Ediebah Divine E, Galindo-Garre Francisca, Uitdehaag Bernard M J, Ringash Jolie, Reijneveld Jaap C, Dirven Linda, Zikos Efstathios, Coens Corneel, van den Bent Martin J, Bottomley Andrew, Taphoorn Martin J B
Quality of Life Department, European Organisation for Research and Treatment of Cancer, Brussels, Belgium,
Qual Life Res. 2015 Apr;24(4):795-804. doi: 10.1007/s11136-014-0821-6. Epub 2014 Oct 14.
In cancer research, outcome measures may co-vary. Treatment and treatment related impairment of health-related quality of life (HRQoL) may affect survival. When these effects are analyzed separately, bias may arise. Therefore, we investigated the combined effect of treatment and longitudinally measured HRQoL on survival.
Patients with anaplastic oligodendrogliomas (n = 288) who were randomized (EORTC 26951) to radiotherapy (RT) alone or RT plus procarbazine, lomustine, and vincristine (PCV) chemotherapy were analyzed. HRQoL [appetite loss (AP)] was assessed with the EORTC QLQ-C30. We compared survival results from different analysis strategies: Cox model with treatment only [model 1 (M1)] or with treatment and time-dependent AP score [model 2 (M2)] and the joint model combining longitudinal AP score and survival [model 3 (M3)].
The estimated hazard ratio (HR) for RT plus PCV was 0.76 (95 % CI 0.58-1.00) for M1, 0.72 (0.55-0.96) for M2, and 0.69 (0.52-0.92) for M3. This corresponds to a lower risk of death of 24 % in M1, 28 % in M2, and 31 % in M3, for patients treated with RT plus PCV chemotherapy. AP resulted in an increased risk of death, with estimated HR of 1.06 (1.01-1.12) for M2 and 1.13 (1.03-1.23) for M3: Every 10-point increase of AP resulted in a 13 % increased risk of death in M3 as compared to 6 % in M2.
Part of the survival benefit of treatment with RT plus PCV chemotherapy can be masked by the negative effect that this treatment has on patients' HRQoL. In our study, up to 7 % of the theoretical treatment efficacy was lost when AP was not adjusted through joint modeling.
在癌症研究中，结果指标可能会共同变化。治疗及与治疗相关的健康相关生活质量（HRQoL）损害可能会影响生存。当分别分析这些影响时，可能会产生偏差。因此，我们研究了治疗和纵向测量的HRQoL对生存的综合影响。
分析了288例间变性少突胶质细胞瘤患者，这些患者被随机分组（欧洲癌症研究与治疗组织26951）接受单纯放疗（RT）或RT联合丙卡巴肼、洛莫司汀和长春新碱（PCV）化疗。使用欧洲癌症研究与治疗组织QLQ-C30评估HRQoL[食欲减退（AP）]。我们比较了不同分析策略的生存结果：仅包含治疗因素的Cox模型[模型1（M1）]或包含治疗和时间依赖性AP评分的Cox模型[模型2（M2）]，以及结合纵向AP评分和生存情况的联合模型[模型3（M3）]。
对于M1，RT联合PCV的估计风险比（HR）为0.76（95%CI 0.58-1.00）；对于M2，为0.72（0.55-0.96）；对于M3，为0.69（0.52-0.92）。这相当于接受RT联合PCV化疗的患者在M1中的死亡风险降低24%，在M2中降低28%，在M3中降低31%。AP导致死亡风险增加，M2的估计HR为1.06（1.01-1.12），M3为1.13（1.03-1.23）：与M2中每10分的AP增加导致死亡风险增加6%相比，M3中每10分的AP增加导致死亡风险增加13%。
RT联合PCV化疗的生存获益部分可能被该治疗对患者HRQoL的负面影响所掩盖。在我们的研究中，当未通过联合建模对AP进行调整时，高达7%的理论治疗效果丧失。
