Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada.
Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
J Natl Cancer Inst. 2021 May 4;113(5):562-571. doi: 10.1093/jnci/djaa151.
It is unclear whether late-effect risks among childhood cancer survivors vary internationally. We compared late mortality in the North American Childhood Cancer Survivor Study (CCSS) and British Childhood Cancer Survivor Study (BCCSS).
Late mortality was assessed among 49 822 5-year survivors of childhood cancer diagnosed before 15 years of age from 1970 to 1999 (CCSS, n = 31 596; BCCSS, n = 18 226) using cumulative mortality probabilities (CM%) and adjusted ratios of the standardized mortality ratio.
The all-cause CM% at 10 years from diagnosis was statistically significantly lower in the CCSS (4.7%, 95% confidence interval [CI] = 4.5% to 5.0%) compared with the BCCSS (6.9%, 95% CI = 6.5% to 7.2%), attributable to a lower probability of death from recurrence or progression of the primary cancer, with statistically significant differences observed in survivors of leukemia, lymphoma, central nervous system tumors, and sarcoma. However, at 40 years from diagnosis, the CCSS had a greater CM% (22.3% vs 19.3%), attributable to a twofold higher risk of mortality from subsequent malignant neoplasms, cardiac and respiratory diseases, and other health-related causes. Differences increased when assessed by follow-up interval, with the CCSS faring worse as time-since-diagnosis increased. Finally, the gap in all-cause mortality widened more recently, with CCSS survivors diagnosed in 1990-1999 experiencing one-half the excess deaths observed in the BCCSS (ratios of the standardized mortality ratio = 0.5, 95% CI = 0.5 to 0.6).
Our findings suggest that US survivors may have received more intensive regimens to achieve sustainable remission and cure, but the cost of this approach was a higher risk of death from late effects. Although the clinical impact of these differences is unclear, our results provide important evidence to aid the discussion of late effects management.
目前尚不清楚儿童癌症幸存者的晚期发病风险是否存在国际差异。我们比较了北美儿童癌症幸存者研究(CCSS)和英国儿童癌症幸存者研究(BCCSS)的晚期死亡率。
对 1970 年至 1999 年期间诊断为 15 岁以下的 49822 名儿童癌症 5 年幸存者(CCSS,n=31596;BCCSS,n=18226)的晚期死亡率进行了评估,使用累积死亡率概率(CM%)和标准化死亡率比的调整比值。
与 BCCSS(6.9%,95%置信区间[CI]为 6.5%至 7.2%)相比,CCSS 的全因 10 年 CM%(4.7%,95%CI 为 4.5%至 5.0%)显著降低,这归因于原发性癌症复发或进展导致死亡的概率较低,在白血病、淋巴瘤、中枢神经系统肿瘤和肉瘤幸存者中观察到了显著差异。然而,在诊断后 40 年,CCSS 的 CM%更高(22.3%比 19.3%),这归因于后续恶性肿瘤、心脏和呼吸疾病及其他与健康相关的原因导致的死亡率风险增加了两倍。当按随访间隔评估时,差异会增加,随着诊断后时间的增加,CCSS 的表现会更差。最后,全因死亡率的差距最近进一步扩大,CCSS 幸存者中在 1990 年至 1999 年诊断的患者,其超额死亡人数是 BCCSS 的一半(标准化死亡率比=0.5,95%CI 为 0.5 至 0.6)。
我们的研究结果表明,美国幸存者可能接受了更强化的治疗方案以实现可持续缓解和治愈,但这种方法的代价是晚期发病风险增加。尽管这些差异的临床影响尚不清楚,但我们的结果为讨论晚期发病风险的管理提供了重要证据。