Chapter 1
Cancer is a general word for aggregation of different diseases ; it involves malignant tumour or growing caused when cells multiply without control destructing healthy tissues. It is the 3rd most common cause of certified deceases in Ministry of Healthy Malaysia infirmaries ( www.moh.gov.my ) . The World Health Organization statistics ( W.H.O ) shows that malignant neoplastic disease accounted for 7.9 million deceases in 2007 ( 13 % of all deceases worldwide ) and predicted about 12 million in 2030. The most common malignant neoplastic diseases for work forces it is lung, prostate, colon, caput and cervix, and vesica whereas for adult females are breast, uterus, colon, lung and ovary ( Lemoigne and Caner 2009 ) .
1.2 Head and Neck Cancer
Head and cervix malignant neoplastic disease represents a hard aggregation of tumours affecting mucosal surfaces of the upper aero-digestive piece of land ( Adelstein 2005 ) . Cell carcinoma of the caput and cervix affects more than 40,000 people each twelvemonth in the U.S. This represents 4 % to 5 % of the entire figure of malignant neoplastic diseases diagnosed per annum and at least 13,000 people each twelvemonth dice of this disease ( Brockstein and Masters 2003 ) . Carcinomas of the nasopharynx are more often diagnosed as a caput and cervix malignance in Southeast Asia. Nasopharyngeal carcinoma ( NPC ) is a squamous cell carcinoma ( SCC ) that normally develops around the ostium of the Eustachian tubing in the sidelong wall of the nasopharynx ( Sham, Choy et Al. 1990 ) . The first published of 14 instances of NPC was in 1901 and characterized clinically in 1922 ( Wei and Sham 2005 ) . However, they represent a comparatively rare disease in Western states ( Lu, Cooper et Al. 2009 ) . Malayan Chinese have the 2nd highest incidence of NPC in the universe hypertext transfer protocol: //thestar.com.my.
Harmonizing to the universe Health Organization ( WHO ) , NPC is classified into three types, WHO type 1 is keratinising SCC, WHO type 2 is transitional cell and WHO type 3 is undifferentiated. WHO type 1 is similar in visual aspect to SCC in other sites throughout the upper aero-digestive piece of land. The other two types of NPC are nonkeratinizing and represent less differentiated signifiers of NPC. These uniform signifiers, WHO types 2 and 3, are more common in the endemic part.
The incidence of NPC is lower than 1/105 in most countries. High-incidence countries are centralized in the southern portion of China ( including Hong Kong ) as shown in table 1.1. The highest incidence is found in Guangdong state, and the incidence in male can make 20-50/100000 ( Wei and Sham 2005 ; Lu, Cooper et Al. 2009 ) . Furthermore, the incidence of NPC is higher in male than female and the ratio is 2-3: 1 ( Parkin, Muir et Al. 1992 ; Wei and Sham 2005 ) . Dietary every bit good as familial factors affect to partial lessening in hazard to the development of NPC ( Bland, Daly et Al. 2001 ) . The incidence of NPC is increased with age after 30 old ages which the extremum is between 40 and 59 old ages in the high incident countries ( Lu, Cooper et Al. 2009 ) . Patients with WHO types 2 and 3 have a significantly higher 5- twelvemonth endurance rate ( 60 % to 7o % ) compared to patients with WHO type 1, keratinising SCC ( 20 % 5-year endurance ) ( Wen-Zhan, Dao-Lan et Al. 1989 ) . The factor that has the most serious impact on endurance is the presence and feature of lymph node. The caput and cervix part has a rich web of lymphatic vass, and SCC originated from the caput and neck country including NPC can metastasise to regional cervical cervix lymph nodes even in its early phases. Therefore, apprehension of the normal anatomy of the cervix lymph nodes is important for the intervention of caput and cervix malignant neoplastic diseases. To guarantee effectual communicating, a standard nomenclature is needed in the treatment of the complex lymph node parts. Assorted categorizations have been developed for this intent as shown in table 1.2 and Fig. 1.1 ( Lu, Cooper et Al. 2009 ) . The mere presence of regional lymph node engagement, particularly nodal engagement that is big is related with a hapless endurance ( Bland, Daly et Al. 2001 ) .
Table 1.1: incidence of nasopharyngeal carcinoma ( NPC ) in some malignant neoplastic disease registers of five continents in 1998-2002 ( N,1/105 ) ( Lu, Cooper et Al. 2009 )
Region and population
Age -standard incident rate
Male
Female
China
China Zhongashan
26.9
10.1
China Gaungzhou
22.2
9.8
China Hong Kong
17.8
6.7
China Shanghai
4.1
1.5
China Nangang District Harlin metropolis
1.1
0.5
Southeast Asia
Malaysia, Sarawak
15.0
6.5
Malaysia, Penang
9.3
3.3
Singapore
11.0
3.6
Singapore: Chinese
12.8
4.1
Singapore: Indian
1.8
0.1
Singapore: Malay
5.5
2.0
Philippines, Manila
5.8
2.4
Thailand, Chiang Mai
3.9
1.5
Thailand, Songkhla
2.7
0.9
Thailand, Lampang
2.5
1.5
USA
USA, Hawaii: Chinese
9.9
1.1
USA, Hawaii: Filipino
3.3
1.3
USA, Hawaii: Hawaiian
2.0
0.2
USA, San Francisco: Chinese
8.1
4.0
USA, San Francisco: Filipino
3.1
1.0
USA, Los Angeles: Chinese
6.0
1.9
USA, Los Angeles: Filipino
3.8
0.8
Middle East/North Africa
Algeria, Setif
5.4
1.7
Tunisia, Sousse
4.6
1.9
Uganda, Kyadondo
2.3
1.3
Koweit: Kuwaitis
1.7
0.8
Europe
Oesterreichs
0.4
0.2
Suomi
0.3
0.1
North-polar
Canada, Northwest Territories
4.3
1.3
USA, Alaska
1.5
0.9
Table 1.2: Theatrical production of nasopharyngeal carcinoma
( a ) ( B )
Figure 1.1: ( a ) Lymph secretory organs are joined together by a web of lymph channels. Lymph is a fluid that forms between the cells of the organic structure. ( B ) The sidelong wall of nasopharynx. ( http: //standardlifehealthcare.medi-health.info )
1.3 Role of radiation Therapy in intervention malignant neoplastic disease
Radiation therapy ( RT ) is the intervention of malignant neoplastic disease patients with average energy X ray, high energy X ray, gamma beam, proton, neutron or negatron beams. Radiation may be delivered to tumor sites from an external beginning ( i.e. Teletherapy or Linear Accelerators ) or at a short distance to the sites of tumour by utilizing certain radioactive beginnings called internal radiation therapy or Brachytherapy ( Khan 2009 ) . The biological effects of ionising radiation originate chiefly from harm to the Deoxyribonucleic acid of normal and tumour cells. Normal tissue cells suffer the same type of harm, but have better capacity to mend and command mechanisms. Any uncertainness on delivered dosage may either consequence in an under dose of the tumour or a complication for normal tissue. ICRU Report No. 50 ( Unit of measurements and Measurements 1993 ) recommends a mark dose uniformity within +7 % and -5 % of the dosage delivered to a chiseled prescription point within the mark. Patient apparatus, organ gesture and distortion and machine uncertainness e.g. gauntry angle and field sizes of the beam are the beginnings of the mistakes that degrade the exact dose bringing in PTV ( ICRU-83 ) . With the modern radiation therapy equipment and quality confidence plan, the machine mistakes are little compared to patient apparatus divergences and variety meats gesture. Therefore, intervention with external beam radiation therapy should be done carefully and exactly to accomplish conformal dose distribution to the tumour site and crisp dose autumn off to normal tissues.
Patients with malignant tumours can be treated with radiation therapy merely or as regards of other interventions such as surgery or chemotherapy as shown in Fig. 1.2. Approximately one tierce of patients still fail locally after healing Radiation Therapy ( RT ) with the betterment in malignant neoplastic disease remedy observed in the last 2-3 decennaries. In order to better local tumour control rates with RT the bringing of high doses to the tumour volume may be necessary ( Lemoigne and Caner 2009 ) .
Figure 1.2: About half of all malignant neoplastic disease patients receive radiation therapy, either as portion of their primary intervention or in connexion with returns or palliation. For Europe it was found that radiation therapy ( alone/in combination ) is successful in 18 % ( Lemoigne and Caner 2009 ) .
1.3.1 Three-dimensional Conformal Radiation Therapy ( 3D CRT ) of Nasopharyngeal Carcinoma
Three dimensional conformal radiation therapy ( 3-D CRT ) is used to stand for computing machines and particular imaging techniques such as CT, MRI or PET scans to demo the size, form and location of the tumour every bit good as environing organs.A ItA depends on 3-dimensional imagination to specify the mark ( tumour ) and to separate it from normal tissues. Therefore, this technique is to be able to maximise the mark dosage and to minimise the dosage to neighbored variety meats at hazard by multiple radiation beams and multileaf collimator MLCs. Once a suited dosage distribution has been reached, assorted other parametric quantities relevant to the intervention can be used, such as proctor units and patient apparatus parametric quantities. Modern, high-precision radiation therapy ( RT ) techniques are needed in order to implement the end of optimum tumour devastation and to present the minimal dosage to the environing tissues.
Nasopharyngeal carcinoma ( NPC ) is extremely sensitive to ionising radiation, and radiation therapy is the support intervention mode for non-metastatic disease ( Kam, Chau et Al. 2003 ) . For decennaries, NPC radiation therapy uses conventional intervention using planar and recently 3-dimensional techniques. Both techniques chiefly use opposed sidelong Fieldss with or without an anterior field focused to the primary tumour ( En-Pee, Pei-Gun et Al. 1989 ; Waldron, Tin et Al. 2003 ) . Disease control utilizing conventional radiation therapy techniques has been acceptable ; nevertheless, deficient dosage to parts of the marks and insufficient to protect critical constructions such as ocular decussation, middle/inner ear, eyes, spinal cord, and/or brain-stem may ensue in decreased disease control in advanced NPC. The comparing between intensity-modulated radiation therapy ( IMRT ) intervention programs and 3DCRT intervention programs for figure of nasopharyngeal carcinoma instances utilizing the dose-volume histograms of mark volumes and dose to the sensitive normal tissue constructions ( Xia, Fu et Al. 2000 ; Cozzi, Fogliata et Al. 2001 ; Hunt, Zelefsky et Al. 2001 ; Kam, Chau et Al. 2003 ; Poon, Xia et Al. 2007 ) . Their consequences showed that IMRT demonstrated better mark coverage and saving to a figure of variety meats at hazard ( OAR ) A including parotid secretory organs, A brain-stem, oculus, in-between and interior ear and spinal cord than that of 3D CRT. There are restrictions for utilizing 3DCRT such as
Need big figure of beams unless mark form is really simple.
Optimal beam angles frequently non-axial and hard or impossible to utilize.
In caput and neck country, big figure of sensitive tissues. So few beam waies work.
No acceptable program for concave mark.
So, caput and cervix malignant neoplastic diseases, particularly NPC is ideally suited for intervention with IMRT to save of critical normal constructions and better mark coverage ( Laskar, Bahl et Al. 2008 ) .
1.3.2 Intensity Modulated Radiotherapy ( IMRT )
Intensity-modulated radiation therapy ( IMRT ) is capable of bring forthing complex 3-dimensional dosage distributions to conform closely to the mark volume, even in tumours with concave isodose forms ( 30 % of tumour ) ( Nutting, Dearnaley et Al. 2000 ) . It represents one of the most important proficient progresss in radiation therapy ( Ezzell, Galvin et Al. 2003 ) . In the IMRT, the strength of the incident fluence radiation field can be varied and each field can be consisted of several little strength modulated beams ( beamlets ) to fit the projection of the planning mark volume ( PTV ) . So, the fluence from each beam creates acceptable uniform dosage within the PTV and low dosage to OARs. The subsequent dosage distributions from IMRT are extremely conformal and unambiguously. It can bring forth a concave dose distribution and consequences in steep dose gradients between be aftering mark volumes ( PTV ) and organs at hazard ( OAR ) ( Nutting, Dearnaley et Al. 2000 ) . An acceptable intervention program is one in which be aftering mark dose uniformity is within +7 % and -5 % of the dosage delivered to a well defined prescription point within the mark, and the doses to OAR are low. Furthermore, by utilizing this technique it is Possible to administer the dose homogeneousness to suit tumours with complex form ( e.g. concave form ) while saving critical normal tissues ( Dogan, Leybovich et al. 2002 ; Kam, Chau et Al. 2003 ) .
Figure 1.3: Comparison of 3DCRT ( left ) and IMRT ( right ) . The ability for 3DCRT to change isodose lines was limited to determining of i¬?eld boundaries with MLCs or blocks, the usage of cuneuss or compensators for losing tissues, and cardinal blocks for screening critical constructions. The IMRT beams can hold extremely non-uniform beam strengths ( i¬‚uences ) and are capable of bring forthing a more concave-shaped absorbed-dose distribution ( Cheung 2006 ) .
1.4 Treatment planning methods
The package codification used to cipher dose distributions in a patient or apparition is called the “ intervention planning system ” ( TPS ) . There are two methods of TPSs. The first is called A« Forward be aftering A» used in 3DCRT. For this method of intervention planning, the contriver defines the beam parametric quantities like beam ( way, figure of beams, and size of the beam ) , collimator scene ( place of MLCs ) , beam burdening factors of each field, the usage of cuneuss, compensators or blocks. Next, the dosage is calculated for each isodose profile or point dosage utilizing the intervention planning system. For the worse instance, the contriver shall modify some parametric quantities of the beam manually till he gets a satisfactory program ( Eisbruch, Marsh et Al. 1998 ; Fogliata, Cozzi et Al. 1999 ) . The 2nd method is called A« Inverse planning A» used in IMRT. The reverse intervention planning is the method of be aftering where aims such as mark volumes and OARs are allowed for automatically computation dosage distribution harmonizing to a preselected algorithm. The algorithm is used to find beam parametric quantities like figure of beamlets, place of MLCs and figure of MUs in order to acquire a better dose distribution that corresponds every bit much as possible to the ab initio defined aims.
In fact there is a big difference between the two intervention be aftering techniques: The forward planning is a manual iterative procedure by the contriver boulder clay he obtains an acceptable consequence. In reverse intervention planning system, the contriver inquires the Personal computer what it would desire to obtain as dose distribution to the mark ( tumour ) and OARs. The algorithm will transport out these aims to obtain the desired dose distribution. The reverse intervention planning seems to be more efficient. However, one should be careful because it implies besides many troubles in comparing with forward planning. This troubles include ( Jiang, Earl et Al. 2005 ) :
Treatment clip of a patient is more than 3D CRT.
Increased quality confidence attempts.
aˆ? The escape through lingua and channel could go important in IMRT ( Huq, Das et Al. 2002 ) .
aˆ? Increased shielding demands due to increased escape radiation and neutron taint.
1.5 Different IMRT bringing techniques
All intensity-modulated interventions are performed by altering the multi-leaf collimator ( MLC ) form to enlighten different subdivisions of the mark volume. By altering the form of sub-field and supervise units ( dosage ) associated with each MLC section. Different parts of the mark are irradiated individually. The summing up of these MLC forms makes the entire dosage to the irradiated volume. This combination of beam angles, strength of dosage and MLC sections is designed to present extremely conformal dose distributions. ( Wu, Yin et Al. 2010 ) . So, the multiaˆ?leaf collimator ( MLC ) based IMRT techniques are most presently used and fall into three classs:
– The metameric MLC ( SMLC ) manner, frequently referred to as the measure and shoot manner.
– The dynamic MLC ( DMLC ) manner sometimes referred to as the sliding window manner.
– Intensity modulated arc therapy ( IMAT )
The segmented MLC ( inactive IMRT ) manner referred to as measure and shoot, in this technique the beam is merely turned on when the MLC foliages are stationary in each of the prescribed beamlet during bringing. The strength modulated Fieldss are delivered with a sequence of little sections or beamlets, each beamlet with a unvarying strength. To accomplish maximal conform dosage to the mark volume 4 to 9 beam waies may be required depending on the complexness of the PTV ( Jiang, Earl et Al. 2005 ) . Inactive IMRT technique is used in Mt Miriam Hospital in Pulau Penang for intervention figure of tumour particularly NPC instances. The single Fieldss may dwell of 3 to 20 beamlets, which are delivered in sequence. The figure of beamlets result in the addition of intervention clip for IMRT to approximately 2.5 times more than 3D – CRT3 ( Nutting, Dearnaley et Al. 2000 ) . To cut down bringing times of reverse be aftering systems, direct aperture optimisation ( DAO ) should be used. It is used to cut down the proctor units of the beamlet and/or cut down the figure of beamlets ( Ludlum and Xia 2008 ; McGarry C K and R 2011 ; McGarry, Butterworth et Al. 2011 ) .
In the dynamic MLC manner ( dynamic IMRT ) the bringing of the strength modulated Fieldss are carried out while the foliages of the MLC are traveling during patient intervention in a dynamic manner. In this manner IMFs ( strength modulated Fieldss ) are created by agencies of traveling matching foliages independently with a different speed as a map of clip, while the beam is on. Desirable dosage can be got by altering the place of MLCs and velocity of them. The dynamic IMRT intervention clip is much faster than inactive IMRT technique ; typical bringing clip for a five aˆ? field prostate intervention is 14 min ( Nutting, Dearnaley et Al. 2000 ) .
Figure 1.4: Dynamic IMRT technique ( Schlegel and Mahr 2001 )
The strength modulated arc therapy ( IMAT ) bringing method uses the sliding window attack while the gauntry rotates around the patient. The advantage of utilizing IMAT technique includes ; faster bringing clip than dynamic MLC ( estimated at 5 – 10 min ) and the capableness of utilizing fewer strength degrees than dynamic MLCs ( Boyer and Yu 1999 ) . The Skiding window IMRTA and IMAT produce better mark dose homogeneousness compared to step & amp ; shoot IMRT ( Wiezorek, Brachwitz et Al. 2011 ) . The chief difference between IMAT and IMRT is that IMRT consists of a few gauntry angles with figure of beamlets for each beamA way while IMAT has a individual MLC section at each of many beamA way, but the section forms are restricted by the MLCs foliages and gauntry rotary motion velocities. Fig. 1.5 ( a ) and ( B ) show the distribution of beams and beamlets for the IMRT and the IMAT techniques, severally ( Wu, Yin et Al. 2010 ) .
Figure 1.5: beams directionA and beamlets for IMRT and IMAT distribute around a patient. ( a ) For IMRT, a few beams distributed around the patient, with figure of beamlets associated for each beam. ( B ) For IMAT, many beams distributed aroundA the patient, with one MLC segmentA connected with one beam ( Wu, Yin et Al. 2010 ) .
1.5 IMRT confirmation
A conformal intervention program consists of two to four unfastened Fieldss, each with a homogenous dosage profile. These Fieldss are applied from different waies. In the other manus, IMRT uses non-uniform radiation beam strengths which are determined utilizing computer-based optimisation techniques. The dose distribution on the mark can be further shaped by modulating the strength of each field used. Due to the complexness of the technique, confirmation of the dose bringing is of import. In IMRT, it is necessary to verify the deliberate dose distribution from TPS and the existent dosage distribution in patient via apparition. There are several methods available for IMRT confirmation. The most widely used are movies which have good spacial declaration but the movies have to be calibrated against dosage. Gafchromic movies which were developed for industrial radiation monitoring have been refined for clinical radiation therapy dosimetry ( Chu, Lewis et al. 1990 ; Devic, Seuntjens et Al. 2004 ) . These movies are self-developing and necessitate no physical/chemical processing. The optical denseness of the irradiated movie is measured utilizing optical mensurating systems such as densitometers and document scan- ners ( Devic, Seuntjens et Al. 2005 ; Sankar, Ayyangar et Al. 2006 ) . Electron portal imagination devices ( EPIDs ) do hold good spacial declaration but require standardization and they age with radiation. EPIDs are available on intervention machines and are used for place confirmation of patients. EPID dosimetry utilizing deconvolution methods are used to gauge dosage in a patient ( Wendling, Louwe et Al. 2006 ; Wendling, McDermott et Al. 2009 ) . The 2aˆ?D sensor array that can be placed on top of the intervention sofa or attached to the gas pedal caput can better confirmation clip compared to movie measurings. 2D array of pel ionisation Chamberss do hold poorer declaration but provide direct measuring of dosage without frequent standardization ( Spezi, Angelini et Al. 2005 ; Herzen, Todorovic et Al. 2007 ) . The measurings are in existent clip.
1.6 Aims of the Study
To analyze the features of a commercialised array of 2D pixel ionisation Chamberss I’mRT MatriXX from Scanditronix Wellhofer utilizing Siemens Artist LINAC ( 6 and 10 MV ) .
To implement I’mRT MatriXX for IMRT quality confidence in NPC IMRT intervention program confirmation utilizing Siemens Artist LINAC ( 6 and 10 MV ) .
To measure the capableness of a commercialised array of 2D pixel ionisation Chamberss Seven29TM ( PTW, Freiburg, Germany ) with the aim to implement for IMRT quality confidence for NPC IMRT intervention program confirmation on Varian clinac 2300 EX ( 6 and 18 MV ) .
To rectify the response of the I’mRT MatriXX in high gradient part utilizing Deconvolution rectification method.
To use the deconvolution method, the true beam profile for different field sizes and IMRT programs were measured utilizing little ionisation chamber ( IC03 ) and Gafchromic movies ( EBT2 movies ) and calculated utilizing Monte Carlo simulation BEAMnrc/DOSXYZnrc.
To analyze the consequence of inhomogeneity of caput and cervix form, a semi cylindrical apparition was designed for figure of NPC IMRT QA instances.
To imitate semi-cylindrical apparition for different field sizes utilizing BEAMnrc/DOSXYZnrc ( Linux version ) .
Structure of this Thesis
This thesis contains eight chapters holding the common subject ; rating of an array of 2D pixel ionisation Chamberss ( I’mRT MatriXX ) for nasopharynx instances ( NPC ) for strength modulated radiation therapy ( IMRT ) confirmation. Chapter 1 provides background information on external NPC radiation therapy, spread of lymphatic paths of NPC anatomy, description of intervention types, and the chief aims of this research.
A literature reappraisal ; rating of an array of 2D pixel ionisation Chamberss ( I’mRT MatriXX ) for nasopharynx instances ( NPC ) for strength modulated radiation therapy ( IMRT ) confirmation in chapter 2. It is divided into four wide classs: I ) features of 2D Array sensors and Film Dosimeters and Their capablenesss to implement for IMRT QA, two ) Detector Size Effectss for little field sizes, three ) deconvolution rectification method, four ) Monte Carlo Simulation EGSnrc ( BEAMnrc/DOSXYZnrc ) . Chapter 3 describes a basic natural philosophy of interaction of photon with affair. Chapter 4 describes the instrumentality utilized in this research. There were two chief classs of instruments used, viz. the sensors and their package with the accessory equipments. The sensors employed included I’mRT MatriXX and Seven29TM. The package of the I’mRT MatriXX is called OmniPro-I’mRT Software and Seven29TM has two package called MatrixScan Software and VeriSoft Software. Besides Gafcromic movies and two types of ionisation chamber were used. Three types of apparitions were described, viz. the solid H2O apparition and the Perspex apparition for Nasopharynx. As a treatise in instrumentality, the simulator and additive gas pedal ( LINAC ) is besides described. Validation of the experimental work for dose computations and measurings is provided in the undermentioned four chapters. Chapter 5 nowadayss represent survey of the features of the 2D array ( I’mRT MatriXX and Seven29TM ) . Deconvolution method to rectify sensor response map for little Fieldss in 2D array I’mRT MatriXX was applied in chapter 6. It includes measurings for beam profiles utilizing Gafcromic movies and Monte Carlo simulation. In chapter 7 was approximately clinical Application of the I’mRT MatriXX and Seven29TM for Quality Assurance in IMRT Treatments. Finally, chapter 8 concludes the thesis supplying a sum-up of the major consequences and possible avenues for future work.
