In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.

Transfer of a herpes simplex virus-derived thymidine kinase (HSV-tk) gene into brain tumor cells and subsequent ganciclovir (GCV) treatment has been shown by others to be an effective treatment in rats with intracerebrally inoculated 9L gliosarcomas. Mechanism of action and reproducibility are, however, still a matter of debate. We have used the same model to test the therapeutic effects of both retrovirus- and adenovirus-mediated transfer of the HSV-tk gene followed by GCV treatment. Survival time of rats with intracerebral 9L tumors was significantly prolonged after a single administration of adenovirus carrying a HSV-tk gene as compared to controls. Retrovirus-mediated gene transfer also resulted in significantly prolonged survival time when recombinant retrovirus-producing cells were transplanted. Direct injection of the recombinant retrovirus, HSV-tk-expressing cells, virus-producing cells without GCV administration and recombinant retrovirus-lacZ or interleukin-2 (IL-2)-producing cells did not result in tumor cell kill. In the present study, no significant difference in survival of 9L brain tumor carrying rats was found after treatment with adenovirus as compared to retrovirus-mediated HSV-tk-mediated gene transfer and subsequent GCV treatment.

Replication-defective adenovirus vectors were generated inoculated on day 0 with 10 5 II-45 cells into the pleural in which the gene of interest (lacZ, luciferase or HSV-tk) is cavity, received 7 × 10 9 infectious particles of IG.Ad. driven by the adenovirus major late promoter (MLP) or CMV.TK on day 1, day 2, day 4 or day 8. One day after the human cytomegalovirus immediate-early gene virus administration, 25 mg/kg GCV or PBS (controls) was promoter/enhancer (CMV). In vitro experiments with rat (IIinjected i.p. (intraperitoneally) twice daily. On day 15, all 45) and human (MERO 25) mesothelioma cell lines animals were killed. Significant tumor regression, equivalrevealed that the CMV promoter was stronger than the ent to 5 log cell kill, occurred in the treated rats suggesting MLP promoter regarding levels of expression of the luciferan impressive bystander effect. In a survival study, animals ase reporter gene and ganciclovir (GCV) killing efficiency were treated 9 days after inoculation of 10 5 tumor cells with after tk gene transfer. Following administration of IG.Ad.CMV.TK and a 14 days course of GCV. This treat-IG.Ad.CMV.lacZ recombinant adenovirus (Introgene, IG) ment prolonged symptom-free survival time from 19 days into the pleural cavity of Fischer rats with established in the controls to 33 days in the treated group. These mesothelioma, a widespread distribution of infectious virus responses can be best explained by assuming continued particles through the thorax contents was demonstrated.tk expression in or around the tumor tissue during GCV However, a relatively small proportion of tumor cells were treatment. Our results confirm and extend earlier findings transduced. Nevertheless, a strong tumor growth inhibition with the same model and demonstrate the potential of the was observed following treatment with IG.Ad.CMV.TK herpes simplex virus thymidine kinase suicide gene recombinant adenovirus and GCV. Separate groups of rats therapy as a local treatment for malignant mesothelioma.

Purpose: An MR-only postimplant dosimetry workflow for low dose rate (LDR) brachytherapy could reduce patient burden, improve accuracy, and improve cost efficiency. However, localization of brachytherapy seeds on MRI scans remains a major challenge for this type of workflow. In this study, we propose and validate an MR-only seed localization method and identify remaining challenges. Methods and materials: The localization method was based on template matching of simulations of complex-valued imaging artifacts around metal brachytherapy seeds. The method was applied to MRI scans of 25 prostate cancer patients who underwent LDR brachytherapy and for whom postimplant dosimetry was performed after 4 weeks. The seed locations found with the MR-only method were validated against the seed locations found on CT. The circumstances in which detection errors were made were classified to gain an insight in the nature of the errors. Results: A total of 1490 of 1557 (96%) seeds were correctly detected, while 67 false-positive errors were made. The correctly detected seed locations had a high spatial accuracy with an average error of 0.8 mm compared with CT. A majority of the false positives occurred near other seeds. Most false negatives were found in either stranded configurations without spacers or near other seeds. Conclusions: The low detection error rate and high localization accuracy obtained by the complexvalued template matching approach are promising for future clinical application of MR-only dosimetry. The most important remaining challenge is robustness with regard to configurations of multiple seeds in close vicinity, such as in strands of seeds without spacers. This issue could potentially be resolved by simulating specific configurations of multiple seeds or by constraining the treatment planning to avoid these configurations, which could make the proposed method competitive with CTbased seed localization.

We report a case of perineal recurrence of prostate cancer 6 years after low-dose-rate (LDR) brachytherapy for localized prostate cancer. The most common approach to treat such perineal masses, including those occurring after prior biopsy or surgery, is local excision. We report the use of stereotactic radiotherapy with volumetric modulated arc therapy (VMAT) as a novel non-invasive, potentially curative, and patient-friendly alternative to local excision.