Höckel M, Vorndran B, Schlenger K, Baussmann E, Knapstein P G
Department of Obstetrics and Gynecology, University of Mainz, Germany.
Gynecol Oncol. 1993 Nov;51(2):141-9. doi: 10.1006/gyno.1993.1262.
Experimental evidence suggests that hypoxia may increase the malignant potential and reduce the sensitivity toward nonsurgical treatment modalities in solid rodent tumors. However, the importance of tumor hypoxia in human malignancies is still uncertain. We have developed a clinically applicable standardized procedure for the determination of intratumoral pO2 in advanced cervical cancers by use of a computerized polarographic needle electrode histograph. To evaluate the significance of tumor oxygenation as a new oncologic parameter we initiated an open prospective clinical trial at the University of Mainz Medical Center in June 1989. Until October 1992 50 patients with advanced cervical cancers entered the study. Tumor oxygenation measured in these 50 patients was independent from various patient and tumor characteristics, including hemoglobin concentration, FIGO stage, and tumor size. Thirty-three patients receiving standard radiotherapy with or without chemotherapy (RT +/- CT) were analyzed for treatment outcome. Intratumoral pO2 histography revealed median pO2 < or = 10 mm Hg (low pO2 tumors) in 15 of the 33 patients; in 19 tumors pO2 fractions < or = 5 mm Hg (low pO2 fractions) were found. After a median follow-up of 24 months (range 6 to 40 months) Kaplan-Meier life table analysis showed significantly shorter survival and recurrence-free survival for patients with low pO2 tumors treated with RT +/- CT. According to the Cox proportional hazards model the low pO2 fraction was the most powerful single predictor of survival and recurrence-free survival. The results of this study are consistent with the view that radiobiologically hypoxic tumors are less radiocurable but mechanisms of treatment failure other than the effect of hypoxia on the radiation response cannot be excluded. Intratumoral pO2 histography in advanced cervical cancers enables pretherapeutic selection of low pO2 tumors as candidates for modified treatment approaches.
实验证据表明，缺氧可能会增加实体啮齿动物肿瘤的恶性潜能，并降低其对非手术治疗方式的敏感性。然而，肿瘤缺氧在人类恶性肿瘤中的重要性仍不确定。我们已开发出一种临床适用的标准化程序，通过使用计算机化极谱针电极组织分析仪来测定晚期宫颈癌的瘤内氧分压（pO2）。为了评估肿瘤氧合作为一项新的肿瘤学参数的意义，我们于1989年6月在美因茨大学医学中心启动了一项开放性前瞻性临床试验。截至1992年10月，50例晚期宫颈癌患者进入该研究。在这50例患者中测量的肿瘤氧合情况与各种患者和肿瘤特征无关，包括血红蛋白浓度、国际妇产科联盟（FIGO）分期和肿瘤大小。对33例接受标准放疗加或不加化疗（RT +/- CT）的患者的治疗结果进行了分析。瘤内pO2组织分析显示，33例患者中有15例的中位pO2≤10 mmHg（低pO2肿瘤）；在19个肿瘤中发现pO2分数≤5 mmHg（低pO2分数）。经过中位24个月（范围6至40个月）的随访，Kaplan-Meier生存表分析显示，接受RT +/- CT治疗的低pO2肿瘤患者的生存期和无复发生存期明显缩短。根据Cox比例风险模型，低pO2分数是生存期和无复发生存期最有力的单一预测指标。本研究结果与以下观点一致，即放射生物学上缺氧的肿瘤放射治愈性较低，但不能排除除缺氧对放射反应的影响之外的其他治疗失败机制。晚期宫颈癌的瘤内pO2组织分析能够在治疗前选择低pO2肿瘤作为改良治疗方法的候选对象。
