radiation-induced adverse events include an inflammatory response and oxidative stress.23 Inflammatory markers involved in acute inflammation secondary to ionizing radiation, including IL-1, IL-6, TNF-alpha, and TGF-beta, can be expressed within hours after the first fraction of RT.23 Intrinsic factors that influence the severity of RD include demographic or disease-related characteristics.23 In patients with breast cancer, these include age, race and ethnicity, skin type, smoking, obesity, breast size, pre-or postmenopausal status, and co-existing morbidities such as diabetes or cardiovascular disease.6-10,23 Extrinsic factors include treatment-related characteristics such as technique, dose, volume fractionation, beam energy, use of bolus, immobilization devices, and the administration of systemic and targeted therapies.6-10,23 Certain systemic treatments, such as DNA repair-based regimens (cetuximab and 5-fluorouracil), are acute radiosensitizers that cause cellular damage and delay tissue repair.23 Concurrent administration of immunotherapies with RT may also enhance RD and cause cAEs independently. Sequencing of RT with targeted therapies such as EGFR inhibitors increases the risk for severe RD. Co-administration of immunotherapies may result in concomitant cAEs and/or exacerbation of RD.23 Other anatomic factors include the clinical treatment site, eg, areas of skin folds, which are more subject to the development of RD than flat, irradiated surfaces.6-10,23
Classification systems for radiation dermatitis
The 2 most commonly utilized instruments for grading RD are RTOG (Radiation Therapy Oncology Group) and CTCAE v5 (Common Terminology Criteria for Adverse Events).24 The two classification systems are described in Table 1. The CTCAE system has 5 grades, ranging from 1 (faint erythema and dry desquamation) to 5 (death) and differentiating between moist desquamation within skin folds vs flat areas. In contrast, the RTOG assessment tool has 6 classes from 0 (no visible signs of RD) to 4 (ulceration, bleeding, necrosis) and separates patchy moist desquamation from confluent moist desquamation.19,24 For the development of the USCOM algorithm, the advisors opted to use the CTCAE v5 grading system for acute RD.24
Clinical evidence from topical treatments on the efficacy for acute RD reduction was graded using a pre-established grading system (American Academy of Dermatology evidence-based guideline development process).17 This grading system rates study types ranging from level A (clinical double-blind RCT of high quality), B (RCT of lesser quality), or C (Comparative trial with severe methodologic limitations). The grading system further rates the likelihood of changing confidence in the study's measured effect (level 1–unlikely to level 4– very uncertain). The chosen grading system is relevant for clinical algorithm development and considers the development of knowledge in a fast-evolving field. The panel graded the evidence on topical treatment and skin care for RD.17
The multidisciplinary USCOM panel of physicians with expertise in oncodermatology and radiation oncology from 4 academic medical centers in the US developed the algorithm based on their research and clinical expertise and a detailed discussion of peer-reviewed literature. Given the lack of studies on skin care, the advisors graded the evidence on components of skin care as "useful" (Table 2A) or "not useful" (Table 2B) for RD. Furthermore, the advisors graded skincare products based on their composition and evidence to support healthcare providers in making an informed choice when recommending skincare products for their patients. Finally, the advisors drafted an algorithm aiming to minimize toxicity during RT, reduce inflammation, and minimize the extent of acute RD with topical treatments and skincare regimens before, during, and after RT.
