Does Intravenous Contrast Agent Affect Dose Calculations Biology Essay

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The use of computed tomography (CT) with intravenous contrast leads to high accuracy in delineating target volumes and organs at risk (OAR) during treatment planning for conformal radiotherapy. The dose calculation algorithm using CT scan depends on the tissue density which is presented by Hounsfield units (HUs). Due to the high atomic number of injected contrast media, high HU values are obtained during CT scanning thereby the treatment planning system considers it high density tissue. This misinterpretation results in high absorption of photon beams and thus affects the dose calculation.

Results: The percentage dose difference between CT non-contrast based calculation and CT contrast based calculation ranges from 0 to 4% with mean difference 0.9± 0.7% with non significant p value 0.5. The mean difference for pelvic tumors was 1.2% while for head & neck tumors 0.8%. Also, the organs at risk did not show any significant difference between contrast and non contrast with mean difference 1.5±2.3%, 1.1±1.2%, 1.3±0.4%, and 0.95±0.8% in the spinal cord, brain stem, small bowel and rectum respectively. The pelvic tumors showed non significant difference between enhanced CT and non enhanced CT based calculations with p value 0.06, and the same for head and neck tumors with p value 0.09.

Conclusions: The three dimensional (3D) treatment planning calculations in head and neck and pelvic tumors based on CT scans with intravenous contrast do not result in statistical significant difference in dose calculations compared to the standard non contrast CT.

INTRODUCTION

Three dimensional conformal radiotherapy (3D-CRT) has enabled dose escalation to the clinical target volume (CTV) and dose reduction to surrounding organs at risk (OARs) thus leading

to better tumor control probability (TCP) and lower normal tissue complication probability (NTCP).

The success of these techniques depends heavily

on the accuracy in targeting the CTV, and achieving the aimed sparing of the normal tissues. The addition of intravenous contrast material improves the visualization of normal and malignant tissues on

CT scan.(1-2) Many radiation oncologists are concerned that intravenous contrast may affect dose calculations. The prescribed dose may be over estimated by the use of contrast media, resulting in delivery of higher monitor units (MUs) than planned to the target and organs at risk.

As these calculations use algorithms depending on the anatomical information that comes from CT scans. The HU and tissue density are affected by IV contrast and this lead to errors in 3D calculation, when heterogeneity corrections be applied to treatment plans as per task group No. 65 (TG 65) of American association of medical physics (AAPM) recommendations.(3) The international basic safety standards (BSS 115) stated that "any medical exposures should be justified by weighing diagnostic or therapeutic benefits they produce against the radiation detriment they might cause by taking into account the benefits and risks of available alternative techniques that do not involve medical exposure".(4) In radiation therapy, it is generally assumed that the radiation dose delivered during imaging for verification and localization does not add to the patient's burden because the doses from such procedures are very small compared with treatment dose. So the accuracy of dose delivery and sparing of normal tissues justify double exposure to CT scan if there is significant difference between the calculations with contrast CT and non contrast CT.

ISSN 1110-0834The objective of this study was to determine if the use of intravenous contrast in head and neck and pelvic cancer patients results in significant difference in dose calculations compared to the standard calculation based on non enhanced CT scans.

METHODS

There is a prospective treatment planning study performed at Prince Sultan Hematology Oncology Center (PSHOC), King Fahad Medical City (KFMC), Saudia Arabia during the period from June 2007 till October 2007. Twenty patients included in the study (12 head and neck cancer and 8 pelvic tumors).

The patients were immobilized according to the case. Two sets of CT scans for treatment planning were taken for the patients using Siemens scanner with inner radius cavity 84cm (SOMATOM Sensation). The scans were initially taken without intravenous contrast and then with contrast material (XENETIX, 300 mg I/ml, Iohexol) in the same position and coordinates. The automatic injector (meDRaD) was used to inject 100 ml in head and neck (H&N) cancer patients and 150 ml in pelvic tumor patients. The scan started 5 seconds after injection in H&N patients and 30 seconds after injection in pelvic cancer patients. Reconstruction of the images was performed with 3mm cuts for head and neck and 5mm in pelvic cases.

Both scans were sent to Eclipse planning system (version 8.1) via AREA network and the target volume with the critical structures were drawn on the CT with contrast after fusing the images with the CT without contrast. The 3D dose calculation was done based on CT without contrast and then applying the same planning parameters to CT with contrast to recalculate the dose based on enhanced CT. The ECLIPSE treatment planning system was used with pencil beam algorithm for dose calculations with applying heterogeneity correction in both plans. Figure 1,2 show 3D plan for head & neck and pelvic cases respectively with CT with and without contrast

Statistical analysis

The mean doses of the planning target volumes and the OARs were compared between the 3D planning based on the CT without contrast and CT with contrast. The OARs included spinal cord and brain stem for H&N plans in addition to small bowel and rectum in pelvis plans. Statistical package for social science (SPSS, Release 10) was used for data analysis. Mean and standard deviation were used for quantitative data description. The differences were analyzed by Wilcoxon's signed rank test.

RESULTS

The twenty patients included in the study were eligible for analysis of the difference between the mean dose of all volumes (PTV, spinal cord, brain stem, bowel and rectum) for CT without contrast and CT with contrast based calculations.

The patient characteristics are shown in table I.

Table II summarizes these differences and its p value. The percentage difference of PTV dose was in the range from 0 to 4% with mean difference 0.9± 0.7% with non significant p value 0.5. The mean difference in head and neck cases was 0.8±0.9% while in pelvic tumors was 1.2±0.7%. There were no significant statistical difference between calculated dose based on CT with contrast compared to CT without contrast in head and neck cancer and pelvic tumors (p value were 0.09 and 0.06 respectively). Figure 3 (a&b) shows the difference in PTV dose percent between the two CT sets for head and neck cancer and pelvic tumors.

The mean dose to organs at risk did not differ significantly between contrast and non contrast based calculations with mean difference 1.5±2.3%, 1.1±1.2%, 1.3±0.4%, and 0.95±0.8% in the spinal cord, brain stem, small bowel and rectum respectively. The p value was 0.18 for spinal cord, 0.17 for brain stem, 0.4 for bowel and 0.26 for rectum

The patient characteristics are shown in table I

Table I: Patient characteristics (n=20)

Patient charcteristcs

No of patients

H&N Tumours

Site Nasophrynx

Hypopharynx

Larynx

Salivary gland

Brain tumour

T Stage Tx

T1

T2

T3

T4

LN LN positive

LN negative

12

4

1

2

3

2

3

0

3

5

1

7

5

Pelvic Tumours

Site Rectal cancer

Gyn. Cancer

T Stage Tx

T1

T2

T3

T4

LNs LN positive

LN negative

8

5

3

0

0

2

5

1

6

2

Gyn.= Gynaecological, T= Tumour and LN=Lymph nodes

H&N=head and neck, Dc=dose calculated on contrast CT. Dnc= dose calculated on non contrast CT,

PTV=planning target volume

Table II: The dose difference between the contrast and non contrast

based dose calculations for all patients

Volume

No of Pts

Percentage dose difference

(Dc-Dnc)

P value

Min

Max

Mean±SD

PTV All cases

20

0

4.0

0.9± 0.7

0.5

PTV H&N

12

0

3.0

0.8±0.9

0.09

PTV pelvis

8

0.2

4

1.2±0.7

0.06

Spinal cord

12

0

3

1.5 ± 2.3

0.18

Brain stem

12

0

3.5

1.1± 1.2

0.17

Bowel

8

0.8

1.9

1.3 ± 0.4

0.4

Rectum

8

0.1

2.7

0.9 ± 0.8

0.26

PTVc= planning target volume dose in CT with contrast, PTVnc= planning target volume dose in CT without contrast.

Fig 1: 3D plan for head and neck case. Wedge pair technique with oblique fields

for non contrast and contrast CT.

Fig 2: 3D plan for pelvic tumor case. Box technique with two lateral wedge fields for

non contrast and contrast CT was used

Fig 3: The PTV dose difference between CT with contrast and without contrast

for head and neck cases (A) and pelvic cases (B).

DISCUSSIONS

Three dimensional treatment planning algorithm (3D-TPS) depend on density information of different tissues in the CT scan for dose calculations. The attenuation of radiation at therapeutic energies is dominated by Compton scatter, which is dependent on electron density. The Hounsfield units (HU)

from the CT scan used to create density conversion tables within the planning system. The electron density allows the attenuation of the fluence to be based on the mass attenuation of the specific material within a given voxel.(5-6) The contrast-enhanced CT scans would be used to assist in delineating CTV. However, due to the heterogeneity correction applied for dose calculation, the presence of contrast introduces an error in the dose calculation that must be considered and corrected for if significant; otherwise, systematic error will be introduced into the treatment at the planning stage.(7) Previous studies using phantoms or mathematical calculations have shown that contrast media do influence dose calculation when used at high concentrations, however, there might be little influence in clinical setting because concentrations of contrast media in tissues will not so high.(8-10) They recommended that each center has to have his own studies for the different tumor sites, as the calculations differ by adding CT contrast according to the change of HU. This change of HU after contrast enhancement depends on the injection rates and concentrations of contrasts, CT acquisition time after injection, and tissue types.(10)

In our department we standardized the CT simulation procedure for all sites including the use of contrast agents and its way of administration. The effect of CT contrast agent on the dose calculations for head & neck cancers and pelvic tumors were studied. We have shown that the error resulting from using contrast-enhanced CT scans in dose calculations is as low as 4%. The difference ranges from 0 to 3% in head and neck cancers with mean difference less than 1%. The same for pelvic tumors, the dose difference ranges from 0.2% to 4% with mean difference 1.2%. The p value is non significant in both sites however there is trend for significance in pelvic malignancies (0.06). The organs at risk did not show significant difference in dose calculations by using IV contrast.

These results are comparable to Liauw et al study who reported 0.2% difference between a planning set of images using intravenous contrast and a set of images without contrast in 5 head and neck cancer cases.(11)

The effect of IV contrast on dose calculations in pelvic tumors were studied by Verellen et al, they compared the treatment monitor units (MU) calculations for 10 pelvic fields using images from simulator-based CT and diagnostic CT.(12) The difference is within 1% to 2% which is compared to our results which showed 1.2% difference. Liauw and Varellen used the same IV contrast material and dose but the time of acquisition of CT showed minor difference; Liauw take the images 20 seconds after injection compared to 5 seconds in our cases and this may justify the minor difference 0.9% in our study compared to 0.2% in Liauw cases. Chu et al.,(13) showed 2% difference in MU calculations in pelvic cases and 1% difference in brain cases by adding IV contrast material using the collapsed cone convolution algorithm implemented in a commercial planning system (Pinnacle, ADAC Labs, Milpitas, CA). Shibamoto et al, performed the same study on 26 patients, with mean increases in MU by contrast media were less than 1% in planning of brain, neck, mediastinal, and pelvic irradiation.(14)

Choi et al enrolled 15 head and neck cancer patients with involved neck nodes in a similar study. IMRT plan of nine equiangular beams with a 6 MV X-ray was created. The radiation doses calculated from the two sets of CTs were compared with

regard to PTV, parotid glands and the spinal cord. The doses of PTV70 and PTV59.4 calculated

from the enhanced CTs were lower than those from the non-enhanced CTs (p <0.05), but the dose differences were less than 1% compared to the

doses calculated from the enhanced CTs. The doses of PTV50.4, parotid glands, and spinal cord were

not significantly different between the non-

enhanced and enhanced CTs.(10) On the other hand, Ramm et al showed a significant difference of

the calculated dose for the CT contrast based calculations compared to that without contrast. A bolus diameter of 9 cm and a contrast material concentration of 10 mg/cm3 (HU of up to 180) caused an overdose of up to 6.8% and 5.5% for 6 and 25 MV photon beams, respectively.(7)

Conclusions and Recommendations

The 3D planning dose calculations for head and neck and pelvic tumors based on CT scans with intravenous contrast does not result in statistical significant difference in the dose calculations, if compared to the standard 3D planning based on non contrast CT. We recommend that each radiotherapy department have to examine the effect of IV contrast on dose calculations in the different sites by using their internal policy and procedure for injecting IV contrast agents.

Acknowledgements

We want to thank all staff members of the radiotherapy department at PSHOC, KFMC, Saudia Arabia specially the radiotherapist and nursing staff for their careful management of the patients.

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