BACKGROUND Ataxia Telangiectasia (A-T) is a DNA repair disorder with cancer predisposition. OBJECTIVE Characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T. METHODS Data was retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios of cancer, survival probability after cancer diagnosis, and standardized mortality ratios were calculated. Cox regression estimated risk of death based on chemotherapy (standard v reduced) dosing and multivariable logistic regression evaluated cancer risk associations with ATM exons and variants. RESULTS Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, 62 (74%) were hematologic in origin and 22 (26%) were solid organ cancers. The cumulative incidence of cancer was 29% by age 35 years. Non-Hodgkin lymphoma occurred most frequently (n=39), while solid cancers disproportionately affected those ≥18 years old (n=22). The standardized mortality ratio was 24.6 (95% CI:21.1-28.4) overall and 232.9 (95% CI:178.1-299.2) among individuals with cancer. Risk of death was higher when treated with standard/unknown versus modified chemotherapy (HR 2.2, 95% CI:1.1-4.4, p=0.024). Chemotherapy-associated toxicities developed in 58% of individuals, predominantly neurologic (n=14) and gastrointestinal (n=10) systems. Three exons were enriched for cancer-associated variants. CONCLUSION Individuals with A-T experience a wide array of blood and solid organ malignancies, high mortality rates, and treatment related toxicities, highlighting need for targeted therapies to mitigate toxicity and optimize survival. CLINICAL IMPLICATION A-T patients with cancer face elevated mortality rates, underscoring the urgency for tailored therapies to minimize toxicity and improve survival outcomes.

中文翻译：

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共济失调毛细血管扩张症患者癌症的患病率和结果以及治疗相关毒性。


背景 共济失调毛细血管扩张症 （A-T） 是一种具有癌症易感性的 DNA 修复障碍。目的 描述 A-T 个体血液癌和实体癌的患病率和结果以及治疗相关毒性。方法 回顾性分析来自约翰霍普金斯大学共济失调毛细血管扩张症临床中心队列的数据。计算癌症的累积发病率和标化发病率、癌症诊断后的生存概率和标化死亡率。Cox 回归根据化疗 （标准 v 减少） 剂量估计死亡风险，多变量 logistic 回归评估癌症风险与 ATM 外显子和变异的关联。结果 508 例个体中有 84 例 （16.5%） 被诊断为原发性癌症，62 例 （74%） 为血液学起源性癌症，22 例 （26%） 为实体器官癌。到 35 岁时，癌症的累积发病率为 29%。非霍奇金淋巴瘤发生率最高 （n=39），而实体癌不成比例地影响 ≥18 岁 （n=22）。总体标准化死亡率为 24.6 （95% CI：21.1-28.4），癌症个体标准化死亡率为 232.9 （95% CI：178.1-299.2）。与改良化疗相比，标准/未知化疗的死亡风险更高 （HR 2.2,95% CI：1.1-4.4，p=0.024）。58% 的个体出现化疗相关毒性，主要是神经系统 （n=14） 和胃肠道 （n=10） 系统。三个外显子富集了癌症相关变异。结论 A-T 患者会出现各种血液和实体器官恶性肿瘤、高死亡率和治疗相关毒性，突出了靶向治疗以减轻毒性和优化生存率的必要性。 临床意义 A-T 癌症患者面临更高的死亡率，这凸显了定制疗法以最大限度地减少毒性并改善生存结果的紧迫性。