MASCC Releases New Recommendations for Radiation Dermatitis Prevention, Management

Most patients undergoing external-beam radiotherapy (EBRT) will experience acute radiation dermatitis (ARD), also known as radiation-induced skin reactions or “radiation burns,” during or shortly after treatment.^1,2 Up to 95% of women undergoing EBRT for breast cancer will experience some degree of ARD, for example.^1,2

ARD can be painful and presents as erythema, edema, or dry or moist desquamation.^1,3 In severe cases, it can seriously impact patients’ quality of life and even disrupt treatment.¹ The condition is associated with sometimes-severe fatigue and anxiety.⁴

Despite the large number of patients who experience ARD, prevention and treatment practices vary widely between cancer centers, with most radiation oncology departments using their own guidelines.¹ Recent advances in evidence-based practice, described in this review, should help to remedy this inconsistency in clinical practice.^1,2,4-6

Epidemiology and Pathobiology 

ARD typically develops within 2 to 4 weeks of starting radiation therapy and often resolves within a month of completing treatments, although some patients develop chronic or late radiation dermatitis after treatment, which can last for years.² ARD risk and severity vary depending on patient genetics and anatomy; comorbidities such as diabetes, lupus erythematosus, scleroderma, or Fanconi anemia; smoking history; and age; as well as tumor location, treatment volume, total radiation dose, fractionation schedule, and radiotherapeutic modality.¹ EBRT innovations such as intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) appear to reduce the risk of ARD.¹ 

Irradiation of skin folds, such as when breast, vulvar, or anal tissues are included in treatment volumes or beam paths, appears to increase the risk ARD.¹ Treatment planning and patient positioning for treatment should therefore seek to minimize skin fold irradiation.¹ 

The role of race and skin color in ARD risk is unclear. African American patients are less likely to have physician-reported ARD but might have higher risk of ARD compared with other patients, suggesting the condition is underdiagnosed in this population when physician-rated diagnostic scales are used.⁷

The pathogenesis of ARD is a complex process that involves skin cells, stem cells, their DNA, and surrounding tissues. Ionizing radiation damages cellular DNA and cytokine signaling pathways, impairing cell function and triggering apoptotic cell death.¹   

ARD can begin within 24 hours of initial irradiation with acute transient erythema, followed by hyperpigmentation and progressive erythema by the beginning of the 2nd to 4th week. At 3 to 4 weeks, dry desquamation may develop, sometimes followed by moist desquamation at 4 weeks or longer after the initiation of radiotherapy.¹ 

Grading ARD

Patient scores should be determined at baseline, prior to the initiation of radiotherapy, and repeated during treatment to detect ARD. There are at least 19 published scales designed for documenting and evaluating ARD severity, only 4 of which include patient-reported elements.³ 

The most commonly used grading systems are the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; see table) and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) systems, each of which grade ARD severity on a scale of 1 through 5 where grade 1 involves faint erythema and dry desquamation and grade 5 is patient death.^1,3,8 

Table. Acute Radiation Dermatitis Signs and Symptoms by Grade

Grade 1	Faint erythema or dry desquamation
Grade 2	Moderate to brisk erythemaPatchy moist desquamation, mostly confirmed to skin folds and creasesModerate edema
Grade 3	Moist desquamation in areas other than skin folds and creasesBleeding induced by minor trauma or abrasion
Grade 4	Life-threatening consequencesSkin necrosis or ulceration of full thickness dermisSpontaneous bleeding from involved siteSkin graft indicated
Grade 5	Death

Source: National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. US Department of Health and Human Services; November 27, 2017. Accessed November 8, 2023. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5×11.pdf

The MASCC Clinical Practice Guidelines

The evidence base for preventing and managing ARD is spotty and immature, with numerous low-quality studies. To assess the current state of the science, the Multinational Association of Supportive Care in Cancer (MASCC) Oncodermatology Study Group systematically reviewed the published literature — 235 studies, including 149 randomized, controlled clinical trials — and then convened a panel of 42 experts from around the world to examine that literature and arrive at consensus recommendations.^5,6 

Of 113 agents identified in the research literature as potential preventive or therapeutic agents for ARD — ranging from herbal ointments, vitamins, barrier dressings, and laser therapies to growth factors, topical nonsteroidal agents, topical corticosteroids, and soap and water — the MASCC Oncodermatology Study Group arrived at consensus recommendations on just one for ARD management (Mepilex Lite wound dressings, thin, soft foam silicone dressings with an adhesive that does not stick to the moist wound bed).⁶ 

The MASCC panelists separately recommended only 6 agents for ARD prevention.⁶ 

As did a separate expert panel convened by the International Society of Nurses in Cancer Care (ISNCC), MASCC’s study group did not recommend aloe vera for ARD prevention or management. The plant product is widely used — and marketed online — as a folk remedy for different types of skin burns, including ARD. “On the basis of the evidence, more than 90% of panel members did not recommend the use of aloe vera-based, Gln [amino-acid]-based, honey-based, and vitamin-based products, as well as several other natural products,” the group wrote.⁶ 

Perhaps surprisingly, however, MASCC panelists did recommend one (and only one) natural plant product as a preventive agent: olive oil.⁶ (Despite the consensus recommendation, some panel members voiced concerns based on anecdotal observations that oil-based formulations can lead to greater erythema. Others worried that findings about olive oil to prevent ARD are too heterogeneous to make a strong conclusion about its effectiveness.⁶) 

The MASCC panelists also recommended 5 other ARD-preventive agents:

• Betamethasone A topical anti-inflammatory corticosteroid.
• Hydrofilm A thin, transparent, semi-permeable polyurethane film dressing that allows moisture to pass through.
• Mepitel film (for people with breast cancer) Mepitel is a thin, transparent, and semipermeable (breathable) silicone film dressing that creates a somewhat protective barrier for skin, reducing friction and absorbing moisture.
• Mometasone A topical anti-inflammatory corticosteroid.
• Photobiomodulation (PBM) therapy Also known as low-level laser therapy (LLLT) or red-light therapy, PBM uses nonionizing light sources, such as lasers, light-emitting diodes (LEDs), or broadband light absorbed by cellular chromophores to reduce inflammation and induce tissue repair.⁹

Just because the evidence supports these agents’ use for ARD prevention does not mean they are useful in managing ARD once it occurs. For example, the panel recommended olive oil, mometasone, and hydrofilm for prevention but could not recommend those agents for ARD management because of “a complete absence of evidence evaluating the agent in the context of symptom management.”⁶ 

The MASCC Oncodermatology Study Group will update its recommendations as new evidence comes to light about the best ways to prevent or treat ARD.⁶ One potentially important strategy for preventing ARD they did not evaluate, because the relevant research was published after they completed their work, was bacterial decolonization.⁶ ARD severity was recently tied to Staphylococcus aureus skin bacteria, as was evidence that topical antibiotics can prevent more severe cases.^10,11 

References

1. Kim DY, McAvoy S, Fontanilla H. 28 – Management of skin toxicity. In Vapiwala N, Jones JA, Dharmarajan V, eds. Palliative Radiation Oncology. Elsevier; 2023:323-334. doi:10.1016/B978-0-323-87688-9.00037-4

2. Kole AJ, Kole L, Moran MS. Acute radiation dermatitis in breast cancer patients: challenges and solutions. Breast Cancer (Dove Med Press). 2017;9:313-323. doi:10.2147/BCTTS109763

3. de Souza Maggi Bontempo P, Gomes de Menêses A, Ciol MA, Ferreira EB, dos Reis PED. Instruments and scales for the evaluation of acute radiation dermatitis: a systematic review. Crit Rev Oncol Hematol. 2023;191:104116. doi:10.1016/j.critrevonc.2023.104116

4. Milton L, Behroozian T, Li N, et al. Symptom burden associated with radiation dermatitis in breast cancer patients undergoing radiotherapy. Clin Breast Cancer. 2022;22(3):e387-e398. doi:10.1016/j.clbc.2021.10.005

5. Behroozian T, Goldshtein D, Wolf JR, et al; Multinational Association of Supportive Care in Cancer (MASCC) Oncodermatology Study Group Radiation Dermatitis. MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review. eClinicalMedicine. 2023;58:101886. doi:10.1016/j.eclinm.2023.101886

6. Behroozian T, Bonomo P, Patel P, et al; Multinational Association of Supportive Care in Cancer (MASCC) Oncodermatology Study Group Radiation Dermatitis. Multinational Association of Supportive Care in Cancer (MASCC) clinical practice guidelines for the prevention and management of acute radiation dermatitis: international Delphi consensus-based recommendations. Lancet Oncol. 2023;24(4):e172-e185. doi: 10.1016/S1470-2045(23)00066-0

7. Purswani JM, Bigham Z, Adotama P, et al. Risk of radiation dermatitis in patients with skin of color who undergo radiation to the breast or chest wall with and without regional nodal irradiation. Int J Radiat Oncol Biol Phys. 2023;117(2):468-478. doi:10.1016/j.ijrobp.2023.04.006

8. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341-1346. doi:10.1016/0360-3016(95)00060-C.

9. Dompe C, Moncrieff L, Matys J, et al. Photobiomodulation — underlying mechanism and clinical applications. J Clin Med. 2020;9(6):1724. doi:10.3390/jcm9061724

10. Kost Y, Rzepecki AK, Deutsch A, et al. Association of Staphylococcus aureus colonization with severity of acute radiation dermatitis in patients with breast or head and neck cancer. JAMA Oncol. 2023;9(7):962-965. doi:10.1001/jamaoncol.2023.0454

11. Kost Y, Deutsch A, Mieczkowska K, et al. Bacterial decolonization for prevention of radiation dermatitis: a randomized clinical trial. JAMA Oncol. 2023;9(7):940-945. doi:10.1001/jamaoncol.2023.0444