1

Bianca Tester
Case Study
April 8, 2018

Case Study for Clinical Trial NSABP B-51 (arm 2B)

History of Present Illness: The patient, JG, was a 44-year-old premenopausal woman, who
presented with a palpable mass in her left breast in February 2016. The palpable mass would
come and go with her periods, but by March 2017 the mass persisted and she then sought
medical attention. On 4/13/17, JG had a diagnostic mammogram which showed a 3-cm mass in
the 1:00 position of the left breast. There was also a 2.6-cm enlarged left axillary lymph node
suspicious for metastatic disease. When JG was notified of the abnormal mammogram, the next
step for her was to have an ultrasound-guided needle biopsy. The biopsy demonstrated a grade 3
invasive ductal carincoma, ER/PR and HER-2/neu were all positive. Her Ki-67 was 38%. “Ki-
67 is a protein in cells that increases as they prepare to divide into new cells. A staining process
can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells
there are, the more quickly they are dividing and forming new cells. In breast cancer, a result of
less than 10% is considered low, 10-20% borderline, and high if more than 20%.”1
After receiving her ultrasound-guided needle biopsy results, she next underwent a fine-
needle aspiration to the left axillary node, which confirmed it was metastatic breast cancer. After
she received this news, a PET/CT was ordered, as well as an MRI, to look for any distance
metastasis. The PET/CT scan showed hypermetabolic activity within the left breast and left
axilla but no distant metastatic disease. The breast MRI was notable for the same. There was an
indeterminate 9 x 5 mm enhancing breast mass on the right side.
JG decided to undergo TCHP (Taxotere, Carboplatin, Herceptin, Perjeta) chemotherapy
and started in June 2017; her last cycle was on 9/18/17. The patient noticed dramatic response,
and this was confirmed by both ultrasound and subsequent MRI (both studies showed no
definitive persistent disease.) Genetic testing came back negative on a 28-gene panel but given
her mother’s history of breast cancer at an early age, JG decided to undergo bilateral
mastectomies. Surgery was done on 10/17/17 and was notable for a complete pathologic
response in both the primary site and in her axillary nodes (0 of 11 nodes). JG’s case was
presented at the Multidisciplinary Breast Conference and the recommendation was made for her
 2

to hear about adjuvant radiation therapy.

Past Medical History: JG presented with negligible medical history background (prior to her
diagnosis of breast cancer) consisting of: ADHD, and depression. JG did not report any past
hospitalization/surgeries until her bilateral mastectomy performed on 10/17/17.
Social History: JG, a medical assistant, is married and has three children. JG admits to
smoking ½ a pack of cigarettes for 3-4 years before quitting in 2009. The patient drinks roughly
4 drinks per month, and reports no alcohol/substance abuse or addiction. The patient did report
having a familial history of cancer. JG’s mother passed away at the age of 59, due to metastatic
breast cancer; JG’s aunt (mother’s sister) also had breast cancer in her 50’s, but is still doing well
twenty years later. Due to JG’s mother and aunt’s history of breast cancer, this increased JG’s
risk of developing breast cancer.2
Medications: At the time of the consult, the patient reported taking the following medications:
citalopram, methylphenidate HCl, hydrocodone-acetaminophen, Percocet, Keflex, Tums, and
melatonin.
Diagnostic Imaging: JG unknowingly neglected to seek medical attention for a palpable mass
that came and went during her menstruations, until the mass became consistent (almost a year
after she first felt the lump) then the patient sought medical attention. A diagnostic mammogram
was done 4/13/17 which showed a 3-cm mass in the 1:00 position of the left breast, as well as a
suspicious looking 2.6-cm enlarged left axillary lymph node. JG underwent an ultrasound-
guided needle biopsy as well as a fine-needle aspiration of the left axillary node. After having
the tissue samples analyzed, the results revealed that JG had a grade 3 invasive ductal carcinoma,
ER/PR and HER-2/neu were all positive; the left axillary node confirmed metastatic breast
cancer.
Radiation Oncologist Recommendations: The Radiation Oncologist had a lengthy discussion
with JG, regarding treatment options. The Radiation Oncologist was on the fence about offering
radiation therapy to JG because he cannot tell JG how much improvement in local regional
control to expect – he explained that although we know radiation reduces the risk of local
regional failure by about 60-65% regardless of baseline risk, but we don’t have a ‘good feel’ for
what the baseline risk is in patients with her set of clinical characteristics. Radiation is known to
be effective for patients (particularly in young patients) with clinically positive axillary disease
post mastectomy – had she not had neo-adjuvant chemotherapy the Radiation Oncologist would
 3

recommend radiation therapy. The Radiation Oncologist mentioned data from the NSABP B-18
and B-27, stating that in these trials, 3000 women underwent neo-adjuvant chemotherapy.
Among the patients with tumors less than 5 cm, who underwent a mastectomy, only 21 patients
had a pathologic complete response in both the breast and axilla, but of these 21 patients, none
had chest wall or axillary recurrence with no radiation. These results have led to the current
NRG B-51 clinical trial. This trial randomizes patients in this situation to either: no further
treatment versus chest wall and axillary radiation. JG met with her Medical Oncologist one more
time before deciding to enroll in the NRG B-51 clinical trial.
The Plan (prescription): Per the randomization of the trial, JG was placed in the 2B arm of the
clinical trial. Patients on the 2B arm of the trial had a mastectomy and will receive chest wall
and regional nodal irradiation, as well as additional systemic therapy as planned.3 JG received
neo-adjuvant TCHP (Taxotere, Carboplatin, Herceptin, Perjeta). Following the protocol’s
instructions, the Radiation Oncologist prescribed 2.0 Gy daily, for 25 fractions, for a total of 50
Gy.3 3D-CRT and IMRT were both allowed as treatment modalities, but due to the patient’s age
(young and healthy) and location of tumor bed, it was felt that IMRT would prove to be a better
treatment technique for JG, as the intent was to try and spare as much dose to the heart and lungs
as possible.
Patient Setup/Immobilization: After completing chemotherapy, JG came in for her CT
simulation on 1/4/18. JG was positioned head-first supine, with her arms above her head using a
wingboard and vac-lok placed ontop of the wingboard (to make her arm placement more
reproducible). A memory foam pad was placed just below the wingboard, and a knee sponge
was placed under JG’s knees for comfort (Figures 1 & 2). Radio-opaque markers were placed on
the patient’s skin to facilitate contouring segmentation of the CT data-set. The markers were
used to identify: 1) the mastectomy scare, and 2) the clinical outline at least from 2 o’clock to 10
o’clock representing the physician’s clinical assessment of the “at risk” chestwall (which can
include postoperative changes and where the ipsilateral breast previously was located.)4 The
simulation was completed using a deep inspiration breath hold CT. With this technique, the
chestwall moves away from the heart, to aid in delivering less radiation to the heart.
Anatomical Contouring: Following the CT simulation, the treatment planning CT was
imported into MIM and Pinnacle to contour normal structures. (The Radiation Oncologist
prefers to contour in MIM and the dosimetrist worked on the normal OAR’s in Pinnacle). Per
 4

the protocol, the CTV, PTV, and normal structures generally follow the RTOG-endorsed
guidelines, however, the target volume names must be used exactly as seen from the protocol
(underscores when used are required, and names are case sensitive).4 The Radiation Oncologist
contoured the Levels I, II, and III lymph nodes for the axilla and supraclavicular. The
dosimetrist contoured organs at risk (OAR) such as: the left and right lung, heart, thyroid,
carina, spinal cord, larynx, scar, skin, esophagus, and right breast. Besides the OAR’s, the
dosimetrist also contoured the PTV, and the scar wire. The dosimetrist was given instructions
per the protocol4 on how to draw the PTV.
Beam Isocenter/Arrangement: Once the Radiation Oncologist was done drawing his volumes,
it was obvious that a 3D plan wouldn’t be acceptable for heart and lung constraints per the
protocol (no more than 35% of the ipsilateral lung should receive 20 Gy)4, the dosimetrist
decided to try using a modified half beam block (HBB) VMAT technique. The treatment was
planned for a Varian Trilogy 4013 machine, that has either 6 or 15 MV photon energies. The
isocenter was placed roughly in the center of the PTV volume, but about 6 cm (deep) away from
the chest wall (somewhat centralized in the ipsilateral lung volume) (Figures 3-6). The isocenter
was placed in such a way that the entire PTV could be covered within the field size (the volume
was very large and was at the limitation of the jaws/MLC’s) (Figures 7-10).
Treatment Planning: The treatment planning was done using Philips Pinnacle version 16.0. In
order to meet the heart and lung constraints set forth in the NRG B-51, a modified VMAT plan
was created. With the use of MLC’s, the leaves could close down and spare dose to the lungs
while treating just along the chestwall. Many case studies have been done to compare 3D plans
versus IMRT and lowering dose to specific OARs. One case study in particular was done to
compare treatment techniques for a woman that presented with left sided inflammatory breast
cancer. In this case study, partially wide tangents (PWT) were considered the most appropriate
balance of tumor volume coverage and tissue sparing and the results were: mean heart dose
(MHD) was 13.6 Gy, and ipsilateral lung V20 was 56.9%.5 Another technique looked at, was a
photon/electron technique (20/80 mix). The MHD was 12.4 Gy and V20 Gy was 56.8%. These
two techniques showed no benefit between lowering heart and lung dose. Lastly, a VMAT plan
was done, and the MHD was 6.4% and the ipsilateral lung V20 was 27.2%.5 As you can see, the
MHD was almost lowered by 50% when comparing the first two techniques with the VMAT
technique. Although JG’s case and this other woman’s case had different diagnoses the same
 5

concept applies – treat the PTV effectively and spare as much heart and lung volume as possible.
Due to the size of the PTV volume, in order to have good coverage, a modified VMAT
plan using HBB technique was used because the PTV volume exceeded the collimators 40 x 40
cm field size. In addition to using the HBB technique, the collimator had to be rotated slightly to
ensure coverage to the most superior and inferior portion of the PTV (and also aid in reducing
the overlap of inter-leaf leakage of the MLCs between the arc fields). The beam arrangement
(gantry angles) for JG was chosen to avoid the contralateral lung as much as possible, as well as
minimizing the dose to the ipsilateral lung and heart (Figure 11). The first arc had a gantry
rotation from 230° to 114° with a collimator rotation of 163°. Arc 2 had a gantry rotation from
114° to 2° with a collimator rotation of 195°. Arc 3 had a gantry rotation from 2° to 114° with a
collimator rotation of 195°. Arc 4 had a gantry rotation from 114° to 230° with a collimator
rotation of 163°. By using a VMAT technique, this helped increase the conformity of the dose to
the PTV while keeping the dose off of the heart and lungs (Figures 17-19). The plan was left at
100% normalization to the ROI (region of interest) mean (ROI mean was the PTV to 50 Gy). A
DVH (dose volume histogram), seen in Figure 20, shows the modified VMAT plan illustrating
the PTV receiving the prescription dose while keeping the OARs below the acceptable limits
outlined in the protocol. A score card had to be manually built in the Pinnacle TPS by the
dosimetrist to show the physician if the OARs met the dose constraints listed from the protocol
(Figure 12).
Quality Assurance/Physics Check: Our department uses a Sun Nuclear Arc Check model 1220
cylindrical diode array for doing QA on IMRT and VMAT plans. The diode spacing is 10 mm
over the central 21 cm diameter and 21 m length of the detector. The diode array was calibrated
to absolute dose by comparison to a PTW 30006 ion chamber with an ADCL calibration.
Agreement between the treatment planning computer calculation and measured values at a
selected point was within 0.4%. Isodose curves for the patient treatment were calculated with
the Pinnacle TPS in a cylindrical phantom geometry. Using the identical cylindrical phantom
geometry, isodose curves were measured at the same effective depth using the ArcCheck array
with the patient treatment beams on the Trilogy (the beams were loaded onto the ArcCheck
phantom for physics to put in QA mode to run on the Trilogy). The diode array isodose curves
and Pinacle planned isodose curves were analyzed using the Sun Nuclear dosimetry system
software. The comparison (overlay) between computed and measured values was acceptable.
 6

Array measurement points with a disagreement of greater than 2.0% were flagged for DTA
(distance to agreement) analysis. Measurement points that were outside the DTA threshold of 2
mm were indicated by detector positions highlighted in blue (lower than expected) or red (higher
than expected) (Figure 13-15). A separate calculation form was documented for the IMRT plan
and monitor unit (MU) calculation (Figure 16). The IMRT QA for the treatment plan and the
MU second check were both approved prior to JG receiving her first treatment.
Conclusion: Due to the size of the PTV and the complexity of the location of the treatment area,
a modified VMAT plan was done. Although all the dose constraints, how the PTV was drawn,
etc. had to be done according to the NSABP B-51 trial4, the dosimetrist that worked on this plan
used a separate study6 to get his treatment technique. In this study they were comparing VMAT
for left sided chest wall patients with a flattening filter free technique versus flattened beams.
The study utilized 3 different techniques with RapidArc: conventional-VMAT (C-VMAT),
modified-VMAT plan (M-VMAT), and modified-VMAT plan using FFF (flattening filter free)
beams (M-VMAT-F), and a fourth technique was used for comparison using a ‘normal’ 3D
conformal technique (3DCRT). The study revealed that there was no “substantial difference”
between the four plans, however the VMAT plans showed greater conformity compared to the
3DCRT. The study also revealed that both the M-VMAT and M-VMAT-F could not only reduce
the area in the medium to high doses, but also have smaller volumes in the low-dose regions for
normal tissue.6
This case study helped me realize how time-consuming planning a protocol patient can
be. I had no idea the number of guidelines that were put in place to ensure that facilities are
following the protocol to a ‘t’ (the full protocol PDF has 114 pages!) When you’re doing
contours, the target volume names must be worded exactly as they’re seen in the protocol or your
plan would get bounced back and they’d ask you to make the corrections and re-submit it.
Another thing that I learned from this case study, is that although there are many guidelines in
place there is also a decent amount of wiggle room (at least that was the case for this protocol)
and that there was room for using different treatment techniques to achieve a ‘good’ plan – I had
assumed that protocol patient’s were only allowed to be planned one way (only 3D, only IMRT,
etc.)
One concept that I struggled with is realizing that sometimes a larger volume of healthy
tissue receiving a lower dose is acceptable in order to ensure the healthy tissue isn’t receiving a
 7

higher dose to a smaller volume, by using a different treatment technique (ie: VMAT vs 3D).
Another concept that I struggled with was within the world of VMAT, there are multiple ways to
run a VMAT plan, as the study by Lai, et al6 explained. I thought VMAT plans were pretty rigid
on how they were accomplished, and this case study really opened my eyes to many new
concepts that I look forward to learning as I continue to explore the world of treatment planning
and Dosimetry.
 8

References

1. Breastcancer.org. Breastcancer.org Web site.

http://www.breastcancer.org/symptoms/diagnosis/rate_grade. Updated January 26, 2017.
Accessed April 5, 2018.
2. Slattery M, Kerber R. A comprehensive evaluation of family history and breast cancer
risk: The Utah population database. JAMA. 1993; In press.
doi:10.1001/jama.1993.03510130069033. https://jamanetwork.com/journals/jama/article-
abstract/408683?redirect=true
3. NRG Oncology. NRG Oncology Web Site. http://www.nsabp.pitt.edu/B-51.asp.
Accessed April 5, 2018.
4. NSABP B-51 Clinical Trial (PDF available upon request)
5. Dumane VA, Ohri N, Green S. Volumetric-modulated arc therapy improved heart and
lung sparing for a left-sided chest wall and regional nodal irradiation case. Appl Rad
Oncol. 2017;6(3):28-36.
6. Lai Y, Chen Y, Wu S, et al. Modified Volumetric Modulated Arc Therapy in left sided
breast cancer after radical mastectomy with flattening filter free versus flattened beams.
Medicine. 2016;95(14): http://dx.doi.org/10.1097/MD.0000000000003295