Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.
US Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology, Silver Spring, MD.
J Clin Oncol. 2020 Dec 10;38(35):4149-4162. doi: 10.1200/JCO.20.00264. Epub 2020 Sep 18.
Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood.
We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden.
We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors.
Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.
在美国，广泛使用多柔比星、博来霉素、长春碱和达卡巴嗪，放疗使用减少的时代，接受经典霍奇金淋巴瘤（cHL）治疗的患者的死亡率尚不清楚。
我们在 2000 年至 2015 年期间，在美国人群癌症登记处中，确定了 20007 名年龄在 20 至 74 岁之间，接受初始化疗治疗的 I/II 期（早期）或 III/IV 期（晚期）cHL 的患者（随访至 2016 年）。我们使用标准化死亡率比（SMR）来比较 cHL 后特定原因的相对死亡风险与一般人群中的预期风险，并估计特定疾病的死亡负担的超额绝对风险（EAR；每 10000 患者年）。
我们在 cHL 队列中发现了 3380 例死亡，其中 1321 例（39%）与淋巴瘤无关。总体而言，非癌症 SMR 增加了 2.4 倍（95%CI，2.2 至 2.6；观察值，559；EAR，61.6），晚期和早期 cHL 的分别增加了 1.6 倍（95%CI，1.4 至 1.7；观察值，473；EAR，18.2）与美国一般人群相比。SMR 和 EAR 因死亡原因和 cHL 分期而异。非癌症死亡原因中 EAR 最高的是心脏病（EAR，15.1；SMR，2.1）、感染（EAR，10.6；SMR，3.9）、间质性肺病（ILD；EAR，9.7；SMR，22.1）和与药物/药物相关的不良事件（AE）（EAR，7.4；SMR，5.0），晚期 cHL 后和心脏病（EAR，6.6；SMR，1.7）、ILD（EAR，3.7；SMR，13.1）、感染（EAR，3.1；SMR，2.2）后，EAR 最高的是心脏病、ILD 和感染。cHL 后不到 1 年，ILD、感染和 AE 的 SMR 显著升高。年龄在 60-74 岁的晚期 cHL 患者因心脏病、ILD、感染、AE 和实体瘤而导致死亡的风险过高。
尽管 cHL 治疗方法不断发展，但患者仍面临多种潜在可预防原因导致的非淋巴瘤死亡风险增加。监测、早期干预和 cHL 治疗的改进可能会有利地影响患者的寿命，尤其是在高风险亚组中。
