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Urethral Dose Sparing in SCC of Anal Canal using Proton Therapy with
Prior Brachytherapy of Prostate Cancer: A Case Study
Ontida Apinorasethkul, B.S., CMD, Ashley Pyfferoen, M.S., CMD,
Nishele Lenards, M.S., CMD, R.T.(R)(T), FAAMD
Medical Dosimetry Program at the University of Wisconsin La Crosse, WI
Abstract
Introduction
Given the history of prostate brachytherapy and very high dose delivered to the anterior
rectal wall directly adjacent to the tumor, there was a high risk of complications with reirradiation. The potential complications included recto-urethral fistula and urethral stricture of
the prostatic urethra, potentially resulting in urinary obstruction and need for dilation or urinary
diversion. Because urethral reconstruction has a high failure rate, it is essential to reduce the risk
of complication on this patients re-irradiation to the anal cancer.
Case Description
A 76-year old male was presented with a secondary radiation-induced malignancy given
the proximity to the prostate brachytherapy seeds and the 10 year time frame from prior radiation
therapy. The examination at the time revealed recurrent disease at the top of the anal canal,
extending into the rectum. A rectal examination revealed a bulky tumor involving the left
superior-most aspect of the anal canal extending superiorly into the rectum. The inferior extent
was palpable approximately 3 cm from the anal verge, and the superior extent of the mass was
difficult to appreciate on examination, but the tumor appeared to measure greater than 5 cm in
the superior-inferior dimension. Chemoradiation was suggested as the patient was opposed to
APR and colostomy.
Conclusion
The use of rapid dose fall off of proton therapy matching with electron fields in the reirradiation setting could help reduce the complications. Two lateral proton beams were designed
to treat the bulky tumor volume, while matching to 2 electron beams treating the nodal volumes.
This complication of treatment fields may help spare the prostatic urethra and reduce the risk of
urinary obstruction in the future.
Key Words: urethral sparing, proton therapy, urethral stricture, anal cancer reirradiation
Introduction

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Patients with prostate brachytherapy often experience urinary complications such as late
catheter use, urgency and urge incontinence, retention, and urethral stricture and fistula.1-3
Urethral stricture is a common complication from radiation therapy for prostate cancer. The risk
of ulceration and fistula could potentially increase, because the tumor involved the anterior rectal
wall directly adjacent to the prostate. This complication could cause a blocked or reduced flow of
urine. Urethral reconstruction such as stricture dilation and visual internal urethrotomy has a high
failure rate4, therefore, it is essential to attempt to reduce the possibility of complication. As the
patient already received 145 Gy minimum peripheral dose to the prostate from brachytherapy,
multiple clinical and treatment parameters were evaluated to minimize the development of
urethral stricture and fistula for the re-irradiation to the anal cancer. Given the history of the high
dose of prostate brachytherapy, the use of proton therapy with its physical characteristic of rapid
dose fall off can improve the sparing of urethral dose, which could reduce severe acute and late
toxicities.
Case Description
Patient Selection
The patient is a 76 year-old married male. He was a 30-year tobacco user of half a pack
per day and quit in 1986. He had 3-4 alcoholic drinks per day and denied any drug use. There
was no known family history of cancer. The patient had a past medical history of low risk
prostate cancer treated with prostate brachytherapy in July 2004. The patient was treated with I125 seeds to a minimum peripheral dose of 145 Gy. His most recent PSA tests have been
undetectable. The patient was doing well with regard to toxicity, with the exception of hematuria
in 2008, which prompted cystoscopy showing some urethral scarring but with normalized
urinary function.
In September 2013, the patient presented with hematochezia and a tumor that he was able
to feel within the anal canal. The medical oncologist performed transanal excision of a T2N0
squamous cell carcinoma (SCC) of the upper anal canal with close margins. The patient was not
a candidate for radiotherapy at that time because of the history of prostate brachytherapy. The
post-op staging work-up revealed no evidence of systemic disease.
In December 2014, the patient developed persistent diarrhea. The examination at the time
revealed recurrent disease at the top of the anal canal, extending into the rectum. A rectal
examination revealed a bulky tumor involving the left superior-most aspect of the anal canal

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extending superiorly into the rectum. The inferior extent was palpable approximately 3 cm from
the anal verge, and the superior extent of the mass was difficult to appreciate on examination, but
the tumor appeared to measure greater than 5 cm in the superior-inferior dimension. The mass
was fixed and the anal sphincter tone was intact. The patient indicated he did not want to
undergo abdominoperineal resection (APR) because he was concerned about quality of life with
a colostomy. Therefore, he was referred for a radiotherapy treatment consultation.
The CT study of the abdomen and pelvis in December 2014 showed a new mass in the
distal sigmoid colon, which did not appear to be associated with obstruction or associated
adenopathy. There was no evidence of metastatic disease. There appeared to be an invasion of
the tumor through the left posterolateral rectal wall, into the perirectal fat, extending towards the
pelvic sidewall and the sacrum, with several adjacent peri-rectal lymph nodes. The largest bulk
of disease was seen at the level of the seminal vesicles, although there did appear to be tumor
adjacent to the prostate gland, which contained multiple brachytherapy seeds; many of which
were visualized directly adjacent to the left anterior rectal wall.
This diagnosis might represent a secondary radiation-induced malignancy given the
proximity to the prostate brachytherapy seeds and the 10 year time frame from prior radiation
therapy. However, it was unclear whether this would render the tumor any less sensitive to
chemoradiotherapy. Since the patient was opposed to APR and colostomy, chemoradiation
therapy was suggested as durable palliation and potentially curable given that this was SCC,
stage T3N0M0.
Target Delineation
The patient was scanned head first in supine position. After the CT simulation scan was
completed, the radiation oncologist set the isocenter to the center of the treatment volume. The
CT data set was then transferred into Eclipse treatment planning system (TPS). The medical
dosimetrist contoured organs at risk (OR) and related structures for planning purposes which
included: air, brachytherapy seeds, skin markers, CT artifacts of the skin markers and seeds,
bladder, large bowel, small bowel, and femoral heads.
Since a proton beams stopping power is based on CT number conversion on the CT
scan5, it is essential that all the artifacts and air in the bowels were contoured and corrected
(Figures 1-2). The uncorrected Hounsfield Unit (HU) number could result in undershoot or
overshoot of the proton beam. Artifact from the brachytherapy seeds was overridden to the

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neighboring HU number. The skin markers were overridden as air to -1000 HU because they
would not be there at time of treatment. As shown in Figure 2, air was overridden to 0 HU since
it might not be at the same position daily and it could contribute to the range variation in proton
beam delivery.6 The radiation oncologist contoured gross tumor volume (GTV), clinical target
volumes (CTVs), planning target volumes (PTVs), genitalia, perineal skin, prostate and prostatic
urethra. The PTV4500 and PTV5040 structures had a margin of 5mm from CTV4500 and
CTV5040, respectively. The PTV5940 structure had a margin of 3mm from CTV5940. After
treatment volumes were drawn, the medical dosimetrist created Pencil Beam Scanning treatment
volumes (PBSTVs) as proton planning volumes to account for any range uncertainty in the
direction of the beams distal edge. This is to account for CT calibration curve error or mass
density curve error, which may cause some dose deviations to the treatment volumes and/or OR.5
The PBSTV margin was 3.5% multiply by the nominal range of the beam plus 3mm in the beam
direction. The PBSTV4500 and PBSTV5040 structures had a margin of 1.2cm left and right
from CTV and match PTV in all other directions. The PBSTV5940 structure had a margin of
1.1cm left and right from CTV and match its PTV in all other directions. The PBSTVs were then
used as optimizing targets in the treatment plan, however, the PTVs and CTVs were used to
evaluate in the dose volume historgram (DVH).
Treatment Planning
The radiation oncologists recommendation to the patient was the use of proton therapy to
reduce toxicity in the re-irradiated high dose previously treated region. The prescription dose for
the initial plan was 45 Gy to treating the tumor directly adjacent to the prostate (PTV4500) and
50.4 Gy to the inguinal, internal iliac and perirectal nodes (PTV5040) concurrently in 28
fractions. The boost prescription to the bulky portion of the tumor (PTV5940) that was located
more superior was 9 Gy in 5 fractions; therefore the total prescription was 59.4 Gy.
The medical dosimetrist placed an isocenter in the middle of the target at midline. There
is no aperture or fields to be set in Pencil Beam Scanning (PBS) planning. Since the patient had
previous treatment to the prostate, lateral proton beams were decided for this plan so the smallest
beam penumbra could be used to spare prostate and prostatic urethra as much as possible. Beam
energies in a PBS plan are delivered by spots and layers. The spots deposits beyond 7.5 cm water
equivalent distance (WED) from the skin surface. The issue with using lateral beams for this case
was that the node volumes did not get coverage near the surface because WED was less than 7.5

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cm (Figure 3). Therefore, electron beams were used to cover the left and right node volumes
matching with lateral proton beams. The 2 lateral proton beams were arranged at 90 and 270.
The 2 electron beams of 16 MeV were arranged at the gantry of 10 with a couch rotation of 25
and another at 350 with a couch rotation of 335 to match with the 2 lateral proton beams
(Figure 4). The couch rotations were designed to reduce the dose overlap from the bulging of
electron beam isodose curves with 5 mm gap. A prior study by Sun et al7 showed that a shift of
an electron field away from a matched photon field by 2 mm did not create any cold spot at the
junction. Therefore, 5 mm was decided as a field gap used. This technique was not to perform a
perfect match, but to deliver a safe treatment plan to the patient. The boost plan also consisted of
the 2 lateral proton beams to only the bulky tumor volume.
Plan Analysis & Evaluation
The usual proton beam arrangement in treating anal cancer is to use 2 posterior oblique
fields. With that technique, distal edge of the beams would be pointing directly into the prostate
and prostatic urethra if air in the beam path changes. To reduce range uncertainty to these 2 dose
limiting structures, the medical dosimetrist recommended using mixed modalities of matching
electrons with lateral PBS fields. Both electron plans used 16 MeV, prescribed to 90% isodose
line. The objective was to limit toxicity to the previously high dose irradiated area of prostate and
prostatic urethra. With the proton and electron matching technique, there was a cold match
around the nodal area of 45 Gy in which the nodal area received at least 30 Gy (Figure 5). The
cold match was created to account for set up uncertainties between the proton and photon
treatment set ups. The patient had to switch treatment rooms daily from proton to photon,
therefore, having the proton match line marked first daily was safer for the patient to not risk
overlapping fields. On every treatment session, a radiation therapist delivering proton treatment
would draw a line at the proton isocenter on patients skin (since the match was at the proton
isocenter) and another therapist delivering photon treatments would ensure that there was at least
0.5 cm gap from the line to the edge of the electron blocks as seen in Figure 6. In addition to
matching the fields on the patients skin, kV films were imaged daily to align the electron fields
to bony anatomy to accompany the same treatment set up method as the proton beams. All
treatment volumes received adequate and homogenous dose distribution, except for the nodal
matching region. Many of the OR were not meeting the constraints (Table 1, Figure 7) because
they were part of the treatment volumes. The small bowel received a maximum dose of 58 Gy,

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while the desired dose objective was 54 Gy. A volume of 226 cc of small bowel received 15 Gy
or more, though the objective was set for 120 cc. The prostate received a maximum dose of 52.7
Gy, while the desired objective was 45 Gy. All the bladder constraints were also not met due to
the overlapping of the structures to the treatment volumes. The PTVs were adequately covered
besides PTV4500 in the nodal area (Figure 8). The radiation oncologist was willing to
compromise the nodal coverage with using proton/electron match because there was a clear
advantage of using lateral PBS fields with a small penumbra to the prostatic urethra and prostate
(Figure 9).
Conclusion
Challenges are usually presented when the plan involves matching fields. During
treatment planning, it was given considerable thought of where the cold match would be located
and where it would be acceptable within the treatment volume. Discussions with the radiation
oncologist were crucial to understand the expectations of both radiation oncologist and medical
dosimetrist.
The proton range uncertainties were reviewed with the physicist to ensure that the bowel
movements and the bladder filling would not shift the spread of Bragg peak (SOBP) out of the
acceptable range nor would it affect the treatment volume coverage. Because the patient needed
to be set up at the proton treatment room, then switched to the photon treatment room, more
challenges could be encountered. During the first 5 treatment delivery sessions, the medical
dosimetrist was present at both the proton treatment and the photon treatment to ensure that the
daily match was reproducible. Although the electron fields were not exactly at the same position
as marked, the dose would be smeared out clinically since the proton isocenter line was drawn as
a benchmark to match with electron fields daily. (should have been mentioned earlier in the
paper)
Another possible planning technique was considered as well. Instead of using photon and
proton match, an anterior proton beam was to replace the electron beams. However, the anterior
beam would need a proton bolus to shift the proton range in order to have the WED equal to at
least 7.5 cm from the skin surface. With the sharp dose fall off of the proton beam, the match
would have to be very precise, since the treatment volume could get double dose in case of the
beam overlap or the volume could get no dose at all from the gap. It seemed to be too risky to
match multiple rapid dose fall off beams on this volume, therefore, mix modalities was the best

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option for this patient for the urethra dose sparing. (This should have been included in the
treatment planning section. You want the reader to know you considered other options but why
you chose the method you did for planning.
This conclusion should be highlights from the paper as well as suggestions for future study and
anything additional you want to contribute.)

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References
1. Crook J, Fleshner N, Roberts C, et al. Long-term urinary sequelae following 125Iodine
prostate brachytherapy. J Urol. 2008;179(1):141-146.
http://dx.doi.org/10.1016/j.juro.2007.08.136
2. Merrick GS, Butler, WM, Wallner, KE, et al. Risk factors for the development of prostate
brachytherapy related urethral strictures. J Urol. 2006;175(4):1376-1381.
http://dx.doi.org/10.1016/S0022-5347(05)00681-6
3. Merrick GS, Butler WM, Tollenaar BG, et al. The Dosimetry of prostate brachytherapyinduced urethral strictures. Int J Radiat Oncol Biol Phys. 2002;52(2):461-468.
http://dx.doi.org/10.1016/S0360-3016(01)01811-9
4. Baumgartner T, Ebertowski J, Canby-Hagino E, et al. Incidence, timing, and management of
urethral stricture following primary radiation therapy for prostate cancer. J Urol.
2015;193(4):e478-e479. http://dx.doi.org/10.1016/j.juro.2015.02.1449
5. Jiang H, Seco J, Paganetti H. Effects of hounsfield number conversion on CT based proton
monte carlo dose calculations. Med Phys. 2007;34(4):1439-1449.
http://dx.doi.org/10.1118/1.2715481
6. Engelsman M, Schwarz M, Dong L. Physics controversies in proton therapy. Semin Radiat
Oncol. 2013;23(2):88-96. http://dx.doi.org/10.1016/j.semradonc.2012.11.003
7. Sun C, Cheng C, Shimm DS, et al. Dose profiles in the region of abutting photon and
electron fields in the irradiation of head and neck tumors. Med Dosim. 1998;23(1):5-10.
http://dx.doi.org/10.1016/S0958-3947(97)00120-9

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Figures

(a)

(b)

Figure 1. Axial CT slices demonstrating (a) the patients brachytherapy seeds in pink from
previous treatment and (b) the contour of seed artifacts in blue.

Figure 2. Axial CT slices demonstrating (a) air in bowel and (b) overridden HU of air contour to
0 HU in proton treatment plan. (show the (a) picture)

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Figure 3. This measurement displayed the water equivalent distance (WED) of the proximal
nodal volume to the skin surface was less than 7.5cm WED.

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Figure 4. White body contour showed field entry view of the 2 electron fields.

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Figure 5. Three different anatomical planes displayed cold match of proton and electron plans in
the plan sum. (make arrows to the cold match) (sum all the texts to figures)

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Figure 6. A proton isocenter line (dotted black line) on the patients skin with 0.5cm gap abutting
the 2 electron fields (green and blue lines with x as the isocenter).

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Bladder

Prostate
Small Bowel
Urethra
Femoral heads
Genitalia

Figure 7. Shown is a plot of the DVH of all OR in the plan sum. (sum all the texts to figures)

PTV_5040
PTV_5940

PTV_4500

Figure 8. Shown is a plot of the DVH of all treatment volumes in the plan sum. (sum all the
texts to figures)

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Figure 9. Image shown demonstrated urethra sparing from the plan sum of lateral proton beams
and electron fields. The dose color wash is showing 1000 cGy. (make red arrow to urethra)

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Tables
Table 1. The chart demonstrated desired objectives and achieved objectives of the OR in the plan
sum.
Organs at Risk
Genitalia
Bowel_small
Prostate
Prostatic urethra
Bladder

Femoral Heads

Achieved
Desired Objective
36Gy max
V20 < 50%
V30 < 35%
54Gy max
V15 < 120cc
45Gy max
V30 < 25%
25Gy max
V35 < 50%
V40 < 35%
V50 < 5%
50Gy max
V30 < 50%
V40 < 35%
V44 < 5%

Objective
26.7Gy max
V20 = 0.7%
58Gy max
V15 = 226cc
52.7Gy max
V30 = 27%
25.5Gy max
V35 = 50%
V40 = 41%
V50 = 29%
47Gy max
V30 = 3%
V40 = 0.2%
V44 = 0.04%