A Randomized Study to Assess the Effectiveness of Aloe vera gel on Acute Radiation Dermatitis

Jisa George T¹*, Dr. Kamlesh K Sharma²

¹M.Sc Nursing Student, All India Institute of Medical Sciences (AIIMS), New Delhi. (At the time of writing thesis)

²Lecturer, College of Nursing, All India Institute of Medical Sciences (AIIMS), New Delhi

*Corresponding Author Email: jisagt@gmail.com

ABSTRACT:

Background: Majority of patients who undergo external beam radiation therapy develop radiation-induced skin toxicity. Sometimes radiation induced skin toxicity may be very severe and may require temporary or permanent treatment cessation. We undertook a prospective randomized trial to assess the effectiveness of Aloe vera gel in preventing acute radiation dermatitis.

Methodology: This prospective, randomized controlled trial included head and neck cancer patients scheduled to undergo radiation therapy (RT), with or without chemotherapy, at an academic cancer centre in Delhi. 57 patients were randomly assigned to either experimental group (N=27) or control group (N=30). Subjects in experimental group were advised to apply Aloe vera gel 2 times a day to the site of radiotherapy within 2-3 days of start of radiotherapy and control group received standard care. Radiation dermatitis grading and pain score in treatment field site were recorded prospectively at baseline, then fortnightly till completion of RT and one month after completion of RT.

Results: Two groups were homogenous with regard to all demographic and clinical variables. There was significantly delayed onset of dermatitis in Aloe vera group (4.81 vs.3.53 weeks; p=0.002) during RT course. Compared to Aloe vera group, standard care patients showed higher incidence of Grade III-IV dermatitis at end of RT course (3.7% vs.30%;p=0.01).

Conclusion: Aloe vera gel was effective in delaying onset and reducing severity of radiation dermatitis during the course of radiotherapy. Low cost and good patient compliance for this topical application can make it a safe practice.

KEY WORDS: Aloe vera gel, Radiation dermatitis, prevention, management.

INTRODUCTION:

Many patients who undergo radiation therapy treatment develop radiation-induced skin toxicity. Numerous studies have been conducted to identify skin care management and topical agents that may alleviate the severity of radiation dermatitis.

However, only a small number of publications have demonstrated statistically significant results, and this lack of sufficient evidence could be because of variation in practices¹.

Radiation therapy (RT) is a common cancer treatment modality for many cancer patients. The global estimated number of new cancer cases each year is expected to rise from 10 million in 2000 to 15 million by 2020. 60% of all these new cases will occur in the less developed parts of the world². The modern treatment approach to cancer care is multidisciplinary, with more than 50% of newly diagnosed patients and nearly 20-30% of recurrent cancer patients are in need of RT, either as a primary treatment or as an adjuvant, and as combined approach with surgery and/or chemotherapy, in both curative and palliative aims³.

The goal of radiation therapy is to cause maximum tumor cell kill with minimal toxicities. The effect of radiation therapy is directly loco regional causing morbidities on skin, mucosa, lungs, heart, liver, intestine, kidney, heart, skeletal and nervous system etc. which come within the radiation fields⁴. By modern radiotherapy techniques, currently these side effects are minimum and critical organs are maintained within safe radiation tolerance limits, for both acute and late radiation-induced morbidities. However, one of the most common side-effects of radiation therapy is acute skin reactions and more than 80% of the patients will experience a dose-dependent skin reaction at the treated area^5,6,7. These radiation-induced skin morbidities range from mild rash (grade I) to the most severe ulceration and necrosis (Grade IV) in a graded manner (RTOG) Radiation dermatitis is to some extent, an inevitable consequence of radiotherapy, particularly where skin folds are present.

Although the widespread use of linear accelerators has reduced the severity of skin reactions through more sophisticated skin sparing techniques, the increased use of concomitant chemotherapy and high dose radiotherapy means that skin reactions can still be a significant problem for patients⁸. Unacceptable normal tissue reactions remain the limiting factor for delivering a tumoricidal dose in radiotherapy. Skin morbidities are among the most common side effects of cancer treatment reported by patients, especially those undergoing radiation therapy for breast cancer and head and neck cancer^9,10. Concomitant chemotherapy and radiotherapy can further increase the risk of an adverse reaction because chemotherapeutic drugs can induce radiosensitivity¹¹. Many patients suffer from acute radiation dermatitis which develop around 2- 3 weeks of radiotherapy and persist for up to 4-8 weeks after the treatment has finished¹². The grade II (erythema and patchy desquamation) and higher skin reactions are painful, often leads to localized and occasionally systemic infection and may cause permanent scarring. At times, radiation induced skin toxicity may require temporary or permanent treatment cessation^13,14. It is therefore extremely important that radiation induced skin reactions be prevented whenever possible, or at least treated optimally to reduce its severity and possible complications.

The prevention and treatment of radiation induced skin reactions remains an unsolved problem and limits the efficacy of radiation therapy. The research literature identified a vast number of interventions that have been investigated to determine their effectiveness in the prevention or treatment of radiation induced skin reactions in cancer patients. Range of interventions being used to prevent or treat radiation induced dermatitis are extensive that includes Biafine, chamomile cream, almond ointment, topical vitamin C, gentian violet, transparent hydrocolloid, and hydrogel dressings, sucralfate cream, calendula cream and corticosteroid cream^15-,20. Literature review shows weak evidence for currently used interventions as effective agents for prevention of radiation induced skin reactions.

The use of Aloe vera in the treatment of radiation induced dermatitis has been reported in the literature as early as 1935²¹. It has been reported that Aloe vera gel has a protective effect against radiation induced damage to the skin^22,23. Anticancer activity of Aloe vera has been studied and found that Aloe vera enhances the immune system's response to cancer and promotes the growth of new and healthy cells, thereby revitalizing the body in its fight against the cancer²⁴. When radiation and chemotherapy are necessary as a treatment modality to treat cancer Aloe vera helps to minimize the damage done to the body by these treatments.

This prospective study has been designed to assess the clinical effectiveness of Aloe vera topical gel in comparison to normal institutional practice on radiation dermatitis during the radiotherapy course and immediately after radiotherapy in head and neck cancer patients, who receive curative intent therapy. With generally higher rates of radiation dermatitis, patients undergoing radiation therapy for head and neck region seem to be an ideal population to further investigate the interventions which can reduce this common treatment-related morbidity²⁵. The head and neck site has been chosen as this a common cancer in India constituting nearly 25% of global head and neck cancer burden and >15% of clinical oncology practice at major cancer centers in this country. Hence reduced acute radiation morbidities can improve optimal compliance of radiotherapy and may lead to improved survival and cure.

MATERIALS AND METHODS:

Head and Neck cancer patients with histopathologically confirmed cancer, planned to undergo curative dose of radiation therapy-as radical RT alone, chemotherapy combined with RT or surgery combined with postoperative RT, registered at Dr. Bhim Rao Ambedkar Institute Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, were included prospectively into this randomized study.

Ethical approval for conducting this study was obtained from institutional ethics committee of All India Institute of Medical Sciences (AIIMS), New Delhi.

Patients of more than 18 years, of either sex, can understand English or Hindi and receiving conventional radiation dose in range of 50 Gy – 70Gy, at 180-200 cGy per fraction daily, 5 days of RT per week, were enrolled in this randomized controlled trial. We excluded patients receiving internal beam radiotherapy, those who are allergic to aloe vera and who are likely to receive radiation dose <50 Gy. From the beginning of June 2008 to the end of January 2009, 57 head and neck cancer patients who met eligibility criteria were randomly assigned to either experimental or control group using sealed envelopes. Illustration of the sample size is given in the figure 1.

Figure 1-Illustration of sample size

Tools used for data collection were study Performa for collecting demographic and treatment related data, Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria for assessing skin morbidity associated with radiotherapy, Numerical rating scale for assessing pain associated with radiotherapy induced skin reactions. The numerical rating scale, a standardized pain scale has well established reliability of r = 0.78 – 0.93²⁶. The acute morbidity criterion is used to score/grade toxicity from radiation therapy. The criterion is relevant from day one, the commencement of therapy, through day 90.

Patients receiving external beam radiotherapy who met eligibility criteria were randomly assigned to either experimental group (Aloe vera group) or control group (standard care group). Experimental group was instructed to use Aloe vera gel for topical application within 2-3 days of starting of the radiation therapy and continued till one month after completion of radiation therapy and control group received standard institutional care. Patients in the control group were instructed not to apply anything to the site of radiotherapy.

Experimental group applied Aloe vera gel to the site of radiotherapy twice a day. Both groups have received standard institutional care. No other prophylactic cream or lotions were to be topically applied to the radiation field while a patient was participating in the study. However treatment of established radiation dermatitis was allowed. If any skin reaction develops, then both the groups were treated with gentian violet 2- 3 times per day.

Patients followed up fortnightly and skin reaction grading was done fortnightly using RTOG Acute radiation morbidity scoring criteria and pain scoring using numerical rating scale till the completion of radiation therapy and 1 month after completion of treatment. Data were collected and recorded on the study proforma each time.

Statistical analysis:

Data analysis was done using SPSS. Both descriptive and inferential statistics were used. Descriptive statistics used in the study were frequencies, percentage, mean median, range and standard deviation. Inferential statistics used in the study were Chi square, Fishers exact, two sample t test and Wilcoxson rank sum Mann Whitney test.

Table 1: Distribution of subjects according to gender, TNM stage of cancer, type of radiation therapy received. N=57

Variables		Experimental group (n=27)	Control group (n=30)	p value
		Frequency	Frequency
Gender	Male	25 ( 92.59 )	26 (86.67 )	0.67
	Female	2 (7.41)	4 (13.33 )
TNM stage of tumor	I	1 (3.70)	2(6.67)	0.42
	II	4 (14.81)	3 (10 )
	III	13 (48.15 )	9 (30 )
	IV a/b	9 (36)	16 (53.33 )
Type of radiotherapy	Radical	10 (37.74)	15 (50)	0.244
	Post Operative	2 (7.41)	5(16.67)
	Concurrent chemoradiation	15(55.56)	10(33.33)

Fisher’s exact test.

Table 2: Distribution of subjects according to age and radiation field size N= 57

Va Variable	Experimental group (n=27)		Control group (n=30)		p value
	Mean+/-SD	Range	Mean+/-SD	Range
Age	54.59+/- 8.98	35 -70	54.1+/-10.49	29 – 70	0.42
Radiation field size	180.59+/-51.23	50 - 252	182.73+/38.09	81- 270	0.42

Two sample t test

RESULTS:

The study groups were homogenous with regard to demographic and clinical variables. There was no statistically significant difference between the groups in terms of their age (p=0.42), gender (p=0.67), stage of cancer (p=0.67), type of radiation therapy received (p=0.244) and field size for radiation ((p=0.42). (Table 1 and 2).

Both the groups were also compared for treatment related variables like use of analgesics, antibiotics, antifungal and local anesthetics during the course of radiotherapy. Significant difference was seen in both the groups for analgesic use. (p= 0.04).All subjects (100%) in the control group received analgesics during the course of radiotherapy as compared with lesser use in experimental group (85 %). There was no significant difference seen in both the groups in terms of antibiotic antifungal and local anesthetic use (p=0.75, p=0.06, p=0.11 respectively).

There was significantly delayed onset of dermatitis in the Aloe vera group (4.81 vs.3.53 weeks; p=0.002) during RT course. . During the later course of radiotherapy (at 6^th /7^th week), significant difference between two groups for mean pain scores (1.2 vs.2.6) was observed. There was no significant difference in the two groups on the perception of pain was seen at 2^nd week, 4^th week and one month post radiotherapy.

Aloe vera significantly reduced severity of radiation dermatitis during the course of radiation therapy. At the end of second and fourth week of radiotherapy significantly reduced severity of radiation dermatitis was seen in Aloe vera group as compared to standard care patients (p= 0.013, p=0.005). Compared to the Aloe vera group, the standard care patients showed higher incidence of bothersome Grade III-IV dermatitis at end of RT course (3.7% vs.30%;p=0.01). (Table 3)

The present study compared the occurrence of radiotherapy induced skin reactions related complications (weight loss, need for interruption of radiotherapy and hospitalization) in the two groups and found no significant difference between the two groups. Mean weight loss during the course of radiotherapy was 4 kg in both the groups which was not significant. Treatment interruptions and hospitalizations during the course of radiotherapy due to radiation dermatitis was reported in 3 and 2 patients in experimental group compared to 7 and 6 in control group, which was not significant. Patients in the Aloe vera group reported good compliance to the prescribed regimen. No patients reported adverse effects and none withdrew from the study because of the side effects

Table 3: Comparison of the severity of radiotherapy induced skin reaction in both the groups at various time points. N=57

Week Skin reaction Grade		Experimental group (n=27)	Control group (n=30)	p value
		Freq.	Freq.
2^nd week	Grade 0	26 (96.30)	21(70)	0.013**
	Grade I and II	1(3.70)	9(30)
	Grade III and IV	0	0
4^th week	Grade 0	12 (44.44)	3(10)	0.005**
	Grade I and II	15(55.55)	26(86.67)
	Grade III and IV	0	1(3.33)
6^th week	Grade 0	0	0	0.01*
	Grade I and II	26(96.29)	21(70)
	Grade III and IV	1(3.70)	9(30)
One month post RT	Grade 0	24(88.89)	21(70)	0.10
	Grade I and II	3(11.11)	9(30)
	Grade III and IV	0	0

Freq.= Frequency

Fisher’s exact test..

*p value significant at 0.05 level.

**p value significant at 0.01 level.

DISCUSSION:

This randomized controlled trial was conducted to assess the effectiveness of Aloe vera gel in preventing skin reactions associated with radiotherapy in head and neck cancer patients undergoing radical or post operative radiation therapy.

Based on the literature review this is the first study of this kind in which effectiveness of Aloe vera gel in preventing radiotherapy skin reactions in head and neck cancer was studied. Two previously conducted randomized controlled trials evaluated the effectiveness of Aloe vera gel as a prophylactic agent for radiation induced skin toxicity in breast cancer patients and patients with various types of cancer. One study conducted in breast cancer patients reported no significant effect of Aloe vera for reducing incidence of radiotherapy induced skin reactions²⁷. Another study has shown that when the cumulative dose was high (>2700 cGy), Aloe vera has a protective role in reducing radiotherapy induced skin reactions²⁸.

The incidence of radiotherapy induced skin reactions in the present study was 100% during the course of radiotherapy which was congruent with findings reported in some previous studies. All subjects had developed some skin changes over the baseline assessment. However the severity of radiotherapy induced skin reactions was lesser in the experimental group.

One previous study has shown that mean time interval for the development of radiotherapy induced skin reactions were significantly delayed in group who received Aloe vera gel as compared to the control group²⁷. Our study concurred these reports and shown that mean time interval for the development of radiotherapy induced skin reactions were 4.81weeks in experimental group and 3.53 weeks in control group (p= 0.002).

In the present study Aloe vera significantly reduced severity of radiotherapy induced skin reactions during the course of radiation therapy in head and neck cancer patients undergoing radical or post operative radiation therapy. This result do not concur with two randomized controlled trials reported no significant effect of Aloe vera gel in preventing skin reactions associated with radiotherapy in breast cancer patients^13,26. But the present study was conducted in head and neck cancer patients. Our study however, has few limitations. It is a small sample size study and the results need to be confirmed by larger multicenteric studies.

CONCLUSION:

We therefore conclude that even though Aloe vera gel was not effective in preventing radiotherapy induced skin reaction, it was effective in delaying the onset as well as reducing the severity of radiotherapy induced skin reactions in head and neck cancer patients. Aloe vera gel significantly reduced pain associated with radiotherapy induced skin reactions during the later period of radiotherapy. Low cost and good patient compliance for this topical application can make it a safe practice. A protocol can be prepared regarding the management of radiotherapy induced skin reactions for patients undergoing radiation therapy and which can be included in the curriculum. Nursing personnel working in the Radiation Oncology unit need to be made aware of side effects of radiation therapy; its assessment and the management of radiotherapy induced skin reactions in patients undergoing radiotherapy and can be employed in providing health education to patients undergoing radiation therapy to effectively manage the side effects of radiation therapy.

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Received on 27.05.2015 Modified on 11.05.2015

Accepted on 26.06.2015 © A&V Publication all right reserved

Int. J. Nur. Edu. and Research 3(3):July-Sept., 2015; Page 288-293

DOI: 10.5958/2454-2660.2015.00010.1