Abstract
Background/Aim: Head and neck cancer is a major malignancy worldwide. The treatment strategy for head and neck cancer usually involves radiotherapy. The main side effect of radiotherapy is radiation dermatitis. Thus, determining the most effective topical regimen for the prevention of radiation dermatitis in head and neck cancer patients is a critical issue.
Patients and Methods: PRISMA-NMA guidelines were used in this network meta-analysis. We included only randomized control trials. A random effects model was used. Heterogeneity was evaluated by I2 and Cochran’s Q tests.
Results: We included a total of 1,304 patients in the network meta-analysis. Among them, olive oil was the only effective regimen when compared with usual care (OR=0.18, 95%CI=0.03-0.95). The I2 value was 56%. The test of heterogeneity yielded a p-value of 0.10.
Conclusion: Olive oil was the most effective regimen for the prevention of radiation dermatitis.
Keywords: Radiotherapy, head and neck cancer, radiation dermatitis, meta-analysis
Head and neck cancers are a major malignancy worldwide and include nasopharyngeal, oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers. The global burden of head and neck cancer has been increasing (1). Treatment strategies for head and neck cancer include radiotherapy, chemotherapy, targeted therapy, immunotherapy, and surgery. Following radiotherapy for head and neck cancer, the most common side effects in cancer survivors are radiation dermatitis and oral mucositis (2).
Radiation dermatitis (RD) usually appears within a few weeks after the start of radiation therapy. Despite advances in radiotherapy techniques, skin reactions are still inevitable. Specifically, approximately 85% of radiated patients with head and neck cancer develop moderate to severe skin reactions (3), the severity of which can be evaluated using the Common Terminology Criteria for Adverse Events proposed by National Cancer Institute (NCI-CTCAE) criteria (4) or the Radiation Therapy Oncology Group (RTOG) criteria (5). Early symptoms include generalized erythema, dry desquamation, pruritus, epilation, scaling, dyspigmentation, and hair loss (6). Radiation dermatitis can affect the patient’s quality of life. When symptoms are severe, radiation therapy may even need to be interrupted.
Because radiation dermatitis may interfere with the course of radiation therapy, it is common in clinical practice to adopt prophylactic interventions prior to the onset of radiation dermatitis; such prophylaxis consists of general skin care measures and topical agents (7,8). The main topical agents used in clinical practice include topical corticosteroids, trolamine, Aloe vera, sucralfate, or hyaluronic acid. Most of the studies investigating this issue use different interventions, but the effects are still controversial, thus finding safe and effective prevention strategies is a priority for clinicians and patients.
Although few systematic reviews have reported whether each specific regimen may alleviate radiation dermatitis in patients with head and neck cancer (9,10), there is a lack of studies demonstrating cross-intervention comparisons between different prevention strategies for radiation dermatitis. Since determining the most effective topical regimen for the prevention of radiation dermatitis in head and neck cancer patients is critical, we conducted this network meta-analysis to identify the most effective prophylactic regimen.
Patients and Methods
Study protocol. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for Network Meta-Analyses (NMA) (11). We registered this meta-analysis on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD: CRD42021282759).
Literature search. Three authors (CHH, MYW, and YCW) independently queried three electronic databases, including PubMed, Cochrane, and Embase, from inception to October 2021. Inconsistency among the search results was resolved by consensus. We set the keywords as [(head and neck cancer) OR (head and neck neoplasm) OR (head and neck tumor) OR (head and neck carcinoma) OR (nasopharyngeal cancer) OR (oropharyngeal cancer) OR (oral cavity cancer) OR (laryngeal cancer) OR (hypopharyngeal cancer)] AND [(radiodermatitis) OR (radiation dermatitis) OR (radiodermatitis) OR (skin toxicity) OR (skin reaction) OR (skin damage) OR (skin reactions)) AND ((prevention) OR (prophylaxis)] (9). We also checked the references of related articles for additional studies.
Inclusion and exclusion criteria. The systematic review included: 1. studies investigating the topical prevention of radiation dermatitis in head and neck cancer patients; 2. randomized control trials; 3. human studies; 4. studies written in English. After including articles meeting the above-mentioned criteria, articles that were: 1. case reports, case series, cohort studies, case-control studies, nonrandomized clinical trials, and self-control trials; 2. studies evaluating radiodermatitis of patients with other cancer (breast cancer, skin cancer, etc.), 3. without available full text; 4. conference posters; 5. conducted on pediatric patients, were excluded.
Data extraction. Three authors (CHH, MYW, and YCW) independently extracted data from the included studies; when there was a discrepancy, a senior author (YSK) was consulted. The primary endpoint was set as grade 3 or more radiation dermatitis. Since the RTOG radiation dermatitis grading and CTCAE radiation dermatitis grading are similar, we viewed both as equivalent (4,5). A second endpoint was set as the occurrence of grade 2 or more radiation dermatitis. We extracted the data according to the intention-to-treat analysis. The most severe radiation dermatitis grade was collected. Other information, including the author, year of publication, nation in which the study was conducted, patient number, details of treatment, cancer type, and study duration were also extracted.
Statistical analysis. Generalized linear mixed models (GLMMs) were used to conduct network meta-analysis with the restricted maximum likelihood method for estimation. The p score was used to evaluate the ranking of the included treatment modalities. We checked the evidence inconsistency if there was a closed loop in the network. The heterogeneity among the studies was evaluated by using I2 and Cochran’s Q tests.
Statistical analysis was undertaken by using statistical software R (version 3.6.1) within the R studio environment (Version 1.2.5019). A p-value less than 0.05 was considered significant. For Cochran’s Q test, the p-value threshold was set as 0.10, according to the recommendation from Cochran’s handbook (12).
Bias analysis. The risk of bias (ROB) tool was used to evaluate the quality of the included randomized controlled trials. CHH and MYW evaluated the risk of bias independently using a standardized protocol, and YCW made the final decision when disagreement occurred. The ROB figure was generated by Revman 5.4. A funnel plot and Egger’s test was used to evaluate publication bias.
Results
A total of 615 articles were initially identified from the three databases. A total of 145 articles were excluded as duplicates. An additional 207 articles were excluded after initial screening. A total of 249 articles were excluded after eligibility was assessed. Fourteen articles remained in the final review. The article collection flowchart is shown in Figure 1. The characteristics of the included articles are demonstrated in Table I.
Table I. Characteristics of included studies in the systematic review.
EG: Egypt; TW: Taiwan; CH: China; CA: Canada; BZ: Brazil; IT: Italy; IN: India; GE: Germany; FR: France; JP: Japan; Pt No: patient number; LC: Laryngeal cancer, OC: oral cavity cancer; OPC: oropharyngeal cancer; NPC: nasopharyngeal cancer; RT tech: radiotherapy technique; 2D: 2DRT; 3D-CRT: 3D-conformal radiotherapy; IMRT: intensity modulated radiotherapy; EBRT: external beam radiotherapy; LINAC: linear accelerator; VMAT: volumetric modulated arc therapy; QD: Once a day; BID: twice a day; TID: three times a day; O.D.: five times a day; JBO: Johnson’s Baby Oil; EFA: essential fatty acids.
Network meta-analysis. A total of 1,304 patients were included in our network meta-analysis. The network plot is shown in Figure 2. Twelve studies were involved in the final meta-analysis. One article was excluded from the final meta-analysis due to the absence of grade 3 side effects (17). One article reported results, but the study was terminated early (22). A total of 11 treatment arms were involved in this meta-analysis. When compared with the usual care, only olive oil showed significantly better prevention ability (OR=0.18, 95%CI=0.03-0.95). The I2 was 56%, and the test of heterogeneity showed a p-value of 0.10. The statistical results are shown in Figure 3.
P score ranking. The p-scores of the included treatment arms were as follows: Vicco® turmeric (0.8470), calendula (0.7565), Aloe vera (0.6687), Xonrid® gel (0.6403), usual care (0.5873), RGTA® (0.5643), trolamine (0.4460), steroid (0.3617), StrataXRT® (0.2922), NS-21 (0.2384), and olive oil (0.0976). From the p score ranking, we can conclude that olive oil has the best prevention abilities among the included treatment regimens.
Bias analysis. The risk of bias in the included studies is summarized in Figure 4 and Figure 5. Six studies were considered at high risk of bias because one or more items were assessed as high risk. Seven studies were rated as unclear risk of bias because one or more criteria were deemed unclear. One study was considered at low risk of bias because all domains received an evaluation of low risk. The overall quality of the studies was medium. Publication bias was evaluated by a funnel plot, and the results are shown in Figure 6. From the funnel plot, we can conclude that there is no publication bias in this meta-analysis.
Discussion
To our knowledge, this study is the first network meta-analysis of the topical prevention of radiation dermatitis in head and neck cancer patients. After screening for available clinical trials and observational studies, based on findings in the present systematic review and network meta-analysis, the most effective regimen for the prevention of radiotherapy-induced dermatitis is suggested to be olive oil.
Treatment strategies differ for each type of cancer, and different areas of the body have different sensitivity to radiation. The risk factors for radiation dermatitis include body site, comorbidity, lifestyle, concurrent chemotherapy, and radiation dose and duration (27). The pathology and mechanism of radiation dermatitis are not fully understood. Radiation-induced fibrosis, changes in skin lipid metabolism, apoptosis, and changes in the neovascularization process may be involved (28). To find appropriate preventive strategies, understanding the possible risk factors and pathological mechanisms is important; however, there is still a lack of research confirming which preventive strategies are the most effective.
Olive oil is a widely available treatment regimen. A previous study showed that olive oil is also effective in the prevention of radiation dermatitis in breast cancer patients (29). Since the mechanism of radiation dermatitis is similar in nasopharyngeal cancer and breast cancer, the effect of olive oil is more convincing.
According to our network meta-analysis, NS-21, RGTA®, StragtaXRT, Vicco® turmeric, Aloe vera, calendula, Xonrid® gel, trolamine, and steroids were not statistically significant in reducing radiation dermatitis in patients with head and neck cancer, and further studies are needed to verify their effectiveness.
Aloe vera is a natural anti-inflammatory treatment that can relieve skin discomfort, but there is insufficient evidence that Aloe vera can reduce severe radiation-induced skin damage (30). Trolamine is a commonly used agent in the prevention of radiation dermatitis. However, a previous meta-analysis showed that trolamine is not effective in preventing radiation dermatitis in breast cancer and head and neck cancer patients (31). Our network meta-analysis confirms that Aloe vera and trolamine are not effective in preventing radiation dermatitis in head and neck cancer patients.
Topical steroids have anti-inflammatory effects. According to a previous meta-analysis, topical steroids are thought to improve wet desquamation and radiation dermatitis scores (32). However, in patients with head and neck cancer, topical steroids are considered to cause skin thinning and bacterial infections and are not recommended (33). In our study, the effects of topical steroids were not statistically significant in preventing moderate to severe radiation dermatitis in patients with head and neck cancer. More evidence is needed to determine whether topical steroids are effective in preventing radiation dermatitis in patients with head and neck cancer.
Mepitel Film, a soft silicone dressing, showed a reduction in the incidence of radiation dermatitis in patients with breast cancer (34), but a randomized clinical trial (RCT) on the prevention of radiation dermatitis in head and neck cancer patients was terminated early because 46.4% of the patients could not tolerate Mepitel® Film (22). Compared to urea, chamomile may have an effect in delaying grade 2 radiation dermatitis, but more studies are needed to verify its effect (17).
The strength of our study is that we only studied radiation dermatitis in patients with head and neck cancer and only included RCTs with high levels of evidence. Second, we conducted a comprehensive search of the literature with two independent reviewers to assess the quality of the studies and to reduce any potential bias.
There are some limitations to this network meta-analysis. First, the usual care in each study may have differed. However, in most of the studies, the usual care was thought to be ineffective. The clinical studies were conducted to improve the efficacy of prevention measures. As a result, viewing all usual care as the same is reasonable. Second, although all RCTs were considered reasonable in terms of quality, some studies had small sample sizes. Third, most of the comparisons in the network meta-analysis were indirect. More head-to-head studies are needed in the future to compare the effects of different treatments.
Studies of topical agents used in the prevention of radiation dermatitis in patients with head and neck cancer should include larger sample sizes and placebo controls to confirm the effectiveness and safety of the interventions in patients. Continuous evaluation of appropriate skincare and prophylaxis is important, and future studies should ensure randomization, blindness, and intention-to-treat using appropriate methods to reduce the possible risk of bias. In addition, trials should use appropriate control groups to assess outcomes. More high-quality RCTs are needed in the future to confirm these results.
Conclusion
Our results indicate that olive oil is the most effective treatment for the prevention of radiation dermatitis in head and neck cancer patients. However, there is inadequate evidence to make any recommendation about prevention strategy. Further large-scale, high-quality RCTs are needed to evaluate the efficacy of the prevention of radiation dermatitis in head and neck cancer patients.
Conflicts of Interest
The Authors declare no competing interests in relation to this study.
Authors’ Contributions
YSK, KSM, and CHH conceived and designed the research; YSK, MYW, YCW, and CHH contributed to the data acquisition; YSK, YKT, and CHH analyzed data and interpreted the results; YSK, KSM, and CHH drafted, edited, and revised the manuscript; YSK, KSM, MYW, YCW, YKT, and CHH approved the final version of the manuscript.
References
- 1.Rahman QB, Iocca O, Kufta K, Shanti RM. Global Burden of head and neck cancer. Oral Maxillofac Surg Clin North Am. 2020;32(3):367–375. doi: 10.1016/j.coms.2020.04.002. [DOI] [PubMed] [Google Scholar]
- 2.Chow LQM. Head and neck cancer. N Engl J Med. 2020;382(1):60–72. doi: 10.1056/NEJMra1715715. [DOI] [PubMed] [Google Scholar]
- 3.Salvo N, Barnes E, van Draanen J, Stacey E, Mitera G, Breen D, Giotis A, Czarnota G, Pang J, De Angelis C. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature. Curr Oncol. 2010;17(4):94–112. doi: 10.3747/co.v17i4.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Common Terminology Criteria for Adverse Events (CTCAE) Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50. [Last accessed on November 1, 2021]
- 5.Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) Int J Radiat Oncol Biol Phys. 1995;31(5):1341–1346. doi: 10.1016/0360-3016(95)00060-C. [DOI] [PubMed] [Google Scholar]
- 6.Hymes SR, Strom EA, Fife C. Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006. J Am Acad Dermatol. 2006;54(1):28–46. doi: 10.1016/j.jaad.2005.08.054. [DOI] [PubMed] [Google Scholar]
- 7.McQuestion M. Evidence-based skin care management in radiation therapy: clinical update. Semin Oncol Nurs. 2011;27(2):e1–17. doi: 10.1016/j.soncn.2011.02.009. [DOI] [PubMed] [Google Scholar]
- 8.Chan RJ, Webster J, Chung B, Marquart L, Ahmed M, Garantziotis S. Prevention and treatment of acute radiation-induced skin reactions: a systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 2014;14:53. doi: 10.1186/1471-2407-14-53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Ferreira EB, Vasques CI, Gadia R, Chan RJ, Guerra EN, Mezzomo LA, De Luca Canto G, Dos Reis PE. Topical interventions to prevent acute radiation dermatitis in head and neck cancer patients: a systematic review. Support Care Cancer. 2017;25(3):1001–1011. doi: 10.1007/s00520-016-3521-7. [DOI] [PubMed] [Google Scholar]
- 10.Iacovelli NA, Galaverni M, Cavallo A, Naimo S, Facchinetti N, Iotti C, Fallai C, Orlandi E. Prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients: a systematic review. Future Oncol. 2018;14(3):291–305. doi: 10.2217/fon-2017-0359. [DOI] [PubMed] [Google Scholar]
- 11.Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, Ioannidis JP, Straus S, Thorlund K, Jansen JP, Mulrow C, Catalá-López F, Gøtzsche PC, Dickersin K, Boutron I, Altman DG, Moher D. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777–784. doi: 10.7326/M14-2385. [DOI] [PubMed] [Google Scholar]
- 12.Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available at: https://training.cochrane.org/handbook. [Last accessed November 1, 2021]
- 13.Abbas H, Bensadoun RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck. Support Care Cancer. 2012;20(1):185–190. doi: 10.1007/s00520-011-1110-3. [DOI] [PubMed] [Google Scholar]
- 14.Chou HL, Shueng PW, Liao LJ, Hsu CX, Kuo DY, Lo WC, Hou PY, Wang LY, Chou SF, Hsieh CH. Prophylactic NS-21 maintains the skin moisture but does not reduce the severity of radiation dermatitis in patients with head and neck cancer: a randomized control trial. Radiat Oncol. 2019;14(1):90. doi: 10.1186/s13014-019-1302-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Cui Z, Xin M, Yin H, Zhang J, Han F. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. Int J Clin Exp Med. 2015;8(7):11000–11006. [PMC free article] [PubMed] [Google Scholar]
- 16.Elliott EA, Wright JR, Swann RS, Nguyen-Tân F, Takita C, Bucci MK, Garden AS, Kim H, Hug EB, Ryu J, Greenberg M, Saxton JP, Ang K, Berk L, Radiation Therapy Oncology Group Trial 99-13 Phase III Trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13. J Clin Oncol. 2006;24(13):2092–2097. doi: 10.1200/JCO.2005.04.9148. [DOI] [PubMed] [Google Scholar]
- 17.Ferreira EB, Ciol MA, de Meneses AG, Bontempo PSM, Hoffman JM, Reis PEDD. Chamomile gel versus urea cream to prevent acute radiation dermatitis in head and neck cancer patients: results from a preliminary clinical trial. Integr Cancer Ther. 2020;19:1534735420962174. doi: 10.1177/1534735420962174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Ingargiola R, De Santis MC, Iacovelli NA, Facchinetti N, Cavallo A, Ivaldi E, Dispinzieri M, Franceschini M, Giandini C, Romanello DA, Di Biaso S, Sabetti M, Locati L, Alfieri S, Bossi P, Guglielmo M, Macchi F, Lozza L, Valdagni R, Fallai C, Pignoli E, Orlandi E. A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients. Radiat Oncol. 2020;15(1):193. doi: 10.1186/s13014-020-01633-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Chan RJ, Blades R, Jones L, Downer TR, Peet SC, Button E, Wyld D, McPhail S, Doolan M, Yates P. A single-blind, randomised controlled trial of StrataXRT® - A silicone-based film-forming gel dressing for prophylaxis and management of radiation dermatitis in patients with head and neck cancer. Radiother Oncol. 2019;139:72–78. doi: 10.1016/j.radonc.2019.07.014. [DOI] [PubMed] [Google Scholar]
- 20.Menon A, Prem SS, Kumari R. Topical betamethasone valerate as a prophylactic agent to prevent acute radiation dermatitis in head and neck malignancies: a randomized, open-label, phase 3 trial. Int J Radiat Oncol Biol Phys. 2021;109(1):151–160. doi: 10.1016/j.ijrobp.2020.08.040. [DOI] [PubMed] [Google Scholar]
- 21.Palatty PL, Azmidah A, Rao S, Jayachander D, Thilakchand KR, Rai MP, Haniadka R, Simon P, Ravi R, Jimmy R, D’souza PF, Fayad R, Baliga MS. Topical application of a sandal wood oil and turmeric based cream prevents radiodermatitis in head and neck cancer patients undergoing external beam radiotherapy: a pilot study. Br J Radiol. 2014;87(1038):20130490. doi: 10.1259/bjr.20130490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Rades D, Narvaez CA, Splettstößer L, Dömer C, Setter C, Idel C, Ribbat-Idel J, Perner S, Bartscht T, Olbrich D, Schild SE, Carl J. A randomized trial (RAREST-01) comparing Mepitel® Film and standard care for prevention of radiation dermatitis in patients irradiated for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN) Radiother Oncol. 2019;139:79–82. doi: 10.1016/j.radonc.2019.07.023. [DOI] [PubMed] [Google Scholar]
- 23.Rao S, Hegde SK, Baliga-Rao MP, Palatty PL, George T, Baliga MS. An aloe vera-based cosmeceutical cream delays and mitigates ionizing radiation-induced dermatitis in head and neck cancer patients undergoing curative radiotherapy: a clinical study. Medicines (Basel) 2017;4(3):44. doi: 10.3390/medicines4030044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Schneider F, Danski MT, Vayego SA. [Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial] Rev Esc Enferm USP. 2015;49(2):221–228. doi: 10.1590/S0080-623420150000200006. [DOI] [PubMed] [Google Scholar]
- 25.Tao Y, Auperin A, Sire C, Martin M, Saliou MG, Bardet E, Sun XS, Chatellier T, Morand C, Cornely A, Angokai M, Di Rito A, Kichenin K, Blanchard P, D’Onofrio I, Bourhis J. Multicenter randomized double-blind, placebo-controlled trial GORTEC (Groupe Oncologie Radiotherapie Tete et Cou) 2009-01 evaluating the effect of the regenerating agent on radiodermatitis of head and neck cancer patients. Int J Radiat Oncol Biol Phys. 2017;99(3):590–595. doi: 10.1016/j.ijrobp.2017.07.019. [DOI] [PubMed] [Google Scholar]
- 26.Yokota T, Zenda S, Ota I, Yamazaki T, Yamaguchi T, Ogawa T, Tachibana H, Toshiyasu T, Homma A, Miyaji T, Mashiko T, Hamauchi S, Tominaga K, Ishii S, Otani Y, Orito N, Uchitomi Y. Phase 3 randomized trial of topical steroid versus placebo for prevention of radiation dermatitis in patients with head and neck cancer receiving chemoradiation. Int J Radiat Oncol Biol Phys. 2021;111(3):794–803. doi: 10.1016/j.ijrobp.2021.05.133. [DOI] [PubMed] [Google Scholar]
- 27.Jaschke W, Schmuth M, Trianni A, Bartal G. Radiation-induced skin injuries to patients: what the interventional radiologist needs to know. Cardiovasc Intervent Radiol. 2017;40(8):1131–1140. doi: 10.1007/s00270-017-1674-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Yang X, Ren H, Guo X, Hu C, Fu J. Radiation-induced skin injury: pathogenesis, treatment, and management. Aging (Albany NY) 2020;12(22):23379–23393. doi: 10.18632/aging.103932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Chitapanarux I, Tovanabutra N, Chiewchanvit S, Sripan P, Chumachote A, Nobnop W, Tippanya D, Khamchompoo D. Emulsion of olive oil and calcium hydroxide for the prevention of radiation dermatitis in hypofractionation post-mastectomy radiotherapy: a randomized controlled trial. Breast Care (Basel) 2019;14(6):394–400. doi: 10.1159/000496062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Richardson J, Smith JE, McIntyre M, Thomas R, Pilkington K. Aloe vera for preventing radiation-induced skin reactions: a systematic literature review. Clin Oncol (R Coll Radiol) 2005;17(6):478–484. doi: 10.1016/j.clon.2005.04.013. [DOI] [PubMed] [Google Scholar]
- 31.Menêses AG, Reis PEDD, Guerra ENS, Canto GL, Ferreira EB. Use of trolamine to prevent and treat acute radiation dermatitis: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2018;26:e2929. doi: 10.1590/1518-8345.2035.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Haruna F, Lipsett A, Marignol L. Topical management of acute radiation dermatitis in breast cancer patients: a systematic review and meta-analysis. Anticancer Res. 2017;37(10):5343–5353. doi: 10.21873/anticanres.11960. [DOI] [PubMed] [Google Scholar]
- 33.Russi EG, Moretto F, Rampino M, Benasso M, Bacigalupo A, De Sanctis V, Numico G, Bossi P, Buglione M, Lombardo A, Airoldi M, Merlano MC, Licitra L, Denaro N, Pergolizzi S, Pinto C, Bensadoun RJ, Girolomoni G, Langendijk JA. Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus. Crit Rev Oncol Hematol. 2015;96(1):167–182. doi: 10.1016/j.critrevonc.2015.06.001. [DOI] [PubMed] [Google Scholar]
- 34.Herst PM, Bennett NC, Sutherland AE, Peszynski RI, Paterson DB, Jasperse ML. Prophylactic use of Mepitel Film prevents radiation-induced moist desquamation in an intra-patient randomised controlled clinical trial of 78 breast cancer patients. Radiother Oncol. 2014;110(1):137–143. doi: 10.1016/j.radonc.2014.01.005. [DOI] [PubMed] [Google Scholar]