280 - Characterization of Skin Microbiome Profile before and during Radiation Therapy and Its Correlation to the Occurrence and Severity of Radiation Dermatitis

R. Abdah-Bortnyak^1,2, H. Brand³, R. Nisimov³, G. Peri^4,5, D. Shwartz³, M. Brandwein⁶, A. Katz³, M. Nuriel-Ohayon³, M. Ben-Simon¹, S. Billan^1,2, and S. Luder³; ¹Rambam Health Care Campus, Haifa, Israel, ²Technion Israel Institute of Technology, the Ruth and Bruce Rappaport Faculty of Medicine., Haifa, Israel, ³Acemanan Ltd., Tel-Aviv, Israel, ⁴Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel, ⁵Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel, ⁶Department of Molecular Biology, Ariel University, Ariel, Israel

Purpose/Objective(s): Radiation dermatitis (RD) is one of the most common side effects of radiation therapy (RT) to breast. The purpose of this study is to characterize the skin microbiome profile of breast cancer patients before, during and shortly after RT course, and evaluate the relationship between the microbiome profile and severity of RD. Materials/

Methods: In this observational, single center, single arm study, breast cancer patients received RT at Rambam Health Care Campus from November 2020 to July 2021. Skin assessments and skin microbiome samples were collected from all patients at several points: before starting of RT course, weekly during RT, end-of-therapy and at follow-up visit after the completion of treatment. The outcome measures were: RD grade, microbiome composition according to microbiome profiling to determine the community composition and to evaluate the richness and diversity at baseline and during RT treatment, as well as comparison between skin microbiome of treated and untreated breast and forehead.
Results: 640 skin samples were collected from 86 breast cancer patients, bacterial DNA was extracted, and 16S rDNA was amplified and sequenced. Samples were analyzed from three time points: baseline before treatment commenced, mid-treatment and last treatment. All patients received irradiation to breast after breast conserving surgery in dose 45 Gy; 50 patients were subjected to an additional sequential boost to the lumpectomy cavity to a total dose of 55-57.5 Gy. At mid-treatment bacterial family Clostridiaceae was unique to patients later diagnosed with severe dermatitis, with bacteria of this family being present in 30% of the samples (p-value = 0.002038, q-value = 0.218074). An unknown species of Anaerococcus, designated Anaerococcus US436, was unique to patients in the severe dermatitis group at mid-treatment (21.67% in this group, p-value = 0.002038). To increase sample size and reduce noise, we collected all treated samples from all time points and compared the microbiome composition between the groups of dermatitis severity. The Clostridiaceae family and Clostridium genus remained significantly enriched in the severe group (p-value = 0.002095 and 0.004269, q-value = 0.06912 and 0.1631, respectively), as well as the Anaerococcus genus and its mentioned unknown species (p-value = 0.001825 and 0.007104, q-value = 0.1379 and 0.1454, respectively). The treated samples for each patient were summed up, and examined each bacterium, for at least one appearance per patient during the treatment. One species, Granulicatella elegans, was enriched in the severe group (p-value = 0.000512, q-value = 0.2333) and another, Bacillus thuringiensis – was enriched in the mild group (p-value = 0.000595, q-value = 0.2333).
Conclusion: A "bacterial signature" associated with severe RD was identified. This signature is composed of Clostridium, Anaerococcus US436 and Granulicatella elegans.