Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 2, pp.

505–510, 2005
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doi:10.1016/j.ijrobp.2005.02.024

CLINICAL INVESTIGATION Skin

RADIATION THERAPY FOR BOWEN’S DISEASE OF THE SKIN

LAUREN A. LUKAS VANDERSPEK, M.D.,* GREGORY R. POND, M.SC.,†

WOODROW WELLS, M.D., F.R.C.P.C.,* AND RICHARD W. TSANG, M.D., F.R.C.P.C.*
Departments of *Radiation Oncology and †Clinical Study Co-ordination and Biostatistics, Princess Margaret Hospital,
University Health Network, University of Toronto, Toronto, Ontario, Canada

Purpose: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin
(Bowen’s disease). We focused on the local control rate and the toxicity according to the biologically effective dose
(BED).
Methods and Materials: A retrospective review was performed on 44 patients with Bowen’s disease treated at
Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients,
whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp,
9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%).
Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen:
some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses
because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment
area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect
in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control
was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4
toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months.
Results: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment
lesion size was 2.65 cm2 (range, 0.07–34.56 cm2). Complete remission was achieved in 42 patients, with follow-up
unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1–1.5
years after complete remission. One recurrence was Bowen’s disease (local); the others were squamous cell
carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site.
As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0 –11.8
years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease.
The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The
crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment
tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4
toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity
lesions.
Conclusions: Radiation therapy is an effective treatment option for Bowen’s disease of the skin. Local recurrences
seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens
(dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity. © 2005 Elsevier Inc.

Bowen’s disease, Radiotherapy.

INTRODUCTION treating BD, particularly regarding dosing and toxicity. Our

First described in 1912, Bowen’s disease (BD) is a form of
intraepidermal (in situ) squamous cell carcinoma (SCC) (1).
Based on retrospective case series, the risk of progression to
SCC is approximately 3%, though a risk of up to 20% has
also been suggested, with one third of these invasive lesions
potentially metastasizing (2– 4). There are sparse data in the
literature regarding the utility of radiation therapy (RT) for
impression has been that RT is a good treatment, with an
excellent local control rate, even after moderate doses.
The clinical picture of BD is one of a scaly, crusted,
sharply demarcated erythematous plaque ranging in size
from a few millimeters to several centimeters, presenting as
a solitary lesion in two thirds of cases (5, 6) (Fig. 1). More
than 75% are associated with actinic damage, and thus the
majority appear on the head, neck, and hands (5, 6). Other

Reprint requests to: Lauren A. Lukas VanderSpek, M.D., London
Regional Cancer Centre, The University of Western Ontario, 790
Commissioners Road East, London, Ontario N6A 4L6, Canada. Tel:
(519) 685-8650; Fax: (519) 685-8627; E-mail; lauren.vanderspek@
lrcc.on.ca
Presented in poster form at the Annual Meeting of the American
Society for Therapeutic Radiology and Oncology, October 3–7,
2004, Atlanta, Georgia.
Received Dec 22, 2004, and in revised form Feb 15, 2005.
Accepted for publication Feb 15, 2005.

505
506 I. J. Radiation Oncology ● Biology ● Physics
Fig. 1. (a) A 66-year-old man with Bowen’s disease of the leg, 4
cm ⫻ 6 cm, located over the tibia, before radiation therapy. (b)
Complete remission of the lesion after treatment with 25 Gy in 10
fractions (125-kV beam, source–skin distance 50 cm, half-value
layer 3.5 mm Al). Mild pigmentation and telangiectasia were seen
3 years after treatment.
areas, such as the anogenitalia, oral mucosa, nail beds, and
conjunctiva might be affected (5), with the risk of invasion
quoted in several studies to be 10% in the genital region (2,
7–9) and similarly in the neck according to another study (2,
10). It is predominantly a disease of the elderly, with a mean
age at diagnosis in the sixth decade and presenting rarely
before the third decade, with a slight male-to-female pre-
dominance, though lesions on the lower limbs are predom-
inant in women, whereas lesions of the scalp and ears are
predominant in men (5, 11). The histopathology shows an
epidermis replaced by grossly disordered keratinocytes with
nuclear atypia, bizarre mitotic figures, a relatively intact
basal layer, and often involvement of the pilosebaceous
apparatus (5, 7, 11).
Etiologic agents that have been associated with BD in-
clude chronic actinic damage, arsenic exposure, immuno-
suppression, viral agents (e.g., human papillomavirus [HPV],
especially HPV16), therapeutic and other ionizing radiation,
and various forms of skin injury or chronic dermatoses (e.g.,
Volume 63, Number 2, 2005
lupus vulgaris or chronic lupus erythematosus); association
with seborrheic keratoses, porokeratoses, and a Becker’s nevus
have also been reported (2). Although controversial for some
time, the association between internal malignancy and BD has
not been justified, as concluded by larger studies and a meta-
analysis in 1989 (2).
Treatment options for BD include observation, surgery,
cryotherapy, electrodesiccation and curettage, Moh’s micro-
graphic surgery, topical application of 5-fluorouracil or imi-
quimod, combination of isotretinoin and interferon ␣, pho-
todynamic therapy, and RT (2, 6, 12). Radiation therapy has
included contact radiation, grenz ray therapy, strontium 90,
proton radiotherapy, ␤-emitting radionuclides, orthovoltage
therapy, and electrons (2, 6).
Radiation therapy is advantageous in patients who refuse
surgery, for large or multiple lesions, for lesions in cosmet-
ically sensitive areas, and in patients who are predisposed to
formation of keloids, with a high cure rate cited in the
literature (2, 6, 13–19). The retrospective analyses of BD
treated with RT are summarized in Table 1. As was also the
experience in this retrospective study at Princess Margaret
Hospital, the treatment regimens varied greatly. Concerns
are raised in the literature regarding the side effects of RT,
particularly poor wound healing in the lower extremity (15,
20 –24).
The objectives of this study were two-fold: to investigate
whether RT is an effective treatment option for BD of the
skin, even with low to moderate doses; and to explore
whether there is an association between the biologic effec-
tive dose (BED) and tumor control and/or toxicity (within a
dose range of 12–52 Gy, with dose per fraction ranging
2–20 Gy).
METHODS AND MATERIALS
Patients
The charts of 44 patients with a diagnosis of BD referred to and
managed at Princess Margaret Hospital from April 1985 to
November 2000 were identified and reviewed retrospectively.
Each lesion, with the exception of one clinical diagnosis, was
confirmed by histology. Radiation therapy was the primary treat-
ment for 32 patients, whereas 12 patients received RT for residual
disease after local ablative therapy or incomplete excision. The
records of patients with an incidental diagnosis of BD that was not
treated but who had a concurrent, nonrelated cancer treated at
Princess Margaret Hospital were not included in the study. Patients
with vulvar intraepithelial neoplasia were not included in the
study. Patient characteristics are outlined in Table 2.
Table 1. Summary of doses applied since 1985 to treat Bowen’s
disease with radiation therapy
Study (reference) Total dose (Gy)
Blank and Schnyder [1995] (14) 40–48
Cox and Dyson [1995] (15) 10–42
Caccialanza et al. [1999] (19) 40–70
Dupree et al. [2001] (6) 44.2–52.5
Present study [2004] 10–52
 RT for Bowen’s disease of the skin ● L. A. LUKAS VANDERSPEK et al. 507

Treatment Table 3. Dose–fractionation schedule for high- and

Orthovoltage X-rays were used in the majority of cases, though moderate-dose regimens
there was no standard fractionation regimen. Some physicians
High dose Moderate dose
prescribed higher doses, as for invasive skin cancer, whereas
(n ⫽ 24) (n ⫽ 20)
others prescribed lower doses because of the noninvasive nature of
the disease, a sensitive anatomic location (e.g., extremity), or large Fractionation regimen Dose (Gy) n Dose (Gy) n
treatment area. A high-dose regimen, defined as total dose ⱖ15 Gy
(single fraction), ⱖ26 Gy (4 –5 fractions), ⱖ35 Gy (7–10 frac- Single treatment (1 fraction) ⱖ15 6 ⬍15 2
tions), or ⱖ45 Gy (ⱖ15 fractions) was given in 24 patients (55%), 1 wk (5 fractions) ⱖ26 8 ⬍26 7
with a mean field size of 10.6 cm2. Others were moderate-dose 2 wk (7–10 fractions) ⱖ35 7 ⬍35 10
3 wk (⬎15 fractions) ⱖ45 3 ⬍45 1
regimens (45%), typically 25 Gy in 10 fractions, with a mean field
size of 20.1 cm2 (Table 3). The dose-fractionation for each patient See text for definitions of dose regimens.
was also converted into a biologically effective dose (BED) value,
expressed in Gy, for both tumor control and late effects. The BED
values were calculated according to the following formula (25):
Oncology Group toxicity scoring, as previously described (29).
Specifically, Grade 4 toxicity was defined as necrosis (cartilage/
BED ⫽ nd ⫻ [1 ⫹ d ⁄ 共␣ ⁄ ␤兲] bone damage) and/or ulceration with an additional requirement for
a duration of ⬎3 months.
Where n ⫽ number of fractions, and d ⫽ dose per fraction.
Because human skin cancers have been characterized by ␣/␤
ratios of 13.8 Gy (26) and 8.5 Gy (27), an ␣/␤ ratio of 10 Gy was Statistical analysis
used for this study. For late skin reactions, an ␣/␤ ratio of 2.8 – 4.3 The primary outcomes analyzed included local control after
Gy was reported (28), and therefore a value of 3 Gy was used in radiation, regional (lymph node) control, and disease-free survival,
this study. Therefore, as well as Grade 4 toxicity of treatment. Summary statistics, such
as the mean, median, proportion, and frequency, were used to
BEDtumor control ⫽ nd ⫻ (1 ⫹ d ⁄ 10) and describe the patient sample. To determine whether BED is predic-
tive of recurrence or survival, Cox proportional hazards regression
BEDlate effect ⫽ nd ⫻ (1 ⫹ d ⁄ 3)
models were used. To determine whether BED is associated with
patient or treatment characteristics, a Pearson correlation coeffi-
For example, 60 Gy given in 2 Gy fractions will give cient was estimated (␳). To test whether BED was associated with
BEDtumor control of 72 Gy, and BEDlate effect of 100 Gy. the presence or absence of the toxicities listed, a logistic regression
model was used. For all tests, a p value of ⱕ0.05 was considered
Recurrence/toxicity statistically significant.
Local control was defined as the lack of persistent or recurrent
disease at the initial site for the follow-up period. Treatment-
related toxicity was defined in accordance with Radiation Therapy
RESULTS
Patient and treatment characteristics
Table 2. Patient and radiation therapy (RT) characteristics The patient characteristics are outlined in Table 2. The
Gender (n) patients were predominantly male, with a diagnosis of BD
Male 29 in the sixth decade. The disease occurred predominantly on
Female 15 sun-exposed areas, such as the face, extremities, and scalp.
Mean age (y) (SD) 67.7 (14.5) Of the patients who received prior therapies, 1 patient each
Previous skin cancer (n) (RT/no RT) 10/5
Previous adjuvant treatment (n)
received betamethasone cream, topical 5-fluorouracil, and
Topical creams 7 hydrocortisone cream. Two patients had prior excisions: 1
Excision 2 had an incomplete excision, and the other had a recurrence
Cryotherapy 2 after initial surgery and was subsequently referred for RT.
Curettage and electrodesiccation 1 Most patients were treated with orthovoltage X-rays, with a
Location (n)
Face 12
median energy of 100 kV (range, 60 –250 kV). The median
Extremity 12 number of days between the start and end of treatment was 6
Scalp 9 (range, 0 –59 days), and the median field size was 6.87 cm2
Trunk 6 (range, 1.5–58.9 cm2). The median BEDtumor control was 49.3
Anal 3 Gy (range, 26.4 – 65.3 Gy), and the median BEDlate effect was
Penis 2
Pretreatment size (cm2) (minimum,
88.3 Gy (range, 42.2–153.3 Gy).
2.65 (0.07, 34.56)
maximum) Ten patients had documented immunosuppression: 4 re-
RT Modality (n) ceived chemotherapy, 3 had chronic corticosteroid use, 2
Orthovoltage X-rays 39 had diabetes, 5 had other causes of immunocompromise,
Electrons 3 such as chronic lymphocytic leukemia, and some of the
Cobalt 2
above patients had a combination of these conditions.
508 I. J. Radiation Oncology ● Biology ● Physics
Follow-up
The median follow-up was 2.6 years (range, 0 –11.8
years), with the longest follow-up period being 12 years.
Because the majority of patients were more than 65 years
old and were also followed by dermatologists, patients were
relied on to contact the clinic if future lesions should arise.
Thus, many patients were lost to follow-up, with median
follow-up duration being 2.3 years (range, 0.1– 8.6 years)
for those who died and 2.9 years (range, 0.1–11.9 years) for
those who were alive at last follow-up. Three patients had
evidence of disease at last follow-up: 2 were not followed
further because the focus of therapy turned to other comor-
bidities and the third for reasons unclear in the chart.
Recurrence
Complete remission was achieved in 42 patients, with
follow-up unavailable for the remaining 2 patients. Subse-
quently, 3 patients experienced recurrences at 0.2, 1.1, and
1–1.5 years after complete remission. One recurrence was
BD that recurred locally in the previously treated field. The
lesion was a penile lesion treated with a moderate dose of
25 Gy in 10 fractions. It was subsequently treated with
5-fluorouracil, but disease was still present at the last fol-
low-up 1 year later. The other two recurrences were SCC,
one of which was a lesion that recurred approximately 14
months later on the hairless scalp in the field previously
treated with a lower dose of 20 Gy in 5 fractions. It was
subsequently treated with 35 Gy in 5 fractions, and there
was no evidence of disease at the last follow-up. The second
recurrence of SCC was a marginal skin recurrence of a
cheek lesion previously treated with a higher dose of 42.5
Gy in 10 fractions. Further follow-up consisted of observa-
tion, because the patient had metastatic SCC, of which the
first SCC lesion had been diagnosed simultaneously with
the initial BD lesion, though at a distant location. Four
patients experienced a new squamous skin lesion at a distant
site, including the patient with the marginal skin recurrence
of SCC on the cheek.
Survival
As of last follow-up, 32 patients (73%) were known to be
alive. All but 3 patients were disease-free at last follow-up,
1 of whom died with distant, but not local disease. Median
overall survival was estimated to be 8.4 years (95% CI
6.4 –NA), and the 5-year overall survival rate was 68%
(95% CI 52%–90%). Recurrence-free survival estimates
were similar because only 3 patients had disease recurrence
before death.
Dose and BED effects on recurrence and toxicity
In comparing patients treated with high-dose regimens
(n ⫽ 24) with those who were not (n ⫽ 20), the high-dose
patients had smaller mean tumor size (3.49 cm2 vs. 9.15 cm2,
p ⫽ 0.05). Recurrence was not significantly different (1 of
24 in the high-dose group, 2 of 20 in the moderate-dose
group). To deal with the varying biologic effectiveness due
to the various fractionation schemes, the BED values were
Volume 63, Number 2, 2005
analyzed to assess whether there was an association be-
tween BED and recurrence and/or toxicity. Although there
was a trend toward high radiation doses being used for
smaller pretreatment tumor sizes and smaller radiation
fields, there was not a statistically significant association
between BED and pretreatment tumor or field size (Table
4). Likewise, there was no significant association between
BED and recurrence (Table 5). For the 44 patients, there
was a recurrence rate of 3 of 44, which is a crude local
control rate of 93%. Biologically effective dose was also not
associated with survival (Table 5).
Regarding toxicity, the BEDlate effect was not significantly
associated with Grade 4 toxicity; however, the 3 cases of
Grade 4 toxicity occurred in patients treated with higher
radiation doses for extremity lesions. One of the 3 patients
treated with 42.5 Gy in 10 fractions (field size ⫽ 3.9 cm2,
age ⫽ 71.7 years, BEDlate effect ⫽ 102.7 Gy) had damage
resulting in deformity of the underlying nailbed and the
occurrence of an ulcer 1 year after complete remission,
possibly related to the abnormal nail growth. Another pa-
tient with a leg lesion treated with 32.5 Gy in 5 fractions
(field size ⫽ 4.9 cm2, age ⫽ 62.8 years, BEDlate effect ⫽
102.9 Gy) had a persistent nonhealing ulcer 2 years after RT
and required surgical excision of the ulcer/eschar, with no
subsequent recurrence at 12 years follow-up. A third patient
had a finger lesion treated with 45 Gy in 10 fractions (field
size 12.6 cm2, age ⫽ 48.9 years, BEDlate effect ⫽ 112.5 Gy)
resulting in both a nonhealing ulcer and underlying bone
damage that required amputation of the finger due to radi-
ation necrosis.
DISCUSSION
The results of this study demonstrate that RT is an effec-
tive primary treatment of BD. The 42 patients who received
follow-up initially had a complete response to treatment,
and of the 3 patients that recurred, 1 was subsequently
successfully treated with a higher dose of RT. The other 2
patients had disease at last follow-up, having been treated
with topical 5-fluorouracil and observation, respectively. It
is questionable whether the patient who had the marginal
SCC recurrence 1–1.5 years later was a true recurrence of
the BD lesion, because an SCC lesion had been diagnosed
simultaneously with the initial BD lesion, and metastatic
disease was found at other sites at approximately the same
time course as the marginal SCC recurrence.
Table 4. Pearson correlation coefficients for BED and
pretreatment tumor size or field size
BEDtumor control
Variable ␳ p value
Pretreatment size ⫺0.29 0.059
Field size ⫺0.23 0.13
Abbreviation: BED ⫽ biologically effective dose.
 RT for Bowen’s disease of the skin
Table 5. Cox proportional hazards regression results for BED
prediction of recurrence or survival
BEDtumor control
Variable Hazard ratio (95% CI) p value
Recurrence 0.97 (0.88–1.05) 0.43
Median survival 0.99 (0.94–1.03) 0.48
Abbreviations: BED ⫽ biologically effective dose; CI ⫽ con-
fidence interval.
There are no studies in the literature directly comparing
other treatment options with RT. Excluding two studies in
which either contact radiation or grenz rays were used, the
retrospective studies in the literature in which orthovoltage
or electron therapy were used had local control rates ranging
from 98% to 100% (6, 15, 18, 19, 30). The study in which
contact radiation was used, published in 1985, was the first
comprehensive study in the literature, treating 52 patients
with BD (6, 14). The healing rate was as high as 100% at 6
months after completing RT (6, 14). In the current study,
1985 was chosen as a starting date both for comparison with
the literature and to facilitate access to records, which is
often limited in older files. In a recent retrospective review
of 44 patients with 71 lesions treated with RT, a recurrence
rate of 3 of 71 was reported, which is a crude local control
rate of 96% or an actuarial rate of control of 92% at 3 years
(31). Two lesions were salvaged with Moh’s surgery and the
third with a wider excision and skin flap, with no evidence
of disease at last follow-up (31). The median dose pre-
scribed was 49 Gy (range, 25– 66 Gy) (31) of either 6- or
9-MeV electrons, with the earlier retrospective studies in the
literature ranging in dose from 10 Gy to 70 Gy (Table 1).
In this study, orthovoltage radiation was used primarily,
and availability of this treatment modality differs across
radiation centers. The orthovoltage treatment fields have
been defined with sheets of lead placed on the patients’ skin,
with a “cut out” in the middle conforming to the treatment
field. The penumbra from 50% (field edge) to 90% pre-
scribed dose has been measured to be 2–3 mm. This gen-
erally allows tighter margins as compared with electrons,
for which the equivalent penumbra is often 5– 8 mm.
As mentioned previously, there is a wide range of doses
used in the literature and in this review, and it was of
interest whether dose intensity has an effect on local control
or toxicity. In this study, BED was not associated with
recurrence. This is consistent with the literature, which
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