Laser therapy as a treatment for chronic radiation fibrosis

Abstract

Background

Chronic radiation fibrosis (CRF) is a long‐term sequala of radiation therapy that has a significant impact on patient quality of life. There is no standard of care or single therapeutic modality that has been found to be consistently effective.

Objective

To describe our experience using fractional 10,600 nm carbon dioxide (CO₂) laser therapy and vascular laser therapy in a series of patients with CRF.

Methods

Patients presenting to the dermatology service for CRF were evaluated for laser therapy eligibility. Patients were eligible if they had a clinical diagnosis of CRF confirmed by physical examination.

Results

We identified five patients with CRF treated with fractional ablative CO₂ laser and vascular laser. Patients were a median age of 57 years old, and the amount of time between the initiation of radiotherapy and laser treatment ranged between 3 months and 40 years. The satisfactory response was achieved in all cases.

Limitations

Lack of standardized laser protocol, small sample size, lack of a control group, different anatomical locations

Conclusion

Fractional ablative and vascular laser therapy may serve as an additional treatment for CRF, leading to functional improvements.

INTRODUCTION

Radiotherapy is an essential modality in the modern cancer management regiment, with nearly 50% of cancer patients receiving radiation therapy either alone or as an adjuvant to chemotherapy, surgery, or both. ¹ , ² Chronic radiation fibrosis (CRF) is a form of chronic radiation dermatitis that occurs at least 90 days after radiation therapy. Radiation‐induced skin fibrosis, a frequently occurring late adverse effect of radiation exposure, is due to an uncontrolled wound healing response resulting in aberrant expression of transforming growth factor‐β and excessive extracellular matrix deposition at the radiation injury site. ² , ³ , ⁴ , ⁵ This fibrotic process, which has a significant impact on cosmesis and patient quality of life, can present clinically as pain, range of motion limitations, impaired wound healing, loss of skin appendages with dyspigmentation, decreased sweating, and xerosis. ⁶

There are limited therapeutic treatments for chronic radiation‐induced fibrosis with moderate clinical success. As researchers learn more about the pathology of CRF, new therapeutics modulating steps in the pathophysiology are being proposed. Some of these proposed therapeutics include antioxidants like tocopherol targeting transforming growth factor beta, autologous fat transfer targeting fibroblast activity, and adipose‐derived stem cells which work through the release of growth factors and cytokines contributing to the mitigation of radiation‐damaged skin. ⁷ , ⁸ , ⁹ Although these therapies show clinical promise, to date, no single therapeutic option has been consistently effective in the management of CRF. ²

Fractional laser therapy has been shown to treat fibrosis associated with hypertrophic scars leading to tissue repair and thus, we propose its utility in the treatment of CRF to support normal tissue remodeling. We report five patients with refractory CRF who were treated with vascular laser and/or fractional carbon dioxide laser therapy. The characteristics and clinical course of these patients are presented.

METHODS

This was a retrospective review to investigate the efficacy of laser treatment for refractory CRF. We included five patients who had undergone prior oncology treatments at Memorial Sloan Kettering Cancer Center (MSKCC) and were referred to the corresponding author's (A. M. R.) dermatologic surgery clinic for laser treatment between May 2016 and October 2020. The lasers used for treatment were the 10,600 nm Lumenis Ultrapulse, CO₂ Laser, 532 nm Cutera Excel V, and the 595 nm Pulsed Dye Laser (Candela Laser).

Posttreatment instructions were given to all patients based on the laser type they received. For fractional CO₂ lasers, patients were told to conduct dilute acetic acid soaks with white vinegar and a tablespoon to a cup of water. Additionally, they were told to apply bland emollients 4–5 times per day. Finally, they were instructed to use sunscreen SPF 30 or above when exposed to the sun. Patients treated with vascular lasers were instructed to apply gentle emollients daily and sunscreen of SPF 30 or above when exposed to the sun. Side effects for the fractional CO₂ group included crusting and scabbing while the vascular laser group had expected purpura and slight swelling. Follow‐up after the last treatment is ongoing and all patients have had a follow‐up duration for at least 1 year.

Since radiated skin is slower to heal than nonradiated skin, it was best to employ conservative settings when combining lasers. The vascular laser is used first to target hemoglobin in the telangiectasias followed by a fractional ablative laser to induce ablative channels for wound healing and tissue remodeling.

Demographic data, characterization of chronic radiation dermatitis, prior therapies and further medical information were obtained from patient chart review. Retrospective analysis of the study was approved by the MSKCC institutional review board (IRB 16‐458). Differences in demographics and CRF characteristics were summarized descriptively. Due to the small sample size, the analyses were exploratory and descriptive without the conduction of statistical comparison.

RESULTS

A total of five CRF patients were included in this series. The median age of the included patient group was 57 years (range = 44–68) and all patients were women. Two out of the five patients had a history of smoking and reradiation. The median time lapse between radiation therapy and the onset of laser therapy was 13 years (3 months–40 years). Patients were treated with laser therapy for an average of six sessions (3–12 sessions). Patient characteristics and laser therapy regime are summarized in Table 1. Satisfactory response, defined as a patient's desire to continue seeking laser therapy and clinician documentation of CRF improvement, was observed in all patients. Minor pinpoint bleeding was observed during the treatment. No standard measuring tool was used for a skin evaluation.

Table 1.

Patient data and outcomes regarding laser treatment for chronic radiation fibrosis

Patient	Age	Cancer	Age at diagnosis	Time lapse between radiation and CRF	CRF Indication	Laser type	Wavelength (nm)	Spot size/density	Fluence	Pulse	Frequency of follow‐ups	Sessions
1	57	Reticulum cell sarcoma	9	40 years	Atrophy, telangiectasias, fibrosis	KTP, PDL, and Fractional CO2	KTP 532 PDL 595 Fractional DEEP FX: 10,6000	7–10 mm DEEP FX: Density 10%	5.6–9 J/cm2 DEEP FX: 15 mJ	6–12 ms DEEP FX: 1 pass, square pattern	12–24 weeks	12
2	64	Tongue squamous cell carcinoma	56	3 years	Telangiectasias, fibrosis	PDL and Fractional CO2	PDL: 595 Fractional DEEP FX: 10,6000	PDL: 7–10 mm DEEP FX: Density 10%	PDL: 7–8 J DEEP FX: 15 mJ	PDL: 3–6 ms DEEP FX: 1 pass, square pattern	12–24 weeks	5
3	44	Mandibular osteosarcoma	38	3 months	Hypopigmentation, hyperpigmentation, scarring, fibrosis	PDL and Fractional CO2	PDL: 595 Fractional DEEP FX: 106000	PDL: 7–10 mm DEEP FX: Density 5–10%	PDL: 5–8 mJ DEEP FX: 15 mJ	PDL: 6 ms DEEP FX: 1 pass, square pattern	12 weeks	8
4	53	Tongue squamous cell carcinoma	50	1 year	Telangiectasias Atrophy Fibrosis Decreased motility	PDL and Fractional CO2	PDL: 595 Fractional DEEP FX: 106000	PDL: 5–10 mm DEEP FX: Density 5–10%	PDL: 8.6 J/cm2 DEEP FX: 12.5–17.5 mJ	PDL: 10 ms DEEP FX: 1 pass, square pattern	4–6 weeks	3
5	68	Breast cancer	42	13 years	Telangiectasias, scarring, fibrosis	KTP and Fractional CO2	KTP: 532 Fractional DEEP FX: 106000	KTP: 5–7 mm DEEP FX: Density 5–10%	KTP: 5.6–8.6 J/cm2 DEEP FX: 12.5–17.5 mJ	KTP: 3–10 ms DEEP FX: 1 pass, square pattern	5–6 weeks	3

Note: Ablative Fractional CO₂ Laser—DEEP Fx—Lumenis—California, USA. PDL: Pulse Dye Laser—Candela, California, USA. KTP: Cutera Excel V—California, USA.

Case 1

A 57‐year‐old female with a history of reticulum cell sarcoma diagnosed at Age 9 status postcobalt radiation to the right neck, and chemotherapy presented to dermatology with recalcitrant radiation dermatitis and fibrosis. The chronic radiation fibrosis of her neck caused her to experience swelling, facial edema, and gradual loss of neck range of motion, resulting in difficulty with her head turning right and blind spot while driving. Despite prior treatments with physical therapy, acupuncture, and manual lymphatic massage, she still suffered from a limited range of motion and discomfort. The physical examination revealed chest and neck atrophy, radiation fibrosis, telangiectasias, and tightness of the skin upon turning the head to the right. Initial small test spots with the potassium titanyl phosphate (KTP) laser and fractional CO₂ laser had no adverse results. She began noticing improvements in neck range of motion after two sessions spaced at 5–6‐week intervals. After her 8th session, the patient described laser therapy as very helpful and shared that her neck range of motion had returned to baseline (Table 1).

Case 2

A 64‐year‐old female with a history of squamous cell carcinoma of the tongue, diagnosed at age 56 treated with hemiglossectomy and selective neck dissection, chemotherapy, and radiation began developing symptoms of CRF approximately 3 years after radiotherapy. Physical examination revealed telangiectasias and fibrotic skin in the area of the left and right neck, which she believed had worsened despite physical therapy. She complained of decreased cervical range of motion that affected her ability to do household chores, place objects overhead, and turn her head to scan the environment. After five laser sessions with pulsed dye laser (PDL) and fractional CO₂ with concurrent physical therapy spaced across a 2‐year interval, she regained increased cervical mobility near baseline with the ability to scan the environment and achieve circumferential neck extension (Table 1).

Case 3

A 44‐year‐old female with a history of osteosarcoma of the mandible status postresection and radiotherapy was referred for chronic radiation fibrosis after 2 years of physical and lymphedema therapy. A physical examination of the neck revealed decreased range of motion with atrophy of soft tissue, a well‐healed horizontal hypopigmented scar, and a hypertrophic erythematous scar. She underwent eight sessions of combined fractional CO₂ and KTP laser therapy with marked improvement of scarring and range of motion (Table 1).

Case 4

A 53‐year‐old female with a history of squamous cell carcinoma of the tongue, diagnosed at age 50 status posthemiglossectomy and radiation was referred to dermatology for chronic radiation fibrosis. Physical examination of the neck and chin revealed dyspigmentation, hypertrophic scarring, and atrophy with limited range of motion. She underwent two sessions of fractional CO₂ laser therapy and one session of combined fractional CO₂ and PDL therapy spaced at 4–6‐week intervals. She also underwent onobotulinum toxin injections into the platysma at regular 4‐month intervals. The patient has experienced improvement in her neck and chin mobility and decreased scarring and dyspigmentation (Figure 1).

Figure 1.

Dyspigmentation, hypertrophic scarring, and atrophy of the neck and chin following radiation for a squamous cell carcinoma of the tongue.

Case 5

The patient is a 65‐year‐old woman with a history of left breast cancer status postexcision, lumpectomy, endocrine therapy, mastectomy, and whole breast radiation whose treatment course was complicated by substantial dehiscence of her mastectomy incision (Figure 2). She presented to dermatology bothered by the appearance of the scars and the decreased range of motion of her left arm due to substantial radiation fibrosis. Physical examination revealed dyspigmentation and contractures of the skin. She underwent two sessions of fractional CO₂ therapy and one combined session of fractional CO₂ and PDL. Each session of fractional CO₂ laser therapy also included topical drug delivery of 1 cc of Kenalog 40 mg/cc. This patient eventually noted an improved elasticity of her skin and moderate improvements in arm overhead range of motion.

Figure 2.

Contractures of the skin, dyspigmentation, and substantial radiation fibrosis surrounding the left axilla following lumpectomy, mastectomy, and radiation therapy for a left breast cancer.

DISCUSSION

Radiation therapy is an efficacious tool against cancer. However, the cutaneous adverse effects that occur due to off target neighboring ionizing radiation can have debilitating sequala like chronic radiation fibrosis. Chronic radiation fibrosis significantly impacts patient quality of life through limitation of movement, tissue retraction, and pain. ¹⁰ This is a difficult‐to‐treat process that dermatologists are frequently involved in managing. We reported five cases of chronic radiation fibrosis treated using a combination of vascular (KTP and PDL) and/or fractional CO₂ ablative laser therapy.

Treatment options targeting the fibrosis associated with chronic radiation dermatitis include physical therapy, pentoxifylline alone or in combination with tocopherol (vitamin E), and laser therapy. ¹¹ Physical therapy involving deep tissue massaging and exercise help the affected area by improving mobility and preventing contracture formation. A randomized prospective study of 20 women that focused on treating radiation‐induced skin fibrosis with a mobilizing massage technique and physical therapy found a significant reduction in skin hardening, erythema, pain, and pruritus. ¹² Vitamin E may also be utilized, as it is an antioxidant that targets reactive oxygen species, which are responsible for promoting differentiation and persistence of myofibroblast cells during the development of radiation fibrosis. ² When combined with pentoxifylline it helps to block TGF‐β signaling in irradiated tissue. ² , ⁹

Prior successes with the use of PDL in the treatment of other forms of chronic radiation dermatitis alongside studies highlighting the efficacy of fractional CO₂ laser in the treatment of fibrosis due to hypertrophic scars influenced the decision to treat CRF in our patients. ¹³ There are multiple studies that document the use of dye lasers for the telangiectasias associated with chronic radiation dermatitis. ¹³ A study comparing the effect of dye laser with intense pulsed light in 13 females with telangiectasias revealed that both treatments were effective for telangiectasias. ¹¹ , ¹⁴ Another study following 11 breast cancer patients who developed telangiectasias to radiotherapy also revealed clinical improvement of the telangiectasias after pulsed dye laser treatment. ¹³

While there are multiple studies with vascular lasers for telangiectasias, there are few studies that utilize ablative laser therapy for fibrosis morphology. ¹¹ , ¹³ , ¹⁴ A case series by Tran et al. reported successful improvement of fibrosis and disfigurement in the skin that developed due to the outdated treatment of hemangiomas with radioactive phosphorus P3 using a combination of laser treatment, including pulsed‐dye laser, fractional CO₂ laser, and epidermal grafting. ¹⁵ A recently published pilot study by Tran et al. highlighted the use of fractional CO₂ in the setting of 10 CRF patients showed overall patient satisfaction. ¹⁶

The pathophysiology behind the efficacy of fractional CO₂ laser therapy in chronic radiation fibrosis may be analogous to pathophysiology behind the use of fractional laser therapy in the treatment of fibrosis associated with hypertrophic scars. Histopathologically, laser therapy contributes to normalization of dermal collagen and significantly decreases the expression of TGF‐B1 expression in hypertrophic scars. ¹⁷ Similar to CRF, hypertrophic scars and keloids are characterized intravascular thrombi and excess proliferation of endothelial cells that lead to vascular occlusion and congestion. ¹⁸ Studies observing the histological changes in burn tissue noted 50% decrease in type I collagen, and 50% increase in type III collagen, normalization of collagen architecture, and increase vascularity of the superficial dermis. ¹⁸ , ¹⁹ Future studies are needed to further define the exact mechanism behind the role of CO₂ laser therapy in chronic radiation fibrosis.

Chronic radiation fibrosis is particularly difficult to manage due to the overall fragility of irradiated skin and other coinciding morphologies such as telangiectasias and skin atrophy—both of which are indicative of significant cutaneous injury. ¹⁰ Persistent telangiectasias commonly appear following boost dosing and acute grade 3 radiation dermatitis, and are believed to be secondary to microvasculature damages. ²⁰ , ²¹ Epidermal and dermal atrophy occur because of a reduced population of dermal fibroblasts and the reabsorption of collagen. ¹⁰ , ²² This contributes to fragility and predisposes to painful erosions and ulcerations, which may be slow healing and predispose to superinfection. ¹⁰ , ²² In the setting of chronic radiation fibrosis there is further predisposition for ulcers and skin breakdown because of eccentric myointimal proliferation of the small arteries and arterioles that can progress to thrombosis or obstruction. ¹⁰ , ²³ Radiation fibrosis is comparable to scar management with loss of adnexal structure, disarranged collagen, vasculature, and lymphatics. Thus, the approach to induce collagen, vascular, and dermal lymphatic remodeling is similar. ¹⁸

As seen in many of the cases presented, often irradiated skin has undergone other invasive procedures like surgery and reconstruction that result in further tissue compromise. Furthermore, fibrosed skin is associated with slower wound healing. ²⁴ The delicacy of fibrosed radiated skin presents a challenge for undergoing laser therapy, necessitating the use of conservative settings with low‐density fractional ablation to avoid complete tissue injury. On the Lumenis Ultrapulse, this translated to a 5%–10% density at 15 mJ. Additionally, single nonoverlapping pulses and adequate cooling is needed to protect against unwarranted epidermal injury. The risk of scarring, infection, and dyspigmentation are important to consider in the setting of laser therapy especially in patients that may also be on immunosuppressive medications.

Finally, we want to emphasize the importance of treating conservatively as radiation fibrosis may be slow to heal following injury. Similar to burn scar treatment paradigms, we employ a low‐density, higher fluence, method to allow for depth of penetration into the fibrotic dermis and healing from intact stroma. Laser settings vary between different platforms and therefore, it is best to adapt this concept for the different lasers used. These settings also allow for topical drug delivery of steroids if needed. ²⁵

CONCLUSION

Chronic radiation fibrosis is a long‐term sequela of radiation therapy that has a significant impact on patient quality of life as illustrated by the experiences of patients. All patients initially presented with chronic radiation fibrosis characterized by a reduced range of motion and loss of elasticity. Skin improvement assessed by a range of motion and increased skin elasticity was seen in all patients. While each of our five patients experienced significant improvement with the use of laser therapy in the setting of chronic radiation fibrosis, our study's findings are limited by the small sample size. Laser treatment with ablative fractional lasers and vascular lasers appears to be an effective treatment for patients with chronic radiation fibrosis and dermatitis. However, further randomized controlled studies are warranted to confirm our reported beneficial findings and to determine if early intervention would help mitigate late radiation effects.

AUTHOR CONTRIBUTIONS

Anthony Rossi, Christian Menzer, and Abdullah Aleisa conceived the presented idea. Britney Wilson, Christian Menzer, Abdullah Aleisa, and Anthony Rossi developed the theory while Anthony Rossi performed the procedural aspects. Britney Wilson and Rohan Shah wrote the manuscript with supervision from Abdullah Aleisa, Christian Menzer, and Anthony Rossi. All authors discussed the results and contributed to the final manuscript while acknowledging its submission.

CONFLICT OF INTEREST

Dr. Anthony Rossi has no relevant conflicts of interest related to this manuscript but has received grant funding from The Skin Cancer Foundation and the A.Ward Ford Memorial Grant. He also served on advisory board, as a consultant, or given educational presentations for Almirall; Allergan, Inc; Galderma Inc; Evolus Inc; Elekta; Biofrontera, Quantia; Merz Inc; Dynamed; Skinuvia; Perf‐Action; Cutera; and LAM therapeutics. Dr. Christian Menzer is supported by a fellowship from the German Research Foundation (DFG) (ME 5482/1‐1). The remaining authors declare no conflict of interest.

Wilson B, Shah R, Menzer C, Aleisa A, Rossi A. Laser therapy as a treatment for chronic radiation fibrosis. Lasers Surg Med. 2023;55:82–88. 10.1002/lsm.23617