Scalp cooling resulted in significant reductions in hair loss in about half of all women who were treated before, during, and after chemotherapy for breast cancer in both the Scalp Cooling Alopecia Prevention (SCALP) randomized clinical trial and in a multicenter prospective cohort study.

However, the effects of the reduced alopecia on quality of life measures were mixed, according to the findings of the studies, which were published online in JAMA.

Courtesy DignItana AB

The findings of the multicenter SCALP trial are from a planned interim analysis of data from 95 women with breast cancer who were undergoing chemotherapy and who were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS), and 47 controls. Successful hair preservation occurred in 50.5% of those in the scalp cooling group, compared with 0% of those in the control group – results which led to early study termination, reported Julie Nangia, MD, of Baylor College of Medicine, Houston, and her colleagues (JAMA 2017 Feb 14. doi: 10.1001/jama.2016.20939).

No serious adverse device-related events occurred in the cooling group, but there also were no significant differences between the groups with respect to changes in quality of life scales from baseline to chemotherapy cycle 4, the investigators found.

Study subjects were women with a mean age of 52.6 years who were receiving anthracycline-based chemotherapy (36%) or taxane-based chemotherapy (64%). Successful hair preservation was defined as grade 0 or 1 based on the Common Terminology Criteria for Adverse Events version 4.1 scale, representing no hair loss or less than 50% hair loss not requiring a wig, respectively. Five women had grade 0 hair loss, and 43 had grade 1 hair loss.

Quality of life was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-30), the Hospital Anxiety and Depression Scale (HADS), and a summary scale of the Body Image Scale. Changes in emotional and social functioning as measured using the EORTC-QLQ-30 did not differ between the groups, including among those with and without hair preservation, after four treatment cycles, and HADS anxiety and depression summary scores were normal both at baseline and after four cycles in both groups, regardless of hair preservation.

Patients will be followed for 5 years to assess for safety and overall survival, the investigators noted.

During a presentation of these findings at the San Antonio Breast Cancer Symposium in December, Dr. Nangia noted that the maker of the OPHLPS is seeking Food and Drug Administration clearance based on the findings, and if approved, the system would compete with the DigniCap (Dignitana AB), which has already received Food and Drug Administration clearance.*

The DigniCap was the device evaluated (at the time under an FDA investigational device exemption) in the prospective cohort study also published in JAMA.

In that study, 106 women receiving adjuvant or neoadjuvant chemotherapy for stage 1 or II breast cancer were treated with scalp cooling between August 2013 and October 2014, and, along with 16 control subjects, were followed for a median of 29.5 months. Self-estimated hair loss at 4 weeks after the last chemotherapy dose was 50% or less, based on the Dean scale (score of 0-2) in 67 of 101 evaluable patients in the scalp cooling group, vs. 0 of 16 in the control group, reported Dr. Hope S. Rugo, MD, of the Helen Diller Family Comprehensive Cancer Center, San Francisco, and her colleagues.

Five patients had no hair loss, and 62 had less than 50% hair loss, the investigators said (JAMA. 2017 Feb 14. doi: 10.1001/jama.2016.21038).

Three of five quality of life measures, as assessed using the EORTC-QLQ, were significantly better at 1 month after the end of chemotherapy vs. at baseline in the cooling group, compared with the control group. For example, 27.3% vs. 56.3% of treatment and control subjects, respectively, reported feeling less physically attractive. The results were similar among those with 50% or less hair loss vs. controls, they noted.

Adverse events associated with cooling included mild headache in four patients. Three patients discontinued treatment due to feeling cold.

The mean age of the women was 53 years. None of those in the treatment group received anthracyclines, thus further research is needed to assess scalp cooling outcomes after treatment with anthracycline regimens, the investigators said, noting that additional research is also needed to assess long-term measures of alopecia and adverse effects. Patients will be followed for a total of 5 years.

Taken together, the findings of these two studies suggest that increased use of scalp cooling is warranted, as it has the potential to both reduce a troublesome side effect of chemotherapy and to remove a common concern – and sometimes a deterrent – among women considering chemotherapy, according to Dawn L. Hershman, MD, of the Herbert Irving Comprehensive Cancer Center at Columbia University.

In an editorial, Dr. Hershman noted that adjuvant chemotherapy reduces the 10-year relative risk of death from breast cancer by about 35%, but that “a substantial number of women who are advised to undergo chemotherapy choose not to receive treatment because of concerns about adverse effects.”

About 50% of patients consider hair loss the most traumatic aspect of chemotherapy, and about 8% said they would decline chemotherapy because of concerns about hair loss, she said.

“Therefore an intervention that could reduce the adverse effects of chemotherapy may lead to improvement in the initiation and completion of therapy, in quality of life, and in survival outcomes,” she wrote (JAMA. 2017 Feb 14;317[6]:587-8).

At face value, the “reassuringly similar” findings from these two studies appear to represent a major step forward for improving the quality of life for individuals with cancer, she added, explaining that while the quality of life data suggest a limited effect, they should be interpreted with caution as the overall effects of the patients’ diagnoses, surgery, and treatment may have influenced the patient-reported outcomes, diminishing the likelihood of detecting differences in quality of life associated with lower rates of alopecia.

Further, the unblinded nature of the intervention may also bias patient-reported outcomes results, she said, adding that “better measures may be needed to capture the effect of treatments on outcomes that are meaningful to patients so that important adverse effects are fully captured in comparative clinical trials.”

Although questions about cost and coverage of scalp cooling remain, Dr. Hershman concluded that until chemotherapy is no longer necessary and some of the distressing adverse effects of cancer treatment can be avoided, interventions such as scalp cooling that can reduce or eliminate toxic effects will help ease the distress and may thereby improve outcomes for patients with breast cancer.

In a separate editorial, Howard (Jack) West, MD, of the Swedish Cancer Institute in Seattle, further notes that a “lingering concern” with respect to scalp cooling is “the speculated potential for increased scalp metastases ... owing to poor local circulation of chemotherapy.”

However, this has not been observed in studies to date, he noted (JAMA. 2017 Feb 14. doi: 10.1001/jamaoncol.2017.0051).

“While some may argue that we need long-term data on timing and patterns of recurrence as well as overall survival to ensure that there is no increased risk of scalp metastases or otherwise compromised outcomes for scalp cooling, there is no evidence thus far to suggest this,” he said, concluding that “it is arguable that growing attention on interventions to reduce chemotherapy-induced alopecia are reaching an inflection point that justifies far more widespread adoption.”

The SCALP trial was supported by Paxman Coolers Ltd. Dr. Nangia reported having no disclosures. The study by Dr. Rugo et al. was funded in part by Dignitana AB, the Laszlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Dr. Rugo, Dr. Hershman, and Dr. West reported having no disclosures.

*Correction, 4/5/17: An earlier version of this article misstated the device's FDA status.

sworcester@frontlinemedcom.com

Scalp cooling reduces hair loss in 50% or more of women in separate studies