Rising numbers of patients in the field of radiation therapy require an optimization of the efficiency and automatism of the work process. One approach is the computer-assisted segmentation with atlas-based segmentation programs (ABAS) of clinical target volumes (CTV) and organs at risk (OAR), which automatically generate an estimate of CTV and OAR. We tested and evaluated the quality of those delineated volumes in context of treatment planning for breast and anorectal cancer. The algorithm used (Electa Software, St. Louis, MO) is based on the principle that an atlas with defined CTV serves as a template case to delineate automatically target volumes of sample patient cases. Automatic delineation results are compared with CTV's of breast and anorectal cancer, which are contoured manually according to guidelines of the Radio Therapy Oncology Group (RTOG). Results are quantified by analyzing the Dice Similarity Index (DSC), the logit Dice transformation (logitDSC) and Percent Overlap (PO). Dice Indices > 0.84 and logDSC > 0.750 are defined to be acceptable. Furthermore this study introduces an additional feature of the software, Staple, which is designed to improve the delineation outcome. ABAS produced good results for the CTV of the breast and the rectum. However, delineations of the inguinal lymphatic flow were dissatisfying. Average DSC for CTV of the breast were between 0.86 and 0.9056 (Range [0,1]), of the average logit(DSC) between 0.7944 and 0.9889 (Range [-inf,inf]) and of the average PO between 75.5% and 82.89%. For anorectal cancer average DSC lied in between 0.7917 and 0.8467, average logit(DSC) in between 0.6083 and 0.7667 and average PO in between 68% and 73.67%. Generally ABAS produced satisfactory and time-saving results for the clinical target volumes of breast and anorectal cancer. In addition the introduction of Staple succeeded in enhancing the contouring outcome. Small target volumes with inaccurate definition of boundary layers are yet to be delineated manually.

To investigate health-related quality of life (HRQOL) in Japanese men with localized prostate cancer who underwent prostate brachytherapy (BT) or retropubic radical prostatectomy (RRP).A total of 70 patients who underwent BT and 67 who underwent RRP were enrolled in our study. The Medical Outcomes Study 36-Item Short Form (SF-36), University of California, Los Angeles, Prostate Cancer Index, and the International Prostate Symptom Score were administered before and 1, 3, 6, and 12 months after treatment. No patients received neoadjuvant or adjuvant therapy.The RRP group reported significantly lower scores in several domains of the SF-36 at 1 month (P <0.05), but these domains returned to baseline within 6 months. The BT patients reported no significant changes in any of the general HRQOL domains throughout the follow-up period. The RRP group reported a lower posttreatment urinary function score, which reflected leakage, than the BT group. However, the BT patients experienced a significantly delayed recovery of the urinary bother score. The data from the International Prostate Symptom Score showed adverse effects from BT on voiding symptoms for the initial 6 months after treatment. No differences were found in bowel symptoms. RRP was associated with worse sexual function than BT, although nerve-sparing surgery minimized the difference.The results of this study have indicated that BT and RRP have meaningfully different profiles in the recovery of general QOL. The differences in the recovery of disease-specific HRQOL were pronounced during the first 12 months after treatment.

Background. Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis.Material. A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated.Result. The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time.Conclusion. BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.

Purpose/Objective: Prostate brachytherapy has been reported to have less morbidity for patients than radical prostatectomy or external beam irradiation. However, information regarding long-term treatment-specific quality-of-life (QoL) is scant. We evaluated the impact of permanent implant brachytherapy on general, cancer specific and symptom domains of QoL for up to 6 years using validated patient-administered quality-of-life instruments. Materials/Methods: A total of 295 men consecutively treated in a single medical center between June 1998 and December 2003 were mailed two standardized questionnaires (the EORTC prostate cancer quality of life questionnaire QLQ-PR25 and the ICS-male questionnaire) to assess health-related QoL. We subclassified two groups of patients: group 1 with patients younger than 65 years of age (n=45, median age 62, range 45–64), group 2 with patients 65 years of age or older (n=186, median age 73, range 65–85). The minimal follow up after treatment was 12 month (mean 50.3 months; range 12–78 months). 106 (45,9%) men have also been treated with hormonal therapy. Results: A total of 231 questionnaires were returned (78.3% response rate), 221 were suitable for analysis, 12.9% of the patient had died. 76.7% of group 1 and 73.2% of group 2 reported that they were in good, very good, or excellent health. Table 1 provides an overview of the QoL outcomes and side effects. 53.5% (group 1) and 70.7% (group 2) referred strong or moderate pollakisuria, 39.2% reported nocturia, without relevant differences between both groups, and 5.5% of patients suffered from strong or moderate dysuria (p>0.05). 2.3% patients reported strong stress incontinence; 24.7% reported moderate, and 22.0% strong urge incontinence. A total of 13% used pads. There was no evidence of severe rectal dysfunction. 75.6% (group 1) and 60.9% (group 2) had sex during the last four weeks. The most common problems were erectile dysfunction (48.6% vs. 75%, p<0.001) and decrease in ejaculation (39.4% vs. 59.6%, p<0.001). Whereas sexual complaints were age associated, this was not the case for urinary and bowel complaints. Most patients (95.9%) would recommend (125)I seed brachytherapy to others.Table 1Quality of life outcomes, frequency of multi-item incontinence, bowel and sexual function scores* Men with sexual activity over past 4 weeks. * Men with sexual activity over past 4 weeks. Conclusions: Our data substantiate the favorable long-term QoL outcomes associated with modern brachytherapy techniques. Significant age differences were observed in all quality of life measures, with the largest occurring in sexual and urinary symptoms. Sexual function was significantly worse in patients 65 years of age and older (p <0.05).

Radiation-induced apoptosis has only minor influence on clonogenic survival of tumor cells from most solid tumors. However, normal hematopoietic cells are particularly sensitive to ionising radiation with apoptosis as a major inactivation pathway. Overexpression of the multidrug resistance 1 (MDR1) gene product, P-glycoprotein (P-gp), leads to suppression of apoptosis. Therefore, gene therapy with MDR1 might provide protection of the bone marrow/normal tissue cells during radiotherapy. The aim of this study was to test the feasibility of this approach by demonstrating that human CD34+ blood stem cells can be protected from the effect of radiation by MDR1 gene transduction. We further tested the mechanism to suppress radiation induced apoptosis by MDR1 gene transduction of human lymphoblastoid cell lines with different p53 status and apoptosis susceptibility. As a tumor model we used a human ovarian cancer cell line. CD34+ cells were isolated from three individual donors. After pre-stimulation, cells were exposed to retroviral supernatant containing the hybrid vector SF1m carrying the MDR1 gene. After retroviral transduction, 1x105 cells of transduced and non-transduced CD34+ control cells, respectively, were irradiated with 0–6 Gy and held in liquid culture under differentiation conditions. Ten days after irradiation, cell counts were performed and MDR-1 gene expression was determined by their ability to efflux Rhodamine-(Rh-)123. Secondly, human lymphoblastoid cell lines TK6, TK6E6, WTK1 retrovirally transduced with the MDR1 gene, the human ovarian cancer cell line A2780 and P-gp-overexpressing A2780/M250 were irradiated. Apoptosis was measured using the Nicoletti sub-G1 assay and clonogenic survival was determined by colony formation. Ten days after irradiation of CD34+ cells, the total number of cells was significantly higher (3-10-fold) in MDR1-transduced compared to non-transduced cultures. At the clinical relevant fraction size, D = 2 Gy for non-transduced controls, the mean dose-modifying factor for transduction with MDR1 was 0.54 (range: 0.49–0.62). The Rh-123 data showed that 12.3 ± 3.6% (mean ± std.dev.) of the cells in the transduced cultures were Rh-123 negative (i.e. expressed P-gp) independently of the radiation dose whereas only 1% of non-transduced cells were Rh-123 negative. In the human lymphoblastoid cell lines TK6, TK6E6, WTK1 and in the human ovarian cancer cell line A2780/M250, P-gp overexpression suppressed radiation-induced apoptosis. However, for the tumor cells, this was not accompanied by an increase of clonogenic radioresistance. For the p53 wild-typ TK6 cells the MDR-1 gene transfer increases also the clonogenic radioresistance, similar to the effects of PMA or caspase inhibition. The more radioresistant TK6E6 cells (p53 neg.) were less affected by P-gp expression, and no change in survival was recorded for the WTK1 cells (p53 mutated). Inhibition of P-gp with Cyclosporin A restored vincristine toxicity in A2780/M250 cells but had no effect on suppression of radiation-induced apoptosis, indicating that P-gp may act through different pathways. The results demonstrate that efficient radio-protection of human blood stem cells by MDR1 gene transduction is feasible. Thus, enhancing repopulation by surviving stem cells may increase the tolerance of hematopoietic cells and thus contribute to widening the therapeutic range in radiotherapy

We previously documented a high rate (45%) of alterations in p16 gene in squamous cell carcinoma (SCC) of the head and neck.However, the association of the /)I6 gene alterations with resistance to radiotherapy remains unclear.In the present study, we