Disease control of uterine cervical cancer: relationships to tumor oxygen tension, vascular density, cell density, and frequency of mitosis and apoptosis measured before treatment and during radiotherapy.
Identification of biological parameters of major importance for the control of malignant diseases can be useful for the design of optimal treatment regimes for individual patients. Tumor oxygen tension (pO2), vascular density, cell density, and frequency of mitosis and apoptosis were measured before treatment (40 patients) and after 2 weeks of radiotherapy (22 patients) in patients with uterine cervical cancer. The aim was to investigate whether one of the parameters was more important for disease control than the others. Three sets of data were considered; the pretreatment parameters, the parameters measured after 2 weeks of radiation, and the changes in the parameters during this time. The pO2 was measured polarographically; the other parameters were determined by histological analyses of tumor biopsies. Hypoxic subvolume (HSV5), ie., the fraction of pO2 readings <5 mm Hg multiplied with tumor volume, showed the strongest correlation to control. Patients with a small HSVs before treatment had a higher control probability after a median follow-up time of 50 months than patients with a large HSV5 (P < 0.001). All other parameters or changes in parameters showed impaired correlation to control compared with pretreatment HSV5. The present results suggest that pretreatment oxygenation is more important for disease control of cervical cancer than the oxygenation after 2 weeks of radiotherapy or the changes in oxygenation during this time. Moreover, vascular density, cell density, and frequency of mitosis and apoptosis before treatment or after 2 weeks of therapy are probably not as important as pretreatment oxygenation as well. Although significant correlations between disease control and some of the parameters other than pretreatment oxygenation can occur in studies based on a large number of patients, the specificity of these parameters in the prediction of control is probably not as high as for oxygenation.
Lyng
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Department of Biophysics, The Norwegian Radium Hospital, Oslo. heidi.lyng@labmed.uio.no
Sundfør
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Tropé
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Rofstad
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D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*; D002452:Cell Count / Q000528:radiation effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000528:radiation effects; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000473:pathology / Q000532:radiotherapy*
D010100:Oxygen