1

Stereotactic radiosurgery (SRS) for brain metastases and the implications to normal brain
tissue with flattening filter free (FFF) versus flattening filter (FF) beams: A Case Study
Authors: Melissa Wojno, Dakota Sturgess, R.T.(T), Chelsea Gehrig, R.T.(T), Nishele Lenards,
PH.D., CMD, R.T.(R)(T), FAAMD, Ashley Hunzeker, M.S., CMD, Matt Tobler, CMD, R.T.(T),
FAAMD
Medical Dosimetry Program at the University of Wisconsin - La Crosse
Introduction
Radiation therapy planning requires calculating accurate dose to a treatment volume
while avoiding any surrounding organs at risk (OAR) and normal tissue. Specific dose limits are
assigned to OAR which determines what treatment technique is used and how much dose of
radiation is prescribed. With normal tissue sparing techniques, negative side effects from
radiation therapy treatment can decrease. For central nervous system (CNS) treatment, avoiding
radiotoxicity to OAR, such as healthy brain tissue, can reduce many side effects.
Acute side effects of radiotoxicity to brain tissue can occur within 48 hours after a single
fraction delivered and reside days or weeks after radiation exposure. These effects can include
fatigue, vomiting, and cephalgia.1 Additionally, subacute effects may occur and are not always
reversible. The reaction to radiation toxicity at this level can include decrease in fine motor
skills, decrease in sensory function, difficulty speaking, and cognitive impairment.1 Late side
effects are due to the necrosis of brain tissue or intercranial pressure caused from radiation
damage. These effects can be very harmful and include seizure disorders, amnesia, and long-term
hemiparesis.2 To decrease these responses to radiation treatment, dose constraints to healthy
tissue are used to avoid negative reactions from the radiation.
Some dose constraints used for brain metastases measure the volume of healthy tissue, in
cubic centimeters (cc), receiving a dose value. According to a study that was completed by
Lawrence et al,3 the volume of brain receiving 12 Gy or more has a correlation with radiation
necrosis of brain tissue. Therefore, it has been recommended by Lawrence et al3 the volume of
healthy brain receiving 12 Gy should be used as the standard metric to report the dose received
by healthy brain tissue to avoid side effects from radiotoxicity. The risk of toxicity increases
when more healthy brain tissue is exposed to radiation, Quantitative Analysis of Normal Tissue
Effects in the Clinic (QUANTEC) recommends that a dose constraint to the volume of healthy
2

brain tissue is less than 5 to 10 cc receiving 12 Gy.3 This dose constraint becomes more
challenging to meet when multiple lesions are being targeted.
Different techniques of radiation therapy treatment are used to limit dose to OAR.
Intensity modulated radiation therapy (IMRT) uses field shaping to create small margins around
the treatment volume to reduce the exposure of radiation to surrounding tissue. Volumetric
modulated arc therapy (VMAT) technique uses dynamic field shaping and dynamic radiation
source angles to avoid treating healthy tissue and keep tighter margins around treatment
volumes. During treatment, patients are immobilized to reproduce the same position while
receiving radiation. The accuracy of the reproduceable position ensures that the beam placement
is more precise, adequately treating the target, while limiting dose to nearby OAR.
Dose prescription and fractionation can affect the dose received by OAR. The
prescription may be lowered to meet constraints of surrounding tissues but must remain at an
adequate dose level to treat the area intended. The fractionation of a treatment plan can also be
adjusted to spare healthy tissue. For example, hypofractionation is a treatment technique that
prescribes the same amount of dose in less fractions. This treatment type has been used to deliver
dose to a treatment volume, without causing additional side effects compared to conventional
fractionation.4 For brain metastases, stereotactic radiosurgery (SRS) is a common technique using
hypofractionation. Stereotactic radiosurgery delivers high dose to tumor volumes in a single
fraction and may have better response rates for radioresistant tumors. Although treatment times
of SRS techniques are longer due to the high dose given in a single fraction, it does not increase
the probability or severity of CNS side effects. To decrease these treatment times without
decreasing dose delivered, some treatment machines can deliver SRS using flattening filter free
(FFF) beams and shorten the time the beam is delivering treatment. Lower treatment times are
beneficial to avoid patient movement of the during treatment.
Traditionally, the flattening filter (FF) has been used in radiation therapy to provide a
uniform beam of photons over a collimated field.5 In a standard linear accelerator, the FF is
located between the primary collimator and the monitor chamber.6 It is conical in shape and is
made of a material with a high atomic number (Z), allowing it to flatten the forward peaked
bremsstrahlung spectrum of photons. The utilization of the FF for a pre-defined depth allows for
a flat dose profile with a homogenous dose variation across the treatment beam. The photon
beam dose rate is substantially reduced with the FF in its path and is a main source of scattered
3

photons. Without the FF in the beam’s path, the flattening filter free beam has an increased dose
rate, x-ray spectra softened, head scatter radiation reduced, and a nonuniform beam profile is
produced. Because of the increased dose rate, intrafractional target motion may be reduced with
the decreased delivery time. There is also decreased far field peripheral dose distributed to the
patient with the reduced head leakage. 5 Treatment plans utilizing FFF technology may result in a
simpler dose calculation with the decrease in scatter factors and beam quality along the field.5
When FFF beams are used, smaller field sizes are typically required to produce a conformal
beam, allowing them to be particularly beneficial in SRS. For patients with 1 to 4 brain
metastases, FFF beams may be the preferred form of treatment to ensure the peripheral dose
constraint of healthy brain tissue receiving 12 Gy. Though, for patients with more lesions, field
sizes may be larger and the FFF beams may not spare normal brain tissue when compared to FF
beams.
As patients continue to experience side effects resulting from stereotactic radiosurgery
treatment, limiting the dose to healthy brain tissue is a high priority. The use of FFF beams is
becoming a common technique with SRS. The problem is that brain metastases patients with 5 to
9 targets receive a higher total dose of radiation resulting in higher volume of healthy brain tissue
receiving a dose of 12 Gy. Studies about the use of FFF beams have shown reduced peripheral
dose for patients with 1 to 4 lesions, however, there is a paucity of literature assessing the effects
of FFF on normal brain tissue for patients with more than 4 lesions. The purpose of this study
was to determine if FFF beams will decrease the volume of healthy brain tissue receiving 12 Gy
when treating 5 to 9 targets when compared to FF beams. Researchers tested a hypothesis that
(H1A) using FFF beams for SRS brain VMAT plans will reduce the volume of normal tissue
receiving 12 Gy compared to FF beams.
Case Description
Patient Selection and Setup
Five patients who received SRS from a single institution were selected for the
retrospective study. The inclusion criteria of this study consisted of a diagnosis of 5 to 9
metastatic brain lesions with a single isocenter. To remain consistent, patients included were
prescribed a dose of 22 Gy with one isocenter. Of the selected group, two patients had 5 lesions,
one patient had 6 lesions, one patient had 7 lesions, and one patient had 9 lesions.
4

Patients were simulated with Encompass SRS Fibreplast Masks to aid in reproducibility
during treatment. The patients underwent a CT scan headfirst in supine position for simulation.
The CT scans had a slice thickness of 1 mm and included the entire head and neck region of the
patient.
Target Delineation
After completion of CT simulation, the patient’s dataset was exported to Eclipse
treatment planning system for contouring and planning. Each patient planning CT was fused to
an MRI scan to assist in target determination. A radiation oncologist contoured the multiple
gross tumor volumes (GTVs) of each patient. A medical dosimetrist expanded the GTV by 1 mm
to create a planning target volume (PTV).
The medical dosimetrist contoured the OAR on the planning CT. An entire brain tissue
volume was contoured. The healthy brain tissue contour was created by the dosimetrist by using
the entire brain volume and avoiding the PTV contours interiorly, creating “Brain-PTV” volume.
Other contours that were created include the brainstem, cochlea, eyes, optic chiasm, optic nerves,
spinal cord, and lenses. These contours were used for data analysis.
Treatment Planning
Two plans were created for each patient, one with 6 FFF and one with 6 FF beams on a
Varian True Beam Edge linear accelerator. This linear accelerator is equipped to treat SRS plans
with extra-fine 2.5 mm Multi-Leaf Collimator (MLC) leaves. The VMAT arc geometry
arrangement varied per patient due to the amount and location of lesions (Figure 1). Each patient
was planned isocentricly with 3 to 5 arcs (Table 1). The gantry angles rotated both clockwise and
counterclockwise at least once for each patient. The collimator for each patient was rotated
anywhere from 5° to 300° dependent on patient anatomy. The table position was rotated at a
different angle for each beam to ensure full coverage of the lesion and to avoid any surrounding
OAR. Common couch angles used were 0°, 30°, 45°, 270°, 315°, and 330°. The couch rotations
allow the beam to travel across different planes of the patient, not just the transverse plane.
For each patient, the 6 FFF beams were planned first. The volume Brain-PTV receiving
12 Gy (V12) was used as an objective and lowered as much as possible during treatment planning,
without losing coverage of the PTV. The plan was then copied, and the beams were changed to 6
FF with the objectives remaining the same. The copied plan was optimized and compared to the
original plan to ensure the plan met the same requirements. Each plan was normalized so that
5

100% of prescription dose covered at least 99.5% of the multiple PTV volumes. This
requirement ensured that the plan comparisons would be accurate.
Plan Analysis and Evaluation
The plans were optimized to reduce the V12 constraint as much as possible, but were
higher than desired due to the volume of PTV in the brain (Table 2).2 The mean volume of all
PTV contours was 3.04 cc. The final dose to healthy brain tissue between the 6 FF and 6 FFF
plans was compared by using a dose volume histogram (DVH) for all 5 patients (Figures 2 & 3).
This was completed by examining V12 Gy of Brain-PTV.
The data of healthy brain dose was examined to determine the method of statistical
testing required to analyze the data. To compare the difference in peripheral dose between the FF
and FFF beams, a one-tailed paired T-test was implemented resulting in a p value. After stats
computation was preformed, values of P < 0.05 were considered significant to determine if the
null hypothesis (H10) could be rejected.
Comparing the healthy brain volume receiving 12 Gy between the FFF beam plan and the
FF beam plan, all 5 patients had lower volumes with the FFF beams (Table 2). The change in V12
Gy between the two plans ranged from -0.14 cc to -0.65 cc. The P-value for the V12 Gy healthy
brain tissue metric was 0.014, therefore, the null hypothesis (H10) was rejected. The results from
the data collected in this study are consistent with other research. The number of lesions did not
affect if the peripheral dose is reduced by using flattening filter free beams.
Conclusion
Creating treatment plans with adequate dose to target volumes while minimizing the amount of
dose to surrounding OAR is the goal of radiation treatment planning. The FFF beams used for
SRS cases to reduce the peripheral dose for patients with 1 to 4 brain metastases. An
investigation was needed to determine if the results are consistent with more brain metastases.
The problem is that brain metastases patients with 5 to 9 targets receive a higher total dose of
radiation resulting in higher volume of healthy brain tissue receiving a dose of 12 Gy. The
purpose of this study was to determine if FFF beams will decrease the volume of healthy brain
tissue receiving 12 Gy when treating 5 to 9 targets when compared to FF beams. The results of
this study demonstrated that the use of FFF beams reduced the volume of healthy brain tissue
receiving 12 Gy. Though the change in volume between FFF and FF plans was minimal, the
statistical t-test showed significant results. Not only does the beam profile reduce the peripheral
6

dose, it also is more beneficial during treatment planning due to the decrease in beam delivery
time.
This research involved a case study with a small pool of patient data, from the same
institution. Further research on this topic should be conducted including a larger number of
patient cases from a variety of institutions, using different treatment planning systems and
treatment machines, to establish validity. The inclusion criteria of this study involved patients
with 5 to 9 brain metastases; therefore, further investigation with SRS treatments to metastases
not located in the brain could demonstrate if the results are accurate with different anatomical
structures.
We would like to thank the Statistical Consulting Center at University of Wisconsin - La Crosse
for its advisement of which statistical test should be used for this study; however, any errors of fact or
interpretation remain the sole responsibility of the author.
7

References
1. Belka C, Budach W, Kortmann RD, Bamberg M. Radiation induced CNS toxicity--
molecular and cellular mechanisms. Br J Cancer. 2001;85(9):1233-9.
http://doi.org/10.1054/bjoc.2001.2100
2. Groenewald C, Konstantinidis L, Damato B. Effects of radiotherapy on uveal melanomas
and adjacent tissues. Eye (Lond). 2013;27(2):163-171.
http://doi.org/10.1038/eye.2012.249
3. Lawrence YR, Li XA, el Naqa I, et al. Radiation dose–volume effects in the brain. Int J
Radiat Oncol Biol Phys. 2010;76(3). https://doi.org/10.1016/j.ijrobp.2009.02.091
4. Liu L, Yang Y, Guo Q, et al. Comparing hypofractionated to conventional fractionated
radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review.
Radiat Oncol. 2020;15(17). http://doi.org/10.1186/s13014-020-1463-1
5. Cohen-Inbar O, Sheehan JP. The role of stereotactic radiosurgery and whole brain
radiation therapy as primary treatment in the treatment of patients with brain
oligometastases - A systematic review. J Radiosurg SBRT. 2016;4(2):79-88.
6. Kretschmer M, Sabatino M, Blechschmidt A, Heyden S, Grunberg B, Wurschmidt F. The
impact of flattening-filter-free beam technology on 3D conformal RT. Radiat Oncol.
2013;8(133). http://doi.org/10.1186/1748-717X-8-133
7. Sharma SD. Unflattened photon beams from the standard flattening filter free
accelerators for radiotherapy: advantages, limitations and challenges. J Med Phys.
2011;36(3):123-125. http://doi.org/10.4103/0971-6203.83464
8

Figures

Figure 1. Transverse, 3D, coronal, and sagittal view show the location multiple PTV in relation
to the whole brain tissue of Patient B.
9

Figure 2. Dose volume histogram (DVH) of the PTV volumes and Brain-PTV volume of the
FFF Beam plan of Patient B.

Figure 3. Dose volume histogram (DVH) of the PTV volumes and Brain-PTV volume of the FF
Beam plan of Patient B.
10

Tables

Table 1. Example of arc geometry for the flattening filter and flattening filter free plans shows
the path of the gantry, the collimator rotation, and couch rotation used for one patient test case.

Arc Number Gantry Angles Collimator Couch

Angles Rotation
Flattening Filter 1 181.0 CW 79.0 85° 0°
Beam (FF) 2 179.0 CCW 0.0 85° 45°
3 0.0 CW 181.0 30° 315°
4 181.0 CCW 0.0 30° 270°
Flattening Filter 1 181.0 CW 179.0 85° 0°
Free Beam (FFF) 2 179.0 CCW 0.0 85° 45°
3 0.0 CW 181.0 30° 315°
4 181.0 CCW 0.0 30° 270°
*Clockwise (CW); counterclockwise (CCW)

Table 2. Dose limits serve as planning constraints for the organs at risk (OAR) in plan
evaluation.

Patient Flattening Filter Number PTV Volume Brain-PTV Brain-PTV

Beam (FF) vs. of (cm3) Volume (cm3) Volume
Flattening Filter Lesions Receiving 12
Free Beam (FFF) Gy (cm3)
1 FF 9 2.5 1313.3 13.95
FFF 13.79
2 FF 5 4.5 1285.7 14.08
FFF 13.57
3 FF 6 3.4 1365.1 15.19
FFF 14.93
4 FF 5 0.8 1270.1 6.01
FFF 5.87
5 FF 7 4 1076.8 14.82
FFF 14.17
Mean FF 6.4 3.04 1262.2 12.81
Mean FFF 12.47