Although the majority of skin reactions heal within several weeks from completion of therapy, skin reactions may cause distressing symptoms to patients, and occasionally may be dose limiting or cause a therapy break (Banning, 2011). An extensive range of topical agents and dressings have been studied for prevention and management of radiodermatitis (Feight et al., 2011). For example, corticosteroid products have been tested in a few clinical trials, but so far, no clear benefits regarding the effect on ARSR have been demonstrated (Feight et al., 2011; Miller et al., 2011). The effects of Aloe Vera products have also been investigated in randomized controlled trials (RCTs) but failed to show significant benefits in preventing or minimizing ARSR (Hoopfer et al. 2015). Other types of products containing such agents as sucralfate, urea and hyaluronic acid have shown no or limited positive effects in preventing or reducing ARSR (Pinnix et al., 2012).
The effects of skin care products containing Calendula officinalis (marigold plant) on ARSR in patients with breast cancer have been investigated by Pommier and colleagues (2004) and also Sharp and colleagues (2013,a). In Pommier’s study, patients in the experimental group, treated with Calendula cream had a statistically significant lower incidence of severe ARSR, pain and treatment interruptions in comparison with the patients in the control group, treated with trolamine. However, Sharp and colleagues (2013) did not find any differences in ARSR between patients randomized to two groups using either Calendula or Essex cream (i.e. an aqueous, moisturizing cream). These results called for further investigations. Therefore, we designed and conducted a randomized, open-label study to test whether skin care using topical Calendula officinalis was superior to aqueous cream (Aquaphor)/Aloe Vera in reducing the risk of severe ARSR in patients with breast cancer treated with adjuvant RT. We had also learned from the literature (Schurn et al. 2011) that only a few studies had been conducted on acute toxic effects experienced and assessed by patients undergoing curative RT and that there was a need for close investigation on the skin assessment scale in use.
The purpose of this study was to describe the skin toxicity assessments in breast cancer patients treated with radiotherapy, and the level of agreement and variability between observers’/ investigators’ scorings. The objective was to evaluate up- or downgrading in the prospectively collected data on acute toxic effects, photos and patient-reported outcomes in our randomized, open-label study comparing Calendula versus Aquaphor/Aloe Vera.
Methods: In our study, skin assessments were conducted weekly (weeks 0 – 7) using the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria and documented in the data collection tool by four RT nurses of our research team. An educational session was organized for these nurses, prior to the study, regarding the data collection and the RTOG Acute Radiation Morbidity Criteria, and including photos of skin reactions. All nurses of the research team completed a written quiz and scored correctly at least 85% or higher of the skin assessments. A refresher education was organized annually.
The RTOG scale grades ARSR from 0 to 4 (0= No change over baseline; 1= Follicular, faint, or dull erythema; epilation, dry desquamation, or decrease in sweating, 2= Tender, bright erythema; patchy, moist desquamation or moderate edema, 3= Confluent, moist desquamation other than skin folds; pitting edema, 4= Ulceration, hemorrhage, necrosis). In this study, we used the RTOG scores and digital photos that were taken of the treatment area on weeks 0, 2, 4, 6. The digital photos were reviewed and scored, using the RTOG, by a radiation therapy RN, physician/Radiation Oncologist and a research nurse.
Self-reported skin care, reactions and symptoms from the irradiated area (i.e. skin reactions, sensation, skin color and pain) were documented in a home journal weekly by patients. The data from the patients’ perspectives in this study were comprised of the documented skin reactions (i.e. reactions= yes or no; sensation/itchy skin=no, slight/mild, very; color=no, pink, red, very red, brown; pain=no, mild, moderate, severe) during weeks 2, 4 and 6.
Descriptive statistical methods were used. Interobserver variability was calculated using Cohen’s and Fleiss’ Kappa methods and correlations were determined with Spearman’s correlation test. P–values of <.05 were considered statistically significant. The analyses were performed using the Statistical Analysis System (SAS) Version 9.1 and Statistical Package for Social Sciences (SPSS) Version 17.0.
Results: Patients (n=148) were enrolled between 4/10/13 – 3/8/16 and randomly assigned to the usual care (Aloe Vera/Aquaphor, n= 71, 48%) or intervention (Calendula, n= 77, 52.0%) groups. The women were primarily Caucasian (99.3%) with fair skin type (79.7%). Average age was 60.7 years (SD 9.25) with a BMI of 30.9 kg/m2. They used the skin care products an average of 30 days and spent 33 days in the study. More than one in five subjects (22.1%) received silver sulfadiazine ointment for skin irritation over the course of radiation therapy and 4.2% experienced a break in radiation treatment. The majority of subjects (99%) reported daily skin cleaning per instructions, but adherence was reduced towards the end of the treatment. Self-reported skin reactions increased from 14% at week 1 to 80% by weeks 5 and 6. Most women (88% - 98%) reported no/or mild pain throughout the treatment.
No RTOG changes (99.3%) were documented during the appointment at week 0. However, the scores indicating follicular faint erythema increased during week 2 (29.1%) and week 4 (62.8%). At week 6, the documented scores indicated that all study subjects had skin reactions (follicular faint erythema= 42%, tender or bright erythema = 50%, confluent, moist desquamation=8%). The calculated interobserver variability decreased from moderate to fair agreement (Week 0: Fleiss’ Kappa=0.328, p<.000; Week 2: Fleiss’ Kappa=0.464, p<.000; Week 4: Fleiss’ Kappa=0.292, p<.000; Week 6: Fleiss’ Kappa=0.266, p<.001). Upgrading or downgrading the RTOG scores was more common during weeks 4 and 6. Over half of the study subjects (64%) reported no skin reactions during week 2, however over half had documented reactions during week 4 (77.4%) and week 6 (72.4%). Skin sensation changes were rare during week 2 (slight/mild=22.5%), but these increased during week 4 (slight/mild=63.2%) and week 6 (slight/mild=51.7; very=3.4%). Over half of the study subjects reported skin color changes during week 2 (no change=39.4%, pink=49.2%, red=10.6%, brown=0.8%), and these changes increased during week 4 (no change=5.1%%, pink=55.6%, red=34.2%, very red =4.3%, brown=0.9%), and week 6 (no change=9.7%%, pink=38.7%, red=35.5%, very red =12.9%, brown=3.2%). The documented RTOG scored correlated positively and significantly, but weakly with the self-reported skin reactions during weeks 2 and 4 (week 2: r=0.273, p<.01, week 4: 2=0.251, p<.05), self-reported skin reactions during week 4 (r=0.197, p<0.05) and self-reported skin color changes during week 2 (r=0.232, p<0.05)
Conclusion: The results of this study demonstrate that the rating criteria of the RTOG scale are likely to be interpreted subjectively, especially during longitudinal observations when there are more acute radiation skin reactions. The education that was organized to the nurses of our research team may have decreased the variability between the documented scores and the scorings of the digital pictures. However, the variability and the upgrading or downgrading of the RTOG scores increased during weeks 4 and 6. The self-reported skin reactions supported the documented RTOG scores, but strong associations were not demonstrated. We conclude that more research is needed to determine the best, objective measures to evaluate radiodermatitis, including the experiences from a patient perspective.
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