**Motion Challenge of Thoracic Tumors at Radiotherapy by Introducing an Available Compensation Strategy by Introducing an Available Compensation Strategy**

**Motion Challenge of Thoracic Tumors at Radiotherapy** 

Ahmad Esmaili Torshabi and Seyed Amir Reza Dastyar Seyed Amir Reza Dastyar Additional information is available at the end of the chapter

Ahmad Esmaili Torshabi and

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/67444

#### **Abstract**

In this chapter a description is explained about radiotherapy as common available method in treatment of thoracic tumors located at thorax region of patient body and move mainly due to respiration. In radiotherapy of dynamic tumors, the correct and accurate information of tumor position during the therapeutic irradiation determine the degree of treatment success. In this chapter we investigate quantitatively the effect of tumor motion on treatment quality by considering to possible drawbacks and errors at external surrogate's radiotherapy as clinical treatment modality. For this aim, tumor motion information of a group of real patients treated with Cybeknife Synchrony system (from Georgetown University Hospital) was taken into account. A fuzzy logic based correlation model was employed for tumor motion tracking. Final results represent graphically the amount of tumor motion estimated by our utilized correlation model on three dimensions with targeting error calculation. It's worth mentioning that each strategy that can improve targeting accuracy of dynamic tumors may strongly enhance treatment quality by saving healthy tissues against additional high dose. In this chapter we just tried to introduce readers with thoracic tumor motion error as challenging issue in radiotherapy and motion compensation solutions, implemented clinically up to now.

**Keywords:** radiotherapy, moving thoracic tumors, external surrogate's radiotherapy, correlation model, motion compensation

### **1. Introduction**

Cancer is a range of diseases including abnormal cells that grow out of control. Cancerous cells can be formed in the tissues or organs of patient body, and the damaged cells can invade surrounding tissues. Among different types of cancers, some of them that are known as most

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

common cancers such as lung, breast, and prostate cancers cause many deaths independent of human race or ethnicity. It should be noted that with early detection and treatment, most people continue a normal life [1, 2] .

There are three common available methods for treatment of different cancers known as surgery, chemotherapy, and radiotherapy alone or in combination mode as surgery-chemotherapy, surgery-radiotherapy, chemotherapy-radiotherapy, or surgery-chemotherapy-radiotherapy as the best treatment modality. Each treatment strategy depends on how the cancer is diagnosed and its stage. In clinical treatment, doctor will discuss with patients about which treatments are most suitable for them [1–7]. In the following, a description is explained about common treatment methods ranging from surgery to radiotherapy.

The first and oldest option of treatment modality for a variety range of cancers is surgery or operation that means to perform surgery. The type of surgery will depend on the type of each cancer. Surgery is usually followed by chemotherapy or radiotherapy in modern methods in order to enhance treatment quality. In this method, whole cancerous cells or lesion must be cut and removed. Moreover, surrounding cells around tumors that may potentially be cancerous cells are removed to avoid growing secondary tumors after operation. The tissue surrounding the tumor volume is called the margin. Removing this nearby margin depends directly on the medical doctor decision during surgery. All forms of surgery are considered as invasive procedures. With conventional surgery, the surgeon makes large incisions through skin, muscle, and sometimes bone. In some situations, surgeons can use surgical techniques that are less invasive. These less-invasive techniques may speed recovery and reduce pain afterward. At surgery strategy, in order to avoid growing secondary cancer, whole organ that include tumor cells are removed. For example, there are two main types of breast cancer surgery as: First mode, surgery to remove the cancerous cells, entitled as breast-conserving surgery, where just the tumor and a little surrounding breast tissue are removed. Second mode, surgery to remove the whole breast, is called a mastectomy. However, in some cases, a mastectomy can be implemented by reconstructive surgery to recreate a bulge replacing the removed breast.

Chemotherapy involves using anti-cancer or cytotoxic medication to kill the cancer cells. Chemotherapy is usually given as an outpatient treatment, which means patients will not have to stay in hospital overnight. The medications are usually given through a drip straight into the blood through a vein. Chemotherapy is also usually used after surgery to destroy any cancer cells that have not been removed. This strategy is called as adjuvant chemotherapy. In some cases, chemotherapy is done before surgery, which is often used to shrink big tumors as much as possible. Several different medications are used for chemotherapy depending on tumor type and its site. For example, the choice of medication and the combination will depend on the type of breast cancer and how much it is spread [3, 6, 7]. Some patients may have chemotherapy sessions once every 2–3 weeks, over a period of 4–8 months, to give the body a rest in between treatments time. The main side effects of chemotherapy are caused by their influence on normal, healthy cells, such as immune cells.

Radiotherapy is the use of ionizing radiation beams such as high-energy X-rays or charge particles for cancer treatment. The therapeutic ionizing beam is generated by means of machines called linear accelerator or cyclotron or synchrotron and can damage and destroy cancer cells within the area being irradiated. Radiotherapy is a very specialist treatment and is a common treatment for various ranges of cancer such as head and neck or thoracic tumors. In most cases, radiotherapy is given after surgery. This reduces the risk of cancer coming back by getting rid of any possible cancer cells that are still in the area. **Figure 1** shows schematically the performance of linear machine as particle accelerator for therapeutic beam generation and irradiation to the patient [4, 5, 8].

common cancers such as lung, breast, and prostate cancers cause many deaths independent of human race or ethnicity. It should be noted that with early detection and treatment, most

There are three common available methods for treatment of different cancers known as surgery, chemotherapy, and radiotherapy alone or in combination mode as surgery-chemotherapy, surgery-radiotherapy, chemotherapy-radiotherapy, or surgery-chemotherapy-radiotherapy as the best treatment modality. Each treatment strategy depends on how the cancer is diagnosed and its stage. In clinical treatment, doctor will discuss with patients about which treatments are most suitable for them [1–7]. In the following, a description is explained about common

The first and oldest option of treatment modality for a variety range of cancers is surgery or operation that means to perform surgery. The type of surgery will depend on the type of each cancer. Surgery is usually followed by chemotherapy or radiotherapy in modern methods in order to enhance treatment quality. In this method, whole cancerous cells or lesion must be cut and removed. Moreover, surrounding cells around tumors that may potentially be cancerous cells are removed to avoid growing secondary tumors after operation. The tissue surrounding the tumor volume is called the margin. Removing this nearby margin depends directly on the medical doctor decision during surgery. All forms of surgery are considered as invasive procedures. With conventional surgery, the surgeon makes large incisions through skin, muscle, and sometimes bone. In some situations, surgeons can use surgical techniques that are less invasive. These less-invasive techniques may speed recovery and reduce pain afterward. At surgery strategy, in order to avoid growing secondary cancer, whole organ that include tumor cells are removed. For example, there are two main types of breast cancer surgery as: First mode, surgery to remove the cancerous cells, entitled as breast-conserving surgery, where just the tumor and a little surrounding breast tissue are removed. Second mode, surgery to remove the whole breast, is called a mastectomy. However, in some cases, a mastectomy can be implemented by

Chemotherapy involves using anti-cancer or cytotoxic medication to kill the cancer cells. Chemotherapy is usually given as an outpatient treatment, which means patients will not have to stay in hospital overnight. The medications are usually given through a drip straight into the blood through a vein. Chemotherapy is also usually used after surgery to destroy any cancer cells that have not been removed. This strategy is called as adjuvant chemotherapy. In some cases, chemotherapy is done before surgery, which is often used to shrink big tumors as much as possible. Several different medications are used for chemotherapy depending on tumor type and its site. For example, the choice of medication and the combination will depend on the type of breast cancer and how much it is spread [3, 6, 7]. Some patients may have chemotherapy sessions once every 2–3 weeks, over a period of 4–8 months, to give the body a rest in between treatments time. The main side effects of chemotherapy are caused by

Radiotherapy is the use of ionizing radiation beams such as high-energy X-rays or charge particles for cancer treatment. The therapeutic ionizing beam is generated by means of machines

people continue a normal life [1, 2] .

264 Radiotherapy

treatment methods ranging from surgery to radiotherapy.

reconstructive surgery to recreate a bulge replacing the removed breast.

their influence on normal, healthy cells, such as immune cells.

**Figure 1.** A schematic layout of linear accelerator and the process of therapeutic beam generation.

Ionizing rays are able to produce biological damages physically and chemically. They release their energy by colliding with cells. This can produce fast-moving electrons, which ultimately produce the biological damage to tissues. As seen in **Figure 2**, the therapeutic beam can directly break the DNA known as physical effect or prepare a toxic environment around the cancerous cell for killing them known as chemical effect.

It should be noted that healthy tissues surrounding the tumor volume are affected by ionizing radiation, but their cells can usually recover themselves better than cancer cells implementing proper treatment planning strategies.

In radiotherapy, the main principle is delivering the maximum dose onto tumor volume while keeping the normal nearby tissues save against the high dose at the same time. Treatments are usually given regularly over a period of time so that they have the greatest effect on the cancer cells [5]. Radiotherapy can also be given implanting radioactive seeds into tumor volume. This is called internal radiotherapy or brachytherapy. By this strategy, the normal cells will be saved against additional dose that may have side effects. In this technique, tumor accessibility is very important to implant radioactive seeds. Therefore, intra-cavity tumors are subjects for brachytherapy.

**Figure 2.** DNA damage of tumor cells by means of ionizing radiations.

**Figure 3** represents various steps of a successful radiotherapy based on 2D or 3D treatment planning system for tumor definition and localization. For this aim, tomography images are utilized as first step of treatment process. Simulation step realizes the best area to be irradiated as target using high dose of irradiation while causing the fewest possible side effects considering critical organs or organs at risk (OAR). Moreover, patient positioning and verification is another important issue of radiotherapy that must be carefully considered [4].

In general, total tumors can be categorized into two groups as static and dynamic tumors. This dividing comes from physical motion properties of tumors that is highly important during patient positioning and verification. In modern radiotherapy, tumor motion property is highly effective on treatment quality and must be taken into account during treatment planning process. In radiotherapy of dynamic tumors, the correct and accurate information of tumor position during the therapeutic irradiation determine the degree of treatment success. Among total tumors, dynamic tumors have been located in thorax and abdomen regions of patient body

**Figure 3.** Block diagram of treatment process during radiotherapy.

**Figure 3** represents various steps of a successful radiotherapy based on 2D or 3D treatment planning system for tumor definition and localization. For this aim, tomography images are utilized as first step of treatment process. Simulation step realizes the best area to be irradiated as target using high dose of irradiation while causing the fewest possible side effects considering critical organs or organs at risk (OAR). Moreover, patient positioning and verification is another important issue of radiotherapy that must be carefully considered [4].

**Figure 2.** DNA damage of tumor cells by means of ionizing radiations.

266 Radiotherapy

In general, total tumors can be categorized into two groups as static and dynamic tumors. This dividing comes from physical motion properties of tumors that is highly important during patient positioning and verification. In modern radiotherapy, tumor motion property is highly effective on treatment quality and must be taken into account during treatment planning process. In radiotherapy of dynamic tumors, the correct and accurate information of tumor position during the therapeutic irradiation determine the degree of treatment success. Among total tumors, dynamic tumors have been located in thorax and abdomen regions of patient body move due to breathing cycle phenomena, heart beat, and gastrointestinal system motions. The first case has the most important effect on targeting accuracy in radiation treatment. This motions and/or possible deformation that are usually nonregular cause a constraint to achieve the accurate knowledge of tumor location during the treatment process. This nonregularity issue refers to variations on breathing motion amplitude and frequency, while these two parameters are highly variable at each time for each patient and therefore require caution at clinical settings. It is obvious that the parameters of breathing motion phenomena are different at each patient, and a sort of adaptive treatment planning must be depicted for each patient on a case by case basis, and this issue is problematic for operators and needs more accuracy at treatment planning process. This motion error that is known as intra-fractional organs motion error may lead to a significant uncertainty of tumor localization. Therefore, a great amount of over or under dosage is happened onto tumor, and healthy surrounding tissues may receive high dose that is far away from prescribed dose that has been determined before irradiation [8–14]. Apart from intra-fraction motion error, we face with another motion error known as inter-fraction motion that refers to patient body displacement on treatment couch. This motion error must be considered at patient positioning stage during patient setup in pretreatment time few minutes before irradiation starting. Our focus in this chapter is on intra-fraction motion error.

At radiotherapy of dynamic tumors using old strategy, considerable margins were added around the planning target volume as treatment site to cover whole tumor displacement and possible deformation (known as internal target volume), and therefore, normal tissues surrounding the target may irradiate unnecessarily. During the past decade, radiation treatment of moving tumors has been undergone major technological and methodological strategies. Such this development has been obtained by investments in research programs, computer development, and technology transfer from research to medicine, and generating of new generation therapy units dedicated on tumor motion tracking in real time. These assessments were motivated by the requirements to enhance radiotherapy quality in patients with dynamic thoracic tumors such as those with lung, liver, or pancreas cancers. Several strategies have been proposed to compensate the effect of motion error on planned dose such as breathholding, respiratory motion-gating, and real-time tumor-tracking techniques [15–20].

In breath-holding technique, the goal is to immobilize the breast tumor by asking the patient to keep breathing in a specific level. Breath-holding technique requires cooperating patients that are problematic for patients with noncontrolled breathing [15, 17]. Respiratory-gated radiotherapy was proposed as another method to save normal surrounding tissue of dynamic region against additional high dose by irradiating the therapeutic beam only in a predefined phase of the breathing cycle [18, 19]. In real-time tumor-tracking technique, the irradiation beam is continuously repositioned dynamically to trace breast tumor motion in real time. In this method that is still under developing, the beam is always ON during a treatment fraction.

The developed technologies and methods for tumor tracking in X-ray radiotherapy can also be implemented for applications in hadron therapy using protons or heavier ions as therapeutic beams. Recent assessments show the using of particle therapy at worldwide in recent years, while 39 facilities were operational at the end of 2011, 33 with protons and six with carbon ions. Moreover, 20 new facilities are currently in the planning stage or under construction. As an example, hypo-fractionated particle therapy shows promising results in local control and overall survival in stage one of non–small lung cancer cells. Due to physical properties of charged particles, therapeutic beams can be steered by fast magnets to follow dynamic targets in real-time mode. Therefore, for treatment of moving tumors, charged particles such as protons and carbon ions have better geometrical and biological selectivity in regard with photon beam, and this useful property can improve tumor tracking and localization at clinical applications. At particle therapy, conventional dose delivery system is based on passive range modulation of the beam. Some scattering strategies are implemented to provide lateral beam flattering according to transverse size of tumor volume. Moreover, some passive devices such as ridge filters are used to make spread out Bragg peak (SOBP) as responsible to flat the beam longitudinally in direction of beam propagation inside tumor volume. Thus, 3D uniform dose can be generated onto tumor volume simultaneously. In particle therapy, the treatment of dynamic tumors can be taken into account on the basis of passive modulation technique or wobbling magnets performance.

case by case basis, and this issue is problematic for operators and needs more accuracy at treatment planning process. This motion error that is known as intra-fractional organs motion error may lead to a significant uncertainty of tumor localization. Therefore, a great amount of over or under dosage is happened onto tumor, and healthy surrounding tissues may receive high dose that is far away from prescribed dose that has been determined before irradiation [8–14]. Apart from intra-fraction motion error, we face with another motion error known as inter-fraction motion that refers to patient body displacement on treatment couch. This motion error must be considered at patient positioning stage during patient setup in pretreatment time few minutes

268 Radiotherapy

before irradiation starting. Our focus in this chapter is on intra-fraction motion error.

holding, respiratory motion-gating, and real-time tumor-tracking techniques [15–20].

In breath-holding technique, the goal is to immobilize the breast tumor by asking the patient to keep breathing in a specific level. Breath-holding technique requires cooperating patients that are problematic for patients with noncontrolled breathing [15, 17]. Respiratory-gated radiotherapy was proposed as another method to save normal surrounding tissue of dynamic region against additional high dose by irradiating the therapeutic beam only in a predefined phase of the breathing cycle [18, 19]. In real-time tumor-tracking technique, the irradiation beam is continuously repositioned dynamically to trace breast tumor motion in real time. In this method that is still under developing, the beam is always ON during a treatment fraction. The developed technologies and methods for tumor tracking in X-ray radiotherapy can also be implemented for applications in hadron therapy using protons or heavier ions as therapeutic beams. Recent assessments show the using of particle therapy at worldwide in recent years, while 39 facilities were operational at the end of 2011, 33 with protons and six with carbon ions. Moreover, 20 new facilities are currently in the planning stage or under construction. As an example, hypo-fractionated particle therapy shows promising results in local control and overall survival in stage one of non–small lung cancer cells. Due to physical properties of charged particles, therapeutic beams can be steered by fast magnets to follow dynamic targets in real-time mode. Therefore, for treatment of moving tumors, charged particles such as protons and carbon ions have better geometrical and biological selectivity in regard with photon beam, and this useful property can improve tumor tracking and localization at clinical applications. At particle therapy, conventional dose delivery system is based on passive range modulation of the beam. Some scattering strategies are implemented to provide lateral beam flattering according to transverse

At radiotherapy of dynamic tumors using old strategy, considerable margins were added around the planning target volume as treatment site to cover whole tumor displacement and possible deformation (known as internal target volume), and therefore, normal tissues surrounding the target may irradiate unnecessarily. During the past decade, radiation treatment of moving tumors has been undergone major technological and methodological strategies. Such this development has been obtained by investments in research programs, computer development, and technology transfer from research to medicine, and generating of new generation therapy units dedicated on tumor motion tracking in real time. These assessments were motivated by the requirements to enhance radiotherapy quality in patients with dynamic thoracic tumors such as those with lung, liver, or pancreas cancers. Several strategies have been proposed to compensate the effect of motion error on planned dose such as breathIn order to implement respiratory gated and real-time tumor-tracking radiotherapy techniques that mentioned above, tumor position information must be extracted as function of time during treatment. These strategies make use of time-resolved 4D imaging systems during treatment planning process in combination with technologies of image guiding. This solution enhances targeting accuracy during irradiation. Moreover, in treatment planning by using 4D computed tomography, images can highly improve target and sensitive organs around the tumors can be saved against additional doses accordingly in comparison with conventional radiotherapy. In other word, enlargement of margins around the dynamic tumors is significantly reduced using new technology considering tumor motion tracking.

Based on above descriptions, tumor motion monitoring requires additional imaging hard wares at treatment room to represent inter and intra fraction motions for patient geometrical setup in pre-treatment and real-time tumor tracking during treatment, respectively. Among several monitoring methods, some of clinically available techniques range from continuous X-ray imaging (i.e., fluoroscopy) to the use of external surrogates radiotherapy [20–33]. In an ideal form, the tumor motion would be observed continuously using fluoroscopic imaging system at external beam radiotherapy. This aim can also be achieved using cone beam computed tomography (CBCT) installed at radiotherapy treatment room. It is worth mentioning that with conventional megavoltage X-ray radiotherapy, inter-fraction daily variations can be obtained by time-resolved on-board images taken by CBCT that show respiratory-correlated tumor motion before treatment.

While tumor contrast is not proper during imaging of some organs by fluoroscopy or CBCT, a fiducial marker is implanted near or inside tumor volume representing a given point of that nonvisible tumor [8]. Therefore, internal clips represent tumor position with a 3D spatial point shown by x(t), y(t), and z(t) over treatment time.

During each irradiation fraction, implanted fiducial is traced by means of fluoroscopy imaging system, providing 3-dimensional (3D) coordinates at usually 30 frames per second. The tumor motion information is then utilized to turn the beam ON, while the tumor is in the desired place at radiotherapy based on respiratory motion-gated strategy. Apart from some advantageous points of using fluoroscopy imaging, this method would deliver significant imaging dose mainly at hypo-fractionated radiotherapy and radiosurgery [8, 9]. Therefore, a trade off must be taken into account between additional imaging dose and motion monitoring accuracy. As solution, using external surrogate's technique, the patient is kept away additional imaging dose versus fluoroscopy-based tumor motion monitoring.

At external surrogate's radiotherapy, the external rib cage and abdomen skin motion is synchronized and correlated with internal tumor motion by developing a proper correlation model in training step before the treatment. It should be mentioned that the external motion is traced by means of specific external markers placed on thorax region (rib cage and abdomen) of patient body and recorded by some monitoring systems such as infrared optical tracking (OTS) or laser-based systems. In contrast, the internal tumor motion is tracked using implanted internal clips inside or near the tumor volume and is visualized using orthogonal X-ray imaging system in snapshot mode. The generated correlation model can estimate the tumor motion from external markers data as input when internal marker data are out of access. The end result is a nonlinear mapping from the motion data of external markers as input to an output, which is the estimate of tumor position versus time. Recently, several respiratory motion prediction models have been developed in different mathematical approaches [34–37]. Since the breathing phenomena have inherently high uncertainty and therefore cause a significant variability in input/output data set, a mathematical model with highest accuracy may correlate input data with tumor motion estimation with less uncertainty error [8].

Since explaining all proposed strategies concerning tumor motion management is very extensive, we concentrated on external surrogate's radiotherapy in this chapter as clinical available strategy. Therefore, in this chapter, we quantitatively investigate the effect of motion error of thoracic tumors on treatment process at external surrogate's radiotherapy. To do this, the motion information of a group of real patients treated with Cyberknife Synchrony system (from Georgetown University Hospital) was taken into account, and the amount of possible errors of target localization was calculated using available statistical metrics [15].
