**4. IMRT planning**

To achieve the dosimetric superiority of IMRT described in the last section, the planning procedure adopts an inverse approach. Inverse planning is a process to determine the optimal beam intensity. Numerous inverse planning approaches have been proposed and they can be classified as dose-volume based or biological index based [30]. The inverse planning procedure starts with the delineation of the regions of interest (ROI) which includes the PTV and OAR, followed by the beam configuration, objective function setting, and computer optimization. The workflow of IMRT planning is illustrated in **Figure 3**.

The procedures which require human input, including the setting of ROI delineation, beam configuration, and objective function, and evaluation of the plan are further discussed in the following sections.

#### **4.1 Target delineation**

Target delineation is the first and a very important step in IMRT planning to ensure effective treatment. The delineation of targets in head and neck cancers includes the high-risk, intermediate-risk, and low-risk planning target volume (PTV) [31]. The

intermediate-risk PTV refers to the regional lymph nodes and the isotropic margins of the high-risk PTV, the low-risk PTV refers to selective negative lymph nodes for prophylactic treatment, and the high-risk PTV encompasses the primary tumor or tumor bed and the positive lymph nodes. The consensus guideline on the delineation of elective lymph nodes levels is well-established [32]. The guideline classifies the regional lymph nodes in the head and neck region into 10 levels and defines their anatomical boundaries. While the selection of lymph nodes levels to be treated largely depends on different oncologists' judgment and individual patients' conditions, there have been published guidelines to review the criteria for the lymph nodes levels selection for treatment in different types of head and neck cancers [32, 33]. Contrary to the well-established consensus in the delineation of PTV for the regional lymph

*Treatment of Head and Neck Cancers Using Radiotherapy DOI: http://dx.doi.org/10.5772/intechopen.103678*

#### **Figure 3.**

*Comparisons in NPC patients with 3DCRT and IMRT plans. (a) Isodose distribution; (b) 3-dimensional dose color wash; (c) dose-volume histogram.*

nodes, the high-risk PTV delineation technique varies among oncologists. It can either be based on the isotropic expansion of the gross tumor volume or the inclusion of anatomical sub-sites [31]. The method of isotropic expansion to form PTV and the margins needed has been described [34]. The aim of the margins is to account for the uncertainties in the delivery of radiation to avoid target miss. On the other hand, the aim of the inclusion of anatomical subsites in the high-risk PTV in addition to the gross tumor volume is to include regions with possible microscopic extension [33].

The delineation of PTV is closely associated with the dose optimization regarding the skin dose. Usually, oncologists contour a clinical target volume (CTV) that covers all clinical and subclinical malignancy to be irradiated [35]. PTV, on the other hand, would add geometrical margins to CTV to ensure that the prescribed dose is adequately delivered. The CTV to PTV margins can be determined by previously reported margin recipes, accounting for systematic and random error during irradiation [36]. It is worth to note that there is a common circumstance when the head and neck cancers CTV stops just below the skin surface, i.e. no disease in the skin, while the PTV would cover the skin surface or even go beyond it after adding the CTV to PTV margins. In this case, the inverse planning procedure of IMRT would unnecessarily attempt to deliver an extra dose into the skin surface region [37], leading to excessive dose to the skin and adverse skin reactions [38]. Special attention is suggested to these cases, where the target is close to but not involving skin surface so PTV margins should be modified to avoid excessive skin surface normal tissue dose. Many imaging modalities contribute to the delineation of the target. It is important for the definition of tumor extent, the assessment of lymph nodes involvement, and the evaluation of perineural spread [39]. The common modalities include computed tomography (CT) and magnetic resonance imaging (MRI). Both CT and MRI are imaging modalities that provide sectional images with 3-dimensional reconstruction. Each of them has their unique strengths and therefore can provide complementary information in the localization of tumors and organs at risk.

Although both CT and MRI generate sectional images, their image generation mechanisms are not the same. The CT generates images using X-ray. By rotating the X-ray tube, a fan beam of X-ray is irradiated around the patients. After passing through the patient's body and being attenuated differentially by different body tissue with various densities, the X-ray detector receives many projections from the scanned body region. The computer then generates cross-sectional images based on the information gathered from the detected X-ray projections [40]. The resultant images are shown in grayscale according to the tissue density, which can be illustrated by appearing white for bone (high density), gray for soft tissue (medium density), and black for air (low density) [40]. In addition to the visualization of internal anatomy for the diagnosis purpose, the grayscale which is derived from the CT numbers and the robust geometrical information make the CT images suitable to be used for the dose calculation in radiotherapy planning [41].

On the other hand, MRI works by detecting the reaction of the MR-active nuclei in different parts of the body, mainly hydrogen, to the magnetic fields generated by the MRI machine [42]. MR-active nuclei refer to the particles that have net spins of the protons and neutrons, which create magnetic fields on the nuclei [43]. These MR-active nuclei, therefore, react to the strong magnetic field applied by the MRI machine. The image formation is first done by the application of magnetic field to patients' body to align the spinning axis of the MR-active nuclei in the body tissue. Then, by the application of short pulse radiofrequency, the alignment is displaced and then relaxed. This procedure, called relaxation, leads to the release of energy detected

#### *Treatment of Head and Neck Cancers Using Radiotherapy DOI: http://dx.doi.org/10.5772/intechopen.103678*

by the receiver coil [42, 44]. The two main types of relaxation are longitudinal relaxation time (T1) and transverse relaxation time (T2). T1 determines the rate of the spinning axis of the MR-active nuclei to realign to the MRI machine magnetic field, while T2 determines the rate of the MR-active nuclei to lose phase from the alignment [43]. The detection of the energy released can then be processed by computers to generate the cross-sectional images. The differences in the relaxation time (T1 or T2) and the density of the nuclei contribute to the tissue contrast in MRI images [43].

Utilization of both CT and MRI images in head and neck cancers is common because they are complementary to each other. In general, MRI is better in soft-tissue contrast while CT is better in detecting bone erosion. For example, T1 weighted MRI images are the most suitable to delineate NPC tumors because of better soft-tissue contrast and more sensitive in detecting the perineural extension of the tumor [45]. However, MRI images may fail to detect subtle skull base bone erosion, which can be complemented by coronary CT images in the bone window [46]. Also, in the cancer of the oral cavity, contrast-enhanced T1 weighted MRI images are the best for the delineation of tumor margin [47], while CT images are useful for the detection of the small lytic lesion in the cortical mandible [48].

In addition, PETCT also provides useful information to the commonly used CT and MRI images. The PETCT utilizes the mechanism of the increased uptake of the fluorodeoxyglucose (FDG) in tumor cells than in normal cells because of their higher metabolic activity [49]. The FDG uptake site can then be localized by scanners by detecting the radioactivity of the FDG. There are several circumstances that PETCT can provide supplementary information in addition to CT and MRI images. PETCT has been reported to have superior performance than CT and MRI in the detection of involved cervical lymph nodes. This is illustrated by the sensitivity of 90% and specificity of 94% in PETCT, compared with about 80% sensitivity and specificity in MRI and CT [50]. Also, PETCT is better in the detection of the unknown primary tumor, which is essential to decide the treatment regimen [51]. Furthermore, PETCT is useful in determining the presence of distant metastasis. It has the sensitivity and specificity of 89% and 95% respectively which indicates a very accurate diagnosis of the metastatic stage of the disease [52].

#### **4.2 Organs at risk delineation**

Inverse planning of IMRT involves the estimation of OAR dose for the calculation of the beam modulated intensity. The accuracy of the OARs delineation is crucial for the estimation of OARs dose, and hence the inverse planning procedure. There has been a consensus guideline on the OARs delineation in the head and neck regions [53]. This guideline listed the anatomical boundaries of 25 OARs in the head and neck region for the purpose of consistency in the delineation. Detailed atlas has also been supplemented for reference. **Figure 4** shows part of the atlas provided by the guideline

#### **4.3 Beam arrangement**

In the early application of IMRT, an equally spaced beam arrangement was commonly used [54, 55]. There are two other beam arrangement options available in the Eclipse treatment planning system (Varian Medical System, Palo Alto, USA). These include volumetric modulated arc therapy (VMAT) that enables rotational beams and beam angle optimization (BAO) that automatically chooses optimal static beam angles in either coplanar or non-coplanar beam arrangements.

**Figure 4.** *Part of the OAR delineation atlas. Adapted from [53]. Copyright 2015 the Authors.*
