1 University of Maastricht, Nassaulaan 11a, 6224 JT Maastricht; 2 Department of Internal Medicine, Catharina Hospital, Eindhoven, The Netherlands
* Correspondence to: Dr W. P. M. Breed, Lissevenlaan 13, 5582 KB Waalre, The Netherlands. Tel: +31-40-2213807; Fax: +31-40-2214508; Email: wpmbreed{at}planet.nl
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Abstract |
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Methods: This review from 53 publications and three personal communications focuses on the efficacy of the treatment, side-effects, possible disadvantages and the controversies in these areas.
Results: 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. Scalp cooling should not be used if chemotherapy is given with a curative intent in patients with generalised haematogenic metastases. The majority of patients tolerate cooling very well.
Conclusion: Scalp cooling is effective but not for all chemotherapy patients. 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. Multicentre trials should be carried out to gather this information.
Key words: alopecia, chemotherapy-induced hair loss, cold cap, hair preservation, hypothermia, scalp cooling
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Introduction |
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This review of literature will focus on the following areas: the efficacy of the treatment, side-effects, possible disadvantages and the controversies in these areas.
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Results |
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Results of hair preservation
In six out of the seven randomised studies, a significant advantage was seen when scalp cooling was used (Table 1). In 13 out of the 14 non-randomised studies with historical control groups, the authors concluded positive results of scalp cooling for certain indications (Tables 2 and 3). The 35 studies without historic controls showed 31 positive results (Tables 2 and 3).
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The average success rate of the studies carried out before 1995 was 56% and from 1995 onwards 73% (Table 4).
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In 13 studies, liver function or the presence of liver metastasis were taken into consideration for the hair protective effect of scalp cooling. In six out of these 13 studies, impaired liver function seemed to be related to less benefit from cooling [10, 29
, 35
, 50
, 52
, 54
].
Side-effects. The most often reported side-effects were: headaches, complaints of coldness and/or uncomfortable sensations, among others claustrophobia. These side-effects were in general not serious. There were a few studies in which in more than 10% of the patients side-effects were a reason for stopping the cooling procedure [9, 18
, 31
, 32
]. Dougherty even reported that in the group of patients in which cooling had been ineffective, 38% of those patients felt they would want the scalp cooling procedure if they needed another chemotherapeutic treatment [1
].
Scalp cooling is contra-indicated in cases of cold sensitivity, cold agglutinin disease, cryoglobulinemia and cryofibrinogenemia.
Long-term adverse consequences?
Scalp metastases. In only 24 out of 58 studies (including the two studies with only one patient), was attention paid to the presence of scalp skin metastases after cooling. Sixteen of those 24 studies mentioned explicitly that no scalp skin metastases were found. In six studies, scalp skin metastases were found in nine patients out of a total of about 2500 patients in the 56 studies [14, 23
, 46
, 48
, 54
, 57
, 58
]. Both Witman et al. and Forsberg had a patient (one with mycosis fungoides, one with leukaemia) in whom they thought there was a relation between the skin metastases and the cooling [57
, 58
]. Only Lemenager et al. [21
] and Ridderheim et al. [25
] looked systematically for the incidence of scalp skin metastases after cooling. In the 15 years that Lemenager et al. used scalp cooling, they did not find increased incidence in scalp metastases after cooling (median post-cooling follow-up of 9 months) [21
]. Ridderheim et al. found no scalp metastases during a median follow-up period of 15 months among 74 patients [25
].
One study even reported a decrease in size of a scalp skin metastasis despite cooling during chemotherapy [14].
Survival. No research has been carried out to evaluate the influence of scalp cooling on the survival time.
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Discussion |
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The original idea was to analyse the studies to find the relation between the temperature of the scalp obtained in the various studies and the effect of scalp cooling; however, temperature measurements were only done in one study.
Success rates
It is evident that cooling can prevent hair loss. However, it is very difficult to compare most studies, because of differences in patient characteristics, chemotherapy, cooling and hair loss assessment. This is demonstrated in hair preservation with similar CMF regimens in two randomised trials: 17% and 63% in controls.
The success of cooling is most apparent in the randomised studies (Table 1), but in a number of the 49 non-randomised studies, cooling also seems effective (Tables 2 and 3). Table 4 suggests better results from 1995 onwards than before that period, although this might be influenced by publication bias.
The wide variation in reported success rates is unexplained. The success of scalp cooling depends on many factors like type of cytostatics, the doses, the number of chemotherapy courses and the admission method [14, 28
, 35
, 49
]. In particular, when anthracyclines or taxanes were used, the positive effect has been proven [7
, 14
, 21
, 45
]. If a combination of anthracyclines and taxanes were used, the results were considerably less positive [9
, 14
, 18
]. As hair loss induced by paclitaxel is considerably increased if patients have undergone previous chemotherapy [59
], it seems likely that the results of cooling will also be influenced by previous chemotherapy. Therefore previous chemotherapy treatments should always be taken into consideration when analysing results of scalp cooling.
Few studies have been made to find out which method of scalp cooling is the most effective [1, 13
, 43
]. Careful application of the cooling cap might be more important than the cooling system itself, as the contact between the cold cap and the scalp skin is decisive for scalp temperature as has been suggested in numerical modelling of scalp cooling [60
].
Furthermore, the importance of the degree of hypothermia of the scalp skin has hardly been studied. In 1982, in a study with a limited number of patients, Gregory et al. found the best protective effect against hair loss in the group of patients with the lowest intradermal temperatures [41]. There have been no further studies to confirm this. Although accurate measurement of the scalp skin temperature during cooling is extremely difficult, temperature measurements or other parameters for skin temperature are necessary to determine the optimal hypothermia, pre-cooling times and optimal application of the cap.
Post-infusion cooling time also seems to be relevant for the results of cooling (Table 5). Theoretically, the cooling period after infusion of cytostatics should be related to the half-life time of the cytostatic used and their active metabolites but this is rarely done and has never been investigated [15, 53
].
The importance of liver function to the success rate of scalp cooling is controversial. In six out of 13 studies with abnormal liver function or liver metastasis, less benefit from cooling was observed [29, 35
, 45
, 50
, 52
, 54
].
Side-effects
Scalp skin cooling is generally well tolerated. Although side-effects are rarely a reason to stop the cooling, further research to improve tolerance for cooling might improve the results.
Long term adverse consequences?
In several publications, authors have been concerned about the possible protective effect of cooling on (micro-)metastases of the scalp skin [9, 12
, 14
, 25
, 45
]. Although the findings of Lemenager et al. and Ridderheim et al. seem to be very reassuring, one has to bear in mind that their conclusions were based on only a 9 month follow-up period [21
, 25
]. A good systematic study to look for the influence of cooling on scalp skin metastases and on survival time of patients would require very large numbers of patients and a long-term follow-up. It is clear that in the case of haematological malignancies with haematogenic metastases, cooling is contraindicated [57
, 58
]. Scalp cooling is controversial in patients with non-haematological malignancies who undergo chemotherapy with a curative intention.
Fear of undoing the effect of chemotherapy on (micro) brain metastases by cooling seems unrealistic as the current cooling techniques do not cause a significant decrease in brain temperature [60].
Recommendations
Based on the results of these studies, scalp cooling should be applied more. However, it is not possible to advise on the optimum application of the cooling methods (system, duration and temperature). Careful application of the cooling cap might be more important than the cooling system itself. We recommend multicentre trials to study the optimal method, temperature and duration of cooling with various chemotherapy regimens. Patient satisfaction should be the most important criteria for success, because efforts to obtain objective measurements are very difficult and less important than the contentment of the patient.
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Conclusions |
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If chemotherapy is given with a curative intent, scalp cooling should not be used in patients with extensive haematological malignancies as cooling might prevent the effect of chemotherapy on tumour cells in the scalp skin; in other patients, an adverse long-term effect of scalp cooling has not been described. The majority of patients tolerate cooling very well and side-effects are not frequent and not serious.
Further psychological, clinical and biophysical research is needed to determine the exact indications for cooling and to improve the hair-protective effect, tolerance, side-effects and the technical cooling procedure. Multicentre trials should be carried out to gather this information.
Received for publication June 22, 2004. Accepted for publication October 26, 2004.
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References |
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