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Effect of an Essential Oil Mixture on Skin Reactions in Women Undergoing Radiotherapy for Breast Cancer: A Pilot Study Margo A. Halm, Clarice Baker and Val Harshe J Holist Nurs published online 25 March 2014 DOI: 10.1177/0898010114527184 The online version of this article can be found at: http://jhn.sagepub.com/content/early/2014/03/20/0898010114527184
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527184
JHNXXX10.1177/0898010114527184Journal of Holistic NursingEssential Oils for Radiation-Associated Skin Reactions /Halm et al.
1
Quantitative Research
Effect of an Essential Oil Mixture on Skin Reactions in Women Undergoing Radiotherapy for Breast Cancer A Pilot Study
jhn
research-article2014
Journal of Holistic Nursing American Holistic Nurses Association Volume XX Number X XXXX 201X 1–14 © The Author(s) 2014 10.1177/0898010114527184 http://jhn.sagepub.com
Margo A. Halm, RN, PhD, ACNS-BC Salem Hospital, Salem, OR
Clarice Baker, CCAP, OTR/L, NCTMB Sholom Home East, St. Paul, MN
Val Harshe, BS, RT(T) University of Minnesota Physicians, Minneapolis, MN
Purpose:This pilot study compared the effects of an essential oil mixture versus standard care on skin reactions in breast cancer patients receiving radiation. Method: Using an experimental design, 24 patients were randomized to standard care (i.e., RadiaPlexRx™ ointment) or an essential oil mixture. Products were applied topically three times a day until 1 month postradiation. Weekly skin assessments were recorded and women completed patient satisfaction and quality of life (QOL) instruments at 3-, 6-, and 10-week intervals. Results: No significant differences were found for skin, QOL, or patient satisfaction at interim or follow-up time points. Effect sizes were as follows: skin = .01 to .07 (small-medium effect); QOL = .01 to .04 (small effect); patient satisfaction = .02 (small effect). Conclusion: The essential oil mixture did not provide a better skin protectant effect than standard care. These findings suggest the essential oil mixture is equivalent to RadiaPlexRx, a common product used as standard care since it has been shown to be effective in protecting skin from radiation. Thus, this pilot provides evidence to support botanical or nonpharmaceutical options for women during radiotherapy for breast cancer. Keywords: essential oils; radiation-associated skin reactions; breast cancer population
In 2011, the American Cancer Society estimated 230,480 new invasive breast cancer diagnoses. Prognosis of breast cancer depends on disease stage at the time of diagnosis. Women diagnosed with breast cancer usually undergo surgical resection, often followed by chemotherapy and/or a course of radiation therapy via external beam therapy. Radiation to the breast is almost always recommended after a lumpectomy, and in some circumstances, following mastectomy. The mode of radiation therapy depends on the type and stage of cancer. Radiation treatments typically begin 1 month following surgery and last for 5 to 7 weeks (American Cancer Society, 2012).
Skin reactions are a common problem associated with radiation. The incidence of such reactions in women undergoing radiotherapy for breast cancer ranges from 87% to 96% (Fisher et al., 2000; Porock
Authors’ Note: This study was funded in part by the United Hospital Foundation. The authors would like to acknowledge Basia Lutz, RN, BSN, for her dedication to data collection, as well as Kathryn E. Farniok, MD, and Mark Palmer, MD, at the St. Paul Cancer Center. The authors would also like to thank MPM Medical Inc. for donating the RadiaPlex for this study; this donation did not influence study design or analysis. Please address correspondence to Margo A. Halm, RN, PhD, ACNS-BC, Salem Hospital, 890 Oak St. SE, Salem, OR 97301; e-mail: [email protected].
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2 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
& Kristjanson, 1999). Such reactions vary from mild erythema to brisk moist desquamation or even ulceration and, thus, may be associated with mild to severe pain. Skin reaction severity is influenced by factors such as anatomic treatment area; radiation energy, fractionation, and total dose; concomitant chemotherapy; and patient differences like skin complexion, obesity, bra/cup size, and smoking history (Blackmar, 1997; Porock, Kristjanson, Nikoletti, Cameron, & Pedler, 1998; Richardson, Smith, McIntyre, & Pilkington, 2005; Sitton, 1992; Wells & McBride, 2003). Typically, radiation reactions appear between 10 and 14 days from beginning of therapy and continue to increase in severity until treatment is completed. The symptoms associated with these skin reactions may affect patient tolerance and compliance with radiation, potentially reducing the effectiveness of treatment (Knobf & Sun, 2005).
Background While topical applications to treat radiation skin toxicity have been used in clinical practice, supporting evidence for these therapies is limited (Porock & Kristjanson, 1999; Wheat, Currie, & Coulter, 2006). Few studies have been conducted to test the effectiveness of topical applications containing herbal extracts or oils to reduce radiotherapy skin reactions in breast cancer patients. Pure essential oils are distillates from aromatic plants and often carry the same physiological or psychological effects of the plant from which they are derived. Topical essential oil or botanical preparations tested in animal models include evening primrose and Aloe vera, whereas wheatgrass, calendula, chamomile, and Aloe vera gel have been studied in clinical trials. In one animal study, Morris et al. (1997) studied cell proliferation in large female white pigs receiving daily application of 10% evening primrose oil and lioxasol (a compound used for radiation burns). Pigs treated with evening primrose had more pronounced proliferative cell activity, increasing the size of the epidermis at 6 weeks, suggesting this botanical modulated the skin’s response to radiation. In a second animal model, Aloe vera (oral administration) significantly accelerated wound contraction, inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of transforming growth factor β-1 and basic fibroblast growth factor in radiation-delayed wound healing (Atiba et al., 2011).
Four clinical trials examined the effects of Aloe vera gel on radiation skin reactions. Heggie et al. (2002) compared TID application of Aloe vera to aqueous cream (N = 225) throughout the treatment period and for 2 weeks after radiation therapy. Aqueous cream was significantly better than Aloe vera gel in reducing dry desquamation and treatment-related pain. Subjects in the Aloe vera group who underwent axilla surgery also experienced more pain, erythema, and itching. However, nonchemotherapy patients receiving Aloe vera had a reduced incidence of moderate erythema. Williams et al. (1996) also reported no difference between Aloe vera and control subjects on skin reaction in two trials (N = 194, N = 108). The final Aloe vera trial (Olsen et al., 2001) compared skin reactions in 73 patients who cleansed with a mild unscented soap versus those who liberally applied Aloe vera gel after radiation. No difference in skin reactions between groups was found at low cumulative doses (90% interrater reliability in skin assessments. Skin Diary. In a formal skin diary, women recorded the number of daily topical applications through the duration of the study. If more or less than three applications were used, women documented the reason as well as any other topical products (and number of applications) used on their breast tissue. Women were instructed to bring their diary each week to review so compliance could be reinforced as well as at the final 1-month follow-up appointment. Pain Visual Analog Scale. A 100-mm visual analog scale (VAS) was used to evaluate pain. The VAS was anchored by terms including “the least pain felt in my breast” and “the worst pain felt in my breast.” Women were requested to place a line across the VAS at a point that represents their intensity of pain at that moment in time. Measurements were taken each week during a radiation visit and at the 1-month follow-up appointment (Week 10). Responses were scored by measuring the distance from the lower anchor point to the subject’s mark across the line (Cline, Herman, Shaw, & Morton, 1992). Studies have shown vertical lines are more sensitive and easier to use, especially for those under stress or with a narrowed visual field (Gift, 1989). The VAS has ½ inch perpendicular lines placed at the end, since Edwards, Herman, Wallace, Paw, and Paw (1991) found subjects marked off the scale unless such lines were present. No intermediate marks, gradations, or terms were placed on the VAS since it has been argued that using gradations decreases sensitivity, imposes another’s language on the subjects, and requires a higher reading level (Gift, 1989). Reliability is a strength of this measurement approach (Bjur, Silver, & Gallagher, 2001; Gallagher, Liebman, & Bjur, 2001). When subjective experiences are reported on the VAS, subjects need
to be in a sitting position since reliability is reduced in the supine position (Edwards et al., 1991). Quality of Life Index (QLI). The QLI-Cancer version contains 33 items that measure satisfaction with four life domains: (a) health/functioning, (b) psychological/spiritual, (c) social/economic, and (d) family. The reported internal consistency reliability of the overall QLI was 0.95. Coefficients of .90, .93, .84, and .66 were reported for the four subscales as listed above, respectively. Support for concurrent validity has been provided by a strong correlation (r = .80) between the QLI and a measure of life satisfaction (Ferrans, 1990). Women completed the QLI at baseline, at the end of radiation therapy (6 weeks), and on 1-month follow-up. In addition, women completed five items pertaining to skin changes associated with radiation from the European Organization for the Research and Treatment of Cancer (EORTC) Core QOL Questionnaire to assess disease-specific indicators. These items specifically were rashes, dryness, sweating, painful skin, and skin ulcers. Reliability of the physical functioning scale ranges from .75 to .77, whereas reliability coefficients for the pain symptom scale ranges from .75 to .87 (Kaasa et al., 1995). Patient Satisfaction. A patient satisfaction item was developed to evaluate topical skin applications. On a 5-point Likert-type response format, women reported their level of satisfaction with the topical preparation used to prevent and treat skin changes during the course of their radiation at 3 weeks, 6 weeks, and 10 weeks (1-month follow-up). Reliability testing was not possible since a single question about satisfaction was asked.
Procedure Once the study was reviewed and approved by the institutional review board, potential subjects were identified from the clinic roster. As new breast cancer patients presented for radiation treatment, clinic nurses screened them to ensure inclusion/ exclusion criteria were met. Patients who met the criteria were invited to participate in the study at their initial appointment for treatment planning. After informed consent was obtained, baseline measures were obtained by the study RN.
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6 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
After baseline measures, the clinic manager randomly assigned subjects using a computerized list of random numbers to one of two groups: (a) control group (RadiaPlexRx ointment TID) or (b) experimental group (essential oil blend TID). Subjects then received a patch test of the two topical applications on their forearm. A double-strength concentration of the essential oil blend and regular strength concentration of RadiaPlexRx were used for patch testing. To allow time for delayed hypersensitivity to present, the RN assessed the forearm for signs of sensitivity (e.g., erythema) at a radiation visit 48 hours later. If no sensitivities were found, women were provided with an initial 2-ounce supply of their assigned product in a concealed bag. Subjects were instructed to request additional supplies of their product at future appointments when their supply was low. This procedure was used to promote uniform product integrity, as the chemistry of essential oils may change with exposure to heat and light. Blinding of the skin preparations, to either the subjects or data collectors, was not possible due to the strong smell/odor of the treatment product. Patient education included teaching women to apply the oil to cover the entire radiation site TID (i.e., morning, mid day, before bed) until their 1-month follow-up appointment. However, women were instructed to remove their assigned product with soap and water immediately prior to all radiation treatments. Other safety precautions emphasized that the product was for topical use only and the importance of keeping the container out of reach of children, and the cap screwed on tightly when not in use. Women were also advised to wash their hands after application to avoid getting the oils in their eyes. In the event of eye exposure, women were instructed to flush their eye with vegetable oil for 5 minutes, followed by water prior to seeking medical attention. If pronounced negative reactions were experienced, women were instructed to discontinue the applications and report these reactions to the clinic.
missing values following best-practice recommendations (Graham, 2009). Missing data were imputed using the IVEWare (Raghunathan, Solenberger, & Van Hoewyk, 2002), which uses all available data to impute missing data via a sequential regression approach. The observed and imputed data were compared to ensure they showed similar distributions (Abayomi, Gelman, & Levy, 2008). Missing data points were replaced with imputed data in 20 data sets, which were analyzed separately. Model parameters and standard errors, which incorporate within and between model parameter variability, were combined following Rubin (1987). Preliminary Analyses. We examined the distribution of variables and evaluated potential sources of nonindependence. No evidence of substantial skew or kurtosis was detected and thus approximated normal distributions. We tested if conditions differed at baseline on outcomes and demographic variables reported in Table 2 to test whether randomization created equivalent groups. The groups did not statistically differ on any measure. However, the trend level differences in pain (p = .09) was associated with a large effect size (Cohen’s d = .70). Analytic Models. Skin ratings were the main study outcome; QOL total score and patient satisfaction were secondary outcomes. Analysis of covariance models (ANCOVA) were used to examine group differences in skin, QOL, and patient satisfaction ratings at the interim (3 weeks for skin and patient satisfaction ratings, 6 weeks for QOL ratings) and follow-up assessments (6 weeks for skin and patient satisfaction ratings, 10 weeks for QOL ratings) with study condition as a two-level predictor (1 = experimental, 0 = control) and baseline measures of the outcome (except for patient satisfaction) and pain ratings as covariates.
Results Description of the Sample
Statistical Methods Missing Data. Rates of missing data ranged from 4% to 17% at baseline, 8% to 17% at interim, and 17% to 25% at the follow-up assessment. Of the 24 subjects, 12 (50%) provided complete data. Failure to provide data was not related (at p > .10) to any of the measures. Multiple imputation was used to replace
A total of 24 subjects were enrolled in this pilot study. The control and experimental groups were composed of 11 and 13 subjects, respectively (Figure 1). No women reported allergies during the consent process. In addition, no sensitivities to the essential oil or RadiaPlexRx ointment were found through patch testing. As shown in Table 2, no
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 7 Table 2. Sample Characteristics (N = 24) Control (n = 11)
Experimental (n = 13)
Mean
SD
Mean
SD
t Value
p Value
55.91 28.41 2.55 4.80 5545.50
12.35 8.48 0.82 4.78 438.75
55.92 29.36 2.39 19.39 5398.92
10.89 5.12 0.77 27.96 507.19
0.01 0.34 0.50 1.85 .717
.10 .74 .63 .09 .48
n
%
n
%
χ2
p Value
Chemotherapy (% yes) Tumor history Infiltrating ductal Lobular Other Bra size 34 or smaller 36 38 40 42 44 or larger
3
27.30
3
25.00
0.01 1.23
7 1 3
63.64 9.09 27.27
9 0 4
69.23 0.00 30.77
2 3 3 1 0 1
18.2 27.27 27.27 9.09 0.00 9.09
1 3 3 2 3 0
7.69 25.00 25.00 15.38 25.00 0.00
.90 .54 .48
Age Body mass index Pathak Scale Baseline pain Total cumulative radiation dose
4.52
significant differences were found in the demographic and baseline clinical characteristics between groups. No women reported allergies during the consent process. In addition, no sensitivities to the essential oil or RadiaPlexRx ointment were found through patch testing.
Aim 1: Differences in Skin Reactions, QOL Perceptions, and Patient Satisfaction The first primary aim of this pilot study was to determine if significant differences existed in the degree of skin reaction, patient satisfaction, and QOL in breast cancer patients undergoing radiotherapy who use RadiaPlexRx ointment (standard care) versus an essential oil blend (experimental treatment). Descriptive statistics of the skin, patient satisfaction, and QOL measures (baseline, interim, and follow-up) and results of the ANCOVA models are reported in Tables 3 and 4, respectively. Examination of group means shows an increase in skin and QOL ratings for both groups, and a slight decrease for both groups in patient satisfaction. Results of the test of group differences are shown in Table 4. The parameter estimates indicate how much an outcome for the experimental group
changes in relation to the control group at the interim and follow-up assessment after adjusting for baseline differences in the outcome and pain scores (with the exception of satisfaction which only adjusts for baseline pain scores). Overall, results indicate no group differences in the mean covariate adjusted study outcomes at the interim or follow-up assessments. The models were run again, but with available data only (i.e., not using imputed data). The direction and magnitude of the means were similar to the results of the imputed data and no significant group differences were found. In addition to this main analysis, t tests explored disease-specific QOL outcomes in the two groups (Table 5). Trends were observed in three diseasespecific outcomes, although these were not significant (p > .05). First, rash ratings were higher in control subjects at both 6 and 10 weeks compared with the experimental group. Painful skin ratings were also slightly higher in control subjects at Week 6, but skin ulcer ratings were higher in experimental group at Weeks 6 and 10.
Aim 2: Estimation of Effect Sizes A second primary aim was to estimate effect sizes that could be used for sample size calculations for a
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8 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
Enrollment
Assessed for eligibility (n = 36) Excluded (n = 9) Not meeting inclusion criteria (n = 0) Refused to participate (n = 9) Other reasons (n = 0)
Analysis
Follow up
Allocation
Randomized (n = 27) Allocated to intervention (n = 12)
Allocated to intervention (n = 15)
Received allocated intervention (n = 12)
Received allocated intervention (n = 15)
Did not receive allocated intervention (n = 0)
Did not receive allocated intervention (n = 0)
Lost to follow up (n = 0)
Lost to follow up (n = 0)
Discontinued intervention (n =1) (skin treatment perceived as too oily)
Discontinued intervention (n = 2) (disliked smell of essential oil mixture)
Analyzed (n = 11)
Analyzed (n = 13)
Excluded from analysis (n = 0)
Excluded from analysis (n = 0)
Figure 1. CONSORT Diagram
larger clinical trial testing this essential oil intervention. As shown in Table 4, effect sizes for the main study outcomes for the interim and follow-up assessments range from .01 to .07 for skin ratings (representing a small to medium effect), .01 to .04 for QLI ratings (representing a small effect), and .02 for patient satisfaction ratings (representing a small effect).
Aim 3: Feasibility Assessment The third primary aim was to evaluate the feasibi lity of implementing this new intervention for breast
cancer patients undergoing radiation. Feasibility assessment focused on assessing factors that affected implementation, including recruitment and availability of subjects; randomization; acceptability of the intervention to patients/caregivers; adherence and safety aspects of the intervention; retention rates; and adequacy and utility of study measures. Accrual into the pilot was smooth, with ample numbers of women to recruit most likely due to the large number of women treated for breast cancer at this cancer center. No women were excluded from the study during recruitment as no sensitivities were
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 9 Table 3. Descriptive Statistics Control Group (n = 11)
Interima
Baseline
Experimental Group (n = 13) Follow-Upb
Interima
Baseline
Follow-Upb
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Skin rating Quality of life Patient Satisfaction
0.14 4.95 NA
0.20 0.65 NA
0.73 4.91 4.42
0.29 0.75 0.75
1.65 5.06 3.76
0.60 0.62 1.36
0.28 5.18 NA
0.31 0.64 NA
0.73 5.19 4.09
0.41 0.85 1.20
1.38 5.31 3.98
0.65 0.58 0.94
Note: SD = standard deviation; NA = not assessed. a. Interim: 3 weeks—Skin rating and patient satisfaction; 6 weeks—Quality of life. b. Follow-up: 6 weeks—Skin rating and patient satisfaction; 10 weeks—Quality of life.
Table 4. Results of Analysis of Covariance Models (ANCOVA) Interim Test Statistics Skin rating Quality of life Patient satisfaction
Follow-Up Test Statistics
Est.
SE
t Value
p Value
η2
Est.
SE
t Value
p Value
η2
−0.04 0.04 −0.21
0.16 0.24 0.47
−0.24 0.15 −0.45
.81 .88 .64
.01 .01 .02
−0.34 0.09 0.30
0.28 0.24 0.53
−1.21 0.40 0.57
.23 .69 .57
.07 .04 .02
Note: Est. = parameter estimate; η2 =eta-square, measure of effect size (.01 small, .06 medium, .14 large). Means, standard deviations, and effect sizes are averaged across the 20 imputed data sets. Parameter estimates and corresponding test statistics are pooled across the 20 imputed data sets.
Table 5. Disease-Specific QOL Items (N = 24) Control Group (n = 11) Rash Week 6 1 Month follow-up Dryness Week 6 1 Month follow-up Sweating Week 6 1 Month follow-up Painful skin Week 6 1 Month follow-up Skin ulcers Week 6 1 Month follow-up
Experimental Group (n = 13)
Mean
SD
Mean
SD
2.67 1.73
1.32 1.10
1.90 1.44
0.88 .53
2.00 1.91
1.00 0.70
2.30 1.67
1.16 0.71
1.67 1.82
1.00 0.98
1.80 1.78
1.23 0.97
2.67 1.78
1.00 0.67
2.60 1.78
1.17 0.67
1.22 1.09
0.44 0.30
1.40 1.22
0.52 0.67
detected to the essential oil mixture during the patch testing procedure. Randomization into treatment groups also did not pose challenges. No subjects refused to participate due to group assignment. Only two women randomized to the experimental group
p .16 .46 .56 .45 .80 .93 .90 .68 .43 .57
dropped from the study (Week 1 and Week 3) due to dislike of the smell of the essential oil mixture. In total, three subjects withdrew from the study (1 control and 2 experimental). Therefore, the overall retention rate was 87.5%. Nurses in the cancer
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10 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX Table 6. Protocol Adherence and Use of Additional Topical Applicationsa by Group (N = 24) Average Adherence Control group (n = 11) Adherence to TID application Additional topical applications Experimental Group (n = 13) Adherence to TID application Additional topical applications
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
64% 1
64% 1
64% 0
60% 18
60% 27
71% 19
60% 28
81% 2
55% 2
78% 8
78% 24
55% 44
45% 66
40% 57
Overall Adherenceb 63% 94 62% 203
a. Ointments (analgesic, antibiotic, Benadryl, Cortisone, Silver Sulfadiazene); Emollients (Aquaphor, Aloe Vera); Silicone gel pads; Vigilon; unspecified oils; unspecified products. b. Chi-square analyses nonsignificant (p values = .19-.97).
center also viewed the essential oil mixture as an acceptable intervention to test in this patient population, as evidenced by their active involvement in executing the study protocol. Other aspects of the acceptability of the intervention include clarity of the protocol as well as appropriateness of the dose and safety. Women were instructed to apply the essential oil mixture or RadiaPlexRx TID, congruent with what is prescribed in actual practice today as well as with clinical trial investigations of various skin prevention protocols in this population. While women did apply additional products to their breast tissue over time, this practice is customarily seen with radiation treatment and, therefore, may not be a direct indication of the appropriateness of the intervention dose. As skin reactions begin to occur over the course of radiation, patients use additional agents to treat other associated symptoms like itching or blistering. Two women in the experimental group developed rashes, and yet, rashes can be a normal reaction to radiation. Therefore, it is not known if this reaction was in response to the essential oil mixture or the radiation treatment itself. Further study could identify the degree of potential harms associated with this intervention. Additionally, no subjects dropped from the study due to rash or discomfort. No adverse reactions or unforeseen side effects to the essential oil mixture were reported. With regard to intervention fidelity, subjects had high adherence with recording daily applications of assigned skin treatments and additional agents in their skin diary. Experimental subjects had similar adherence rates (62%) to their control counterparts (63%; Table 6). Chi-square tests compared groups on rates of adherence at each week and no significant
differences were found (p values = .19-.97). While control subjects had steady adherence over the course of the trial (60% to 71%), the experimental group had higher adherence at Weeks 1, 3, and 4, with adherence dipping in Weeks 5 to 7. Furthermore, application of additional topical agents increased in both groups in Weeks 5 to 7, but experimental subjects applied more additional agents than the control group. Finally, study measures proved feasible in this pilot as there was a low-moderate rate of missing data. The data collection forms and instruments were well-defined and clearly understood by patients and data collectors. While subject burden was low overall (Weeks 1 to 5 only required response to 3-4 items), it was highest at the time of enrollment with a 33-item QOL instrument, and at Week 6 and the 1-month follow-up when response to a total of 37 items was required.
Discussion No studies were found that examined the skin protective effect of essential oil blends on radiotherapy-related skin reactions in women with breast cancer. Prior studies on the application of a single topical botanical or essential oil products have demonstrated some degree of effect in preventing or delaying radiation skin reactions in the breast cancer population. These studies enrolled small numbers of women (N = 29-254) and tested Aloe vera, Wheatgrass, Chamomile, or Calendula. Two studies found the time to peak skin reactions significantly increased from 1 to 2 weeks (Olsen et al., 2001; Wheat et al., 2006), with a greater protectant effect at higher radiation doses (>2,700 cGy; Olsen et al.,
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 11
2001). This pilot study of 24 women examined the effect of the topical application of a mixture of four essential oils in a base of four carriers. While skin ratings increased in both groups each week as expected due to higher cumulative radiation doses, the essential oil mixture did not provide statistically significant greater protection over standard care as hypothesized. These findings may be due to the small sample size as not enough power was achieved to determine a true treatment effect in this pilot investigation. The lack of group differences remained even when mean covariate adjusted study outcomes were analyzed at the interim or follow-up assessments. However, mean skin ratings (1.38 on a 5-point scale) for the experimental group are lower at the follow-up assessment point compared with the control group (1.65 on a 5-point scale), a finding that may be clinically significant. QLI and patient satisfaction ratings are also higher at follow-up for the experimental (5.31 QLI and 3.98 patient satisfaction on a 5-point scale) versus control group (5.06 QLI and 3.76 patient satisfaction on a 5-point scale). Despite these preliminary findings, it is important to note it would be unethical to compare the essential oil mixture to a true placebo. There are products, such as RadiaPlexRx, that are part of usual care since they have been shown to be an effective in protecting skin from the effects of radiation. The findings of this study suggest that the essential oil mixture is equivalent to RadiaPlexRx. Although essential oils are not regulated by the FDA, those used in this study are commonly used in the food/ flavor/cosmetics industries and are designated as “GRAS” (generally regarded as safe). As a result, an additional benefit of these findings is that patients have options. An essential oil mixture may be an especially helpful choice for those patients that prefer a botanical, nonpharmaceutical, or scented skin product. As options in care are an essential component of holistic care, some women may opt for essential oils if this treatment is shown to be as feasible and efficacious as standard care. In addition to providing a nonpharmaceutical option, essential oil mixtures may be less expensive than standard care. The retail cost of RadiaPlexRx is approximately $33 for a 6-week course of therapy, whereas a similar regime of an essential oil blend could be as low as approximately $18 depending on the oils and concentrations used.
In contrast, other researchers found topical botanicals significantly reduced the number and onset of Grade 2 erythema with the application of Chamomile (Maiche et al., 1991), as well as lowered the incidence of moderate/severe dermatitis and associated pain with the use of Calendula (Pommier et al., 2004). In the latter study, women were also more satisfied with their dermatitis and pain relief whereas women in the current study reported less satisfaction at the follow-up time point. This finding may suggest that as skin reactions progressed as cumulative radiation dose increased (as expected), women experienced more distress and became less satisfied with the results they had hoped to see with their skin treatment. Since there were no differences in patient satisfaction between the control and treatment groups, no conclusions can be drawn about how satisfying these products were to women. Like skin ratings, QOL ratings in this pilot also improved over time for both groups suggesting the essential oil treatment did not provide an advantage over the RadiaPlexRx ointment. This finding is similar to Wheat et al. (2006), who found QOL outcomes significantly improved at 5 to 6 weeks. These findings are interesting as this time period in the radiation course is when skin reactions generally tend to increase, threatening QOL perceptions. The QLI instrument used in this pilot provides a broad measure of cancer-associated QOL. The diseasespecific ratings also assessed in this study offer a more targeted assessment of the effect the topical applications had on radiation-related skin changes. Despite lack of statistical significance, which may be related to the low power in this pilot study, the slightly higher ratings for skin rash (Weeks 6 and 10) and painful skin (Week 6) in the control group may have some clinical significance. Folliculits is common during radiotherapy as follicles can get plugged if more products are used to help with skin repair. Thus, it is interesting the control group reported higher rashes when these subjects used less topical agents than their experimental counterparts. On the other hand, higher skin ulcer ratings were reported in the experimental group at Weeks 6 and 10 (although these ratings were not statistically significant). Accrual into this pilot study posed no challenges most likely due to the large number of women treated for breast cancer at this center. Women were also amenable to randomization procedures, with a
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12 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
low overall dropout rate (11%). Overall treatment adherence protocol ranged from 62% to 63% for experimental and control subjects, respectively. Experimental subjects had highest adherence at Week 1. By Week 2 adherence dropped and then increased until Week 5. It is interesting that adherence dropped at Week 5 in both groups, a time when women started using substantially more additional topical agents. This finding may suggest women were responding to the progressive skin changes over the course of their radiation treatment. As a result, it is conceivable as women experienced progressive skin reactions they adhered less to the treatment protocol and instead relied on trial and error with other products to assist with skin healing.
Limitations and Recommendations The main limitation of this pilot was the small sample limited to English speaking patients. The inability to blind the essential oil mixture to either the patient or data collectors also reduces control over bias. Another potential limitation was the smell associated with the essential oil mixture. Two subjects in the experimental group dropped out because they disliked the smell of the essential oil mixture, one at Week 1 and another after Week 3. Anecdotally, women reported they were surprised the oil mixture did not have a more enjoyable smell/odor given the study was centered on an aromatherapy intervention that tends to be associated with pleasurable scents. It would be advantageous to blind the smell of oils to minimize bias in the reactions of subjects and data collectors. If a method to reliably blind the smell/odor of oils is not possible, future studies could manage patient expectations around the scent of essential oil treatments with an explanation in the informed consent to potentially improve long-term adherence. Thus, by managing expectations, sufficient numbers of subjects could be retained in a larger clinical trial to evaluate the effectiveness of such treatments on skin, pain, patient satisfaction, and QOL outcomes. Due to the small effect size of this essential oil mixture, another recommendation for further research involves testing a different blend of essential oils with therapeutic skin properties to try to increase treatment effectiveness in this population. Essential oils with therapeutic skin properties that are potential considerations include Matricaria recutita (common name German chamomile), Chamaemelum nobile
(roman chamomile), Commiphora myrrh (common name myrrh), Rosa damascene (common name rose), Aniba rosaeodora (common name rosewood), Tanacetum annum (common name blue tansy), or Achillea millefolium (common name yarrow). Carrier oil considerations include Centella asiatica (common name Gota kola), Calendula officinale (common name Calendula), or Rosa rubiginosa (common name rosehip seed oil; Battaglia, 2004; Buckle, 2003; LisBalchin, 2006; Price & Price, 2007). In relation to study measures, electronic methods could be explored for recording topical applications in the daily diary to ease subject burden. It is also recommended that instruments be translated into other languages to allow non-English women to participate as variations in acceptability and response to the essential oil intervention may be found with other ethnicities. Future investigators wishing to evaluate aromatherapy interventions for this population may also weigh the amount of potential data gleaned from a full QLI versus an approach to reduce respondent burden by evaluating only the five disease-specific outcomes directly affected by intervention and overall skin treatment satisfaction. Thus, while the QLI-Cancer version is a measure of broad life satisfaction in the health/functioning, psychological/spiritual, social/economic, and family domains, the disease-specific QOL items on the EORTC Core QOL Questionnaires may be a more sensitive measure to assess skin changes for this intervention.
Conclusion The essential oil mixture did not provide a better skin protectant effect than standard care. These findings may be due to the small sample size and low statistical power. However, the study findings revealed the essential oil mixture is equivalent to RadiaPlexRx in preventing radiation-associated skin toxicity. As a result, the pilot study provides evidence to support botanical or nonpharmaceutical options in this population. Further investigation is needed.
References Abayomi, K., Gelman, A., & Levy, M. (2008). Diagnostics for multivariate imputations. Journal of the Royal Statistical Society: Series C (Applied Statistics), 57, 273-291. American Cancer Society. (2012). Breast cancer facts & figures: 2011-2012. Atlanta, GA: Author. Retrieved from http://www
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 13 .cancer.org/research/cancerfactsfigures/breastcancerfactsfigures/breast-cancer-facts-and-figures-2011-2012 Arain, M., Campbell, M., Cooper, C., & Lancaster, G. (2010). What is a pilot or feasibility study? A review of current practice and editorial policy. BMC Medical Research Methodology, 10, 1-7. Atiba, A., Nishimura, M., Kakinuma, S., Hiraoka, T., Goryo, M., Schimada, Y., . . .Uzuka, Y. (2011). Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production. American Journal of Surgery, 201, 809-818. Battaglia, S. (2004). The complete guide to aromatherapy. Zillmere, Australia: Perfect Potion. Bjur, P., Silver, W., & Gallagher, E. (2001). Reliability of the visual analog scale for the measurement of acute pain. Academic Emergency Medicine, 8, 1153-1157. Blackmar, A. (1997). Radiation-induced skin alterations. Medsurg Nursing, 6, 172-175. Buckle, J. (2001). The role of aromatherapy in nursing care. North Carolina Nurses Association, 36(1), 57-72. Buckle, J. (2003). Clinical aromatherapy in nursing: Essential oils in practice. New York, NY: Churchill Livingstone. Cline, M., Herman, J., Shaw, E., & Morton, D. (1992). Standardization of the visual analogue scale. Nursing Research, 41, 378-380. Edwards, J., Herman, J., Wallace, B., Paw, M., & Paw, J. (1991). Comparison of patient-controlled and nursecontrolled anti-emetic therapy in patients receiving chemotherapy. Research in Nursing & Health, 14, 249-257. Ferrans, C. (1990). Development of a quality of life index for patients with cancer. Oncology Nursing Forum, 17(3 Suppl.), 15-19. Fisher, J., Scott, C., Stevens, R., Marconi, B., Champion, L., Freedman, G., . . .Wong, G. (2000). Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation therapy oncology group (RTOG) 97-13. International Journal of Radiation Oncology, Biology, Physics, 48, 1307-1310. Fitzpatrick, T. (1988). The validity and practicality of sunreactive skin types I through VI. Archives of Dermatology, 124, 869-871. Gallagher, E., Liebman, M., & Bjur, P. (2001). Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Academic Emergency Medicine, 38, 633-638. Gift, A. (1989). Visual analogue scales: Measurement of subjective phenomena. Nursing Research, 38, 286-288. Graham, J. (2009). Missing data analysis: Making it work in the real world. Annual Review Psychology, 60, 549-576. Heggie, S., Bryant, G., Tripcony, L., Keller, J., Rose, P., Glendenning, M., & Heath, J. (2002). A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nursing, 25, 442-451.
Hulley, S., Cummings, S., Browner, W., Grady, D., & Newman, T. (2007). Designing clinical research. Philadelphia, PA: Wolters Kluwer. Kaasa, S., Bjordal, K., Aaronson, N., Wist, E., Hagen, S., & Kvikstad, A. (1995). The EORTC core quality of life questionnaire (QL Q-C30): Validity and reliability when analyzed with patients treated with palliative radiotherapy. European Journal of Cancer, 31A(13-14), 2260-2263. Knobf, M., & Sun, Y. (2005). A longitudinal study of symptoms and self-care activities in women treated with primary radiotherapy for breast cancer. Cancer Nursing, 28, 210-218. Lis-Balchin, M. (2006). Aromatherapy science: A guide for healthcare professionals. Grayslake, IL: Pharmaceutical Press. Maiche, A., Gröhn, P., & Mäki-Hokkonen, H. (1991). Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncologica, 30, 395-396. Moore, K., Haas, M., & Lloyd, K. (2005). Patients undergoing radiation treatment were clinically evaluated for skin integrity, pain and itching in a preliminary trial using RadiaPlexRx gel containing 0.2% hyaluronic acid. Oncology Nursing Forum, 32(2), 479. Morris, G., Hopewell, J., Harold, M., Ross, G., Nadejina, N., Gusev, I., . . .Flockhart, I. (1997). Modulation of the cell kinetics of pig skin by the topical application of evening primrose oil or Lioxasol. Cell Proliferation, 30, 311-323. Olsen, D., Raub, W., Bradley, C., Johnson, M., Macias, J., Love, V., & Markoe, A. (2001). The effect of aloe vera gel/ mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncology Nursing Forum, 28, 543-547. Pathak, M., & Fanselow, D. (1983). Photobiology of melanin pigmentation: Dose/response of skin to sunlight and its contents. Journal of the American Academy of Dermatology, 9, 724-733. Pommier, P., Gomez, F., Sunyach, M., D’Hombres, A., Carrie, C., & Montbarbon, X. (2004). Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. Journal of Clinical Oncology, 22, 1447-1453. Porock, D., & Kristjanson, L. (1999). Skin reactions during radiotherapy for breast cancer: The use and impact of topical agents and dressings. European Journal of Cancer Care, 8, 143-153. Porock, D., Kristjanson, L., Nikoletti, S., Cameron, F., & Pedler, P. (1998). Predicting the severity of radiation skin reactions in women with breast cancer. Oncology Nursing Forum, 8, 143-153. Price, S., & Price, L. (2007). Aromatherapy for health professionals. Philadelphia, PA: Churchill Livingstone. Raghunathan, T., Solenberger, P., & Van Hoewyk, J. (2002). IVEware: Imputation and variance estimation software. Ann Arbor: Institute for Social Research, University of Michigan.
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14 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX Radiation Therapy Oncology Group. (2009). Acute Radiation Morbidity Scoring Criteria. Philadelphia, PA: Author. Retrieved from http://www.rtog.org/members/toxicity/acute .html Ranzato, E., Martinotti, S., & Burlando, B. (2011). Wound healing properties of jojoba liquid wax: An in vitro study. Journal of Ethnopharmacology, 134, 443-449. Reuter, J., Jocher, A., Stump, J., Grossjohann, B., Franke, G., & Schempp, C. M. (2008). Investigation of the antiinflammatory potential of aloe vera gel (97.5%) in the ultraviolet erythema test. Skin Pharmacology Physiology, 21, 106-110. Richardson, J., Smith, J., McIntyre, M., & Pilkington, T. (2005). Aloe vera for preventing radiation-induced skin reactions: A systematic literature review. Clinical Oncology, 17, 478-484. Rubin, D. (1987). Multiple imputation for nonresponse in surveys. New York, NY: Wiley. Schnaubelt, K. (1998). Advanced aromatherapy: The science of essential oil therapy. Rochester, VT: Healing Arts Press. Sitton, E. (1992). Early and late radiation-induced skin alterations. Part I: Mechanisms of skin changes. Oncology Nursing Forum, 19, 801-807. Thabane, L., Ma, J., Chu, R., Cheng, J., Ismaila, A., Rios, L., . . .Goldsmith, C. H. (2010). A tutorial on pilot studies: The what, why and how. BMC Medical Research Methodology, 10, 1-10. Visuthikosol, V., Chowchuen, B., Sukanarat, Y., Sriurairatana, S., & Boonpucknavig, V. (1995). Effect of aloe vera gel to healing of burn wounds: A clinical and histological study. Journal of the Medical Association of Thailand, 78, 403-409. Wells, M., & McBride, S. (2003). Radiation skin reactions. In S. Faithfull & M. Wells (Eds.), Supportive care in radiotherapy (Chapter 8). Edinburgh, Scotland: Churchill Livingstone. Wheat, J., Currie, G., & Coulter, K. (2006). Wheatgrass extract as a topical skin agent for acute radiation skin toxicity in breast radiation therapy: A randomized controlled trial. Journal of the Australian Traditional-Medicine Society, 12, 135-137.
Williams, M., Burk, M., Loprinzi, C., Hill, M., Schomberg, P., Nearhood, K., . . .Eggleston, W. D. (1996). Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. International Journal of Radiation Oncology, 36, 345-349. Woollard, A., Tatham, K., & Barker, S. (2007). The influence of essential oils on the process of wound healing: A review of the current evidence. Journal of Wound Care, 16, 255-257. Worwood, S. (1995). Essential aromatherapy: A pocket guide to essential oils and aromatherapy. Novato, CA: New World Library. Margo A. Halm, RN, PhD, ACNS-BC, is the Director of Nursing Research, Professional Practice and Magnet at Salem Hospital, Salem Oregon. Dr. Halm completed her PhD from the University of Minnesota and master’s/baccalaureate degrees in nursing from the University of Iowa. At the time this study was conducted, Dr. Halm was the Director of Nursing Research/ Quality at United Hospital in St. Paul, MN. Clarice Baker, CCAP, OTR/L, NCTMB, is a staff occupational therapist at Sholom Home East, a skilled nursing facility offering rehabilitation services to transitional care, long term care, outpatients, and home care patients. She is a certified massage therapist and certified clinical aromatherapy practitioner/ instructor and offers these services through her private practice, Bridges to Health, as well as in her medical facility in addition to providing educational opportunities within professional and community organizations. At the time this study was conducted, Lisa was the Lead Integrative Health & Healing Clinician at United Hospital in St. Paul, MN. Val Harshe, BS, RT(T), is the Director of Oncology Operations for University of Minnesota Health, Cancer Care. Val completed her BS from St. Mary’s University and has been in oncology-related fields for the past 39 years. At the time this study was conducted, Val was the Radiation Oncology Manager at the St. Paul Cancer Center in St. Paul, MN.
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Effect of an Essential Oil Mixture on Skin Reactions in Women Undergoing Radiotherapy for Breast Cancer: A Pilot Study Margo A. Halm, Clarice Baker and Val Harshe J Holist Nurs published online 25 March 2014 DOI: 10.1177/0898010114527184 The online version of this article can be found at: http://jhn.sagepub.com/content/early/2014/03/20/0898010114527184
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527184
JHNXXX10.1177/0898010114527184Journal of Holistic NursingEssential Oils for Radiation-Associated Skin Reactions /Halm et al.
1
Quantitative Research
Effect of an Essential Oil Mixture on Skin Reactions in Women Undergoing Radiotherapy for Breast Cancer A Pilot Study
jhn
research-article2014
Journal of Holistic Nursing American Holistic Nurses Association Volume XX Number X XXXX 201X 1–14 © The Author(s) 2014 10.1177/0898010114527184 http://jhn.sagepub.com
Margo A. Halm, RN, PhD, ACNS-BC Salem Hospital, Salem, OR
Clarice Baker, CCAP, OTR/L, NCTMB Sholom Home East, St. Paul, MN
Val Harshe, BS, RT(T) University of Minnesota Physicians, Minneapolis, MN
Purpose:This pilot study compared the effects of an essential oil mixture versus standard care on skin reactions in breast cancer patients receiving radiation. Method: Using an experimental design, 24 patients were randomized to standard care (i.e., RadiaPlexRx™ ointment) or an essential oil mixture. Products were applied topically three times a day until 1 month postradiation. Weekly skin assessments were recorded and women completed patient satisfaction and quality of life (QOL) instruments at 3-, 6-, and 10-week intervals. Results: No significant differences were found for skin, QOL, or patient satisfaction at interim or follow-up time points. Effect sizes were as follows: skin = .01 to .07 (small-medium effect); QOL = .01 to .04 (small effect); patient satisfaction = .02 (small effect). Conclusion: The essential oil mixture did not provide a better skin protectant effect than standard care. These findings suggest the essential oil mixture is equivalent to RadiaPlexRx, a common product used as standard care since it has been shown to be effective in protecting skin from radiation. Thus, this pilot provides evidence to support botanical or nonpharmaceutical options for women during radiotherapy for breast cancer. Keywords: essential oils; radiation-associated skin reactions; breast cancer population
In 2011, the American Cancer Society estimated 230,480 new invasive breast cancer diagnoses. Prognosis of breast cancer depends on disease stage at the time of diagnosis. Women diagnosed with breast cancer usually undergo surgical resection, often followed by chemotherapy and/or a course of radiation therapy via external beam therapy. Radiation to the breast is almost always recommended after a lumpectomy, and in some circumstances, following mastectomy. The mode of radiation therapy depends on the type and stage of cancer. Radiation treatments typically begin 1 month following surgery and last for 5 to 7 weeks (American Cancer Society, 2012).
Skin reactions are a common problem associated with radiation. The incidence of such reactions in women undergoing radiotherapy for breast cancer ranges from 87% to 96% (Fisher et al., 2000; Porock
Authors’ Note: This study was funded in part by the United Hospital Foundation. The authors would like to acknowledge Basia Lutz, RN, BSN, for her dedication to data collection, as well as Kathryn E. Farniok, MD, and Mark Palmer, MD, at the St. Paul Cancer Center. The authors would also like to thank MPM Medical Inc. for donating the RadiaPlex for this study; this donation did not influence study design or analysis. Please address correspondence to Margo A. Halm, RN, PhD, ACNS-BC, Salem Hospital, 890 Oak St. SE, Salem, OR 97301; e-mail: [email protected].
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2 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
& Kristjanson, 1999). Such reactions vary from mild erythema to brisk moist desquamation or even ulceration and, thus, may be associated with mild to severe pain. Skin reaction severity is influenced by factors such as anatomic treatment area; radiation energy, fractionation, and total dose; concomitant chemotherapy; and patient differences like skin complexion, obesity, bra/cup size, and smoking history (Blackmar, 1997; Porock, Kristjanson, Nikoletti, Cameron, & Pedler, 1998; Richardson, Smith, McIntyre, & Pilkington, 2005; Sitton, 1992; Wells & McBride, 2003). Typically, radiation reactions appear between 10 and 14 days from beginning of therapy and continue to increase in severity until treatment is completed. The symptoms associated with these skin reactions may affect patient tolerance and compliance with radiation, potentially reducing the effectiveness of treatment (Knobf & Sun, 2005).
Background While topical applications to treat radiation skin toxicity have been used in clinical practice, supporting evidence for these therapies is limited (Porock & Kristjanson, 1999; Wheat, Currie, & Coulter, 2006). Few studies have been conducted to test the effectiveness of topical applications containing herbal extracts or oils to reduce radiotherapy skin reactions in breast cancer patients. Pure essential oils are distillates from aromatic plants and often carry the same physiological or psychological effects of the plant from which they are derived. Topical essential oil or botanical preparations tested in animal models include evening primrose and Aloe vera, whereas wheatgrass, calendula, chamomile, and Aloe vera gel have been studied in clinical trials. In one animal study, Morris et al. (1997) studied cell proliferation in large female white pigs receiving daily application of 10% evening primrose oil and lioxasol (a compound used for radiation burns). Pigs treated with evening primrose had more pronounced proliferative cell activity, increasing the size of the epidermis at 6 weeks, suggesting this botanical modulated the skin’s response to radiation. In a second animal model, Aloe vera (oral administration) significantly accelerated wound contraction, inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of transforming growth factor β-1 and basic fibroblast growth factor in radiation-delayed wound healing (Atiba et al., 2011).
Four clinical trials examined the effects of Aloe vera gel on radiation skin reactions. Heggie et al. (2002) compared TID application of Aloe vera to aqueous cream (N = 225) throughout the treatment period and for 2 weeks after radiation therapy. Aqueous cream was significantly better than Aloe vera gel in reducing dry desquamation and treatment-related pain. Subjects in the Aloe vera group who underwent axilla surgery also experienced more pain, erythema, and itching. However, nonchemotherapy patients receiving Aloe vera had a reduced incidence of moderate erythema. Williams et al. (1996) also reported no difference between Aloe vera and control subjects on skin reaction in two trials (N = 194, N = 108). The final Aloe vera trial (Olsen et al., 2001) compared skin reactions in 73 patients who cleansed with a mild unscented soap versus those who liberally applied Aloe vera gel after radiation. No difference in skin reactions between groups was found at low cumulative doses (90% interrater reliability in skin assessments. Skin Diary. In a formal skin diary, women recorded the number of daily topical applications through the duration of the study. If more or less than three applications were used, women documented the reason as well as any other topical products (and number of applications) used on their breast tissue. Women were instructed to bring their diary each week to review so compliance could be reinforced as well as at the final 1-month follow-up appointment. Pain Visual Analog Scale. A 100-mm visual analog scale (VAS) was used to evaluate pain. The VAS was anchored by terms including “the least pain felt in my breast” and “the worst pain felt in my breast.” Women were requested to place a line across the VAS at a point that represents their intensity of pain at that moment in time. Measurements were taken each week during a radiation visit and at the 1-month follow-up appointment (Week 10). Responses were scored by measuring the distance from the lower anchor point to the subject’s mark across the line (Cline, Herman, Shaw, & Morton, 1992). Studies have shown vertical lines are more sensitive and easier to use, especially for those under stress or with a narrowed visual field (Gift, 1989). The VAS has ½ inch perpendicular lines placed at the end, since Edwards, Herman, Wallace, Paw, and Paw (1991) found subjects marked off the scale unless such lines were present. No intermediate marks, gradations, or terms were placed on the VAS since it has been argued that using gradations decreases sensitivity, imposes another’s language on the subjects, and requires a higher reading level (Gift, 1989). Reliability is a strength of this measurement approach (Bjur, Silver, & Gallagher, 2001; Gallagher, Liebman, & Bjur, 2001). When subjective experiences are reported on the VAS, subjects need
to be in a sitting position since reliability is reduced in the supine position (Edwards et al., 1991). Quality of Life Index (QLI). The QLI-Cancer version contains 33 items that measure satisfaction with four life domains: (a) health/functioning, (b) psychological/spiritual, (c) social/economic, and (d) family. The reported internal consistency reliability of the overall QLI was 0.95. Coefficients of .90, .93, .84, and .66 were reported for the four subscales as listed above, respectively. Support for concurrent validity has been provided by a strong correlation (r = .80) between the QLI and a measure of life satisfaction (Ferrans, 1990). Women completed the QLI at baseline, at the end of radiation therapy (6 weeks), and on 1-month follow-up. In addition, women completed five items pertaining to skin changes associated with radiation from the European Organization for the Research and Treatment of Cancer (EORTC) Core QOL Questionnaire to assess disease-specific indicators. These items specifically were rashes, dryness, sweating, painful skin, and skin ulcers. Reliability of the physical functioning scale ranges from .75 to .77, whereas reliability coefficients for the pain symptom scale ranges from .75 to .87 (Kaasa et al., 1995). Patient Satisfaction. A patient satisfaction item was developed to evaluate topical skin applications. On a 5-point Likert-type response format, women reported their level of satisfaction with the topical preparation used to prevent and treat skin changes during the course of their radiation at 3 weeks, 6 weeks, and 10 weeks (1-month follow-up). Reliability testing was not possible since a single question about satisfaction was asked.
Procedure Once the study was reviewed and approved by the institutional review board, potential subjects were identified from the clinic roster. As new breast cancer patients presented for radiation treatment, clinic nurses screened them to ensure inclusion/ exclusion criteria were met. Patients who met the criteria were invited to participate in the study at their initial appointment for treatment planning. After informed consent was obtained, baseline measures were obtained by the study RN.
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6 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
After baseline measures, the clinic manager randomly assigned subjects using a computerized list of random numbers to one of two groups: (a) control group (RadiaPlexRx ointment TID) or (b) experimental group (essential oil blend TID). Subjects then received a patch test of the two topical applications on their forearm. A double-strength concentration of the essential oil blend and regular strength concentration of RadiaPlexRx were used for patch testing. To allow time for delayed hypersensitivity to present, the RN assessed the forearm for signs of sensitivity (e.g., erythema) at a radiation visit 48 hours later. If no sensitivities were found, women were provided with an initial 2-ounce supply of their assigned product in a concealed bag. Subjects were instructed to request additional supplies of their product at future appointments when their supply was low. This procedure was used to promote uniform product integrity, as the chemistry of essential oils may change with exposure to heat and light. Blinding of the skin preparations, to either the subjects or data collectors, was not possible due to the strong smell/odor of the treatment product. Patient education included teaching women to apply the oil to cover the entire radiation site TID (i.e., morning, mid day, before bed) until their 1-month follow-up appointment. However, women were instructed to remove their assigned product with soap and water immediately prior to all radiation treatments. Other safety precautions emphasized that the product was for topical use only and the importance of keeping the container out of reach of children, and the cap screwed on tightly when not in use. Women were also advised to wash their hands after application to avoid getting the oils in their eyes. In the event of eye exposure, women were instructed to flush their eye with vegetable oil for 5 minutes, followed by water prior to seeking medical attention. If pronounced negative reactions were experienced, women were instructed to discontinue the applications and report these reactions to the clinic.
missing values following best-practice recommendations (Graham, 2009). Missing data were imputed using the IVEWare (Raghunathan, Solenberger, & Van Hoewyk, 2002), which uses all available data to impute missing data via a sequential regression approach. The observed and imputed data were compared to ensure they showed similar distributions (Abayomi, Gelman, & Levy, 2008). Missing data points were replaced with imputed data in 20 data sets, which were analyzed separately. Model parameters and standard errors, which incorporate within and between model parameter variability, were combined following Rubin (1987). Preliminary Analyses. We examined the distribution of variables and evaluated potential sources of nonindependence. No evidence of substantial skew or kurtosis was detected and thus approximated normal distributions. We tested if conditions differed at baseline on outcomes and demographic variables reported in Table 2 to test whether randomization created equivalent groups. The groups did not statistically differ on any measure. However, the trend level differences in pain (p = .09) was associated with a large effect size (Cohen’s d = .70). Analytic Models. Skin ratings were the main study outcome; QOL total score and patient satisfaction were secondary outcomes. Analysis of covariance models (ANCOVA) were used to examine group differences in skin, QOL, and patient satisfaction ratings at the interim (3 weeks for skin and patient satisfaction ratings, 6 weeks for QOL ratings) and follow-up assessments (6 weeks for skin and patient satisfaction ratings, 10 weeks for QOL ratings) with study condition as a two-level predictor (1 = experimental, 0 = control) and baseline measures of the outcome (except for patient satisfaction) and pain ratings as covariates.
Results Description of the Sample
Statistical Methods Missing Data. Rates of missing data ranged from 4% to 17% at baseline, 8% to 17% at interim, and 17% to 25% at the follow-up assessment. Of the 24 subjects, 12 (50%) provided complete data. Failure to provide data was not related (at p > .10) to any of the measures. Multiple imputation was used to replace
A total of 24 subjects were enrolled in this pilot study. The control and experimental groups were composed of 11 and 13 subjects, respectively (Figure 1). No women reported allergies during the consent process. In addition, no sensitivities to the essential oil or RadiaPlexRx ointment were found through patch testing. As shown in Table 2, no
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 7 Table 2. Sample Characteristics (N = 24) Control (n = 11)
Experimental (n = 13)
Mean
SD
Mean
SD
t Value
p Value
55.91 28.41 2.55 4.80 5545.50
12.35 8.48 0.82 4.78 438.75
55.92 29.36 2.39 19.39 5398.92
10.89 5.12 0.77 27.96 507.19
0.01 0.34 0.50 1.85 .717
.10 .74 .63 .09 .48
n
%
n
%
χ2
p Value
Chemotherapy (% yes) Tumor history Infiltrating ductal Lobular Other Bra size 34 or smaller 36 38 40 42 44 or larger
3
27.30
3
25.00
0.01 1.23
7 1 3
63.64 9.09 27.27
9 0 4
69.23 0.00 30.77
2 3 3 1 0 1
18.2 27.27 27.27 9.09 0.00 9.09
1 3 3 2 3 0
7.69 25.00 25.00 15.38 25.00 0.00
.90 .54 .48
Age Body mass index Pathak Scale Baseline pain Total cumulative radiation dose
4.52
significant differences were found in the demographic and baseline clinical characteristics between groups. No women reported allergies during the consent process. In addition, no sensitivities to the essential oil or RadiaPlexRx ointment were found through patch testing.
Aim 1: Differences in Skin Reactions, QOL Perceptions, and Patient Satisfaction The first primary aim of this pilot study was to determine if significant differences existed in the degree of skin reaction, patient satisfaction, and QOL in breast cancer patients undergoing radiotherapy who use RadiaPlexRx ointment (standard care) versus an essential oil blend (experimental treatment). Descriptive statistics of the skin, patient satisfaction, and QOL measures (baseline, interim, and follow-up) and results of the ANCOVA models are reported in Tables 3 and 4, respectively. Examination of group means shows an increase in skin and QOL ratings for both groups, and a slight decrease for both groups in patient satisfaction. Results of the test of group differences are shown in Table 4. The parameter estimates indicate how much an outcome for the experimental group
changes in relation to the control group at the interim and follow-up assessment after adjusting for baseline differences in the outcome and pain scores (with the exception of satisfaction which only adjusts for baseline pain scores). Overall, results indicate no group differences in the mean covariate adjusted study outcomes at the interim or follow-up assessments. The models were run again, but with available data only (i.e., not using imputed data). The direction and magnitude of the means were similar to the results of the imputed data and no significant group differences were found. In addition to this main analysis, t tests explored disease-specific QOL outcomes in the two groups (Table 5). Trends were observed in three diseasespecific outcomes, although these were not significant (p > .05). First, rash ratings were higher in control subjects at both 6 and 10 weeks compared with the experimental group. Painful skin ratings were also slightly higher in control subjects at Week 6, but skin ulcer ratings were higher in experimental group at Weeks 6 and 10.
Aim 2: Estimation of Effect Sizes A second primary aim was to estimate effect sizes that could be used for sample size calculations for a
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8 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
Enrollment
Assessed for eligibility (n = 36) Excluded (n = 9) Not meeting inclusion criteria (n = 0) Refused to participate (n = 9) Other reasons (n = 0)
Analysis
Follow up
Allocation
Randomized (n = 27) Allocated to intervention (n = 12)
Allocated to intervention (n = 15)
Received allocated intervention (n = 12)
Received allocated intervention (n = 15)
Did not receive allocated intervention (n = 0)
Did not receive allocated intervention (n = 0)
Lost to follow up (n = 0)
Lost to follow up (n = 0)
Discontinued intervention (n =1) (skin treatment perceived as too oily)
Discontinued intervention (n = 2) (disliked smell of essential oil mixture)
Analyzed (n = 11)
Analyzed (n = 13)
Excluded from analysis (n = 0)
Excluded from analysis (n = 0)
Figure 1. CONSORT Diagram
larger clinical trial testing this essential oil intervention. As shown in Table 4, effect sizes for the main study outcomes for the interim and follow-up assessments range from .01 to .07 for skin ratings (representing a small to medium effect), .01 to .04 for QLI ratings (representing a small effect), and .02 for patient satisfaction ratings (representing a small effect).
Aim 3: Feasibility Assessment The third primary aim was to evaluate the feasibi lity of implementing this new intervention for breast
cancer patients undergoing radiation. Feasibility assessment focused on assessing factors that affected implementation, including recruitment and availability of subjects; randomization; acceptability of the intervention to patients/caregivers; adherence and safety aspects of the intervention; retention rates; and adequacy and utility of study measures. Accrual into the pilot was smooth, with ample numbers of women to recruit most likely due to the large number of women treated for breast cancer at this cancer center. No women were excluded from the study during recruitment as no sensitivities were
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 9 Table 3. Descriptive Statistics Control Group (n = 11)
Interima
Baseline
Experimental Group (n = 13) Follow-Upb
Interima
Baseline
Follow-Upb
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Skin rating Quality of life Patient Satisfaction
0.14 4.95 NA
0.20 0.65 NA
0.73 4.91 4.42
0.29 0.75 0.75
1.65 5.06 3.76
0.60 0.62 1.36
0.28 5.18 NA
0.31 0.64 NA
0.73 5.19 4.09
0.41 0.85 1.20
1.38 5.31 3.98
0.65 0.58 0.94
Note: SD = standard deviation; NA = not assessed. a. Interim: 3 weeks—Skin rating and patient satisfaction; 6 weeks—Quality of life. b. Follow-up: 6 weeks—Skin rating and patient satisfaction; 10 weeks—Quality of life.
Table 4. Results of Analysis of Covariance Models (ANCOVA) Interim Test Statistics Skin rating Quality of life Patient satisfaction
Follow-Up Test Statistics
Est.
SE
t Value
p Value
η2
Est.
SE
t Value
p Value
η2
−0.04 0.04 −0.21
0.16 0.24 0.47
−0.24 0.15 −0.45
.81 .88 .64
.01 .01 .02
−0.34 0.09 0.30
0.28 0.24 0.53
−1.21 0.40 0.57
.23 .69 .57
.07 .04 .02
Note: Est. = parameter estimate; η2 =eta-square, measure of effect size (.01 small, .06 medium, .14 large). Means, standard deviations, and effect sizes are averaged across the 20 imputed data sets. Parameter estimates and corresponding test statistics are pooled across the 20 imputed data sets.
Table 5. Disease-Specific QOL Items (N = 24) Control Group (n = 11) Rash Week 6 1 Month follow-up Dryness Week 6 1 Month follow-up Sweating Week 6 1 Month follow-up Painful skin Week 6 1 Month follow-up Skin ulcers Week 6 1 Month follow-up
Experimental Group (n = 13)
Mean
SD
Mean
SD
2.67 1.73
1.32 1.10
1.90 1.44
0.88 .53
2.00 1.91
1.00 0.70
2.30 1.67
1.16 0.71
1.67 1.82
1.00 0.98
1.80 1.78
1.23 0.97
2.67 1.78
1.00 0.67
2.60 1.78
1.17 0.67
1.22 1.09
0.44 0.30
1.40 1.22
0.52 0.67
detected to the essential oil mixture during the patch testing procedure. Randomization into treatment groups also did not pose challenges. No subjects refused to participate due to group assignment. Only two women randomized to the experimental group
p .16 .46 .56 .45 .80 .93 .90 .68 .43 .57
dropped from the study (Week 1 and Week 3) due to dislike of the smell of the essential oil mixture. In total, three subjects withdrew from the study (1 control and 2 experimental). Therefore, the overall retention rate was 87.5%. Nurses in the cancer
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10 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX Table 6. Protocol Adherence and Use of Additional Topical Applicationsa by Group (N = 24) Average Adherence Control group (n = 11) Adherence to TID application Additional topical applications Experimental Group (n = 13) Adherence to TID application Additional topical applications
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
64% 1
64% 1
64% 0
60% 18
60% 27
71% 19
60% 28
81% 2
55% 2
78% 8
78% 24
55% 44
45% 66
40% 57
Overall Adherenceb 63% 94 62% 203
a. Ointments (analgesic, antibiotic, Benadryl, Cortisone, Silver Sulfadiazene); Emollients (Aquaphor, Aloe Vera); Silicone gel pads; Vigilon; unspecified oils; unspecified products. b. Chi-square analyses nonsignificant (p values = .19-.97).
center also viewed the essential oil mixture as an acceptable intervention to test in this patient population, as evidenced by their active involvement in executing the study protocol. Other aspects of the acceptability of the intervention include clarity of the protocol as well as appropriateness of the dose and safety. Women were instructed to apply the essential oil mixture or RadiaPlexRx TID, congruent with what is prescribed in actual practice today as well as with clinical trial investigations of various skin prevention protocols in this population. While women did apply additional products to their breast tissue over time, this practice is customarily seen with radiation treatment and, therefore, may not be a direct indication of the appropriateness of the intervention dose. As skin reactions begin to occur over the course of radiation, patients use additional agents to treat other associated symptoms like itching or blistering. Two women in the experimental group developed rashes, and yet, rashes can be a normal reaction to radiation. Therefore, it is not known if this reaction was in response to the essential oil mixture or the radiation treatment itself. Further study could identify the degree of potential harms associated with this intervention. Additionally, no subjects dropped from the study due to rash or discomfort. No adverse reactions or unforeseen side effects to the essential oil mixture were reported. With regard to intervention fidelity, subjects had high adherence with recording daily applications of assigned skin treatments and additional agents in their skin diary. Experimental subjects had similar adherence rates (62%) to their control counterparts (63%; Table 6). Chi-square tests compared groups on rates of adherence at each week and no significant
differences were found (p values = .19-.97). While control subjects had steady adherence over the course of the trial (60% to 71%), the experimental group had higher adherence at Weeks 1, 3, and 4, with adherence dipping in Weeks 5 to 7. Furthermore, application of additional topical agents increased in both groups in Weeks 5 to 7, but experimental subjects applied more additional agents than the control group. Finally, study measures proved feasible in this pilot as there was a low-moderate rate of missing data. The data collection forms and instruments were well-defined and clearly understood by patients and data collectors. While subject burden was low overall (Weeks 1 to 5 only required response to 3-4 items), it was highest at the time of enrollment with a 33-item QOL instrument, and at Week 6 and the 1-month follow-up when response to a total of 37 items was required.
Discussion No studies were found that examined the skin protective effect of essential oil blends on radiotherapy-related skin reactions in women with breast cancer. Prior studies on the application of a single topical botanical or essential oil products have demonstrated some degree of effect in preventing or delaying radiation skin reactions in the breast cancer population. These studies enrolled small numbers of women (N = 29-254) and tested Aloe vera, Wheatgrass, Chamomile, or Calendula. Two studies found the time to peak skin reactions significantly increased from 1 to 2 weeks (Olsen et al., 2001; Wheat et al., 2006), with a greater protectant effect at higher radiation doses (>2,700 cGy; Olsen et al.,
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Essential Oils for Radiation-Associated Skin Reactions /Halm et al. 11
2001). This pilot study of 24 women examined the effect of the topical application of a mixture of four essential oils in a base of four carriers. While skin ratings increased in both groups each week as expected due to higher cumulative radiation doses, the essential oil mixture did not provide statistically significant greater protection over standard care as hypothesized. These findings may be due to the small sample size as not enough power was achieved to determine a true treatment effect in this pilot investigation. The lack of group differences remained even when mean covariate adjusted study outcomes were analyzed at the interim or follow-up assessments. However, mean skin ratings (1.38 on a 5-point scale) for the experimental group are lower at the follow-up assessment point compared with the control group (1.65 on a 5-point scale), a finding that may be clinically significant. QLI and patient satisfaction ratings are also higher at follow-up for the experimental (5.31 QLI and 3.98 patient satisfaction on a 5-point scale) versus control group (5.06 QLI and 3.76 patient satisfaction on a 5-point scale). Despite these preliminary findings, it is important to note it would be unethical to compare the essential oil mixture to a true placebo. There are products, such as RadiaPlexRx, that are part of usual care since they have been shown to be an effective in protecting skin from the effects of radiation. The findings of this study suggest that the essential oil mixture is equivalent to RadiaPlexRx. Although essential oils are not regulated by the FDA, those used in this study are commonly used in the food/ flavor/cosmetics industries and are designated as “GRAS” (generally regarded as safe). As a result, an additional benefit of these findings is that patients have options. An essential oil mixture may be an especially helpful choice for those patients that prefer a botanical, nonpharmaceutical, or scented skin product. As options in care are an essential component of holistic care, some women may opt for essential oils if this treatment is shown to be as feasible and efficacious as standard care. In addition to providing a nonpharmaceutical option, essential oil mixtures may be less expensive than standard care. The retail cost of RadiaPlexRx is approximately $33 for a 6-week course of therapy, whereas a similar regime of an essential oil blend could be as low as approximately $18 depending on the oils and concentrations used.
In contrast, other researchers found topical botanicals significantly reduced the number and onset of Grade 2 erythema with the application of Chamomile (Maiche et al., 1991), as well as lowered the incidence of moderate/severe dermatitis and associated pain with the use of Calendula (Pommier et al., 2004). In the latter study, women were also more satisfied with their dermatitis and pain relief whereas women in the current study reported less satisfaction at the follow-up time point. This finding may suggest that as skin reactions progressed as cumulative radiation dose increased (as expected), women experienced more distress and became less satisfied with the results they had hoped to see with their skin treatment. Since there were no differences in patient satisfaction between the control and treatment groups, no conclusions can be drawn about how satisfying these products were to women. Like skin ratings, QOL ratings in this pilot also improved over time for both groups suggesting the essential oil treatment did not provide an advantage over the RadiaPlexRx ointment. This finding is similar to Wheat et al. (2006), who found QOL outcomes significantly improved at 5 to 6 weeks. These findings are interesting as this time period in the radiation course is when skin reactions generally tend to increase, threatening QOL perceptions. The QLI instrument used in this pilot provides a broad measure of cancer-associated QOL. The diseasespecific ratings also assessed in this study offer a more targeted assessment of the effect the topical applications had on radiation-related skin changes. Despite lack of statistical significance, which may be related to the low power in this pilot study, the slightly higher ratings for skin rash (Weeks 6 and 10) and painful skin (Week 6) in the control group may have some clinical significance. Folliculits is common during radiotherapy as follicles can get plugged if more products are used to help with skin repair. Thus, it is interesting the control group reported higher rashes when these subjects used less topical agents than their experimental counterparts. On the other hand, higher skin ulcer ratings were reported in the experimental group at Weeks 6 and 10 (although these ratings were not statistically significant). Accrual into this pilot study posed no challenges most likely due to the large number of women treated for breast cancer at this center. Women were also amenable to randomization procedures, with a
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12 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX
low overall dropout rate (11%). Overall treatment adherence protocol ranged from 62% to 63% for experimental and control subjects, respectively. Experimental subjects had highest adherence at Week 1. By Week 2 adherence dropped and then increased until Week 5. It is interesting that adherence dropped at Week 5 in both groups, a time when women started using substantially more additional topical agents. This finding may suggest women were responding to the progressive skin changes over the course of their radiation treatment. As a result, it is conceivable as women experienced progressive skin reactions they adhered less to the treatment protocol and instead relied on trial and error with other products to assist with skin healing.
Limitations and Recommendations The main limitation of this pilot was the small sample limited to English speaking patients. The inability to blind the essential oil mixture to either the patient or data collectors also reduces control over bias. Another potential limitation was the smell associated with the essential oil mixture. Two subjects in the experimental group dropped out because they disliked the smell of the essential oil mixture, one at Week 1 and another after Week 3. Anecdotally, women reported they were surprised the oil mixture did not have a more enjoyable smell/odor given the study was centered on an aromatherapy intervention that tends to be associated with pleasurable scents. It would be advantageous to blind the smell of oils to minimize bias in the reactions of subjects and data collectors. If a method to reliably blind the smell/odor of oils is not possible, future studies could manage patient expectations around the scent of essential oil treatments with an explanation in the informed consent to potentially improve long-term adherence. Thus, by managing expectations, sufficient numbers of subjects could be retained in a larger clinical trial to evaluate the effectiveness of such treatments on skin, pain, patient satisfaction, and QOL outcomes. Due to the small effect size of this essential oil mixture, another recommendation for further research involves testing a different blend of essential oils with therapeutic skin properties to try to increase treatment effectiveness in this population. Essential oils with therapeutic skin properties that are potential considerations include Matricaria recutita (common name German chamomile), Chamaemelum nobile
(roman chamomile), Commiphora myrrh (common name myrrh), Rosa damascene (common name rose), Aniba rosaeodora (common name rosewood), Tanacetum annum (common name blue tansy), or Achillea millefolium (common name yarrow). Carrier oil considerations include Centella asiatica (common name Gota kola), Calendula officinale (common name Calendula), or Rosa rubiginosa (common name rosehip seed oil; Battaglia, 2004; Buckle, 2003; LisBalchin, 2006; Price & Price, 2007). In relation to study measures, electronic methods could be explored for recording topical applications in the daily diary to ease subject burden. It is also recommended that instruments be translated into other languages to allow non-English women to participate as variations in acceptability and response to the essential oil intervention may be found with other ethnicities. Future investigators wishing to evaluate aromatherapy interventions for this population may also weigh the amount of potential data gleaned from a full QLI versus an approach to reduce respondent burden by evaluating only the five disease-specific outcomes directly affected by intervention and overall skin treatment satisfaction. Thus, while the QLI-Cancer version is a measure of broad life satisfaction in the health/functioning, psychological/spiritual, social/economic, and family domains, the disease-specific QOL items on the EORTC Core QOL Questionnaires may be a more sensitive measure to assess skin changes for this intervention.
Conclusion The essential oil mixture did not provide a better skin protectant effect than standard care. These findings may be due to the small sample size and low statistical power. However, the study findings revealed the essential oil mixture is equivalent to RadiaPlexRx in preventing radiation-associated skin toxicity. As a result, the pilot study provides evidence to support botanical or nonpharmaceutical options in this population. Further investigation is needed.
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14 Journal of Holistic Nursing / Vol. XX, No. X, Month XXXX Radiation Therapy Oncology Group. (2009). Acute Radiation Morbidity Scoring Criteria. Philadelphia, PA: Author. Retrieved from http://www.rtog.org/members/toxicity/acute .html Ranzato, E., Martinotti, S., & Burlando, B. (2011). Wound healing properties of jojoba liquid wax: An in vitro study. Journal of Ethnopharmacology, 134, 443-449. Reuter, J., Jocher, A., Stump, J., Grossjohann, B., Franke, G., & Schempp, C. M. (2008). Investigation of the antiinflammatory potential of aloe vera gel (97.5%) in the ultraviolet erythema test. Skin Pharmacology Physiology, 21, 106-110. Richardson, J., Smith, J., McIntyre, M., & Pilkington, T. (2005). Aloe vera for preventing radiation-induced skin reactions: A systematic literature review. Clinical Oncology, 17, 478-484. Rubin, D. (1987). Multiple imputation for nonresponse in surveys. New York, NY: Wiley. Schnaubelt, K. (1998). Advanced aromatherapy: The science of essential oil therapy. Rochester, VT: Healing Arts Press. Sitton, E. (1992). Early and late radiation-induced skin alterations. Part I: Mechanisms of skin changes. Oncology Nursing Forum, 19, 801-807. Thabane, L., Ma, J., Chu, R., Cheng, J., Ismaila, A., Rios, L., . . .Goldsmith, C. H. (2010). A tutorial on pilot studies: The what, why and how. BMC Medical Research Methodology, 10, 1-10. Visuthikosol, V., Chowchuen, B., Sukanarat, Y., Sriurairatana, S., & Boonpucknavig, V. (1995). Effect of aloe vera gel to healing of burn wounds: A clinical and histological study. Journal of the Medical Association of Thailand, 78, 403-409. Wells, M., & McBride, S. (2003). Radiation skin reactions. In S. Faithfull & M. Wells (Eds.), Supportive care in radiotherapy (Chapter 8). Edinburgh, Scotland: Churchill Livingstone. Wheat, J., Currie, G., & Coulter, K. (2006). Wheatgrass extract as a topical skin agent for acute radiation skin toxicity in breast radiation therapy: A randomized controlled trial. Journal of the Australian Traditional-Medicine Society, 12, 135-137.
Williams, M., Burk, M., Loprinzi, C., Hill, M., Schomberg, P., Nearhood, K., . . .Eggleston, W. D. (1996). Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. International Journal of Radiation Oncology, 36, 345-349. Woollard, A., Tatham, K., & Barker, S. (2007). The influence of essential oils on the process of wound healing: A review of the current evidence. Journal of Wound Care, 16, 255-257. Worwood, S. (1995). Essential aromatherapy: A pocket guide to essential oils and aromatherapy. Novato, CA: New World Library. Margo A. Halm, RN, PhD, ACNS-BC, is the Director of Nursing Research, Professional Practice and Magnet at Salem Hospital, Salem Oregon. Dr. Halm completed her PhD from the University of Minnesota and master’s/baccalaureate degrees in nursing from the University of Iowa. At the time this study was conducted, Dr. Halm was the Director of Nursing Research/ Quality at United Hospital in St. Paul, MN. Clarice Baker, CCAP, OTR/L, NCTMB, is a staff occupational therapist at Sholom Home East, a skilled nursing facility offering rehabilitation services to transitional care, long term care, outpatients, and home care patients. She is a certified massage therapist and certified clinical aromatherapy practitioner/ instructor and offers these services through her private practice, Bridges to Health, as well as in her medical facility in addition to providing educational opportunities within professional and community organizations. At the time this study was conducted, Lisa was the Lead Integrative Health & Healing Clinician at United Hospital in St. Paul, MN. Val Harshe, BS, RT(T), is the Director of Oncology Operations for University of Minnesota Health, Cancer Care. Val completed her BS from St. Mary’s University and has been in oncology-related fields for the past 39 years. At the time this study was conducted, Val was the Radiation Oncology Manager at the St. Paul Cancer Center in St. Paul, MN.
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