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儿童癌症治疗后的结直肠腺瘤和癌症:DCOG-LATER 记录链接研究。

Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study.

机构信息

Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.

Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.

出版信息

J Natl Cancer Inst. 2018 Jul 1;110(7):758-767. doi: 10.1093/jnci/djx266.

Abstract

BACKGROUND

Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.

METHODS

The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n = 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided.

RESULTS

Among 5843 five-year survivors (median follow-up = 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval [CI] = 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI = 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference = .07) and vs 1.0% (95% CI = 0.3% to 2.6%) among siblings (6 cases) (Pdifference = .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] = 2.12, 95% CI = 1.24 to 3.60), total body irradiation (TBI; HR = 10.55, 95% CI = 5.20 to 21.42), cisplatin (HR = 2.13; 95% CI = 0.74 to 6.07 for <480 mg/m²; HR = 3.85, 95% CI = 1.45 to 10.26 for ≥480 mg/m²; Ptrend = .62), a hepatoblastoma diagnosis (HR = 27.12, 95% CI = 8.80 to 83.58), and family history of early-onset CRC (HR = 20.46, 95% CI = 8.10 to 51.70). Procarbazine was statistically significantly associated among survivors without AP-RT/TBI (HR = 2.71, 95% CI = 1.28 to 5.74). Thirteen CRCs occurred.

CONCLUSION

We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors. Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposis-associated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of CRC screening among high-risk childhood cancer survivors warrants consideration.

摘要

背景

虽然结直肠腺瘤是结直肠癌(CRC)在其他高危人群中监测的主要目标,但儿童癌症后腺瘤风险的数据却很缺乏。我们评估了儿童癌症幸存者中组织学确认的结直肠腺瘤的风险。次要目的是评估 CRC 风险。

方法

DCOG-LATER 队列研究包括五年期荷兰儿童癌症幸存者和一个同胞对照组(n=883)。结直肠肿瘤从基于人群的荷兰病理学登记处(PALGA)中确定。我们计算了幸存者和同胞中腺瘤/CRC 的累积发生率。对于腺瘤,多变量 Cox 回归模型用于评估潜在的危险因素。所有统计检验均为双侧。

结果

在 5843 名五年期幸存者中(中位随访时间=24.9 年),有 78 人发生了腺瘤。45 岁时的累积发病率为接受腹盆放疗(AP-RT;49 例)的患者为 3.6%(95%置信区间 [CI]:2.2%至 5.6%),未接受 AP-RT 的幸存者为 2.0%(95% CI:1.3%至 2.8%)(28 例;差异=.07),而同胞为 1.0%(95% CI:0.3%至 2.6%)(6 例)(差异=.03)。与腺瘤风险相关的因素包括 AP-RT(风险比 [HR] = 2.12,95%CI:1.24 至 3.60)、全身照射(TBI;HR = 10.55,95%CI:5.20 至 21.42)、顺铂(HR = 2.13;95%CI:480 mg/m² 以下时为 0.74 至 6.07;480 mg/m² 以上时为 3.85,95%CI:1.45 至 10.26;趋势检验=.62)、肝母细胞瘤诊断(HR = 27.12,95%CI:8.80 至 83.58)和家族性早发性 CRC 史(HR = 20.46,95%CI:8.10 至 51.70)。对于未接受 AP-RT/TBI 的幸存者,丙卡巴肼有统计学意义的相关性(HR = 2.71,95%CI:1.28 至 5.74)。发生了 13 例 CRC。

结论

我们提供了儿童癌症幸存者结直肠腺瘤和 CRC 风险增加的证据。腺瘤的危险因素包括 AP-RT、TBI、顺铂和丙卡巴肼。肝母细胞瘤(家族性腺瘤性息肉病相关)和早发性 CRC 家族史被确认为强危险因素。有必要对高危儿童癌症幸存者的 CRC 筛查进行全面的获益-风险评估。

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