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Abstract

Background

Radiodermatitis is a common skin injury in patients undergoing radiotherapy, especially in cases of head and neck cancer, and may impair treatment adherence and the patient’s quality of life. Therefore, the search for effective and low-cost interventions for the prevention and management of radiodermatitis is essential. In this context, Calendula- and Chamomile-based creams have been considered in oncological care.

Objective

To evaluate the effectiveness of topical Calendula and Chamomile creams in the prevention and treatment of radiodermatitis in head and neck cancer patients undergoing radiotherapy combined with chemotherapy.

Methods

This is a protocol for a randomized, controlled, triple-blind clinical trial employing a quantitative approach. The protocol adheres to the guidelines advocated by the Consolidated Standards of Reporting Trials (CONSORT) 2025 and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025. A total of 99 participants will be randomly allocated into 3 groups. Data will be collected using a four-section instrument and analyzed with Microsoft Office Excel and Statistical Package for Social Sciences (SPSS) version 20.0.

Results

This study aims to validate the effectiveness of Calendula and Chamomile creams in controlling radiodermatitis and to identify the most efficient option for preventing adverse effects.

Conclusion

The findings are expected to underscore the necessity of promoting and implementing systematic, scientifically grounded protocols in oncological patient care, emphasizing a humanized approach.

Trial and Protocol Registration

Brazilian Registry of Clinical Trials (ReBEC), RBR-8gxt823, https://ensaiosclinicos.gov.br/rg/RBR-8gxt823.

Keywords

calendula chamomile head and neck neoplasms radiodermatitis oncological nursing

Background/Rationale

Among non-communicable diseases (NCDs), cancer is the second leading cause of illness and death worldwide, second only to cardiovascular diseases. Data from the Global Cancer Observatory (Globocan), developed by the International Agency for Research on Cancer (IARC), estimate that 19.3 million new cancer cases will occur globally.¹

Cancer is the second most significant cause of illness and death worldwide, with non-melanoma skin cancer being the most prevalent type in Brazil. In the state of Rio Grande do Norte, approximately 11 500 new cases are predicted annually. Head and Neck Cancer (HNC) refers to a generic term used to define malignant tumors affecting regions such as the lips, oral cavity, pharynx (oropharynx, nasopharynx, and hypopharynx), larynx, maxillary sinuses, nasal cavity, paranasal sinuses, ethmoid sinuses, salivary glands, and thyroid gland, which have high prevalence rates.²

Excluding non-melanoma skin tumors, oral cavity cancer ranks as the eighth most frequent type of cancer. Globally, in 2020, approximately 530 000 new cases (2.0%) of oral cavity cancer were recorded. Among men, there were 373 000 new cases, corresponding to 8.46 cases per 100 000, being more common in men over 40 years old.¹ Oncology treatment frequently involves surgery, chemotherapy, and Radiotherapy (RT), the latter being widely used despite its associated adverse effects, such as Radiation Dermatitis (RD).

Radiotherapy is a therapeutic modality employing ionizing radiation to eliminate or reduce malignant cells, preventing their multiplication and/or causing cell death. Pre-calculated doses of radiation are divided into equal daily fractions to target as many tumor cells as possible while sparing surrounding normal tissue.

Head and neck cancer is among the most prevalent malignancies globally and is associated with a high mortality rate. Patients diagnosed with HNC frequently encounter significant challenges, not only with their treatment and prognosis but also with the adverse effects of therapy, particularly RD, a radiation-induced skin inflammation, and one of the most common and debilitating side effects of RT. It profoundly compromises a patient’s quality of life, leading to pain, discomfort, and complications that may necessitate interruptions in oncological treatment. It is estimated that up to 95% of patients undergoing RT develop some degree of RD.

RD affects up to 90% of patients undergoing RT in the head and neck region. This high incidence is due to the skin’s sensitivity and factors such as a compromised nutritional status, which often means less subcutaneous fat is present in the irradiated area, making the skin particularly vulnerable. These patients also often receive concurrent chemotherapy, which amplifies this adverse effect.^3-5 This condition can significantly impact the continuity and efficacy of treatment, as interruptions may be necessary for skin lesion healing, thus delaying curative therapy.

Moreover, RD-induced lesions can impair a patient’s quality of life, as these dermatological reactions cause pain (due to exposed nerve endings), local hypersensitivity, skin irritation, pruritus, desquamation, and depigmentation. In some cases, therapeutic doses may need to be reduced.^3,4,6 Pain in this context demands a multidisciplinary and individualized approach, considering its intensity, associated risk factors, and the patient’s functional status. Each person may require different interventions, both pharmacological and non-pharmacological.⁷

Beyond conventional RD treatments, such as corticosteroids and other topical medications, there is growing interest in complementary therapies, including natural creams. Topical creams formulated with calendula and chamomile have demonstrated efficacy in various dermatological conditions, yet their specific application in RD management remains underexplored. This scarcity of rigorous studies investigating these substances for radiodermatitis in HNC patients highlights a gap in care; these individuals face significant adverse effects that could potentially be avoided or mitigated by these therapeutic alternatives.

Various approaches have been studied for the prevention and treatment of RD, including compresses with chamomile tea, lotions containing Essential Fatty Acids (EFA) or Unsaturated Fatty Acids (UFA), Aloe Vera, ultrathin hydrocolloid dressings, and others. These are often classified as Integrative and Complementary Therapies, characterized as low-cost, simple techniques that provide relief, pain reduction, and other benefits.⁸ Notably, one of the recommended products is EFA, which has been standardized by the nursing team at the institution involved in this research for the prevention and treatment of RD.^9,10

Furthermore, treating symptoms in isolation with medications may result in polypharmacy, increasing the likelihood of drug interactions and adverse effects. This underscores the necessity of employing alternative methodologies for symptom relief and control.¹¹

Nevertheless, researchers have intensified studies in recent years to determine effective measures for preventing and treating RD, although no consensus has been reached.^3,4,9 Attention to the prevention and management of RD is fundamental in the clinical routine of nurses working in oncology units. In this context, it is crucial that professionals are well-informed and confident when providing guidance to patients, fostering a relationship of trust that facilitates adherence to instructions and ensures patient safety throughout the treatment process.

Additionally, according to Brazilian Federal Nursing Council Resolution No. 581/2018, nursing care for oncology patients must be provided by a specialized nurse who possesses the scientific knowledge and technical skills required to handle complex clinical situations. Through clinical practice, establishing a trusting relationship with the patient and their families is essential for offering humanized, high-quality care aimed at minimizing the impacts of treatment.¹²

Thus, it is imperative for nurses to acquire mastery over all phases of the radiotherapy process, guiding their actions with safety, critical analysis, and deep investigation into patient care. Antineoplastic therapy carries inherent risks and increasingly necessitates specific skills and knowledge from healthcare professionals to minimize its adverse effects.¹³

Furthermore, research must align with the Brazilian Health Research Priorities Agenda to strengthen this field and prioritize themes consistent with the National Policy on Science, Technology, and Innovation in Health and the principles of Brazil’s Unified Health System (SUS).¹⁴

The social impact of this research is substantial, given that HNC disproportionately affects low-income populations and those with lower education levels.^15,16 Low-cost therapies, such as natural creams, could significantly impact patient care by offering effective symptom relief and enhancing treatment adherence.

The Study

Objective

This study outlines the protocol for a randomized controlled clinical trial designed to assess the effects of topical creams on radiodermatitis in HNC patients undergoing radiotherapy combined with chemotherapy. Specifically, the research aims to:

• Identify sociodemographic, clinical, oncological treatment, and health-disease history characteristics of HNC patients undergoing RT combined with chemotherapy.

• Evaluate the effectiveness of calendula cream in preventing and treating RD in HNC patients undergoing RT combined with chemotherapy.

• Evaluate the effectiveness of chamomile cream in preventing and treating RD in HNC patients undergoing RT combined with chemotherapy.

• Compare the effectiveness of calendula cream and chamomile cream in preventing and treating RD in HNC patients undergoing RT combined with chemotherapy.

Research Question

What is the effectiveness of topical calendula or chamomile creams in preventing and treating radiodermatitis in head and neck cancer patients undergoing radiotherapy combined with chemotherapy?

Study hypotheses

The hypotheses of this research are summarized in Table 1.

Table 1.

Study Hypotheses

Null hypotheses (H₀)	0.1. No statistical difference exists between calendula and chamomile cream properties in preventing and treating radiodermatitis in head and neck cancer patients undergoing chemoradiotherapy
	0.2. Calendula cream is not effective in preventing and treating RD in head and neck cancer patients undergoing chemoradiotherapy
	0.3. Chamomile cream is not effective in preventing and treating RD in head and neck cancer patients undergoing chemoradiotherapy
Alternative hypotheses (H₁)	1.1. Statistical differences exist in the efficacy of calendula and chamomile creams in preventing and treating RD in head and neck cancer patients undergoing chemoradiotherapy
	1.2. Calendula cream is effective in preventing and treating RD in head and neck cancer patients undergoing chemoradiotherapy
	1.3. Chamomile cream is effective in preventing and treating RD in head and neck cancer patients undergoing chemoradiotherapy

Source: Own research (2025).

Detailed Methods

Design

This study outlines a randomized, controlled, triple-blind clinical trial protocol with a quantitative approach, adhering to the standards recommended by the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)¹⁵ (Supplemental document 1. SPIRIT 2025 Checklist of Essential Items to Include in a Randomized Trial Protocol to Promote Transparency and Adequate Description of Study Planning) and the Consolidated Standards of Reporting Trials (CONSORT).¹⁶ (Supplemental Document 2 – Consolidated Standards of Reporting Trials to Standardize How the Results of Randomized Clinical Trials Are Reported). The study is registered on the Brazilian Clinical Trials Registry (ReBEC) (registration no. RBR-8gxt823, available at https://ensaiosclinicos.gov.br/rg/RBR-8gxt823).

Study Setting and Sampling

The study will be conducted in the radiotherapy department of a non-profit institution recognized by the Ministry of Health (MS) as a High Complexity Oncology Center (CACON). This institution, which provides services ranging from medical consultations to advanced radiotherapy techniques, has previously hosted other research projects.¹⁷

The radiotherapy department was selected as the primary entry point for oncology patients specializing in head and neck conditions who are beginning antineoplastic treatment. It experiences high daily demand and follows well-established protocols. Additionally, the department features 4 radiotherapy machines operating across morning, afternoon, and evening shifts, supported by a multidisciplinary team comprising nurses, physicians, physicists, nursing technicians, and radiotherapy technicians.

The study population will consist of patients diagnosed with head and neck cancer admitted to the radiotherapy department to commence radiotherapy treatment in conjunction with chemotherapy.

The sample size calculation considered the following parameters: the number of groups evaluated in the study (three: Control: EFA; Experimental 1: Calendula; Experimental 2: Chamomile), the number of scale applications per patient (approximately 7 evaluations), significance level (α = 0.05), and test power (1 – β) = 0.80. As this is a pioneering study with no prior research available as a basis for estimating an effect size, a small effect size of 0.10 was assumed. Based on these parameters, the sample size calculation was performed using the GPower 3.1.9.7 software, considering a repeated-measures ANOVA statistical test, resulting in a total sample size of 99 patients, therefore 33 in each group.

Inclusion and/or Exclusion Criteria

The inclusion criteria for this research are as follows: being 18 years of age or older, having a histologically confirmed diagnosis of head and neck cancer with an indication for radiotherapy treatment combined with chemotherapy, absence of prior antineoplastic treatment history, absence of prior radiotherapy history in the same treatment field/site, and having intact and continuous skin in the head and neck region on the first day of radiotherapy treatment.

The exclusion criteria are as follows: patients who interrupt oncologic treatment for a period exceeding 8 days, use any other type of product on the skin in the radiotherapy treatment area, or have any allergy or hypersensitivity to EFA, calendula, or chamomile.

Study Interventions

The study will comprise 3 groups: a Control Group (CG) and 2 Experimental Groups (G1 and G2). Randomization will be conducted using a simple randomization process through an online virtual platform, available at https://www.randomization.com/. In this study, randomization will be applied to the tested interventions rather than to the patients. Instead of randomly assigning participants to different treatment groups, randomization will occur at the intervention level, meaning each participant will be randomly assigned to one of the interventions being compared. This procedure is intended to ensure an equitable comparison between the tested interventions, minimizing potential selection and control biases. The choice to randomize interventions rather than patients is justified by the goal of evaluating the relative efficacy of different therapeutic approaches in a specific patient sample while maintaining triple blinding.

Thus, the CG will include patients using essential fatty acids (EFA) topically to prevent and treat RD. Experimental group 1 (G1) will include patients using calendula topically for the same purposes, while experimental group 2 (G2) will consist of patients using chamomile topically.

To verify the feasibility of the protocol and make necessary adjustments to the instruments and procedures, a pilot test will be conducted with the first 3 participants. This preliminary phase aims to validate the methodology employed and ensure standardization and proper adherence to the proposed intervention.

In addition, to assess the patient’s perspective on health outcomes, we will apply Patient-Reported Outcome Measures (PROMs). This approach is highly valued, as the patient is the primary beneficiary of the study, and its use can also increase patient satisfaction with the treatment.^18,19

Study Schedule

Table 2 presents the adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 schedule, systematically outlining participant enrollment, interventions, and evaluations across respective periods. Furthermore, treatment adherence will be monitored using a patient diary. Patients will be instructed to record their cream use 3 times a day by marking an “x” for the morning, afternoon, and evening applications.

Table 2.

Adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 - Participant Timeline: Schedule of Enrollment, Interventions, and Assessments

Timepoint	Trial period
	Enrollment		Post-randomization					Close-out
	-t_i to 0	0	t ₁	t ₂	t ₃	t ₄	etc.	t _x
Enrollment
Eligibility screen	x
Informed consent	x
Randomization
Intervention/comparator
Group 1: Calendula cream			→ (Daily, 3x/day during RT)	→	→	→	→	→ Until 7 days post RT
Group 2: Chamomile cream			→ (Daily, 3x/day during RT)	→	→	→	→	→ Until 7 days post RT
Group 3: EFA cream (control)			→ (Daily, 3x/day during RT)	→	→	→	→	→ Until 7 days post RT
Assessments
Sociodemographic/clinical data	x
RTOG – Skin toxicity assessment			X (weekly during RT)	x	x	x		X (7 days post RT)
VAS – Pain assessment			X (weekly during RT)	x	x	x		X (7 days post RT)
Adherence (diary review)			X (weekly check)	x	x	x
Adverse events monitoring			Continuous monitoring

Abbreviations: RTOG: Radiation Therapy Oncology Group; VAS: Visual Analog Scale; EFA: Essential Fatty Acids; RT: Radiotherapy.

Source: Own research (2025).

Fidelity of Intervention

In this clinical trial, a triple-blind design is adopted, ensuring that patients, researchers, and statisticians involved in data analysis remain blinded to intervention allocation. The data will only be revealed after data collection is completed and published in an open access journal. The purpose of blinding is to prevent expectation bias, a tendency to interpret intervention results more favorably or unfavorably based on the researcher’s or analyst’s perspective.¹⁸

Throughout the study, the cream containers will be labeled with numerical codes ranging from 1 to 99, randomly assigned to ensure that neither patients nor researchers can identify which cream corresponds to the CG or experimental groups (G1 or G2). Furthermore, all containers for the topical application creams will be identical in color and size, ensuring that all creams appear indistinguishable.

Blinding the statistician aims to ensure that data analysis is conducted impartially and free from any preconceived notions. The statistician responsible for data analysis will have no access to information regarding patient allocation, thereby avoiding any conscious or unconscious influence on the analyses. To achieve this, the data will be analyzed using a coded database, where interventions assigned to each patient will be identified solely by code numbers. This strategy guarantees that the statistician remains blinded to the distribution of interventions, preserving the integrity of the analysis and preventing bias in result interpretation.

The only individual with access to the cream randomization list will be the pharmacist responsible for cream preparation, and even then, access will only be granted after formal authorization to disclose the list post-analysis.

Pharmaceutical Composition

A partnership will be established with a compounding pharmacy possessing a valid Brazilian Registry of Legal Entities (CNPJ) and certification from the National Health Surveillance Agency (Anvisa), operating under the supervision of a licensed pharmacist registered with the Regional Pharmacy Council (CRF). The pharmacy will prepare the study products (EFA, calendula, and chamomile) in a manner ensuring identical presentation, thereby maintaining the trial’s triple-blind protocol. Table 3 elucidates the pharmaceutical specifications of the study products.

Table 3.

Pharmaceutical Specifications of Study Products

Product	Components	Volume/vial
Essential fatty acids (EFA)	Sunflower oil Q.S.	30 g
	Vitamin A 1%
	Vitamin E 0.2%
	Caprylic acid 5%
	Carbopol gel Q.S.
Calendula	Calendula glycolic extract 10%	30 g
	Vitamin A 1%
	Carbopol gel Q.S.
Chamomile	Chamomile glycolic extract 10%	30 g
	Vitamin A 1%
	Carbopol gel Q.S.

Source: Own research (2025).

The administered dose will depend on the size of the treatment field for each participant. It is estimated that an average of 10 mg will be applied per session; however, this dosage may be adjusted as necessary to ensure sufficient product to cover the entire irradiated surface.

The formulation of the products will be safe, with stability lasting approximately 5 months in compliance with regulations and considering microbiological control. The products will be produced based on the number of study participants to avoid expiry before usage.

Instrument With Validity and Reliability/Data Source

The data collection instrument is divided into 4 sections: (1) Patient identification and sociodemographic data; (2) Clinical data and details of the antineoplastic treatment; (3) Data related to RD according to the criteria from the Radiation Therapy Oncology Group (RTOG); and (4) Pain data assessed using the Visual Analog Scale (VAS). The RTOG developed the Acute Radiation Morbidity Scoring Criteria in 1982.¹⁹

The scoring criteria are classified from grades 0 to 4, characterizing RT effects. This scoring system, established over 30 years ago by RTOG, remains widely recognized and accepted by global medical and nursing communities. The RTOG scale criteria are as follows: Grade 0 – no reaction, intact skin; Grade 1 – mild erythema, epilation, and/or dry desquamation; Grade 2 – painful erythema, localized moist desquamation, and/or moderate edema; Grade 3 – confluent moist desquamation and/or significant edema; Grade 4 – ulceration, hemorrhage, and/or necrosis.

To evaluate the reported oncology-related pain intensity and degree, the VAS will be employed, ranging from 0 to 10, where 0 represents the absence of pain and 10 indicates maximum pain tolerable by the patient. The preparations are not odorless; however, this did not affect the use of the creams or adherence to the treatment.²⁰

The primary goal of using the RTOG scale is to assess primary study outcomes related to RD prevention and/or treatment. However, given the influence of pain on quality of life and the continuation of oncological treatment, pain will also be assessed as a secondary outcome using the VAS.²¹

Data Collection and Analysis

Data collection is expected to commence in February 2025 and approximately last 10 months. The data collection process will conclude only once the sample size established by statistical analysis has been achieved. In the event of withdrawals or losses of participants during the study, new participants will be recruited to maintain the planned sample size.

Patients will be approached by the principal investigator (P1) on the first day of radiotherapy treatment, either in the morning or afternoon, based on their schedule. Eligibility for study participation will be evaluated against inclusion criteria.

Once deemed eligible, the patient or their responsible party will be informed of the research objectives, risks, and benefits. Upon agreement, they will be asked to read and sign the Informed Consent Form, which will be collected by P1.

If the patient consents to participate, P1 will perform participant allocation using a pre-randomized list generated from a designated website. Following allocation, P1 will collect the data for the first 2 sections of the data collection instrument: ‘Patient and sociodemographic data’ and ‘Clinical and antineoplastic treatment data’. This initial data collection will require access to the participants’ physical and electronic medical records and radiotherapy treatment files. It is emphasized that RD evaluation will be carried out by the collaborating researcher (P2) and documented in the Patient’s Electronic Record (PER). Subsequently, these data will be compiled by P1, and the third section of the data collection instrument—comprising RD evaluation through RTOG criteria—will be completed.

The first 3 participants will constitute the pilot test, and their data will help refine and adjust the study. If no changes are required in data collection dynamics, these participants will be included in the final sample.

Participants will be instructed to apply the topical cream daily, 3 times per day, starting from the first radiotherapy treatment day. This will allow for evaluation regarding RD prevention. Should participants develop any RD grading, they will remain in the study and continue product use to assess its treatment efficacy.

In cases of allergic reactions to the product, participants will be immediately excluded from the study, and product use will be discontinued. Such participants will be monitored by the research team, nursing staff, and the responsible physician for local care and treatment. Participants will also be instructed to adhere strictly to the researchers’ guidance to avoid introducing biases. All participants will be thoroughly informed about the correct application and storage of the product, and compliance with these guidelines will be verified at each evaluation.

It is reiterated that participation in the study is voluntary and free of charge, allowing withdrawal at any time at the participant’s discretion without any consequence or loss of benefits.

Ethical Considerations

The research project was initially submitted to the Research and Extension Committee (ComPEx) of the cancer league and subsequently to the Research Ethics Committee. It received approval under Certificate of Ethical Appreciation number 86642625.2.0000.5293. Participation from patients, caregivers, or professionals will be voluntary, contingent upon signing the Informed Consent Form, with the option to withdraw at any time without prejudice to treatment or fear of judgment or penalties.

The study will adhere to the ethical principles outlined in Resolution 466 of December 12, 2012, by the Brazilian National Health Council, ensuring respect for human dignity and protection of participants in research involving human beings.²²

Risk Analysis

Participants in this study may face risks associated with allergic reactions in the product application area. However, it is emphasized that the products are approved by Anvisa and are already employed in Radiotherapy services.

Should any significant discomfort, hypersensitivity, or allergy occur, participants will be immediately excluded from the study and product use will cease. Participants will then be monitored by the research team, and any necessary treatments will be administered. In cases of severe radiodermatitis, alternative interventions will be prescribed by the radiotherapy physician and nurse.

Confidentiality-related risks will be addressed through data usage strictly for scientific purposes, with participant names kept confidential in a secure database to ensure anonymity. Physical data will be stored exclusively by the principal investigator in a private, locked cabinet at the investigator’s residence, ensuring a controlled environment to prevent damage, theft, or unauthorized access. Security measures include cataloging efficiency and periodic review of archives. Additionally, digital data will be stored on a password-protected computer for exclusive use by the principal investigator and research supervisor, located at the responsible institution through virtual spreadsheets with exclusive access to team members who have signed the Confidentiality Agreement, not allowing third parties to handle any documentation that comprises or has resulted from the research project activities. Data will be managed in compliance with the General Data Protection Law and National Research Ethics Commission guidelines, secure deletion of data will occur after a maximum retention period of 5 years following study completion.

Characteristics of the Sample

Participants will be randomly assigned to one of 3 groups: a control group using topical essential fatty acid cream, Experimental Group 1 using topical Calendula cream, or Experimental Group 2 using topical Chamomile cream. We estimate a sample size of 33 patients per group, for a total of 99 patients. Product application will follow the protocol described in Table 4.

Table 4.

Step-by-Step Product Application During the Study

Description of cream application technique	Applications will be performed on the entire irradiated area during treatment, following these steps:
	(1) Wash hands with running water and soap
	(2) Ensure the application area is clean and dry
	(3) Open the cream vial and dispense approximately 10 mL onto the pads of the ring and middle fingers
	(4) Apply the topical cream evenly over the entire irradiated region
	(5) The cream should be well spread on the skin for adequate absorption, avoiding excess product. The cream should be used 3 times a day throughout the entire radiotherapy treatment
1st Application	Patients will receive instructions on product use and then perform the first application under supervision, with additional guidance provided as needed
Subsequent applications	Subsequent applications will be performed at home by the study participant, a family member, or a caregiver, in accordance with the instructions given during the first application

Source: Own research (2025).

The participant will have their skin assessed on the first day of radiotherapy treatment. Subsequently, the evaluation will occur once a week throughout the radiotherapy treatment to observe the presence and/or progression of RD. The final evaluation will take place 7 days after the conclusion of the radiotherapy sessions, as RD is still considered acute during this period. The assessment will be conducted by the collaborating researcher (P2), who, like P1, will not have knowledge of the group to which the patient belongs, thus avoiding bias and maintaining the study’s integrity.

Radiotherapy treatment is administered 5 days a week, from Monday to Friday. However, the designated cream must be used by the patient every day, including weekends. Additionally, the patient will receive a cream usage diary to encourage adherence to the proper use of the product. The diary will include instructions on the correct use of the cream and an adapted calendar divided into weeks, days, and time slots, corresponding to the prescribed schedule for cream application throughout the radiotherapy treatment. Patients will be instructed to mark an “X” in the box corresponding to the time of application once they have used the cream or leave the box blank if the cream was not applied at the predetermined time.

Concomitant interventions were allowed when clinically indicated, especially in cases of advanced radiodermatitis requiring specialized medical and nursing care. According to institutional protocol, during the radiotherapy period, patients were instructed not to use any other topical products on the irradiated area and to apply exclusively the cream provided during the initial consultation with the specialized oncology nurse.

A strict fixed time for cream application will not be enforced, as the patient must ensure that their skin is clean and dry, free of any creams or lotions, before undergoing radiotherapy. Therefore, the recommendation is to use the cream 3 times a day, once during each shift, at times chosen by the patient. The objective of the cream usage diary is to evaluate adherence to the protocol proposed in the study.

Table 5 presents the model of the cream usage diary for the patient, considering a 20-day treatment example:

Table 5.

Patient Cream Use Diary Template

Week 1

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Week 2

Day 8

Day 9

Day 10

Day 11

Day 12

Day 13

Day 14

Week 3

Day 15

Day 16

Day 17

Day 18

Day 19

Day 20

Day 21

Week 4

Day 22

Day 23

Day 24

Day 25

Day 26

Day 27

Day 28

Abbreviations: M: Morning; PM: Afternoon; HS: Night.

Source: Own research (2025).

Statistical Analysis

The collected data will be stored and processed using Microsoft Office Excel and Statistical Package for the Social Sciences (SPSS) version 20.0. Descriptive and inferential statistics will be performed, with data presented in tables, charts, and figures. The Chi-square test, Fisher’s exact test, or ANOVA will be used to assess relationships between variables. Additional statistical tests will be applied as needed. A significance level of 5% will be adopted throughout the study.

Discussion

The literature supports the beneficial properties of both calendula and chamomile for skin regeneration and healing. Calendula, in particular, is recommended for topical use for anti-inflammatory and healing therapeutic interventions.²³ Additionally, studies on chamomile have demonstrated its efficacy in angiogenesis and in the treatment of complex skin lesions, such as those in patients with ostomies.²⁴ Thus, the main expected result is the confirmation of the efficacy of the described calendula and chamomile creams in treating RD in patients with HNC undergoing concurrent chemoradiotherapy.

Furthermore, through this evaluation, the study aims to identify which of these topical treatments may be most effective in preventing and managing the adverse effects of RT, such as pain, inflammation, impaired skin integrity, cognitive disorders, and even death of bone tissue that can result in chronic and difficult-to-heal injuries.²⁵ Consequently, the study will contribute to improved clinical management of RD by offering more affordable and accessible therapeutic alternatives that can be easily integrated into treatment protocols for oncological patients. Confirming the efficacy of these creams could result in their inclusion in the therapeutic arsenal for RD patients, significantly alleviating the clinical condition of these individuals.

Regarding the use of natural and complementary treatments, recent decades have seen research into new radioprotective products as alternatives for managing the adverse effects of cancer treatment, as these compounds show the potential to be as effective as existing ones.²⁶ For example, a randomized, double-blind clinical trial involving patients undergoing radiotherapy for breast cancer compared the use of liposomal gel with and without chamomile extract for the prevention of radiation dermatitis. The study’s primary outcome was the occurrence of dry desquamation; researchers found that no statistically significant differences were observed between the 2 gels, indicating the effectiveness of both. However, a lower occurrence of reported symptoms was found in the chamomile liposomal gel group during the first 3 weeks.²⁷

Another randomized, double-blind clinical trial compared liposomal gel with and without chamomile extract, focusing on the treatment and prevention of RD in head and neck cancer patients undergoing radiotherapy. The primary outcomes were the occurrence of dry desquamation and the cumulative dose of ionizing radiation at the first occurrence of dry desquamation. The study found no statistically significant differences between the 2 groups. However, the chamomile liposomal gel group demonstrated lower degrees of RD.²⁸

Current research, such as the studies cited above, has demonstrated that chamomile can be effective in reducing the adverse effects of radiodermatitis.^27-29 Therefore, the results of this research are expected to impact not only the clinical management of RD but also pave the way for future investigations into the use of these treatments.

The research outcomes are expected to have a meaningful impact both on the reduction of medical treatment costs and on improving the quality of life of patients. The use of low-cost topical creams, such as calendula and chamomile, may provide an effective and easily implementable alternative for treating RD patients, reducing the need for more complex interventions or expensive medications, given the significant costs of treatment.³⁰

Another anticipated outcome is the development and training of human resources through the preparation of new researchers and healthcare professionals to apply the obtained results and implement new therapeutic strategies for cancer patients. This research will foster the development of technical and scientific skills applicable to future investigations or clinical practice. Cancer remains a prevalent disease, with thousands of cases registered annually,¹ demanding continuous and urgent advancements in oncology.

The study will also result in scientific publications in high-impact journals, contributing to the advancement of technical-scientific knowledge in the field of oncological nursing. Additionally, the findings will be presented at national and international conferences, aiming to share the results with the scientific community and healthcare professionals, expanding the reach and application of the discoveries. Public dissemination of the results may also generate increased awareness regarding the importance of effective management of RD and the use of alternative therapies, such as calendula and chamomile, which can directly benefit patients, their families, and healthcare professionals.

The study could impact the formulation of policies, protocols, and practices related to the topic if the results indicate such feasibility. Furthermore, the clinical findings could effectively contribute to improved healthcare quality and accessibility by providing low-cost therapeutic alternatives, thereby enhancing and expanding treatment options while promoting adherence to oncological care protocols. Moreover, research like this can support strategies aimed at broadening access to healthcare for low-income and low-education populations, who are most affected by HNC.^15,16

Thus, the study may complement the clinical practice of nurses working in oncology units, enabling them to apply complementary therapies with minimal side effects during the management of patients undergoing RT and presenting RD, delivering more effective care and providing the patient with better comfort and recovery.

Conclusion

Therefore, this study primarily aims to assess the effects of topical calendula and chamomile creams on patients with head and neck cancer undergoing radiotherapy combined with chemotherapy. The study’s relevance is justified by its clinical, scientific, and social significance, potentially contributing to the improvement of therapeutic options available for patients with this type of cancer, as well as enabling a more affordable and integrated approach to radiation dermatitis treatment, given the existing gap in the literature regarding the efficacy of topical methods for pain control. The investigation is also justified by the need for a greater understanding of the effects of radiotherapy on oncological patients and the exploration of alternatives that can mitigate the negative impact of radiotherapy, improving these individuals’ quality of life.

Supplemental Material

Supplemental Material - Use of Topical Calendula and Chamomile Creams for the Management of Radiodermatitis in Cancer Patients: A Randomized Clinical Trial Protocol

Supplemental Material for Use of Topical Calendula and Chamomile Creams for the Management of Radiodermatitis in Cancer Patients: A Randomized Clinical Trial Protocol by Tâmara Taynah Medeiros da Silva, Kauanny Vitoria Gurgel dos Santos, Guilherme Moises Alves Fernandes, Danielle de Oliveira Rocha, Lara Dantas de Rubim Costa, Kleyton Santos de Medeiros, Kátia Regina Barros Ribei in Global Advances in Integrative Medicine and Health

Footnotes

ORCID iDs

Tâmara Taynah Medeiros da Silva

Kauanny Vitoria Gurgel dos Santos

Guilherme Moises Alves Fernandes

Danielle de Oliveira Rocha

Lara Dantas de Rubim Costa

Kleyton Santos de Medeiros

Kátia Regina Barros Ribeiro

Daniele Vieira Dantas

Rodrigo Assis Neves Dantas

Ethical Considerations

The experimental protocols were approved by the Ethics and Research Committee (ERC) of the League Against Cancer (No. 86642625.2.0000.5293) on March 13 of 2025. All research activities followed ethical precepts and were carried out in accordance with the hospital’s standards. Informed consent for the use of topical creams for research purposes was obtained from all patients before the start of the intervention. They had the option to refuse to participate,choosing not to participate.

Consent to Participate

The Ethics and Research Committee of the League Against Cancer approved our interviews (approval: 86642625.2.0000.5293) on March 13 of 2025. Interviewees gave written informed consent for review and signature before the intervention began.

Funding

The authors received no financial support for the research,authorship,and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. *

Supplemental Material

Supplemental material for this article is available online.

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Supplementary Material

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