Anda di halaman 1dari 11

1

Effectiveness and Risk Assessment of Radiotherapy for Post-Keloid Excision

Management: A System Review

A.J. Hicks

Department of Allied Health Sciences

University of North Carolina at Chapel Hill

ahicks47@live.unc.edu

Honor Code Signature: AJ Hicks

Word CountAbstract: 168

Word CountMain Text: 1114

References: 20
2

Abstract

Overview: Determine the effectiveness and potential risks of various radiotherapy methods for

treating of keloid scarring.

Methods: PubMed and Google Scholar were the main databases used for research. Articles

used had to concentrate on the effectiveness of radiotherapy post-surgical excision and its

effect on keloid recurrence.

Results: There is a fair degree of variability due to different methods of radiation administration,

scar evaluation, and post-treatment patient recall. Also, keloids were assessed differently

depending on location.

Conclusions: Any form of post-keloidectomy radiation therapy was more effective at stopping

keloid recurrence than surgical excision alone. External beam radiation therapy prevailed as the

preferred method when compared to brachytherapy. High dose rate (HDR) brachytherapy

outperformed low dose rate (LDR) brachytherapy when directly compared. The biologically

effective dose (BED) appeared to be the main determining factor of effectiveness with higher

BED leading to lower recurrence. In all, this field needs more research to determine the best

radiation protocol; also, patients need to be tracked longer post-radiotherapy to determine

chances of secondary malignancies.

Keywords

Radiotherapy; External Beam Radiation Therapy; Brachytherapy; Biological Effective Dose

(BED); Keloid treatment; Radiation-Induced Cancer (RIC)


3

Introduction

Keloid scarring is a hyper-proliferative disorder in which skin trauma causes scars to

continuously grow beyond the site of injury; there is 20-fold collagen production in the dermis

compared to normal skin. Similar to hypertrophic scarring, these cutaneous growths are benign

and are symptomatic with chief complaints of aesthetic disfiguration, burning, itching, and

pruritus. Unlike their counterpart, keloid scars form up to years after initial injury and do not

regress over time unless addressed clinically.1 While any demographic is susceptible of forming

keloids, higher pigmentation increases the likelihood 15-fold. Black, Asian, and Hispanic

populations have the highest incident rate of 4.5-16%, the gender ratio is 1:1 and the age of

onset is ~10-30 years old.2,3

Due to the complexity of scar formation, current research on the subject is often

misleading and poorly understood. This leads to much debate about which treatment regimen

will serve as the most effective method, the goal being to decrease the recurrence rate of

previously excised scars in the safest manner. Surgical excision alone leads to recurrence rates

of >45%. Radiotherapy post-surgical excision has been identified as a method that decreases

recurrence rates to ~10-20%.4 There are 4 methods of radiation that are pertinent with keloids:

external beam radiation therapy (EBRT, megavoltage electrons), kilovoltage radiotherapy, and

high- and low-dose brachytherapy (HDR and LDR). No modality has been deemed the golden

standard of care because there are many patient factors that contraindicate the different RT

methods. With that said, this systematic review aims to assess how effective radiotherapy halts

the regrowth of keloids, which delivery method is best, and the effects it has on surrounding

tissues.

Methods

Derived from the compilation of articles from multiple online databases, this review was

made to assess the risk versus reward of using radiation therapy to stunt the recurrence of
4

keloid scars post-surgical excision. The main databases used were PubMed and Google

Scholar. Main search terms used were: (Radiotherapy OR Radiation Therapy OR External

Beam Radiation Therapy OR Brachytherapy AND keloid treatment OR keloid surgery OR keloid

excision OR scar treatment) and (Radiotherapy OR radiation therapy AND keloid treatment AND

Radiation Induced Cancer OR dose effects) and (Radiotherapy AND keloid recurrence OR

effectiveness OR efficacy OR patient satisfaction). In order for a study to qualify for this

systematic review, the article must focus on radiotherapy usage as a treatment method to

minimalize keloid scarring recurrence after being surgically excised. There will be multiple

surgical practices and methods of radiotherapy given to patients, along with multiple patient

demographics, even though there are demographics prone to scarring. Due to the lack of

substantial research around keloid scarring, there are few restrictions on study selection for the

sake of data inclusion; however, articles that focused on radiotherapy used for hypertrophic

scarring or cancer treatments were excluded.

Of the search terms used, PubMed produced 107 articles and Google Scholar produced

4218 articles making it a total of 4325 articles. There were 3 additional articles recommended

through PubMed bringing the total to 4328 articles in total. After reviewing titles and abstracts of

those articles 20 were selected as being the most relevant to the topic, this excludes 4308

articles. Publication years of articles in this study ranged from 2005-2016.

Searches Conducted:

PubMed: External beam radiation therapy for keloids, Radiation Induced Cancer and Keloids,

Radiotherapy with steroid injection for keloids, Keloid pathophysiology. n=107

Google Scholar: external beam radiation treatment for keloid scars, external beam radiation

therapy for keloid scar treatment OR keloid excision. N=3590


5

Decision Tree

Decision Tree

Articles found Additional


through database articles (n=8)
Identificati searches (n=576)
on

Articles total
(n=4328)

Articles excluded
Screening Articles screened (n=4308)
n=4328)

Full-text articles
assessed for
eligibility (n=20)
Eligibility
Articles including Articles including
pertinent variables radiation risks (n=2)
(radiation therapy, keloid
recurrence) (n=18)

Article types: Case series,


Included Studies included: quantitative, qualitative,
20 meta-analysis, literature
reviews
6

Results

Searches conducted mostly presented quantitative studies that focused on the use of

different forms of radiotherapy and its effect on keloid recurrence. EBRT, kilovoltage electrons,

LDR and HDR brachytherapy treatments came from different radiation sources, were given in

different doses, and had different dose scheduling depending on the article. The only common

factor between all of the articles was that radiotherapy was given post-surgical excision.

Brachytherapy was given both superficially and interstitially depending on the treatment center

administering the radiation; interstitial and superficial methods were not compared directly.

Multiple meta-analyses focused on the biologically effective dose (BED) which was determined

mathematically based on dose, dose source, and tissue irradiated. These articles also

calculated BED for all radiotherapy methods. There were 2 articles that presented laser therapy

as an alternate method to radiotherapy. Both contributed to the 4 articles that focused on

earlobe keloids only, based on the prevalence of this kind of keloid due to ear piercing. One

article presented the comparison of steroid injections (triamcinolone) and radiotherapy post-

surgical excision. There was an article that presented shave excision and post-second intention

radiotherapy, an alternative method to classical excision and RT during the healing process.

Literature reviews assessing the pathophysiology of keloids and adverse effects of radiotherapy

were also included.

Discussion

The research studies analyzed presented many significant findings. There was a general

consensus that the use of radiotherapy post-surgical excision of keloids had a significantly

positive effect on keloid recurrence.1,316 Compared individually with surgical excision alone,

radiotherapy led to decreased keloid recurrence, improved cosmetic outcomes, and increased

patient satisfaction. There was a good amount of debate between whether EBRT or

brachytherapy is the preferred method of radiation administration4,6 and it was determined that
7

EBRT led to a longer period of recurrence. There were also comparisons of HDR and LDR

brachytherapy, but there was no conclusive evidence on which method was better due to study

limitations and similar effects on recurrence.16 A significant factor that was analyzed was the

BED of radiotherapy, which determines how the tissue irradiated as a whole receives the

radiation dose. Based on location and radiation source, it was determined that higher BED led

to better dose homogeneity and decreased keloid recurrence.3,6,810,12,13,1517

This finding presents major concern of radiation-induced cancer (RIC), which is always a

concern when radiation is administered. As the BED goes up, the dosage administered goes up

which raises many red flags.1,7,18 This revelation opens the door for alternative post-

keloidectomy methods such as laser treatments, which eliminate the risk of RIC with minimally

proven effectiveness.2,19 The use of triamcinolone steroid injections was also compared to

radiotherapy yielding similar results with no risk of RIC.14

While radiotherapy presents itself as an effective method for stunting keloid recurrence,

more concrete evidence is needed. While BED gives the radiation oncologist more control over

keloid recurrence, there is no agreed method of radiation administration in terms of source,

dose schedule and dose fractionation.20 There also needs to be more long-term cohort studies

following patients to evaluate RT effectiveness and secondary malignancies. A deeper

understanding of keloid mechanisms could also assist in the finding of a golden standard.
8

References

1. Berman B, Maderal A, Raphael B. Keloids and Hypertrophic Scars: Pathophysiology,

Classification, and Treatment. Dermatol Surg 2016. doi:10.1097/DSS.0000000000000819.

2. Scrimali L, Lomeo G, Tamburino S, et al. Laser CO2 versus radiotherapy in treatment of

keloid scars. and Laser Therapy 2012. Available at:

http://www.tandfonline.com/doi/abs/10.3109/14764172.2012.671524.

3. van Leeuwen MCE, Stokmans SC, Bulstra A-EJ, Meijer OWM, van Leeuwen PAM,

Niessen FB. High-dose-rate brachytherapy for the treatment of recalcitrant keloids: a

unique, effective treatment protocol. Plast Reconstr Surg 2014;134(3):527-534.

doi:10.1097/PRS.0000000000000415.

4. Hoang D, Reznik R, Orgel M, Li Q, Mirhadi A, Kulber DA. Surgical Excision and Adjuvant

Brachytherapy vs External Beam Radiation for the Effective Treatment of Keloids: 10-Year

Institutional Retrospective Analysis. Aesthet Surg J 2016. doi:10.1093/asj/sjw124.

5. Keeling BH, Whitsitt J, Liu A, Dunnick CA. Keloid Removal by Shave Excision With

Adjuvant External Beam Radiation Therapy. Dermatol Surg 2015;41(8):989-992.

doi:10.1097/DSS.0000000000000417.

6. Reznik R, Hoang D, Li Q, et al. Surgical Excision and Postoperative External Beam

Radiation Therapy Versus High-Dose-Rate Interstitial Brachytherapy in the Treatment of

Keloids-Ten-Year Single-Institutional Retrospective Analysis. Int J Radiat Oncol Biol Phys


9

2016;96(2S):E502. doi:10.1016/j.ijrobp.2016.06.1888.

7. McKeown SR, Hatfield P, Prestwich RJD, Shaffer RE, Taylor RE. Radiotherapy for benign

disease; assessing the risk of radiation-induced cancer following exposure to intermediate

dose radiation. Br J Radiol 2015;88(1056):20150405. doi:10.1259/bjr.20150405.

8. Kuribayashi S, Miyashita T, Ozawa Y, et al. Post-keloidectomy irradiation using high-dose-

rate superficial brachytherapy. J Radiat Res 2011;52(3):365-368.

9. Kim K, Son D, Kim J. Radiation Therapy Following Total Keloidectomy: A Retrospective

Study over 11 Years. Arch Plast Surg 2015;42(5):588-595.

doi:10.5999/aps.2015.42.5.588.

10. Sakamoto T, Oya N, Shibuya K, Nagata Y, Hiraoka M. Dose-response relationship and

dose optimization in radiotherapy of postoperative keloids. Radiother Oncol

2009;91(2):271-276. doi:10.1016/j.radonc.2008.12.018.

11. Ogawa R, Ono S, Akaishi S, Dohi T, Iimura T, Nakao J. Reconstruction after Anterior

Chest Wall Keloid Resection Using Internal Mammary Artery Perforator Propeller Flaps.

Plastic and reconstructive surgery. Global open 2016;4(9):e1049.

doi:10.1097/GOX.0000000000001049.

12. Flickinger JC. A radiobiological analysis of multicenter data for postoperative keloid

radiotherapy. Int J Radiat Oncol Biol Phys 2011;79(4):1164-1170.

doi:10.1016/j.ijrobp.2009.12.019.
10

13. Bennett KG, Kung TA, Hayman JA, Brown DL. Treatment of Keloids With Excision and

Adjuvant Radiation: A Single Center Experience and Review of the Literature. Ann Plast

Surg 2016. doi:10.1097/SAP.0000000000000903.

14. Shin JY, Lee J-W, Roh S-G, Lee N-H, Yang K-M. A Comparison of the Effectiveness of

Triamcinolone and Radiation Therapy for Ear Keloids after Surgical Excision: A Systematic

Review and Meta-Analysis. Plast Reconstr Surg 2016;137(6):1718-1725.

doi:10.1097/PRS.0000000000002165.

15. Kal HB, Veen RE. Biologically effective doses of postoperative radiotherapy in the

prevention of keloids. Dose-effect relationship. Strahlenther Onkol 2005;181(11):717-723.

doi:10.1007/s00066-005-1407-6.

16. De Cicco L, Vischioni B, Vavassori A, et al. Postoperative management of keloids: low-

dose-rate and high-dose-rate brachytherapy. Brachytherapy 2014;13(5):508-513.

doi:10.1016/j.brachy.2014.01.005.

17. Eaton DJ, Barber E, Ferguson L, Mark Simpson G, Collis CH. Radiotherapy treatment of

keloid scars with a kilovoltage X-ray parallel pair. Radiother Oncol 2012;102(3):421-423.

doi:10.1016/j.radonc.2011.08.002.

18. Gieringer M, Gosepath J, Naim R. Radiotherapy and wound healing: Principles,

management and prospects (Review). Oncology reports 2011. Available at:

http://www.ingentaconnect.com/content/sp/or/2011/00000026/00000002/art00001.
11

19. Scrimali L, Lomeo G, Nolfo C, et al. Treatment of hypertrophic scars and keloids with a

fractional CO2 laser: a personal experience. J Cosmet Laser Ther 2010;12(5):218-221.

doi:10.3109/14764172.2010.514924.

20. Khansa I, Harrison B, Janis JE. Evidence-Based Scar Management: How to Improve

Results with Technique and Technology. Plast Reconstr Surg 2016;138(3 Suppl):165S-

78S. doi:10.1097/PRS.0000000000002647.