Vaupel Peter, Mayer Arnulf, Höckel Michael
Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany.
Strahlenther Onkol. 2006 Feb;182(2):63-71. doi: 10.1007/s00066-006-1543-7.
Tumor hypoxia has been linked to tumor progression, the development of treatment resistance, and thus poor prognosis. Since anemia is a major factor causing tumor hypoxia, the association between blood hemoglobin concentration (cHb) and tumor oxygenation status has been examined.
Published data on the relationship between pretreatment cHb values and tumor oxygenation (in terms of median pO(2) values, hypoxic fractions) have been summarized. Pretreatment O(2) tension measurements were performed in histologically proven experimental tumors, human breast cancers, squamous cell carcinomas of the head and neck, and cancers of the uterine cervix and of the vulva. In order to allow for a comparison between solid tumors and normal tissues, pO(2) measurements were also performed in healthy tissue in anemic and nonanemic patients. cHb was determined at the time of the pO(2) measurements.
Based on current information from experimental and clinical studies there is increasing evidence that anemia is associated with a detrimental tumor oxygenation status. Increasing cHb values are correlated with significantly higher pO(2) values and lower hypoxic fractions. Maximum tumor oxygenation in squamous cell carcinomas is observed at normal (gender-specific) cHb values (approximately 14 g/dl in women and approximately 15 g/dl in men). Above this "optimal" Hb range, the oxygenation status tends to worsen again. In anemic patients, tumor oxygenation is compromised due to a decreased O(2) transport capacity of the blood. At the upper edge of the Hb scale, a substantial increase in the blood's viscous resistance to flow in "chaotic" tumor microvessels is thought to be mainly responsible for the observed restriction of O(2) supply.
Review of relevant clinical data suggests that a maximum oxygenation status in solid tumors is to be expected in the range 12 g/dl < cHb < 14 g/dl for women and 13 g/dl < cHb < 15 g/dl for men. Considering the "optimal" cHb range with regard to tumor oxygenation, the concept of "the higher, the better" is therefore no longer valid. This finding has potentially far-reaching implications in the clinical setting (e. g., inappropriate erythropoietin treatment of nonanemic tumor patients).
肿瘤缺氧与肿瘤进展、治疗抵抗的产生以及不良预后相关。由于贫血是导致肿瘤缺氧的主要因素，因此对血液血红蛋白浓度（cHb）与肿瘤氧合状态之间的关联进行了研究。
总结了关于治疗前cHb值与肿瘤氧合（以中位pO₂值、缺氧分数表示）之间关系的已发表数据。在组织学证实的实验性肿瘤、人类乳腺癌、头颈部鳞状细胞癌、子宫颈癌和外阴癌中进行了治疗前O₂张力测量。为了能够比较实体瘤与正常组织，还对贫血和非贫血患者的健康组织进行了pO₂测量。在进行pO₂测量时测定cHb。
基于当前来自实验和临床研究的信息，越来越多的证据表明贫血与有害的肿瘤氧合状态相关。cHb值升高与显著更高的pO₂值和更低的缺氧分数相关。在正常（性别特异性）cHb值（女性约为14 g/dl，男性约为15 g/dl）时观察到鳞状细胞癌的最大肿瘤氧合。高于此“最佳”血红蛋白范围，氧合状态往往会再次恶化。在贫血患者中，由于血液的O₂运输能力降低，肿瘤氧合受到损害。在血红蛋白范围的上限，血液在“混乱”的肿瘤微血管中流动的粘性阻力大幅增加被认为是观察到的O₂供应受限的主要原因。
对相关临床数据的回顾表明，女性实体瘤的最大氧合状态预计在12 g/dl < cHb < 14 g/dl范围内，男性在13 g/dl < cHb < 15 g/dl范围内。考虑到肿瘤氧合方面的“最佳”cHb范围，“越高越好”的概念因此不再有效。这一发现在临床环境中可能具有深远影响（例如，对非贫血肿瘤患者进行不适当的促红细胞生成素治疗）。
