Effectiveness and Determinant Factors of Successfull Scalp Cooling in Preventing Chemotherapy Induced Alopecia in Breast Cancer Patients : Literature Review

Background: Chemotherapy induced Alopecia (CIA) is one of the most complained and cause the highest distress in breast cancer patients with chemotherapy. Cryotherapy or Scalp Cooling is an alternative intervention to reduce metabolism of cytotoxic agents against hair follicle by lowering the temperature of the scalp. Literature that discusses the effectiveness of Cryotherapy in breast cancer patients is still limited. Objective: Summarize and investigate the effect of Cryotherapy on preventing Chemotherapy induced Alopecia in breast cancer patients and its determinant factors of successfull Cryotherapy . Design: Literature Review Data Sources: A search was performed by using Ebscohost, Scopus, Science Direct, and ProQuest database from 2009 to 2019 for research article. Review methods: A systematic process was used to analyze and extract data include studies using CASP. Result: From 278 articles that have been observed using CASP, only 10 articles match the inclusion criteria. Total respondents in 10 articles were 1201 breast cancer patients undergoing chemotherapy. All articles used in this study showed positive results about the effect of Cryotherapy on decreasing the severity of Chemotherapy Induced Alopecia (CIA) measured by hair preservation, hair loss, hair regrowth, and decreasing use a wig or head covering. The importance of continuously monitoring the patient's condition to manage the side effects caused by Cryotherapy such as headaches, cold, and nausea. Conclusion: Cryotherapy significantly reduce the severity of CIA by inhibit the process of mitosis and vasoconstriction. There are several factors that must be considered when giving Cryotherapy, such as type of chemotherapy, dosages, device, duration of administration, and temperature. For further research, it is important to considered some factors that can affect the successfull of Cryotherapy and the patient response


INTRODUCTION
Chemotherapy induced Alopecia (CIA) is one of the most complained and cause the highest distress in breast cancer patients with chemotherapy (1,2). According to Charalambous (2019), the incidence of CIA is 70% and usually occured in women diagnosed with breast cancer. The implications of the emergence of CIA in patients have an impact on decreasing body image, decreasing patient selfesteem, and increasing psychological distress which result in decreased quality of life in breast cancer patients (2,4). In fact, many breast cancer patients refuse to continue chemotherapy due to several side effects caused by anticancer drugs, one example is alopecia (5).
CIA occurs because chemotherapy induce mitotic activity quickly and interfere with normal anagen growth in hair follicles, resulting in hair loss (6). CIA usually is just temporary and the hair begin to grow again in 3-4 weeks after the patients completed their chemotherapy (3). The severity of the patient's hair loss depend on the type of anticancer drug, dosage, drug combination and the sensitivity of the patient itself (7). Based on several studies, it is found that chemotherapy with doxorubicin, paclitaxel, docetaxel, cyclophosphamide, andor epirubicin regimens has a very high effect of alopecia (6,8,9).
Cryotherapy or Scalp-cooling has been done for a long time to support cancer patients because it is very cheap and easy to do on patients (10). Scalp Cooling reducing the temperature of the patient's scalp with the aim of reducing the exposure and metabolism of cytotoxic agents to hair follicles (3,11,12). According to several studies that have been done, mechanism of Scalp Cooling that can reduce the incidence of alopecia by low temperature resulting in vasoconstriction, and decreased metabolic activity thus limiting the concentration of chemotherapy agents to cells so that it can decreases the effects of cytostatic agents (4,11,12).
There are several techniques for administering Scalp Cooling starting with frozen caps that are replaced every 30 minutes, and Scalp Cooling systems (Paxman, and Dignicap) that provide a cold sensation to the patient's head covering. (12). Many studies said Scalp Cooling is effective to reduce the occurrence of alopecia, but this positive effect was not occured in all patients. Many studies used less valid evaluation indicators such as the use of wigs, and subjective assessment of hair loss in patients agents (13). There are even several studies that indicate a risk of metastatic cancer to the head caused by the use of Scalp Cooling (10). Study that discussed scalp cooling in cancer patients to prevent alopecia is still limited. Previous literature review conducted by Ross (15) regarding to the effectiveness of scalp cooling on the prevention of alopecia. This study will review the factors that can determine the success rate of giving scalp cooling to breast cancer patients, health professionals to pay attention to these factors so that the results obtained are as expected.

Cryotherapy (Scalp Cooling)
Cryotherapy is one of the methods used to reduce the incidence of CIA. There are 10 journals in this study that get positive results with the use of Cryotherapy (Scalp Cooling) which can significantly affect the incidence of CIA. There are several ways in giving Cryotherapy to patients, starting from the use of different devices such as Paxman, Dignicap @

Figure 1. Flow chart-PRISMA recommendations
Searching was performed in four database (Scopus, Ebscohost, Science direct, and Pubmed) with a total 1654 articles which were screened including duplicates removed, language, design, title and abstract become 25 articles. 25 articles were reviewed using CASP (PICO) so that 10 articles were obtained.

Mechanism of Cryotherapy (Scalp Cooling)
There are several theories that explain how the mechanism of Cryotherapy can prevent the occurrence of CIA. In this study, based on 10 journals that have been analyzed, showed that giving Cryotherapy has a significant positive effect on reducing CIA. The mechanism of Cryotherapy in reducing CIA is that it causes vasoconstriction in the scalp area of the patient, resulting the decrease of blood flow to hair follicle areas and decreasing the uptake of chemotherapy agents (12).

Adverse effect of Cryotherapy
There were some patients who complains mild side effects from Cryotherapy (Scalp Cooling) and there also patients who couldn't tolerate the side effects, so they were dropped out from the study. Based on the analysis that has been done, the most complained side effects from the patients during the study were headaches, felt uncomfortable due to cold, nausea and even appeared blister in patient's forehead area after given Cryotherapy. Therefore, it is important to continuously monitoring the patient's condition in order to anticipate the emergence of side effects from Cryotherapy.

CONFLICT OF INTEREST
The author declared no conflict interest

LIMITATION OF STUDY
Only studies published in English language from four databases (Ebscohost, Scopus, Science direct, Proquest) were accessed for this study. There are several types of research designs in the literature used and small number of RCT's identified (5 articles). Critical appraisal only used CASP for assess all studies.

CONCLUSSION
Cryotherapy significantly reduce the severity of CIA by inhibit the process of mitosis and vasoconstriction. There are several factors that must be considered when giving Cryotherapy, such as type of chemotherapy, dosages, devices, duration of administration, and temperature.
The number of adverse effects caused in scalp cooling is one of the determining factors for patients to continue scalp cooling or not. The nurses who are health professional have the longest contact with patients, must monitor the patient's condition (side effect of scalp cooling) regularly, so if problem arise, health professional can be anticipated properly and do not interfere process of giving scalp cooling. For further research, it is important to considered some factors that can affect the successfull of Cryotherapy and the patient response.