. Other radiotherapy (RT) solutions using hadron beams (hadron therapy) are too costly in the medium term in most clinical settings [2].
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PBT is now firmly established the era of precision medicine [3]. In oncology, the principles of medicine must be well defined: Interdisciplinarity and molecular individuation. Technological excellence will only be achieved when it encompasses the different medical specialties involved in treating each individual patient. Multidisciplinary Tumor Boards (MTD) are an essential part of an efficient approach to cancer management [4]. Personalized cancer treatment is characterized by a detailed analysis of the molecular configuration and evolution of each patient’s tumor (gene expression profile and nanobiology) [5]. The latest evidence suggests that tumors are probably unique to each patient, and that each tumor within the same patient (metastasis, primary site or recurrence) has its own biological pattern of progression and host adaptation pathway [6].
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1.2 Vectors in radiation oncology: individualized, functional, accurate and precise therapy
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RT currently helps to achieve cure over half of all patients that require this treatment; it relieves symptoms in 2 out of every 3 patients, and in general terms is a crucial therapeutic component in 3 out of every 4 cancer patients [7]. Furthermore, RT preserves organs and tissue structures (in contrast to the status resulting from radical extended surgery) and can be used in the context of radical treatment for oligometastatic and oligo-recurrent disease [8, 9]. Forecasts in healthcare systems in countries like the US suggest that by 2020, indications for RT in all types of cancer will have increased by 25%, and by 35% in the case of gastrointestinal malignancies [10].
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The foregoing estimations are based on the enormous technological advances made in RT in the last 30 years. If medical advances in clinical oncology have ushered in the era of precision medicine, interdisciplinary approach in recent decades in oncological RT (which specifically uses ionizing radiation to treat cancer) have ushered in the era of accurate precise RT.
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Precision RT is very efficient in promoting the local control (LC) of macroscopically identifiable cancer lesions (targeted by image-guided RT), and has an excellent therapeutic index, in other words, minimal, toxicity in normal radiation-sensitive tissue [11]. Because accurate precise RT has minimum effect on the function of the organs, systems (blood, liver, lungs, etc.) and tissues where the tumor is located, it has allowed clinicians to explore the radiobiological effects of hypofractionation, heterogeneous dose distribution within target volumes (adjusted for bio-heterogeneity), and of immunomodulatory, radiation-enhancing, radiation-sensitive and radiation-protective drug interactions [12]. Finally, one of the most promising aspects of accurate precise RT is the potencial of radiation-induced immunogenicity induced by hypofractionated (>8 Gy) RT [13]. Checkpoint inhibitors and other inmunomodulators allow clinicians to explore the potential of combining systemic immunotherapy effects with precision local and atoxic RT [14].
In the next decade, technological advances in PBT will bring further technological developments in precision RT into mainstream clinical practice. The dosimetric precision of PBT compares favorably with photon therapy and, guided by beam homogeneity in the delivery and imaging systems for precision control (4D and quasi-real-time control), its results in clinical practice will be equivalent and reproducible (Figure 1).
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The value of a treatment is defined as the outcomes obtained divided by the cost, measured over the entire cycle of care [15]. The clinical potential of proton cancer therapy requires sophisticated and realistic assessment of integral cost of care estimations including “costicity” (the cost of toxicity and general health-related supportive care). A collaborative effort between clinicians, patients, and policy makers is needed to design clinical trials with meaningful patient engagement. In particular, patients may help to identify and refine approaches that will lead to improved enrollment and retention in clinical trials as evidence generators sources. One crucial element in arriving at meaningful conclusions from such analyses is the need to account for the costs of managing not only acute RT toxicity but also long-term morbidities that can occur years to decades after RT is completed.
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In 2016, Mishra et al. reviewed the context of developing evidence in cancer proton therapy [16]. PBT clinical trials identified from clinicaltrials.gov and the World Health Organization International Clinical Trials Platform Registry showed a total of 122 active PBT clinical trials, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%) were interventional and 21% were observational studies. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%), tumors of the central nervous system (15%), and prostate cancer (12%). Five active studies (lung, esophagus, head and neck, prostate, breast) randomize patients between protons and photons, and 3 between protons and carbon ion therapy.
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The medical vision in 2020 and ahead, confirms that PBT clinical trial portfolio expands rapidly. Results of PBT studies, generated with synchrotron technology, need additional evaluation in terms of comparative effectiveness, as well as incremental effectiveness and health value offered by PBT in comparison with conventional radiation modalities among other topics of clinical relevance.
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Aside from future technological improvements, PBT has already been well received in the international medical community, and is now available in more than 57 centers worldwide [17].
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As in other precision RT techniques, phase III randomized clinical trials (RCTs) are not the best research setting, as they have intrinsic limitations in design and data analysis that prevent the positive findings of randomized trials investigating pharmaceuticals agents to be extrapolated to phase III studies with medical technologies. New availability of pencil-beam scanning and the consideration of new biological rationales such as avoidance of bone marrow and circulating blood radiation exposure, may be especially relevant to patients due to the central role of the immune system in cancer therapy.
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3. Evolutive and consolidated clinical outcomes
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Clinical results based on novel treatments need both time to mature, and a method of comparison that can define the best indications in the context of currently available accurate precise RT. Mature results from some studies recommend PBT for extreme indications in radioresistant, indolent yet highly infiltrative and extensive cancer lesions, and in patients requiring re-irradiation due to symptomatic oligo-recurrence.
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The following is a summary of the clinical results of a selective review of the latest, most influential, clinical studies analyzing synchrotron-based PBT institutional outcomes. The data available generally relates to established and developmental indications, together with some comparative analysis with other RT technologies. The information was obtained from a specific literature search and systematic reviews spanning 2010–2020.
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3.1 Pediatric tumors
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In 2020 PBT is the radiation therapy technology of election for pediatric oncology patients. The evolution towards this practice status has been fast. A survey conducted between July 2017 and June 2018 in all proton centers treating pediatric patients in 2016 worldwide identified a total of 54 centers operating in 11 countries (Particle Therapy Co-Operative Group, PTCOG website). Among the 40 participating centers (74%), a total of 1860 patients were treated in 2016 (North America: 1205, Europe: 432, Asia: 223.
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More than 30 pediatric tumor types were identified, mainly treated with curative intent. About half of the patients were treated with pencil beam scanning [18].
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Pediatric cancer patients referred to proton therapy centers do benefit from expert dedicated highly specialized care both in terms of normal tissue protection to radiation exposure during treatment delivery and from early access to medical integral care and radiotherapy process (5 weeks median starting time) [19].
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A critical milestone to facilitate long-term clinical outcomes research in the modern era has been achieved. The Pediatric Proton Consortium Registry (PPCR) has reported a total of 1854 patients enrolled from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors were the most frequent group of diseases (61%). The most common non-CNS tumors diagnoses were: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55) (Table 1) [20].
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Figure 1.
Clinical practice-based example of dose distribution in a craneospinal irradiation represented in 2D and 3D images. Treatment planning implementation in PBT enhances the perception of clinical benefit expected by protecting normal anatomy from unnecessary irradiation.
Median, range (Gy): IMRT: 50.4 (45–59.4) PBT: 50.4 (45–54)
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PB
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Post-RT enlargement rates PBT vs. IMRT: HR 2.15, 95% CI 1.06–4.38, p = 0.04). RT dose >50.4Gy(RBE) > rates of PsP (HR 2.61, 95% CI 1.20–5.68, p = 0.016)
In pts. undergone PBT LAR was lower than IMXT estimated LAR useful marker of secondary cancer induced by radiotherapy
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Table 1.
Clinical experiences with synchrotron PBT in pediatric tumors (AT/RT: atypical teratoid rhabdoid tumors; OS: overall survival; PFS: progression-free survival; LC: Local control; SMN: secondary malignant neoplasms; LET: linear energy transfer; TD50; dose at which 50% of patients would experience toxicity; PsP: Pseudoprogression; EFS: event-free survival; PB: passive beam; IMRT: intensity modulated radiotherapy; IMPT: intensity modulated proton therapy; CSI craniospinal irradiation).
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3.2 Central nervous system
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Radiotherapy confers survival advantages to patients with glioblastoma, medulloblastoma, germ cell, ependymoma and other intracranial neoplasms. This cost-effective and accessible treatment modality has proven efficacy in the adjuvant and definitive setting, as a first-line treatment or after prior lines of therapy. Neuro-radiation oncology has witnessed a burgeoning of new techniques, technologies and strategies that will better optimize the therapeutic ratio. Proton beam therapy (PBT) offers the potential to minimize late-onset toxicities while preserving disease-related outcomes. Multidisciplinary efforts explore synergies between the effects of radiotherapy and novel systemic therapies to tailor the delivery by molecular profile (Table 2) [41].
-mFT 4.4y −4-y actuarial rate hormone deficency, GH, TH, ACTH and FSH/LH were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. -Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency.
Risk of second cancer: 3-field 6MV photon vs. 4-field PBT
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CSI 23.4 RBE
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PB
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Lifetime risk second cancer 7.7 vs. 92%. Proton therapy confers lower predicted risk of second cancer for the pediatric medulloblastoma patient compared with photon therapy.
Clinical experiences in CNS tumors treated with synchrotron technology (2012–2019). OARs: organs at risk; RBE: radiobiological equivalence; CNS: central nervous system; ChT: Chemotherapy).
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3.3 Head and neck cancer
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PBT has emerged as a novel means to reduce toxicity and potentially further improve tumor control in head and neck cancer patients. The unique physical properties of charged particles allow a steep dose gradient with a reduced integral dose delivered to the patient in a proportion that can meaningfully reduce dose-related toxicity.
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For the National Comprehensive Cancer Network guidelines, proton therapy is a standard of care for base of skull tumors and is an optimized option for periorbital tumors. The use of proton therapy is expanding for other cancer sites. Novel forms of proton therapy such as IMPT, and technical improvements in dose modeling, patient setup, image guidance and radiobiology, will help further enhance the benefits of proton therapy. The present cost of delivering PBT is approximately 2–3 times higher than for delivering IMRT photons in the head and neck (H&N) cancer model of health care. However, the cost difference is reduced when costs are considered over the entire cycle of care. Predictive models using comorbidity scales could defined a subpopulation of patients for whom proton therapy is likely to reduce side effects and subsequent use of health care resources (Table 3) [52].
Prognostic impact of leukocyte counts before and during radiotherapy. IMRT vs. IMPT
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70 RBE/35 fx
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IMPT
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The radiotherapy type (IMRT vs. IMPT) was not associated with lymphopenia. Poor progression-free survival was associated with pretreatment leukocytosis and T status in univariate analysis, and pretreatment neutrophilia and advanced age on multivariate analysis.
mFT: 13.6 m 1-y: LC 68.4% OS 83.8% PFS 60% DMFS 75% 30% toxicity G3.
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Table 3.
Clinical experiences in head and neck cancer treated with synchrotron technology (2014–2019). (mFT: median follow up time).
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3.4 Lung cancer
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The call for designing and conducting “smart” proton therapy trials for lung cancer patients requires establishing clinical evidence and patient selection criteria to make proton therapy a truly personalized form of treatment. Comparative trials could focus on endpoints such as cardiac toxicity, low-dose radiation bath, and lymphopenia. The enhancement of dosimetric and biological advantages of PBT to improve clinical outcomes requires further developments in image-guided hypofractionated intensity modulated proton therapy (IMPT) and combinations of hypofractionated proton therapy with immunotherapy [63].
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For early-stage non-small cell lung cancer (NSCLC), the optimal clinical context for proton beam therapy (PBT) is challenging due to the increasing evidence demonstrating high rates of local control and good tolerance of stereotactic ablative body radiation (SABR). The potential advantage may be significant in treating larger tumors, multiple tumors, or central tumors. Most of the published studies are based on passive scattering PBT. Dosimetric benefits are likely to increase whith pencil beam scanning/intensity-modulated proton therapy (IMPT) [64]. A prospective longitudinal observational study of 82 patients with unresectable primary or recurrent NSCLC treated with 3-dimensional conformal radiation therapy (3DCRT), IMRT, or proton therapy included patient-reported symptom burden, assessed weekly for up to 12 weeks with the validated MD Anderson Symptom Inventory. Despite the fact that the proton group received significantly higher target radiation doses (P < 0.001), patients receiving proton therapy reported significantly less severe symptoms than did patients receiving IMRT or 3DCRT [63]. (Table 4).
IMRT(85 pts) vs. PSPT(49 pts) Esophageal toxicity (clinical and image)
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60–70 Gy/30–35 fx
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PB
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No significant difference in esophageal toxicity found between proton and photon-based radiation therapy for the study cohort, based on imaging biomarker or CTCAE grade
Concurrent ChT Analyze dosimetric variables and outcomes after adaptive replanning
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74 RBE/37 fx
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PB
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-Adaptative planning more often performed in large tumors. −107.1 cm 3 adaptive VS 86.4 cm 3nonadaptive. - Median n° fx: 13 -Improvement in esophagus and SC.
Central or superior tumors. Photon SBRT vs. PSPT vs. IMPT
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50 Gy/4 fx
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PB/IMPT
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When the PTV was within 2 cm of the critical structures, the PSPT and IMPT plans significantly reduced the mean maximal dose to the aorta, brachial plexus, heart, pulmonary vessels, and spinal cord.
-Change in pulmonary function over time with PBT -Concurrent ChT. -PBT (60) vs. 3DCRT (93) vs. IMRT (97)
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74 RBE
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PB
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Lung diffusing capacity for carbon monoxide is reduced in the majority of patients after radiotherapy with modern techniques. Multiple factors, including gross tumor volume, preradiation lung function, and dosimetric parameters, are associated with the DLCO decline.
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Table 4.
Clinical experiences in lung cancer treated with synchrotron technology (2011–2019).
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3.5 Esophageal cancer
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Radiation therapy (RT) has become an important component in the curative management of esophageal cancer (EC). Since most of the ECs seen in the Western hemisphere (i.e., Europe and the United States) are located in the mid- to distal-esophageal locations, heart and lungs invariably receive significant radiation doses. Proton beam therapy (PBT) provides the ability to further reduce normal tissue exposure because of its lack of exit dose, which is expected to provide clinically meaningful benefit for at least some EC patients [90].
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Investigators at MD Anderson Cancer Center have reported a phase IIb randomized trial comparing PBT and IMRT for patients with EC (NCT01512589). The primary endpoints are progression-free survival and total toxicity burden, which is a composite endpoint including serious adverse events and postoperative complications. Among the 145 patients randomized, total toxicity burden was 2.3 times higher for photon IMRT and the postoperative complications (50% of patients were operated) was 7.6 times higher in photon IMRT cohort. The 3-year overall survival was similar in both groups (44%) [91]. Results from prospective clinical trials will greatly improve our knowledge regarding the role and benefits expected from proton therapy for EC. (Table 5).
Total toxicity burden and postoperative complications significantly lower in PBT cohort. 3-y OS 44%.
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Table 5.
Clinical experiences in esophageal cancer treated with synchrotron technology (2012–2019).
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3.6 Hepatocellular cancer
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Proton beam therapy has the unique dosimetric performance, particularly valuable for the treatment of hepatocellular carcinoma (HCC). Clinical data is available in a limited number of patients, especially from Japan. In a systematic review from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC, a total of 13 cohorts from 11 papers. The reported actuarial local control rates ranged from 71 to 95% at 3 years, and the overall survival rates ranged from 25–42% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥ 3 late adverse events were reported among the 787 patients included in the analysis.
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The American Society for Radiation Oncology (ASTRO) issued a Model Policy on PBT in 2014 and PBT for HCC is covered by medical insurance in the United States. The Japanese Clinical Study Group of Particle Therapy (JCPT), the Japanese Society for Radiation Oncology (JASTRO), the Japanese Radiation Oncology Study Group (JROSG) and other groups are conducting multi-institutional prospective clinical trials in order to obtain approval for national health insurance for HCC and other cancers. The NCCN guidelines recommend that PBT may be appropriate in specific situations. In the Japanese guidelines, can be considered for HCCs that are difficult to treat with other local therapies, such as those with portal vein or inferior vena cava tumor thrombus and large lesions. The Korean Liver Cancer Study Group also mentioned the efficacy of PBT in their guidelines [104]. Guidelines from expert hepatologists evaluating the of data available for HCC patients will influence on the pattern of clinical practice considering the option of PBT as upfront therapy in the decision-making process (Table 6) [105].
Flow citometry lymphocite populations. CTLs NK prior/during/after.
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67.5 RBE / 15 fx
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PB
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• mOS 0.6 months for HCC and 14.5 months for ICC patients. • Longer OS significantly correlated with CTLs. • 42 months follow-up.
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Table 6.
Clinical experiences in liver cancer treated with synchrotron technology (2016–2019); RILD: radiation induced liver disease; mOS: median overall survival.
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3.7 Lymphoma
\n
In adult lymphoma survivors, radiation treatment with increase excess of radiation dose to organs at risk (OARs) does increase the risk for side effects, especially late toxicities. Minimizing radiation to organs at risk (OARs) in adult patients with Hodgkin and non-Hodgkin lymphomas involving the mediastinum is the decisive factor to select the treatment modality.
\n
Proton therapy reduces the unnecessary radiation to the OARs and reduces toxicities, especially the risks for cardiac morbidity and second cancers. In modern guidelines for adult lymphoma patients, the benefit from proton therapy and the advantages and disadvantages of proton treatment are considered. The dosimetric advantage of reducing the unnecessary dose to lung, breast, heart, spinal cord, vessels, vertebrae, thyroid and other structures in certain lymphoma involvements can be significant and highly desirable for patients that will be extreme long-term survivors at risk for severe chronic conditions and second malignancies (Table 7) [112].
IMPT significantly reduced lung and cardiac doses.
\n
\n\n
Table 7.
Clinical experiences in malignant lymphoma treated with synchrotron technology (2016–2017).
\n
\n
\n
3.8 Prostate
\n
PBT for prostate cancer patients has been a continuously growing option due to its promising characteristics of high precision dose distribution in the target and a sharp distal fall-off. Considering the large number of proton beam facilities in Japan, the further increase of patients undergoing this treatment will be related to the policies of the Japanese National Health Insurance (NHI) together with the development of medical equipment and technology. A review conducted review to identify and discuss research studies of proton beam therapy for prostate cancer in Japan (up to June 2018) included 23 articles (14 observational, focused on the adverse effects), and 7 interventional on treatment planning, equipment parts, as well as target positioning. Favorable clinical results of PBT were consistent and future research should focus on longer follow-up clinical data. PBT is a suitable treatment option for localized prostate cancer [116].
\n
At present, as particle beam therapy for prostate cancer is covered by the Japanese national health insurance system (since April 2018), and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically [117]. (Table 8).
No toxicity or QoL differences between PB and IMPT.
\n
\n\n
Table 8.
Clinical experiences in prostate cancer treated with synchrotron technology (2013–2018); GU: genitourologic; GI: gastrointestinal; QoL: Quality of life; ADT: androgen deprivation.
\n
\n
\n
3.9 Miscellaneous neoplasms and oncological clinical conditions
\n
PBT has been explored in a variety of cancer sites, histological subtypes and disease stages, including localized breast cancer, seminoma, pancreatic cancer, oligo-recurrences and other cancer conditions. (Table 9).
Dosimetric benefit shown in OARs. Lower mean doses to the contralateral lung, heart, esophagus, liver, and ipsilateral kidney, with increased contralateral lung sparing when mediastinal boost was required for nodal disease.
Clinical experiences in miscellaneous neoplasms and cancer conditions treated with synchrotron technology (2015–2017); LC: Local Control.
\n
A special challenge for defining PBT health value are geriatric cancer patients. Aging and chronic comorbidity is a medical reality in the present and future of oncology practice. It is projected that 1 of 5 Americans will be aged ≥65 years in 2050 and that 60% of cancers will occur in this group. As PBT resources are limited, centers have designed decision-making systems for prioritization. Elderly cancer patients are as fragile as pediatric oncology patients in terms of “normal” tissues protection importance, their tissues are not that “normal” at all but link to comorbid and biological senescence. A small pilot survey of international academic radiation oncologists with particular experience in geriatric care recommended a preference for irradiation with PBT, due to the age condition and cancer stage. Although this finding may sound provocative, it shows that, while currently inclined toward pediatrics, many practitioners see strong indications in the elderly population.
\n
The Eurocare showed that the age-standardized death rate for cancer was ≥12 times higher among elderly persons than among younger persons, in part, because treatments most commonly associated with cancer cure are less commonly given to elderly patients. The use of PBT will, through reducing morbidity, make the delivery of curative therapy more possible, merits a serious thought. Older patients are more likely to be admitted for cancer treatment as a result of an emergency or at an advanced stage. These factors may be associated with increased costs. The societal cost of delayed or inadequate treatment will require formal measurement against the cost of these advanced radiation technologies. PT should now be regarded as a relevant method to limit the short- and long-term toxicity of irradiation and reduce the need for costly supportive care.
\n
While research protocols no longer exclude patients based solely on age, many currently do so because of these patients’ comorbidities. It is time to consider the inclusion of comprehensively assessed elderly men and women in clinical trials of PBT. It is among these patients that some of the greatest benefits may yet be revealed. Until specific trials report their findings, a proactive guidance for the allocation of geriatric patients to PBT in the non-study situation is needed urgently [132].
\n
\n
\n
\n
4. Clinica Universidad de Navarra Proton Unit: early clinical experience
\n
In March 2020, after a 28 months installation period, the first cancer patient was treated. This is the first synchrotron equipment for PBT operating in Europe (Figure 2) and the third 360° gantry available for clinical use worldwide. (Figure 3). It is important to emphasize that the initiation of clinical activities was coincident with COVID pandemic, in one of the cities in the world (Madrid, Spain) with the more devastating epidemiologic and medical compromise. Under the strict institutional protective policy, none of the professionals involved in PBT intra-hospital process have had a positive test for COVID infection (up to the moment of writing the present manuscript October 2020), but several patients (11%) under treatment were detected to be infected along the treatment period (Table 10).
\n
Figure 2.
Characteristics of the Proton Beam Therapy Unit structure at the Cancer Center Universidad de Navarra, CCUN (Madrid Campus, Spain).
\n
Figure 3.
Distribution of exclusive synchrotron technology for PBT in the world. Institutions with active 360° gantry equipment available.
\n
\n
\n
\n
\n\n
\n
Patient characteristics
\n
\n
\n
\n
#
\n
%
\n
\n\n\n
\n
N° patients
\n
\n
\n
\n
55
\n
100
\n
\n
\n
Age, years
\n
\n
\n
Median (range)
\n
42 (3–86)
\n
\n
\n
\n
<30
\n
20
\n
36.3%
\n
\n
\n
>30
\n
35
\n
63.6%
\n
\n
\n
Gender
\n
\n
\n
Female
\n
29
\n
52.7%
\n
\n
\n
Male
\n
26
\n
47.3%
\n
\n
\n
Reirradiation
\n
\n
\n
Yes
\n
19
\n
34.5%
\n
\n
\n
No
\n
36
\n
65.4%
\n
\n
\n
COVID-19
\n
\n
\n
Positive
\n
6
\n
11%
\n
\n
\n
TUMOR
\n
\n
\n
Site
\n
\n
\n
Brain
\n
17
\n
30.9%
\n
\n
\n
Skull base
\n
4
\n
7.3%
\n
\n
\n
Head & Neck
\n
7
\n
12.7%
\n
\n
\n
Thorax
\n
5
\n
9%
\n
\n
\n
Spine
\n
8
\n
14.5%
\n
\n
\n
Upper abdomen
\n
2
\n
3.6%
\n
\n
\n
Pelvis
\n
12
\n
21.8%
\n
\n
\n
Histology
\n
\n
\n
Chordoma/chondrosarcoma
\n
9
\n
16.3%
\n
\n
\n
Rhabdomyosarcoma/Soft Tissue Sarcoma
\n
3
\n
5.4%
\n
\n
\n
Medulloblastoma
\n
5
\n
9%
\n
\n
\n
Ependimoma
\n
3
\n
5.4%
\n
\n
\n
Craneopharingioma
\n
2
\n
3.6%
\n
\n
\n
Malignant glioma
\n
7
\n
12.7%
\n
\n
\n
Lymphoma
\n
2
\n
3.6%
\n
\n
\n
Adenocarcinoma
\n
11
\n
20%
\n
\n
\n
Squamous Cell
\n
6
\n
10.9%
\n
\n
\n
Others
\n
7
\n
12.7%
\n
\n
\n
TREATMENT
\n
\n
\n
Previous surgery Previous radiotherapy Concomitant ChT
\n
33 19 10
\n
60% 34.5% 18.1%
\n
\n
\n
Proton Beam technique
\n
\n
\n
IMPT MFO synchrotron
\n
55
\n
100%
\n
\n
\n
N° incidences (median, range)
\n
3 (1–4)
\n
\n
\n
\n
1 2 3 >3
\n
1 15 27 12
\n
1.8% 27.3% 49% 21.8%
\n
\n
\n
Total doses
\n
\n
\n
\n
\n
<30 Gy RBE >30 Gy RBE
\n
2 53
\n
3.7% 96.3%
\n
\n
\n
Fractionation (median, range)
\n
24 (5–37)
\n
\n
\n
\n
<10 10–20 >20
\n
2 20 33
\n
3.6% 36.3% 60%
\n
\n
\n
Volume
\n
\n
\n
\n
\n
-Focal -Extended
\n
32 23
\n
58.2% 41.8%
\n
\n\n
Table 10.
Early clinical demographic data in patients treated in the Clinica Universidad de Navarra synchrotron PBT system: 6 months period (March–October 2020).
\n
\n
\n
5. Conclusions
\n
In principle, PBT offers a substantial clinical advantage over conventional photon therapy. This is because of the unique dose-deposition characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may allow escalation of tumor doses and greater sparing of normal tissues from unnecessary irradiation exposure, thus potentially improving local control and survival while at the same time reducing toxicity, carcinogenesis and improving quality of life. Synchrotron technology matches these benefits with proven reproducibility of its dosimetric properties and clinical observations.
\n
Despite the high potential of PBT, the clinical evidence supporting the broad use of protons is still under consolidation. The clinical data generated in institutions with synchrotron technology is abundant and of high scientific quality in terms of bibliometric records. An update has been summarized in the present publication. Clinical scientists operating with synchrotron proton beams are remarkably active in generating knowledge on topics such as cost effectiveness, the implementation of randomized trials and the collection of outcomes data in multi-institutional registries.
\n
Some fundamental issues to understand clinical outcomes are unsolved. This includes the equivalence of passive beams versus pencil beam radiation delivery and the relative biological effectiveness (RBE) of protons which is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc.
\n
From 2012 to 2017, both ASTRO’s Emerging Technology Committee report and ASTRO Model Policy document on proton beam therapy consider its recommendation reasonable in instances where sparing the surrounding normal tissue cannot be adequately achieved with photon-based radiotherapy and is of added clinical benefit to the patient. Based on the medical necessity requirements or the generation of clinical evidence in IRB-approved clinical trials or in multi-institutional patient registries adhering to Medicare requirements, PBT is expanding widely in clinical practice [133].
\n
For a practicing oncologist evaluating treatment plans has uncertainties about the radiobiological equivalences (RBE) and other dosimetric elements that are taken into current models, which means that, the dose displayed on a commercial treatment plan is likely to be less accurate. These features are not intuitive for oncologists and allied cancer specialties clinicians and need further refinement in the assessment of dosimetric displays. It means the dose effects may extend past the isodose lines shown on paper, not considering certain uncertainties and this effect beyond the target will always be in non-target normal tissues [134].
\n
Synchrotron technology is a component of the integral health care of a patient requiring radiotherapy and all the elements involved in the medical process need to be optimized to achieve an improved quality and safety standards in proton cancer therapy [135].
\n
\n
Acknowledgments
\n
\n“Authors express their recognition to all the health professionals involved in the initial efforts to start and consolidate the proton therapy program at Clinica Universidad de Navarra in Spain”.\n
\n
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"cancer, proton therapy, synchrotron, oncology, radiotherapy",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74496.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74496.xml",downloadPdfUrl:"/chapter/pdf-download/74496",previewPdfUrl:"/chapter/pdf-preview/74496",totalDownloads:21,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 7th 2020",dateReviewed:"November 6th 2020",datePrePublished:"December 22nd 2020",datePublished:null,dateFinished:"December 18th 2020",readingETA:"0",abstract:"Proton therapy is an efficient high-precision radiotherapy technique. The number of installed proton units and the available medical evidence has grown exponentially over the last 10 years. As a technology driven cancer treatment modality, specific sub-analysis based on proton beam characteristics and proton beam generators is feasible and of academic interest. International synchrotron technology-based institutions have been particularly active in evidence generating actions including the design of prospective trials, data registration projects and retrospective analysis of early clinical results. Reported evidence after 2010 of proton therapy from synchrotron based clinical results are reviewed. Physics, molecular, cellular, animal investigation and other non-clinical topics were excluded from the present analysis. The actual literature search (up to January 2020) found 192 publications, including description of results in over 29.000 patients (10 cancer sites and histological subtypes), together with some editorials, reviews or expert updated recommendations. Institutions with synchrotron-based proton therapy technology have shown consistent and reproducible results along the past decade. Bibliometrics of reported clinical experiences from 2008 to early 2020 includes 58% of publications in first quartile (1q) scientific journals classification and 13% in 2q (7% 3q, 5% 4q and 17% not specified). The distribution of reports by cancer sites and histological subtypes shown as dominant areas of clinical research and publication: lung cancer (23%), pediatric (18%), head and neck (17%), central nervous system (7%), gastrointestinal (9%), prostate (8%) and a miscellanea of neplasms including hepatocarcinoma, sarcomas and breast cancer. Over 50% of lung, pediatric, head and neck and gastrointestinal publications were 1q.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74496",risUrl:"/chapter/ris/74496",signatures:"Felipe Angel Calvo Manuel, Elena Panizo, Santiago M. Martin, Javier Serrano, Mauricio Cambeiro, Diego Azcona, Daniel Zucca, Borja Aguilar, Alvaro Lassaletta and Javier Aristu",book:{id:"10231",title:"Proton Therapy",subtitle:null,fullTitle:"Proton Therapy",slug:null,publishedDate:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10231.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Background",level:"1"},{id:"sec_1_2",title:"1.1 Cancer medicine: precision, interdisciplinary and personalization",level:"2"},{id:"sec_2_2",title:"1.2 Vectors in radiation oncology: individualized, functional, accurate and precise therapy",level:"2"},{id:"sec_4",title:"2. Developing proton beam therapy clinical evidence",level:"1"},{id:"sec_5",title:"3. Evolutive and consolidated clinical outcomes",level:"1"},{id:"sec_5_2",title:"3.1 Pediatric tumors",level:"2"},{id:"sec_6_2",title:"3.2 Central nervous system",level:"2"},{id:"sec_7_2",title:"3.3 Head and neck cancer",level:"2"},{id:"sec_8_2",title:"3.4 Lung cancer",level:"2"},{id:"sec_9_2",title:"3.5 Esophageal cancer",level:"2"},{id:"sec_10_2",title:"3.6 Hepatocellular cancer",level:"2"},{id:"sec_11_2",title:"3.7 Lymphoma",level:"2"},{id:"sec_12_2",title:"3.8 Prostate",level:"2"},{id:"sec_13_2",title:"3.9 Miscellaneous neoplasms and oncological clinical conditions",level:"2"},{id:"sec_15",title:"4. Clinica Universidad de Navarra Proton Unit: early clinical experience",level:"1"},{id:"sec_16",title:"5. Conclusions",level:"1"},{id:"sec_17",title:"Acknowledgments",level:"1"},{id:"sec_20",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nJaffray DA, Knaul FM, Atun R, et al. Global task force on radiotherapy control. 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Cancer Sci. 2017;108(3):444–447. doi:10.1111/cas.13140\n'},{id:"B23",body:'\nMizumoto M, Murayama S, Akimoto T, et al. Proton beam therapy for pediatric malignancies: a retrospective observational multicenter study in Japan. Cancer Med. 2016;5(7):1519–1525. doi:10.1002/cam4.743\n'},{id:"B24",body:'\nBuszek SM, Ludmir EB, Grosshans DR, et al. Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma. Pediatr Blood Cancer. 2019;66(11). doi:10.1002/pbc.27952\n'},{id:"B25",body:'\nMerchant TE. Proton beam therapy in pediatric oncology. Cancer J. 2008;15(4):298–305. doi:10.1097/PPO.0b013e3181b6d4b7\n'},{id:"B26",body:'\nAntonini TN, Ris MD, Grosshans DR, et al. Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy. Radiother Oncol. 2017;124(1):89–97. doi:10.1016/j.radonc.2017.06.010\n'},{id:"B27",body:'\nKahalley LS, Ris MD, Grosshans DR, et al. Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors. J Clin Oncol. 2016;34(10):1043–1049. doi:10.1200/JCO.2015.62.1383\n'},{id:"B28",body:'\nTaddei PJ, Khater N, Youssef B, et al. Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers. Biomed Phys Eng Express. 2018;4(2). doi:10.1088/2057-1976/aaa1ce\n'},{id:"B29",body:'\nPeeler CR, Mirkovic D, Titt U, et al. Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma. Radiother Oncol. 2016;121(3):395–401. doi:10.1016/j.radonc.2016.11.001\n'},{id:"B30",body:'\nGunther JR, Sato M, Chintagumpala M, et al. Imaging changes in pediatric intracranial ependymoma patients treated with proton beam radiation therapy compared to intensity modulated radiation therapy This work was presented previously at the 56th Annual American Society for Radiation Oncology Meetin. Int J Radiat Oncol Biol Phys. 2015;93(1):54–63. doi:10.1016/j.ijrobp.2015.05.018\n'},{id:"B31",body:'\nSato M, Gunther JR, Mahajan A, et al. Progression-free survival of children with localized ependymoma treated with intensity-modulated radiation therapy or proton-beam radiation therapy. Cancer. 2017;123(13):2570–2578. doi:10.1002/cncr.30623\n'},{id:"B32",body:'\nLudmir EB, Mahajan A, Paulino AC, et al. Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy. Neuro Oncol. 2019;21(5):686–695. doi:10.1093/neuonc/noz042\n'},{id:"B33",body:'\nZhang R, Howell RM, Taddei PJ, Giebeler A, Mahajan A, Newhauser WD. A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric medulloblastoma patients treated with photon or proton craniospinal irradiation. Radiother Oncol. 2014;113(1):84–88. doi:10.1016/j.radonc.2014.07.003\n'},{id:"B34",body:'\nBagley AF, Grosshans DR, Philip N V., et al. Efficacy of proton therapy in children with high-risk and locally recurrent neuroblastoma. Pediatr Blood Cancer. 2019;66(8):1–7. doi:10.1002/pbc.27786\n'},{id:"B35",body:'\nMcGovern SL, Okcu MF, Munsell MF, et al. Outcomes and acute toxicities of proton therapy for pediatric atypical teratoid/rhabdoid tumor of the central nervous system. Int J Radiat Oncol Biol Phys. 2014;90(5):1143–1152. doi:10.1016/j.ijrobp.2014.08.354\n'},{id:"B36",body:'\nGrant SR, Grosshans DR, Bilton SD, et al. Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics. Radiother Oncol. 2015;116(2):309–315. doi:10.1016/j.radonc.2015.07.022\n'},{id:"B37",body:'\nMizumoto M, Murayama S, Akimoto T, et al. Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan. Cancer Med. 2018;7(5):1870–1874. doi:10.1002/cam4.1464\n'},{id:"B38",body:'\nLadra MM, Edgington SK, Mahajan A, et al. A dosimetric comparison of proton and intensity modulated radiation therapy in pediatric rhabdomyosarcoma patients enrolled on a prospective phase II proton study. Radiother Oncol. 2014;113(1):77–83. doi:10.1016/j.radonc.2014.08.033\n'},{id:"B39",body:'\nLadra MM, Szymonifka JD, Mahajan A, et al. Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. J Clin Oncol. 2014;32(33):3762–3770. doi:10.1200/JCO.2014.56.1548\n'},{id:"B40",body:'\nTamura M, Sakurai H, Mizumoto M, et al. Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients. J Radiat Res. 2017;58(3):363–371. doi:10.1093/jrr/rrw088\n'},{id:"B41",body:'\nLudmir EB, Mahajan A, Ahern V, et al. Assembling the brain trust: the multidisciplinary imperative in neuro-oncology. Nat Rev Clin Oncol. 2019; 16(8):521–522. Doi: 10.1038/s41571-019-0235-z\n'},{id:"B42",body:'\nBronk JK, Guha-Thakurta N, Allen PK, Mahajan A, Grosshans DR, McGovern SL. Analysis of pseudoprogression after proton or photon therapy of 99 patients with low grade and anaplastic glioma. Clin Transl Radiat Oncol. 2018;9:30–34. doi:10.1016/j.ctro.2018.01.002\n'},{id:"B43",body:'\nWilkinson B, Morgan H, Gondi V, et al. Low Levels of Acute Toxicity Associated With Proton Therapy for Low-Grade Glioma: A Proton Collaborative Group Study. Int J Radiat Oncol. 2016;96(2):E135. doi:10.1016/j.ijrobp.2016.06.930\n'},{id:"B44",body:'\nAmsbaugh MJ, Grosshans DR, McAleer MF, et al. Proton therapy for spinal ependymomas: Planning, acute toxicities, and preliminary outcomes. Int J Radiat Oncol Biol Phys. 2012;83(5):1419–1424. doi:10.1016/j.ijrobp.2011.10.034\n'},{id:"B45",body:'\nJaramillo S, Grosshans DR, Philip N, et al. Radiation for ETMR: Literature review and case series of patients treated with proton therapy. Clin Transl Radiat Oncol. 2019;15:31–37. doi:10.1016/j.ctro.2018.11.002\n'},{id:"B46",body:'\nVatner RE, Niemierko A, Misra M, et al. Endocrine deficiency as a function of radiation dose to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. J Clin Oncol. 2018;36(28):2854–2862. doi:10.1200/JCO.2018.78.1492\n'},{id:"B47",body:'\nStoker JB, Grant J, Zhu XR, Pidikiti R, Mahajan A, Grosshans DR. Intensity modulated proton therapy for craniospinal irradiation: Organ-at-risk exposure and a low-gradient junctioning technique. Int J Radiat Oncol Biol Phys. 2014;90(3):637–644. doi:10.1016/j.ijrobp.2014.07.003\n'},{id:"B48",body:'\nBarney CL, Brown AP, Grosshans DR, et al. Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. Neuro Oncol. 2014;16(2):303–309. doi:10.1093/neuonc/not155\n'},{id:"B49",body:'\nBrown AP, Barney CL, Grosshans DR, et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys. 2013;86(2):277–284. doi:10.1016/j.ijrobp.2013.01.014\n'},{id:"B50",body:'\nZhang R, Howell R, Giebeler A, Taddei P, Mahajan A, Newhauser W. SU-E-T-257: Risk of Radiogenic Second Cancer after Photon and Proton Craniospinal Irradiation. Med Phys. 2012;39(6Part13):3762–3962. doi:10.1118/1.4735324\n'},{id:"B51",body:'\nBielamowicz K, Okcu MF, Sonabend R, et al. Hypothyroidism after craniospinal irradiation with proton or photon therapy in patients with medulloblastoma. Pediatr Hematol Oncol. 2018;35(4):257–267. doi:10.1080/08880018.2018.1471111\n'},{id:"B52",body:'\nBlanchard P, Gunn GB, Lin A, Foote RL, Lee NY, Frank SJ. Proton Therapy for Head and Neck Cancers. Semin Radiat Oncol. 2018;28(1):53–63. doi: 10.1016/j.semradonc.2017.08.004\n'},{id:"B53",body:'\nBlanchard P, Wong AJ, Gunn GB, et al. Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort. Radiother Oncol. 2016;121(3):381–386. doi:10.1016/j.radonc.2016.08.022\n'},{id:"B54",body:'\nFrank SJ, Cox JD, Gillin M, et al. Multifield optimization intensity modulated proton therapy for head and neck tumors: A translation to practice. Int J Radiat Oncol Biol Phys. 2014;89(4):846–853. doi:10.1016/j.ijrobp.2014.04.019\n'},{id:"B55",body:'\nBagley AF, Ye R, Garden AS, et al. Xerostomia-related quality of life for patients with oropharyngeal carcinoma treated with proton therapy. Radiother Oncol. 2020;142:133–139. doi:10.1016/j.radonc.2019.07.012\n'},{id:"B56",body:'\nJensen GL, Blanchard P, Gunn GB, et al. Prognostic impact of leukocyte counts before and during radiotherapy for oropharyngeal cancer. Clin Transl Radiat Oncol. 2017;7:28–35. doi:10.1016/j.ctro.2017.09.008\n'},{id:"B57",body:'\nZhang W, Zhang X, Yang P, et al. Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer. Radiother Oncol. 2017;123(3):401–405. doi:10.1016/j.radonc.2017.05.006\n'},{id:"B58",body:'\nSio TT, Lin HK, Shi Q, et al. Intensity modulated proton therapy versus intensity modulated photon radiation therapy for oropharyngeal cancer: First comparative results of patient-reported outcomes. Int J Radiat Oncol Biol Phys. 2016;95(4):1107–1114. doi:10.1016/j.ijrobp.2016.02.044\n'},{id:"B59",body:'\nGunn GB, Blanchard P, Garden AS, et al. Clinical Outcomes and Patterns of Disease Recurrence after Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma. Int J Radiat Oncol Biol Phys. 2016;95(1):360–367. doi:10.1016/j.ijrobp.2016.02.021\n'},{id:"B60",body:'\nLudmir EB, Grosshans DR, McAleer MF, et al. Patterns of failure following proton beam therapy for head and neck rhabdomyosarcoma. Radiother Oncol. 2019;134(January 2006):143-\n'},{id:"B61",body:'\nLudmir EB, Paulino AC, Grosshans DR, et al. Regional Nodal Control for Head and Neck Alveolar Rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2018;101(1):169–176. doi:10.1016/j.ijrobp.2018.01.052\n'},{id:"B62",body:'\nPhan J, Sio TT, Nguyen TP, et al. Reirradiation of Head and Neck Cancers With Proton Therapy: Outcomes and Analyses. Int J Radiat Oncol Biol Phys. 2016;96(1):30–41. doi:10.1016/j.ijrobp.2016.03.053\n'},{id:"B63",body:'\nLiao Z, Simone CB. Particle therapy in non-small cell lung cancer. Transl Lung Cancer Res. 2018; 7(2):141–152. doi:10.21037/tlcr.2018.04.11\n'},{id:"B64",body:'\nGomez DR, Li H, Chang JY. Proton therapy for early-stage non-small cell lung cancer (NSCLC). Transl Lung Cancer Res. 2018; 7(2):199–204. doi:10.21037/tlcr.2018.04.12\n'},{id:"B65",body:'\nLiu W, Schild SE, Chang JY, et al. Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer. Radiat Oncol Biol. 2016;95(1):523–533. doi:10.1016/j.ijrobp.2015.11.002\n'},{id:"B66",body:'\nWelsh J, Amini A, Ciura K, et al. Medical Dosimetry Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer. Med Dosim. 2013;38(4):442–447. doi:10.1016/j.meddos.2013.08.001\n'},{id:"B67",body:'\nMatney J, Park PC, Bluett J, et al. 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Proton Beam Therapy for Histologically or Clinically Diagnosed Stage I Non-Small Cell Lung Cancer (NSCLC): The First Nationwide Retrospective Study in Japan. Int J Radiat Oncol Biol Phys. 2020;106(1):82–89. doi:10.1016/j.ijrobp.2019.09.013\n'},{id:"B71",body:'\nElhammali A, Blanchard P, Yoder A, et al. Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer. Radiother Oncol. 2019;136:136–142. doi:10.1016/j.radonc.2019.03.029\n'},{id:"B72",body:'\nNakajima K, Iwata H, Ogino H, et al. Clinical outcomes of image-guided proton therapy for histologically confirmed stage i non-small cell lung cancer. Radiat Oncol. 2018;13(1):1–9. doi:10.1186/s13014-018-1144-5\n'},{id:"B73",body:'\nNantavithya C, Gomez DR, Wei X, et al. Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer. 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Predictors of high-grade esophagitis after definitive three-dimensional conformal therapy, intensity-modulated radiation therapy, or proton beam therapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;84(4):1010–1016. doi:10.1016/j.ijrobp.2012.01.071\n'},{id:"B78",body:'\nKoay EJ, Lege D, Mohan R, Komaki R, Cox JD, Chang JY. Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1093–1100. doi:10.1016/j.ijrobp.2012.02.041\n'},{id:"B79",body:'\nRegister SP, Zhang X, Mohan R, Chang JY. Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage i non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;80(4):1015–1022. doi:10.1016/j.ijrobp.2010.03.012\n'},{id:"B80",body:'\nChang JY, Komaki R, Lu C, et al. Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer. Cancer. 2011;117(20):4707–4713. doi:10.1002/cncr.26080\n'},{id:"B81",body:'\nShusharina N, Liao Z, Mohan R, et al. Differences in lung injury after IMRT or proton therapy assessed by 18FDG PET imaging. Radiother Oncol. 2018;128(1):147–153. doi:10.1016/j.radonc.2017.12.027\n'},{id:"B82",body:'\nJeter MD, Gomez D, Nguyen QN, et al. Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume With Intensity Modulated (Photon) Radiation Therapy or Intensity Modulated Proton Therapy and Concurrent Chemotherapy for Stage II to III Non-Small Cell Lung Cancer: A P. Int J Radiat Oncol Biol Phys. 2018;100(3):730–737. doi:10.1016/j.ijrobp.2017.10.042\n'},{id:"B83",body:'\nChang JY, Verma V, Li M, et al. Proton beam radiotherapy and concurrent chemotherapy for unresectable stage III non–small cell lung cancer: Final results of a phase 2 study. 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Prospective Study of Patient-Reported Symptom Burden in Patients with Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. J Pain Symptom Manage. 2016;51(5):832–838. doi:10.1016/j.jpainsymman.2015.12.316\n'},{id:"B88",body:'\nMcAvoy S, Ciura K, Wei C, et al. Definitive reirradiation for locoregionally recurrent non-small cell lung cancer with proton beam therapy or intensity modulated radiation therapy: Predictors of high-grade toxicity and survival outcomes. Int J Radiat Oncol Biol Phys. 2014;90(4):819–827. doi:10.1016/j.ijrobp.2014.07.030\n'},{id:"B89",body:'\nLopez Guerra JL, Gomez DR, Zhuang Y, et al. Changes in pulmonary function after three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;83(4):e537-e543. doi:10.1016/j.ijrobp.2012.01.019\n'},{id:"B90",body:'\nLin SH, Hallemeier CL, Chuong M. 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Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Int J Radiat Oncol Biol Phys. 2017;99(3):667–676. doi:10.1016/j.ijrobp.2017.06.2450\n'},{id:"B95",body:'\nShiraishi Y, Fang P, Xu C, et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy. Radiother Oncol. 2018;128(1):154–160. doi:10.1016/j.radonc.2017.11.028\n'},{id:"B96",body:'\nPrayongrat A, Xu C, Li H, Lin SH. Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. Adv Radiat Oncol. 2017;2(3):301–307. doi:10.1016/j.adro.2017.06.002\n'},{id:"B97",body:'\nShiraishi Y, Xu C, Yang J, Komaki R, Lin SH. 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Proton beam therapy and concurrent chemotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;83(3):e345-e351. doi:10.1016/j.ijrobp.2012.01.003\n'},{id:"B102",body:'\nZhang X, Zhao K le, Guerrero TM, et al. Four-Dimensional Computed Tomography-Based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophageal Cancer. Int J Radiat Oncol Biol Phys. 2008;72(1):278–287. doi:10.1016/j.ijrobp.2008.05.014\n'},{id:"B103",body:'\nLin SH, Hobbs BP, Verma V, et al. Randomized phase IIB trial of proton beam therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer. J Clin Oncol. 2020;38(14):1569–1578. doi:10.1200/JCO.19.02503\n'},{id:"B104",body:'\nIgaki H, Mizumoto M, Okumura T, Hasegawa K, Kokudo N, Sakurai H. A systematic review of publications on charged particle therapy for hepatocellular carcinoma. Int J Clin Oncol. 2018; 23(3):423–433. 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Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Int J Radiat Oncol Biol Phys. 2019;105(1):64–72. doi:10.1016/j.ijrobp.2019.01.076\n'},{id:"B110",body:'\nHong TS, Wo JY, Yeap BY, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2016;34(5):460–468. doi:10.1200/JCO.2015.64.2710\n'},{id:"B111",body:'\nGrassberger C, Hong TS, Hato T, et al. Differential Association Between Circulating Lymphocyte Populations With Outcome After Radiation Therapy in Subtypes of Liver Cancer. Int J Radiat Oncol Biol Phys. 2018;101(5):1222–1225. doi:10.1016/j.ijrobp.2018.04.026\n'},{id:"B112",body:'\nDabaja BS, Hoppe BS, Plastaras JP, et al. Proton therapy for adults with mediastinal lymphomas: The international lymphoma radiation oncology group guidelines. Blood. 2018; 132(16):1635–1646. 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Long-term outcomes of proton therapy for prostate cancer in Japan: a multi-institutional survey of the Japanese Radiation Oncology Study Group. Cancer Med. 2018;7(3):677–689. doi:10.1002/cam4.1350\n'},{id:"B121",body:'\nNakajima K, Iwata H, Ogino H, et al. Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer. Int J Clin Oncol. 2018;23(2):353–360. doi:10.1007/s10147-017-1209-8\n'},{id:"B122",body:'\nTakagi M, Demizu Y, Terashima K, et al. Long-term outcomes in patients treated with proton therapy for localized prostate cancer. Cancer Med. 2017;6(10):2234–2243. doi:10.1002/cam4.1159\n'},{id:"B123",body:'\nRana S, Cheng CY, Zhao L, et al. Dosimetric and radiobiological impact of intensity modulated proton therapy and RapidArc planning for high-risk prostate cancer with seminal vesicles. J Med Radiat Sci. 2017;64(1):18–24. doi:10.1002/jmrs.175\n'},{id:"B124",body:'\nPugh TJ, Munsell MF, Choi S, et al. Quality of life and toxicity from passively scattered and spot-scanning proton beam therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2013;87(5):946–953. doi:10.1016/j.ijrobp.2013.08.032\n'},{id:"B125",body:'\nGuttmann DM, Frick MA, Carmona R, et al. A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma. Radiother Oncol. 2017;124(2):271–276. doi:10.1016/j.radonc.2017.06.024\n'},{id:"B126",body:'\nHashimoto S, Shibamoto Y, Iwata H, et al. Whole-pelvic radiotherapy with spot-scanning proton beams for uterine cervical cancer: A planning study. J Radiat Res. 2016;57(5):524–532. doi:10.1093/jrr/rrw052\n'},{id:"B127",body:'\nHaque W, Wages C, Zhu XR, et al. Proton therapy for seminoma: Case report describing the technique, efficacy, and advantages of proton-based therapy for seminoma. Pract Radiat Oncol. 2015;5(2):135–140. doi:10.1016/j.prro.2014.07.006\n'},{id:"B128",body:'\nPan HY, Jiang S, Sutton J, et al. Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series. Pract Radiat Oncol. 2015;5(4):e345-e353. doi:10.1016/j.prro.2014.11.005\n'},{id:"B129",body:'\nDemizu Y, Mizumoto M, Onoe T, et al. Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan. Cancer Sci. 2017;108(5):972–977. doi:10.1111/cas.13192\n'},{id:"B130",body:'\nSmith NL, Jethwa KR, Viehman JK, et al. Post-mastectomy intensity modulated proton therapy after immediate breast reconstruction: Initial report of reconstruction outcomes and predictors of complications. Radiother Oncol. 2019;140:76–83. doi:10.1016/j.radonc.2019.05.022\n'},{id:"B131",body:'\nMutter RW, Remmes NB, Kahila MM, et al. Initial clinical experience of postmastectomy intensity modulated proton therapy in patients with breast expanders with metallic ports. Pract Radiat Oncol. 2017;7(4):e243-e252. doi:10.1016/j.prro.2016.12.002\n'},{id:"B132",body:'\nThariat J, Sio T, Blanchard P, et al. Using Proton Beam Therapy in the Elderly Population: A Snapshot of Current Perception and Practice. Int J Radiat Oncol Biol Phys. 2017; 98(4):840–842. doi: 10.1016/j.ijrobp.2017.01.007\n'},{id:"B133",body:'\nMohan R, Grosshans D. Proton therapy – Present and future. Adv Drug Deliv Rev. 2017; 109:26–44. doi:10.1016/j.addr.2016.11.006\n'},{id:"B134",body:'\nWoodward WA, Amos RA. Proton Radiation Biology Considerations for Radiation Oncologists. Int J Radiat Oncol Biol Phys. 2016; 95(1):59–61. doi: 10.1016/j.ijrobp.2015.10.022.\n'},{id:"B135",body:'\nCalvo FA, Chera BS, Zubizarreta E, et al. The role of the radiation oncologist in quality and patient safety: A proposal of indicators and metrics. Crit Rev Oncol Hematol. 2020;154(July):103045. doi:10.1016/j.critrevonc.2020.103045\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Felipe Angel Calvo Manuel",address:"fcalvom@unav.es",affiliation:'
Department of Radiation Oncology, Clinica Universidad de Navarra Cancer Center, Spain
Department of Radiation Oncology, Clinica Universidad de Navarra Cancer Center, Spain
'}],corrections:null},book:{id:"10231",title:"Proton Therapy",subtitle:null,fullTitle:"Proton Therapy",slug:null,publishedDate:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10231.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"183733",title:"Dr.",name:"Dorota",middleName:null,surname:"Hoja-Łukowicz",email:"dorota.hoja-lukowicz@uj.edu.pl",fullName:"Dorota Hoja-Łukowicz",slug:"dorota-hoja-lukowicz",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"2",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"Bitter Sweetness of Malignant Melanoma: Deciphering the Role of Cell Surface Glycosylation in Tumour Progression and Metastasis",slug:"bitter-sweetness-of-malignant-melanoma-deciphering-the-role-of-cell-surface-glycosylation-in-tumour-",abstract:"Malignant melanoma is the sixth most commonly diagnosed cancer in developed countries. Like in many cancers, survival rates are closely associated with the time of melanoma detection. Regrettably, most cases of melanoma are caught at diffuse state and methods used in clinical practice and experimental trials are not effective. Thus, there is a great interest in discovering biomarkers that could be used for screening those with melanoma, as prognostic and prediction factors as well as new potential targets for melanoma treatment. For this purpose, many groups have examined alteration in the structure and expression of carbohydrate part of glycoconjugates to identify changes that occur with melanoma. The observed changes include increased β1,6 branching correlating with higher abundance of polylactosamine extension, increased sialylation accompanied by differences in the position of sialic acid residues, increased fucosylation, higher levels of T and Tn antigens as well as changes in the expression of ganglioside structures. As a consequence of glycan modification, the loosened matrix adhesion, increased motility, higher invasive potential and metastasis formation have been observed. Growth and migration of melanoma cells have been also found to be stimulated by advanced glycation end products. Biomarker discovery is a multi-step process and the recent glycomic data on melanoma are mostly related to the discovery phase, as the first one leading to validation and standardisation steps.",signatures:"Małgorzata Przybyło, Marcelina E. Janik and Dorota Hoja-Łukowicz",authors:[{id:"182917",title:"Dr.",name:"Małgorzata",surname:"Przybyło",fullName:"Małgorzata Przybyło",slug:"malgorzata-przybylo",email:"malgorzata.przybylo@uj.edu.pl"},{id:"183174",title:"Dr.",name:"Marcelina",surname:"Janik",fullName:"Marcelina Janik",slug:"marcelina-janik",email:"marcelina.janik@uj.edu.pl"},{id:"183733",title:"Dr.",name:"Dorota",surname:"Hoja-Łukowicz",fullName:"Dorota Hoja-Łukowicz",slug:"dorota-hoja-lukowicz",email:"dorota.hoja-lukowicz@uj.edu.pl"}],book:{title:"Human Skin Cancer, Potential Biomarkers and Therapeutic Targets",slug:"human-skin-cancer-potential-biomarkers-and-therapeutic-targets",productType:{id:"1",title:"Edited Volume"}}},{title:"Cadherins and their Role in Malignant Transformation: Implications for Skin Cancer Progression",slug:"cadherins-and-their-role-in-malignant-transformation-implications-for-skin-cancer-progression",abstract:"Cadherins are a large family of Ca2+dependent adhesion proteins. They are transmembrane or closely related to membrane glycoproteins localized in specialized adhesive junction. The expression of various cadherins may be concomitant with cancer progression steps and the term ‘cadherin switch’ has been created due to the observation of down-regulation of E-cadherin (suppressor of metastatic potential) and up-regulation of N-cadherin (promoter of metastatic potential) expression during tumour progression. These changes are thought to be closely related to epithelial-to-mesenchymal transition of cells of many different types of cancer including skin cancers, and accompany the increase of their motility and invasion abilities resulting in the metastasis formation. The cadherin polypeptide is a potential substrate for post-translational modification, for example, N-glycosylation, and its important role in the regulation of cadherin function has been described. The changed glycosylation of cadherins has been described in various skin cancers including melanoma and was consistent with cadherins’ role in epithelial-to-mesenchymal transition. The detailed analysis of cadherin expression and cadherin-related glycosylation changes taking place during malignant transformation could be a key for better understanding of the nature of this process and may open new opportunities for the creation of more effective anticancer therapeutics and diagnostic tools.",signatures:"Marcelina E. Janik, Dorota Hoja-Łukowicz and Małgorzata Przybyło",authors:[{id:"182917",title:"Dr.",name:"Małgorzata",surname:"Przybyło",fullName:"Małgorzata Przybyło",slug:"malgorzata-przybylo",email:"malgorzata.przybylo@uj.edu.pl"},{id:"183174",title:"Dr.",name:"Marcelina",surname:"Janik",fullName:"Marcelina Janik",slug:"marcelina-janik",email:"marcelina.janik@uj.edu.pl"},{id:"183733",title:"Dr.",name:"Dorota",surname:"Hoja-Łukowicz",fullName:"Dorota Hoja-Łukowicz",slug:"dorota-hoja-lukowicz",email:"dorota.hoja-lukowicz@uj.edu.pl"}],book:{title:"Human Skin Cancer, Potential Biomarkers and Therapeutic Targets",slug:"human-skin-cancer-potential-biomarkers-and-therapeutic-targets",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"32293",title:"Prof.",name:"Mandi",surname:"Murph",slug:"mandi-murph",fullName:"Mandi Murph",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32293/images/163_n.jpg",biography:"Mandi Murph is a Georgia Cancer Coalition Scholar and an Assistant Professor in the College of Pharmacy at the University of Georgia in Athens, Georgia. Before coming to Georgia, Murph was a postdoctoral fellow in Systems Biology at the University of Texas M.D. Anderson Cancer Center in Houston. She won a young investigator award from the Biochemical Journal. She is an author on publications in Cancer Cell, Molecular Cancer, Journal of the National Cancer Institute, Molecular Cancer Research, PLoS ONE, Clinical Cancer Research and the Journal of Biological Chemistry. She has received grant funding from the Georgia Cancer Coalition and the National Cancer Institute, which is part of the National Institutes of Health.",institutionString:null,institution:{name:"University of Georgia",institutionURL:null,country:{name:"United States of America"}}},{id:"182917",title:"Dr.",name:"Małgorzata",surname:"Przybyło",slug:"malgorzata-przybylo",fullName:"Małgorzata Przybyło",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},{id:"182953",title:"Dr.",name:"Ewa",surname:"Pocheć",slug:"ewa-pochec",fullName:"Ewa Pocheć",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},{id:"183174",title:"Dr.",name:"Marcelina",surname:"Janik",slug:"marcelina-janik",fullName:"Marcelina Janik",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},{id:"183245",title:"Dr.",name:"Robert",surname:"Rollins",slug:"robert-rollins",fullName:"Robert Rollins",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183802",title:"Prof.",name:"Anna",surname:"Lityńska",slug:"anna-litynska",fullName:"Anna Lityńska",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183811",title:"Dr.",name:"Kimberly",surname:"Kim",slug:"kimberly-kim",fullName:"Kimberly Kim",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"185977",title:"Mr.",name:"Ali",surname:"Alshamrani",slug:"ali-alshamrani",fullName:"Ali Alshamrani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"191333",title:"Prof.",name:"James",surname:"Franklin",slug:"james-franklin",fullName:"James Franklin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"191334",title:"Prof.",name:"Aaron",surname:"Beedle",slug:"aaron-beedle",fullName:"Aaron Beedle",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"publication-agreement-chapters",title:"Publication Agreement - Book Chapter",intro:'
IntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors. To that end we maintain a flexible Copyright Policy guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
',metaTitle:"Publication Agreement - Chapters",metaDescription:"IN TECH aims to guarantee that original material is published while at the same time giving significant freedom to our authors. For that matter, we uphold a flexible copyright policy meaning that there is no transfer of copyright to the publisher and authors retain exclusive copyright to their work.\n\nWhen submitting a manuscript the Corresponding Author is required to accept the terms and conditions set forth in our Publication Agreement as follows:",metaKeywords:null,canonicalURL:"/page/publication-agreement-chapters",contentRaw:'[{"type":"htmlEditorComponent","content":"
The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
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Corresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
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The aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
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3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
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Comply with all instructions and guidelines provided by IntechOpen;
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Produce the Chapter with all due skill, care and diligence, and in accordance with good scientific practice;
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Submit all the corrections in due time as defined during the publishing process schedule.
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The Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
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All payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
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3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
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The Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
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3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
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4. CORRESPONDING AUTHOR'S WARRANTY
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4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
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The Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
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5. TERMINATION
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5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
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In case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
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6. INTECHOPEN’S DUTIES AND RIGHTS
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6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
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6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
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6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
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7. MISCELLANEOUS
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7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
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7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
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7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
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7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
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7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
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Any modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
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7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
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7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n
1. DEFINITIONS
\n\n
Corresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
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Co-Author: All other Authors of the Chapter besides the Corresponding Author.
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IntechOpen: IntechOpen Ltd., the Publisher of the Book.
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Book: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
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2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
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2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
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Last updated: 2020-11-27
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