年轻人与老年人的结肠直肠癌发病率趋势：癌症登记数据分析 (1/11/2025)
Colorectal cancer incidence trends in younger versus older adults: population-based cancer registry data
先前的研究表明，在多个高收入西方国家，年轻人（年龄 <50 岁）的结肠直肠癌发病率正在增加，而老年人（年龄 ≥50 岁）的发病率则保持稳定或下降趋势。本研究旨在调查年轻人与老年人的当代结肠直肠癌发病率趋势。
方法: 从世卫组织-国际癌症研究机构五大洲癌症发病率数据库中提取了 50 个国家和地区的结肠直肠癌发病率数据，包括诊断年份, 性别和 5 岁年龄组。2022 年人类发展指数来自联合国发展计划署，分为非常高 (>0.80), 高 (0.70–0.79), 中等 (0.55–0.69) 和低 (<0.55) 类。早发性为25 至 49 岁之间诊断, 晚发性为50 至 74 岁之间诊断。研究每 100 ,000 人年的年龄标准化发病率 (ASR)。主要研究目标是研究当代年轻人与老年人的结肠直肠癌发病率趋势。按诊断年龄分层（25-49 岁或 50-74 岁）, 估计年均百分比变化 (AAPC)。
结果: 最近 5 年,早发性结直肠癌发病率最高的国家为澳大利亚（ASR 16.5 [95% CI 16.1-16.9]）, 美国（波多黎各；15.2 [14.2-16.2]）, 新西兰（14.8 [14.0-15.6]）, 美国（14.8 [14.7-14.9]）和韩国（14.3 [14.0-14.5]），最低的是乌干达（4.4 [3.6-5.2]）和印度（3.5 [3.3-3.7]）。老年人群发病率最高的国家是荷兰（168.4 [166.9–170.0]）和丹麦（158.3 [155.8–160.9]），最低的国家是乌干达（45.9 [38.5–51.4]）和印度（23.5 [22.8–24.3]）。就年均百分比变化而言，最近10年，23个国家早发性结直肠癌发病率保持稳定，但27个国家的发病率有所上升，年增幅最大的国家是新西兰（AAPC 3.97% [95% CI 2.44–5.52]）, 智利（3.96% [1.26–6.74]）, 波多黎各（3.81% [2.68–4.96]）和英格兰（3.59% [3.12–4.06]）。 27 个国家和地区中，有 14 个国家和地区的老年人口趋势稳定（阿根廷、法国、爱尔兰、挪威和波多黎各）或下降（澳大利亚, 加拿大, 德国, 以色列, 新西兰, 斯洛文尼亚, 英格兰, 苏格兰和美国）。
解释: 在接受调查的 50 个国家和地区中，有 27 个国家和地区的早发性结直肠癌发病率正在上升，其中 20 个国家的发病率上升速度要么是早发性疾病独有的，要么比老年人发病率的上升速度更快。研究结果强调，需要加大力度找出推动这些趋势的因素，并提高认识，以促进早期发现。
Previous studies have shown that the incidence of colorectal cancer is increasing in young adults (age <50 years) in several high-income Western countries, whereas the incidence in older adults showed a stabilizing or decreasing trends in incidence in older adults (age ≥50 years). This study aimed to investigate contemporary trends in colorectal cancer incidence in younger versus older adults. Methods: Data on colorectal cancer incidence for 50 countries and territories were extracted from the WHO-IARC Five Continents Cancer Incidence Database, including year of diagnosis, sex, and 5-year age groups. The 2022 Human Development Index was obtained from the United Nations Development Program and was categorized into very high (>0.80), high (0.70–0.79), moderate (0.55–0.69), and low (<0.55). Early onset was diagnosed between 25 and 49 years of age, and late onset was diagnosed between 50 and 74 years of age. Age-standardized incidence rates (ASRs) per 100 ,000 person-years were studied. The primary study objective was to investigate contemporary trends in colorectal cancer incidence in younger versus older adults and estimated average annual percentage change (AAPC) by age at diagnosis (25-49 years or 50-74 years).
Results: In the most recent 5 years (most countryies from 2013 to 2017), the countries with the highest incidence of early-onset colorectal cancer were Australia (ASR 16.5 [95% CI 16.1-16.9]), the United States (Puerto Rico; 15.2 [14.2-16.2]), New Zealand (14.8 [14.0-15.6]), the United States (14.8 [14.7-14.9]), and South Korea (14.3 [14.0-14.5]). The lowest were Uganda (4.4 [3.6-5.2]) and India (3.5 [3.3-3.7]). The highest incidence rates among the elderly were in the Netherlands (168.4 [166.9–170.0]) and Denmark (158.3 [155.8–160.9]), and the lowest rates were in Uganda (45.9 [38.5–51.4]) and India (23.5 [22.8–24.3]). In terms of average annual percentage change, the incidence of early-onset colorectal cancer remained stable in 23 countries over the past 10 years, but increased in 27 countries, with the largest annual increases in New Zealand (AAPC 3.97% [95% CI 2.44–5.52]), Chile (3.96% [1.26–6.74]), Puerto Rico (3.81% [2.68–4.96]), and England (3.59% [3.12–4.06]). In 14 of the 27 countries and territories, trends in the older population were stable (Argentina, France, Ireland, Norway, and Puerto Rico) or declining (Australia, Canada, Germany, Israel, New Zealand, Slovenia, England, Scotland, and the United States).
Interpretation: Early-onset colorectal cancer rates are increasing in 27 of the 50 countries and territories surveyed, and in 20 of these countries the rate of increase is either unique to early-onset disease or faster than the rate of increase in older adults. The findings highlight the need for greater efforts to identify the factors driving these trends and to increase awareness to promote early detection.
参考文献 Reference
Sung H et al. Lancet Onc 2025;26:51
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蒽环类药物对复发评分>31淋巴结阴性 HR+/HER2- 乳腺癌的影响 (1/5/2025)
Impact of anthracyclines in RS >31 node-negative HR+/HER2- breast cancer
背景：对于激素受体阳性乳腺癌患者，在含紫杉烷的化疗中添加蒽环类药物并不能明显改善无侵袭性疾病生存率, 但尚未研究蒽环类药物对高 Oncotype DX 复发评分 (RS) 患者的益处。
方法：研究者分析了 TAILORx 试验 (NCT00310180) 中接受紫杉烷 + 蒽环类/环磷酰胺和类似方案 (T-AC) 或紫杉烷 + 环磷酰胺 (TC) 化疗的患者的数据，该试验招募了 I/II 期, 淋巴结阴性, HR+/HER2 阴性乳腺癌患者。RS 在 11 至 25 之间的患者随机接受内分泌治疗或内分泌治疗加医生选择的化疗，而 RS > 26 的患者接受医生选择的化疗。使用调整后的风险比 (aHR) 比较了远处无复发间隔, 无复发间隔, 远处无复发生存期, 无复发生存期和总生存期。结果按 RS > 31 和 < 31 分层。
结果：在符合条件的 2,528 例病例中，437 例接受 T-AC 治疗，2,091 例接受 TC 治疗。 T-AC 组的治疗方案包括1) 蒽环类 + 环磷酰胺（剂量密集或 标准），然后接受紫杉烷（n = 298, 68%），2) 同时接受蒽环类, 环磷酰胺和 多西他赛（n = 59, 14%），3) 其他蒽环类 + 紫杉烷组合（n = 80, 18%）。 TC 组所有患者均接受紫杉烷和环磷酰胺治疗。32% 的患者 RS > 26（n = 816），20% 的患者 RS > 31（n = 501）。平均年龄为 55 岁，中位随访时间为 7.3 年。
与接受 TC 治疗的患者相比，接受 T-AC 治疗的患者 RS 更高（平均 30 vs 23），肿瘤更大（平均 20 毫米 vs 18 毫米），并且高级别的可能性更大（38% 高级别 vs 25%）。在调整协变量后 RS > 31 的患者中，接受 T-AC 与 5 年结果改善相关，T-AC 组的远处无复发间隔调整率为 97.5%, TC 组为 89.4%（aHR 0.27，p = 0.01），TAC 组的远处无复发间隔调整率为 96.5%，TC 组为 88.3%（aHR 0.45，p = 0.03），T-AC 组的无复发生存期调整 5 年率为 94.6%，TC 组为 86.6%； aHR 0.45，p = 0.02)，且 5 年总生存期有改善趋势 （T-AC 组调整后比率为 97.7%，TC 组为 92.5%；aHR 0.58，p = 0.22）。
在 RS < 31 的病例中，接受 T-AC 与远处无复发间隔改善 (aHR 1.12，p = 0.73), 远处无复发生存期 (aHR 1.09，p = 0.75) 或其他结果改善无关。样条回归估计表明随着 RS 的增加，蒽环类药物的益处增加。
结论：早期, HR+/HER2 阴性乳腺癌和高 RS 值（> 31）患者可能从辅助紫杉烷和含蒽环类药物的治疗中获益多于从 TC 中获益。
Background: For patients with hormone receptor (HR)-positive breast cancer, the addition of anthracyclines to taxane-containing chemotherapy does not significantly improve invasive disease-free survival, but the benefit of anthracyclines in patients with high Oncotype DX recurrence scores (RS) has not been studied.
Methods: The researchers analyzed data from patients who received either taxane + anthracycline/cyclophosphamide and similar regime (T-AC) or taxane + cyclophosphamide (TC) chemotherapy in the TAILORx trial (NCT00310180), which enrolled patients with stage I/II, node-negative, HR+/HER2-negative breast cancer. Patients with RS between 11 and 25 were randomized to endocrine therapy or endocrine therapy plus physician’s choice of chemotherapy, whereas patients with RS > 26 received physician’s choice of chemotherapy. Distant recurrence-free interval (DRFI), recurrence-free interval (RFI), distant recurrence-free survival, recurrence-free survival (RFS), and overall survival (OS) were compared using adjusted hazard ratios (aHRs). Results were stratified by RS > 31 and < 31.
Results: Of the 2,528 eligible cases, 437 were treated with T-AC and 2,091 with TC. Treatment regimens in the T-AC group included 1) anthracycline + cyclophosphamide (dose-dense or standard) followed by taxane (n = 298, 68%), 2) concurrent anthracycline, cyclophosphamide, and docetaxel (n = 59, 14%), and 3) other anthracycline + taxane combinations (n = 80, 18%). All patients in the TC group received taxane and cyclophosphamide. Among them, 32% of patients had RS > 26 (n = 816), and 20% had RS > 31 (n = 501). The mean age was 55 years, and the median follow-up was 7.3 years. Patients treated with T-AC had higher RS (mean 30 vs 23), larger tumors (mean 20 vs 18 mm), and were more likely to be high grade (38% high grade vs 25%) compared with those treated with TC. Among patients with RS > 31 after adjustment for covariates, receiving T-AC was associated with improved 5-year outcomes, with adjusted rates of DRFI of 97.5% in the T-AC group and 89.4% in the TC group (aHR 0.27, p = 0.01), adjusted rates of distant recurrence-free interval of 96.5% in the TAC group and 88.3% in the TC group (aHR 0.45, p = 0.03), and adjusted 5-year rates of recurrence-free survival of 94.6% in the T-AC group and 86.6% in the TC group; aHR 0.45, p = 0.02), and a trend towards improved 5-year overall survival (adjusted rates 97.7% in the T-AC group and 92.5% in the TC group; aHR 0.58, p = 0.22).
In cases with RS < 31, receiving T-AC was not associated with improved distant recurrence-free interval (aHR 1.12, p = 0.73), distant recurrence-free survival (aHR 1.09, p = 0.75), or other outcomes. Spline regression estimates indicated that the benefit of anthracyclines increased with increasing RS.
Conclusions: Patients with early-stage, HR+/HER2-negative breast cancer and high RS values (> 31) may benefit more from adjuvant taxane- and anthracycline-containing therapy than from TC.
参考文献 Reference
Chen N 2024 San Antonio Breast Cancer Symposium (SABCS; Abstract GS3-03)
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新一代雌激素受体降解剂 Imlunestrant+/-阿贝西尼治疗晚期乳腺癌 (1/4/2025)
Next-generation ER degrader Imlunestrant with or without abemaciclib for advanced breast cancer
Imlunestrant 是一种新一代脑渗透性口服选择性雌激素受体 (ER) 降解剂，即使对于 ERα 编码基因 (ESR1) 发生突变的癌症，也能持续抑制 ER。
方法: 在一项 III 期开放标签试验中 (NCT04975308)，研究者招募了 ER 阳性, HER2 阴性的晚期乳腺癌患者，这些患者在芳香化酶抑制剂单独使用或与细胞周期依赖性激酶 4 和 6 (CDK4/6) 抑制剂一起使用期间或之后复发或进展。患者按 1:1:1 的比例分配接受 Imlunestrant、标准内分泌单药治疗或 Imlunestrant-阿贝西尼治疗。主要终点是研究者评估的在所有 ESR1 突变患者中，使用Imlunestrant与标准疗法相比的无进展生存期，以及在所有同时接受随机分组的患者中，使用Imlunestrant -阿贝西利与Imlunestrant相比的无进展生存期。
结果: 总体而言，874 名患者接受了随机分组，其中 331 名患者接受Imlunestrant治疗，330 名患者接受标准疗法治疗，213 名患者接受Imlunestrant -阿贝西利治疗。在 256 名 ESR1 突变患者中，使用Imlunestrant的中位无进展生存期为 5.5 个月，使用标准疗法的中位无进展生存期为 3.8 个月。在19.4 个月时, 估计的平均限制生存时间在使用Imlunestrant患者中为 7.9 个月（95% 置信区间 [CI]，6.8 至 9.1），使用标准疗法的患者为 5.4 个月（95% CI，4.6 至 6.2）（差异为 2.6 个月；95% CI，1.2 至 3.9；P<0.001）。在总体人群中，使用Imlunestrant的患者中位无进展生存期为 5.6 个月，使用标准疗法的患者中位无进展生存期为 5.5 个月（进展或死亡风险比为 0.87；95% CI，0.72 至 1.04；P=0.12）。在 426 名接受Imlunestrant -阿贝马西利相比于Imlunestrant治疗的患者中，中位无进展生存期分别为 9.4 个月和 5.5 个月（风险比为 0.57；95% CI，0.44 至 0.73；P<0.001）。Imlunestrant治疗组 3 级或以上不良事件发生率为 17.1%，标准治疗组为 20.7%，Imlunestrant -阿贝马西利治疗组为 48.6%。
结论: 在 ER 阳性、HER2 阴性晚期乳腺癌患者中，接受Imlunestrant治疗的患者（ESR1 突变患者）的无进展生存期明显长于标准治疗，但总体人群并非如此。与Imlunestrant相比，Imlunestrant -阿贝马西利显著改善了无进展生存期，无论 ESR1 突变状态如何。
Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen receptor (ER) degrader that provides sustained ER inhibition even in cancers with mutations in the gene encoding ERα (ESR1).
Methods: In a phase III, open-label trial (NCT04975308), investigators enrolled patients with ER-positive, HER2-negative advanced breast cancer who had relapsed or progressed during or after an aromatase inhibitor alone or in combination with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. The primary endpoints were investigator-assessed progression-free survival with imlunestrant compared with standard therapy in all patients with ESR1 mutations and with imlunestrant- abemaciclib compared with imlunestrant in all patients who underwent concurrent randomization.
Results: Overall, 874 patients underwent randomization, with 331 receiving imatinib, 330 receiving standard therapy, and 213 receiving imatinib- abemaciclib. Among the 256 patients with ESR1 mutations, median progression-free survival was 5.5 months with Imlunestrant and 3.8 months with standard therapy. At 19.4 months, the estimated mean restricted survival was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) in patients who received Imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) in those who received standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, median progression-free survival was 5.6 months with Imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P=0.12). Among the 426 patients who received Imlunestrant-abemaciclib versus Imlunestrant, median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001).
Adverse events of grade 3 or higher occurred in 17.1% of patients treated with Imlunestrant, 20.7% with standard therapy, and 48.6% with Imlunestrant-abemaciclib.
Conclusions: Among patients with ER-positive, HER2-negative advanced breast cancer, progression-free survival was significantly longer in patients treated with Imlunestrant (those with ESR1 mutations) than in the standard of care, but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival compared with Imlunestrant, regardless of ESR1 mutation status.
参考文献 Reference
Jhaveri KL et al. N Engl J Med Dec 11 2024. DOI: 10.1056/NEJMoa2410858