Favier Olav, Heutte Natacha, Stamatoullas-Bastard Aspasia, Carde Patrice, Van't Veer Mars B, Aleman Berthe M P, Noordijk Evert M, Thomas José, Fermé Christophe, Henry-Amar Michel
Clinical Research Unit, François Baclesse Cancer Center, Caen, France.
Cancer. 2009 Apr 15;115(8):1680-91. doi: 10.1002/cncr.24178.
The objective of this study was to analyze cause-specific excess mortality in adult patients with Hodgkin lymphoma (HL) with respect to treatment modality.
The study population consisted of 4401 Belgian, Dutch, and French patients aged 15 to 69, in all stages of disease, who were treated between 1964 and 2000. Excess mortality was expressed by using a standardized mortality ratio (SMR) and calculating the absolute excess risk (AER). Relative survival was calculated and analyzed using a previously described regression model.
At a median follow-up of 7.8 years, 725 of 4401 patients (16.5%) had died, 51% of HL, 10% of treatment-related toxicity, 18% of second cancer, 5% of cardiovascular diseases, 2% of infections, 8% of other causes, and 6% of an unspecified cause. Overall, the SMR was 7.4 (95% confidence limits [CL], 6.9-8.0), and the AER was 182.8 (95% CL, 167.7-198.8). These indicators were 3.8 (95% CL, 3.2-4.5) and 27.9, respectively, for deaths from a second cancer and 4.0 (95% CL, 2.3-6.7) and 3.3, respectively for deaths from infection. After 15 years, the observed survival rate was 75%, and the relative survival rate was 80%. In patients with early-stage disease, the overall excess mortality was associated with age > or =40 years (P = .007), men (P < .001), unfavorable prognosis features (P < .001), and 2 treatments: combined nonstandard nonalkylating chemotherapy plus involved-field radiotherapy (P = .002) and mantle-field irradiation alone (P = .003). With follow-up censored at the first recurrence, no treatment modalities were associated with excess mortality.
Progressive disease remained the primary cause of death in patients with HL in the first decades after treatment. Excess mortality in patients with early-stage disease was linked significantly to treatment modalities that were associated with poor treatment failure-free survival.
本研究的目的是分析霍奇金淋巴瘤(HL)成年患者因治疗方式导致的特定病因超额死亡率。
研究人群包括4401例年龄在15至69岁之间、处于疾病各阶段的比利时、荷兰和法国患者,他们在1964年至2000年期间接受了治疗。超额死亡率通过使用标准化死亡率(SMR)并计算绝对超额风险(AER)来表示。使用先前描述的回归模型计算并分析相对生存率。
在中位随访7.8年时,4401例患者中有725例(16.5%)死亡,其中51%死于HL,10%死于治疗相关毒性,18%死于第二原发癌,5%死于心血管疾病,2%死于感染,8%死于其他原因,6%死因不明。总体而言,SMR为7.4(95%置信区间[CL],6.9 - 8.0),AER为182.8(95%CL,167.7 - 198.8)。第二原发癌死亡的这些指标分别为3.8(95%CL,3.2 - 4.5)和27.9,感染死亡的指标分别为4.0(95%CL,2.3 - 6.7)和3.3。15年后,观察到的生存率为75%,相对生存率为80%。在早期疾病患者中,总体超额死亡率与年龄≥40岁(P = 0.007)、男性(P < 0.001)、不良预后特征(P < 0.001)以及两种治疗方式相关:联合非标准非烷化化疗加受累野放疗(P = 0.002)和单纯斗篷野照射(P = 0.003)。在首次复发时进行随访截尾,没有治疗方式与超额死亡率相关。
在治疗后的头几十年里,疾病进展仍然是HL患者的主要死亡原因。早期疾病患者的超额死亡率与无治疗失败生存期较差相关的治疗方式显著相关。