CME International Journal of

Radiation Oncology
biology physics

www.redjournal.org

Critical Review

Scrotal Irradiation in Primary Testicular Lymphoma:

Review of the Literature and In Silico Planning
Comparative Study
Charlotte L. Brouwer, MSc,* Esther M. Wiesendanger, MD,* Peter C. van der Hulst, MSc,*
Gustaaf W. van Imhoff, MD, PhD,y Johannes A. Langendijk, MD, PhD,*
and Max Beijert, MD*
Departments of *Radiation Oncology and yHematology, University of Groningen, University Medical Center Groningen,
Groningen, the Netherlands

Received Mar 16, 2012, and in revised form Jun 8, 2012. Accepted for publication Jun 13, 2012

We examined adjuvant irradiation of the scrotum in primary testicular lymphoma (PTL) by means of a literature review in MEDLINE,
a telephone survey among Dutch institutes, and an in silico planning comparative study on scrotal irradiation in PTL.
We did not find any uniform adjuvant irradiation technique assuring a safe planning target volume (PTV) coverage in published
reports, and the definition of the clinical target volume is unclear. Histopathologic studies of PTL show a high invasion rate of the
tunica albuginea, the epididymis, and the spermatic cord. In retrospective studies, a prescribed dose of at least 30 Gy involving
the scrotum is associated with best survival. The majority of Dutch institutes irradiate the whole scrotum without using a planning
computed tomography scan, with a single electron beam and a total dose of 30 Gy. The in silico planning comparative study showed
that all evaluated approaches met a D95% scrotal dose of at least 85% of the prescription dose, without exceeding the dose limits of
critical organs. Photon irradiation with 2 oblique beams using wedges resulted in the best PTV coverage, with a mean value of 95% of
the prescribed dose, with lowest maximum dose.
Adjuvant photon or electron irradiation of the whole scrotum including the contralateral testicle with a minimum dose of 30 Gy is
recommended in PTL. Computed tomography-based radiation therapy treatment planning with proper patient positioning and position
verification guarantees optimal dose coverage. Ó 2013 Elsevier Inc.

Introduction of bilateral occurrence. PTL can have recurrences in the

Primary testicular lymphoma (PTL) is the most frequent
testicular malignancy in men older than 50 years and represents
5%-9% of all testicular malignancies with the highest incidence
contralateral testis, the central nervous system (CNS), and
extranodal sites. Testis, CNS, and eye are so-called immuno-
privileged or sanctuary sites, where lymphoma cells may escape
from T-lymphocyte-mediated immunosurveillance and where,

NotedAn online CME test for this article can be taken at http://
astro.org/MOC.
Reprint requests to: Charlotte L. Brouwer, MSc, Department of Radi-
ation Oncology, University Medical Center Groningen, P.O. Box 30001,
9300 RB Groningen, The Netherlands. Tel: (þ31) 50-3614329; Fax: (þ31)
50-3611692; E-mail: c.l.brouwer@umcg.nl
C. L. Brouwer and E. M. Wiesendanger contributed equally to this
study.
Conflict of interest: none.
AcknowledgmentdThe authors thank all Dutch radiotherapy institutes for
their contribution to the survey, in particular the radiotherapy department
of the Medical Center Alkmaar for providing additional information and
photo material of their irradiation setup. They also thank Erik Korevaar for
his help with the electron Monte Carlo dose calculations and his
suggestions for the manuscript.

Int J Radiation Oncol Biol Phys, Vol. 85, No. 2, pp. 298e308, 2013
0360-3016/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ijrobp.2012.06.019
Volume 85  Number 2  2013
because of the blood-testis barrier, chemotherapy has less effi-
cacy (1, 2).
The clinical presentation is often a painless testicular swelling
that grows slowly over weeks or months. Current treatment consists
of a diagnostic and therapeutic unilateral orchidectomy with
systemic immune chemotherapy, intrathecal chemotherapeutic
CNS prophylaxis and irradiation of the contralateral testicle (3-7).
Overall survival (OS) of testicular lymphoma depends on
tumor stage and histology. A recent international phase 2 trial (8)
showed that combined treatment with rituximab added to cyclo-
phosphamide, doxorubicin, vincristine, and prednisone, intra-
thecal methotrexate, and testicular radiation therapy was
associated with increased 5-year progression-free survival and OS
rates reaching 74% and 85%, respectively.
Scrotal irradiation is expected to produce dose-dependent
hypogonadism (9-14). However, if irradiation is omitted from
the treatment protocol, high recurrence rates are observed in
sanctuary sites such as the contralateral testis (15-19). A relapse of
a testicular lymphoma is difficult to treat and often has a dismal
prognosis.
Many different radiation techniques for scrotal irradiation are
available and are currently used. However, details on the advan-
tages and disadvantages of these different approaches are scarcely
described in literature.
The current study was composed of 3 parts: (1) a literature
review on PTL focusing on (a) local extension of PTL and (b)
scrotal irradiation (rationale, radiation technique, volume, and
dose); (2) a survey to evaluate which radiation delivery techniques
are currently used in the Dutch radiation oncology departments in
testicular lymphoma; and (3) an in silico planning comparative
study to investigate which of the most frequently used irradiation
techniques is most optimal by comparing the dose distributions in
target volumes and organs at risk (OARs).
With the results of this study, we aimed at providing recom-
mendations for the most efficient and effective approach for
irradiation of the scrotum in PTL.
Methods and Materials
Literature review
A literature search was performed in MEDLINE to retrieve studies
concerning irradiation in PTL. The following keywords were
used: ([lymphoma AND testis] OR testicular lymphoma) AND
(radiation OR irradiation). Reference lists of articles were
screened to identify additional relevant articles. Articles up to
May 2012 were included, and both prospective and retrospective
studies were reviewed. To be selected for this review, studies had
to fulfill the following additional eligibility criteria: (1) original
studies including adult primary testicular lymphoma patients and
(2) a minimum number of 10 patients.
Articles in languages other than English, German, and French
were excluded. Articles were analyzed on local extension based
on histopathologic studies, irradiated volumes, applied irradiation
technique, and administered irradiation dose.
Survey of all Dutch radiation oncology institutes
Radiation oncologists and medical physicists of all 21 radiation
oncology institutes in the Netherlands were interviewed by
Scrotal irradiation in primary testicular lymphoma 299
telephone (December 2009) using a standardized questionnaire. If
these institutes were familiar and experienced with testicular
irradiation, 11 questions were asked:
1. Is a planning computed tomography (CT) scan included in the
radiation treatment planning procedure?
2. How is the clinical target volume (CTV) defined?
3. Which margins are used for CTV to planning target volume
(PTV)?
4. Which radiation modality is used (electron, megavoltage
photon, or orthovoltage radiation)?
5. Which beam arrangement is used?
6. Which energy is generally used?
7. What is the prescribed total dose?
8. Is build-up bolus used to reduce skin sparing?
9. Are shielding devices used?
10. Which fractionation schedule is generally used?
11. What kind of position verification protocol is used?
In silico planning comparative study
The most frequently applied scrotal irradiation techniques
mentioned in the literature and in our survey among the Dutch
institutes were analyzed further using a research version (8.1y) of
the Pinnacle planning system containing a module for electron
Monte Carlo dose calculation. For comparison of these irradiation
techniques, we used a CT scan of 3 patients treated at our
department.
If electrons were used, the PTV should be encompassed within
90% of the prescription dose (or any other appropriate minimum
dose, eg, 85%, 95%) (20, 21), whereas in conventional photon
irradiation the PTV should be covered by 95%-107% of the
prescription dose (22-24).
The following dose distribution parameters were evaluated:
1. Minimum dose to 95% of the PTV (D95%), expressed in
percentage of the prescription dose
2. Maximum patient dose in percentage of the prescription dose
3. Hot spot volume: volume outside the PTV with a dose >100%
of the prescription dose
4. Mean dose to urethra, anus, bulbus, and rectum
5. Maximum dose to the urethra
Results
Literature search
We were able to identify 452 publications on PTL. After all
eligibility criteria were checked, 47 articles were included, of
which the vast majority were small, single-center, and retrospec-
tive studies (8, 15-19, 25-65). Only 4 of the selected studies were
prospective (8, 26, 27, 45). The majority of the reports were
excluded because they did not meet the inclusion criteria; they
described patients with other diseases, failed to report original
results, or included very few patients.
Local extension of PTL
We were able to identify 14 studies, including 439 patients,
reporting on histopathologic analysis of the lymphoma (Table 1)
(15, 17, 25, 28, 30, 34, 37, 41, 45, 48, 52, 57, 58, 65). The
majority of these studies concerned diffuse large B-cell
300 Brouwer et al. International Journal of Radiation Oncology  Biology  Physics

Table 1 Review of local extension of primary testicular Scrotal irradiation

lymphoma The results of several studies indicate that adjuvant irradiation to
the scrotum is associated with better survival (19, 49, 53, 62). If
Local extension scrotal irradiation is omitted, contralateral testis recurrence is
Study n Stage (% invasion) relatively frequent and is associated with poor outcome (15-19).
Linassier et al (45) 16 I-IIE Tunica albuginea 69% For example, the multi-institutional retrospective study of
Rete testis 63% Zucca et al (19) showed that prophylactic scrotal radiation therapy
Epididymis 56% is a prognostic factor for OS, cause-specific survival, and
Spermatic cord 31% progression-free survival. The median OS survival in patients
Zouhair et al (65) 36 I-IV Spermatic cord 25% receiving radiation therapy was 5.9 years, vs 2.0 years in patients
Ahmad et al (25) 17 I, II, IV Tunica albuginea 0% not being irradiated.
Spermatic cord 29% Without scrotal irradiation, scrotal relapse up to 35% was
Scrotal skin 18% observed (15-19), compared with 0%-10% in patients after scrotal
Ferry et al (34) 64 I-IV Tunica albuginea 48% irradiation (8, 16, 19, 26, 27, 29, 35, 43, 47, 53, 60, 62, 63, 65).
Epididymis 63% The study of Zucca et al (19) showed a continuous risk of
Spermatic cord 39% recurrence in the contralateral testis (15% at 3 years, 42% at 15
Moller et al (48) 33 I, II, IV Tunica albuginea 42% years) in patients not receiving radiation therapy to the contra-
Epididymis and/or lateral testis. Progression-free survival in this group was 36%,
spermatic cord 67% compared with 70% in the group receiving prophylactic radiation
Vascular 30% therapy to the contralateral testis, and OS was 38% vs 66%,
Crellin et al (30) 34 I-IV Tunica albuginea 35% respectively.
Spermatic cord 53% In the prospective study of Aviles et al (26), the efficacy of
Scrotal skin 10% irradiation to eliminate microscopic foci of tumor cells was
Baldetorp et al (15) 24 I-IV Invasion into adnexa, confirmed, and no relapses in irradiated sites were seen. In general,
usually epididymis 71% in-field relapses after scrotal irradiation are rarely observed (8, 16,
Buskirk et al (28) 17 I, II, IV Tunica albuginea 29% 19, 26, 27, 29, 35, 43, 47, 53, 60, 62, 63, 65).
Epididymis 18% If chemotherapy was considered not feasible because of clin-
Spermatic cord 24% ical contraindications, almost all patients experienced systemic
Paladugu et al (52) 27 I, II, IV Epididymis 37% dissemination even if the retroperitoneal nodes were irradiated
Spermatic cord 19% (19, 49, 53, 62).
Skin 0% Irradiated volumes (target volumes), radiation techniques, and
Sussman et al (17) 37 IE Tunica albuginea 38% delivered doses (dose prescription) mentioned in the various
Spermatic cord 30% studies are listed in Table 2.
Talerman (58) 32 IE Epididymis 78%
Spermatic cord 69% Local irradiation volume
Sampat et al (57) 14 I, II 10 specimen analyzed: In most studies, the target volume for local irradiation was defined
Tunica vaginalis 30% as the scrotum.
Epididymis 100%
Spermatic cord 30% Scrotal irradiation dose
Kiely et al (41) 31 I, II 17 specimen analyzed: The prescription doses mentioned in the various studies ranged
Epididymis 82% from 18-56 Gy. Among patients in the study of Zucca et al (19)
Spermatic cord 43% receiving radiation therapy locoregional to the primary testicular
Border of tumor with site of involvement, the OS was longer for those receiving an
diffuse infiltration irradiation dose of at least 30 Gy (PZ.02).
Gowing et al (37) 57 NR Frequent extension into:
Epididymis and Scrotal irradiation techniques
spermatic cord Scrotal radiation techniques were described in only a limited
Scrotal skin 2% number of articles. Generally, in older studies, suboptimal irra-
Abbreviations: E Z extranodal; I-IV Z tumor stage of lymphoma; diation techniques were applied, resulting in marginal or inade-
n Z number of patients; NR Z not reported. quate PTV coverage (orthovolt 250 kV and cobalt-60 and also low
energy electron irradiation [4-8 MeV]) (15, 26, 28, 29, 32, 33, 42,
51, 59). Later on, modern radiation delivery techniques, such as
high-energy electrons (25 MeV) and/or megavolt irradiation (4-8
lymphoma and reported on local extension. Microscopic inva- MV) were used, but these techniques were applied by only
sion of the epididymis was observed in 61%  21% of patients a limited number of institutes (15, 28, 56, 59, 65). In a more recent
(183 specimens analyzed), invasion of the tunica albuginea in study (42), 10 to 25 MV photons were applied.
40%  15% of patients (218 specimens analyzed), invasion of
the spermatic cord in 37%  14% of patients (307 specimens
analyzed), and invasion of scrotal skin in 6%  6% of patients Survey in Dutch radiation oncology institutes
(135 specimen analyzed). In 1 pathologic study the surgical
margins were analyzed and partly infiltrated by malignant Currently, in 16 of the 21 radiation oncology institutes in the
lymphoma cells (58). Netherlands, testicular lymphomas are treated with prophylactic
Volume 85  Number 2  2013 Scrotal irradiation in primary testicular lymphoma 301

Table 2 Review irradiation in testicular lymphoma

RT technique
(modality, energy,
Study n Study design Stage % RT shielding) RT volume RT dose (Gy)
Vitolo et al (8) 53 Prospective I-II 89 NR Testis 25-30
Stage II: IF-RT 30-45
Mazloom et al (47) 75 Retrospective I-IV 96 NR Scrotum (45 pat, 63%) 30.6 (24-56)
Plus nodal (18 pat, 25%):
paraortic, iliac, inguinal
Aviles et al (27) 38 Prospective IE 86 NR Scrotum in I 30
Phase 2 study IIE Scrotum and nodal in II 30
Aviles et al (26) 34 Prospective IE 100 Electrons 6 MeV Scrotum in I 25
Phase 2 study IIE Shielding Scrotum and nodal in II: 30/15 fx
paraortic, iliac, pelvic
Hasselblom et al (39) 35 Retrospective I, II, IV 49 NR 12 scrotal 24-40/12-20 fx
5 nodal: paraortic, iliac
Zucca et al (19) 373 Retrospective I-IV 53 NR Scrotal only (36%) vs 18-50
extended field
with/without
contralateral testis
Zouhair et al (65) 36 Retrospective I-IV 61 Photons and/or 13 scrotum only 31 (20-44)/
electrons 9 testis, iliac, paraortic 17fx (10-24)
Lagrange et al (42) 84 Retrospective I-IV 43 Cobalt or photons Paraortic, iliac, inguinal 40/16-22 fx
10-25 MV 4 scrotum, 6 testis
Visco et al (62) 43 Retrospective I-IV 67 NR 20 testis, 9 additional 30-40
inguinal/pararotic and
abdominal fields
Seymour et al (16) 25 Retrospective I, II, IV 44 NR 6 contralateral testis (24%) 30 (25-40)
8 inguinal, iliac, 36 (25-40)
and paraortic (32%)
Tondini et al (18) 29 Retrospective I, II 41 NR Retroperitioneal nodes 36 (32-44)
Contralateral testis If bulky testis, preoperative
shielding ipsilateral scrotal RT
IV 0 NR NR NR
Niitsu and 19 Retrospective IE 100 NR Field including the 30-40
Umeda (49) contralateral testis
Ostronoff et al (51) 16 Retrospective I-IIE 75 Photons inverted Y Locoregional with/without 35-40/20 fx
Orthovoltage 250 kV whole scrotum 35-40/20 fx
3 RT of testicle tumor 36
Ferry et al (34) 64 Retrospective I-IV 36 NR Scrotum and/or regional 12-46
nodes in 4 IF-RT of foci
beyond the abdomen
or pelvis
Poulsen et al (55) 13 Retrospective I, II 100 NR Inverted y (paraortic 35/20 fx lymph
and pelvic) 25 scrotal dose
Scrotum
III, IV pall No testicular RT
Connors et al (29) 29 Retrospective IE 79 Orthovoltage 250 kV Entire scrotum 30/10 fx
(prospective Lead suspension
CT) Lead plate
IIE 93 Photons orthovoltage Pelvic, paraortic region, 35/20 fx
250 kV and scrotum 25/10 fx
Martenson et al (46) 30 Retrospective IE 81 Photons Pelvic and/or paraortic 28-41
nodal areas, 1 inguinal
No scrotal RT
IIE, IV 57 Photons Pelvic and paraortic 27-40
nodal areas
1 scrotal RT 30
(continued on next page)
302 Brouwer et al. International Journal of Radiation Oncology  Biology  Physics

Table 2 (continued )
RT technique
(modality, energy,
Study n Study design Stage % RT shielding) RT volume RT dose (Gy)
Tepperman et al (59) 16 Retrospective IE, IIE 88 Cobalt 60 or Paraortic, most combined 20-25/20fx
electrons 25 MeV with pelvis 1 inguinal,
1 upper abdomen,
1 scrotum
Read (56) 51 Retrospective I/IIE 88 Photons 4-8 MV Scrotum, iliac, inguinal 30/16-20fx
Parallel opposed Later inclusion of
paraortic region
II-IV 26 Photons 4-8 MV Palliation (12 pat) 20-25/8fx
Duncan et al (32) 24 Retrospective I-IV 79 Cobalt 50 or Pelvic and paraortic nodal 34/34fx
electrons 6-8 MeV areas, 1 scrotal RT
Eckert and 30 Retrospective NR 66 Orthovoltage 250 kV Paraortic, iliac, inguinal nodes 25/25fx
Smith (33) 3-4 fields or also including the scrotum
electrons 4 MeV 30/20fx
Parallel opposed
Lead blocks
Abbreviations: CT Z computed tomography; E Z extranodal; fx Z fractions; I-IV Z tumor stage of lymphoma; IF-RT Z involved field radiation
therapy; kV Z kilovolt; MeV Z megaelectronvolt; MV Z megavolt; n Z number of patients included; NR Z not reported; pat Z patients; RT Z
radiation therapy; %RT Z percentage of patients receiving radiation therapy.
Studies lacking details of radiation treatment are not listed.

irradiation of the contralateral testis. The remaining 5 institutes do
not treat this patient category. In 10 institutes, electrons are used,
whereas MV and kV (orthovoltage) photons are used in 4 and 2
departments, respectively. The applied energies vary with the
chosen treatment depth, with a maximum available energy of
15-17 MeV for electron irradiation and 200 kV for orthovoltage
irradiation. Electron and orthovoltage irradiation is always per-
formed using a single beam, whereas the beam arrangements for
MV photons vary from a single beam to 2 beams with wedges. In
all institutes performing photon (MV) irradiation, a planning CT
scan with delineation of at least the CTV is used. Only 1 of the 10
institutes using electrons uses irradiation based on planning CT
scans. In most cases (94%), the scrotum is considered to be the
CTV and is determined either by palpation (62%) or by delinea-
tion (32%). In the remaining 6% of cases, the CTV is considered
to be the testicles and the epididymis, determined by palpation. In
13 institutes, a CTV to PTV margin of 1 cm is used (81%), and in
3 centers (19%), a margin of 1.5 cm is used. The use of build-up
bolus is common practice in cases of photon irradiation. Two
centers, using electrons, also use build-up bolus. Centers applying
photons do not use body shielding, whereas 9 of 10 centers
applying electrons do use some form of body shielding. The
shielding consists of a lead shield surrounded by plastic to absorb
the backscattered electrons. The penis is moved outside of the
irradiated volume by fixation to the abdominal wall.
All institutes apply fractions of 2 Gy, 5 times per week, but
differences were noted with regard to the total administered dose.
In most centers, a total dose of 30 Gy is prescribed. However, 2
centers (1 using electron and 1 using orthovoltage) use a total dose
of 18 Gy, 2 centers (electron) prescribe 20 Gy, and in 1 center
(orthovoltage) the total dose is 26 Gy.
Wide variation exists regarding the choice of the dose
prescription point. In most centers, the dose is prescribed on the
International Commission on Radiation Units and Measure-
ments (ICRU) point (for electron beams this is the depth of
maximum dose) (21-24), but also prescription points at 1 cm
depth or 85%-95% isodose lines are used, and prescription on
the skin.
In all centers, position verification consists of visual inspection
of the light field on the patient, except for 1 center that uses an
online cone-beam CT verification protocol.
In silico planning comparative study
As a result of the survey, the following 4 irradiation techniques
were selected for comparison: (1) single electron beam (without
a planning CT scan), (2) single photon beam, (3) 2 oblique photon
beams using wedges, and (4) 2 opposing photon beams.
The beam arrangements of the evaluated techniques are shown
in Fig. 1. For all patients the chosen electron energy was 14 MeV,
and the photon plans were constructed using 6 MV.
The setup for single electron beam irradiation is depicted in
Fig. 2a. An individual insert was made to match the desired
field dimensions. The applied shielding consisted of a lead
shield surrounded by plastic to absorb the scattered electrons
from the lead. The leg position of the patient was fixed by
means of an ankle immobilization device constructed in house,
to keep the angle between the legs constant. The penis was
taped to the abdominal wall. Photo documentation in the
patient chart supported the reproducible setup. The prescription
dose was 15  2 Gy at the depth of maximum dose (Dmax) of
the chosen electron energy. To evaluate the resulting electron
dose distributions, CT scans were made along with a dummy
shielding material to avoid streaking artifacts. The dummy
shielding material was overridden with the correct density, and
a Monte Carlo dose calculation was performed. The dose was
prescribed to a sphere of 1 cm in diameter and calculated on
a 0.2  0.2  0.2 cm3 dose grid until an uncertainty of less
than 1% was reached.
Volume 85  Number 2  2013
Fig. 1. Beam arrangements for the different irradiation setups:
(a) single electron beam (transverse view), (b) single photon beam
(transverse view), (c) 2 oblique photon beams using wedges
(transverse view), and (d) 2 opposing photon beams (sagittal
view). The photon beam arrangements were provided with a build-
up bolus of 1 cm thickness.
Scrotal irradiation in primary testicular lymphoma 303
In the photon irradiation setups (irradiation techniques b, c,
and d), a build-up bolus with a thickness of 1 cm was used. The
prescription dose for photons was 15  2 Gy to a point according
to ICRU recommendations (22, 23). Dose calculation was done
using a collapsed cone algorithm.
The irradiation setup for a photon irradiation strategy is shown
in Fig. 2b. A patient-specific wax immobilization device was
constructed for reproducible positioning of the scrotum and penis.
Sandbags were used to keep the immobilization device in place.
Furthermore, a patient-specific build-up was constructed with
a close connection to the patient surface. The beam isocenter was
annotated at the patient, immobilization device, and build-up
surface.
The CTVs and OARs were delineated according to the replies
from the survey by 2 radiation oncologists of our department
(E.W., M.B.). The CTV was defined as the entire scrotum. The
initial part of the spermatic cord until the end of the cranial
border of the epididymis was included in the CTV. For the
electron plans, a CTV to PTV margin of 1 cm was used in the
lateral and cranial-caudal directions and no margin in the ventral-
dorsal direction (positional changes in ventral-dorsal direction do
not influence the dose-depth distribution in an orthogonal single
beam electron irradiation). For the photon plans a uniform
margin of 1 cm was used. The PTV to field edge margin varied
from 0.5-1.0 cm, depending on the irradiation technique.
The D95 for the scrotum was lowest for the electron plans with
a mean value of 85% of the prescribed dose (Table 3) but was
considered acceptable in our clinical routine. The maximum dose
was highest for the electron plans with a mean value of 130% of
the prescribed dose. Photon irradiation with 2 oblique beams using
wedges resulted in the best PTV coverage, with a mean value of
95% of the prescribed dose and with the lowest maximum dose
(mean value of 112% of the prescription dose) (Table 3).
The hot spot volumes varied among patients, but the irradiation
technique of 2 opposing photon beams consequently resulted in
the largest hot spot volumes (Table 3).
The doses to the OARs were highest for the single photon
beam plans, but for all cases, the prescribed dose remained below
the organ tolerance doses (66-71).
Cumulative dose-volume histograms for 1 of the patients are
shown in Fig. 3.
Discussion
Most of the articles reporting on scrotal irradiation are retro-
spective evaluations, including only a limited number of patients
from single institutes. Because of the low incidence of PTL, large
prospective studies are probably not feasible, and it is unlikely that
such studies will be carried out in the near future.
PTL is an aggressive disease, which needs optimal local and
systemic therapy to reach satisfactory cure rates. Besides unilat-
eral orchidectomy and chemoimmunotherapy including CNS
prophylaxis, irradiation of the entire scrotum has been shown to be
an important part of the treatment strategy (19, 49, 53, 62).
Irradiation volume and definition of CTV
Given the frequent invasion of PTL in the tunica albuginea,
the epididymis, and the spermatic cord, these structures
should be part of the CTV. It is recommended that the initial
304 Brouwer et al. International Journal of Radiation Oncology  Biology  Physics

Fig. 2. (a) Scrotal irradiation setup for electron treatment, showing field edge, shielding material, and positional devices. The shielding
device consists of a lead core covered by plastic to absorb the scattered electrons from the lead and, like the ankle immobilization, is made
in house. (b) Scrotal irradiation setup for photon treatment, showing the in-house made immobilization and build-up material. Photographs
(b) courtesy of the Medical Center Alkmaar.

part of the spermatic cord up to the cranial edge of the
epididymis be included in the CTV. The scrotal skin is rarely
invaded by malignant lymphoma cells and therefore does not
need to be included in the CTV. However, we do recommend
inclusion of the scrotal skin in the CTV in cases of initial
skin invasion. Considering the mobility of the testicle in the
scrotal bag and the histopathologic findings, adjuvant irradi-
ation of the whole scrotum including the contralateral testicle
is recommended.
Irradiation dose
In a recently published randomized controlled trial, a dose
reduction from 40-45 Gy to 30 Gy did not result in worse local
control in aggressive non-Hodgkin lymphoma patients (72). Zucca
et al (19) observed a dose-dependent prognostic impact of radia-
tion therapy, with longest OS for patients receiving an irradiation
dose of at least 30 Gy. We therefore recommend a scrotal dose of
30 Gy in the treatment of primary testicular lymphoma. Further
reduction of the scrotal irradiation dose might become possible in
the future, owing to the higher effectiveness of modern chemo-
therapeutic agents.
Gonadal function
A dose of 30 Gy is expected to result in a significant risk of
hypogonadism in treated men (9-14). Infertility, reflecting
insufficient exocrine function of the testicles, is expected in all
men after an irradiation dose of 30 Gy. Besides testicular irra-
diation, other factors may influence testicular endocrine func-
tion. Higher age (73) is associated with a higher incidence of
hypogonadism as is a higher tumor stage (74). In some
lymphoma patients, preexisting gonadal functions in the
remaining testicle are already decreased (74). Additionally,
patients with testicular lymphoma receive aggressive chemo-
therapy, such as alkylating chemotherapy, which increases the
risk of altered testicular endocrine function (74). On the basis of
the literature available, it remains unclear which total dose of
scrotal irradiation results in severe hypogonadism (9-14).
Subclinical hypogonadism has been observed after a total dose
of 14 Gy (9, 11) whereas other authors estimated a tolerance

Table 3 Results of the in silico planning comparative study, mean values  1 SD of the 3 evaluated patients

D95 (%) Hot spot volume* Max patient Max urethra OAR mean dose (Gy)
Irradiation technique PTV PTV (cm3) dose (%) dose (Gy) Urethra Anus Rectum Bulbus
Electrons: Single beam 85  2 19  5 130  10 31.1  1.0 13.5  4.6 <0.1 <0.1 0.2  0.4
Photons: Single beam 93  3 11  9 116  3 33.8  0.9 23.9  3.0 17.2  2.1 2.8  2.4 15.9  9.0
Photons: 2 oblique beams 95  3 11  10 112  7 32.0  1.5 22.6  1.0 1.2  0.2 0.4  0.2 7.0  4.6
Photons: 2 opposing beams 94  4 30  9 114  10 33.4  2.1 18.0  1.1 1.7  2.2 0.1  0.1 2.0  2.2
Abbreviations: D95% Z dose to 95% of the PTV (the scrotum); Max Z maximum; OAR Z organs at risk; PTV Z planning target volume.
Dose (%) is relative to the prescription dose.
* Hot spot volume: volume outside the PTV with a dose >100% of the prescription dose.
Volume 85  Number 2  2013 Scrotal irradiation in primary testicular lymphoma 305

Fig. 3. Dose-volume histogram results of the in silico planning comparative study for one of the patients. PTV Z planning target
volume.

dose of 30-40 Gy in adult patients (10, 14). It is hoped that testosterone in an earlier phase. Orchidectomy can be considered
awareness of the side effects of treatment will lead to early as alternative to radiation, although it will result in immediate
detection of (subclinical) hypogonadism and substitution of severe hypogonadism.
306 Brouwer et al.
OARs and tolerance dose
Treatment plan optimization and better sparing of the OARs might
be possible, eg, by rescanning the patients in a wider leg position.
When a single photon beam is used, an option might be to put some
attenuation material behind the scrotum to reduce the anal dose.
The scrotal skin dose of the photon plans with build-up is some-
what higher than that of the electron plans. For 6 MV photons, the
dose is w65% at 2 mm, w75% at 4 mm, and w85% at a depth of 6
mm. Given that the average depth of the ventral side of our CTV
was 3 mm, the aimed dose coverage of 90%-95% will not be met
without the use of build-up. For 10 mm build-up, as is used in our
case, the surface dose will be w99% (field size w10  10 cm).
The use of a lesser thickness of build-up could be considered to
decrease the skin dose. For 14 MeV electrons, the dose in the first
millimeter of skin is 80%-90%, so for the electron irradiation setup
the skin dose is somewhat lower (w27 Gy) than for the photon
irradiation setup with bolus (w30 Gy). The physiologic thickness
of the skin varies between 1 and 3.5 mm (epidermis and dermis)
(75). Reducing the skin dose might potentially result in a lower
dose in the tunica albuginea, which is located adjacent to the skin.
Inasmuch as an average invasion rate of 40% to the tunica albu-
ginea was found in our histopathologic review, we suggest
acceptance of the treatment dose on the skin. The expected acute
side effects with a total dose of 30 Gy are temporary erythema of
the scrotal skin, possibly accompanied by urethritis. The doses in
our planning comparative study are below the tolerance doses of
the OARs (maximum dose to the urethra 31.1/33.8 Gy, mean
dose to the anus <0.1/17.2 Gy, mean dose to the penile bulbus
<0.2/15.9 Gy, mean dose to the rectum <0.1/2.8 Gy: electrons/
photons respectively, from Table 3) (66-71).
Irradiation technique and therapy planning
Most articles report few technical details concerning (suboptimal)
irradiation techniques. Therefore, no complete overview of
applied radiation techniques in testicular lymphoma is presently
available.
Most institutes in the Netherlands use a technically pragmatic
way (the “classic approach”) for irradiation of the scrotum in
testicular lymphoma; electron irradiation of 30 Gy using
a conventional simulator without making use of a CT scan. Our
planning comparative study showed that this approach meets the
requirements when a D95% of 85% is considered an acceptable
PTV coverage. The PTV coverage of the electron treatment plans
of our 3 evaluated patients could have been increased by using
a CT scan because this most likely would have led to the choice of
a higher electron energy. Apparently there is a risk of under-
estimating the thickness of the scrotum. Higher electron energies
do generally result in larger hot spot areas caused by (step-shaped)
patient contour irregularities (76), which should be taken into
account.
Orthovoltage irradiation is not taken into account in our
planning comparative study. Although a less homogenous PTV
coverage is expected (steeper percentage depth dose than electrons
and photons), and without noticeable overdosage superficially,
a PTV coverage of 80%-90% of the prescribed dose cannot be
reached.
In general, more extensive recording and reporting of radiation
treatments including dose-volume parameters could allow a better
evaluation of clinical outcome. Furthermore, it could enable better
International Journal of Radiation Oncology  Biology  Physics
interinstitutional comparisons of treatments. From this point of
view, CT-based treatment planning from which dose-volume
parameters could be determined would show advantages over the
classic approach. Moreover, the use of a CT scan would minimize
the pitfalls of underdosage.
A challenge in scrotal irradiation is reproducible patient
positioning. The scrotum shows high variability in shape and size,
caused, for instance, by environmental temperature or emotions
such as nervousness. Reproducible patient positioning should be
aided by the construction of patient-specific molds and (online)
position verification.
The irradiation technique applying 2 oblique photon beams
with wedges resulted in the best dose coverage with low doses to
the normal tissues, but as has already been mentioned, attention
should be paid to patient immobilization and position verification,
because direct visual setup control is not possible. EPID or cone-
beam CT position verification should be used if photon irradiation
with oblique beams is applied.
With a classic approach using electron irradiation, on the other
hand, time is needed on a conventional simulator to determine the
required field size, and sometimes an individual electron insert
needs to be made. Positioning of the electron setup on the
treatment machine can be done accurately and fast by visual
inspection of the light field on skin marks, which allows accurate
verification if the scrotum is within the projection of the light
field.
Summary
Irradiation of the whole scrotum in testicular lymphoma with
a total dose of a minimum of 30 Gy is recommended as a standard
treatment in PTL. The Dutch survey showed that most institutes
use conventional electron beam treatment without CT-based
treatment planning. This results in acceptable dose coverage of the
PTV, but the risk of underdosage at the dorsal part of the PTV
should be taken into account, together with the risk of hotspots
located near irregular patient surfaces. CT based photon treatment
planning with 2 oblique beams showed the best PTV coverage
(95% of the prescription dose to 95% of the PTV) with minimum
dose to the surrounding tissues. Reproducible patient positioning
and appropriate verification techniques should be warranted.
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