Research Paper Outline

ABSTRACT: This will be left blank until the end of the semester

Introduction: This section will include all of the background information that your reader needs to
understand your research. This section will take some time to develop because it contains most of your
outside research and literature development and your citations.

I. Introduction
A. Radiation therapy is an effective treatment for cancer of the breast, but has been shown to
cause several negative health effects especially for left-sided patients.
1. One of these effects is increased levels of radiation induced heart disease within
patients.1-3
B. In addition to an increased risk of heart disease, another negative effect is an increased
risk of developing a secondary lung cancer.1-5
C. The deep inspiration breath hold (DIBH) technique is a method of radiation treatment for
left-sided breast cancer tumors that has been shown to be effective in reducing the
incidence of heart disease following radiation treatment.6-9
1. However, deep inspiration breath hold technique has been shown to lead to
higher contralateral breast doses.10
2. Also, the patient setup using DIBH is often challenging to reproduce, requiring
longer treatment times which can be an issue in busy departments.
a) Because of this, some departments choose to simulate patients utilizing a
free breathing (FB) CT and a DIBH CT, with the intention of using the
FB CT.
D. There has been little evidence to suggest a reliable anatomical predictive marker that
indicates planning on the free breathing CT scan vs. the DIBH CT scan. 11,12
1. Register et al showed that only the heart volume within the treatment field shows
promise as a parameter that could be used to predict patients that would benefit
from DIBH.11
E. RapidPlan (RP) is a knowledge based treatment planning tool from Varian that allows the
practitioner to generate predictive dose volume histograms (DVHs) once the patients
contoured anatomy is input into the system.
F. Knowledge based treatment planning has been researched in various bodily regions such
as head and neck, lung, esophagus, spine liver and multiple pelvic cancers.13-18
1. The aim of this paper is to analyze if RP could be used as a tool to predict which
patients would benefit from DIBH over FB.

Methods and Materials

Patients: Should include inclusion criteria for why certain patients selected. Should also contain
information on the general CT/simulation procedure.
Contouring: Should include all information relating to treatment planning system and target creation.

Treatment Planning: Should talk about all information related to treatment planning: prescription for
each patient in the case study (or a summary provided in a table), doses to critical structures, beam
angles, collimator rotations, treatment unit type ect.. This section should discuss the goals of treatment
planning outlined by the physician or others, not the results.

II. Methods and Materials

A. Patient Selection
1. All patients selected for the study were treated for left-sided breast cancer in the
supine position at the Stephanie Spielman Comprehensive Breast Center
(SSCBC) from 2014 to present.
a) Depending on the stage of the disease, patients included either underwent
whole breast irradiation (WBI) or intact breast and chestwall treatment
with irradiation of involved regional lymph nodes.
i. The involved lymph nodes included the supraclavicular, axillary,
and internal mammary groups.
b) Patients were excluded from the study if the plan used for treatment was
intensity modulated radiation therapy (IMRT) or if the patient was
diagnosed with bilateral disease.
c) Patients treated in the prone position were also not included in the study.
2. As part of the procedure at the SSCBC for left-sided supine treatments, all
patients were simulated in the supine position and underwent a FB and a DIBH
CT scan.
a) The patients were positioned with the arms overhead on a Qfix breast
board (Figure 1).
b) A vaclok bag was placed under the left arm for further immobilization of
the affected side (Figure 2)
c) The FB scan was completed first, followed by the DIBH scan
i. Varian Real-Time position management (RPM) system was used
to complete the DIBH scan.
This RPM system was used to assess the breathing cycle
of the patient and create an acceptable range for breath
hold immobilization.
d) Computed tomography scans were completed using a GE
Discovery scanner with 2.5 mm axial slice thickness
B. Contouring
1. Following simulation, patient datasets were imported into the Eclipse treatment
planning system for delineation of targets and organs at risk (OR).
a) Target volumes were contoured by the physician according to the
guidelines the Breast Cancer Atlas for Radiation Therapy Planning.19
For intact breast patients without inclusion of regional
lymph nodes, planning target volumes (PTVs) used for
 dose analysis included the Lumpectomy PTV Eval, and
Breast PTV Eval
For intact breast or chestwall patients receiving regional
nodal irradiation, volumes used for dose analysis
included: Lumpectomy PTV Eval, Breast PTV Eval,
Chestwall PTV Eval, Mastectomy Scar PTV Eval,
Supraclavicular PTV, Axillary PTV, and Internal
Mammary Node (IMN) PTV.
b) Critical structures were contoured by the planning dosimetrist in
accordance with RTOG 100520 and 130421 and included the heart,
ipsilateral and contralateral lung, contralateral breast, thyroid, sternum,
esophagus, and spinal cord.
A. Treatment Planning
1. Treatment planning was completed utilizing a three-dimensional conformal
radiation therapy (3D-CRT) technique and patient plans were created using the
Eclipse treatment planning system.
a) Depending on the stage of the disease and the decision of the treating
physician, patients were prescribed 50 Gy in 25 fractions, 42.56 Gy in 16
fractions, or 40 Gy in 15 fractions.
Sequential boosts were usually prescribed for 10-14 Gy in 5-7
fractions either to the Lumpectomy PTV Eval or Mastectomy Scar
PTV Eval
b) Treatments were performed using a Varian Truebeam linear accelerator and
treatment beams utilized 6 and 15 MV energies.
c) Beam angles for tangential fields were chosen by the planning dosimetrist in
order to best achieve coverage to the breast or chestwall PTV Eval and limit
the dose to the heart, ipsilateral lung, and contralateral breast.
d) In patients being treated for whole breast irradiation (WBI) excluding nodal
involvement, collimator angles were chosen by the planning dosimetrist
based on the need for a wedge and/or the best angle to block the most lung
and heart while staying conformal to the planning PTV.
e) Patients being treated to regional nodes were planned using a monoisocentric
setup with a half beam block for matching of tangent and nodal fields.
Gantry angles for the nodal fields were chosen in order avoid the
spinal cord and esophagus (generally around angle 345).
2. The RTOG 100520 and RTOG 130421 constraints were used for planning
depending on the prescribed dose (Figure 3).
a) Along with meeting the criteria for the breast PTV, the RapidPlan generated
dose volume histograms will be evaluated and can give insight on which CT
scan to plan on, either free breathing or breath hold. Dose received by the
contralateral breast, lungs and heart will be compared.
B. Model Creation/Validation
1. In order to create a comprehensive database, 72 past patient plans were exported
into RapidPlan.
 a) These plans were previously treated and clinically approved at the
SSCBC.
b) Forty intact breast only and 32 chest wall patients with regional nodal
involvement were included.
i. The database was split to increase the range of PTV and OR
geometries for both types of patients
ii. The database also consisted of a balance of patients treated using
FB and DIBH techniques.
iii. Table 1 shows the composition of patients included within the
database.
c) Matched structures that were used for RP to extract DVH information
from included the contralateral breast, heart, left lung, right lung, PTV
High, PTV Low, Sternum and Thyroid
i. Structures labeled PTV High included: Lumpectomy PTV Eval,
Breast PTV Eval, Chestwall PTV Eval, Mastectomy Scar PTV
Eval, Supraclavicular PTV, and Axillary PTV
ii. The PTV Low was defined as the IMN PTV.
a. This nodal group is often deep seated and located in
close relationship to the heart.
b. Recurrence within the IMN chain is rare even when
these nodes are excluded from treatment.22
For this reason, a lower dose is accepted as
outline in RTOG 1304.
2. After the completion of the database, the model was trained with the given
patient plans.
a) Any matched structures from patient plans with a Cooks Distance
greater than 20 were then excluded from the database.
i. The Cooks Distance is a statistical measure of how influential a
data point is on the rest of the data (an outlier).
b) The model was then exported to Varian Model Analytics in order to
identify patient structures that should further be excluded from the
model.
i. All structures suggested to be excluded were then removed from
the model and the model was retrained.
3. In order to ensure that the model provided accurate DVH predictions, 10 new
patient plans were created using the RapidPlan model.
a) Previously approved patient plans that were not used in training the
model were used for model validation.
i. The patient plans were copied and all reduced fields were
deleted.
ii. All beam energies were changed to 10 MV in order to
approximate the use of a mixed energy treatment plan.
a. Optimization was completed utilizing the Photon
Optimizer (PO) version 13.6.23
 b. Dose calculations were completed using Acuros External
Beam version 13.6.23
b) Before optimization, several RapidPlan predicted values were recorded
based on plan dose constraints which included:
i. Heart constraints recorded included: dose to 5% of heart, dose to
35% of heart and mean heart dose
ii. Lung constraints that were recorded include: volume receiving
20 Gy (V20), volume receiving 10 Gy (V10), and volume
receiving 5 Gy (V5).
iii. Contralateral breast constraints recorded included: volume
receiving 3 Gy (V3).
c) Optimization was then completed using the constraints shown in Figure 5
d) The completed IMRT plan DVH was then evaluated in comparison to the
predicted values and the clinically achieved heart mean for the original
plan.
C. Model Testing
1. In order to test the model, RapidPlan generated plans were created for the FB CT
scan from patients treated DIBH that were included within the model.
2. For these patients, planning had been attempted on the FB scan, but due to not
meeting heart constraints, the patient was planned using the DIBH.
a) Due to this, clinical plan values were recorded for the heart mean for
comparison purposes only.
b) The same process was used as outlined for model validation.
i. A total of 29 patients were included.
c) Before optimization, several RapidPlan predicted values were recorded
based on plan dose constraints which included:
i. Heart constraints recorded included: dose to 5% of heart, dose to
35% of heart and mean heart dose
ii. Lung constraints that were recorded include: volume receiving
20 Gy (V20), volume receiving 10 Gy (V10), and volume
receiving 5 Gy (V5).
iii. Contralateral breast constraints recorded included: volume
receiving 3 Gy (V3).
d) Optimization was then completed using the constraints shown in Figure 5
i. The completed IMRT plan DVH was then evaluated in
comparison to the predicted values and the clinically achieved
heart mean value for the original plan.
Results: This section should reflect on each patient and the results of the treatment planning (ex: what
the dose to the target was, dose to each OR structure ect.). This is the section where you pull in your
statistical analysis parameters

III. Results
A. Model Validation
1. After analyzing DVH data from imported plans, RapidPlan generates statistics
based off of structures matched within the database
a) Overall, structures flagged for dose evaluation were PTV high, PTV low,
heart, left lung, right lung, contralateral breast, sternum, and thyroid.
b) Regression analysis shows that a strong correlation is seen between the
heart, left lung, sternum, and thyroid (Figure 6).
i. This is a measure of how accurately the model can predict doses
to new patients.
2. Following completion of the patient plans, predicted, generated and clinical plan
values were recorded and results can be seen in Table 2.
a) Regression analysis between the RP generated plan and the clinically
completed plan values for the heart, left lung, and contralateral was
performed. Corresponding scatterplots and R2 values can be seen in
Figure 7.
B. Prediction Ability on Free Breathing Scans
1. Following completion of the FB RapidPlan generated plans, predicted and
generated values were recorded. Along with these values, heart means for the
clinically attempted plan were also recorded and results can be seen in Tables 3a
& 3b.
a) A regression analysis was ran between all variables between the RP
generated plan and the clinically completed plan values for the heart, left
lung, and contralateral breast through the creation of scatterplots. Results
can be seen in Figure 8.
b) A poor correlation was seen for the heart and contralateral breast
constraints when comparing RP predicted and RP generated plan values.
c) A strong correlation was shown between the heart mean for the RP plan
and the achieved clinical plan value resulting in a p-value of 2.9E-19.
d) A scatterplot of these two values can be found in Figure 9.
i. From this scatterplot, a trend line was added and a slope formula
representing the relationship between the two groups was
created.
ii. This formula was then applied to the RP values and the
difference between the resulting value of this formula and the
clinical value was recorded (Table 4).
iii. The standard deviation between these values was calculated,
resulting in 48.6 cGy.
Discussion: This is the section that draws your independent research together with your literature
review to discuss your results and if they make sense. Questions you should answer while writing your
discussion: What do you conclude based on the results of your study? Is this consistent with the
literature you found? If not, why do think that is?

IV. Discussion
A. The preliminary results from our study correspond to results of other researchers
analyzing RapidPlan.
1. Lower doses to OR are achieved while maintaining coverage to PTVs
2. However, this is expected due to the clinically achieved plans being conformal
with reduced fields in comparison to optimized IMRT plans.
B. RapidPlan accurately predicted heart doses within +/- 50cGy and predicted that these
plans would exceeded clinical acceptance confirming that it could potentially be
utilized to predict which patients will benefit from DIBH.
1. Only a few contours would be needed on the free-breathing CT before a
RapidPlan can be generated: a chestwall/breast PTV and heart contour.
a) This could save time by limiting the need to fully contour on multiple CT
scans.
2. This was tested by introducing 5 new patients to RapidPlan and generating plans.
a) The RP generated plan values and clinically approved plan values can be
seen in Table 6.
b) P-testing was then performed, resulting in a p-value of ___.

Conclusion: Should be a short summary of your paper and answer these questions: Are there limitations
to your study such as sample size, varying clinical sites ect.? What further research should be done on
your topic? You should include citations to support you research findings.
 Figures

Figure 1. Example of patient setup lying supine on the breastboard from Qfix with the arms
positioned overhead.

Figure 2: Image showing positioning of the vaclock bag under the left arm.
Figure 3. Target and normal tissue constraints outlined by RTOG 1005.13
Figure 4a. Target and normal tissue constraints outlined in RTOG 1304.14
Figure 4b. Target and normal tissue constraints outlined in RTOG 1304.14
Figure 4c. Target and normal tissue constraints outlined in RTOG 1304.14
Figure 4d. Target and normal tissue constraints outlined in RTOG 1304.14
Figure 4e. Target and normal tissue constraints outlined in RTOG 1304.14
Figure 5. Image showing optimization objectives created for RapidPlan.

Figure 6. Summary of model training results

Figure 7. Scatter plots representing RP generated values against Clinical generated values for the
constraints of interest.
Figure 8. Scatter plots representing RP predictions against RP generated values for the
constraints of interest.
Figure 9. Scatter plot comparing RP plan and clinical plan values.
 Tables

Table 1. Complete composition of patients included within the created database.

FB DIBH

Breast Only 15 9

Breast and regional nodes 4 8

Chestwall and regional nodes 12 20

Breast and Axillary Nodes 3 1

TOTAL 72

Table 2. Model validation results.

Table 3a. Prediction ability results on free-breathing CT scans.
Table 3b. Prediction ability results on free-breathing CT scans.
Table 4. Difference in applied formula values versus the clinical plan value for free-breathing
scans.
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