Study: Does scalp cooling help prevent hair loss after chemotherapy?

IN DEPTH REVIEW OF RESEARCH

Study background:

Many women who receive chemotherapy experience hair loss, commonly rated by patients with breast cancer as one of the most distressing adverse effects. Though scalp cooling has been available in Europe for a few decades, it has only recently been approved for use in the United States.

Hope Rugo and colleagues from the University of California, San Francisco and Julie Nangia and colleagues published work in the Journal of the American Medical Association (JAMA) in February 2017, looking at the use of scalp cooling in patients who received chemotherapy after a diagnosis of early-stage breast cancer. 

Researchers of these studies wanted to know:

Whether scalp cooling is associated with less hair loss in women who have received chemotherapy for early-stage breast cancer.

Population(s) looked at in the Rugo and colleagues study:

The patients involved in this study were women who:

• were at least 18 years old
• were diagnosed with stage I or II breast cancer
• completed a planned chemotherapy regimen in six months (patients who were going to receive sequential or combination anthracycline and taxane therapy were excluded). The chemotherapy regimens included were docetaxel and cyclophosphamide, doxorubicin and cyclophosphamide, docetaxel and carboplatin (with HER2-targeted therapy), weekly paclitaxel, dose-dense paclitaxel, paclitaxel and carboplatin, and docetaxel with HER2-targeted therapy. 

The study included 122 women, of whom 77% were white: 106 patients received scalp cooling and 16 patients did not. The researchers used the DigniCap, a silicone cap that was placed on the patients’ heads 30 minutes before each chemotherapy cycle. The cap was then cooled to 37 degrees Fahrenheit throughout chemotherapy, and for 90-120 minutes afterward.   

The researchers used before-and-after photos to assess hair loss. Patients looked at photographs taken of their hair before the start of each chemotherapy cycle and 3-6 weeks after their last chemotherapy cycle. The patients then estimated the percentage of hair loss using the Dean scale (measurement of 0-4, where 2 represents less than 50% hair loss). An independent panel of people also scored the photos to validate the results. 

Rugo study findings: 

Among patients who received scalp cooling therapy (and were followed up 4 weeks after their last chemotherapy treatment):

1. Approximately 2/3 lost less than 50% of their hair compared to 0 patients who received the same chemotherapy treatment without scalp cooling therapy.
2. About 27% of patients reported feeling less physically attractive compared to about 56% of patients who did not receive scalp cooling therapy.
3. The patients who received scalp cooling therapy reported the following side effects:
   • About 43% reported having headaches that were triggered or made worse by scalp cooling.
   • About 71% of patients reported scalp pain.

Population(s) looked at in Nangia and colleagues study:

The patients involved in this study were woman who:

• were diagnosed with stage I or II breast cancer
• were planning to receive at least 4 cycles of taxane- and/or anthracycline-based chemotherapy.  The chemotherapy regimens included were doxorubicin with cyclophosphamide, doxorubicin with fluorouracil and cyclophosphamide, weekly paclitaxel, weekly paclitaxel with carboplatin, docetaxel, docetaxel with pertuzumab and trastuzumab, docetaxel with cyclophosphamide, or docetaxel with carboplatin.

The SCALP randomized clinical trial was conducted at 7 sites in the United States and included 182 women.  This study was stopped early due to positive results.  At the time the study was stopped, 142 participants were evaluable. The mean age of the patients was 52.6 (10.1) years; 36% (n = 51) received anthracycline-based chemotherapy and 64% (n = 91) received taxane-based chemotherapy.

In this study, scalp cooling was done using the Orbis Paxman Hair Loss Prevention System which was cooled to 37 degrees Fahrenheit and placed on participant’s heads 30 minutes prior to and during and 90 minutes after each chemotherapy treatment.

The researchers assessed hair loss at baseline and after each cycle of chemotherapy using the Common Terminology Criteria for Adverse Events (a scale of 0-2 where 0 represents no hair loss, 1 represents <50% hair loss not requiring a wig or 2 which represents >50% hair loss requiring the use of a wig).  Hair loss was assessed by three independent means. Patients did their own self-assessment on their hair loss. They were also assessed by their own doctor and finally by a clinician who was “blinded” (unaware of whether or not each patient received scalp cooling therapy) in order to avoid bias.

Nangia study findings:   

Nangia and colleagues reported similar results to the Rugo study.

1. Approximately 1/2 of patients lost less than 50% of their hair compared to 0 patients who received similar chemotherapy treatments without scalp cooling therapy.
   • Estimated hair preservation with anthracycline-based chemotherapy was 16%.
   • Estimated hair preservation with taxanes was 59% and certain taxane-based regimens such as weekly paclitaxel had higher rates of hair preservation versus every-3-week docetaxel.
2. There was variability in the rate of hair preservation between the 7 sites doing the research which is likely due to fitting of the cap, type of chemotherapy, and patient hair characteristics such as hair from people of different ethnicities and hair thickness.
3. Patients who received scalp cooling therapy reported the following side effects:  chills, dizziness, headache, nausea, paresthesia (abnormal sensation of tingling, numbness, or burning), pruritus (itching), sinus pain, skin and tissue disorders, skin ulceration, and scalp pain.  While no severe adverse effects of scalp cooling were reported in this study, the authors recommend further research to assess longer-term efficacy and adverse effects of scalp cooling during chemotherapy.

Limitations:

Because patients in the Rugo study did not receive anthryacycline-based chemotherapy regimens, those results cannot be generalized to all chemotherapy treatments. Additionally, the findings reported in this study were patient-reported results.  Unlike trials that include a placebo, these patients knew whether or not they received the treatment, which may have biased the results. Nor was this study was randomized, and the control group (women who did not have scalp cooling treatment) was much smaller than the group that did receive scalp cooling therapy. The researchers defended their study design by explaining that the chemotherapy regimens used in this study are known to cause hair loss, so they determined that a small study that included a limited number of controls was adequate.

The Nangia study also had some limitations which included variability of results at each site, assessing for successful hair retention after only 4 cycles of chemotherapy when some patients may have received additional cycles.  Because this trial was stopped early statistical power was decreased. However, 60 additional patients were enrolled in this trial with the last participant scheduled to complete chemotherapy in early 2017 following which a final analysis will be completed.

There is some concern that scalp cooling may increase the risk of metastasis to the scalp.  Because the follow-up in the Rugo (2.5 years) and Nangia (5 years) studies were relatively short a study with a longer follow-up period is needed to rule out this possibility.  However, published data demonstrate that the incidence of scalp metastasis following chemotherapy in breast cancer is low, and it is exceedingly rare for the scalp to be the first site of metastasis.

Finally, the UCSF study was partially paid for by the Swedish company Dignitana which manufactures DigniCap while the Baylor study was partially funded by the English company which manufactures the Orbis Paxman Hair Loss Prevention System. Industry-sponsored research is common, and doesn't necessarily influence results, but it is an important consideration when evaluating potential sources of bias in research studies. 

Conclusions:

These studies suggest that patients who receive scalp cooling during chemotherapy for early-stage breast cancer have less hair loss than patients who do not receive scalp cooling.  The Nangia study suggests that efficacy of scalp cooling may be less at sites where more anthracycline-based chemotherapy is used or where there is less training on proper cap fitting.  Thus these substantial differences between sites and technique may impact how effective scalp cooling will be in wider clinical practice.

An accompanying editorial written by Dawn Hershman, MD from Columbia University Medical Center raises questions about the cost of scalp cooling devices and who will pay for them, and notes that more work should be done to study outcomes after scalp cooling treatment. However, she wrote that until targeted therapies are the mainstay and chemotherapy leading to hair loss is no longer needed, “identifying interventions, such as scalp cooling for the prevention of chemotherapy-induced alopecia [hair loss], that reduce or eliminate treatment-associated toxic effects will help ease the distress associated with chemotherapy and may, as a result, improve outcomes for patients with breast cancer.” Interested patients should discuss scalp cooling with their health care providers.

Posted 5/15/17

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