Importance  Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.

Objective  To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (≥40 years) patients with the same SPMs.

Design, Setting, and Participants  This was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed from 1992 to 2008 and followed through 2013. Data analysis was performed between June 2016 and January 2017.

Main Outcomes and Measures  Five-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age at diagnosis. The impact of SPM status on cancer-specific death was examined using multivariable Cox proportional hazards regression.

Results  A total of 15 954 pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14 cancers occurring as a PM or SPM were included. Overall, 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults compared with a PM at the same age. For the most common SPMs in AYAs, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central nervous system cancer. Adolescents and young adults with secondary Hodgkin lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1-3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]); and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival compared with AYAs with the same PMs.

Conclusion and Relevance  The adverse impact of SPMs on survival is substantial for AYAs and may partially explain the relative lack of survival improvement in AYAs compared with other age groups. The impact of a particular SPM diagnosis on survival may inform age-specific prevention, screening, treatment, and survivorship recommendations.

重要性  尽管第二原发性恶性肿瘤 (SPM) 的发病率增加是众所周知的癌症后的晚期效应，但很少有研究将 SPM 后的生存率与作为原发性原发性恶性肿瘤 (PM) 发生的相同癌症的生存率按年龄进行比较。

目的  评估 SPMs 对青少年和年轻成人 (AYAs) (15-39 岁) 与儿童 (<15 岁) 和老年人 (≥40 岁) 具​​有相同 SPMs 的患者的生存影响。

设计、设置和参与者  这是一项基于人群的回顾性队列研究，对象为美国 13 个监测、流行病学和最终结果地区的癌症患者，从 1992 年到 2008 年诊断并随访至 2013 年。数据分析于 2016 年 6 月进行和 2017 年 1 月。

主要结果和措施  总体上计算五年相对生存率，并根据诊断时的年龄计算每种癌症作为 PM 或 SPM 发生的情况。使用多变量 Cox 比例风险回归检查 SPM 状态对癌症特异性死亡的影响。

结果  共纳入 15 954 名儿科、125 750 名 AYA 和 878 370 名被诊断为患有 PM 或 SPM 的 14 种癌症的老年患者。总体而言，与同龄 PM 相比，儿童 SPM 后的 5 年生存率降低 33.1%，AYA 降低 20.2%，老年人降低 8.3%。对于 AYA 中最常见的 SPM，继发性非霍奇金淋巴瘤的 5 年生存率绝对差异降低 42%，继发性乳腺癌降低 19%，继发性甲状腺癌降低 15%，继发性软组织肉瘤降低 13% . 对于甲状腺、霍奇金淋巴瘤、非霍奇金淋巴瘤、急性髓细胞性白血病、软组织肉瘤和中枢神经系统癌，年轻患者的 SPM 状态生存率明显低于老年患者。患有继发性霍奇金淋巴瘤的青少年和年轻人（风险比 [95% CI]，3.5 [1.7-7.1]）；软组织肉瘤 (2.8 [2.1-3.9]); 乳腺癌 (2.1 [1.8-2.4]); 急性髓性白血病 (1.9 [1.5-2.4]); 与具有相同 PM 的 AYA 相比，中枢神经系统癌症 (1.8 [1.2-2.8]) 的生存率更差。

结论和相关性  SPMs 对 AYA 生存的不利影响是显着的，这可能部分解释了与其他年龄组相比，AYA 的生存改善相对缺乏。特定 SPM 诊断对生存的影响可能会为特定年龄的预防、筛查、治疗和生存建议提供信息。