Meattini Icro, De Santis Maria Carmen, Visani Luca, Scorsetti Marta, Fozza Alessandra, Meduri Bruno, De Rose Fiorenza, Bonzano Elisabetta, Prisco Agnese, Masiello Valeria, La Rocca Eliana, Spoto Ruggero, Becherini Carlotta, Blandino Gladys, Moscetti Luca, Colciago Riccardo Ray, Audisio Riccardo A, Brain Etienne, Caini Saverio, Hamaker Marije, Kaidar-Person Orit, Lambertini Matteo, Marrazzo Livia, Saieva Calogero, Spanic Tanja, Strnad Vratislav, Wheelwright Sally, Poortmans Philip M P, Livi Lorenzo
Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
Radiation Oncology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.
Lancet Oncol. 2025 Jan;26(1):37-50. doi: 10.1016/S1470-2045(24)00661-2. Epub 2024 Dec 12.
Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.
This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting.
Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p=0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group.
Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.
Fondazione Radioterapia Oncologica.
老年低风险早期乳腺癌患者保乳手术后的最佳治疗方案仍不明确。EUROPA试验旨在比较放疗和内分泌治疗作为单一治疗方式对该人群健康相关生活质量（HRQOL）和同侧乳腺肿瘤复发（IBTR）结局的影响。
这项非劣效性3期随机研究在意大利的18家学术医院（17个中心）和斯洛文尼亚的1家中心进行。符合条件的患者为70岁及以上的女性，组织学确诊为I期、腔面A型乳腺癌，已接受保乳手术，东部肿瘤协作组体能状态为0或1。患者被随机分配（1:1）接受单一内分泌治疗或放疗。内分泌治疗包括每日口服芳香化酶抑制剂或他莫昔芬，根据临床判断，总计划疗程为5 - 10年，而放疗采用全乳或部分乳腺照射，分5 - 15次进行。随机分组根据老年8项（G8）筛查工具的健康状况和年龄进行分层，分配过程保密且不设盲。共同主要终点为HRQOL的变化，通过欧洲癌症研究与治疗组织生活质量问卷30项核心模块的全球健康状况（GHS）量表在24个月时进行评估，以及5年IBTR率（本文未报告）。在至少152名患者完成24个月GHS HRQOL评估后进行了此次预先计划的中期分析。安全人群包括随机分组后至少接受一次研究干预的患者。该研究已在ClinicalTrials.gov注册，编号为NCT04134598，正在进行且积极招募患者。
在2021年3月4日至2024年6月14日期间，731名女性被随机分配接受放疗（n = 365）或内分泌治疗（n = 366）。该分析包括放疗组的104名患者和内分泌治疗组的103名患者，中位随访时间为23.9个月（IQR 22.9 - 24.2）。患者主要为白人，放疗组207名患者中有204名（99%），内分泌治疗组中位年龄为75.0岁（IQR 73.0 - 80.0），内分泌治疗组为74.0岁（72.0 - 80.）。放疗组86名患者和内分泌治疗组75名患者完成了24个月HRQOL评估。放疗组的平均基线GHS评分为71.9（SD 19.1），内分泌治疗组为75.5（19.3）。在24个月时，放疗组经年龄调整、G8评分调整后的GHS相对于基线的平均变化为 - 3.40（95%CI - 7.82至1.03；p = 0.13），内分泌治疗组为 - 9.79（ - 14.45至 - 5.13；p < 0.0001），调整后的平均差异为6.39（0.14至12.65；p = 0.045），支持放疗。放疗组与治疗相关的不良事件发生率低于内分泌治疗组（97名患者中的65名[67%]）与内分泌治疗组（89名患者中的76名[85%]）。最常见的3 - 4级不良事件为关节痛（内分泌治疗组89名患者中的6名[7%]，放疗组97名患者中为0）、盆腔器官脱垂（3名[3%]对0）、疲劳、潮热、肌痛、骨痛和骨折（每组均为2名[2%]对0）。放疗组15名（15%）患者和内分泌治疗组13名（15%）患者报告了严重不良事件。两组均无与治疗相关的死亡。
在24个月时，通过GHS测量，内分泌治疗与HRQOL的降低幅度大于放疗。虽然这些中期结果表明放疗可能更好地保留低风险早期乳腺癌老年女性的HRQOL，但需要关于疾病控制结局和最终患者入组的进一步数据才能得出明确结论。
肿瘤放射治疗基金会。
