van Dijk Merel R, Steyerberg Ewout W, Habbema J Dik F
Department of Public Health, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
BMC Med Inform Decis Mak. 2008 Jan 3;8:1. doi: 10.1186/1472-6947-8-1.
Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification.
We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT) versus standard-dose chemotherapy (SD-CT) for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility').
We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment.
Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for more aggressive treatments.
分类系统可能有助于将更积极的治疗导向预后相对较差的癌症患者。“预后较差”的定义往往缺乏正式依据。我们提出一种决策分析方法,以明确权衡利弊,从而确定更积极治疗的阈值。晚期睾丸癌的案例研究说明了这种方法,在该案例中,标准治疗下死亡风险高的患者可能符合接受高剂量化疗并辅以干细胞支持的条件,目前这是由国际生殖细胞癌协作组(IGCC)分类定义的。
我们利用已发表的文献来估计高剂量化疗(HD-CT)与标准剂量化疗(SD-CT)对晚期非精原性生殖细胞癌患者的益处和危害。益处和危害分别定义为HD-CT导致的绝对死亡风险降低和增加。危害包括早期和晚期治疗相关死亡以及治疗相关发病率(按“效用”加权)。
我们分别考虑了保守和乐观的益处,即死亡风险降低30%和40%。我们估计额外的治疗相关死亡率为2%。当考虑治疗相关发病率时,HD-CT的危害增加到5%。相对益处为30%且危害为2%或5%时,HD-CT可能对SD化疗下癌症特异性死亡风险超过7%或17%的患者有益,而相对益处为40%时,HD-CT分别在风险超过5%和12.5%时有益。与IGCC分类相比,14%的患者将接受更积极的治疗,2%的患者接受强度较低的治疗。
益处和危害可用于明确界定考虑接受高剂量化疗的非精原性生殖细胞癌患者的“预后较差”情况。这种方法可以很容易地根据新结果进行调整,并扩展到其他癌症,以确定更积极治疗的候选者。