BURN SURGERY AND RESEARCH

Optimizing Radiotherapy for Keloids

A Meta-Analysis Systematic Review Comparing Recurrence Rates
Between Different Radiation Modalities
Peter Mankowski, MD, MSc,* Jonathan Kanevsky, MD, CM,* Jared Tomlinson, MD,*
Alina Dyachenko, MSc,† and Mario Luc, MD*

electron beam, or brachytherapy. Brachytherapy has been demonstrated

Background: The high recurrence rate of keloids has lead to the use of multiple
treatment adjuncts to improve cosmetic outcomes after surgery. To date, there has
been no single, standardized modality agreed upon to produce the best results.
The purpose of this study was to review the radiation-based treatments (brachy-
therapy, electron beam and X-ray) used for keloid management and compare
their outcomes.
Methods: A literature review was performed from 1942 to October 2014 using
the databases: PubMed database of the National Center of Biotechnology Infor-
mation, MEDLINE, Biosis, Embase, Google scholar, and Cochrane database. Ar-
ticles were reviewed for case numbers, patient demographics, keloid location,
follow up, radiation modality, dose, keloid recurrence, and complications.
Results: A total of 72 studies met the inclusion criteria representing 9048 keloids.
These studies were categorized by treatment: brachytherapy, electron, or X-ray.
Meta-analysis demonstrated that radiotherapy after surgery had less recurrence
when compared to radiotherapy alone (22% and 37%, respectively, P = 0.005).
Comparison between modalities revealed that postoperative brachytherapy
yielded the lowest recurrence rate (15%) compared with X-ray and electron beam
(23% and 23%, respectively; P =0.04, P = 0.1). Subgroup analysis by location
demonstrated chest keloids have the highest recurrence rate. The most commonly
reported side effect of radiotherapy was changes in skin pigmentation.
Conclusions: The results of this study reinforce postoperative radiotherapy as
effective management for keloids. Specifically, brachytherapy was the most ef-
fective of the currently used radiation modalities.
Key Words: keloid, meta-analysis, radiotherapy, brachytherapy, recurrence
(Ann Plast Surg 2017;78: 403–411)
K eloids arise from excessive collagen deposition that extend beyond
the margins of an original injury and are thought to occur from an
imbalance in normal wound healing.1,2 These growths are known for
a recurrence rate above 50% when treated by excision alone.2 Many
treatments in various combinations have been applied to keloid man-
agement with a stepwise algorithm having been previously described
by Ogawa.3
Postoperative radiotherapy is 1 treatment option that has shown
to be more effective than either surgery or radiation monotherapy and
is commonly applied after keloid management is refractory to nonsurgi-
cal options such as corticosteroid injection, laser, or cryotherapy.1,3 The
approach of postoperative radiotherapy can include superficial X-ray,
Received April 5, 2016, and accepted for publication, after revision December 12, 2016.
From the *Division of Plastic and Reconstructive Surgery, and †St. Mary’s Research
Centre, University of McGill Health Centre, Montreal, Quebec, Canada.
Conflict of interest and sources of funding: none declared.
Presentation at a meeting: Organization: Association of plastic and aesthetic surgery of
Quebec. Place: Mont Tremblant, Quebec, Canada Date: February 28, 2015.
Supplemental digital content is available for this article. Direct URL citations appear in
the printed text and are provided in the HTML and PDF versions of this article on
the journal’s Web site (www.annalsplasticsurgery.com).
Reprints: Peter Mankowski, MD, MSc, 401-1290W 11 Avenue, Vancouver, British
Columbia, Canada. E-mail: peter.mankowski@mail.mcgill.ca.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0148-7043/17/7804–0403
DOI: 10.1097/SAP.0000000000000989
to be superior to other radiation options for control of keloid recur-
rence.3,4 However, previous meta-analyses comparing the success of
these treatments left the ideal treatment modality in question.1,5 Thus,
the aim of this systematic review is to consolidate the current reports
of keloid radiotherapy treatments and summarize the outcome of differ-
ent radiation treatment modalities by meta-analysis.
METHODS
A review of the literature from 1942 to 2014 was performed
through October 2014 using the databases: PubMed database of the Na-
tional Center of Biotechnology Information, MEDLINE, Biosis,
Embase, Google scholar, and Cochrane database. All relevant studies
describing the use of radiotherapy for the treatment of keloids were in-
cluded without exclusion based on treatment regimen. Keywords used
to search the literature include “keloid,” “radiotherapy,” and “radiation
therapy.” References cited by the retrieved literature were also reviewed.
Inclusion criteria for the study required the use of radiotherapy for the
treatment of keloids with a reported recurrence rate or clearly defining
parameters used to measure the success of radiotherapy treatment. Stud-
ies were excluded if they failed to clearly report the parameters of their
technique or if they failed to quantify the success of their treatment
(Fig. 1). Case series/reports were not included (patient, n <10). All arti-
cles reviewed were published in English. Articles were reviewed for
their case number, patient demographic, keloid location, follow up, eti-
ology, surgery inclusion, radiation type, dose, keloid recurrence, resolu-
tion, and reported complications.
Recurrence rate was obtained from each study as a percentage of
the number of keloids that recurred over the total treatment group size.
For each of the selected studies, the recurrence rate was verified or com-
puted if necessary. If a gradient was used by a study to measure recur-
rence, only keloids that did not show any level of recurrence where
used to calculate the total rate. To allow for comparison of the amount
of radiotherapy administered between studies, biological effective dose
(BED) was calculated for each study in accordance with Kal and Veen.6
Calculation of BED values used a tissue specific alpha/beta ratio that
represents the relationship of cell survival to radiotherapy. For skin,
values of both 10 and 2.08 have been reported in the literature and there-
fore BED calculations where completed using both values.1 For studies
where a range of Gray values were reported, an average BED was cal-
culated and used to represent the study. For studies where the total ke-
loid population contained subgroups of keloids that received different
fractionation dosing schedules, we broke the study population into indi-
vidual treatment groups for meta-analysis comparison.
To proceed with statistic analysis the recurrence rates from the
multiple studies were pooled in a binomial meta-analysis.7,8 We tested
the study homogeneity of the pooled studies and depending on whether
homogeneity was accepted or rejected, we planned to use a fixed or the
random effect model for meta-analysis comparison to calculate the
summary keloid recurrence rate and its 95% confidence interval (95%
CI). We used the Q statistic to test between study homogeneity: homo-
geneity was rejected when the Q statistic P value was less than 0.10.

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Mankowski et al Annals of Plastic Surgery • Volume 78, Number 4, April 2017

FIGURE 1. Overview of literature systematic review. Multiple modalities, either X-ray or electron beam therapy was used. Monotherapy,
radiotherapy alone. Postexcisional, radiotherapy after surgical excision of the keloid.

The binomial meta-analysis was then repeated separately for each com-
parison of interest1: monotherapy versus post-keloid excision,2 radio-
therapy modality type and3 by keloid location. Finally, a mixed effect
logistic meta-analysis was performed to statistically compare the keloid
recurrence rates by reporting a combined odds ratio (OR) and 95% CI
for each of the above covariates.
Dose-response curves using the calculated BED values were
created to assess the relationship between radiation dose and recur-
rence rate. A dose response curve was created for each alpha/beta
value used to calculate BED for each postexcisional treatment modality.
Forest plots were obtained for each radiation treatment modality. The
meta-analysis was conducted using the R 3.1 software.9
RESULTS
A total of 1410 studies where found using our keyword search
methodology. Based on title and abstract screening, 411 studies re-
ceived complete review and 72 studies were identified that met the in-
clusion criteria (Fig. 1). Publications were deconstructed to represent
individual treatment groups representing a unified treatment regimen
(eg, multiple radiotherapy dosing schedules composing different treat-
ment groups within one study). From the collected studies, 98 treatment
groups representing a total of 9048 keloids qualified for meta-analysis.
These treatment groups included 20 brachytherapy, 21 electron beams,
and 42 X-rays.
Assessment of overall consistency of effects across the evaluated
studies was low (I2 = 92%). When the studies were segregated by differ-
ent subgroups the datasets had a high degree of heterogeneity (always
I2 > 64% and P value Q statistics <0.0001). The studies homogeneity
was always rejected, and the random effect models for meta-analysis
were used for each comparison.
Radiotherapy Monotherapy Compared With
Postexcisional Radiotherapy
Of the 98 treatment groups, 22 groups were treated by radiother-
apy alone and 71 groups were treated by surgical excision first followed
by radiotherapy (postexcisional radiotherapy). The remaining groups
were classified as receiving either preoperative radiotherapy or both
preoperative and postoperative radiotherapy but these groups had a
sample size too small for effective comparison.
Meta-analysis was performed to compare the recurrence rates
of keloids treated with radiation therapy with and without surgery. Re-
currence rates were reported based on patient follow up which ranged
0 to 16 years. The average minimum follow up between all studies was
14.4 months. A significantly higher recurrence rate of 37 ± 12% was
identified with radiation monotherapy compared with 22 ± 4% when
radiation was applied after surgical excision (OR, 2.43; 95%CI,
1.31–4.49; P=0.0046)
Efficacy of Multiple Radiotherapy Modalities
The 98 treatment groups were classified into 5 different categories
(Figure 1 and Supplemental digital content 1, http://links.lww.com/SAP/
A220, which summarizes all studies included in the meta-analysis).10–76
An initial meta-analysis was performed to compare recurrence between
treatment modalities. A recurrence rate of 34%, the highest of all

TABLE 1. Meta-Analysis Comparison of Keloid Recurrence Rate by Radiation Modality Including Both Radiation Monotherapy
and Postexcisional Radiotherapy Treatment Groups

Treatment Modality (n = 98) No. Studies Recurrence Rate (95% CI) % of Variation (I2) OR (95% CI) P
Electron 21 21 % (15–30) 90.9% 1.53 (0.69–3.39) 0.2936
X-ray 42 34 % (26–43) 94.2% 3.12 (1.56–6.24) 0.0013
Brachytherapy 20 17 % (13–22) 85.1% 1 reference

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Annals of Plastic Surgery • Volume 78, Number 4, April 2017 Meta-Analysis of Keloid Radiotherapy Modalites

FIGURE 2. Meta-analysis of postexcisional radiation brachytherapy for the treatment of keloids.

FIGURE 3. Meta-analysis of postexcisional X-ray radiation therapy for the treatment of keloids.

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Mankowski et al Annals of Plastic Surgery • Volume 78, Number 4, April 2017

FIGURE 4. Meta-analysis of postexcisional electron beam radiation therapy for the treatment of keloids.

treatment modalities, was identified with X-ray radiotherapy. Both
brachytherapy and electron beam modalities showed decreased rates
of recurrence when compared to X-ray (21% and 17%, respectively,
Table 1). The difference between electron and brachytherapy was
noted to be nonsignificant.
Meta-analysis was then performed again including only post-
excisional radiotherapy studies (Figs. 2, 3, and 4). The lowest recur-
rence rate of 15% was found for brachytherapy with 23% for electron
beam and 23% for X-ray therapies. Recurrence rate comparison be-
tween X-ray and brachytherapy was statistically significant (OR, 1.94;
P =0.04, Table 2) and statistically insignificant between electron beam
and brachytherapy (OR, 1.81; P =0.10, Table 2). Dose-response curves
and regression analysis (R2) was used to quantify the strength of associ-
ation between recurrence and treatment modality (Figs. 5, 6, and 7).
Brachytherapy demonstrated the highest R2 value of 0.39 with electron
beam and X-ray having similar R-squared values (0.15).
Subgroup Analysis of Recurrence Rate by Location
A subgroup analysis of 33 treatment groups was performed to
assess the relationship between keloid location and recurrence rate.
Each treatment group consisted of keloids localized to one of 5 possible
categories (chest and trunk, upper extremity, lower extremity, head, and
neck or ears). Chest and trunk keloids had the highest rate of recurrence
(34%) of all the location groups and were significantly more likely to
recur compared to keloids localized to the ear (12%; P = 0.0025). Re-
currence rates compared between the other treatment groups were noted
to be nonsignificant (Table 3).
Complication Profile of Postexcision Radiotherapy
Of the total keloid population, 59.2% (5356) were collected from
studies with documented posttreatment complication rates. A total of 37
complication types were described. The 5 most common complications
represented multiple classifications of pigmentation changes with a
collective total occurrence of 32.5% (erythema, transient hyperpig-
mentation, hyperpigmentation, hypopigmentation, and unspecified
pigmentation changes). Both infection and wound dehiscence occurred
in less than 1% of cases (0.85% and 0.32%, respectively; Figure 8).
DISCUSSION
Postexcisional Radiotherapy
Radiation monotherapy of keloids is currently used for very
large or nonresectable lesions. In accordance with current management
practices, we initially demonstrated that postexcisional radiotherapy
was more successful at reducing keloid recurrence compared to

TABLE 2. Meta-Analysis Comparison of Keloid Recurrence Rate by Radiation Modality for Postexcisional Radiotherapy Treatment

Treatment Modality (n = 71) No. Studies Recurrence Rate (95% CI) % of Variation (I2) OR (95% CI) P
Electron 18 23 % (17–31) 87.1% 1.81 (0.89–3.69) 0.1002
X-ray 27 23 % (16–3) 92.5% 1.94 (1.01–3.72) 0.0465
Brachytherapy 17 15 % (12–2) 76.7% 1 reference

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Annals of Plastic Surgery • Volume 78, Number 4, April 2017 Meta-Analysis of Keloid Radiotherapy Modalites

FIGURE 5. The relationship of the recurrence rate of keloids treated with postexcisional brachytherapy as function of the BED.

FIGURE 6. The relationship of the recurrence rate of keloids treated with postexcisional X-ray therapy as function of the BED.

FIGURE 7. The relationship of the recurrence rate of keloids treated with postexcisional electron beam therapy as function of the BED.

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Mankowski et al Annals of Plastic Surgery • Volume 78, Number 4, April 2017

TABLE 3. Meta-Analysis Comparison of Keloid Recurrence Rate by Anatomical Location

Location (n = 36) No. Studies Recurrence Rate (95% CI) % of Variation (I2) OR (95% CI) P
Chest and trunk 9 34 % (23–47) 85.7% 4.46 (1.73–11.51) 0.002
Ear 12 12 % (7–22) 77.0% 1 reference
Head and neck 5 9 % (5–15) 23.2% 1.07 (0.33–3.43) 0.916
Extremity 7 16 % (1–25) 1.5% 1.37 (0.45–4.14) 0.5743

radiotherapy alone (22% and 37%, respectively). A previous meta-
analysis cited a similar recurrence rate for radiation monotherapy of
43%; however, they noted postexcisional radiotherapy to be less effica-
cious with recurrence rate of 32%.5 This improvement in keloid control
with postexcisional radiotherapy is most likely attributed to the increas-
ing popularity of the technique that has allowed for a greater sampling
of studies for our analysis. Additionally, postexcisional radiotherapy is
improving with recent reports demonstrating improved recurrence rates
with shorter, stronger dosing fractionation schedules.1
Comparison Between Radiotherapy Modalities
Of the 3 most commonly used radiation modalities for post-
excisional radiotherapy, brachytherapy (15%) was found to have a lower
recurrence rate when compared to electron beam and X-ray therapy by
meta-analysis (23%, P = 0.10 and 23%, P = 0.04 respectively, Table 2).
The dose-response relationship of brachytherapy keloid recurrence was
also noted to be the strongest of the three modalities (Fig. 5). Of the 3
modalities, brachytherapy is unique in offering a focused in situ deliv-
ery and less toxicity to adjacent tissue.77 Thus, brachytherapy is capable
of the highest targeting of keloid tissue compared with the external mo-
dalities. However, although multiple case series have suggested brachy-
therapy is superior to other external beam modalities, few controlled
comparisons have been completed.10,77,78 In a recent cohort study of
258 keloids, Yossi et al79 found an 18.5% greater control with brachy-
therapy over external beam after 5-year follow-up (73.5% and 55%).
However, their difference in recurrence rate was not significant,
and it was suggested that a larger sample size was required to show

FIGURE 8. Rate of treatment complications from radiotherapy management of keloids. Adverse outcomes were reported for a
proportion of the studies reviewed representing a subpopulation of 5356 keloids. The incidence obtained from the studies reviewed
for each complication was then used to calculate the total percentage of each treatment complication within the population of keloids
with complications reported. Minor adverse events with a rate of occurrence less than 0.01% were not included in the figure.

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Annals of Plastic Surgery • Volume 78, Number 4, April 2017
the significance of brachytherapy over electron beam.79 Here, we were
able to reinforce the superiority of brachytherapy of maintaining control
of keloid recurrence compared with X-ray external beam therapy.
Larger studies with comparable keloid dosing profiles and locations
are required to tease apart the subtle difference between electron and
brachytherapy control of keloids.
For the 2 external radiation modalities, X-ray and electron beam,
similar control of keloid recurrence was noted. Additionally, the dose-
response association for both external beam modalities was found to
be similar when the alpha/beta value was 2.08 (Figs. 6 and 7). Our con-
clusion is different from Flickinger,1 who compared electron beam and
X-ray kilovoltage radiation by multivariate regression analysis and
found that electron was superior to X-ray. Flickinger1 attributed the im-
proved control of keloids by electron therapy to the superficial penetra-
tion profile of the modality allowing for maximal dose to be delivered at
the keloid site. They suggest a 95% control rate of non-earlobe keloids
with total postoperative radiotherapy doses of 23.4 to 24.8 Gy.1 These
dose estimates have however been unsuccessful at achieving 95% con-
trol in subsequent cohort studies.11,79 Here, the ability of X-ray and
electron beam therapy to achieve similar recurrence rates suggest that
variation between the penetrance profiles of either modality does not
significantly contribute to keloid control with the doses previously
used. A previous dose-response analysis by Kal and Veen6 suggested
a dose of greater than 30 Gy for 90% control of keloid recurrence with
external beam radiotherapy. For a similar degree of control, we suggest
a dose of 35 Gy, for external beam radiotherapy according to our dose-
response curve.
Keloid Control Comparison Between
Anatomical Localization
The rate of recurrence of keloids has been proposed to be asso-
ciated with the localization of the lesion.12 Variations in the tensile
forces of skin have been suggested to contribute to the development
and control of keloids. Additionally, Ogawa et al10 reported very low re-
currence rates (<10%) for keloids localized to the ear with electron
beam therapy. In our study, a subgroup meta-analysis of 13 studies that
reported keloid recurrence by specific location was performed and
found that chest and trunk localization of lesions to have the signifi-
cantly higher rate of recurrence (34%) compared with other keloid lo-
calizations. This finding is in accordance with previous case series
and further supports the impact of tensile forces or traction from the ad-
jacent tissues on keloid management.80
Specifically for keloids with earlobe localization, we found a
recurrence rate of 12%, which was comparably higher than the rate re-
ported by Ogawa et al10 with electron beam therapy. They proposed
total doses of 10 Gy over 2 fractions (BED =15 Gy) for their treatment
plan, and were able to achieve recurrence rates closer to 5% with elec-
tron beam. Of the studies included in our subgroup analysis of earlobe
keloids, the 5 groups with recurrence rates less than 5% reported using
higher BEDs with an average of 20.2 ± 4.4 Gy. Ogawa et al,12 how-
ever, had previously compared BEDs of 22.5 and 15 Gy (at α/β of
10) for the management of ear keloids and found no statistical differ-
ence in recurrence. Therefore it is likely that a BED of 15 to 22.5 Gy
can manage earlobe keloids with lower doses offering lower risks for
treatment side effects.
Adverse Outcomes of Radiotherapy Management
The most commonly reported side effects of treatment were ery-
thema and varying degrees of pigmentation changes. This is to be ex-
pected secondary to radiation administration to the skin and therefore
pigmentation changes associated with postexcisional radiotherapy are
likely under reported. More severe complications requiring interven-
tion, such as wound dehiscence or wound infection occurred at rates
of less than 1%.
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Meta-Analysis of Keloid Radiotherapy Modalites
No accounts of neoplastic processes were reported in any of the
reviewed studies. The association of cancer as an adverse outcome of
keloid radiation was originally identified by Ragoowansi et al81 who
found 5 case reports of malignancies arising in patients who previously
received radiotherapy for keloid management. However, a subsequent
analysis of these cases by Ogawa et al82 noted that these previous re-
ports did not include their dosing regimens or shielding techniques
and therefore it is difficult to quantify the true associated neoplastic risk.
It was concluded that the risk developing a neoplasm from keloid radio-
therapy was low and the majority of radiation oncologists considers the
technique acceptable.82
CONCLUSIONS
The use of postexcisional radiotherapy for the treatment of ke-
loids is superior to radiation monotherapy. Currently used radiation
modalities are capable of achieving rates of recurrence of approxi-
mately 20% regardless of the type of radiation chosen. Of these,
brachytherapy is a promising option using an interstitial source of radi-
ation to achieve optimal targeting of keloid tissue. Adverse outcomes
associated with the technique are primarily associated with change
in pigmentation.
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