瑞典头皮冷却装置与乳腺癌化疗后脱发的相关性：队列研究

　　化疗所致脱发是一种常见且令人不悦的不良反应。既往关于头皮冷却防止化疗所致脱发的研究，对于使用头皮冷却是否与早期乳腺癌女性接受普通辅助化疗方案所致脱发风险较低有相关性的结论有限。

　　2017年2月14日，《美国医学会杂志》正式发表旧金山加利福尼亚大学、纽约西奈山伊坎医学院、维克弗斯特医学院、洛杉矶加利福尼亚大学、威尔康奈尔医学院、纽约塔吉特医院有限公司、瑞典迪格尼塔纳有限公司、纽约哥伦比亚大学的多中心前瞻队列研究报告，评估了在美国医学中心是否使用头皮冷却系统与接受特定化疗方案的早期乳腺癌女性自我评定脱发量和生活质量变化之间的相关性。

　　该多中心前瞻队列研究于2013年8月～2014年10月在5个美国医学中心入组接受辅助或新辅助化疗方案（排除序贯或联合蒽环类和紫杉类）的I或II期乳腺癌女性122例（头皮冷却组106例，对照组16例；14例按年龄和化疗方案匹配；平均年龄53岁，范围28～77岁；77.0%为白人，9.0%为黑人，10.7%为亚洲人；），并且每年随访持续5年。

　　头皮冷却系统从每个化疗周期之前30分钟开始，整个化疗期间将头皮温度保持在3℃（37℉），之后持续90～120分钟。

　　主要衡量指标：末次化疗4周后，采用迪安量表，通过非盲法，让患者比较前后5张照片进行脱发自我评估。将迪安量表评分0～2（脱发≤50%）定义为治疗成功。若头皮冷却组患者≥50%获得治疗成功，且成功比例的95%置信区间下限大于40%，则证明头皮冷却与脱发风险降低之间有相关性。在基线、在末次化疗周期开始和1个月后评定生活质量。中位随访29.5个月。

　　结果发现，平均2.3个月（中位2.1个月）化疗期间，头皮冷却组患者均未接受蒽环类。

　　头皮冷却组、对照组分别有101例、16例患者完成化疗后可评估脱发，其中分别有67例（66.3%，95%置信区间：56.2%～75.4%）、0例（0%）观察到脱发≤50%（P＜0.001）。头皮冷却组化疗结束1个月后，5项生活质量指标中的3项显著较好。

　　头皮冷却组与对照组相比，报告感觉外表吸引力减少的患者分别占27.3%、56.3%（95%置信区间分别为：18.0%～36.6%、31.9%～80.6%，P=0.02）。

　　头皮冷却组的106例患者，4例（3.8%）有轻度头痛的不良事件，3例（2.8%）由于感冒而停止头皮冷却。

　　因此，根据该多中心研究结果，非蒽环类辅助化疗完成4周后，头皮冷却组、对照组的脱发≤50%（迪安评分为0～2）比例分别为66.3%、0%。在接受非蒽环类辅助化疗的早期乳腺癌女性中，使用这种自行头皮冷却系统与无头皮冷却相比，与末次化疗4周后脱发较少有相关性。接受头皮冷却女性的5项生活质量指标中有3项较好，包括感觉外表吸引力。

　　但是，需要进一步研究评定患者接受蒽环类方案后的转归、脱发长期指标和不良反应。

JAMA. 2017 Feb 14;317(6):606-614.

Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer.

Hope S. Rugo; Paula Klein; Susan Anitra Melin; Sara A. Hurvitz; Michelle E. Melisko; Anne Moore; Glen Park; Jules Mitchel; Erika Bageman; Ralph B. D'Agostino Jr; Elizabeth S. Ver Hoeve; Laura Esserman; Tessa Cigler.

University of California, San Francisco; Icahn School of Medicine at Mount Sinai, New York, New York; Wake Forest School of Medicine, Winston-Salem, North Carolina; University of California, Los Angeles; Weill Cornell Medical College, New York, New York; Target Health Inc, New York, New York; Dignitana AB, Lund, Sweden; Columbia University, New York, New York.

This cohort study evaluates associations between use of a scalp cooling system and self-assessed hair loss and quality of life among women receiving chemotherapy for early-stage breast cancer at US medical centers.

KEY POINTS

QUESTION: Is scalp cooling associated with a lower risk of hair loss when used by women receiving common adjuvant chemotherapy regimens for early-stage breast cancer?

FINDINGS: In this multicenter study, hair loss of 50% or less (Dean score of 0-2) was seen in 66.3% of patients in the scalp cooling group vs 0% of patients in the control group at 4 weeks after completing non-anthracycline-based adjuvant chemotherapy. Three of 5 quality-of-life measurements, including feeling less physically attractive, showed benefit for women who received scalp cooling.

MEANING: This self-contained cooling system was associated with a lower risk of hair loss among women receiving non-anthracycline-based chemotherapy for early-stage breast cancer.

ABSTRACT

IMPORTANCE: Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited.

OBJECTIVES: To evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years.

EXPOSURES: Use of a scalp cooling system. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward.

MAIN OUTCOMES AND MEASURES: Self-estimated hair loss using the Dean scale was assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (≤50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months.

RESULTS: Among the 122 patients in the study, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%; 95% CI, 56.2%-75.4%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P<.001). Three of 5 quality-of-life measures were significantly better 1 month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27.3% (95% CI, 18.0%-36.6%) reported feeling less physically attractive compared with 56.3% (95% CI, 31.9%-80.6%) of patients in the control group (P=.02). Of the 106 patients in the scalp cooling group, 4 (3.8%) experienced the adverse event of mild headache and 3 (2.8%) discontinued scalp cooling due to feeling cold.

CONCLUSIONS AND RELEVANCE: Among women undergoing non-anthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. Further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01831024

DOI: 10.1001/jama.2016.21038