Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia induced radiation resistance rather than hypoxia-induced metastasis

Poor outcome of treatment in advanced cervix carcinoma has been shown to be associated with poor oxygenation of the primary tumour. Hypoxia may cause radiation resistance and promote lymph-node metastasis. The purpose of the study reported here was to investigate whether hypoxia-induced treatment fa ilure in advanced cervix carcinoma is primarily a result of hypoxia-induced radiation resistance or the presence of hypoxia-induced lymph-node metasta ses at the start of treatment. Thirty-two patients with squamous cell carci noma of the uterine cervix were included in the study. Radiation therapy wa s given with curative intent as combined external irradiation and endocavit ary brachytherapy, The oxygenation status of the primary tumour was measure d prior to treatment using the Eppendorf pO(2) Histograph. Pelvic and para- aortal lymph-node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. The primary tumours of the patients with me tastases (n = 18) were significantly more pearly oxygenated than those of t he patients without metastases (n = 14). Multivariate Cox regression analys es involving biological and clinical parameters identified the tumour subvo lume having pO(2) values below 5mmHg (HSV (pO(2) < 5mmHg) as the only signi ficant, independent prognostic factor for locoregional control, disease-fre e survival and overall survival. The probabilities of locoregional control, disease-free survival and overall survival were significantly lower far th e patients with HSV (pO(2) < 5 mmHg) above the median value than for those with HSV (pO(2) < 5 mmHg) below the median value. On the other hand, the ou tcome of treatment was not significantly different for the patients with me tastases and the patients without metastases at the start of treatment, irr espective of clinical end-point. Consequently, treatment failure was primar ily a result of hypoxia-induced radiation resistance rather than hypoxia-in duced lymph-node metastasis, suggesting that novel treatment strategies aim ing at improving tumour oxygenation or enhancing the radiation sensitivity of hypoxic tumour cells may prove beneficial in attempts to improve the rad iation therapy of advanced cervix carcinoma (C) 2000 Cancer Research Campai gn.