Title : Radiation-induced skin toxicity in breast cancer patients: A systematic review of randomized trials
Background: Skin toxicity is one of the most common side effects of Radiation Therapy (RT) in breast cancer patients, and is associated with increased morbidity. Almost 30% of patients receiving RT experience radiation dermatitis (RD); however, no definitive guidelines are available its management with treatments being variable among institutions. Furthermore, RD may differ according to the RT delivery technique. This review evaluates the methods and findings of randomized trials examining the different management strategies for RD.
Methods: Medline, Cochrane, and Embase databases were searched up to August 2017. Randomized trials that compared the effects of ≥ 2 treatments for RD in breast cancer patients who received external beam RT were eligible. Review articles, retrospective studies, case reports, case series, and nonrandomized trials were excluded. Studies of patients with cancer other than breast cancer were excluded, as were studies of intraoperative radiotherapy.
Results: After application of the eligibility criteria, a total of 96 out of 3534 studies were included in the final analysis. Of these, 27 assessed the skin toxicity associated with different modes of RT delivery. Patients who underwent intensitymodulated radiation therapy (IMRT) in all studies experienced significantly less RD compared with those receiving conventional RT. Five studies compared accelerated partial breast irradiation (APBI) and whole-body irradiation (TBI). Although 4 found that patients receiving accelerated partial breast irradiation (APBI) experienced less RD, the fifth and largest study reported significantly worse skin toxicity. One study reported significantly milder skin reactions for patients treated in the supine position, but was contradicted by another study that found the prone position was associated with less RD. Patients receiving simultaneous boost experienced significantly less RD than those treated with sequential boost. Fifty studies compared the effectiveness of various topical products for the prevention and treatment of RD. These included nonsteroidal creams and ointments, steroid and hormone-based creams, barrier products, hyaluronic acid (HA) cream, aloe vera gel, nonmetallic powder, and silver sulfadiazine cream. Among the nonsteroidal creams, oil-inwater emulsions, aqueous creams, and heparinoid cream were significantly better than no treatment in preventing RD. Recombinant human epidermal growth factor cream, boron-based gel, and sucralfate cream were superior to placebo creams. Topical steroid treatments were shown to be more effective than no treatment, emollients, aqueous creams, and petrolatum gel in preventing RD. Several barrier products demonstrated efficacy in preventing and treating RD. The most common scale used to rate skin toxicity where RTOG (n=39) and CTCAE (n=24).
Conclusion: The development of new topical treatments and supplements for the prevention and treatment of RD has been slow. None of the products have been consistently proved effective across large, randomized studies. However, modes of RT delivery such as IMRT and hypofractionation are now widely used and have been shown to decrease skin toxicity. Other methods of positioning might also cause less RD than conventional treatments. Moving forward, continued research into improved modes of RT delivery in addition to products aimed at RD prophylaxis or treatment are important in reducing RD incidence and severity in breast cancer patients.