Background
Hair loss related to chemotherapy can be a very distressing side effect of cancer treatment. 

Chemotherapy attacks rapidly growing cancer cells, but, other cells in the body, including hair grow rapidly, too. Those cells are also impacted by chemotherapy. Hair loss may be seen in numerous areas of the body when being treated with cytotoxic medications and may begin as early as one week after treatment begins.

Description
Scalp cooling has been used to attempt to minimize the loss of scalp hair during chemotherapy treatment. This cooling can be achieved in by using a specially designed scalp cooling device or ice cap during chemotherapy treatment.  

There are two thoughts as to how scalp cooling can reduce hair loss during chemotherapy. The first is that scalp cooling causes vasoconstriction and decreases blood flow to the area during the treatment which would result in decreased plasma concentrations of the chemotherapeutic agent during the treatment. The second is that the cooling results in decreased biochemical activity making the hair follicles less susceptible to the chemotherapeutic agent.

Treatment is generally well tolerated and side effects include headaches and feeling cold while the treatment is applied. 

Policy
Scalp cooling (i.e., using ice-filled bags/bandages, cryogel packs, or specially designed devices (e.g., Chemo Cold Cap, DigniCap, ElastoGel, and Penguin Cold Cap)) is considered NOT MEDICALLY NECESSARY as a means to prevent hair loss during chemotherapy because the effectiveness of this process has not been established.

Rationale 
In a review of the literature, Tollenaar and associates (1994) noted that scalp hypothermia might prevent alopecia only in a cytotoxic regimen containing an anthracycline as the sole alopecia-inducing agent. With current adjuvant chemotherapy for breast cancer, in which a combination of cyclophosphamide and an anthracycline is often used, there is no place for scalp hypothermia. In this regard, Christodoulou et al. (2002) reported that the MSC cold cap system is effective in preventing alopecia from anthracycline, etoposide or taxane, but not from anthracycline-taxane combinations or ifosfamide-containing regimens. Protiere et al. (2002) reported on the results of scalp cooling in 105 women with breast cancer receiving adjuvant chemotherapy with mitoxantrone and cyclophosphamide compared with 109 similarly treated women who were not offered scalp cooling. Although the nurses and subjects reported less hair loss with scalp cooling, study subjects were not randomly assigned to treatment groups, and the study did not include a sham control so that neither the study subjects nor the nurse assessors were blinded to treatment allocation.

In a non-randomized pilot study, Ridderheim et al. (2003) reported that a new digitized scalp-cooling system is safe and effective in preventing chemotherapy-induced alopecia in female patients (n = 74). The authors concluded that this new system makes it suitable for use in future randomized clinical trials designed to explore optimal temperatures and durations of cooling for different chemotherapy regimens in hopes of broadening the application of hypothermia for alopecia prevention in cancer patients. The authors stated that more data is needed on adjuvant treatment of breast cancer patients and long-term effects.

In a randomized controlled study, Macduff et al. (2003) examined the effectiveness of scalp cooling in preventing alopecia for breast cancer patients (n = 30) receiving the combination chemotherapy of epirubicin and docetaxel. The authors concluded that the benefits of scalp cooling in patients treated with taxanes and anthracycline drugs are clearly marginal and less impressive than for some single-drug breast cancer chemotherapy regimens. Despite the limitations of small numbers of patients and high dropout (n = 9), this study has been useful in establishing the extent, and illuminating the nature, of the marginal benefits and disadvantages of having this treatment. In addition, exploratory analyses have raised further questions regarding the criteria for clinical significance and how to prospectively identify individual patients who may do well in scalp cooling treatment.

In a review on the prevention of chemotherapy-induced hair loss by scalp cooling, Grevelman and Breed (2005) stated that scalp cooling is effective but not for all chemotherapy patients. These investigators noted that further psychological, clinical and biophysical research is needed to ascertain the exact indications for cooling and to improve the effect, tolerance, side-effects and the cooling procedure. The authors stated that multi-center clinical studies should be performed to gather this information.

An assessment of scalp cooling by the the Swedish Council on Technology Assessment in Health Care (SBU, 2005) concluded that "[f]urther studies of patient benefit, risks and cost effectiveness are needed." Spaeth et al. (2006) stated that "scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies."

In a systematic review on non-pharmacological strategies for managing common chemotherapy adverse effects, Lotfi-Jam et al. (2008) stated that findings from randomized controlled trials (RCTs) of reasonable quality provided limited support for cognitive distraction, exercise, hypnosis, relaxation and systematic desensitization to reduce nausea and vomiting, psycho-education for fatigue and scalp cooling to reduce hair loss. The authors concluded that although some strategies seem promising, the quality of the RCTs was generally quite low, making it difficult to draw conclusions about the effectiveness of self-care strategies. Future studies with better design and reporting of methodological issues are needed to establish evidence-based self-care recommendations for people receiving chemotherapy.

Mols et al. (2009) described the effectiveness and burden of scalp cooling and the satisfaction with wigs, with hair re-growth and with body image. Breast cancer patients treated with (n = 98) and without (n = 168) scalp cooling completed questionnaires before chemotherapy and 3 weeks and 6 months after completion of chemotherapy. Scalp cooling was effective in preventing chemotherapy-induced hair loss in 32 of 62 available patients (52%). Even though patients knew hair loss was temporary, it was a burden to 54% of them (n = 100). Scalp cooling was a burden for only 17 out of 51 patients (33%). Most patients who used a wig or head cover were satisfied with it (82%, n = 126). Patients were moderately satisfied with the regrowth of their hair after chemotherapy. Successfully cooled patients rated their hair as less important for their body image compared to patients who did experience hair loss (p = 0.014). The authors concluded that chemotherapy-induced hair loss is perceived as burdensome. It may be prevented by offering scalp cooling, which is often an effective method to prevent this form of hair loss and is well-tolerated by patients. However, if possible, scalp-cooling techniques should be improved and their effectiveness should be increased because if scalp cooling is unsuccessful, patients rate their hair loss as more burdensome compared to non-cooled patients.

In a review on chemotherapy-induced alopecia (CIA), Trueb (2009) stated that the major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, anti-oxidants, inhibitors of apoptosis, as well as cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle (e.g., topical application such that the anti-cancer effectiveness of chemotherapy is not hampered). Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

Auvinen and colleagues (2010) analyzed the effectiveness of scalp cooling caps in preventing CIA among 64 patients. Subjects were given one of the following chemotherapeutic treatments: (i) doxorubicin 60 mg/m2, (ii) docetaxel 80 mg/m2, (iii) FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) or (iv) the combination of 3 cycles of docetaxel (80 mg/m2) followed by 3 cycles of FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). All the chemotherapy treatments were given in a thrice-weekly schedule. Patients with early stage disease were given 6 adjuvant chemotherapy cycles, while patients with metastatic disease were given 9 chemotherapy cycles. Patients were provided with detailed instructions on how to treat the hair at home for one to three days following the chemotherapy treatment. Hair loss was evaluated after the third, sixth and final treatments. In the final results, major hair loss was avoided in all patients given doxorubicin treatment, in 83.3% of patients given docetaxel treatment, in 76.5% of patients given FEC treatment and in 78% of patients given docetaxel followed by FEC. In the final evaluation, 87.5% of the patients considered the avoidance of hair loss to be important. Only 20.3% of the patients needed to use a wig. The authors concluded that these findings showed that all the patient groups studied gained some benefit by using scalp cooling caps. The findings of this small study need to be validated by well-designed studies.

Van den Hurk and associates (2010) evaluated the effect of scalp cooling on well-being of breast cancer patients with CIA. A prospective multi-center study was performed in 13 hospitals. Breast cancer patients treated with (n = 98) and without (n = 168) scalp cooling completed questionnaires (EORTC QLQ-C30 and EORTC-QLQ-BR23, BIS, MBA, HADS) before chemotherapy, and 3 weeks and 6 months following the last chemotherapy cycle were included in this analysis. Scalp cooling was effective in 52% of the cases. Alopecia was considered among the most distressing problems at all 3 moments of measurement. A trend toward higher well-being was found in successfully scalp-cooled patients, as indicated by a general better health-related quality of life and better body image, whereas unsuccessfully scalp-cooled patients reported lowest well-being. The authors concluded that scalp cooling contributes not only to the well-being of successfully scalp-cooled patients but also seems to cause additional distress when patients lose their hair despite scalp cooling. This might be related to disappointment due to alopecia despite scalp cooling or possibly to a general higher biological availability of cytostatics. The authors recommended additional support for patients when scalp cooling is not successful and to spend more effort to maximize the effectiveness of scalp cooling.

In a review on CIA, Trueb (2010) stated that 47% of female patients consider hair loss the most traumatic aspect of chemotherapy, and 8% would decline chemotherapy because of fear of hair loss. On the basis of the current understanding of the underlying pathobiology, a number of agents have been evaluated in the treatment of this condition. Among the agents that have been evaluated, topical minoxidil was able to reduce the severity or shorten the duration but could not prevent hair loss. The major approach to minimize CIA is by scalp cooling, although most published data on scalp cooling are of poor quality. Because chemotherapy-induced toxicity has been associated with nutritional status, nutritional assessment and support might confer beneficial effects. Several experimental approaches to the development of pharmacological agents are under evaluation including: anti-oxidants, cytokines and growth factors, cell cycle and proliferation modifiers and inhibitors of apoptosis. The author concluded that at present, no approved pharmacologic treatment of CIA exists. The incidence and severity of the condition are variable and related to the particular chemo-therapeutic protocol. They noted that CIA is mostly reversible, and appropriate hair and scalp care and temporarily wearing a wig may be the most effective coping strategy.

An up-to-date review on “Chemotherapy-induced alopecia “ (Payne, 2013) stated, “Although scalp protection through cooling or tourniquet has been reported to minimize delivery of chemotherapeutic agents to the scalp, thereby potentially decreasing the risk of hair loss, case reports of cutaneous metastases or spread in these settings prevent general recommendation for their use. Because chemotherapy-associated hair loss is transient and usually (although not always) completely reversible after cessation of therapy, adequate counseling and psychological support before and during therapy should take precedence over the use of such devices.”

Komen et al. (2013) stated that the success of scalp cooling in preventing or reducing CIA is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors. These investigators performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggested that a subcutaneous scalp temperature less than 22°C is required for hair preservation. The authors concluded that the effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.

Lemieux et al. (2014) noted that alopecia is a side effect of chemotherapies used in breast cancer. Scalp cooling is a technique preventing alopecia, but its use remains controversial. These researchers conducted a survey about knowledge of scalp cooling and interest in conducting a RCT. An invitation was sent to 1,022 participants and a total of 139 individuals responded to the survey. The majority knew about the existence of scalp cooling; 90% thought that an RCT was needed and would participate. The survey revealed different potential problems associated with the increased chair time, limited space and safety. The authors concluded that an RCT is needed and that the trial must include evaluation on the impact on health care system resources and safety.

Kadakia et al. (2014) stated that conventional chemotherapy leads to multiple adverse mucocutaneous complications (e.g., oral mucositis, alopecia, ocular toxicity and onycholysis). Limited pharmacologic interventions are available for preventing these clinical problems. These investigators reviewed the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms. A narrative review was performed, with an emphasis on RCTs. A comprehensive search using PubMed, Ovid, Embase and Medline was completed. References of all cited articles also were reviewed. Data from the review were composed of articles published between 1970 and May 2013. Available evidence suggested that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity and onycholysis. The major limitations of studies included the absence of blinded control groups and variable clinical end-points. The authors concluded that regional hypothermia decreased the burden of these 4 chemotherapy-induced complications and was well-tolerated. They stated that more research is needed to (i) determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, (ii) the ideal duration of cooling needed and (iii) further improve the ease of use of the cooling devices.

Shin et al. (2015) evaluated the effectiveness of various interventions in the prevention of CIA. They searched PubMed, EMBASE and the Cochrane Library, from June 20, 2013, through Aug. 31, 2013. Two of the authors independently reviewed and selected clinical trials that reported the effectiveness of any intervention for prevention of CIA compared with that of controls. Two authors extracted data independently on dichotomized outcome in terms of CIA occurrence. Relative risks (RRs) and 95% confidential intervals (CIs) were calculated for effectiveness of CIA prevention by using random-effect or fixed-effect models. Out of 691 articles retrieved, a total of 8 RCTs and 9 controlled clinical trials involving 1,098 participants (616 interventions and 482 controls), were included in the final analyses. Scalp cooling, scalp compression, a combination of cooling and compression, topical minoxidil and panicum miliaceum were used as interventions. The participants were mainly breast cancer patients receiving doxorubicin- or epirubicin-containing chemotherapy. Scalp cooling, which is the most popular preventive method, significantly reduced the risk of CIA (RR = 0.38, 95% CI: 0.32 to 0.45), whereas topical 2% minoxidil and other interventions did not significantly reduce the risk of CIA. No serious adverse effects associated with scalp cooling were reported. The authors concluded that these findings suggested that scalp cooling can prevent CIA in patients receiving chemotherapy; however, the long-term safety of scalp cooling should be confirmed in further studies.

On Dec. 8, 2015, the Food and Drug Administration (FDA) cleared for marketing the first cooling cap to reduce alopecia in female breast cancer patients undergoing chemotherapy. The Dignitana DigniCap Cooling System is indicated to reduce the frequency and severity of alopecia during chemotherapy in breast cancer patients in which alopecia-inducing chemotherapeutic agents and doses are used. It is a computer-controlled system that circulates cooled liquid to a head-worn cooling cap during chemotherapy treatment. The cooling cap is covered by a second cap made from neoprene, which holds the cooling cap in place and acts as an insulation cover to prevent loss of cooling. The cooling action is intended to constrict blood vessels in the scalp, which, in theory, reduces the amount of chemotherapy that reaches cells in the hair follicles. The cold also decreases the activity of the hair follicles, which slows down cell division and makes them less affected by chemotherapy. The combined actions are thought to reduce the effect chemotherapy has on the cells, which may reduce hair loss. DigniCap may not work with some chemotherapy regimens. The effectiveness of the cooling system was studied in 122 Stage I and Stage II women with breast cancer who were undergoing chemotherapy, using recognized chemotherapy regimens that have been associated with hair loss. The data from this study may also be applied to some Stage III and IV breast cancer patients because they may have a benefit-risk profile comparable to the patients enrolled in this study. The primary end-point was a self-assessment of hair loss by the women using standardized photographs at 1 month after the last chemotherapy cycle. More than 66% of patients treated with the DigniCap reported losing less than 50% of their hair.

Grevelman and Breed (2015) noted that chemotherapy-induced temporary hair loss is one of the most common and distressing side-effects of cancer therapy. Scalp cooling to reduce this hair loss is a controversial issue for many doctors and nurses. This may be due to inadequate knowledge. These researchers reviewed evidence from 53 publications and 3 personal communications focuses on the effectiveness of the treatment, side-effects, possible disadvantages and the controversies in these areas. Scalp cooling has become an increasingly effective method to prevent hair loss, especially when anthracyclines or taxanes are used. Unfortunately, many studies were small and badly designed and are therefore difficult to compare. There is a considerable variation in the success rates in the various studies. This remains unexplained, but the cooling time, the chemotherapy used and the temperature seem to be influential. The authors stated that scalp cooling should not be used if chemotherapy is given with a curative intent in patients with generalized hematogenic metastases. The majority of patients tolerated cooling very well. The authors concluded that scalp cooling is effective but not for all chemotherapy patients. They stated that further psychological, clinical and biophysical research is needed to determine exact indications for cooling and to improve the effect, tolerance, side-effects and the cooling procedure; multi-center clinical trials should be performed to gather this information.

Currently, there is a phase III clinical trial — “Scalp Cooling to Prevent Chemo-induced Hair Loss (SCALP)” — that is still recruiting subjects (last verified October 2015).  https://clinicaltrials.gov/ct2/show/NCT01986140.

Moreover, an up-to-date review on “Chemotherapy-induced alopecia” (Payne, 2016) states, “The success of scalp cooling for preventing or reducing chemotherapy-induced alopecia is highly variable between patients and chemotherapy regimens." The drugs best suited to this approach include doxorubicin, daunorubicin, paclitaxel, epirubicin, vincristine, vinblastine, actinomycin D and mechlorethamine. Success with combination regimens such as intravenous cyclophosphamide, methotrexate and fluorouracil (CMF) has been reported, but this approach failed with the combination of doxorubicin plus cyclophosphamide. Results are also dose-dependent, with higher doses of anthracyclines being associated with higher rates of alopecia despite the use of scalp cooling. Results of many studies are difficult to interpret secondary to use of multiple cooling systems (ice turban, gel packs, cool caps, thermocirculator, room air conditioner), variable chemotherapy regimens (single versus combined agents), small study populations and varying definitions of alopecia. Nevertheless, at least 4 randomized controlled trials suggest significantly less hair loss with scalp hypothermia. In general, between 50% and 80% of patients have a good to excellent response with this therapy. A meta-analysis of 8 randomized controlled trials and 9 controlled clinical trials involving 1,098 participants (616 interventions and 482 controls) who received a variety of interventions for prevention of chemotherapy-induced alopecia concluded that scalp cooling was the only intervention that significantly reduced the risk of chemotherapy-induced alopecia (relative risk 0.38, 95% CI: 0.32 to 0.45). No adverse events associated with scalp cooling were reported in the meta-analysis. 

Scalp hypothermia may not be as effective in patients with liver dysfunction. This is likely related to delayed drug metabolism, thereby allowing persistence of therapeutic drug levels beyond the protective period. Scalp cooling is contraindicated in patients with cold sensitivity, cold agglutinin disease, cryoglobulinemia and post-traumatic cold dystrophy. In addition, some investigators have raised concerns regarding the possibility of scalp metastasis in association with scalp hypothermia. As an example, one group reported the outcome of a patient with mycosis fungoides who used a cooling cap to prevent alopecia. Following chemotherapy, he developed recurrent disease limited to the scalp. Subsequent treatment without a cooling device resulted in complete clinical remission. However, the clinical significance of these findings is unclear in patients with solid tumors. In one study of 61 patients with disseminated breast cancer receiving chemotherapy who used a cooling cap, 1 patient with underlying liver dysfunction developed cutaneous scalp metastasis. In contrast, 3 separate series, either entirely or predominantly consisting of patients receiving adjuvant treatment for breast cancer reported no increased frequency of scalp metastases in the patients who were treated in conjunction with a scalp cooling device. These case reports suggest that cooling devices may be contraindicated in patients with circulating tumor cells (e.g., lymphoma, leukemia) or in those with liver dysfunction resulting in prolonged drug half-lives. They should be used with caution in patients with breast carcinoma, especially in the setting of adjuvant therapy, as well as other carcinomas associated with risk for cutaneous metastases, such as lung, kidney, stomach, colon and uterus.

Although scalp protection through cooling or tourniquet has been reported to minimize delivery of chemotherapeutic agents to the scalp, thereby potentially decreasing the risk of hair loss, case reports of cutaneous metastases or spread in some settings prevent general recommendation for their use. Because chemotherapy-associated hair loss is transient and usually (although not always) completely reversible after cessation of therapy, adequate counseling and psychological support for alopecia both before and during therapy should take precedence over the use of such devices.

References 

1. National Coverage Determination (NCD) for Scalp Hypothermia During Chemotherapy to Prevent Hair Loss (110.6).
2. Tollenaar RA, Liefers GJ, Repelaer van Driel OJ, van de Velde CJ. Scalp cooling has no place in the prevention of alopecia in adjuvant chemotherapy for breast cancer. Eur J Cancer. 1994;30A(10):1448-1453.
3. Tierney AJ. Preventing chemotherapy-induced alopecia in cancer patients: Is scalp cooling worthwhile? J Adv Nurs. 1987;12(3):303-310.
4. Dorr VJ. A practitioner's guide to cancer-related alopecia. Semin Oncol. 1998;25(5):562-570.
5. Christodoulou C, Klouvas G, Efstathiou E, et al. Effectiveness of the MSC cold cap system in the prevention of chemotherapy-induced alopecia. Oncology. 2002;62(2):97-102.
6. Protiere C, Evans K, Camerlo J, et al. Efficacy and tolerance of a scalp-cooling system for prevention of hair loss and the experience of breast cancer patients treated by adjuvant chemotherapy. Support Care Cancer. 2002;10(7):529-537.
7. Ridderheim M, Bjurberg M, Gustavsson A. Scalp hypothermia to prevent chemotherapy-induced alopecia is effective and safe: A pilot study of a new digitized scalp-cooling system used in 74 patients. Support Care Cancer. 2003;11:371-377.
8. Macduff C, Mackenzie T, Hutcheon A et al. The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel. Eur J Cancer Care. 2003;12:154-161.
9. Grevelman EG, Breed WP. Prevention of chemotherapy-induced hair loss by scalp cooling. Ann Oncol. 2005;16(3):352-358.
10. Swedish Council on Technology Assessment in Health Care (SBU). Scalp cooling to prevent chemotherapy-induced hair loss -- Alert. Stockholm, Sweden: SBU; June 2005.
11. Spaeth D, Rosso N, Clivot L. Chemotherapy-induced alopecia. Rev Prat. 2006;56(18):2020-2024.
12. Lotfi-Jam K, Carey M, Jefford M, et al. Nonpharmacologic strategies for managing common chemotherapy adverse effects: A systematic review. J Clin Oncol. 2008;26(34):5618-5629.
13. Mols F, van den Hurk CJ, Vingerhoets AJ, Breed WP. Scalp cooling to prevent chemotherapy-induced hair loss: Practical and clinical considerations. Support Care Cancer. 2009;17(2):181-189.
14. Lemieux J, Amireault C, Provencher L, Maunsell E. Incidence of scalp metastases in breast cancer: A retrospective cohort study in women who were offered scalp cooling. Breast Cancer Res Treat. 2009;118(3):547-552.
15. Trüeb RM. Chemotherapy-induced alopecia. Semin Cutan Med Surg. 2009;28(1):11-14.
16. Auvinen PK, Mähönen UA, Soininen KM, et al. The effectiveness of a scalp cooling cap in preventing chemotherapy-induced alopecia. Tumori. 2010;96(2):271-275.
17. van den Hurk CJ, Mols F, Vingerhoets AJ, Breed WP. Impact of alopecia and scalp cooling on the well-being of breast cancer patients. Psychooncology. 2010;19(7):701-709
18. Trüeb RM. Chemotherapy-induced alopecia. Curr Opin Support Palliat Care. 2010;4(4):281-284.
19. Roe H. Chemotherapy-induced alopecia: Advice and support for hair loss. Br J Nurs. 2011;20(10):S4-S11.
20. Payne AS. Chemotherapy-induced alopecia. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2013.
21. Komen MM, Smorenburg CH, van den Hurk CJ, Nortier JW. Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist. 2013;18(7):885-891.
22. Lemieux J, Provencher L, Laflamme C. Survey about the use of scalp cooling to prevent alopecia during breast cancer chemotherapy treatment in Canada. Can Oncol Nurs J. 2014;24(2):102-108.
23. Kadakia KC, Rozell SA, Butala AA, Loprinzi CL. Supportive cryotherapy: A review from head to toe. J Pain Symptom Manage. 2014;47(6):1100-1115.
24. Shin H, Jo SJ, Kim do H, et al. Efficacy of interventions for prevention of chemotherapy-induced alopecia: A systematic review and meta-analysis. Int J Cancer. 2015;136(5):E442-E454.
25. Food and Drug Administration. FDA allows marketing of cooling cap to reduce hair loss during chemotherapy. December 8, 2015. FDA: Silver Spring, MD. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476216.htm. Accessed February 9, 2016.
26. Grevelman EG, Breed WP. Prevention of chemotherapy-induced hair loss by scalp cooling. Ann Oncol. 2005;16(3):352-358.
27. Payne AS. Chemotherapy-induced alopecia. UpToDate Inc., Waltham, MA. Last reviewed January 2016.

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