To present the findings of a phase II clinical trial studying the use of MRI guided HDR brachytherapy as a boost in the treatment of intermediate or high risk prostate cancer. Eleven patients were treated with external beam radiation therapy that delivered 46 Gy to the prostate and proximal seminal vesicles (the pelvis was treated in three high risk patients). The patients also received additional HDR brachytherapy boost of 21 Gy in two 10.5 Gy fractions using 192Ir with the guidance of a closed bore MRI. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the RTOG and were recorded weekly throughout treatment as well as up to 75 months after treatment. All patients successfully completed treatment and received the prescribed dose. At diagnosis, median age was 60 (range: 50-75 years of age) and PSA was 8.3 (range 5.2-117.8) and Gleason scores 7-9. The median PTV V100 was 94.32%, median urethra V125 0.035 cm3, median rectum V75 0.225 cm3. During treatment, Grade 2 GU toxicity was noted in 4 patients; Grade 1 in 6 patients; Grade 2 GI toxicity was noted in 4 patients; Grade 1 GI toxicity was noted in 3 patients. At a median of 63 months, long term Grade 2 GI toxicity was seen in 1 patient and Grade 2 GU toxicity was seen in 4 patients. There were no acute or late grade 3 and 4 GU or GI toxicities. The mean PSA nadir was 16.8 months. Three patients had a PSA failure at a median of 44.6 months. All three of the patients presented with high-risk prostate cancer (Gleason score 8 or 9), PSA range of 7-117; and one patient presented with a positive node. Our study shows the novel use of MRI guidance for HDR brachytherapy leading to good PTV coverage, minimal dose to the organs at risk and a low rate of acute and late toxicity with this method.

Purpose/Objective: This study aimed to validate the potential of urinary vascular endothelial growth factor (VEGF) measurement as a clinically useful tumor marker across multiple cancer types. Previous studies have focused on patients' initial serum VEGF measurements obtained before treatment, and their association with disease activity. We aimed to validate urinary VEGF measurement. More importantly, we examined VEGF trends as useful, non-invasive clinical markers of tumor activity. We also stratified patients according to specific types of cancer, such as prostate cancer, in order to confirm tumor marker utility within these cohorts.Materials/Methods: Urine samples were obtained from 80 patients with cancer, who were evaluated for treatment with external beam radiation therapy, and 16 normal controls. Samples were collected prior to radiation treatment, once a week during radiation treatment, and at every follow-up visit. Aliquots were stored at −20°C, and analyzed by VEGF chemiluminescent immunoassay. VEGF trending was characterized three ways: (1) Patients were placed into a binary "up-down" categorization, according to whether their VEGF levels increased or decreased, (2) the quantitative difference was calculated, and (3) the VEGF "slope," or rate of change of VEGF level, was calculated.Results: Initial pre-treatment urinary VEGF levels were significantly higher overall in cancer patients, mean = 305 (range = 0 – 1421), as compared to normal controls, mean = 166 (range = 5 – 318), (p = 0.012). Of prostate cancer patients, initial VEGF levels were also significantly higher (p = 0.028) than in controls, mean = 404 (range = 11 – 1421). Metastatic prostate cancer patients, mean = 631 (range = 248 – 1061), who had failed primary therapy also had significantly higher VEGF levels (p = 0.031) as compared to prostate cancer patients with less aggressive disease. Urinary VEGF trending during radiation in all cancer patients, by methods 1, 2, and 3, all correlated significantly with disease activity (p = 0.009, 0.007, and 0.033, respectively). Urinary VEGF trending after the completion of radiation therapy was significant for methods 1 and 3 (p = 0.007, 0.032), but not method 2. Focusing on the prostate cancer patient cohort, VEGF trending during radiation was also significantly correlated with disease activity using methods 1 and 3 (p = 0.002, 0.05). After the completion of radiotherapy, VEGF trends were again significantly associated with disease status using methods 1 and 3 (p = 0.011, 0.026).Conclusions: Initial pre-radiotherapy urinary VEGF levels were significantly higher in cancer patients as compared to normal controls. In our prostate cancer patient cohort, metastatic prostate cancer patients who failed therapy had the highest VEGF levels, followed by patients with localized disease, then healthy controls. Initial pre-radiation VEGF level was correlated with presence and severity of disease. Yet, initial VEGF level was not as robust a clinical tumor marker as VEGF trending. To our knowledge, previous studies have all focused on this initial, single measurement. We hypothesized that the dynamic change in VEGF level, or VEGF trending, would provide more clinical information than the static measurement of initial VEGF level. Indeed, monitoring VEGF trending was significantly correlated with the patient's disease activity. Patients with increasing VEGF levels primarily had active disease post-radiotherapy; the converse also held true. Therefore, a patient's VEGF pattern serves as a marker for tumor aggressiveness and response to therapy. Within the prostate cancer patient cohort, VEGF trending also significantly correlated with disease status. A larger, longer prospective study is needed to confirm these preliminary conclusions. A longer follow-up period is also needed to validate our hypothesis that measuring the VEGF "slope" may be a more useful predictor of disease free survival than other approaches. Purpose/Objective: This study aimed to validate the potential of urinary vascular endothelial growth factor (VEGF) measurement as a clinically useful tumor marker across multiple cancer types. Previous studies have focused on patients' initial serum VEGF measurements obtained before treatment, and their association with disease activity. We aimed to validate urinary VEGF measurement. More importantly, we examined VEGF trends as useful, non-invasive clinical markers of tumor activity. We also stratified patients according to specific types of cancer, such as prostate cancer, in order to confirm tumor marker utility within these cohorts. Materials/Methods: Urine samples were obtained from 80 patients with cancer, who were evaluated for treatment with external beam radiation therapy, and 16 normal controls. Samples were collected prior to radiation treatment, once a week during radiation treatment, and at every follow-up visit. Aliquots were stored at −20°C, and analyzed by VEGF chemiluminescent immunoassay. VEGF trending was characterized three ways: (1) Patients were placed into a binary "up-down" categorization, according to whether their VEGF levels increased or decreased, (2) the quantitative difference was calculated, and (3) the VEGF "slope," or rate of change of VEGF level, was calculated. Results: Initial pre-treatment urinary VEGF levels were significantly higher overall in cancer patients, mean = 305 (range = 0 – 1421), as compared to normal controls, mean = 166 (range = 5 – 318), (p = 0.012). Of prostate cancer patients, initial VEGF levels were also significantly higher (p = 0.028) than in controls, mean = 404 (range = 11 – 1421). Metastatic prostate cancer patients, mean = 631 (range = 248 – 1061), who had failed primary therapy also had significantly higher VEGF levels (p = 0.031) as compared to prostate cancer patients with less aggressive disease. Urinary VEGF trending during radiation in all cancer patients, by methods 1, 2, and 3, all correlated significantly with disease activity (p = 0.009, 0.007, and 0.033, respectively). Urinary VEGF trending after the completion of radiation therapy was significant for methods 1 and 3 (p = 0.007, 0.032), but not method 2. Focusing on the prostate cancer patient cohort, VEGF trending during radiation was also significantly correlated with disease activity using methods 1 and 3 (p = 0.002, 0.05). After the completion of radiotherapy, VEGF trends were again significantly associated with disease status using methods 1 and 3 (p = 0.011, 0.026). Conclusions: Initial pre-radiotherapy urinary VEGF levels were significantly higher in cancer patients as compared to normal controls. In our prostate cancer patient cohort, metastatic prostate cancer patients who failed therapy had the highest VEGF levels, followed by patients with localized disease, then healthy controls. Initial pre-radiation VEGF level was correlated with presence and severity of disease. Yet, initial VEGF level was not as robust a clinical tumor marker as VEGF trending. To our knowledge, previous studies have all focused on this initial, single measurement. We hypothesized that the dynamic change in VEGF level, or VEGF trending, would provide more clinical information than the static measurement of initial VEGF level. Indeed, monitoring VEGF trending was significantly correlated with the patient's disease activity. Patients with increasing VEGF levels primarily had active disease post-radiotherapy; the converse also held true. Therefore, a patient's VEGF pattern serves as a marker for tumor aggressiveness and response to therapy. Within the prostate cancer patient cohort, VEGF trending also significantly correlated with disease status. A larger, longer prospective study is needed to confirm these preliminary conclusions. A longer follow-up period is also needed to validate our hypothesis that measuring the VEGF "slope" may be a more useful predictor of disease free survival than other approaches.