1

Early Stage Left Breast Cancer Treated with Hypofractionated Radiotherapy: A Case
Study
Author: Alisen Fitzpatrick, B.S., R.T.(T), Nishele Lenards, M.S., CMD, R.T.(R)(T), FAAMD,
Anne Marie Vann, MEd,CMD, RT(R)(T), FAAMD
Abstract
Introduction: This case study assessed hypofractionated, accelerated whole breast radiation to
early stage left breast cancer patients and evaluated the difficulty of achieving dose coverage and
dose constraints in patients that had varied separation and lumpectomy cavity location.
Case Description: Whole breast radiotherapy is a standard part of breast conservation treatment
for early stage breast cancer. Three patients were evaluated who had early stage, left sided breast
cancer and received hypofractionated whole breast radiotherapy. Patient 1 met all ASTRO
guidelines for the suggestion of hypofractionated treatment. Patient 2 met all ASTRO
guidelines, but had a lumpectomy cavity with close proximity to the skin. Patient 3 met all
ASTRO guidelines, but did not meet the recommendation by the Journal of the National Cancer
Institute, which suggests the patient separation distance should be less than 25 cm. Different
techniques were used to achieve dose coverage and dose constraints for each patient habitus.
Conclusion: Each plan was created and evaluated based on coverage to the lumpectomy cavity
and breast tissue, with a goal of restricting the maximum point dose to less than 107% of the
prescription. The DVH was used as a tool for plan evaluation. For all three plans, the
prescription dose was not compromised, rather it was the requested coverage of dose to the
lumpectomy cavity and breast tissue that was adjusted, or the maximum point dose request of
107% was altered. The physician change requests were due to a variety of factors, including
lumpectomy placement within the breast tissue and the maximum separation measurement of the
treated left breast.
Key Words: Breast Radiotherapy, Hypofractionated Whole Breast Irradiation, Accelerated
Whole Breast Radiation Therapy


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Introduction
Breast conservation surgery or lumpectomy is most often recommended for patients with
early stage breast cancer.
1
Following surgery, whole breast irradiation is proven to reduce the
risk of local recurrence for women, and reduce the chance of needing a mastectomy in the future,
conserving the affected breast.
2
With whole breast irradiation, the risk of ipsilateral breast tumor
recurrence is reduced by approximately 70% at 5 years and produces a 5% improvement in 15-
year overall survival.
3
The role of whole breast radiation treatment after breast conservation
surgery is widely practiced and accepted among institutions, but there is no definite agreement
what schedule and treatment fractionation should be used for patients depending on their
pathologic stage, histology, surgical margins, age, presence of adjuvant chemotherapy treatment,
or separation measurement of the affected breast.
Although radiation therapy following a lumpectomy is an important part of breast
conservation therapy, there are several reasons why a patient may choose not to receive
radiotherapy after surgery.
4
One of the reasons may include the inconvenience that comes with a
conventional, standard whole breast radiotherapy course of treatment. With conventional
fractionation, a patient must complete radiation therapy treatments 5 days a week for 6-7 weeks.
For patients who must travel or take time off of work, the expense, combined with the added cost
of direct health care, may be too much of a committment.
3
This contributes to approximately
30% of patients in North America who will undergo breast conservation surgery and not
complete a treatment of breast irradiation. This is highly concerning to practitioners considering
that the rate of local recurrence at 5 years was 8% with the use of breast irradiation as compared
to 30% with no further treatment.
2

A hypofractionated, accelerated whole breast treatment technique has been used in
centers in Canada and the United Kingdom for several years.
1
The idea of hypofractionated
treatment for breast cancer was based upon the idea that a larger dose per fraction given over a
shorter amount of time could be just as effective radiobiologically as the conventional
fractionation for breast radiotherapy that was traditionally practiced. Hypofractionated
treatments can vary from 40-45 Gy in 15-20 fractions and will be delivered over 19-22 treatment
days with a fractionated dose of 2.3-2.7 Gy.
Many radiation oncologists have been hesitant to treat early stage breast cancer with a
hypofractionated treatment regimen due to the lack of long term studies analyzing cardiac and
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pulmonary toxicities, as well as cosmetic outcomes. However, recent published studies
regarding morbidity from cardiac causes and acute toxicities have verified that an accelerated
course of treatment provides no additional risk of cardiac or pulmonary toxicities or cosmetic
outcomes if recommended dose constraints are followed, guided by quantitative analysis of
normal tissue effects in the clinic (QUANTEC) data published in 2010.
5,6,7

Three, left-sided, early stage breast cancer patients will be presented in this case study
that represent different patient separation distances and placements of lumpectomy cavities.
Each patient was treated by the same physician with an identical prescription dose. Dose
coverage of the breast tissue and lumpectomy cavity varies with each patient due to homogeneity
and maximum point dose value restrictions.

Case Description
Patient Selection
In 2011, American Society for Radiation Oncology (ASTRO) published evidence-based
guidelines regarding fractionation for whole breast irradiation, and released 4 criteria that
patients should satisfy before being treated with hypofractionated whole breast irradiation.
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First, the patient must be 50 years or older at diagnosis. This is because the risk of ipsilateral
breast tumor recurrence after breast-conservation surgery followed by adjuvant whole breast
radiotherapy decreases as age increases, and is particularly high for women in their 40s.
Patients must also have a pathologic stage of T1-2N0. This restriction was mentioned because
patients with T3-4 disease are primarily treated with mastectomy and data is not sufficient to
support a hypofractionated course of treatment for these patients. Lymph node treatment is also
excluded because brachial plexopathy may have an increased risk of occurrence, along with
pulmonary toxicity, if regional nodes are treated with an accelerated fractionation schedule. In
addition, the patient cannot have received systemic chemotherapy, again because current data is
not sufficient enough to support a hypofractionated schedule within these patients. Qualification
for a hypofractionated schedule also requires that within the breast, along the central axis, the
minimum dose is no less than 93% and maximum dose is no greater than 107% of the
prescription dose. In order to achieve this dose constraint, it is recommended that a patients
separation along the central axis does not exceed 25 cm.
1
Although this suggestion is stated
specifically in relation to the central axis, it is common that radiation oncologists and medical
4

dosimetrists measure the distance of entrance to exit of a tangential beam on the patients skin to
determine eligibility for a hypofractionated treatment regimen that is not along the central axis,
rather along the widest distance of patient separation that the treatment beam will pass through.
Each patient in this case study was diagnosed with ER+, PR+, HER2- invasive ductal
carcinoma. Each patient had stage T1N0M0 disease with negative margins after breast
conservation surgery and was over 50 years of age. Patients 1 and 3 were simulated in the
supine position, head first into the Phillips CT scanner. Both patients were immobilized using a
supine breast board with arms above their heads. One anterior and two lateral marks were placed
on the patients skin to help with patient set-up on the treatment machine. Patient 2 was
simulated in the prone position, head first into the CT scanner, and immobilized on a prone
CDR Systems breast board with an Alpha cradle bag made for her arms to lie above her head.
Three straightening marks were made posteriorly with 2 leveling marks to help with patient
positioning on the treatment machine. In addition, a mark was made on the patients breast to
align with the prone board each day for treatment. Megavoltage portal imaging was used prior to
the first treatment, and weekly thereafter to verify patient positioning throughout treatment.
Target Delineation
Target delineation was specified using the Varian Eclipse 10.0 treatment planning system
(TPS). With the aid of radio-opaque wires that were placed on the patients at the time of
simulation, the physician contoured the breast tissue for each patient. After reading surgical
notes and looking at clips placed by the surgeon, the radiation oncologist also contoured the
lumpectomy cavity for each patient. Organs at risk (OR) for each plan included the left lung and
the heart. Other contoured structures include the right lung, spinal cord and the carina.
Treatment Planning
The beam energies, arrangements and dose prescriptions are displayed in table 1 for all
patients. The prescription for each patient was hypofractionated, delivering 42.72 Gy in 16
fractions at 2.67 Gy per day. For all patients, 95% of the dose was expected to cover 95% of the
contoured breast tissue, while 100% of the dose was expected to cover 100% of the lumpectomy
cavity. Patient 1 was treated in the supine position and had a separation distance of 24 cm. The
deepest region of the lumpectomy cavity extended 5.5 cm into the breast (Figure 1). The
radiation oncologist prescribed dose constraints of V
20 Gy
20% for the left lung and the heart
could not exceed a mean dose of 26 Gy. The multi-leaf collimator (MLC) block was verified by
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the radiation oncologist to include no more than 2 cm of the left lung and completely block out
the heart.
Patient 2 was treated in the prone position and had a separation of 20.5 cm (Figure 2).
The deepest region of the lumpectomy, expected to be covered by the 100% isodose line, was
measured at a distance of 6.5 cm below the surface of the breast. The radiation oncologist
prescribed the same dose constraints for this patient regarding the left lung and heart. The block
shape was created using a rotated collimator and verified by the radiation oncologist. The jaws
on the machine blocked out the heart and left lung. The field shape easily blocked out these
critical structures because the breast tissue was pulled further from the patient due to her prone
position, allowing a sufficient margin between treated breast tissue and critical structures that
otherwise would not have been achieved with a supine position.
Patient 3 was treated in the supine position and had a separation of 27 cm. The deepest
part of the lumpectomy cavity measured 6.7 cm (Figure 3). The dose constraints used for the left
lung and heart prescribed by the physician were the same as the other 2 patients. The MLC
block was verified by the physician and adjusted so the field did not include more than 2.25 cm
of the left lung and completely blocked out the heart. Due to the wide separation of the patient,
an added volume of left lung was allowed to be within the treatment field to assure that 95% of
the breast tissue was within the 95% isodose line.
For each plan, two opposing tangent beams were placed so that the 100% of the dose
covered 100% of the lumpectomy cavity, and 95% of the dose covered 95% or more of the breast
tissue. The ASTRO guidelines require that the maximum dose is not greater than 107% of the
prescribed dose, therefore different techniques of using wedges, varying energies, and field-in-
field approaches were used to assure that the dose constraints were met. In the event that the
dose constraints could not be met, the physician adjusted the requests, or accepted a point of
maximum of over 107%. Each plan was optimized with heterogeneity turned on to account for
the changes in dose as the radiation traveled though the left lung.
Plan Analysis and Evaluation
For patient 1, the medical dosimetrist designed three different plans to adhere to the
physician dose constraints. First, a plan using only 6 MV beams was created using several field-
in-fields to limit the dose to be 107%. Second, a plan incorporating 6 MV and 23 MV energies
from both sides was used to account for the patient separation and reduce the 120% isodose line
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before starting to use field-in-fields. Lastly, a plan utilizing a 30 wedge on the lateral tangent
fields, 6 MV and 23 MV, was created. After analyzing each one, the physician determined to
use the plan that utilized 6 MV only, due to the surface dose that was achieved by this plan
(Figure 4). In total, there were 3 field-in-fields that were used, on each side, to get the point of
maximum dose to be 107.8%. The medical dosimetrist had difficulty covering the lumpectomy
with the 100% isodose line, therefore the physician decided to accept a global maximum dose >
107% for this patient. The 100% isodose line covered 99.8% of the lumpectomy, whereas the
98% isodose line covered 95% of the breast tissue. The volume of left lung receiving 20 Gy or
more was 12.9%, and the heart received a mean dose of 1.16 Gy, primarily because it was
blocked from all fields. It is important to remember that this patient had a separation of 24 cm.
This is smaller than the recommended measurement of 25 cm that was suggested in the Journal
of the National Cancer Institute in 2002, but because the lumpectomy needed to be covered by
the 100% isodose line, the physician had to increase the limit of overall point of maximum dose
to create an acceptable treatment plan for the patient.
1

Patient 2 was treated with 2 tangential 6 MV beams with only one field-in-field used for
each side to block out areas of high dose. The medical dosimetrist took a different approach on
this plan because the patient separation was only 20.5 cm. Instead of multiple, lightly weighted
field-in-fields, only one heavily weighted subfield was used per side. Approximately 15% of the
prescribed dose was delivered through these 2 field-in-fields. Although the deepest point in the
lumpectomy cavity was 6.5 cm from the skin, the most superficial lumpectomy contours were
drawn less than 0.02 cm away from the skin surface because of the placement of a surgical clip.
Due to the location of the contours, adding more field-in-fields to lower the point of maximum
dose was not in the best interest of the patient because the 100% isodose lines would begin to
shift posteriorly (Figure 5). Adding a higher energy for treatment was also not advised because
the increased energy would cause the isodose lines to curve inward compared to the isodose lines
produced by a lower energy treatment beam. Because of the location of the lumpectomy cavity,
99% of the dose covered 96% of the lumpectomy and 99% of the dose covered 94% of the breast
tissue. The volume of left lung receiving 20 Gy or more was 7.5% and the heart received a mean
dose of 1.34 Gy. Overall, the point of maximum dose was 109.1%.
Patient 3 was treated with 2 tangential 6 MV beams, 2 lightly-weighted tangential 23 MV
beams, and 2 field-in-fields on each side. The plan also incorporated a 30 wedge that was used
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on all 4 lateral fields. After the placement of the initial tangent 6 MV beams, lightly weighted 23
MV tangent fields with the same MLCs were added to decrease the regions of high dose. A 30
wedge was also added on all lateral fields to shift dose from the anterior part of the breast more
posteriorly (Figure 6). This helped reduce areas of high dose in the anterior part of the breast
and provide better dose coverage to the lumpectomy cavity. A physical wedge was necessary to
utilize the block field that was designed by the radiation oncologist. The separation of the
patient measured 27 cm, which is significantly over the suggestion of 25 cm. However, even
with a wider separation, the medical dosimetrist was able to provide a plan with a point of
maximum dose of 107.9%, while covering 100% of the lumpectomy with 100% of the dose, 98%
of the breast tissue with 95% of the dose, a V
20

Gy
of 10.6% and a mean heart dose of 1.86 Gy.
Although not all three radiation therapy plans met the suggestions that were presented in
the Journal of the National Cancer Institute or ASTRO guidelines, all three plans did meet the
dose constraints that are present in RTOG 1005, a phase III trial regarding hypofractionated
radiotherapy for breast cancer.
8
These constraints included a V
20 Gy
15% for the ipsilateral
lung, V
5 Gy
10% for the contralateral lung, and V
20 Gy
5% for the heart on all left sided
breast cancer cases (Figures 7, 8, and 9). The physician evaluated each plan individually and
compromised some constraints in order to provide adequate dose coverage to the lumpectomy
and breast tissue. An evaluation of dose coverage can be seen in Table 2.
Conclusion
In each case, the medical dosimetrist was unable to meet the prescription point of
maximum dose < 107%, and in 2 of the 3 cases, 100% of the lumpectomy cavity was not covered
by the 100% isodose line. Although the radiation oncologist was willing to accept different
coverage than originally requested, the greatest constraint affecting dose coverage was the point
of maximum dose. An important restrictive ASTRO guideline that is different from
conventionally fractionated treatments is the restriction of maximum dose to < 107% of the
prescribed total dose. It is important to note that 107% of 1.8 Gy is a lower daily dose compared
to 107% of 2.67 Gy and the fear is that there will be an increased risk in heart or pulmonary
toxicities as well as cosmetic outcomes in the future for these patients.
Current data suggests that cardiac and pulmonary toxicities are not a concern if ASTRO
and QUANTEC dose guidelines are followed. Women who meet the criteria of these guidelines
could benefit from a hypofractionated treatment regimen if long term studies are able to provide
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additional data regarding treatment related toxicities. It is the goal of RTOG 1005 to suggest that
hypofractionated breast radiotherapy is not inferior to conventional radiotherapy treatment for
women and to provide long term data that can be applied to hypofractionated breast treatments.
There is a need for long term studies that include a wider variety of patients, including women
under 50 years of age, those that had chemotherapy included in their treatment regimen, patients
with positive regional nodes, and those with a separation distance larger than 25 cm. With
additional information collected over a longer course of follow-up, more women can benefit
from a shorter treatment duration with similar risks of toxicities as women who are completing
conventionally scheduled radiotherapy.















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References
1. Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation schedules after
lumpectomy for women with lymph node-negative breast cancer. J Natl Ca Inst.
2002;94(15):1143-1150. http://dx.doi.org/10.1093/jnci/95.10.759-a
2. Whelan T, Pignol JP, Levine M, et al. Long-term results of hypofractionated radiation
therapy for breast cancer. N Engl J Med. 2010;362(6):513-520.
http://dx.doi.org/10.1056/NEJMoa0906260
3. Smith B, Bentzen S, Correa C, et al. Fractionation for whole breast irradiation: an American
Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol
Phys. 2011;81(1):59-68. http://dx.doi.org/10.1016/j.ijrobp.2010.04.042
4. Freedman G, Anderson P, Bleicher R, et al. 5 year local control in a phase II study of
hypofractionated intensity modulated radiation therapy with an incorporated boost for early
stage breast cancer. Int J Radiat Oncol Biol Phys. 2012;84(4):888-893.
http://dx.doi.org/10.1016/j.ijrobp.2012.01.091
5. Chan E, Woods R, McBride M, et al. Adjuvant hypofractionated verses conventional whole
breast radiation therapy for early-stage breast cancer: long term hospitalrelated morbidity
from cardiac causes. Int J Radiat Oncol Biol Phys. 2014;88(4):786-892.
http://dx.doi.org/10.1016/j.ijrobp.2013.11.243
6. Chadha M, Vongtama D, Friedmann P, et al. Comparative acute toxicity from whole breast
irradiation using 3-week accelerated schedule with concomitant boost and the 6.5-week
conventional schedule with sequential boot for early-stage breast cancer. Clin Breast Cancer.
2012;12(1):57-62. http://dx.doi.org/10.1016/j.clbc.2011.09.002
7. Marks L, Yorke E, Jackson A, et al. Use of normal tissue complication probability models in
the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):S10-S19.
http://dx.doi.org/10.1016/j.ijrobp.2009.07.1754
8. Vicini F, Freedman G, White J, et al. A phase III trial of accelerated whole breast irradiation
with hypofractionation plus concurrent boost versus standard whole breast irradiation plus
sequential boost for early-stage breast cancer. Radiation Therapy Oncology Group (RTOG).
http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1005. Updated
June 23, 2014. Accessed July 1, 2014.

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Figures


Figure 1. Breast contour (light green) with placement of lumpectomy cavity (red) for patient 1.

Figure 2. Breast contour (light green) with placement of lumpectomy cavity (red) for patient 2.
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Figure 3. Breast contour (light green) with placement of lumpectomy cavity (red) for patient 3.

Figure 4. Isodose distribution for patient 1. Pink = 105%, Yellow = 100%, Green = 95%, Blue =
50%, Cyan = 20%, Lumpectomy = red.
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Figure 5. Isodose distribution for patient 2. Pink = 105%, Yellow = 100%, Green = 95%, Blue
= 50%, Cyan = 20%, Lumpectomy = red.

Figure 6. Isodose distribution for patient 3. Pink = 105%, Yellow = 100%, Green = 95%, Blue
= 50%, Cyan = 20%, Lumpectomy = red.
13


Figure 7. DVH for patient 1. Lumpectomy = red, breast tissue = green, left lung = yellow, heart
= pink, right lung = blue


Figure 8. DVH for patient 2. Lumpectomy = red, breast tissue = green, left lung = yellow, heart
= pink, right lung = blue
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Figure 9. DVH for patient 3. Lumpectomy = red, breast tissue = green, left lung = yellow, heart
= pink, right lung = blue











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Tables

Table 1. Treatment planning details for patients 1-3.
Treatment Planning Parameters
Planning
Technique
Beam
Energy
Prescription
Dose
Beam
Arrangement
Gantry
Angles
Collimator
Angles
(respective
to Gantry
angles)
Patient 1 3-D CRT 6 MV 42.72 Gy in
16 fx
2 Tangent
Beams 6X, 3
FIF each side
310, 133
0
Patient 2 3-D CRT 6 MV 42.72 Gy in
16 fx
2 Tangent
Beams 6X
1 FIF each
side
101, 275 20, 340
Patient 3 3-D CRT 6 & 23
MV
42.72 Gy in
16 fx
2 Tangent
Beams 6X,
2 Tangent
Beams 23X,
2 FIF 6X
each side
305, 127 0



Table 2. Dose evaluation for patients 1-3.
Dose Evaluation
Patient Prescribed
Dose
Maximum Point
Dose
Breast Tissue
Coverage
Lumpectomy coverage
1 42.72 Gy 107.7% 95% covered by
98.8% of dose
99.8% covered by 100%
of dose
2 42.72 Gy 109.1% 94% covered by
99% of dose
99% covered by 96% of
dose
3 42.72 Gy 107.9% 98% covered by
95% of dose
100% covered by 100%
of dose