Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting

Comparison of radiography- and computed tomography-based treatment planning in cervix cancer in brachytherapy with specific attention to some quality assurance aspects

Introduction: A modern approach in treatment planning for cervix carcinoma is based on a series of computed tomography (CT) sections and 3D dose computation. When these techniques were not yet available, dose evaluation was based on orthogonal radiographs. The CT based planning provides information on target and organ volumes and dose-volume histograms. The radiography based planning provides only dimensions and doses at selected points. The aim of the presented study is to correlate the information obtained with the two approaches for high dose-rate (HDR) brachytherapy of cervix carcinoma. Methods: For the study 28 patients with 35 applications receiving HDR treatment with Ir-192 were investigated The planning system PLATO (Nucletron) was used. The different aspects of available data, results and inaccuracies regarding quality assurance were looked at. Results: From the CT based planning, the volume, location and dose-volume histograms were calculated for the CTV, rectum and bladder. From the radiography-based planning, the dose to point A (prescription), point B, rectum and bladder ICRU reference points [14], points related to the bony structures could be evaluated as well as volumes receiving different dose levels. These two sets of information were compared and following mean Values derived. For a dose prescription of 7 Gy at point A, as an average, 83% (44 cm(3)) of the clinical target volume (CTV) receives at least 7 Gy. The mean dose at the rectum ICRU reference point is 4.3 Gy, and 12% (9 cm(3)) of the rectum is encompassed by the 4.3 Gy isodose. The mean dose at the bladder ICRU reference point is 5.8 Gy, and 8% (16 cm(3)) of the bladder is encompassed by the 5.8 Gy isodose. The maximum dose to the rectum is 1.5 times higher than the dose at the ICRU reference point, and for the bladder 1.4 times higher. Uncertainties caused by the reconstruction of the applicator and merging of isodoses could be evaluated. Discussion: The subdivision of different approaches and the transfer from point doses to Volumes in treatment planning is possible and practical for the treatment of cervix carcinoma in brachytherapy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved

Serum VEGF levels in patients undergoing primary radiotherapy for cervical cancer: impact on progression-free survival

Vascular endothelial growth factor (VEGF) plays an important role in the regulation of tumour growth and metastasis. It was the aim of this study to examine the impact of serum VEGF levels on the likelihood of response to radiotherapy and on the disease-free survival in patient,,, with cervical cancer. Blood was taken before commencing treatment and serum VEGF was assessed by quantitative ELISA in 23 patients with cervical cancer stage IB-IVA undergoing primary radiotherapy. Serum VEGF levels were correlated with clinical and histopathologic factors as well as with response to radiotherapy and time to progression. Nineteen of the 23 patients had a complete response and four patients had persistent disease at 3 months. The median follow-Lip was 25 months (95% confidence interval: 23.5-26.5 months). At the time of analysis, eight patient,,, were tumour-free and 15 patients had tumour progression, 12 of these 15 patients died of disease. Overall, the median serum VEGF level was 244 pg/ml (range 31.9-817.6 pg/ml). All four patients with local failure had VEGF levels >244 pg/ml, whereas 11 of the 19 patients with complete response had serum VEGF of less than or equal to244 pg/ml (P = 0.035). The median time to progression was 5 months in patients with VEGF of >244 pg/ml compared to 19 months in patients with VEGF of : 244 pg/ml (log rank, P = 0.003). In multivariate analysis, serum VEGF, tumour size and histological type, but not the patient's age, stage and grade of histological differentiation influenced the progression-free survival. Elevated pre-therapeutic serum VEGF levels are associated with poor response and a shorter time to progression in patients with cervical cancer undergoing primary radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

The benefit of Beam's eye view based 3D treatment planning for cervical cancer

Purpose: The aim of this study was to evaluate the possibility of Beam's eye view (BEV) based three dimensional (3D) treatment planning, to reduce portions of organs at risk included in the treated volume without increasing the risk of geographical miss in external beam therapy of cervical cancer. Materials and methods: Three dimensional dose distribution of BEV based 3D treatment plans was compared to the 3D dose distribution derived from a four-field-box-technique using standard portals. A total of 20 patients with cervical cancer stage FIGO IIB and FIGO IIIB was included. Dose distribution in the target volumes and in the organs at risk of BEV based treatment planning, was compared to the dose distribution of the standard field technique using dose-volume-histograms. Results: In 4/20 patients (20%) a geographical miss at the cervix uteri was observed for the standard field technique. The BEV based treatment planning resulted in an adequate coverage of target volume and additionally in a reduction of portions of bladder and bowel Volume included in the treated volume (-13.5, -10%). In contrast the BEV based technique resulted in an increase of portions of the rectum volume included in the treated volume compared to standard portals due to a shift of the rectum by the enlarged cervix uteri from its posterior to a lateral position. An overall 7% reduction of treated volume was observed, although the maximum width of lateral fields increased for the BEV technique. Moreover, we have found a remarkable impact of bladder fillings on the amount of bowel and bladder volume included in the treated volume. Conclusion: BEV based 3D treatment planning for external beam therapy of cervical cancer offers a possibility to avoid geographical miss of part of the CTV with reduced portions of bladder and bowel volume included in the treated volume. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved