COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial
COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial
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DOI：
10.1016/s1470-2045(07)70280-2
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发表时间：
2007-10-01
期刊：
影响因子：
51.1
通讯作者：
Dicker, Adam P.
中科院分区：
文献类型：
--
作者：
Khor, Li-Yan;Bae, Kyounghwa;Dicker, Adam P.
背景考克斯-2在某些癌症中过表达，包括前列腺癌;然而，关于考克斯-2过表达对放射治疗的前列腺癌患者的预后的影响知之甚少。我们的目的是研究考克斯-2过表达和结果在一个明确的队列的男性谁接受治疗与短期雄激素剥夺（STAD）加放疗或长期雄激素剥夺（LPEG）加放疗。02试验中获得足够的诊断组织用于免疫组化染色和考克斯-2表达的图像分析。92-02试验中的患者被随机分配接受STAD加放疗或LIPE加放疗治疗。通过考克斯比例风险模型进行多变量分析，以评估考克斯-2染色强度与RTOG 92-02生化失败主要终点之间是否存在相关性（由美国放射治疗和肿瘤学会[ASTRO]和Phoenix标准评估）、局部失败、远处转移、病因特异性死亡率和总死亡率，结果586例患者有足够的诊断组织进行免疫组化染色和考克斯-2表达的图像分析。在多变量分析中，考克斯-2染色强度作为连续协变量是远处转移的独立预测因子（风险比[HR] 1.181 [95% CI 1.077-1.295]，p=0.0004）;两种定义的生化失败（ASTRO，HR 1.073 [1.018-1.131]，p=0.008; Phoenix HR 1.073 [1.014-1.134]，p=0.014）;和任何失败（HR 1.068 [1.015-1.124]，p=0.011）。考克斯-2表达越高，失败的机会越大。作为一个二分协变量，考克斯-2的过度表达似乎是最歧视的结果，那些谁收到STAD相比，那些谁收到LRIMP.Interpretation据我们所知，这是第一个研究，以建立一个协会的考克斯-2的表达与前列腺癌患者的放疗结果。增加考克斯-2表达与生化失败、远处转移和任何失败显著相关。考克斯-2抑制剂可能会改善患者对放疗的反应，无论是否接受雄激素剥夺治疗。我们的研究结果表明，紫杉醇可能会克服考克斯-2过表达的影响。因此，考克斯-2表达可能有助于选择需要LIPE的患者。
Background COX-2 is overexpressed in some cancers, including prostate cancer; however, little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer. We aimed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term androgen deprivation (STAD) plus radiotherapy or long-term androgen deprivation (LTAD) plus radiotherapy.Methods Men with prostate cancer who had participated in the Radiation Therapy Oncology Group (RTOG) 92-02 trial and for whom sufficient diagnostic tissue was available for immumohistochemical staining and image analysis of COX-2 expression were enrolled in this study. Patients in the 92-02 trial had been randomly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy. Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92-02 primary endpoints of biochemical failure (assessed by the American Society for Therapeutic Radiology and Oncology [ASTRO] and Phoenix criteria), local failure, distant metastasis, cause-specific mortality overall mortality, and any failure.Findings 586 patients with sufficient diagnostic tissue for immumohistochemical staining and image analysis of COX-2 expression were included in this study. In the multivariate analyses, the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis (hazard ratio [HR] 1.181 [95% CI 1.077-1.295], p=0.0004); biochemical failure by two definitions (ASTRO, HR 1.073 [1.018-1.131], p=0.008; Phoenix HR 1.073 [1.014-1.134], p=0.014); and any failure (HR 1.068 [1.015-1.124], p=0.011). The higher the expression of COX-2, the greater the chance of failure. As a dichotomous covariate, COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD.Interpretation To our knowledge, this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy. Increasing COX-2 expression was significantly associated with biochemical failure, distant metastasis, and any failure. COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without androgen deprivation. Our findings suggest that LTAD might overcome the effects of COX-2 overexpression. Therefore, COX-2 expression might be useful in selecting patients who need LTAD.