Supplementary Material for: Second primary malignancies in patients with a neuroendocrine neoplasm in England

Introduction Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. Methods Data was extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012-2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine and stomach. WHO International Classification of Disease edition 10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardised incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. Results A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were prostate (20%), lung (20%) and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR=1.85, 95%CI:1.55-2.22), colon (SIR=1.78, 95%CI:1.40-2.27), prostate (SIR=1.56, 95%CI:1.31-1.86), kidney (SIR=3.53, 95%CI:2.72-4.59) and thyroid (SIR=6.31, 95%CI:4.26-9.33). When stratified by sex, statistically significant SIRs remained for lung, renal, colon and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95%CI:1.26-5.57) and bladder cancer (SIR=2.61, 95%CI:1.36-5.02). Discussion/Conclusion This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes is required to enable earlier diagnosis of second non-NEN tumours in these patients.

研究背景：神经内分泌肿瘤（neuroendocrine neoplasms, NENs）患者常可并发其他恶性肿瘤。本研究旨在明确英格兰地区此类继发恶性肿瘤的发生频率。

研究方法：本研究数据提取自英国国家癌症登记与分析服务（National Cancer Registration and Analysis Service, NCRAS），纳入2012至2018年间确诊为神经内分泌肿瘤的患者，覆盖8个神经内分泌肿瘤发病部位群组：阑尾、盲肠、结肠、肺、胰腺、直肠、小肠及胃。采用世界卫生组织国际疾病分类第10版（ICD-10）编码，识别出后续确诊非神经内分泌肿瘤的患者。按性别与发病部位分层，计算索引神经内分泌肿瘤确诊后，各类非神经内分泌肿瘤的标准化发病比（standardised incidence ratios, SIRs）。

研究结果：本研究共纳入20579例患者。神经内分泌肿瘤确诊后最常见的非神经内分泌肿瘤依次为前列腺癌（20%）、肺癌（20%）及乳腺癌（15%）。统计学分析显示，肺癌（SIR=1.85, 95%CI:1.55-2.22）、结肠癌（SIR=1.78, 95%CI:1.40-2.27）、前列腺癌（SIR=1.56, 95%CI:1.31-1.86）、肾癌（SIR=3.53, 95%CI:2.72-4.59）及甲状腺癌（SIR=6.31, 95%CI:4.26-9.33）的标准化发病比具有统计学意义。按性别分层分析后，肺癌、肾癌、结肠癌及甲状腺癌仍表现出具有统计学意义的标准化发病比。此外，女性患者的胃癌（SIR=2.65, 95%CI:1.26-5.57）与膀胱癌（SIR=2.61, 95%CI:1.36-5.02）标准化发病比同样具有统计学意义。

讨论与结论：本研究发现，神经内分泌肿瘤患者异时性新发肺癌、前列腺癌、肾癌、结肠癌及甲状腺癌的发生率高于英格兰普通人群。需对该类患者加强临床监测，并指导其参与现有筛查项目，以实现第二原发非神经内分泌肿瘤的早期诊断。