Journal of Medical Physics
 Home | Search | Ahead of print | Current Issue | Archives | Instructions | Subscription | Login  The official journal of Association of Medical Physicists of India      
 Users online: 689  Home  EMail this page Print this page Decrease font size Default font size Increase font size 


 
 Table of Contents    
TECHNICAL NOTE
Year : 2016  |  Volume : 41  |  Issue : 3  |  Page : 198-204
 

Analysis of dose distribution in organs at risk in patients with prostate cancer treated with the intensity-modulated radiation therapy and arc technique


1 Department of Medical Imaging Technology, Faculty of Biomedical Sciences and Postgraduate Training, Medical University of Lodz, 90 251, Lodz, Poland
2 Department of Medical Physics, Regional Cancer Center, Copernicus Memorial Hospital of Lodz, 93 513 Lodz, Poland

Date of Submission08-Jan-2016
Date of Decision08-May-2016
Date of Acceptance08-May-2016
Date of Web Publication30-Aug-2016

Correspondence Address:
Michal Biegala
Department of Medical Imaging Technology, Faculty of Biomedical, Sciences and Postgraduate Training, Medical University of Lodz, Jaracza Street 63, 90.251 Lodz
Poland
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6203.189490

Clinical trial registration no

Rights and Permissions

 

   Abstract 

This study describes a comparative analysis of treatment plans in 48 patients with prostate cancer treated with ionizing radiation. Each patient was subjected to the intensity-modulated radiation therapy (IMRT) and arc technique. In each treatment plan, the organs at risk were assessed: the urinary bladder, rectum and heads of the femur, as well as the volume of normal tissue. The following features were compared: treatment time, conformity indices for the planning target volume, mean doses and standard deviation in organs at risk, and organ volumes for each particular dose. The treatment period in the arc technique is 13.7% shorter than in the IMRT technique. Comparing the results of the IMRT and arc techniques (arc vs. IMRT), the mean values were 29.21 ± 12.91 Gy versus 28.36 ± 13.79 Gy for the bladder, 20.36 ± 3.16 Gy versus 18.17 ± 5.11 Gy for the right femoral head, and 18.98 ± 3.28 Gy versus 16.67 ± 5.15 Gy for the left femoral head. For the rectum, lower values were obtained after application of the arc technique, not the IMRT technique: 35.84 ± 12.28 Gy versus 35.90 ± 13.05 Gy. The results indicate that the applied therapy has a statistically significant influence on the volume for a particular dose with regard to the urinary bladder. It is advisable to apply the IMRT technique to patients who need the femur heads and urinary bladder protected by exposing them to low irradiation doses.


Keywords: Arc technique; intensity-modulated radiation therapy technique; prostate cancer; radiotherapy


How to cite this article:
Biegala M, Hydzik A. Analysis of dose distribution in organs at risk in patients with prostate cancer treated with the intensity-modulated radiation therapy and arc technique. J Med Phys 2016;41:198-204

How to cite this URL:
Biegala M, Hydzik A. Analysis of dose distribution in organs at risk in patients with prostate cancer treated with the intensity-modulated radiation therapy and arc technique. J Med Phys [serial online] 2016 [cited 2019 Apr 23];41:198-204. Available from: http://www.jmp.org.in/text.asp?2016/41/3/198/189490



   Introduction Top


Prostate cancer is the second most frequently diagnosed neoplastic disease in males in Poland, constituting 13% of neoplasms in 2010. In the last three decades, a five-fold increase has been observed in the number of prostate cancer patients diagnosed in Poland. One of the three methods of treating the growing number of patients affected by this type of cancer is radiotherapy. In recent years, progress in radiotherapy has seen the invention of many modern treatment methods that can efficiently deliver radiation dose to target volumes while protecting healthy tissues and organs. [1],[2],[3] Arc [4],[5] and intensity-modulated radiation therapy ( IMRT) [6] are becoming more popular teleradiotherapy techniques; however, each has its advantages and disadvantages. Hence, the aim of this work was to perform a comparative analysis of treatment plans for prostate cancer using the IMRT (five fields) and arc techniques (2 arcs). In this work we present a comparison of doses to organs at risk (OARs) by these two techniques that can be used in assessing the quality of treatment plans. Such a comparison of doses to OARs by two techniques (5 fields IMRT vs. 2 arcs) is not available in the literature in our knowledge.


   Methods Top


A comparative analysis was performed of treatment plans in 48 patients treated with the IMRT and arc techniques in 2014. The plans were done in the Eclipse treatment planning system (Eclipse 10.0, Varian Medical Systems) using AAA calculation algorithm. [7] RapidArc system (Varian) was used for the treatment planning of arc technique. Treatment delivery was done on a Clinac 2300 medical linear accelerator (Varian).

The planning target volume (PTV) included the prostate with seminal vesicles. A margin of 0.9 cm was added to all sides with the exception in the direction of the rectum, where a margin of 0.5 cm was used. The margins were added according to the clinical treatment guidelines and general recommendations. [8],[9] The patients were administered a total dose of 70.2 Gy, with fractionated doses of 2.6 Gy each (5 days/week), with the application of photon radiation with a nominal energy of 15 MV. The organs at risk included the urinary bladder, rectum, and heads of the femur (left and right). The volume of healthy tissues located in the pelvis area was also included in the analysis.

Before commencing the treatment procedure, computed tomography was performed on a Siemens Somatom Sensation Open CT-simulator, which was the basis for realization of the treatment plan. During the CT examination and ensuing therapy, the pelvis of the patients was properly immobilized and the patients were instructed to keep their urinary bladder full to provide geometric repeatability.

In the treatment plans where the IMRT technique was applied, five therapeutic fields were used with the following head/collimator/table parameters: 260°/15°/0°, 310°/15°/0°, 50°/345°/0°, 100°/345°/0°, and 180°/0°/0°. [10] In the treatment plans based on the arc technique, two arcs were used with the following collimator/table parameters: clockwise from 181° to 180° and 30°/0° and anti-clockwise from 179° to 180° and 330°/0° [Figure 1].
Figure 1: Arc technique - left figure; intensity - modulated radiation therapy technique - right figure

Click here to view


For each of the 48 patients, two treatment plans were generated - one with the arc and the other by the IMRT technique. A comparative analysis was made for the doses to PTV, healthy tissues, and organs at risk. A number of indices were found for determining irradiation area. [11],[12],[13],[14] To compare PTV values in this study, a conformity index with the following formula was used: [15]

CI 95% = V 95% /V PTV

where:

CI 95% - conformity index;

V 95% - PTV within 95% isodose;

V PTV - PTV volume

For organs at risk, tolerance doses and volumes are in compliance with internal clinical treatment guidelines. They are presented in [Table 1].
Table 1: Dose constraints for each organ at risk


Click here to view


No healthy tissues should be irradiated by a dose more than 110% of a prescribed dose. [16]

Mean doses to each OAR were estimated for comparing between techniques.

Statistical analysis

Modern radiotherapeutic methods are similar to each other. Hence, a basic analysis of treatment plans is not sufficient enough to precisely evaluate to what extent organs at risk are exposed to radiation. To make a thorough comparative analysis of the two techniques, standard deviations and dose-volume histograms (DVHs) were interpreted. Statistica 10 software (StatSoft® , Poland) was used for analyses. [17]

Student's t -test

The Student's t-test for independent variables allows a comparison to be made of measurements from two groups. It is used to evaluate the differences between mean values in two groups. The dependent value is a parameter measured in a particular study and its value depends on the selected method. The null hypothesis states that values in both the studied groups are the same. A characteristic feature of the Student's t-test is to emphasize differences in particular cases rather than in differences between mean values for each group.

In this test, α = 0.05 was taken as the level of significance. It was assumed that P < 0.05 confirms a statistical difference between the studied measurements. P 0≥ 0.05 indicates that no such differences exist.

Analysis of dose-volume histograms

Histogram analysis was performed using linear models, which allows basic statistical values to be determined and the points in which the two comparable techniques considerably differ from each other to be identified.

The analysis of variance (ANOVA) test was used to conduct a detailed analysis of histograms with repeated measurements. [18],[19],[20] The variate test of variances with repeated measurements assesses the impact of the following studied parameters: dose, treatment technique and the relationship between the dose and the treatment technique, and the value of the radiotherapy structure volume (RTSV) ratio. As none of the analyzed variables in this study met the assumption of sphericity, the Greenhouse-Geisser, Huynh-Feldt corrections were used to correct the P values. In all analyses, α = 0.05 was adopted as the level of significance. With regard to the study hypothesis, P < 0.05 indicates that the studied parameter has an effect on the value of the RTSV ratio, whereas P ≥ 0.05 indicates that the studied parameter does not have an effect on the value of the RTSV ratio.

The final element of the histogram analysis was a contrast analysis. It is used to assess statistical significance of expected, detailed differences in particular sections of a histogram. Post hoc test and the Fisher's least significant difference test (NIR-test) were used to compare irradiation techniques for particular doses. In the NIR-test, the adopted level of significance was α = 0.05.


   Results Top


Each of the 48 treatment plans was analyzed with regard to the quality of irradiation of PTV. Precision in dose delivery will probably result in successful therapy and curtail side effects of therapy with ionizing radiation. [Table 2] shows the conformity indices for particular treatment techniques.
Table 2: Conformity index for each technique


Click here to view


Irradiation time was also analyzed, as expressed in monitor units (MUs). [Table 3] shows a mean value of MUs for one treatment plan realized with the application of the IMRT and arc techniques.
Table 3: Number of monitor units for each technique


Click here to view


Before conducting a detailed analysis of dose distribution for particular organs, mean doses in particular organs were determined. The results are shown in [Table 4].
Table 4: Mean dose and standard deviation in organ at risk


Click here to view


An essential element of the evaluation of treatment techniques is an analysis of DVHs. [Figure 2] [Figure 3] [Figure 4] [Figure 5] [Figure 6] present the relationship between the dose distribution and the RTSV ratio of an analyzed structure.
Figure 2: Mean dose-volume histogram for bladder

Click here to view
Figure 3: Mean dose-volume histogram for rectum

Click here to view
Figure 4: Mean dose-volume histogram for the right femoral head

Click here to view
Figure 5: Mean dose-volume histogram for the left femoral head

Click here to view
Figure 6: Mean dose-volume histogram for normal tissue

Click here to view


The ANOVA of particular values of RTSV for organs at risk, carried out with the application of the ANOVA Test, determined which factors influencing RTSV were statistically significant. Such factors were assumed to include a treatment technique and a dose. Another significant parameter in this analysis is the interaction between the treatment technique and dose, which will enable us to know the statistical influence of any of the above factors on the RTSV value to be determined. [Table 5] shows the final result of the ANOVA for organs at risk.
Table 5: Analysis of variance values for radiotherapy structure volume-treatment technique and dose


Click here to view


The ANOVA shown in [Table 5] confirmed the presence of an interaction between treatment technique and dose. Hence, it is justifiable to compare RTSV values in particular doses for the studied treatment techniques. A detailed analysis of the RTSV with the use of the Fisher's least significant difference is shown in [Table 6], as well as a comparison of the differences in RTSV values according to dose with percentage RTSV values for the IMRT technique (ΔRTSV).
Table 6: Analysis of dose-volume histogram - the Fisher's least significant difference test (NIR-test)


Click here to view



   Discussion Top


To make a comparative analysis of treatment plans performed with the application of various techniques, one condition must be fulfilled, i.e., the PTVs in each technique must be equally irradiated. To compare the intensity of irradiation, the conformity index was analyzed. The analysis of these indices shown in [Table 2] confirms no statistical significance between the obtained values ( P > 0.05), which in turn, indicates no differences between the plans with regards to the dose coverage of PTV. However, it remains unclear as to what extent the structures located close to the PTV are irradiated.

A statistically significant difference can be seen between the techniques with regard to irradiation time [Table 3]. The treatment time expressed in MUs is 13.7% shorter in the arc technique than in the IMRT technique. In addition, the operator does not need to enter the therapy room to trigger another arc in the arc technique. Unfortunately, the total treatment period is much longer for the IMRT technique as the person setting the next radiation field must be present, which has a great impact on the number of patients treated. The fact that the treatment period in the arc technique is considerably shorter positively contributes to the accuracy of the therapy and increase in patient's comfort.

An analysis of [Table 4] confirms that the mean standard deviation is higher for each studied structure for the IMRT technique than the arc technique. The higher value of the standard deviation confirms a greater difference between the dose and the mean value and thus, a greater difference in the distribution in the studied structure. Unfortunately, the analysis of standard deviations does not indicate the size of the dose to which the whole structure is exposed. To identify slight differences, more parameters of treatment plans should be analyzed.

In the first stage, the mean dose planned for the OAR was determined on the basis of an analysis of dose distribution in the volume of the studied structure. The analysis presented in [Table 4] demonstrates that the larger differences in the mean dose are observed for the heads of the right (12.0%) and left (13.9%) femur. A higher mean value can be observed in the arc technique. A difference in mean doses is also noticeable for the urinary bladder, wherein the mean value is 3% higher in the arc technique than the IMRT technique. For the rectum, the difference in the mean doses is lower than 0.5%. It is worth emphasizing that all the values shown in [Table 4] are not statistically significant, which confirms the fact that the mean dose in the volume is not a reliable parameter to compare plans where differences in dose distribution are scarcely noticeable. Hence, it is necessary to conduct a detailed analysis of the dose, depending on the volume of the studied structure.

The urinary bladder is an organ which requires special attention during radiotherapy. By following suitable bladder protocol, it is possible to daily reproduce same level of bladder fill as that observed in the treatment plan. The RTSV value for the urinary bladder, in the range of 0-40 Gy, is lower in the IMRT technique than in the arc technique. For doses above 40 Gy, the difference between these two techniques is small and it remains within the margin of error. The results of the Fisher's least significant difference test [Table 6] indicate that the RTSV values for the urinary bladder are significant up to a dose of 40 Gy, while these values are not significant above 40 Gy.

While preparing treatment plans, every effort is made to protect the rectum against the application of overdoses, as these might be harmful for the patient. The distribution of doses in the rectum is similar in the two treatment techniques [Figure 3]. A significant difference was observed in the RTSV value only for doses 30, 50, and 60 Gy [Table 6]. However, it should be pointed out that the P value was 12.5 times smaller than 0.05 for a dose of 30 Gy; the other P values were smaller about 0.012 for 50 Gy and 0.03 for 60 Gy, but these differences cannot be considered significant.

A lower RTSV value was observed for doses up to 20 Gy for the heads of the right and left femur examined with the IMRT technique. For doses above 20 Gy, this tendency is reversed. For the head of the right femur, a significant difference in the RTSV value was observed for doses of 10 and 30 Gy, whereas for the head of the left femur, significant differences were noted for doses ranging from 10 to 30 Gy. The results shown in [Table 6] confirm the most noticeable differences in RTSV values between the two treatment techniques. For particular doses, the difference in RTSV value with regard to the heads of the right and left femur ranges from 10% to 40%.

We also analyzed the doses to healthy tissues located around the PTV. Here, lower RTSV values were observed for doses up to 10 Gy after the IMRT technique. Above 10 Gy, the RTSV value was lower for the arc technique. Significant differences between the techniques can be observed up to a dose of 40 Gy. In the arc technique, a greater volume of healthy tissues receives a lower dose in comparison to the IMRT technique.

The ANOVA test provided interesting observations [Table 5]. It showed that the applied technique has a significant influence on the RTSV value of the urinary bladder and volume of healthy tissues, however no such a relationship was observed with regard to other organs at risk. The value of RTSV depends on the applied dose and this regularity is observed in each studied structure. The ANOVA test confirms that in each studied organ, there is a characteristic interaction between the applied technique and irradiation dose. Hence, for some ranges of doses, the applied technique contributes to a change in the RTSV value and the change is dose-dependent.

There are many publications that describe differences between IMRT and arc technique in prostate cancer. [2],[21],[22],[23],[24],[25],[26],[27],[28],[29] [Table 7] shows the mean doses or volume structure in OAR in publication which describes the treatment planning with two arcs or five fields in IMRT. The results of mean doses or volume structure in OAR in these plans are similar to results obtained in this work. The differences in the results are from dose prescription in PTV or optimization parameters. We did not find publications which compared treatment plans using two arcs and five fields IMRT technique.
Table 7: Summary of mean doses and volume structure in organ at risk in intensity-modulated radiation therapy and arc techniques in various treatment planning


Click here to view



   Conclusions Top


The IMRT and arc techniques are commonly followed techniques in the treatment of patients with ionizing radiation. They are equivalent techniques, which we confirmed in our study. Both the techniques allow an advanced procedure of modeling distribution to be applied in patients and they both effectively irradiate PTV, which is the most required condition for their clinical application. The arc technique required a shorter irradiation period than the IMRT technique. The analysis of exposure of organs at risk to radiation confirmed the greatest differences in the heads of the femur and in the urinary bladder for doses below 20 Gy and 40 Gy. The IMRT technique outperforms the arc technique with regard to the exposure of healthy tissues to radiation for low doses (<10 Gy). To protect the heads of the femur and the urinary bladder, it is advisable to apply the IMRT technique at low radiation doses.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Duthoy W, De Gersem W, Vergote K, Boterberg T, Derie C, Smeets P, et al. Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer. Int J Radiat Oncol Biol Phys 2004;60:794-806.  Back to cited text no. 1
    
2.
Sze HC, Lee MC, Hung WM, Yau TK, Lee AW. RapidArc radiotherapy planning for prostate cancer: Single-arc and double-arc techniques vs. Intensity-modulated radiotherapy. Med Dosim 2012;37:87-91.  Back to cited text no. 2
    
3.
Zelefsky MJ, Fuks Z, Happersett L, Lee HJ, Ling CC, Burman CM, et al. Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 2000;55:241-9.  Back to cited text no. 3
    
4.
Webb S, McQuaid D. Some considerations concerning volume-modulated arc therapy: A stepping stone towards a general theory. Phys Med Biol 2009;54:4345-60.  Back to cited text no. 4
    
5.
Teoh M, Clark CH, Wood K, Whitaker S, Nisbet A. Volumetric modulated arc therapy: A review of current literature and clinical use in practice. Br J Radiol 2011;84:967-96.  Back to cited text no. 5
    
6.
Webb S. The physical basis of IMRT and inverse planning. Br J Radiol 2003;76:678-89.  Back to cited text no. 6
    
7.
Tan YI, Metwaly M, Glegg M, Baggarley S, Elliott A. Evaluation of six TPS algorithms in computing entrance and exit doses. J Appl Clin Med Phys 2014;15:4739.  Back to cited text no. 7
    
8.
Huang E, Dong L, Chandra A, Kuban DA, Rosen II, Evans A, et al. Intrafraction prostate motion during IMRT for prostate cancer. Int J Radiat Oncol Biol Phys 2002;53:261-8.  Back to cited text no. 8
    
9.
Huang K, Palma DA, Scott D, McGregor D, Gaede S, Yartsev S, et al. Inter- and intrafraction uncertainty in prostate bed image-guided radiotherapy. Int J Radiat Oncol Biol Phys 2012;84:402-7.  Back to cited text no. 9
    
10.
Stein J, Mohan R, Wang XH, Bortfeld T, Wu Q, Preiser K, et al. Number and orientations of beams in intensity-modulated radiation treatments. Med Phys 1997;24:149-60.  Back to cited text no. 10
    
11.
Huchet A, Caudry M, Belkacémi Y, Trouette R, Vendrely V, Causse N, et al. Volume-effect and radiotherapy [II]. Part II: Volume-effect and normal tissue. Cancer Radiother 2003;7:353-62.  Back to cited text no. 11
    
12.
Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 2000;47:291-8.  Back to cited text no. 12
    
13.
Lu JY, Wu LL, Zhang JY, Zheng J, Cheung ML, Ma CC, et al. Improving target dose coverage and organ-at-risk sparing in intensity-modulated radiotherapy of advanced laryngeal cancer by a simple optimization technique. Br J Radiol 2015;88:20140654.  Back to cited text no. 13
    
14.
Biega³a M, Wieczorkowski £, Spych M. Comparative analysis of stereotactic radiosurgery treatment plans in brain cases with one and two tumour changes using conformity indices. Rep Pract Oncol Radiother 2006;11:197-204.  Back to cited text no. 14
    
15.
Feuvret L, Noël G, Mazeron JJ, Bey P. Conformity index: A review. Int J Radiat Oncol Biol Phys 2006;64:333-42.  Back to cited text no. 15
    
16.
Cozzi L, Dinshaw KA, Shrivastava SK, Mahantshetty U, Engineer R, Deshpande DD, et al. A treatment planning study comparing volumetric arc modulation with RapidArc® and fixed field IMRT for cervix uteri radiotherapy. Radiother Oncol 2008;89:180-91.  Back to cited text no. 16
    
17.
Stanisz A. Przystêpny kurs statystyki z zastosowaniem STATISTICA PL na przyk³adach z medycyny StatSoft Polska Kraków; 2006.  Back to cited text no. 17
    
18.
Kao LS, Green CE. Analysis of variance: Is there a difference in means and what does it mean? J Surg Res 2008;144:158-70.  Back to cited text no. 18
    
19.
van Ginkel JR, Kroonenberg PM. Analysis of variance of multiply imputed data. Multivariate Behav Res 2014;49:78-91.  Back to cited text no. 19
    
20.
Altman DG, Bland JM. Standard deviations and standard errors. BMJ 2005;331:903.  Back to cited text no. 20
    
21.
Zhang P, Happersett L, Hunt M, Jackson A, Zelefsky M, Mageras G. Volumetric modulated arc therapy: Planning and evaluation for prostate cancer cases. Int J Radiat Oncol Biol Phys 2010;76:1456-62.  Back to cited text no. 21
    
22.
Hardcastle N, Tomé WA, Foo K, Miller A, Carolan M, Metcalfe P. Comparison of prostate IMRT and VMAT biologically optimised treatment plans. Med Dosim 2011;36:292-8.  Back to cited text no. 22
    
23.
Ost P, Speleers B, De Meerleer G, De Neve W, Fonteyne V, Villeirs G, et al. Volumetric arc therapy and intensity-modulated radiotherapy for primary prostate radiotherapy with simultaneous integrated boost to intraprostatic lesion with 6 and 18 MV: A planning comparison study. Int J Radiat Oncol Biol Phys 2011;79:920-6.  Back to cited text no. 23
    
24.
Yoo S, Wu QJ, Lee WR, Yin FF. Radiotherapy treatment plans with RapidArc for prostate cancer involving seminal vesicles and lymph nodes. Int J Radiat Oncol Biol Phys 2010;76:935-42.  Back to cited text no. 24
    
25.
Guckenberger M, Richter A, Krieger T, Wilbert J, Baier K, Flentje M. Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes? Radiother Oncol 2009;93:259-65.  Back to cited text no. 25
    
26.
Shaffer R, Morris WJ, Moiseenko V, Welsh M, Crumley C, Nakano S, et al. Volumetric modulated Arc therapy and conventional intensity-modulated radiotherapy for simultaneous maximal intraprostatic boost: A planning comparison study. Clin Oncol (R Coll Radiol) 2009;21:401-7.  Back to cited text no. 26
    
27.
Rao M, Yang W, Chen F, Sheng K, Ye J, Mehta V, et al. Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: Plan quality, delivery efficiency and accuracy. Med Phys 2010;37:1350-9.  Back to cited text no. 27
    
28.
Tsai CL, Wu JK, Chao HL, Tsai YC, Cheng JC. Treatment and dosimetric advantages between VMAT, IMRT, and helical tomotherapy in prostate cancer. Med Dosim 2011;36:264-71.  Back to cited text no. 28
    
29.
Wolff D, Stieler F, Welzel G, Lorenz F, Abo-Madyan Y, Mai S, et al. Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer. Radiother Oncol 2009;93:226-33.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
Print this article  Email this article
  

    

 
   Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (1,169 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Methods
   Results
   Discussion
   Conclusions
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed981    
    Printed13    
    Emailed0    
    PDF Downloaded66    
    Comments [Add]    

Recommend this journal