A.J.

Hicks

Case Study: Effectiveness of Radiation Therapy as a Treatment for Keloid Scarring

To what degree is radiation therapy a successful treatment for keloid scarring?

What factors determine how effective radiation therapy will be?
What areas are lacking in the body of keloid literature?

INTRODUCTION

Keloid scarring is a hyperprolific skin disorder that causes growth factors in the skin to

continue forming scar tissue. This disorder is continually being researched and theories have

been devised but no concrete conclusions have been made as to why these scars grow beyond

their borders. Our understanding of the pathogenesis of cutaneous pathological scars, or keloids

and hypertrophic scars (HS), is complicated by the inconsistent correlation between clinical and

histological diagnosis because pathologically keloids and HS have many similarities making

hard to distinguish1. Research indicates that radiation therapy has an effect on keloid recurrence,

slowing down or completely stunting the ability for keloids to further develop at the surgical site.

The addition of a case study helps demonstrate the level of effectiveness radiation therapy

has in the field of keloid treatment. External beam radiation therapy (EBRT) is one of the

clinically accepted methods of keloid treatment and needs more evidence to prove or disprove its

worth. The following case study will prove significant to radiation therapists, radiation

oncologists, plastic surgeons, and potential patients who want insight into how EBRT affects

keloid recurrence.

CASE DESCRIPTION

A 21-year-old African-American male presented with a large facial keloid along his

mandible and chin accompanied with symptoms of pain, itching, ruptured folliculitis, infection,
and decreased range of motion of the neck. He had a history of neck/chin keloids that were

surgically removed two years prior in February 2012. The failure of post-excision preventative

measures to stunt keloid recurrence caused his surgical scar to proliferate drastically beyond its

borders. He received monthly cortical steroid injections directly into his benign lesions which

produced no significant effect. These injections were later strengthened with a chemotherapy

agent, but this led to lesion necrosis and drainage that gave birth to infection causing the keloid

to grow exponentially.

With the failure of his first surgery, a referral from his dermatologist led him to a new

plastic surgeon and radiation oncologist who devised a treatment plan for his recalcitrant keloid.

Under general anesthesia the benign lesion was excised including the lesion margins, the excised

diameter was over 4.0 cm. The muscle, myocuntaneous, and fasciocutaneous flap of the head and

neck were sutured, a Jackson-Pratt drain was inserted, then the patient was transported to

Radiation Oncology to received immediate adjuvant EBRT. The treatment sites were bilateral

cheek/upper neck and chin and the treatment intent was palliative. The dose scheduling was

divided into three fraction over three days. Each day he was irradiated with enface electrons at 6

MeV beam energy administering a dose of 700 cGy, the total radiation dose to 2100 cGy. The

patient tolerated treatments well without issues.

Post-surgical excision with adjuvant EBRT helped extend the period of keloid recurrence

for this patient; however, he underwent his third keloidectomy 2 years later. The recurring

keloids gradually appeared after the one year and were not as massive and the experienced

symptoms were milder. EBRT was not administered again due to concerns of over radiation.

LITERATURE REVIEW
 Keloids are dermal anomalies that have a broad range of size and location. Treatment

options include but are not limited to non-invasive pressure dressings, surgical excision, and

radiation therapy. However, medical oncologist Dr. Michael H. Tirgan states that for over 100

years the lack of scientific data and evidence-based medicine is the biggest issue in treating

keloid disorder; even as of 2016, we do not know the proper dosage of radiation therapy or

steroids.2 There is not an universally adopted gold standard for keloid treatment which leaves

prescribed treatment in the hands of the radiation oncologist, plastic surgeon, or dermatologist.

Keloids develop through complex pathways and the mechanisms that cause them to initiate,

evolve, and regulate are not fully understood1. However, radiotherapy is a common form of

keloid treatment and that will be the focus of this literature review. Effectiveness of different

types of radiation in terms of the treatments ability to stunt regrowth, how radiation sources

effect the tissue irradiated and the treatments biologically effective dose (BED), and the safety of

radiotherapy will be discussed.

Keloid Formation

Research conducted by Berman, Maderal, and Raphael identifies keloid scarring as 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 skin3.

Similar to hypertrophic scarring (HS), the other, milder form of pathological scarring associated

with keloids, these cutaneous growths are benign and symptomatic with chief complaints of

aesthetic disfiguration, burning, itching, and pruritus. Both aberrant wound healings also display

a prolonged inflammatory process leading to delayed healing caused by abundant macrophages

releasing inappropriate growth factors (cytokines)1. Unlike their HS, keloid scars form up to

years after initial injury and do not regress over time unless addressed clinically3. Keloids have
higher proliferating fibroblasts that are resistant to protein-mediated apoptosis, meaning that

fibroblasts have a longer period to exhibit their overactive cellular multiplication creating larger

amounts of collagen before they die1. If left unaddressed, these scars can continue to grow until

they are physically debilitating and create an even harder prognosis for physicians. 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.4,5

Radiation Therapy

Without adjuvant radiotherapy, surgical excision of keloids alone can lead to recurrence

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

decreases recurrence rates to ~10-20%6. While these methods have been previously reserved for

cancer treatments, the cellular effect radiation therapy has on skin cells makes it an acceptable

treatment. External beam radiotherapy (EBRT) has emerged as the most popular method of

radiotherapy. This method uses linear accelerators to externally deliver high energy photon

beams to the area of interest. These beams range in energy from 1-25 mega-eletronvolts (1x106-

325x106 MeV), with one electronvolt being the energy gained or lost by an electron moving

across an electric potential difference of one volt7. Treatments are given in fractions over

periods of days or weeks; iradium-192, casesium-137, or cobolt-60 are the common radiation

sources8. EBRT also comes in a less energetic form which is reserved for more superficial

keloids that do not have much surrounding tissue such as earlobe keloids that stem mostly from

ear piercings. These kilovoltage, or superficial, X-rays range in energy from 60-120 kilo-

elctronvolts (60x103- 120x103 KeV)9.

 Another commonly used source is brachytherapy which is the more invasive method of

radiotherapy. Also known as internal radiation, brachytherapy utilizes devices such as capsule or

catheters to place a radioactive source inside the treated area. It allows a physician to use a

higher total dose of radiation to treat a smaller area and in a shorter time than is possible with

EBRT10. Brachytherapy has a variation of delivery methods; for instance, brachytherapy can

come in either high dose rate (HDR) or low dose rate (LDR). Brachytherapy can also be

delivered superficially or interstitially, meaning the radiation source can either be laid on the

surface of the keloid or be inserted directly into the keloid. In the literature there was a general

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

positive effect on keloid recurrence3. Compared individually with surgical excision alone,

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

patient satisfaction.

In a study conducted by Dr. Don Hoang, the decision to administer post-surgical EBRT or

post-surgical brachytherapy was determined by factors such as the number of keloid lesions

treated, the resulting width, linearity, depth of the keloid excision site, ability to surgically place

interstitial brachytherapy catheter, and the patient preference with respect to a fractionated vs

single fraction radiotherapy regimen. The results of the study indicated that EBRT was more

effective and led to a longer recurrence period than brachytherapy, meaning that keloids grew

back at a slower and less frequent rate6. 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; however, HDR brachytherapy did exhibit higher

symptomatic relief11. There were no direct comparisons between superficial and interstitial

brachytherapy.
 Biologically Effective Dose

A significant factor that determined the effectiveness of radiotherapy was the ability of

the treatment to irradiate the area of interest as a whole. The more relevant tissue irradiated the

less of a chance there is for keloid recurrence. This factor known as BED is a calculation used

when trying to compare different radiation dose and fractionation schemes. Treatment is

dependent on the performing physician, studies surrounding BED can help mold a universal dose

protocol for keloids and decrease treatment variation. A study conducted by Henk, concluded

that a BED of 30 Gy over the shortest time possible is optimal while the Sakamoto study

proposed that 20 Gy over five fractions, or five separate treatments, is optimal12,13. Both authors

conclude that the higher the BED, or the more radiation administered to affected tissue, the lower

the chance for keloid recurrence.

Radiation-Induced Cancer

Evidence-based studies indicating higher BED leading to decreased recurrence is

combated by the main concern with radiation, safety. Any amount of radiation administered can

have significance on surrounding tissue which is a major concern because treatment losses its

beneficence if it causes other problems to arise. The paramount risk of radiation is cancer which

in this realm is called radiation-induced cancer (RIC). These secondary malignancies occur as

cells in the skin are denatured and begin to take on a cancerous form. Related to keloid

treatments, this concern is of lesser importance to adults whose keloids are located away from

major organs such as the lungs or thyroid. The risk of RIC such as skin cancer is still relevant but

secondary malignancies of that kind can be treated. RIC becomes more devastating when it

affects younger people, especially children, because of their increased radio sensitivity and

expected longevity14. Due to the risk of radiation induced cancer, treatment options post-
keloidectomy methods such as laser treatments, which eliminate the risk of RIC with minimally

proven effectiveness4,15. The use of triamcinolone steroid injections was also compared to

radiotherapy yielding similar results with no risk of RIC16.

CONCLUSION

Just as the literature suggests, EBRT did lengthen the period between post-surgical

excision and keloid recurrence. The patient in the case study did experience therapeutic relief

which lasted for one year until the keloid recurred in a slower and milder manner. This case goes

to show how radiation therapy can have a positive effect on keloid recurrence as compared to

surgical excision alone which in his case caused the patients keloid to exacerbate. However, it is

also shown how radiation therapy is not a cure but possibly therapeutic in some cases.

Additionally, this unsuccessful treatment could potentially lead to secondary malignancies in the

future that now must be monitored yearly. It will take further efforts from plastic surgeons and

pathologists to uncover the exact mechanisms that trigger keloidal scarring during the phases of

skin healing.

Bibliography
1. Huang C, Murphy GF, Akaishi S, Ogawa R. Keloids and hypertrophic scars: update and
future directions. Plastic and reconstructive surgery. Global open 2013;1(4):e25.
doi:10.1097/GOX.0b013e31829c4597.

2. Keloid disorder: a clinical management update | Dermatology Times. Available at:

http://dermatologytimes.modernmedicine.com/news/keloid-disorder-clinical-management-
update. Accessed February 20, 2017.

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

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

4. 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.

5. 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.

6. 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.

7. Electronvolt - Wikipedia. Available at: https://en.wikipedia.org/wiki/Electronvolt. Accessed

April 3, 2017.

8. External beam radiotherapy - Wikipedia. Available at:

https://en.wikipedia.org/wiki/External_beam_radiotherapy. Accessed February 20, 2017.

9. 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.

10. Brachytherapy (Internal radiation therapy). Available at:

http://www.radiologyinfo.org/en/info.cfm?pg=brachy. Accessed February 20, 2017.

11. 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.

12. 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.
13. 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.

14. 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.

15. 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.

16. 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.