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Jenny Kouri
DOS 523 Treatment Planning
Heterogeneity Project
March 2015
Heterogeneity Correction for Palliative Non-Small Cell Lung Cancer (NSCLC)
Objective: The objective of this project involves planning a lung tumor case with heterogeneity
correction and without heterogeneity correction.
Purpose: The lungs supply the body with oxygen-rich air while disposing carbon dioxide, a
cellular waste product. The paired lungs are elastic, air-filled organs located on either side of the
thorax, protected by the rib cage. Much of the spongy lung tissue consists of a highly complex
extension of branching bronchi, bronchioles, and alveolar ducts. These passageways conduct air
throughout all parts of the lungs. Alveoli, approximately 300 million per lung, make up most of
the lung volume and the regions where gases are exchanged with nearby blood vessels. These
sacs protrude from the ends of the smallest alveolar ducts. The air sacs of both lungs have a total
surface area nearly 50 times the total surface area of the skin.1Although lung and soft tissue share
a similar equivalent atomic number; lung has a relatively lower density due to the abundance of
alveolar air spaces. The density of lung is 25% of the density of soft tissue.2
Attenuation of radiation dose is decreased in low-density tissues. Air causes radiation
dose to act in a non-conventional behavior. The ribs, heart muscle, and the bony vertebrae
surround the lungs, and therefore, the various densities will affect the radiation delivered by the
photon beam. Dose perturbations are expected beyond the lung, within the lung, at lung interface
and at the lateral edge of the lung.2 This is shown in Figure 1 below. Dose builds up at the distal
interfaces and lack of build up is seen at the proximal interface of the lung due to a loss of
electronic equilibrium occurs at low density boundaries. 10

Figure 1

Beyond the lung


Dose within Lung
Dose at interface

Dose Perturbations Due to Lung


Increase in dose beyond lung than without lung due to poor attenuation
Lower density gives rise to higher dose within and beyond lung
First layers beyond a large thickness of lung will have a decreased dose

Dose at lateral edge

due to loss of secondary electrons


Loss of lateral electronic equilibrium with high energy photons

Thoracic treatment planning is challenged due to the presence of low-density lung tissue
surrounding higher-density thoracic tumors. Standard isodose charts do not distinguish a
difference of density within various tissues.2, 4,10 Lung, oral cavities, teeth, nasal passageways,
soft tissues, and bones were recognized as density equivalent. Dose distributions were originally
computed from the treatment planning system with the assumption that the patient was
composed entirely of water. This discrepancy was held prior to the 1970s before the
commercialization of computed tomography (CT) and practicality of Hounsfield units in
radiation therapy.5 CT imaging allowed for the identification and localization of critical volumes
as well as the determination of their densities derived by voxelized geometry. In 2004, the
American Association of Physics in Medicine (AAPM) stressed for the certainty of the level of
dose differences in tissue densities. The AAPM emphasized that to maximize the therapeutic
benefit of radiation; the dose uptake must be predicted accurately within the different tissues.
Initially, the crossover between homogeneity to heterogeneity corrections created controversy
due to years of studies and protocols based off of homogeneity factors. 6 Heterogeneity
corrections take into account electron fluency and are dependent upon beam energy, beam field
size, tissue density, and length transverse through density.9
Failure to apply heterogeneity correction algorithms will create a plan with changes in the
absorption of the primary beam. The primary beam included the scatter and the changes to the
secondary electron fluence.10 This will result in an under-dose to the target, leading to a decrease
in tumor control. Furthermore, surrounding critical structures such as the heart, ipsilateral lung,
and spinal cord risk an alteration of dose distribution. It is crucial that these critical tissues
remain below the RTOG recommended tolerance limit. Figure 2 represents the dose constraints
for a palliative NSCLC of ten fractionations. 3,9
Figure 2: Radiation Dose Constraints
Critical Structures DVH Parameters

Limits

Esophagus

Maximum Dose

<47 Gy

Esophagus

Mean Dose

<34 Gy

Toxicity
Rate

Toxicity Endpoint
Esophagitis

5%-20%

Esophagitis

Heart

Maximum Dose

<47 Gy

Heart
Heart
Total Lung
Total Lung

Mean Dose
V45
Mean Dose
V20

<26 Gy
<30%
<20 Gy
<30%

Spinal Cord

Maximum Dose

<36 Gy

Pericarditis
<15%

<20%

Pericarditis
Pericardits
Pneumonitis
Pneumonitis
Myelopathy

Consequently, an alteration of monitor units (MU) units and distorted isodose lines will
present, as well. With advances in dose calculation algorithms, we can account for heterogeneity
and model a more accurate representation of dose absorbed within the patient.7 Even though a
homogeneity plan make look more uniform than a corrected plan, it does not take into account
the true distribution of dose uptake in tissue.
At the University of Oklahoma Health Science Center, a study was conducted to
determine the impact of heterogeneity corrections in Stereotactic Body Radiation Therapy
(SBRT) treatment plans.9 A total of 15 patients with early stage NSCLC were treated with SBRT
with a dose of 60Gy per 3 fractions, normalized to 95%. All treatment plans incorporated 4-6
photon beams with 6MV energy. Each of the plans was calculated with and without the
heterogeneous correction factor. The minimum, mean, and maximum planned target volume
(PTV) were compared. In the non-corrected plans, the dose to the PTV was decreased. The
average minimum, mean, and maximum PTV doses decreased by 13%, 8%, and 6%
respectively.9
Methods and Materials: A 66 year-old male presented with stage IV, metastatic NSCLC of the
posterior left lung. This patient was simulated supine with arms placed down by patients side.
A Philips Brilliance Big Bore computed tomography (CT) machine was used for simulation, and
Pinnacle3 9.0 treatment planning system (TPS) was used to create the treatment. For palliative,
local-control, the oncologist prescribed 300cGy per fraction to the 95% isodose line for 10
fractions. The spinal cord dose was kept below 10% of the total dose. The gross tumor volume
(GTV), left lung, right lung, spinal cord, heart, and esophagus were contoured. Taking into
consideration diaphragm motion, a 2 cm auto-margin was placed around the isocenter using
multi-leaf collimator (MLC) blocking. The couch position and collimator were set at 0-degrees
for all of the fields. Anterior and posterior fields were utilized with mixed energies. The anterior
field (2a) was composed of 6-megavoltage (MV) beam energy. The second anterior field (2b)

and the posterior field (2c) used 18 MV beam energy. Only the anterior fields involved a 30degree wedge. The majority of the dose was delivered posteriorly. 2a was weighted by 21% of
the daily dose; 2b, 15%; and 2c, 64%. Dose was computed using the Collapsed Cone
Convolution Superposition (CC Convolution) algorithm. The difference between the trials is the
secondary trial was computed without heterogeneity correction.
Results: Figures 3-5 display isodose distribution curves derived from Trial 1 in the coronal,
sagittal, and transverse planes. The dose volume histograms (DVH) and MU secondary
calculation checks for Trial 1 are shown as well. Figures 6-8 present the isodose curves, DVH,
and MU calculations for Trial 2.

Figure 3: Transverse, Sagittal, and Coronal CT Images of Heterogeneity Plan, Trial 1

Figure 4: DVH for Heterogeneity Plan, Trial 1

Figure 5: MuCheck for Heterogeneity Plan, Trial 1

Figure 6: Transverse, Sagittal, and Coronal CT Images of Homogeneity Plan, Trial 2

Figure 7: DVH for Homogeneity Plan, Trial 2

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Figure 8: MuCheck for Homogeneity Plan, Trial 2

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The volume of the GTV was 389.72 cc. The percentages of GTV volume receiving the
prescription dose, and minimum, mean, and maximum GTV doses are presented for Trial 1 and
Trial 2 in Figure 9. The minimum, mean, and maximum doses of the surrounding critical
structures are shown as well. Yellow, highlighted data represents the dose constraint was met for
the plan. Refer to Figure 2 for dose constraint requirements. Data is derived from both DVHs.

Figure 9: Comparison of Dose Volumes


Percentage
Trial 1,

Maximum Dose Point


(Gy)

Difference

Heterogeneity

Trial 2,
Homogeneity

Between Trial 1

Plan
3510.0

Correction
4059.0 (Located

and 2
13.5

(Located

anteriorly and

posteriorly and

medially of left

lateraly of left

lung)

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lung)
% GTV volume
receiving 100%

86.5

99.7

13.2

99.7

100.0

0.3

2781.6

2963.9

6.1

3153.5

3196.5

1.3

3459.2

3388.1

2.1

27.6

28.82

3.9

7.2

7.3

1.3

971.7

1062.4

8.5

3424.2

3996.9

14.3

1.6

2.0

20.0

369.1

398.6

7.4

3149.6

3332.1

5.5

0.0

0.0

0.0

44.1

51.1

13.7

1956.5

2190.4

10.6

3215.2

3782.5

10.6

26.7

34.6

22.8

1119.3

1236.7

9.4

2930.2

3155.6

7.1

prescribed dose
% GTV volume
receiving 95%
prescribed dose
GTV Minimum Dose
(Gy)
GTV Mean Dose (Gy)
GTV Maximum Dose
(Gy)
Total Lung V20 (%)
Lung Minimun Dose
(Gy)
Lung Mean Dose (Gy)
Lung Maximum Dose
(Gy)
Spinal Cord Minimum
Dose (Gy)
Spinal Cord Mean Dose
(Gy)
Spinal Cord Maximum
Dose (Gy)
Heart V45 (%)
Heart Minimum Dose
(Gy)
Heart Mean Dose (Gy)
Heart Maximum Dose
(Gy)
Esophagus Minimum
Dose (Gy)
Esophagus Mean Dose
(Gy)
Esophagus Maximum
Dose (Gy)

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The table below in Figure 10 compares the MU between Trial 1 and Trial 2. Data was derived
from Pinnacle3. MuCheck computed a secondary calculation check for both trials. Acceptable
limits are within +/-3% between the primary and secondary calculations. This is shown in Figure
11.
Figure 10: Comparison of Pinnacle 3 MU Calculations
Percentage

Field/Beam

Trial 1

Trial 2

Energy

MU/Fraction

MU/Fraction

Anterior, 6 MV

156

207

Trial 1 and 2
24.6

Anterior, 18 MV

79

95

16.8

Posterior, 18 MV

204

204

0.0

Difference Between

Figure 11: Comparison of MuCheck MU Calculations


Percentage

Field/Beam

Trial 1

Trial 2

Energy

MU/Fraction

MU/Fraction

Anterior, 6 MV

155

209

Trial 1 and 2
25.8

Anterior, 18 MV

79

95

16.8

Posterior, 18 MV

201

203

1.0

Difference Between

Discussion: Similar to the study preformed at the University of Oklahoma Health Science
Center, results from this assignment indicated a decrease in dose to GTV with the heterogeneity
correction. Although the maximum GTV dose was 2.1% higher in the heterogeneity trial; the
GTV minimum and mean dose was reduced by 6.1% and 1.3%, respectively. The maximum dose
point was evidently hotter in Trial 2, the non-corrected plan, by 13.5%. GTV coverage is shown
in the CT images, which displayed a more flat, uniform dose distribution in Trial 2. However,
the discrete coverage is proved unsatisfactory. The dose to the 95% isodose line is 13.2% cooler
in Trial 1, the corrected plan. If Trial 2 were used for treatment, an under-dose to the GTV
would have been delivered unknowingly. A false sense of tumor control and lack of improved

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comfort would have resulted. The different densities of the critical structures resulted in an 8.8%
dose reduction in Trial 1. This is due to the radiation attenuation of various tissues when
corrected for heterogeneity. The lower dose uptake of the surrounding tissues, the more
advantageous the plan will result in.
In Trial 1, a decrease in MUs resulted by, which was expected. Low-density
heterogeneity has decreased areas of scatter not modeled, which will result in lower MUs.
Higher density heterogeneity or uniform homogeneity has increased areas of scatter not modeled.
This will equate to higher MUs than is needed.11 The change in MU is increases more for 6 MV
than 18 MV, since lower energy beams escalate heterogeneity correction.
Conclusion: The goal of radiation therapy is to maximize dose to a thoracic tumor while sparing
the surrounding critical structures such as the heart, ipsilateral lung, and spinal cord. Due to the
varying densities of the thorax the goal can be cumbersome, but achievable with proper
treatment planning techniques and advanced dose calculation algorithms. With these dosimetric
tactics, we can account for heterogeneity and rectify a more accurate representation of dose
absorbed within the patient.11

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References
1. Anatomy and Function of the Normal Lung. American Thoracic Society Web Site.
http://www.thoracic.org/professionals/clinical-resources/copd-guidelines/forpatients/anatomy-and-function-of-the-normal-lung.php. Updated 2015. Accessed March
2, 2015.
2. Inhomogeneity. OzRadOnc Web Site. http://ozradonc.wikidot.com/inhomogeneityphotons. Accessed March 4, 2015.
3. Khan FM, Gerbi B. Treatment Planning in Radiation Oncology. 3rd ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2012.
4. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. 3rd ed. St.
Louis, MO: Mosby-Elsevier; 2010:676.
5. Tissue inhomogeneity corrections for megavoltage photon beams. AAPM Report 85.
Madison, WI: Medical Physics Publishing; 2004.
https://www.aapm.org/pubs/reports/rpt_85.pdf. Accessed March 2015.
6. Discussion with Jim Schmitz, Medical Dosimetrist at the Minneapolis VA Medical
Center. January 2015.
7. Discussion with Lihong Qin, Medical Physicist at the Minneapolis VA Medical Center.
March 3, 2015.
8. Bental G. Radiation Therapy Planning. 2nd ed. New York, NY: McGraw-Hill; 1996:100101.
9. Gore E, Sun A, Ramalingam S, et al. Randomized phase II study comparing prophylactic
cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive disease small cell lung cancer (ED-SCLC). Radiation
Therapy Oncology Group (RTOG).
http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0937.
Accessed March 6, 2015.

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10. Khan F. The Physics of Radiation Therapy. 2nd ed. Baltimore, MD: Lippincott Williams
&Wilkins; 1994.
11. DesRosiers C. Calculation algorithms in radiation therapy treatment planning systems.
[AAMD Region III Lecture, 2013] Indianapolis, IN.
http://www.medicaldosimetry.org/pub/397f61d4-2354-d714-5172-744e9b92e649.
Accessed March 7, 2015.