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Background Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient’s self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. Methods One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. Discussion This study improves cancer patients’ quality of life and provides clinical evidence. Trial registration Registered at ClinicalTrials.gov— NCT05397457 on 1 June 2022.

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.

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.

PurposeScalp cooling as a method to reduce the incidence of chemotherapy-induced alopecia (CIA) is increasingly used in daily practice worldwide. However, in patients treated with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), scalp cooling fails in 48–67% of patients. This study investigated the efficacy of extended duration of post-infusion scalp cooling in breast cancer patients treated with this regimen.MethodsIn this prospective multi-centre randomised study, 102 patients with early breast cancer treated with adjuvant FEC chemotherapy were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 90 or 150 min. The primary endpoint was the need to wear a wig or other head covering to mask visible hair loss.ResultsSixteen out of 48 patients (33%) treated with 90 min of post-infusion cooling did not need any head covering, compared with 21 out of 46 patients (45%) treated with 150 min of post-infusion cooling (p = 0.2). WHO grades 2–3 (moderate-complete) alopecia were reported more often in patients treated with 90-min post-infusion cooling time (n = 25/51 (49%) versus n = 17/51 (33%); p = 0,02). Scalp cooling was well-tolerated (mean Visual Analogue Score 7.4) and only three patients (3%) stopped due to intolerance during treatment.ConclusionsExtending the duration of 90-min post-infusion scalp cooling to 150 min in patients treated with adjuvant FEC chemotherapy was well-tolerated but did not significantly diminish the need for head covering. However, grades 2–3 alopecia was seen less often with prolonged post-infusion scalp cooling.

Purpose For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post-infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time. Methods In this prospective, multi-centre randomised study, 134 patients who started treatment with docetaxel 75–100 mg/m 2 in a 3-weekly schedule were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 45 or 20 min. The primary end point was the need for a wig or other head covering as assessed by the patient. A visual analogue scale (VAS) with a range from 0 (not tolerable) to 10 (very tolerable) was used to measure tolerance. Results Scalp cooling results were similar for 45- and 20-min post-infusion cooling times. Thirty-three out of 45 patients (73 %) treated with 20 min of post-infusion cooling did not need a form of head covering, compared with 41 out of 52 patients (79 %) treated with 45 min of post-infusion cooling ( p  = 0.5). The procedure was well tolerated (mean visual analogue score 8.3). Six patients stopped due to intolerance during the first treatment cycle. Conclusions A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel-induced alopecia. Trial registration Trialregister.nl Identifier, NTR 1856.

Purpose Chemotherapy-induced alopecia is very distressing for a patient and may have an impact on treatment decisions. On docetaxel-based therapy, alopecia occurs in a substantial proportion of patients. We aimed to investigate whether two different methods of scalp cooling can prevent hair loss. Methods In this open-label, prospective, nonrandomized trial, patients with solid tumors receiving docetaxel in a palliative setting were allocated according to patients’ preference to short-term cooling (over 45 min postinfusion) with a Paxman® PSC-2 machine (PAX), with cold cap (CC), or no cooling. The combined endpoint was alopecia World Health Organisation (WHO) III or IV or the necessity to wear a wig. Study identifier is Clinicaltrials.gov NCT01008774. Results Two hundred thirty-eight patients were included in the trial (128 patients PAX, 71 CC, and 39 no cooling). Number of cycles (median 4) and median docetaxel doses were similar across groups (55–60 mg/day on weekly therapy, 135–140 mg/day on 3-weekly therapy). Alopecia occurred with PAX, CC, and no cooling under 3-weekly docetaxel in 23, 27, and 74 % and under weekly docetaxel in 7, 8, and 17 %, respectively. Overall, cooling (PAX and CC combined) reduced risk of alopecia by 78 % (hazard ratio 0.22; 95 % confidence interval 0.12 to 0.41). CC and PAX prophylaxis led to the same degree of prevention of alopecia. Adverse events (AE) were reported in 5 % (most frequently, sensation of cold), and 30 patients (13 %) discontinued cooling measures after cycle 1. Conclusions In this first comparison published to date, both PAX and CC offer efficacious protection against hair loss, in particular when docetaxel is administered in a 3-weekly interval.

Purpose The patient impact of chemotherapy-induced alopecia (CIA) is high. Scalp cooling is applied to reduce CIA. The potential optimum post-infusion cooling times (PICTs) are currently unknown. Methods Scalp cooling was applied in 53 patients receiving docetaxel chemotherapy with 90-min PICT (observational part). Also 15 non-scalp-cooled patients were included. If hair preservation was observed in >80 % of the patients, randomisation between 45 and 90-min PICT was planned. Patients reported tolerance of scalp cooling and use of head covering. Results Observational study: 81 % of scalp-cooled patients did not require head covering versus 27 % of non-scalp-cooled patients. Randomised study: 79 % of 38 patients with 90-min PICT did not need head covering versus 95 % of 38 patients with 45-min PICT ( p  = 0.04). Scalp cooling was very well tolerated (visual analogue scale = 79). Conclusion A 45-min PICT can be recommended in 3-weekly docetaxel regimens with a dose of 75 or 100 mg/m 2 , administered in 60 min. The shorter PICT is a major advantage in time investment for patients. Patients (women and men) who receive docetaxel, except combined with doxorubicin and cyclophosphamide (taxotere, adriamycin and cyclophosphamide (TAC)) should be informed about the protective effect and high tolerability of scalp cooling in avoiding CIA.

Chemotherapy-induced alopecia (CIA) remains one of the most distressing adverse effects of cancer therapy. Yet, no therapy is available to selectively protect healthy hair follicles (HFs) and their epithelial stem cells (eHFSCs) from chemotherapy-induced damage without awarding potential survival benefits to cancer cells. Here, we report how human HFs can be protected against 2 lead CIA-inducing chemotherapeutics by inducing selective transient cell cycle arrest. Pretreating scalp HFs before chemotherapy exposure ex vivo with ALRN-6924, a clinical-stage \"stapled peptide\" drug that binds with high affinity to key endogenous inhibitors of p53, selectively activated p53 signaling only in cells with wild-type TP53 genotype and upregulated p21. This led to temporary cell cycle arrest in healthy tissues without protecting TP53-mutant cancer cells and mitigated chemotherapy-induced HF damage on multiple levels, including excessive hair matrix apoptosis, premature catagen, pigmentary abnormalities, \"mitotic catastrophe,\" and micronucleation. It also protected eHFSCs against DNA damage, apoptosis, and pathological epithelial-mesenchymal transition. Notably, even topically applied ALRN-6924 afforded relative chemotherapy protection ex vivo. These results provide proof of principle for a strategy to selectively protect rapidly proliferating healthy epithelial tissues and their stem cells in patients with TP53-mutant cancers, which promises to protect against acute and permanent CIA.

Chemotherapy-induced alopecia (CIA) is a common and highly visible adverse effect of chemotherapy with substantial psychosocial and quality-of-life burdens. In this issue, Gherardini and colleagues described a targeted strategy to prevent CIA using ALRN-6924, a stapled peptide that transiently activates p53 and induces cell cycle arrest in proliferating TP53 wild-type tissues, such as the hair follicle. In ex vivo human scalp hair follicle culture, ALRN-6924 protected matrix keratinocytes and bulge stem cells from paclitaxel- and cyclophosphamide-induced injury, reducing apoptosis, DNA damage, and other pathologic features. These findings nominate precision chemoprotection as a promising supportive care approach for mitigating CIA.

This narrative review aims to examine the therapeutic potential and mechanism of action of plant extracts in preventing and treating alopecia (baldness). We searched and selected research papers on plant extracts related to hair loss, hair growth, or hair regrowth, and comprehensively compared the therapeutic efficacies, phytochemical components, and modulatory targets of plant extracts. These studies showed that various plant extracts increased the survival and proliferation of dermal papilla cells in vitro, enhanced cell proliferation and hair growth in hair follicles ex vivo, and promoted hair growth or regrowth in animal models in vivo. The hair growth-promoting efficacy of several plant extracts was verified in clinical trials. Some phenolic compounds, terpenes and terpenoids, sulfur-containing compounds, and fatty acids were identified as active compounds contained in plant extracts. The pharmacological effects of plant extracts and their active compounds were associated with the promotion of cell survival, cell proliferation, or cell cycle progression, and the upregulation of several growth factors, such as IGF-1, VEGF, HGF, and KGF (FGF-7), leading to the induction and extension of the anagen phase in the hair cycle. Those effects were also associated with the alleviation of oxidative stress, inflammatory response, cellular senescence, or apoptosis, and the downregulation of male hormones and their receptors, preventing the entry into the telogen phase in the hair cycle. Several active plant extracts and phytochemicals stimulated the signaling pathways mediated by protein kinase B (PKB, also called AKT), extracellular signal-regulated kinases (ERK), Wingless and Int-1 (WNT), or sonic hedgehog (SHH), while suppressing other cell signaling pathways mediated by transforming growth factor (TGF)-β or bone morphogenetic protein (BMP). Thus, well-selected plant extracts and their active compounds can have beneficial effects on hair health. It is proposed that the discovery of phytochemicals targeting the aforementioned cellular events and cell signaling pathways will facilitate the development of new targeted therapies for alopecia.