- Email: [email protected]
1033 poster OUTCOME AUDIT ON POST-OPERATIVE PROSTATE RADIOTHERAPY
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were also qualitatively reviewed for concordance. Results: Patients remained immobilized throughout the procedure. X-ray data was analyzed for 3 procedures to date. The average elapsed time between MRI imaging and the dummy cable check immediately prior to treatment delivery was 81 minutes. Images of the first procedure were analyzed offline, whereby no offset corrections were applied to the treatment plan prior to delivery. Mean SI error between actual and planned conditions was 1.8 mm (SD 1.4mm). First dwell position depth error exceeded MRI voxel resolution in 3/18 catheters, up to 5mm. For the subsequent procedures, offset corrections were applied to the treatment plan prior to delivery. Qualitative image review was concordant with the measured depth errors for all catheters. Depth errors were not predicted by inspecting shifts at the template surface. The first dwell position was revised in 6/29 catheters, with a mean SI correction of -2mm (range -4 to 4mm).
Conclusions: Catheter depth errors were identified despite controlled conditions and relatively short elapsed times between MRI imaging and treatment delivery. Online X-ray imaging can improve SI accuracy by increasing the image resolution of the first dwell position to sub-millimeter scale, and correction of the treatment plan based on the actual depth of the first dwell position
1033 poster OUTCOME AUDIT ON POST-OPERATIVE PROSTATE RADIOTHERAPY S. Vengalil1 , L. Shum1 1
B ELFAST C ITY H OSPITAL, Clinical Oncology, Belfast, United Kingdom
Purpose: BackgroundThe role of post-prostatectomy radiotherapy remains controversial.There is uncertainty whether post-prostatectomy radiotherapy should be administered adjuvantly or for salvage when PSA level rises. But there is mounting evidence that immediate radiotherapy in high risk clinicopathological cases is superior to observation alone. Studies have demonstrated improved biochemical control and/or disease free survival with adjuvant radiotherapy, but it’s benefit in terms of overall survival is not clear. Approximately 15-40% of patients will experience a biochemical recurrence within 10 years after surgery. The factors which identify risk of biochemical failure include positive surgical margins, Gleason score, extra-capsular extension, seminal vesicle invasion, positive lymph nodes and pre-operative PSA levels.ObjectivesTo evaluate outcome and toxicities of adjuvant and salvage radiotherapy treatment following radical prostatectomy and compare with standards published from clinical trials. Materials: Retrospective review of case notes of patients who received postprostatectomy radiotherapy between January 2000 and December 2008 at our institution. We collected information on baseline patient characteristics, pathology details, radiotherapy dose, acute/late radiotherapy toxicity and outcome data (biochemical and clinical control). The RTOG/EORTC criteria were used to evaluate radiotherapy toxicities. We used ASTRO definition to define biochemical failure following EBRT. Survival rate was determined using the Kaplan-Meier life table analysis. Results: Median follow-up was 31.2 months (3.2 - 104.5).Biochemical failure free survival at 36 months was 79.6% for adjuvant radiotherapy compared to 62.8% for salvage radiotherapy (p= 0.2919), which are similar to results published from clinical trials.
1032 poster MLN8054, A NOVEL INHIBITOR OF AURORA KINASE A SENSITIZES ANDROGEN-RESISTANT PROSTATE CANCER MODELS TO RADIATION L. Moretti1 2 3 , K. Niermann2 3 4 , S. Schleicher5 , K. W. Kim5 , P. Kopsombut5 , D. K. Jung5 , B. Lu2 3 4 1 I NSTITUT J. B ORDET, Department of Radiation Oncology, Brussels, Belgium 2 VANDERBILT-I NGRAM C ANCER C ENTER, Nashville, USA 3 VANDERBILT U NIVERSITY M EDICAL C ENTER, Department of Radiation Oncology, Nashville, Tennessee, USA 4 VANDERBILT S CHOOL OF M EDICINE, Nashville, Tennessee, USA 5 VANDERBILT S CHOOL OF M EDICINE, Department of Radiation Oncology, Nashville, Tennessee, USA Purpose: Despite multi-modality treatment, the existence of androgenresistant subpopulations in prostate cancer poses an important therapeutic problem. Expression of Aurora kinase A (AURKA) is increased in human prostate cancer and has been correlated with poor prognosis and cancer progression. Because MLN8054, a specific small-molecule inhibitor of AURKA has been shown to delay G2/M progression and to inhibit proliferation in human prostate carcinoma, we evaluated MLN8054 as a potential radiosensitizer in androgen-insensitive prostate cancer models. Materials: PC3 and DU145 androgen-insensitive prostate cancer cells were treated with various doses of MLN8054 for various time points to determine the cell cycle conditions that yielded maximal increase in G2/M phase and polyploidy cells. To assess DNA damage, γ -H2AX phosphorylation was quantified by immunofluorescence for cells grown under optimal radiosensitizing conditions and subjected to either 0 (control) or 5 Gy radiation. Clonogenic assays of these cells were performed to determine radiosensitivity. A hind limb prostate cancer mouse model was used to study tumor growth delay in vivo. Using immunohistochemistry, tumor sections from prostate cancer xenografts were analyzed for cell proliferation (Ki67), angiogenesis (Von Willebrandt), and apoptosis (caspase-3). Results: We found that inhibition of AURKA by MLN8054 sensitized prostate cancer cell lines, as determined by clonogenic assay (PC3: DER=1.37, p=0.02; DU145: DER=1.27, p=0.019). In both cell lines, 1μM MLN8054 induced significant G2/M accumulation, polyploidy, and DNA damage (PC3: 100% vs. 76%, p=0.035; DU145: 100% vs. 69.33%, p=0.034). In vivo, the addition of MLN8054 to radiation significantly increased tumor growth delay and apoptosis, with reduction in cell proliferation and vascular density. Conclusions: MLN8054, a novel small-molecule AURKA inhibitor enhances the cytotoxic effects of radiation on prostate cancer and its vasculature both in vitro and in vivo, and extends tumor growth delay. Our findings warrant clinical trials to determine the full potential of this combination therapy in patients with prostate cancer.
Conclusions: Our study have demonstrated superior freedom from biochemical failure (FFBF) with adjuvant radiotherapy compared to salvage radiotherapy treatment, in keeping with results from clinical trials and the incidence of grade 3 and 4 acute/late toxicities are within acceptable limits. Currently our patients are enrolled into the RADICALS trial which is also evaluating the role of androgen deprivation therapy in this setting. 1034 poster POSTOPERATIVE HIGH DOSE CONFORMAL RADIOTHERAPY IN PATIENTS WITH HIGH RISK PROSTATE CANCER R. Bellavita1 , M. Massetti1 , F. Arcidiacono1 , V. Radicchia1 , F. Matrone1 , G. Montesi1 , I. Abraha2 , C. Aristei3 1 U NIVERSITY OF P ERUGIA, Department of Radiation Oncology, Perugia, Italy 2 U NIVERSITY OF P ERUGIA, Epidemiology, Perugia, Italy 3 U NIVERSITY OF P ERUGIA - S.M. DELLA M ISERICORDIA H OSPITAL, Department of Radiation Oncology, Perugia, Italy Purpose: To evaluate treatment outcome and toxicity of three-dimensional conformal radiotherapy (3D-CRT) after radical prostatectomy (RP). Materials: From August 1998 to December 2007, 214 patients with positive resection margin and/or pT3-4 or N+ prostatic adenocarcinoma underwent postoperative 3D-CRT. Patient characteristics were as follows: median age 65 years (range 51-77); stage pT2N0 in 48 patients (22%), pT3aN0 in 41 patients (19%), pT3bN0 in 76 (36%), pT4N0 in 17 (8%), N+ in 32 (15%); positive margins in 158 patients (74%); Gleason score (GS) 2-6 in 43 patients (20%), 7 in 91 (42%), and 8-10 in 80 (37%). Median preoperative and pre RT PSA values were 7.93 ng/ml (range 0.57-166) and 0.05 ng/ml (range 0.0026,39) respectively. Median time from surgery to RT was 5.3 months (range 1.2-8.8); 150 patients (70%) received hormonal therapy (HT) with LHRH analogue and/or antiandrogen. 3D-CRT was delivered with 15-18 MV photons to the tumor bed in 182 patients (85%) and to the regional nodes in the 32
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were also qualitatively reviewed for concordance. Results: Patients remained immobilized throughout the procedure. X-ray data was analyzed for 3 procedures to date. The average elapsed time between MRI imaging and the dummy cable check immediately prior to treatment delivery was 81 minutes. Images of the first procedure were analyzed offline, whereby no offset corrections were applied to the treatment plan prior to delivery. Mean SI error between actual and planned conditions was 1.8 mm (SD 1.4mm). First dwell position depth error exceeded MRI voxel resolution in 3/18 catheters, up to 5mm. For the subsequent procedures, offset corrections were applied to the treatment plan prior to delivery. Qualitative image review was concordant with the measured depth errors for all catheters. Depth errors were not predicted by inspecting shifts at the template surface. The first dwell position was revised in 6/29 catheters, with a mean SI correction of -2mm (range -4 to 4mm).
Conclusions: Catheter depth errors were identified despite controlled conditions and relatively short elapsed times between MRI imaging and treatment delivery. Online X-ray imaging can improve SI accuracy by increasing the image resolution of the first dwell position to sub-millimeter scale, and correction of the treatment plan based on the actual depth of the first dwell position
1033 poster OUTCOME AUDIT ON POST-OPERATIVE PROSTATE RADIOTHERAPY S. Vengalil1 , L. Shum1 1
B ELFAST C ITY H OSPITAL, Clinical Oncology, Belfast, United Kingdom
Purpose: BackgroundThe role of post-prostatectomy radiotherapy remains controversial.There is uncertainty whether post-prostatectomy radiotherapy should be administered adjuvantly or for salvage when PSA level rises. But there is mounting evidence that immediate radiotherapy in high risk clinicopathological cases is superior to observation alone. Studies have demonstrated improved biochemical control and/or disease free survival with adjuvant radiotherapy, but it’s benefit in terms of overall survival is not clear. Approximately 15-40% of patients will experience a biochemical recurrence within 10 years after surgery. The factors which identify risk of biochemical failure include positive surgical margins, Gleason score, extra-capsular extension, seminal vesicle invasion, positive lymph nodes and pre-operative PSA levels.ObjectivesTo evaluate outcome and toxicities of adjuvant and salvage radiotherapy treatment following radical prostatectomy and compare with standards published from clinical trials. Materials: Retrospective review of case notes of patients who received postprostatectomy radiotherapy between January 2000 and December 2008 at our institution. We collected information on baseline patient characteristics, pathology details, radiotherapy dose, acute/late radiotherapy toxicity and outcome data (biochemical and clinical control). The RTOG/EORTC criteria were used to evaluate radiotherapy toxicities. We used ASTRO definition to define biochemical failure following EBRT. Survival rate was determined using the Kaplan-Meier life table analysis. Results: Median follow-up was 31.2 months (3.2 - 104.5).Biochemical failure free survival at 36 months was 79.6% for adjuvant radiotherapy compared to 62.8% for salvage radiotherapy (p= 0.2919), which are similar to results published from clinical trials.
1032 poster MLN8054, A NOVEL INHIBITOR OF AURORA KINASE A SENSITIZES ANDROGEN-RESISTANT PROSTATE CANCER MODELS TO RADIATION L. Moretti1 2 3 , K. Niermann2 3 4 , S. Schleicher5 , K. W. Kim5 , P. Kopsombut5 , D. K. Jung5 , B. Lu2 3 4 1 I NSTITUT J. B ORDET, Department of Radiation Oncology, Brussels, Belgium 2 VANDERBILT-I NGRAM C ANCER C ENTER, Nashville, USA 3 VANDERBILT U NIVERSITY M EDICAL C ENTER, Department of Radiation Oncology, Nashville, Tennessee, USA 4 VANDERBILT S CHOOL OF M EDICINE, Nashville, Tennessee, USA 5 VANDERBILT S CHOOL OF M EDICINE, Department of Radiation Oncology, Nashville, Tennessee, USA Purpose: Despite multi-modality treatment, the existence of androgenresistant subpopulations in prostate cancer poses an important therapeutic problem. Expression of Aurora kinase A (AURKA) is increased in human prostate cancer and has been correlated with poor prognosis and cancer progression. Because MLN8054, a specific small-molecule inhibitor of AURKA has been shown to delay G2/M progression and to inhibit proliferation in human prostate carcinoma, we evaluated MLN8054 as a potential radiosensitizer in androgen-insensitive prostate cancer models. Materials: PC3 and DU145 androgen-insensitive prostate cancer cells were treated with various doses of MLN8054 for various time points to determine the cell cycle conditions that yielded maximal increase in G2/M phase and polyploidy cells. To assess DNA damage, γ -H2AX phosphorylation was quantified by immunofluorescence for cells grown under optimal radiosensitizing conditions and subjected to either 0 (control) or 5 Gy radiation. Clonogenic assays of these cells were performed to determine radiosensitivity. A hind limb prostate cancer mouse model was used to study tumor growth delay in vivo. Using immunohistochemistry, tumor sections from prostate cancer xenografts were analyzed for cell proliferation (Ki67), angiogenesis (Von Willebrandt), and apoptosis (caspase-3). Results: We found that inhibition of AURKA by MLN8054 sensitized prostate cancer cell lines, as determined by clonogenic assay (PC3: DER=1.37, p=0.02; DU145: DER=1.27, p=0.019). In both cell lines, 1μM MLN8054 induced significant G2/M accumulation, polyploidy, and DNA damage (PC3: 100% vs. 76%, p=0.035; DU145: 100% vs. 69.33%, p=0.034). In vivo, the addition of MLN8054 to radiation significantly increased tumor growth delay and apoptosis, with reduction in cell proliferation and vascular density. Conclusions: MLN8054, a novel small-molecule AURKA inhibitor enhances the cytotoxic effects of radiation on prostate cancer and its vasculature both in vitro and in vivo, and extends tumor growth delay. Our findings warrant clinical trials to determine the full potential of this combination therapy in patients with prostate cancer.
Conclusions: Our study have demonstrated superior freedom from biochemical failure (FFBF) with adjuvant radiotherapy compared to salvage radiotherapy treatment, in keeping with results from clinical trials and the incidence of grade 3 and 4 acute/late toxicities are within acceptable limits. Currently our patients are enrolled into the RADICALS trial which is also evaluating the role of androgen deprivation therapy in this setting. 1034 poster POSTOPERATIVE HIGH DOSE CONFORMAL RADIOTHERAPY IN PATIENTS WITH HIGH RISK PROSTATE CANCER R. Bellavita1 , M. Massetti1 , F. Arcidiacono1 , V. Radicchia1 , F. Matrone1 , G. Montesi1 , I. Abraha2 , C. Aristei3 1 U NIVERSITY OF P ERUGIA, Department of Radiation Oncology, Perugia, Italy 2 U NIVERSITY OF P ERUGIA, Epidemiology, Perugia, Italy 3 U NIVERSITY OF P ERUGIA - S.M. DELLA M ISERICORDIA H OSPITAL, Department of Radiation Oncology, Perugia, Italy Purpose: To evaluate treatment outcome and toxicity of three-dimensional conformal radiotherapy (3D-CRT) after radical prostatectomy (RP). Materials: From August 1998 to December 2007, 214 patients with positive resection margin and/or pT3-4 or N+ prostatic adenocarcinoma underwent postoperative 3D-CRT. Patient characteristics were as follows: median age 65 years (range 51-77); stage pT2N0 in 48 patients (22%), pT3aN0 in 41 patients (19%), pT3bN0 in 76 (36%), pT4N0 in 17 (8%), N+ in 32 (15%); positive margins in 158 patients (74%); Gleason score (GS) 2-6 in 43 patients (20%), 7 in 91 (42%), and 8-10 in 80 (37%). Median preoperative and pre RT PSA values were 7.93 ng/ml (range 0.57-166) and 0.05 ng/ml (range 0.0026,39) respectively. Median time from surgery to RT was 5.3 months (range 1.2-8.8); 150 patients (70%) received hormonal therapy (HT) with LHRH analogue and/or antiandrogen. 3D-CRT was delivered with 15-18 MV photons to the tumor bed in 182 patients (85%) and to the regional nodes in the 32