Can Antibiotics Prevent Acute Radiation Dermatitis?

New research has confirmed a long-suspected link between acute radiation dermatitis (ARD) severity and Staphyloccocus aureus skin bacteria, and suggests that topical antibiotics can prevent the more serious forms of this condition.^1-3

“Until now, ARD was assumed to result simply from the skin being burned by the radiation, which meant not much could be done to prevent it,” said study coauthor Beth N. McLellan, MD, of Montefiore Einstein Cancer Center in New York City, in a press release.⁴ “The readily available treatment we’ve developed and clinically tested could potentially save hundreds of thousands of people each year in the US from severe ARD and its excruciating side effects.”

Up to 95% of patients undergoing radiation oncology treatments will experience ARD. A frequently painful condition that can cause delays and disruptions in care, the severity and presentation of ARD can vary widely depending on radiation dose and patient factors such as skin pigmentation (darkness).

ARD typically includes acute erythema (skin rash caused by capillary congestion) and desquamation (peeling skin).^5,6 Grade 2 desquamation occurs at skin folds; grade 3, at other areas of the skin.^5,6 Grade 3 cases involve ulcerating or moist desquamation with sores. Grade 4 ARD involves these plus bleeding and skin necrosis. Dry desquamation usually appears 3 to 4 weeks after initiating radiotherapy at doses of 20 to 30 Gy, and moist desquamation occurs 4 or more weeks after treatment with 30 to 40 Gy. Erythema can appear more quickly (1 to 2 weeks after radiotherapy doses ranging from 10 to 40 Gy).^5,6

Table. Acute Radiation Dermatitis Signs and Symptoms by Grade

ARD Grade	Signs and Symptoms
0	None
0.5	Patchy or faint erythema and subtle hyperpigmentation (darkening)
1.0	Faint, diffuse erythema Diffuse hyperpigmentation Mild epilation
1.5	Definite erythema Extreme hyperpigmentation
2.0	Definite erythema and hyperpigmentation with fine dry desquamation, mild edema
2.5	Definite erythema/hyperpigmentation with branny/scaly desquamation
3.0	Deep red erythema with diffuse, dry desquamation Peeling in sheets
3.5	Violet erythema with early moist desquamation Peeling in sheets Patchy crusting
4.0	Violet erythema with diffuse moist desquamation Patchy crusting Ulceration Necrosis

Strategies for preventing and managing ARD vary dramatically and treatments have been, to date, mainly palliative, targeting inflammation or trying to promote skin survival and healing.⁷ Preradiation assessments include screening for radiation hypersensitivity, and patients undergoing radiotherapy are typically told to avoid sun exposure and reduce skin cosmetics within the radiation field to reduce the risk and severity of ARD. Traditional ARD treatments vary from aqueous cream skin emollients, hydrogel dressings, and saline soaks to prophylactic corticosteroids.^5,6

Patients are typically monitored for secondary skin infections at ARD sites.^5,6 But the new studies indicate topical antibacterial therapy can prevent the emergence of higher-grade ARD in the first place.²

In the first of the team’s 2 new phase 2/3 studies, the researchers collected bacteria from the skin and nostril interiors of 76 patients before and after radiotherapy. Approximately 1 in 5 patients tested positive for S. aureus before radiotherapy.¹ Baseline nasal colonization was associated with an increased risk of grade 2 or higher ARD (P =.02).¹ But nearly half of the patients who developed severe ARD had tested positive for S. aureus before treatment.¹

The findings show that the bacteria likely play a “major role” in ARD, Dr McLellan said, confirming past case study indications of such a link.^3,4

“The good news is we have a lot of tools to fight these bacteria,” she said.⁴ “In a second study, we tested a topical antibacterial drug combination we thought would be effective and easy for people to use.”

That second study randomly assigned 75 mostly Black or Hispanic patients with breast cancer and 2 patients with head and neck cancer, to receive standard of care (moisturizing treatment and hygiene; 38 patients) or an antibacterial regimen (chlorhexidine oral rinse plus mupirocin 2% intranasal ointment twice daily every other week; 39 patients) during radiotherapy.² (At the time of the study, topical corticosteroids were not a standard of care at the authors’ cancer center.²) Nearly one-quarter (23.7%) of patients receiving standard of care developed grade 2+ ARD, compared with none of the patients receiving antibacterial therapy.² Average ARD grade was lower for patients in the antibacterial therapy group than the control group (P =.02).²

One patient in the antibacterial treatment group experienced an adverse event (itch) attributed to treatment.² No overall differences were found in patients’ quality of life.²

Citing corticosteroids’ anti-inflammatory effects, the team predicted steroids would synergize with antibiotic therapy to “amplify” protection from grade 2+ ARD, but they cautioned that additional research is needed.²

“Our regimen is simple, inexpensive, and easy, so we believe it should be used for everyone undergoing radiation therapy,” Dr McLellan said.⁴ “I expect this will completely change protocols for people undergoing radiation therapy for breast cancer.”

References

1. 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. Published online May 4, 2023. doi:10.1001/jamaoncol.2023.0454
2. Kost Y, Deutsch A, Mieczkowska K, et al. Bacterial decolonization for prevention of radiation dermatitis: a randomized clinical trial. JAMA Oncol. Published online May 4, 2023. doi:10.1001/jamaoncol.2023.0444
3. Hill A, Hanson M, Bogle MA, Duvic M. Severe radiation dermatitis is related to Staphylococcus aureus. Am J Clin Oncol. 2004;27(4):361-363. doi:10.1097/01.COC.0000071418.12121.C2
4. Albert Einstein College of Medicine. A simple antibacterial treatment can solve severe skin problems caused by radiation therapy [press release]. Medical Xpress. Posted May 4, 2023. Accessed June 15, 2023.
5. Behroozian T, Bonomo P, Patel P, et al; Multinational Association of Supportive Care in Cancer (MASCC) Oncodermatology Study Group Radiation Dermatitis Guidelines Working Group. 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)00067-0
6. Behroozian T, Goldshtein D, Wolf JR, et al; Multinational Association of Supportive Care in Cancer (MASCC) Oncodermatology Study Group Radiation Dermatitis Guidelines Working Group. 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
7. Lucey P, Zouzias C, Franco L, Chennupati SK, Kalnicki S, McLellan BN. Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States. Support Care Cancer. 2017;25(9):2857-2862. doi:10.1007/s00520-017-3701-0