To this day, the cancer patient is often iconically portrayed in popular culture as a weakened, balding person. Certainly, considerable progress has been made in oncology in recent years, and new drugs with new side-effect profiles are available, but the above account, it is known, still has a lot of truth: Although the cells of many types of cancer are generally in division phases more frequently than normal body cells due to their high rate of division, and thus react more strongly to cytostatic drugs – all other cells that naturally divide rapidly, such as cells of the mucosa or, indeed, the hair root, are just as affected. What can be done about it? A study in JAMA has answers.
The results are from the SCALP trial. In this study, the so-called scalp cooling technique was used for hair preservation: The principle of scalp cooling for alopecia prevention under chemotherapy may be familiar to some readers, as corresponding approaches have existed since the 1970s. Scalp cooling is also known in Switzerland and causes (controversial) discussions from time to time, but it has not yet become widely established. The publication of the SCALP trial in the prestigious journal JAMA and the fact that it is a randomized trial conducted at multiple centers suggest a renewed focus on the topic. What is it exactly?
Scalp Cooling – Mode of action
In scalp cooling, a kind of “cooling cap” is locked on the head, which cools the scalp down a few degrees just before, during and after administration of chemotherapy, which hypothetically prevents hair loss via various processes:
- Vasoconstriction, reduction of blood flow in the scalp to 20-40% of normal, resulting in a smaller amount of chemotherapeutic substance reaching the hair follicles
- Reduction of the drug diffusion rate across the membranes of the cells in the hair follicles (lower permeability due to cooling), resulting in lower drug doses reaching the cells
- Reduction of metabolic activity and cell division rate of cells in hair follicles, which could also decrease the toxicity of chemotherapy in scalp.
In principle, driving such processes by cooling is not a new idea. However, the systems used up to now – if one can call ice packs and gel caps, which had to be constantly replaced, systems at all – were characterized by a rather uncomfortable and unpleasant handling for the patient (they were heavy and extremely cold) as well as a high workload for the staff. Furthermore, it is difficult – and yet seemingly crucial – to keep the cooling effect stable. There are also different opinions about the targeted temperatures of the scalp and the duration of cooling. Thus, the variability of the results depending on the patient/chemotherapy has been large so far – which may be due not least to the different cooling techniques [1].
SCALP Study
The SCALP trial is one of the few randomized trials in this area, and one that was stopped early due to the superior effectiveness of scalp cooling. The results thus come from a planned interim analysis and are promising. Sensor-controlled, lightweight silicone caps with coolant were used.
At the time of the interim analysis, 142 of a total of 182 women recruited with breast cancer (stage I-II) and receiving chemotherapy with taxanes and/or anthracyclines
- Scalp cooling achieved an overall hair retention rate of 50.5% (95% CI 40.7-60.4%) versus 0% in the control group (p<0.001)
- the effect of cooling thus exceeded the predefined statistical value for superiority of p=0.0061, which is why the study was stopped
- 5% suffered no hair loss at all with Scalp Cooling and 45% suffered hair loss of less than 50%
- only 63% with Scalp Cooling resorted to artificial hair replacement or headscarves, compared to the full 100% in the control group
- the success of scalp cooling under taxane-based chemotherapy was significantly better.
The latter finding is not new; already in the review by Komen et al. [1] had come to this conclusion.
A total of seven U.S. centers had participated in the study. Hair retention was defined according to the Common Terminology Criteria for Adverse Events version 4.0 scale as grade 0 (no hair loss) and grade 1 (<50% hair loss; visible only on close inspection; hair replacement not necessary, but another haircut at most). A blinded physician performed the appropriate inspection after four cycles of therapy.
Surprising finding: quality of life unchanged
Quality of life, one of the secondary endpoints, surprisingly did not change significantly between the start and end of the four therapy cycles, even with scalp cooling. This was true for both the intervention and control groups, and within the former also for those who had achieved hair retention. This may come as something of a surprise, since one could, and even should, assume that alopecia, which is repeatedly mentioned as the most burdensome side effect of all, is an important defining factor for the quality of life.
But beware: while the study asked about emotional and social functionality in general, as well as anxiety, depression, and body image, it did not specifically ask about the stress caused by a hair loss itself. It could be that the diagnosis “breast cancer” as well as the surgery and chemotherapy as factors had such a strong effect on the variables surveyed that they simply “masked” the effects of alopecia, whether present or not. The secondary endpoint, however, somewhat calls into question the good results of the primary endpoint and makes scalp cooling, as so often in studies, appear unpredictable and highly variable in its effect.
After all, the cooling cap did not produce any serious adverse effects either – all of the 54 events recorded in the intervention group, such as dry, itchy, painful scalp, dizziness, headache and feeling cold (!) were of grade 1 or 2. The concern about possible metastases in the scalp, as the chemotherapeutic agents cannot develop their effect there, was also not confirmed in the study.
Source: Nangia J, et al: Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer – The SCALP Randomized Clinical Trial. JAMA 2017; 317(6): 596-605.
Literature:
- Komen MM, et al: Factors Influencing the Effectiveness of Scalp Cooling in the Prevention of Chemotherapy-Induced Alopecia. Oncologist 2013 Jul; 18(7): 885-891.
InFo ONCOLOGY & HEMATOLOGY 2017; 5(4): 5-6.
