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Background and Purpose To investigate possible relationships between the dose to the sub-segments of the lower urinary tract and lower urinary tract symptoms (LUTS) after brachytherapy of the prostate. Materials and Methods This study involved 225 patients treated for prostate cancer with I-125 seeds. Post-implant dose-volume histograms of the prostate, urethra, bladder wall, bladder neck and external sphincter were determined. Endpoints were the mean and the maximum International Prostate Symptom Score (IPSS) during the first 3 months after the treatment. For binary analysis the patients were stratified in a group with enhanced LUTS and a group with non-enhanced LUTS. Results The dose to 0.5 cm 3 of the bladder neck ‘ D 0.5cc -blne’ ( p = 0.002 and p = 0.005), the prostate volume prior to treatment ‘ V pr -0’ ( p = 0.005 and p = 0.024) and the pre-treatment IPSS (both p D 0.5cc -blne ⩾ 175 Gy and a V pr -0 ⩾ 42 cm 3 , 68% suffered from enhanced LUTS, against just 30% of the other patients ( p Conclusions Pre-treatment IPSS, prostate volume and dose to the bladder neck are correlated with post-implant IPSS. A combination of a large prostate and a high dose to the bladder neck is highly predictive for enhanced early LUTS.

Purpose After prostate implantation, dose calculation is usually based on a single imaging session, assuming no geometrical changes occur during the months of dose accumulation. In this study, the effect of changes in anatomy and implant geometry on the dose distribution was investigated. Materials and methods One day, 1 month and 3 1 2 months after seed implantation, a combined TRUS-CT scan was made of 13 patients. Based on these scans changes in dose rate distribution were determined in prostate, urethra and bladder and a ‘geometry corrected' dose distribution was estimated. Results When based on the day-1 scan, parameters representing high dose volumes in prostate and urethra were largely underestimated: V150 of the prostate 18±10% and V120 of the urethra 47±32%. The dose to a 2cm 3 hotspot in the bladder wall (D2cc), however, was overestimated by 31±35%. Parameters based on scans 1 month post-implant or later were all within ±5% of geometry corrected values. Conclusion Values meant to indicate the adequacy of dose coverage of the prostate, V100 and D90, were not influenced by geometrical changes and were independent of the post-implant scan date. Other parameters representing high dose volumes changed strongly within the first month after implantation.

Background and purpose : In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. Patients and methods : Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. Results: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P =0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P =0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years; P =0.037, disease-specific survival: 76 vs. 92% at 3 years; P =0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P =0.0017), and lower disease specific survival (60 vs. 92%; P =0.0024), disease-free survival (7 vs.35%, P =0.0023) and overall survival (39 vs. 80%; P =0.0018). Conclusion : This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Background and purpose : The three-dimensional (3D) dose distribution in combination with 3D anatomy of 13 patients treated for cervical carcinoma with intracavitary brachytherapy was analyzed. The aim of this study was to determine the correlation between a dose value obtained from the integral dose volume histogram (DVH) of the rectum and (a) the Nederlands Kanker Instituut (NKI) point of reference for the rectum dose ( R ) and (b) the highest dose to the frontal rectum wall in the transverse CT slice near the top of the vagina through point R . Results : The correlation between the DVH rectum dose value for 2 cm 3 in the highest dose region and the rectum dose at point R was poor (regression coefficient 0.50). On the contrary, however, the correlation between the DVH rectum dose value for 2 cm 3 in the highest dose region and the maximum rectum dose value in a transverse CT slice through point R was good (regression coefficient 0.90). Conclusions : The maximal rectum dose value obtained from a transverse CT slice near the top of the vagina through point R was found to be a more representative point for the rectal dose burden and might therefore show a good correlation with complications. The point of reference for the rectal dose ( R ) was found not to be a reliable estimation of the maximal dose in the rectum.

Cell kinetic parameters in human tumours were determined by in vivo labelling with iododeoxyuridine (IUdR) followed by flow cytometric analysis of tumour biopsies after staining with a monoclonal antibody against IUdR-DNA. The purpose of this study was to determine the variation in these kinetic parameters from area to area within the same tumour. Each patient received a single i.v. injection of IUdR and the biopsy or operation specimen was taken several hours later. Multiple biopsies were taken or the operation specimen was cut into several pieces. Tumour material was stored in ethanol. Each piece was subsequently processed and stained for analysis separately. The duration of DNA synthesis (Ts), the labelling index (L.I., percent IUdR-labelled cells) and the potential doubling time (Tpot) were determined for each sample. The mean and standard deviation (variation between pieces) for each parameter was calculated for each tumour. The coefficient of variation (C.V.) provided the measure of intratumoural variation. Thirteen tumours were investigated, 6 of which were transitional cell carcinomas of the bladder and 7 of which were squamous cell carcinomas, mostly of the head and neck. Ts values ranged from 4.1 to 17.2 h (mean 9.5 h), L.I. values from 1.6 to 18.6% (mean 9.7%) and Tpot values from 2.3 to 15.1 days (mean 7.2 days). Mean C.V.s for Ts, L.I. and Tpot were 10, 24 and 27%, respectively. Most of the variation in Tpot (calculated from the other two parameters), came from the L.I., with Ts showing much less intratumoural variations. It is concluded that this kinetic method using low IUdR doses can be successfully applied in human tumours and has sufficient accuracy for predictive assay applications in which tumours need to be classified according to their proliferation rates. Further developments are required to distinguish normal and malignant cells flow cytometrically, particularly for diploid tumours.