Therapeutic Effect of Superficial Scalp Hypothermia on Chemotherapy-Induced Alopecia in Breast Cancer Survivors.

Alopecia is a common adverse effect of neoadjuvant or adjuvant chemotherapy in patients with early breast cancer. While hair typically regrows over time, more than 40% of patients continue to suffer from permanent partial alopecia, significantly affecting body image, psychological well-being, and quality of life. This concern is a recognized reason why some breast cancer patients decline life-saving chemotherapy. It is critical for healthcare professionals to consider the impact of this distressing side effect and adopt supportive measures to mitigate it. Among the various strategies investigated to reduce chemotherapy-induced alopecia (CIA), scalp cooling has emerged as the most effective. This article reviews the pathophysiology of CIA and examines the efficacy of different scalp cooling methods. Scalp cooling has been shown to reduce the incidence of CIA, defined as less than 50% hair loss, by 50% in patients receiving chemotherapy. It is associated with high patient satisfaction and does not significantly increase the risk of scalp metastasis or compromise overall survival. Promising new scalp cooling technologies, such as cryogenic nitrogen oxide cryotherapy, offer the potential to achieve and maintain lower scalp temperatures, potentially enhancing therapeutic effects. Further investigation into these approaches is warranted. Research on CIA is hindered by significant heterogeneity and the lack of standardised methods for assessing hair loss. To advance the field, further interdisciplinary research is crucial to develop preclinical models of CIA, establish a uniform, internationally accepted and standardised classification system, and establish an objective, personalised prognosis monitoring system.

Chemotherapy-Induced Alopecia by Docetaxel: Prevalence, Treatment and Prevention.

Docetaxel is a commonly used taxane chemotherapeutic agent in the treatment of a variety of cancers, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, gastric cancer, and head and neck cancer. Docetaxel exerts its anti-cancer effects through inhibition of the cell cycle and induction of proapoptotic activity. However, docetaxel also impacts rapidly proliferating normal cells in the scalp hair follicles (HFs), rendering the HFs vulnerable to docetaxel-induced cell death and leading to chemotherapy-induced alopecia (CIA). In severe cases, docetaxel causes persistent or permanent CIA (pCIA) when hair does not grow back completely six months after chemotherapy cessation. Hair loss has severe negative impacts on patients' quality of life and may even compromise their compliance with treatment. This review discusses the notable prevalence of docetaxel-induced CIA and pCIA, as well as their prevention and management. At this moment, scalp cooling is the standard of care to prevent CIA. Treatment options to promote hair regrowth include but are not limited to minoxidil, photobiomodulation (PBMT), and platelet-rich plasma (PRP). In addition, a handful of current clinical trials are exploring additional agents to treat or prevent CIA. Research models of CIA, particularly ex vivo human scalp HF organ culture and in vivo mouse models with human scalp xenografts, will help expedite the translation of bench findings of CIA prevention and/or amelioration to the clinic.

Expanding the Availability of Scalp Cooling to All Patients at Risk of Chemotherapy-Induced Alopecia.

Alopecia is an undesirable side effect of cancer chemotherapy. The mitigation of alopecia is a desirable adjunct treatment for patients with cancer. FDA-cleared scalp cooling (SC) devices have been successfully used to prevent or reduce chemotherapy-induced alopecia (CIA). This paper provides an understanding of the implementation and value of the new Insurance-Based Billing Model used in the USA for SC and its benefits compared with the original self-pay model. This improved compensation change will result in all patients in need, including underserved and disadvantaged populations, receiving equitable healthcare by allowing access to this valuable supportive care technology.

Results of the Dutch scalp cooling registry in 7424 patients: analysis of determinants for scalp cooling efficacy.

BACKGROUND: Chemotherapy-induced alopecia is a common consequence of cancer treatment with a high psychological impact on patients and can be prevented by scalp cooling (SC). With this multi-center patient series, we examined the results for multiple currently used chemotherapy regimens to offer an audit into the real-world determinants of SC efficacy. MATERIALS AND METHODS: The Dutch Scalp Cooling Registry collected data on 7424 scalp-cooled patients in 68 Dutch hospitals. Nurses and patients completed questionnaires on patient characteristics, chemotherapy, and SC protocol. Patient-reported primary outcomes at the start of the final SC session included head cover (HC) (eg, wig/scarf) use (yes/no) as a surrogate for patient satisfaction with SC and WHO score for alopecia (0 = no hair loss up to 3 = total alopecia) as a measure of scalp cooling success. Exhaustive logistic regression analysis stratified by chemotherapy regimen was implemented to examine characteristics and interactions associated with the SC result. RESULTS: Overall, over half of patients (n = 4191, 56%) did not wear a HC and 53% (n = 3784/7183) reported minimal hair loss (WHO score 0/1) at the start of their final treatment. Outcomes were drug and dose dependent. Besides the chemotherapy regimen, this study did not identify any patient characteristic or lifestyle factor as a generic determinant influencing SC success. For non-gender specific cancers, gender played no statistically significant role in HC use nor WHO score. CONCLUSIONS: Scalp cooling is effective for the majority of patients. The robust model for evaluating the drug and dose-specific determinants of SC efficacy revealed no indications for changes in daily practice, suggesting factors currently being overlooked. As no correlation was identified between the determinants explaining HC use and WHO score outcomes, new methods for evaluation are warranted.

Effectiveness of increasing the scalp cooling duration to prevent alopecia during adjuvant chemotherapy for breast cancer: a randomized pilot study.

PURPOSE: Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation. METHODS: Patients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss. RESULTS: The success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039). CONCLUSION: Long duration scalp cooling during chemotherapy might increase patients' discomfort and does not appear to improve hair preservation.

[Alopecia due to chemotherapeutics, hedgehog inhibitors, targeted antibody therapies and immune checkpoint inhibitors : Pathogenesis, clinical picture, diagnostics and prophylaxis]. / Alopezie durch Chemotherapeutika, Hedgehog-Inhibitoren, zielgerichtete Antikörpertherapien und Immuncheckpointinhibitoren : Pathogenese, Klinik, Diagnostik und Prophylaxe.

BACKGROUND: The incidence and severity of alopecia vary mainly depending on the chemotherapeutic agent used or other drug groups. The pathogenetic characteristics of the different forms of alopecia are reflected in the clinical presentation and, in some cases, in the resulting recommendations for prophylaxis. OBJECTIVES: To provide an overview of the pathogenesis, clinical presentation, diagnosis and prophylaxis of alopecia with chemotherapeutic agents, hedgehog inhibitors, targeted therapies and immune checkpoint inhibitors. MATERIALS AND METHODS: Based on the current S3 guideline "Supportive therapy", an extensive literature search was carried out. RESULTS AND CONCLUSION: Chemotherapy-induced hair loss (CIA) occurs in up to 65% of cases. Anagen effluvium is observed as early as 1-3 weeks after the start of treatment and is reversible in most cases. Alopecia associated with inhibitors of the Sonic Hedgehog signaling pathway (HHIA) such as vismodegib or sonidegib are observed in up to 60% of cases. They are characterized by telogen effluvium. BRAF or immune checkpoint inhibitors lead significantly less frequently to alopecia (BRAFA, CPIA). According to taxane-based chemotherapy protocols, scalp cooling can help to prevent higher-grade CIA. If CIA or other forms of alopecia are expected, early contact with self-help organizations and early prescriptions for wigs should be offered.

The Efficacy of Paxman Scalp Cooling System in Preventing Hair Loss in Breast Cancer Patients Receiving Chemotherapy in Western India - Multi-centre Retrospective Cohort Study.

Aim: Chemotherapy-induced alopecia (CIA) is the most common side effect of systemic treatment in breast cancer patients. Scalp cooling gained worldwide acceptance in preventing or mitigating CIA in patients undergoing chemotherapy. The objective of this study was to evaluate the efficacy and safety of the Paxman scalp cooling system (PSCS) in Indian breast cancer patients. Materials and Methods: This is a multi-centre, retrospective-observational study including patients registered from 1st March, 2019 to 30th April, 2021 undergoing chemotherapy for breast cancer by using PSCS. The primary end-point was the incidence of CIA after completing cycles of chemotherapy. Results: A total of 91 female patients were enrolled in the study, with a median age of 53 years (IQR: 44-62 years). The prevention of alopecia (grade 0 and grade I) was seen in 81%, while more than 50% hair loss (grade 2) was seen in 16.48% after completion of treatment. The univariate analysis results showed that CIA was significantly higher in patients who received anthracyclines (OR: 2.69; 95% CI: 1.04-6.958; P = 0.041) and in patients with a post-infusion cooling time of >150 minutes (OR: 8.409; 95% CI: 2.295-30.787; P = 0.001). The incidence of grade 2 (>50% hair loss) alopecia was 81.3% in patients <6 weeks and was 18.8% at >6 weeks of start of chemotherapy (P < 0.0001). No adverse events were reported in 71.4% of patients, and the most common adverse event was headache (18.7%). Conclusion: PSCS is an effective and well-tolerated treatment modality for preventing CIA among breast cancer patients undergoing chemotherapy.

Prevention and Treatment of Chemotherapy-Induced Alopecia: What Is Available and What Is Coming?

Millions of new cancer patients receive chemotherapy each year. In addition to killing cancer cells, chemotherapy is likely to damage rapidly proliferating healthy cells, including the hair follicle keratinocytes. Chemotherapy causes substantial thinning or loss of hair, termed chemotherapy-induced alopecia (CIA), in approximately 65% of patients. CIA is often ranked as one of the most distressing adverse effects of chemotherapy, but interventional options have been limited. To date, only scalp cooling has been cleared by the US Food and Drug Administration (FDA) to prevent CIA. However, several factors, including the high costs not always covered by insurance, preclude its broader use. Here we review the current options for CIA prevention and treatment and discuss new approaches being tested. CIA interventions include scalp cooling systems (both non-portable and portable) and topical agents to prevent hair loss, versus topical and oral minoxidil, photobiomodulation therapy (PBMT), and platelet-rich plasma (PRP) injections, among others, to stimulate hair regrowth after hair loss. Evidence-based studies are needed to develop and validate methods to prevent hair loss and/or accelerate hair regrowth in cancer patients receiving chemotherapy, which could significantly improve cancer patients' quality of life and may help improve compliance and consequently the outcome of cancer treatment.

Minimal added value of wetting hair before scalp cooling to prevent chemotherapy-induced alopecia in cancer patients - results from the Dutch Scalp Cooling Registry.

PURPOSE: Preventing chemotherapy-induced alopecia (CIA) is related to the degree of temperature reduction during scalp cooling. Wetting hair before scalp cooling reduces the scalp skin temperature. This observational study investigated the effects of wetting hair before scalp cooling on preventing CIA and on tolerance in cancer patients. METHODS: This Dutch multi-center cohort study comprised 1825 patients receiving ≥1 cycle of docetaxel (D), 5-fluorouracil-epirubicin-cyclophosphamide (FEC), 5-fluorouracil-epirubicin-cyclophosphamide-docetaxel (FECD), paclitaxel (P), or paclitaxel-carboplatin (PC). Patients underwent scalp cooling with wet or dry hair. Primary and secondary outcomes were the effects of wetting hair on head cover use and tolerance, respectively. RESULTS: None of the associations between wetting hair and head cover use in patients on D, FEC, P, or PC was significant; however, results all tended to be in favor of wetting hair. For FECD, univariate (p=0.005; OR=1.6; CI=1.1-2.1) and multivariable associations (p=0.007; OR=1.8; CI=1.2-2.6) were significant. Scalp cooling discontinuation due to intolerance differed significantly between groups that wetted hair or not (3% and 1% respectively; p=0.034). CONCLUSION: In a large patient group with mainly a European hair type and a high hair mass, no convincing evidence was found whether wetting hair prior to scalp cooling contributes to better prevention of CIA. Since it is argued that a higher reduction in scalp skin temperature by wetting hair contributes positively to scalp cooling efficacy, only a randomized controlled trial can provide an ultimate conclusion at the highest level of evidence. Until that time, healthcare professionals have to take into account that wetting hair may introduce lower compliance to the scalp cooling procedure.

[Scalp cooling for the prevention of chemotherapy-induced alopecia: systematic review and meta-analysis.] / Enfriamiento del cuero cabelludo para la prevención de la alopecia secundaria a quimioterapia: revisión sistemática y metanálisis.

OBJECTIVE: Alopecia is one of the most common adverse effects of chemotherapy, having a significant impact on the quality of life of patients who suffer from it. Among the interventions available for its prevention, scalp cooling (SC) is the most widely used. The aim of this study was to assess the efficacy and safety of the use of SC systems during chemotherapy sessions for the prevention or the reduction of the extent of chemotherapy-induced alopecia. METHODS: A systematic review of the literature published up to November 2021 was carried out. Randomized clinical trials were selected. The main outcome measure was alopecia (hair loss>50%) during and after chemotherapy treatment. When possible, a quantitative synthesis of the results was performed through meta-analysis using the Stata v.15.0 software. The risk ratio (RR) of the variable alopecia, was estimated using a random effects model following the Mantel-Haenszel method. Statistical heterogeneity of the results was evaluated graphically and through the test of heterogeneity χ2 and the Higgins I2 statistic. Sensitivity analyses and subgroup analyses were performed. RESULTS: 13 studies were included, with a total of 832 participants (97.7% women). In most studies, the main chemotherapy treatment applied was anthracyclines or the combination of anthracyclines and taxanes. The results obtained indicate that SC prevents alopecia (loss>50%) by 43% compared to the control group (RR=0.57; 95% CI=0.46 to 0.69; k=9; n=494; I2=63.8%). No statistically significant difference was found between the efficacy of automated and non-automated cooling systems (P=0.967). No serious short- or medium-term adverse events related to SC were recorded. CONCLUSIONS: The results suggest that scalp cooling contributes to the prevention of chemotherapy-induced alopecia.

OBJETIVO: La alopecia es uno de los efectos adversos más comunes de la quimioterapia, con un impacto importante sobre la calidad de vida de los/las pacientes que la padecen. Entre las intervenciones disponibles para su prevención, el enfriamiento del cuero cabelludo (ECC) es la que cuenta con un uso más extendido. El objetivo de este estudio fue evaluar la eficacia y la seguridad del uso de sistemas de ECC durante las sesiones de quimioterapia para la prevención o reducción de la extensión de la alopecia secundaria a la quimioterapia. METODOS: Se llevó a cabo una revisión sistemática de la literatura publicada hasta noviembre de 2021. Se seleccionaron ensayos clínicos aleatorizados. La medida de resultado principal fue la alopecia (pérdida de cabello superior al 50%) durante y posteriormente al tratamiento de quimioterapia. Cuando fue posible, se realizó síntesis cuantitativa de los resultados mediante metanálisis con el programa Stata v.15.0. Se estimó el riesgo relativo (RR) de la variable alopecia, utilizando un modelo de efectos aleatorios siguiendo el método de Mantel-Haenszel. La heterogeneidad estadística de los resultados se evaluó gráficamente y mediante el test de la χ2 y el estadístico I2 de Higgins. Se realizaron análisis de sensibilidad y análisis de subgrupos. RESULTADOS: Se incluyeron 13 estudios con un total de 832 participantes (97,7% de mujeres). En la mayoría de los estudios, los agentes quimioterapéuticos principales aplicados fueron las antraciclinas o la combinación de antraciclinas y taxanos. Los resultados obtenidos indican que el ECC reduce la aparición de la alopecia un 43% frente al grupo control (RR=0,57; IC95%=0,46 a 0,69; k=9; n=494; I2=63,8%). No se encontró una diferencia estadísticamente significativa entre la eficacia de sistemas de enfriamiento automatizados y no automatizados (P=0,967). No se registraron eventos adversos graves a corto o medio plazo relacionados con el ECC. CONCLUSIONES: Los resultados sugieren que el ECC contribuye a prevenir la alopecia secundaria a la quimioterapia.

Low temperature upregulating HSP70 expression to mitigate the paclitaxel-induced damages in NHEK cell.

Scalp cooling is the most approved treatment for preventing chemotherapy-induced alopecia (CIA). However, the protective mechanism of scalp cooling has rarely been reported. The goal of the present study was to study the relationship between paclitaxel concentration and temperature and the inhibitory effect of low temperature on paclitaxel-induced alopecia. The results showed that the dose of paclitaxel should not exceed 60-70 mg/mL during scalp cooling treatment, and the optimal cooling temperature under different paclitaxel concentrations was determined. Normal human epidermal keratinocytes (NHEK) cells were analyzed by global transcriptome analysis, functional annotation and pathway analysis of differentially expressed genes (DEGs) and ELISA kit to analyze the mechanism of low temperature therapy. The expression of HSPA8, HSPA1A and HSPA1B, which belongs to HSP70, was up-regulated by low temperature. These genes are important target genes of low temperature treatment, which were confirmed by ELISA. The up-regulation of PLK2 and the down-regulation of TXNIP expression are the upstream of mitochondrial dysfunction and ROS, inhibiting the accumulation of ROS and up-regulating the mitochondrial membrane potential. Our research partially elucidates the therapeutic mechanism of scalp cooling, which provides a new idea on the drug research and development in CIA.

Retrospective cohort study of scalp cooling in breast cancer patients.

For patients with cancer, alopecia is a common side effect that negatively impacts personal identity, body image, self-esteem, quality of life, and medical decision-making. Scalp cooling is a technique used to prevent alopecia in patients undergoing chemotherapy in which patients wear a cooled cap during chemotherapy infusions, causing localized vasoconstriction of blood vessels on the scalp. Because of the recent emergence of scalp cooling, there is a need to explore further the reasons why patients pursue this treatment. A retrospective chart review of women with breast cancer treated at The Ohio State University was conducted to investigate how factors such as patient age, race, ethnicity, insurance status, stage of cancer, and chemotherapy regimen influenced patients' decisions to incorporate scalp cooling into their treatment plan as compared to those who did not. Findings revealed that patient age, race, insurance status, and chemotherapy regimen were predictors of a patient's likelihood to undergo scalp cooling. Patients diagnosed at younger age and those with private insurance were more likely to utilize scalp cooling. In comparison to White patients, non-White patients were less likely to choose scalp cooling. Furthermore, patients placed on the chemotherapy regimen of AC or AC-T were less likely to pursue scalp cooling than patients on PTCH or TC regimens. These findings provide background for the development of educational resources for both patients interested in this therapy and healthcare providers discussing this treatment option in dermatology and oncology settings.

Prospective Study Investigating the Efficacy and Safety of a Scalp Cooling Device for the Prevention of Alopecia in Women Undergoing (Neo)Adjuvant Chemotherapy for Breast Cancer.

The prevention of chemotherapy-induced alopecia still represents an urgent need for every day clinical practice. In this regard, this prospective single-center study included breast cancer (BC) patients who underwent a scalp cooling device (Dignicap®) during (neo)adjuvant chemotherapy with the aim to evaluate the efficacy and safety of this device in preventing alopecia. One hundred and seventy-eight patients (median age 43 years) were enrolled. The chemotherapy regimen included anthracycline and taxane-based chemotherapy (68.1%), docetaxel and cyclophosphamide (25.8%), anthracycline and taxane-based plus carboplatin (3.9%), and paclitaxel alone (2.2%). In 25.3% of cases, a dose dense schedule was used. Overall, the success rate was 68.0%: 100% in paclitaxel alone, 87.0% in docetaxel-cyclophosphamide, 59.5% in anthracycline and taxane, and 71.4% in the sequential regimen plus carboplatin group (anthracycline and taxane-based chemotherapy versus taxane-based chemotherapy, p ≤ 001. No difference in terms of hair preservation between dose-dense or standard schedule was found (p = 0.557). Early discontinuation of the scalp cooling was observed in 50 patients (28.1%). Although 138 patients (77.5%) experienced adverse events, 70.2% of patients were satisfied with this device. In conclusion, this large prospective study confirmed the helpful effect of the scalp cooling system in preventing alopecia in BC patients also undergoing sequential anthracyclines and taxane-based chemotherapy.

Effectiveness, Safety, and Tolerance of Scalp Cooling for Chemotherapy-Induced Alopecia.

PROBLEM IDENTIFICATION: There is a lack of guideline recommendations about the use of scalp cooling for preventing chemotherapy-induced alopecia (CIA). This overview was conducted to summarize effectiveness, safety, and tolerance of scalp cooling for CIA based on systematic reviews. LITERATURE SEARCH: PubMed®, Embase®, Cochrane Library, and CNKI were searched from inception to May 15, 2021. DATA EVALUATION: AMSTAR 2 was used to assess the methodologic quality. Qualitative and quantitative synthesis methods were used to identify the effectiveness, safety, and tolerance of scalp cooling. SYNTHESIS: 14 systematic reviews were identified, and the quality assessment was poor. Scalp cooling has been considered to be effective for preventing chemotherapy-induced alopecia and has been confirmed in patients with breast cancer and other solid tumors. Most adverse effects were mild and moderate, and scalp cooling did not increase the risk of scalp metastases. IMPLICATIONS FOR RESEARCH: This overview could guide nurses to provide access to scalp cooling to reduce the risk of severe or total chemotherapy-induced alopecia for patients undergoing chemotherapy. The large-scale application of scalp cooling may be promoted by establishing reimbursement mechanisms and increasing available devices in the future.