Suche
reference
Zhao H, Zhu W, Zhao X, et al. Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy:a double-blind, placebo-controlled, randomized phase 2 clinical trial.JAMA Dermatol.2022;158(7):779-786.
Study objective
To determine whether a topical green tea extract solution containing epigallocatechin-3-gallate (EGCG) can reduce the incidence of radiation-induced dermatitis (RID) in breast cancer patients undergoing radiation therapy after surgery
Key to take away
Prophylactic use of topical EGCG solution reduced the frequency and severity of RID in patients undergoing adjuvant radiotherapy for breast cancer.
design
Double-blind, placebo-controlled, randomized phase II clinical trial
Participant
The study included women aged 18 years and older with histologically confirmed breast cancer who received postoperative radiation therapy between November 2014 and June 2019. Of the 180 eligible patients (age 26–67 years, mean age 46 years), 111 were treated with EGCG. and 54 were treated with placebo; these 165 were included in the final data set.
There were no restrictions regarding neoadjuvant or adjuvant chemotherapy. Exclusion criteria included patients with unhealed wounds in the radiation area and patients who received anticancer therapies other than concurrent endocrine or anti-ERBB2/HER2 therapy or had known hypersensitivity to EGCG.
intervention
Participants were randomly assigned (2:1) to receive either an EGCG solution (600 µmol/L) or a placebo (0.9% sodium chloride (NaCl) saline) sprayed over the entire irradiation field three times daily from the second day of irradiation to weeks after completion of irradiation.
Evaluated study parameters
Patients reported RID-related symptoms (including pain, burning, itching, pulling, and tenderness) once per week using the Skin Toxicity Assessment Tool (0 = no symptoms; 5 = the worse symptoms). The highest score on each assessment was considered the highest symptom score.
Primary outcome
The primary endpoint was the incidence of grade 2 or worse radiation-induced dermatitis as defined by the Radiation Therapy Oncology Group Scale. Secondary endpoints included radiation-induced symptom index, changes in skin temperature measured by infrared thermal imaging, and safety.
Key findings
Of participants treated with EGCG topical solution, 50.5% had RID grade 2 or worse, versus 72.2% of participants treated with placebo, which was statistically significant (P=0.008). Secondary outcomes included a significantly lower symptom index in the EGCG group.
transparency
Dr. Zhu was supported by the National Natural Science Foundation of China, the Jinan Science and Technology Plan Project (202019163), and the Science and Technology Project of Traditional Chinese Medicine of Shandong Province (2021M013). Prof. Yu was supported by the Academic Promotion Program of Shandong First Medical University (Shandong Academy of Medical Sciences) (2019ZL002) and the Innovation Project of Shandong First Medical University (Shandong Academy of Medical Sciences) (2019-04). Dr. H. Zhao was supported by Shandong Provincial Natural Science Foundation (No. ZR2016HM35). The authors did not disclose any conflicts of interest.
Implications and limitations for practice
Breast cancer accounts for approximately 30% (or 1 in 3) of all new cancer diagnoses in women each year.1
Radiation therapy is an essential part of the treatment plan for patients following breast-conserving surgery or, in certain cases, mastectomy, to improve local control and overall survival.2RID occurs in 95% of breast cancer patients3and is characterized by pain, ulceration, swelling, itching and burning of the skin in the radiation field as well as physical and psychological complaints.4The risk of severe RID is interruption or premature cessation of radiation treatment, which may compromise outcomes and impact patients' quality of life during and after treatment.5
Radiation therapy affects the anatomy and physiology of the skin by causing DNA damage that disrupts the skin's normal cell turnover.6In addition, there is an inflammatory reaction in the skin with the release of histamine and serotonin, as well as a vascular reaction that leads to capillary dilation in the dermis. The skin reacts to radiation with redness (erythema), changes in skin pigmentation, hair loss and the destruction of sweat and sebaceous glands.7
Recent advances in radiation techniques may reduce the occurrence and severity of radiation-related skin reactions. Skin-sparing techniques, including intensity-modulated radiation therapy, hypofractionated radiation therapy, accelerated partial breast irradiation, simultaneous integrated boost, and prone positioning, have consistently demonstrated a reduction in radiation dermatitis rates.8
There is no consensus on the prophylaxis and treatment of RID. However, evidence-based guidelines have been published that emphasize washing the skin with mild soap and using barrier products (such as Aquaphor) after any radiation treatment to create a moist environment to promote wound healing, and/or using a steroid cream.6
This study examined the use of a topical green tea extract solution (EGCG) sprayed on the breast area undergoing radiation therapy compared to placebo. Previous studies have shown that EGCG facilitates the healing process of erythema in human skin caused by ultraviolet radiation.9EGCG has also been shown to improve skin cell viability and reduce apoptosis induced by ionizing radiation.10Additionally, EGCG has been shown to promote skin wound healing through antioxidant, anti-inflammatory, antimicrobial, and antifibrotic effects.11
The results of the study showed significant improvement over placebo in patients who used the EGCG spray.12Given that there are common practices and guidelines but no high-level, evidence-based standards for the prevention of RID,12The implications of this study are important, particularly for the patient population that prefers natural therapeutic interventions as much as possible.
The study has some important limitations. The placebo was a saline spray, and researchers did not allow any topical lotion or agent during radiation therapy.12The saline spray is not considered an evidence-based recommendation for RID prevention, nor is the ban on the use of barrier creams.13To better understand the effectiveness of EGCG, it would be helpful to compare the topical EGCG solution with evidence-based prevention measures commonly used in practice.
Additionally, the study does not specify whether the spray was used every day before or after radiation, only that it was used three times daily.12Other research has shown that EGCG can reach all layers of skin in a cosmetic formulation.14Therefore, it is unknown whether the antioxidant effects of EGCG could potentially interfere with DNA damage to cancer cells, thereby potentially reducing the effectiveness of radiation therapy. In a patient whose intended radiation field is relatively superficial, EGCG could theoretically interfere.
Another limitation is the form of radiation therapy used, conventional fractionated radiation therapy. In contrast, hypofractionated radiation therapy is now more commonly used and tends to result in lower RID rates.15The researchers plan to evaluate topical EGCG in prospective studies in patients undergoing hypofractionated radiation therapy.
Finally, the EGCG solution was prepared fresh daily, which may not be practical for a patient, and it is unlikely that a patient can achieve the same concentration as the preparation used in the study.
Ideally, physicians should inform patients about both the evidence for an intervention such as topical EGCG and the limitations of the research. Additionally, it is important that radiation oncologists be included in the discussion about which natural therapeutics patients may want to use during radiation therapy. Finally, a more cautious approach is to instruct patients to apply topical agents every day after radiation treatment and to wash them well with soap and water before radiation treatment the next day to minimize potential interference with radiation therapy.