Prevention of skin reactions due to teletherapy in women with breast cancer: a comprehensive review

Abstracts

Teleterapia está entre las modalidades de tratamiento para el cáncer y uno de sus principales efectos adversos son reacciones de la piel, comúnmente llamado radiodermatitis. Este estudio objetivó analizar el conocimiento acerca de los productos tópicos utilizados para la prevención de la radiodermatitis que justifiquen la atención en teleterapia en mujeres con cáncer de mama. Se adoptó como método de investigación la revisión integradora de la literatura. Para la selección de los artículos se utilizaron cuatro bases de datos. La muestra fue constituida por 15 artículos. Los datos muestran que entre los productos tópicos analizados la caléndula, esteroides y Clair X tuvo un efecto protector significativo, destacando así por sus acciones. La ausencia de artículos publicados en Brasil se centra en la necesidad de seguir investigando para mejorar la calidad de la atención mediante el uso de productos con una eficacia científicamente probada.

Radiodermatitis; Radioterapia; Neoplasias de la Mama

Dentre as modalidades de tratamento para o câncer está a teleterapia, e um dos principais efeitos adversos dessa modalidade são as reações de pele, comumente chamadas radiodermatites. O presente estudo teve como objetivo analisar o conhecimento sobre as evidências acerca de produtos tópicos, utilizados na prevenção de radiodermatite, que fundamente o cuidado em teleterapia direcionado a mulheres com câncer de mama. Adotou-se como método de pesquisa a revisão integrativa da literatura. Para a seleção da bibliografia utilizaram-se quatro bases de dados. A amostra constitui-se de 15 artigos. Os dados demonstram que, dentre os produtos tópicos analisados, a calêndula, os corticoesteroides e o Xclair tiveram efeito protetor significante, destacando-se, assim, pelas suas ações. A ausência de artigos publicados no Brasil mostra a necessidade de mais pesquisas nessa área, visando a melhor qualidade na assistência a mulheres com câncer de mama, por meio da utilização de produtos com eficácia comprovada cientificamente.

Radiodermatite; Radioterapia; Neoplasias da Mama

REVIEW ARTICLE

Prevention of skin reactions due to teletherapy in women with breast cancer: a comprehensive review

Marceila de Andrade^I; Maria José Clapis^II; Talita Garcia do Nascimento^I; Thaís de Oliveira Gozzo^III; Ana Maria de Almeida^II

^IMaster's students, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, WHO Collaborating Centre for Nursing Research Development, Brazil

^IIFree lecturer, Associate Professor, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, WHO Collaborating Centre for Nursing Research Development, Brazil

^IIIPhD, Professor, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, WHO Collaborating Centre for Nursing Research Development, Brazil

^{Corresponding Author}

ABSTRACT

One of the possible courses of cancer treatment is teletherapy, and one of the most important adverse side effects are skin reactions, an ailment more commonly called radiodermatitis. The main purpose of this study is to analyze knowledge of the evidence about topical products used in the prevention of radiodermatitis, to support care delivery to women with breast cancer during teletherapy. The research method used here is the comprehensive literature review. Four databases were used to select the bibliography. The sample consists of 15 articles. The data shows that, among the topical products analyzed here, Calendula, corticosteroids and Xclair have shown significant protective effects, underlining their actions. The lack of articles published in Brazil highlights the need for further research in this area, seeking better care quality through the use of products with scientifically proven efficiency.

Descriptors: Radiodermatitis; Radiotherapy; Breast Neoplasms.

Introduction

One of the treatment courses for breast cancer is teletherapy, which makes use of ionising radiation. This damages the cell components, with DNA as the main target. Radiotherapy brings about changes or even mutations to the genetic material, and also leads to changes in cell function, until the death of the cell. Thus, ionising radiation causes damage to all living and normal cells, as well as malignant ones, thereby causing side effects⁽¹⁾.

Among local toxic effects, cutaneous reactions are highlighted, known as radiodermatitis: erythema, hyperpigmentation, dry scaling and moist scaling. What characterizes the latter is the exposure of the dermis and seepage of fluid, sometimes accompanied by exudate and crust or ulceration, or even necrosis^(2-3).

The degree of skin reaction depends on several factors, such as: irradiation in places where there is contact between surfaces, areas where the epidermis is thin or where skin integrity has been ruptured, like in the case of burns, concurrent chemotherapy, immunotherapy, associated medical conditions or co-morbidity, chronic exposure to the sun, smoking, localization of the tumor or field treated, tumor staging, large irradiated volume, high dose of total radiation, dose with a fraction of more than 2.0 Gy, and the type of energy used^(2-3).

In about 80% of the patients, radiation leads to dermatitis, varying in severity from moderate to severe erythema and moist scaling. The consequences are many, including decreased quality of life due to pain and interruption of treatment, which can be harmful for local control⁽⁴⁾.

Several studies have been conducted to assess the results of preventive interventions, and the management of skin reactions caused by radiotherapy. There is a continuous lack of evidence to recommend many courses of intervention or products used in clinical practice though. Studies focus on prevention more than management, and are wanting in methodological rigor, making it difficult to repair studies with a view to elaborating specific recommendations. Other methodology problems include small sample size, wide variety in the terms used to describe reactions and measurement tools⁽³⁾.

Considering that radiodermatitis tends to occur quite often and harms the quality of life of radiotherapy patients, and also the lack of consensus about the topical products used in prevention, the main purpose of this study is to analyze knowledge on the topical products used in the prevention of radiodermatitis, with a view to supporting care delivery to women with breast cancer during teletherapy.

Methodological Procedures

For the development of this study, Evidence-Based Practice (EBP) was adopted as the theoretical and methodological framework. A comprehensive literature review was chosen. This method permits the analysis and synthesis of multiple published studies on a certain subject, as well as the identification of gaps that need to be filled through new research, and also general conclusions about a particular study area, with the resulting incorporation of the best and most recent evidence for decision making and improvement of clinical practice^(5-6).

The preparation of the comprehensive review occurred in six stages: identification of the theme and selection of the hypothesis or research question, establishment of criteria for inclusion and exclusion of studies, sampling or search in the literature, definition of the information to be extracted from the selected studies, assessment of the studies included in the review, interpretation of the results and synthesis of knowledge⁽⁶⁾.

The guiding question for this review was: What scientific knowledge has been produced on topical products used in the prevention of radiodermatitis in women with breast cancer and subject to teletherapy?

For the selection of the bibliography, four different databases were used: MEDLINE (Medical Literature Analysis and Retrieval System Online), specifically PubMed, LILACS (Latin American and Caribbean Centre on Health Sciences Information - Literatura Latino-Americana e do Caribe em Ciências da Saúde), CINAHL (Cumulative Index to Nursing and Allied Health Literature) and the Web of Science, which is a set of databases (Science Citation Index, Social Science Citation Index, Arts and Humanities Citation Index, Current Chemical Reactions and Index Chemicus). Figure 1 displays the descriptors used in all the databases.

The criteria for inclusion as adopted to select the articles were: fully available; written in Portuguese, English or Spanish between January 2000 and July 2010; a central theme based on topical products used in the prevention of radiodermatitis in women with breast cancer who have been subject to teletherapy.

A pre-selection was made, comprising 20 references in CINAHL, 16 in Web of Science, 97 in PubMed and 14 in LILACS. Through the reading of the title and abstract, we identified 15 articles that met the previously established inclusion criteria and addressed the guiding question, and were therefore part of the final sample.

In possession of the articles, each was exposed to exploratory reading. With a view to establishing categories and assess the studies, with the consequent interpretation of results, an instrument was used with the following items: identification, the institution where the study was conducted, the type of scientific publication, the methodological characterization of the study and the assessment of methodological rigor⁽⁷⁾. Concepts nursing researchers proposed were used to set limits for the review⁽⁸⁾.

Concerning the identification of the selected papers' level of evidence, the following classification was used: level 1 - evidence from systematic review or meta-analysis of all relevant clinical trials, randomized and controlled, or arising from clinical guidelines based on systematic review of randomized controlled clinical trials; level 2 - evidence derived from at least one randomized well-defined clinical trial; level 3 - evidence obtained from well-defined clinical trials without randomization; level 5 - evidence arising from the systematic review of descriptive and qualitative studies; level 6 - evidence derived from one single descriptive or qualitative study; level 7 - evidence arising from opinions of authorities and/or reports from experts committees⁽⁹⁾.

Data were analyzed descriptively, permitting professionals to assess the quality of evidence about the research theme, thus supporting decision-making and the identification of knowledge gaps with a view to future research.

Results

The analysis of the 15 articles selected showed that, in five cases, the authors were nursing researchers, mostly in partnership with physicians from several different specialties. All were published in international journals and in English. l Research originated in several countries: the United States (3), Australia (2), India (2), Canada (1), France (1), Sweden (1), Germany (1), Israel (1), Spain (1) and Italy (1). In one case, the country of origin could not be established.

As for the studies' methods, thirteen articles had a quantitative approach, twelve being experimental studies (randomized controlled clinical trials) with evidence level 2 and one quasi-experimental study (Phase II clinical trial without randomization), with evidence level 3, considering strong evidence levels according to the classification used. One article was a narrative review of the literature and, as such, did not have an evidence level. The final article was a cohort study with evidence level 4.

Figures 2, 3 and 4 present a summary of the articles analyzed.

Discussion

Through an analysis of the selected publications, we identified a wide range of products used to prevent radiodermatitis in women with breast cancer during radiotherapy, such as covers based on topical corticosteroids, Biafine, Calendula, Tetra-Cream^®, Bepantol^®, Aloe Vera, and others.

Some studies show controversy about the efficiency of using topical corticosteroids in radiodermatitis treatment. In initial trials, the use of less potent corticosteroids, variations in the location and also the period to start the application, patients' heterogeneity in terms of cancer types, doses, regimens and application region of of radiotherapy and subjective analysis methods suggest that there is a lack of preventive effect for this substance. However, in the studies analyzed, we observed a clinical reduction in the severity of the symptoms shown, less damage to the skin permeability barrier and improvement of inflammatory response, resulting from the radiation-induced rupture of the barrier, as well as the significant reduction in the risk of developing moist scaling in patients using corticosteroids compared with those using other products^{(10,12,17-18)}.

According to the results shown, treatment with steroids should start together with the start of radiotherapy, for maximum effect. The importance of applications from the start of treatment is due to the fact that skin toxicity signs caused by radiotherapy may occur soon after the first dose of radiation^(12,17).

The protective effect of corticosteroids could be linked to their anti-inflammatory properties. Short-term observations have not shown any increase in the rate of telangiectasias, skin atrophy or the risk of suppression of the axis formed by the pituitary and adrenal glands. These factors limit their long-term use ⁽¹⁸⁾.

Among the products analyzed, Betamesanone 0.1%, Mometasone Fuorate and Beclometasone spray were the products that showed the best results and are also the most recommended for prophylactic use in the prevention of this co-morbidity.

However, the results of these research studies ^(10,12,17) should be used with care, as some studies have methodology problems that could put the findings at risk, such as non-homogeneity and reduced sample size, loss of patients during follow-up, lack of blinding, lack of control of the main confounding factors and lack of a control group. New studies with greater methodological strictness are necessary to confirm these findings.

Another agent that has shown efficiency in the prevention of radiodermatitis during RT in women with breast cancer is Calendula. Through the results of the study, we have seen that this cover was statistically better in the prevention of Cutaneous toxicity of Grade 2 or higher. The clinical relevance of this result is stressed through the significant improvement in self-assessed pain-related patient satisfaction, low levels of allergies and treatment interruption, except for the facility of application, as the patients consider this difficult to apply ⁽⁴⁾.

MAS065D (Xclair), which is a compound of hyaluronic acid, vitis vinifera, karité butter, telsmetine, glycyrrhizic acid and bisabolol in a hydrolipidic medium has also shown a protective effect in relation to skin toxicity due to radiotherapy. The main aim of this product is to reduce inflammatory reactions and keep a moist environment in the affected surface. Hyaluronic Acid (HA) is a natural biopolymer with a high capacity to retain water. It is the most important element of the extracellular unit of dermal tissue, providing mechanical and structural support. Clinical trials with the topical application of HA have shown improvement in wound cleaning, particularly in cases of radioepithelites, due to its notable rheological (viscosity), viscoelastic and hygroscopic properties (absorption of water), which are relevant in the healing process^(21-22).

Vitis vinifera and telmestine antiprotease have antioxidant properties that are able to inhibit harmful enzymes present in the exudate of the damaged skin and also protect the tissue from the damage free radicals cause. Another key substance that is present in Xclair is glycyrrhizic acid (liquorice root), which has anti-inflammatory properties. In the case of karité butter, extracted from Parkii butyrospermum, it is used for its emollient action⁽²¹⁾.

The results of the study show a global reduction in skin reaction due to radiation, as well as a delay in its appearance. It could also be concluded that Xclair provides an efficient option for radiodermatitis management. Treatment efficiency concerning pain and seepage should be considered in further research, involving groups of patients with specific characteristics⁽²¹⁾.

Final Comments

According to the surveys analyzed, to prevent radiodermatitis due to RT in women with breast cancer, the most recommended products for topical use, according to the level of evidence and the methodological definition of the studies, are topical corticosteroids, Calendula and MAS065D (Xclair), which can therefore be incorporated into clinical practice.

The studies suggest, as an indication for the use of these products, uniform application, starting at the same time as the start of RT, twice a day or more often, depending on the occurrence of dermatitis and pain, until the treatment is completed or continuing for another two weeks after the end of treatment. In the case of Calendula, the restriction on use within 2 hours of the RT session should also be mentioned.

Radiodermatitis is an important side effect, due to its high rate of occurrence among patients submitted to teletherapy. It should be mentioned here that studies with a better methodological definition are needed to prove or reject these study findings. In addition, the lack of articles published in Brazil suggests the need for further research in this area, in order to establish protocol procedures for care related to prevention and appropriate management of the lesions, which institutions in search of better care quality can follow. The researchers hope that, through this study, interest on this subject in general will be enhanced.

Received: June. 21^st 2011

Accepted: Marc. 19^th 2012

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Publication Dates

• Publication in this collection
  12 Sept 2012
• Date of issue
  June 2012

History

• Received
  21 June 2011
• Accepted
  19 Mar 2012