Nicholson H S, Fears T R, Byrne J
Department of Hematology/Oncology, Children's National Medical Center, Washington, DC.
Cancer. 1994 Jun 15;73(12):3094-102. doi: 10.1002/1097-0142(19940615)73:12<3094::aid-cncr2820731231>3.0.co;2-e.
Therapeutic advances have extended survival for most children and adolescents with cancer beyond 5 years from diagnosis. However, excess mortality continues beyond 5 years, and a significant portion results from causes other than the primary cancer. Risk factors for these deaths are not currently known. Thus, the authors studied mortality in a cohort of adult survivors of childhood and adolescent cancer to determine whether survivor characteristics were associated with increased relative risk of death from other causes.
Using 3255 siblings as control subjects, the authors studied survival in a retrospective cohort study of 2319 adults who were at least 5-year survivors of cancer diagnosed before reaching 20 years of age and between 1945 and 1974 (the NCI Five Center Study). Follow-up occurred between 1980 and 1983 at a mean survivor age of 32 years (range, 21-55 years).
Between cohort entry and follow-up, 292 (13%) survivors and 50 (2%) controls died. One-third of the deaths in survivors were from causes other than the primary malignancy. Compared with control subjects, between ages 21 and 40 years, survivors had a more than threefold risk of death from other causes. The relative risk (RR) for death from other causes was greatest for survivors treated with radiation and alkylating agents (RR = 6.1; 95% confidence interval [CI], 3.0-12.4) and for those treated with radiation alone (RR = 3.8; 95% CI, 2.3-6.2; Cox regression analysis containing terms for treatment and cancer diagnosis).
Adult survivors of childhood and adolescent cancer had a higher death rate than their siblings, even after removing the effect of primary cancer as the direct cause. Moreover, death from other causes was most strongly associated with increasing intensity of therapy, and this excess risk did not diminish with increasing age and duration of cancer survival. Because contemporary anticancer therapy is, in general, even more intensive than that received by the survivors described in this study, medical surveillance of cancer survivors is increasingly important to diagnose and treat potentially life-threatening complications that may occur decades after therapy has ceased.
治疗方面的进展已使大多数患癌儿童和青少年的生存期从确诊起延长至5年以上。然而，5年后仍存在额外的死亡风险，且很大一部分死亡是由原发性癌症以外的原因导致的。目前尚不清楚这些死亡的风险因素。因此，作者对一组童年和青少年癌症成年幸存者的死亡率进行了研究，以确定幸存者特征是否与其他原因导致的相对死亡风险增加有关。
作者以3255名兄弟姐妹作为对照，在一项回顾性队列研究中对2319名成年人的生存情况进行了研究，这些成年人是1945年至1974年间20岁之前确诊癌症的至少5年幸存者（国立癌症研究所五中心研究）。随访在1980年至1983年间进行，幸存者的平均年龄为32岁（范围21 - 55岁）。
在队列进入期至随访期间，292名（13%）幸存者和50名（2%）对照死亡。幸存者中三分之一的死亡是由原发性恶性肿瘤以外的原因导致的。与对照相比，在21岁至40岁之间，幸存者因其他原因死亡的风险高出三倍多。接受放疗和烷化剂治疗的幸存者以及仅接受放疗的幸存者因其他原因死亡的相对风险（RR）最高（RR = 6.1；95%置信区间[CI]，3.0 - 12.4）以及（RR = 3.8；95% CI，2.3 - 6.2；包含治疗和癌症诊断项的Cox回归分析）。
童年和青少年癌症成年幸存者的死亡率高于其兄弟姐妹，即使去除原发性癌症作为直接死因的影响也是如此。此外，其他原因导致的死亡与治疗强度增加的关联最为密切，且这种额外风险不会随着年龄增长和癌症生存时间延长而降低。由于当代抗癌治疗总体上比本研究中描述的幸存者接受的治疗强度更大，对癌症幸存者进行医学监测对于诊断和治疗治疗停止数十年后可能出现的潜在危及生命的并发症变得越来越重要。
