Posters— Basic Science/Biology

INTRAMURAL OXYGEN STATUS IN SOFT TISSUE SARCOMA: PROGNOSTIC VALUE WITH RESPECT TO DIFFERENT TREATMENT MODALITIES

Peter Hohenberger, Mathias Schläfke, Birger Bida, Christoph Kettelhack Div.of Surgery and Surgical Oncology, Charité, Humboldt University of Berlin, Germany

Purpose: Intramural oxygen partial pressure (pO₂ ) was reported to be predictive for the likelihood of distant metastases in human soft tissue sarcoma if pO₂ was < 10 mmHg [Brizel, Cancer.Res. 56: 941, 1996]. However, those patients were treated by 50 Gy of irradiation and it is well known that oxygenation interferes with the efficacy of radiation therapy. We were interested to know whether pO₂ also is of predictive value in patients treated surgically and represents an independent prognostic marker.

Methods: In 73 patients suffering from soft tissue sarcoma of the limb or trunk, intratumoral oxygen partial pressure was measured polarographically. We either used an O₂ -sensitive fine needle probe (KIMOC, Eppendorf, Germany, n= 41). The mean of pO₂ , range and proportion of the hypoxic tissue fraction ( <5 mmHg) was evaluated and depicted in histogramas of 200 measurements per tumor. The tissue temperature was recorded along the puncturing canal. Another 32 pts. Were analysed by use of an intratumoral implant probe p(ti)O₂ with a sensitive surface of 7.1 mm2 (LICOX, Med. Systems Corp., Greenvale, NY) during neoadjuvant combined modality therapy. Tumor vascularisation was divided into hyper, iso, hypo-, and avascular pattern according to angiogram and compared with the oxygenation status. DFS was measured by the Kaplan-Meier method and the log-rank technique was used to compare DFS of different groups of patients. Spearman correlation coefficients were calculated to examine the relationship of tumor oxygenation and vascularity.

Results: The mean pO₂ values from 0.6 to 69 mm Hg. G1 tumors showed a markedly higher pO₂ (51.4 mmHg) in contrast to G2 and G3 tumors with 32 mmHg and 29 mmHg resp. The proportion of hypoxic fractions was significantly lower in G1 tumors (6.3%) vs. G2/3 tumors (15% and 18% resp., p=0.01) Liposarcomas showed the highest pO₂ values and there was no correlation to vascularity as determined by angiogram. There were no significant differences in the proportion of patients developing distant metastases whether their primary tumors showed mean pO₂ exceeding or being less than 10 mmHg. Measurements of pO₂ obtained during neoadjuvant treatment, however, showed considerable differences between histological subtypes but also within the same group.

Conclusions: Tumor pO₂ is not a general marker of risk of distant metastases in soft tissue sarcoma if patients are treated without radiotherapy. However, extreme differences between tumors of identical type may severely interfere with drug uptake f.e. during neoadjuvant treatment. Intratumoral pO₂ might be very useful tool to control for effects of systemic or regional drug treatment of sarcomas.

Part of this work was supported by grant of Deutsche Forschungsgemeinschaft SFB 273/C 13.