Preventing Chemotherapy-Associated Alopecia: A Case for Palliation?

A PATIENT UNDERGOING TREATMENT FOR

a chronic or debilitating illness has enough to deal with, with respect to their treatment and care, and challenges with their appearance should be the least of their worries. However, chemotherapy-induced alopecia (CIA) is real, and it can dishearten patients and their attitude toward their care.

Physicians consider alopecia an eventuality of chemotherapy, and very few can offer any advice to patients on how to manage this side effect. However, hair loss, which drastically changes how a person looks and feels, can significantly impact the patient’s quality of life (QOL), over and above the physical exhaustion associated with their treatment.

The incidence and severity of CIA varies based on the drug being used, from 65% to 100%. For patients, alopecia ranks high, next to nausea and vomiting, as the most distressing side effect of treatment. A literature review of the impact of alopecia on a patient’s QOL found that this side effect of cancer treatment can impact patients in a variety of ways—it can cause anxiety and distress; trigger issues with body image, self-esteem, perception of sexuality, and social functioning; and influence the ability to return to work.¹

A survey conducted 25 years ago found that slightly less than 10% of women diagnosed with cancer, in the 24 to 66 age group, were actually ready to forego chemotherapy due to the impending threat of losing their hair.² A more recent study in newly diagnosed cancer patients found that a little over 15% of participants refused cancer treatment partially or completely, and of those, a majority were women refusing adjuvant chemotherapy for their breast cancer.³

To measure this stress, researchers have developed the Chemotherapy-induced Alopecia Distress Scale (CADS). CADS quantifies the distress experienced by patients undergoing treatment for breast cancer. Used in 305 Korean women, the study found that CADS moderately correlated with body image (r = —0.47; P <.001), weakly correlated with the patient’s overall quality of life (r = —0.28; P <.001), but did not correlate with self-esteem (r = —0.07; P = 0.23).⁴

Preventing hair loss would be a game changer for patients, and one way of achieving this is by using scalp cooling technology.

Potential Solution: Scalp Cooling Systems

Several scalp cooling or cold cap systems have been developed for use in patients with solid tumors while they are being treated with chemotherapy agents. Cold cap technology helps alleviate the damage of chemotherapy agents on hair follicles via vasoconstriction—reducing blood flow to follicles. This significantly lowers the dose of the chemotherapy agent that reaches the hair follicles, potentially reducing alopecia.

A few of the products that are currently being marketed include:

1. The Paxman Scalp Cooling System⁵

2. DigniCap⁶

3. Chemo Cold Caps⁷

4. Penguin Cold Caps⁸

Clinical trials have evaluated the efficacy of these devices.⁶ One such trial compared the Paxman system with cold caps in patients receiving treatment with docetaxel in a palliative setting. Of the 238 patients who were enrolled, 128 were on the Paxman system, 71 were on cold cap, and 39 patients were the control group that did not receive any scalp cooling treatment. The primary outcome was benchmarked as alopecia World Health Organization III or IV, or the need to wear a wig.⁹

Although alopecia was observed across all 3 groups being compared, cooling was found to reduce the risk of alopecia by 78% (HR 0.22; 95% CI, 0.12-0.41). Both systems, the study found, were equally effective in preventing alopecia. The intense cold sensation, however, was unbearable for 13% of patients and they subsequently dropped out of the study.

A literature review by Shin et al of articles published in PubMed, EMBASE, and the Cochrane Library, between June 20, 2013, and August 31, 2013, concluded that scalp cooling can prevent CIA in patients receiving chemotherapy; however, longterm safety studies are warranted. Out of 691 articles retrieved by the study authors, a total of 8 randomized control trials and 9 controlled clinical trials involving 1098 participants (616 interventions and 482 controls) were included in the final analyses, a majority of whom were breast cancer patients receiving doxorubicin- or epirubicin-containing chemotherapy. Scalp cooling, the most popular preventive method, significantly reduced the risk of CIA (RR,&thinsp;0.38; 95 % CI,&thinsp;0.32-0.45), whereas topical 2 % minoxidil and other interventions did not, the authors confirmed based on their analysis.¹⁰

Device manufacturers, however, contraindicate the use of scalp cooling technology in individuals with:

• Hematological conditions
• Cold allergy
• Cold agglutinins
• Manifest scalp metastases
• Imminent bone marrow ablation chemotherapy
• Imminent skull irradiation

Of the available scalp cooling systems, DigniCap is the first one to be granted FDA clearance to reduce alopecia in breast cancer patients receiving chemotherapy.¹¹ Dignitana, the manufacturer of the device, told Evidence-Based Oncology™ (EBO™) in an e-mail, that the DigniCap System is the only scalp cooling device to complete FDA-approved multi-center clinical trials at several medical centers within the United States, including the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco; Wake Forest Baptist Medical Center; Weill Cornell Breast Center; Mount Sinai Beth Israel Comprehensive Cancer Center; and Jonsson Comprehensive Cancer Center, University of California, Los Angeles.

DigniCap System

FIGURE 1

FIGURE 2

The DigniCap cooling system () has 2 inbuilt sensors for temperature regulation, and a third safety sensor to ensure that the scalp temperature never falls below 32ºF (0ºC). Safe and effective across multiple ethnicities, clinical studies found that the DigniCap scalp cooling system prevented hair loss in 70.3% of patients with breast cancer receiving adjuvant chemotherapy, compared with the control group that experienced significant hair loss. “Good contact between the cooling cap and the scalp and maintenance of a consistent temperature throughout treatment are key factors to scalp cooling effectiveness,” according to Dignitana ().

FIGURE 1

The company either directly charges the patient or leases the cooling system () to clinics and cancer care facilities, with additional payment attached per use. Following FDA clearance, the past year has seen more than 40 medical centers across the United States offer this preventive intervention to their patients.

Challenges With Using the Technology

According to Nancy Marshall, cofounder of The Rapunzel Project,¹² patient tolerance with using these extremely cold caps may vary. Patients could become numb to the cold after the first cap is placed on their head but may become comfortable by the time of the next change. “Exposed skin (such as forehead, ears, and scalp) can get freezer burn, but patients are taught to change hair part lines and protect other exposed skin with moleskin or similar covering,” Marshall told EBO™. Additionally, the process needs to be well coordinated by a very capable helper who can safely handle the extremely cold caps, while ensuring the schedule of cap changes is maintained, according to Marshall.

The Rapunzel Project finds its inspiration in the experiences of its cofounders, Shirley Billigmeier and Marshall, both breast cancer survivors. Billigmeier, with the support of her oncologist, used the cold caps when she was being treated for her breast cancer. Marshall supported her friend by organizing fundraisers that helped the hospital, where Billigmeier was being treated, purchase a freezer. Motivated by this experience, the 2 women then decided to raise awareness among cancer patients, their physicians, and their hair stylists about this new technology, and The Rapunzel Project was born.

Smaller clinics may not have access to biomedical freezers, which would mean the patient has to bring in dry ice to freeze the individual caps, an added cost of up to $150, according to Marshall. Their organization assists these clinics by donating freezers.

Health Plan Coverage Not Yet Standard Practice

Dignitana is working with third-party payers to establish coverage for use of their cooling device. According to the company, each medical center decides what percentage of the cost of the device and its operation it will absorb, and how much will be shouldered by the patient. Medical and philanthropic foundations are also lending monetary support to patients.

Aetna considers “scalp cooling (ie, using ice-filled bags/ bandages, cryogenic packs, or specially designed devices) experimental and investigational as a means to prevent hair loss during chemotherapy because the effectiveness of this process has not been established.”¹³

The UnitedHealth policy brief on scalp cooling states, “While ice-filled bags or bandages or other devices used for scalp hypothermia during chemotherapy may be covered as supplies of the kind commonly furnished without a separate charge, no separate charge for them would be recognized.”¹⁴ “Insurance reimbursement has occurred in a few instances, but is still highly unlikely,” explained Marshall. She argues that if insurance companies are ready to pay for a wig, paying for these cold caps to avoid wearing a wig should be a no-brainer. She would like to see organizations like the Susan G. Komen Foundation and the American Cancer Society lend support to this cause.

Raising Awareness

Marshall told EBO™ that there is a gap in knowledge, between both patients and care providers, on the efficiency of this technology. “Doctors and clinics were understandably wary of supporting an unapproved product, though many recognized the importance of this issue to patients,” Marshall said. This was compounded by the fact that most manufacturers of these systems were small businesses and the FDA process is expensive.

Marshall acknowledged the persistence of both patients and providers—doctors reviewed the literature and research and concluded they had no issue with their patients trying cold caps, and when the caps worked, the physicians became believers. “This has really led to considerable support, particularly in California, Florida, and New York,” Marshall said.

In a statement, Dignitana told EBO™, “We have been working with our clinical partners to share patient success stories and increase awareness among patients at the community level. Dignitana is also supporting several charities and philanthropic initiatives within the breast cancer community to increase awareness that cost need not be a deterrent with this therapeutic option.” Additionally, educating oncologists and health center staff on the benefits of scalp cooling is also a part of the company’s awareness campaign. The company is also a supporter of HairToStay, a nonprofit that provides financial assistance to those women who cannot afford the cost of hair cooling systems.¹⁵

The Rapunzel Project also reaches out to hair stylists. “We discovered that hair stylists are all too familiar with the trauma prospective hair loss represents for their clients. Faced with the prospect of chemo, many patients consult a stylist (with whom they often have a personal relationship) regarding shaving their head and/or acquiring a wig. This is a critical time window—after diagnosis and before treatment,” Marshall told EBO™. They have partnered with Kenra Professional, a hair care products manufac turer out of Indianapolis, to distribute the project’s literature to Kenra’s salon clients, as well as to educate the stylists.

Dignitana believes their treatment to prevent alopecia in women receiving chemotherapy for their breast cancer is a form of palliative care. “Patients who have been able to save their hair through scalp cooling describe the greater sense of control and well-being that has come along with being able to save their hair during their chemotherapy. This is definitely in keeping with the palliative care goal to improve quality of life for both the patient and the family,” the company told EBO™.

According to Marshall, “The DigniCap system is definitely more user friendly, and, hopefully, there will be cost efficiencies, as well, as volume builds.” She also thinks that having a nurse handle the caps will make the process easier and hassle free for patients and their families.

“We know cold cap therapy is not for everyone, but we strongly believe you can’t make a choice if you don’t know you have a choice,” Marshall continued. “Patients should be informed there is a viable option to save their hair, so they can make the decision that is best for them. And, of course, the process needs to be affordable for all.”References

1. Dmytriw AA, Morzycki W, Green PJ. Prevention of alopecia in medical and interventional chemotherapy patients. J Cutan Med Surg. 2015;19(1):11-16. doi: 10.2310/7750.2014.13200.
2. Tierney AJ, Taylor J, Closs SJ. Knowledge, expectations and experiences of patients receiving chemotherapy for breast cancer. Scand J Caring Sci. 1992;6(2):75-80. doi: 10.1111/j.1471-6712.1992. tb00128.x.
3. Puts MT, Monette J, Girre V, et al. Characteristics of older newly diagnosed cancer patients refusing cancer treatments. Support Care Cancer. 2010;18(8):969-74. doi: 10.1007/s00520-010-0883-0.
4. Cho J, Choi EK, Kim IR, et al. Development and validation of Chemotherapy-induced Alopecia Distress Scale (CADS) for breast cancer patients. Ann Oncol. 2014;25(2):346-351. doi: 10.1093/annonc/mdt476.
5. What is scalp cooling? Paxman Scalp Cooling website. http://paxmanscalpcooling.com/ scalp-cooling. Accessed November 14, 2016.
6. DigniCap website. https://www.dignicap.com/. Accessed November 14, 2016.
7. Chemo Cold Caps website. http://chemocoldcaps.com/. Accessed November 14, 2016.
8. Penguin Cold Caps website. https://penguincoldcaps.com/us/. Accessed November 14, 2016.
9. Betticher DC, Delmore G, Breitenstein U, et al. Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment. Support Care Cancer. 2013;21(9):2565-2573. doi: 10.1007/s00520-013-1804-9.
10. Shin H, Jo SJ, Kim DH, Kwon O, Myung SK. Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. Int J Cancer. 2015;136(5):E442-E454. doi: 10.1002/ijc.29115.
11. FDA allows marketing of cooling cap to reduce hair loss during chemotherapy [news release]. Silver Spring, MD: FDA; December 8, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476216.htm. Accessed November 15, 2016.
12. The Rapunzel Project. Rapunzel Project website. http://www.rapunzelproject.org/OurStory. aspx. Accessed November 16, 2016.
13. Scalp cooling (hypothermia) to prevent hair loss during chemotherapy. Aetna website. http:// www.aetna.com/cpb/medical/data/200_299/0290.html. Reviewed May 27, 2016. Accessed November 15, 2016.
14. Scalp hypothermia during chemotherapy to prevent hair loss (NCD 110.6). UnitedHealthcare website. https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Main%20 Menu/Tools%20&%20Resources/Policies%20and%20Protocols/Medicare%20Advantage%20Policy%20Guidelines/Scalp_Hypothermia_During_Chemo_Prevent_Hair_Loss.pdf. Approved August 10, 2016. Accessed November 16, 2016.
15. HairToStay website. http://www.hairtostay.org/. Accessed November 16, 2016.

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