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A Case Study of DIBH to Spare Abdominal Organs at Risk for Renal Cell Carcinoma MR-
Guided Radiotherapy
Authors: Steven D. Yorio R.T.(R)(VI), Nishele Lenards, Ph.D., CMD, R.T.(R)(T), FAAMD,
Ashley Hunzeker, M.S., CMD, Ashley Fellows, M.S., CMD, R.T.(T)
Medical Dosimetry Program at the University of Wisconsin - La Crosse

Abstract
Introduction: Historically, respiratory induced motion has made renal radiotherapy difficult due
to the potential risk of additional toxicities to the patient due to tumor movement. The use of
deep inspiration breath holds (DIBH) in congruence with magnetic resonance guided
radiotherapy (MRgRT) may be an effective method to manage tumor and organ at risk (OAR)
motion and deliver radiation safer and more effectively. The purpose of this case study was to
evaluate the effectiveness of DIBH in sparing radiation dose to colon and small bowel during
MRgRT of right sided renal cell carcinoma (RCC). The goals were to reduce radiation dose to
colon and small bowel during RCC treatment with these motion management techniques.
Case Description: A retrospective case study of a patient with oligoprogression in the post-
operative renal fossa was found to be a candidate for DIBH using MRgRT. Treatment planning
called for motion management and real-time imaging in order to safely treat the tumor volume.
Results were evaluated by the achievement of specific dosimetric criteria and tolerances and the
regression of disease in the renal fossa.
Conclusion: The use of real-time imaging and simultaneous motion management proved to be
effective tools for the treatment of RCC. This radiation therapy treatment resulted in the
elimination of malignancy at the primary site of disease.

Key Words: Renal cell carcinoma, MR-Linac, OAR, DIBH, MRgRT, IGRT

Introduction
Creating a radiation treatment plan that is both accurate and effective requires newer
modalities that can manipulate the radiation beam and provide a conformal dose distribution to
the tumor. For traditional 3D conformal planning techniques, individual stationary beams are
designed to treat the tumor from various angles while sparing healthy tissue. Technologies have
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advanced in the field of Radiation Oncology to further improve radiation dose conformality.
Advanced technology, such as intensity modulated radiation therapy (IMRT) and volumetric
modulated arc therapy (VMAT), incorporate smaller beams, known as “beamlets,” within the
primary photon beam to alter the overall intensity of different regions of the beam and better
shape the radiation dose. These advanced methods of treatment planning use a retrospective CT
simulation scan and do not always give an accurate depiction of daily dose distribution to organs
that move during respiration or peristalsis. The juxtaposition of some tumors to organs at risk
(OAR) created the need for more advanced image guided radiation therapy (IGRT) methods in
order to successfully treat them without the risk of additional toxicities.
Magnetic resonance-guided radiotherapy (MRgRT) has provided the ability to profile
patient anatomy and better visualize how OAR move within the body in real-time.1 This new
modality has allowed the radiation oncologist to interpret the extent of this motion during a
course of radiation treatment and use additional techniques to avoid normal tissue. Certain tumor
sites that were previously untreatable due to OAR proximity became treatable with MRgRT
when used in tandem with the motion management technique of deep inspiration breath hold
(DIBH).
Historically, DIBH was used to create a greater separation between the chest wall and
heart when treating a left sided breast cancer with radiation therapy to lessen the probability of
cardiac injury. This form of motion management has been proven to decrease the chance
radiation induced cardiac problems and coronary events. Bergom et al2 discovered that the risk
of adverse cardiac effects can be escalated by 4-7 % for every 1 Gray (Gy) increase in the
average overall heart dose received during breast treatment.2 Typically, DIBH is not used for
treatment of lesions other than those located within the left breast, but it has recently been used
for lesions adjacent to the diaphragm, such as the kidneys; thus, creating a wider distance
between the tumor and abdominal OAR.
Corradini et al1 noted that the extent of respiration induced motion of the kidneys can be
greater than originally expected due to the real-time IGRT visualization abilities of MRgRT.
This presents a challenge for renal radiotherapy as the tumor is displaced outside of the planning
target volume (PTV) during diaphragmic contraction and relaxation. Of all types of urological
malignancies, renal cell carcinoma (RCC) is among the deadliest. The gold standard of treatment
for RCC is nephrectomy, but there is a tendency for recurrence in the surgical site for 20 - 40%
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of cases.3 Renal cell carcinoma has always been a radioresistant tumor when using conventional
fractionation schemes. In recent years, the use of stereotactic body radiation therapy (SBRT) has
shown that radiation delivered in 3 or 5 fractions with higher doses per fraction can eliminate the
radioresistance of RCC.4
Respiration-induced motion of the kidneys has been a major challenge of renal
radiotherapy due to tumor displacement outside the planning target volume (PTV) with
diaphragmic contraction and relaxation. In this case study, an alternative treatment was required
to evaluate the use of DIBH in congruence with MRgRT for limiting dose to healthy OAR and
successfully treat RCC in the post-operative tumor bed. This adaptive treatment was required due
to the concern of conventional methods increasing radiation toxicity to the surrounding structures
without the use of motion management and real-time imaging. The purpose of this case study
was to examine the effectiveness of DIBH in sparing radiation dose to colon and small bowel
during MRLinac treatment of right sided RCC. The goals of treatment planning were to reduce
radiation dose to colon and small bowel during RCC treatment with MRgRT and DIBH.
Case Description
Patient Selection & Setup
This study regards a 73-year-old male with metastatic RCC. The disease was controlled
by dual immunotherapy, but the patient developed tumor progression in the operative bed in the
right renal fossa. The patient did not have any internal implants that would interfere with a MR-
linac treatment; therefore, both MRgRT and DIBH were chosen as a potential treatment
technique.
The CT simulation was performed using a Siemens Somatom simulator. The patient was
placed headfirst supine with his arms raised above his head. A customized arm board was used
for immobilization and a bolster was placed beneath his knees for comfort (Figure 1). The
simulation scan was performed using 4DCT to generate a gated treatment plan by dividing the
respiratory cycle into 10 phases to analyze the extent of tumor motion.
The original respiratory-gated treatment plan utilized the mid position of the 4DCT scan,
which places the location of the tumor at the 40%, 50%, and 60% of the respiratory cycle. Along
with the 4DCT, 2 additional CT simulation scans were performed, 1 at the point of deepest
inspiration and 1 at the point of deepest expiration to evaluate change in tumor position (Figure
2). For this patient, the tumor was farthest away from OAR at the point of deepest inspiration,
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making this scan most useful for initial treatment planning. After practicing breath holds during
simulation, it was discovered that the patient was capable of DIBH for up to 25 seconds.
Target Delineation
After the acquisition of the deep inspiration CT scan, the physician and the medical
dosimetrist contoured structures around pertinent anatomy using MIM Maestro® contouring
software. The physician created contours for the gross tumor volume (GTV) and a 1.0 cm
expansion of this structure to generate the PTV structure. The medical dosimetrist contoured all
OAR which included the liver, gallbladder, right and left lungs, heart, left kidney, stomach,
spinal cord, aorta, duodenum, esophagus, ribs, small bowel, and colon.
Treatment Planning
A preliminary treatment plan was designed on the DIBH CT scan to better understand the
dose distribution throughout the patient’s anatomy. The treatment plan was created using
Monaco software version 5.51.10 which is synonymous to the planning software used for daily
adaptive planning MR scans for each fractional treatment with the 1.5 Tesla Elekta Unity MR-
Linac. The physician decided to use stereotactic body radiation therapy (SBRT) with a
prescribed dose to the PTV of 5000 cGy in 5 fractions, and dose constraints for OAR were
predominantly focused on limiting dose to the colon.
The minimum point dose (Dmin) was defined by subtracting 0.03 cubic centimeter (cc)
from the dose covering the entirety of the PTV, and the maximum point dose (Dmax) is quantified
by the maximum dose delivered to 0.03 cc of the PTV.5 The dosimetric criteria for the OAR at
highest concern for toxicities in this case can be found in Table 1. A photon energy of 6MV was
used for this treatment. The Elekta Unity with step-and-shoot IMRT was used with a dynamic
multileaf collimator (DMLC) technique.3 The final treatment plan consisted of 8 beams and 40
segments.
Patient Treatment
Prior to delivery of each fractional dose, a series of scans were acquired to optimize
visibility of patient anatomy as it presents on the day of treatment. Repeat scans for cine images
at the point of DIBH were performed to reduce parallel imaging reconstruction artifacts.
Magnetic resonance scans were performed using the mDixion series, which generates images
due to the differing rates of proton precession between water molecules and fat molecules when
subjected to nuclear resonance.6 As the proton precession alternates between in-phase (IP) and
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opposed-phase (OP) during this acquisition, patient anatomy becomes viewable in 4 different
sequences (Figure 3).6 When protons are IP the matter that is highlighted on the scan is water and
fat, OP enhances water without fat. To better visualize fat only, the sequence must be acquired IP
minus OP, and water only by precessions IP plus OP. The water only scan was used as a
reference.
The Elekta Unity acquires a new MRI scan at the beginning of each fractional dose. This
scan is compared to the CT simulation scan, the original contours and plan, and used in adaptive
planning technique for each treatment fraction. Plan adaptation on this system can be performed
by using adapt to position (ATP) or adapt to shape (ATS) methods. When using ATP, there is no
need to draw new structure contours daily, rather only the isocenter is shifted from the original
position on the CT simulation scan. For the ATS method, structures must be contoured during
each fraction based on how they present from the daily MRI scan.3 The adaptation strategy
utilized for this case was ATS. To expedite the process, the radiation therapist was responsible
for all non-deforming OAR contours, the physician contoured the targets, and the physicist
contoured the air, bone, and external patient outline. Structures for motion monitoring consisted
of the PTV and the colon planned organ at risk volume (PRV) and were drawn to allow for better
interpretation of when the target was settled within the PTV volume during DIBH (Figure 4).
The real-time imaging of MRgRT ensured the treatment team that the patient was able to
allow for full inspiration prior to holding their breath and provided accurate tumor localization.
To deliver treatment with DIBH, manual sequencing groups had to be used to allow the patient
to rest between breath holds. The planning system calculated that there would be seven breath
holds per beam.
Motion monitoring was performed using a single sagittal plane cine with the colon OAR
structure and PTV being visible (Figure 5). The process of delivering DIBH required the
radiation therapist to give breath hold instructions and initiate beam delivery only when the
target anatomy settled into position. The radiation therapist manually paused the beam at the end
of each breath hold or if the anatomy began to drift out of the PTV contour.
Plan Analysis and Evaluation
Each fraction of the adaptive MRgRT plan successfully met all OAR constraints. This
evaluation was performed using a dose volume histogram (DVH) analysis of the doses received
by the target and OAR (Figure 6). The adaptive planning OAR doses varied from the initial plan
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by up to 50 cGy for some structures; however, all organs were within the acceptable dose limits.
The dosimetric criteria for the colon of Dmax < 3000 cGy and D20cc < 1500 cGy were met as the
resulting absorbed doses came to 2015.5 cGy and 992.6 cGy respectively. Similarly, the
dosimetric criteria for small bowel met constraints at 2015 cGy and 1001 cGy, respectively. The
radiation oncologist considered the resulting doses to both structures to be acceptable and in
congruence with the successful RCC treatment.
Utilization of the single sagittal plane MR cine was deemed beneficial for tumor
placement within the PTV by means of DIBH for treatment. Throughout all 5 fractions the
patient experienced no acute side effects from the treatment. The only adverse event that was
noted during this MRgRT was the development of colitis caused of the patient’s adjuvant
immunotherapy. The condition was controlled with the use of steroids.
After receiving follow-up imaging within weeks of treatment completion, the positron
emission tomography (PET) and CT scans showed a complete treatment response in the renal
fossa with no signs of disease progression. Since the MRgRT treatment, the patient returned to
radiation oncology for an additional SBRT treatment to a metastatic lesion within the right iliac
crest. After successful treatment via conventional SBRT to the iliac lesion, the patient concluded
all courses of immunotherapy and remains without any clear evidence of disease progression.
Conclusion
Respiration induced motion of the kidneys increases the level of complexity during the
radiation therapy treatment of RCC. An examination of DIBH, when used in congruence with
MRgRT, was necessary to evaluate efficacy in providing a precise tumor placement for
treatment. The purpose of this study was to spare radiation dose to colon and small bowel during
MRLinac treatment of right sided RCC and both goals were achieved. The difficulty in this case
was to maintain daily contouring precision and timeliness for ATS plan adaptation.
Despite the atypical nature of this tumor positioning technique, the results of this case
study rendered it as a useful tool in decreasing dose to healthy OAR. The use of customized
patient positioning devices proved to also be a crucial benefit in this case. Future scientific study
of this motion management technique must be performed on a larger scale and with various
proprietors of MRLinac treatment machines. This case study involved only one tumor in the
post-operative renal fossa, and this method of irradiation must be compared against other mobile
tumor locations to validate it as a reproducible method of constraining dose to surrounding OAR.
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References
1. Corradini S, Alongi F, Andratschke N, et al. MR-guidance in clinical reality: current
treatment challenges and future perspectives. Radiother Oncol. 2019;14(1).
http://doi.org/10.1186/s13014-019-1308-y
2. Bergom C, Currey A, Desai N, et al. Deep inspiration breath hold: techniques and
advantages for cardiac sparing during breast cancer irradiation. Front Oncol. 2018.
http://doi.org/10.3389/fonc.2018.00087
3. Winkel D, Bol GH, Kroon PS, et al. Adaptive radiotherapy: The Elekta Unity MR-linac
concept. Clinic and Trans Radiat Oncol. 2019;18:54-59.
http://doi.org/10.1016/j.ctro.2019.04.001
4. Rühle A, Andratschke N, Siva S, et al. Is there a role for stereotactic radiotherapy in the
treatment of renal cell carcinoma? Radiother Oncol. 2019;18:104-112.
http://doi.org/10.1016/j.ctro.2019.04.012
5. Yu J, Geng H, Gong Y, et al. Investigation of target minimum and maximum dosimetric
criteria for the evaluation of standardized radiotherapy plan—target minimum and
maximum evaluation. Int J Med Phys Clin Eng Radiat Oncol. 2020;09(02):43-51.
http://doi.org/10.4236/ijmpcero.2020.92005
6. Ding S, Li Y, Liu H, et al. Comparison of intensity modulated radiotherapy treatment
plans between 1.5T MR-Linac and conventional linac. Technol Cancer Res Treat.
2021;20:1-10 http://doi.org/10.1177/1533033820985871
7. Leyendecker JR, Brown JJ, Merkle EM, et al. Practical guide to abdominal and pelvic
MRI. LWW. (2010) ISBN:1605471445.
8. Chin A, Lam J, Figlin R, et al. Surveillance strategies for renal cell carcinoma patients
following nephrectomy. Rev Urol. December 2016.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1471767/. Accessed May 19, 2021.
9. Naumann P, Batista V, Farnia B, et al. Feasibility of optical surface-guidance for position
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hold. Front Oncol. 2020;10. http://doi.org/10.3389/fonc.2020.573279
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Figures

Figure 1. Treatment table for Elekta Unity and patient set up with an adjustable arm board for
comfort.

Mid Position

Deep Expiration

Deep Inspiration

Figure 2. Transverse, sagittal, and coronal images of CT scans using 4DCT, deep expiration
breath hold (DEBH), and deep inspiration breath hold (DIBH) for tumor location comparison.
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Figure 3. Original scan MR scan (left) compared to an optimized MR scan (right) to reduce
parallel imaging reconstruction artifacts.

Figure 4. Sagittal view of the motion monitoring structures, PTV (dual ring structure) + Colon
planning organ at risk volume (PRV).
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Figure 5. Motion monitored single frame of real time MR scan during treatment. Note placement
of tumor inside target contour during DIBH.

Figure 6. Axial view and DVH of planned dose distribution to target and OAR.
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Tables

Table 1. Dose volume histogram statistics and dosimetric criteria for targets and all OAR.
Structure Dosimetric Criteria Actual Value
PTV V5000cGy > 97% (-2%) 95%
Liver-ITV D1226cc < 1500 cGy (+380 cGy) 74.8 cGy
Colon D0.03cc < 3000 cGy (+3300 cGy) 2015.5 cGy
D20cc < 1500 cGy (+4800 cGy) 992.6 cGy
Bowel D0.03cc < 3000 cGy (+3300 cGy) 2015.5 cGy
D20cc < 1500 cGy (+4800 cGy) 1001.0 cGy
Kidney_L D0.03cc < 4513 cGy (+237 cGy) 136.5 cGy
D35% < 1500 cGy (+150 cGy) 42.3 cGy
*Internal target volume (ITV); Planning target volume (PTV); Centigray (cGy); Cubic centimeter (cc); Volume
receiving 5000 cGy (V5000cGy); Dose at 1226cc (D1226cc); Dose at 0.03cc (D0.03cc); Dose at 20cc (D20cc); 35% of the
dose (D35%).