OBJECTIVES: To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. METHODS: Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. RESULTS: With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). CONCLUSIONS: To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.
OBJECTIVES: To investigate whether low partial pressure of oxygen (PO2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP. METHODS: Custom-made Eppendorf PO2 microelectrodes were used to obtain approximately 100 PO2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate PO2, average median muscle PO2, and prostate/muscle PO2 (P/M) ratio. RESULTS: With a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002). CONCLUSIONS: To our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M PO2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result.
Authors: Hyeon Ung Park; Simeng Suy; Malika Danner; Vernon Dailey; Ying Zhang; Henghong Li; Daniel R Hyduke; Brian T Collins; Gregory Gagnon; Bhaskar Kallakury; Deepak Kumar; Milton L Brown; Albert Fornace; Anatoly Dritschilo; Sean P Collins Journal: Mol Cancer Ther Date: 2009-04 Impact factor: 6.261
Authors: Christos Sachpekidis; Christian Thieke; Vasileios Askoxylakis; Nils H Nicolay; Peter E Huber; Michael Thomas; Georgia Dimitrakopoulou; Juergen Debus; Uwe Haberkorn; Antonia Dimitrakopoulou-Strauss Journal: Am J Nucl Med Mol Imaging Date: 2015-01-15
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: John D Martin; Dai Fukumura; Dan G Duda; Yves Boucher; Rakesh K Jain Journal: Cold Spring Harb Perspect Med Date: 2016-12-01 Impact factor: 6.915