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PO-0679 OPTIMAL OUTCOME AFTER PERMANENT SEED PROSTATE BRACHYTHERAPY: THE TRIFECTA ANALYSIS
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ESTRO 31
PO-0678 HYPOFRACTIONATION WITH ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER: RESULTS AT 8 YEARS M. Yassa1, B. Fortin1, M.A. Fortin2, C. Lambert3, T.V. Nguyen3, J.P. Bahary3 1 Maisonneuve-Rosemont Hospital, Radiation Oncology, Montréal, Canada 2 Cité de la Santé, Radiation Oncology, Laval, Canada 3 CHUM - Notre-Dame Hospital, Radiation Oncology, Montréal, Canada
Conclusions: Late radiation-induced toxicity, particularly urinary incontinence and rectal pain, has a significant impact on HRQoL. Based on this outcome we recommend the clinical practice to focus more on limiting the incidences of these toxicities in order to optimize patients' health realted quality of life. PO-0677 EXTERNAL BEAM PROSTATE RADIOTHERAPY: ANORECTAL TOXICITY AND THE INFLUENCE OF ENDORECTAL BALLOONS R. Smeenk1, W.P.M. Hopman2, M. Kunze-Busch1, A.L. Hoffmann3, P. van Kollenburg1, E.N.J.T. van Lin1, J.H.A.M. Kaanders1 1 Radboud University Nijmegen Medical Center, Department of Radiation Oncology, Nijmegen, The Netherlands 2 Radboud University Nijmegen Medical Center, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands 3 MAASTRO clinic, Department of Radiation Oncology, Maastricht, The Netherlands Purpose/Objective: to identify anatomic structures involved in the development of fecal incontinence-related complaints after prostate RT and to investigate dose-effect relations for these structures. Also, to investigate whether an endorectal balloon (ERB) reduces doses to these structures and subsequently anorectal toxicity. Materials and Methods: firstly, two planning studies were performed, both in primary RT (78 Gy) and after prostatectomy (70 Gy), to compare doses to the anal wall (Awall) and rectal wall (Rwall) separately with and without ERB. Secondly, anorectal manometry and barostat testing was performed after prostate RT, and functions were correlated to specific anorectal complaints (incontinence, urgency, and frequency) and dose parameters. Thirdly, individual pelvic floor muscles were delineated and doses to these muscles were compared between patients with and without specific complaints. Subsequently, dose-effect curves were constructed. Finally, interfraction and intrafraction prostate motion were compared between patients with ERB and without ERB using real-time electromagnetic tracking. Results: in primary prostate RT, ERBs reduce Awall mean dose by 12 Gy (3D-CRT) and 7.5 Gy (IMRT), and it is shown that the Awall can be delineated consistently with and without ERB. After prostatectomy, ERBs reduce anorectal doses, especially regarding Awall (6 Gy mean dose reduction). Function testing shows significantly reduced anal squeeze pressure and tolerated Rwall pressure in patients with incontinence and/or urgency; patients with frequency have a reduced rectal capacity and sensory function. Dosimetry shows associations between urgency and several anal and rectal parameters and between incontinence and some anal parameters. No dose parameters are associated with frequency. Further analysis shows that urgency is associated with doses to all investigated pelvic floor muscles; incontinence is associated with the puborectalis muscle (PRM) and external anal sphincter (EAS). Dose-effect curves led to the following constraints regarding mean doses to reduce the risk of urgency: ≤30 Gy (internal anal sphincter), ≤10 Gy (EAS), ≤50 Gy (PRM) and ≤40 Gy (levator ani muscles). Patients treated with ERB reported less incontinence and urgency and received significantly lower doses to Awall, Rwall and all pelvic floor muscles. Finally, real-time tracking showed that ERBs significantly reduce intrafraction motion, suggesting that a 5 mm PTV margin suffices to correct for this motion. Interfraction variation is not reduced by ERBs. Conclusions: specific fecal incontinence-related complaints seem to originate from different anatomic regions, which should be accounted for in RT planning. ERBs reduce Awall, Rwall and pelvic floor muscle doses. Also, they reduce intrafraction prostate motion. These findings suggest that ERBs may reduce late anorectal toxicity.
Purpose/Objective: With a low alpha/beta ratio, prostate cancer (PC) reacts as a late-responding tissue with a higher sensitivity to larger fractions. Hypofractionated radiation may therefore lead to a therapeutic gain with decreased short term side-effects. The long term side effects of such a fractionation remain unknown. Long term results of a combined treatment of hypofractionation and hormone therapy are also unknown. Materials and Methods: Between 2001 and 2002, 42 patients with intermediate-risk PC as defined by the RTOG 9910 protocol were recruited for this study (stage T1b-T4 & gleason 2-6 & PSA 10-100 ug/L; or stage T1b-T4 & gleason 7 & PSA < 20 ug/L; or stage T1b-T1c & gleason > 8 & PSA < 20 ug/L). Treatment consisted of one leuprolide injection (4 month depot) combined with one month of oral antiandrogen. 3D conformal radiation started 8 weeks after the leuprolide injection delivering 57 Gy in 19 daily fractions (biological equivalent to 72 Gy in 36 fractions using an alpha/beta ratio of 1.5 Gy) to the prostate and proximal seminal vesicles. Pelvic nodes were not treated. Prostate localisation using ultrasound was performed daily. Toxicity was scored according to the NCI-CTC version 2 Genitourinary (GU) and Gastrointestinal (GI) scale. Treatment failure was noted if there was clinical evidence of local or distant recurrence, if hormone therapy was started or if there was a biochemical failure (PSA nadir plus 2 ug/L). Results: Acute toxicity has previously been presented and is acceptable. With a median follow-up of 8.4 years, overall survival is 90%, disease-specific survival is 97% and biochemical disease free survival (DFS) is 73%. Based on current classifications, 76% of patients had 'true' intermediate-risk PC (stage T2b-T2c or gleason score of 7 or PSA of 10-20 ug/L), with an 8 year DFS of 79%. Of note, 90% of patients renormalized their testosterone levels post treatment and DFS was not impacted by testosterone levels post treatment. At last follow-up, 82% of patients were asymptomatic. No chronic toxicity ≥ grade 3 was observed. Five patients (13%) had chronic grade 2 GU toxicity requiring alpha blocker medication. No patient had chronic grade 1 GU toxicity. One patient had chronic grade 1 and another had grade 2 GI toxicity. Conclusions: Hypofractionated radiotherapy with combined androgen deprivation is safe and effective in intermediate-risk PC with no increased long term toxicity and good results after 8 years of followup. A current Canadian phase 3 trial (PROFIT trial) is comparing a similar fractionation to 78 Gy in 39 fractions but without androgen deprivation. With the growing evidence in the literature of the benefit from using a combination of hormone and radiation therapy for intermediate-risk prostate cancer patients, our treatment scheme should also be studied in a phase 3 trials PO-0679 OPTIMAL OUTCOME AFTER PERMANENT SEED PROSTATE BRACHYTHERAPY: THE TRIFECTA ANALYSIS 1 2 1 1 A. Tétreault-Laflamme , T. Zilli , G. Delouya , D. Taussky 1 Centre Hospitalier de l'Université de Montréal, Radiation Oncology, Montréal, Canada 2 Hopital Universitaire de Genève, Radiation Oncology, Genève, Switzerland Purpose/Objective: High rates of tumor control have been observed in patients with low- and intermediate-risk prostate cancers treated with permanent seed prostate brachytherapy (PB). While this remains the primary objective, current trends aim at limiting the treatmentrelated toxicities of PB. The purpose of this study was to assess in a combined analysis (Trifecta) the optimal outcome for patients treated with exclusive permanent seed PB, as defined by the likelihood of achieving disease control and preserve normal urinary and sexual functions. Materials and Methods: 384 patients with localized prostate cancer were treated with PB at our institution between 2005 and 2010. Excluding patients without erectile dysfunction (ED) not responding to medication (grade 3 from the Common Terminology Criteria for Adverse Events version 3.0, CTCAE v 3.0) and with a minimal follow-
ESTRO 31
up of one year, a total of 233 patients were considered for the analysis. All patients were implanted with 125I using an intraoperative, inverse planned PB technique at a dose of 144 Gy. Biochemical control (BC), genito-urinary (GU) and sexual toxicity rates were assessed. Patients with concurrent BC, no GU toxicity and preserved sexual potency at 1, 2, 3, and 4 years were classified in the Trifecta group. BC was defined as prostate-specific antigen (PSA) level lower than the preceding PSA and as a PSA ≤ 0,5ng/mL for years 1 and 2 and for years 3 and 4, respectively. Absence of GU toxicity was defined as an International Prostate Symptom Score (IPSS) of no more than three points higher than baseline score at 1 year and as the complete absence of GU toxicity (CTCAE v 3.0 grade 0) on years 2 to 4. Patients with Grade 0 to 2 ED (2 = medication necessary) were deemed as sexually potent. Multivariate analysis was performed to predict for Trifecta at 1, 2 and 3 years in 111 patients with complete data set on each point in time from years 1-3. Results: Trifecta endpoints were achieved in 70% (n=163), 47.4% (n=83), 48.1% (n=50) and 54.5% (n=30) of the patients on years 1 to 4 after PB, respectively. The BC rates were 100%, 76.2%, 64.6% and 75.4% at 1, 2, 3 and 4 years, respectively. The corresponding potency rates were 93.6%, 90%, 93.7% and 95.2%, while the rates of Grade 0 GU toxicity were 74.2%, 61%, 73.3% and 74.6%. In the multivariate analysis, prostate D90 (p=0.047) and V100 (p=0.021) on year 1, and age at year 2 (p=0.038) and 3 (p=0.032) were significant predictors of Trifecta. Conclusions: The Trifecta endpoints were achieved approximately in 50% of the patients in the time range varying from years 2 to 4 after PB. The most common reason excluding patients from the Trifecta group remained urinary toxicity. Although our criteria for Trifecta were very strict, results of this series were comparable with previous prostatectomy studies. PO-0680 DOSIMETRIC COMPARISON OF FORWARD PLANNED IMRT (F-IMRT), INVERSE PLANNED IMRT (I-IMRT) AND VMAT FOR PROSTATE CANCER M. Singhera1, E. Selvadurai1, G. Smythe1, A. Creak1, A. Horwich1, R. Huddart1, D. Dearnaley1 1 The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Academic Urology Unit, Sutton, United Kingdom Purpose/Objective: To perform a dosimetric analysis of f-IMRT,i-IMRT and VMAT for prostate cancer radiotherapy. Materials and Methods: CT datasets and contours of 8 prostate cancer patients randomised within the Conventional or Hypofrationated High dose intensity modulated radiotherapy (CHHiP) trial were used to create IMRT and VMAT plans using Pinnacle. These were compared to the clinical f-IMRT plans. Planning objectives for the planning target volumes (PTVs) and organs at risk (OARs) were as per the CHHiP protocol. f-IMRT plans were forward planned using 3 multi-segmented beams. iIMRT plans had 5 multi-segmented beams using the step and shoot technique. VMAT plans were produced using a single arc which rotated from 179-181 degrees at a 5 degree collimator angle with variable dose rate and control points at 0.4cm/degree. D2%, D98%, homogeneity index (HI), conformity index (CI) and mean dose to each PTV was analysed. We analysed dose as per CHHiP trial dose constraints and mean dose for the rectum and bladder, V60 for the urethral bulb and V50 for the bowel and femoral heads. Dosimetric analysis was done using the paired t-test. Results: There was no statistical difference in mean dose, HI and CI of the PTVs and dose to OARs between the 3 modalities. Mean monitor units (MUs) were 284 for f-IMRT, 334 for i-IMRT and 387 for VMAT. MUs were significantly higher for VMAT compared with i-IMRT (p=0.009) and for i-IMRT compared with f-IMRT (P=0.0005) Conclusions: f-IMRT planning techniques as used in the CHHiP trial provide comparative dosimetry to PTVs and OARs. Contrary to published data, we report increased MUs with VMAT. Further research into planning and treatment time is needed to ascertain whether VMAT provides a temporal advantage thus allowing for reduced intrafraction movement and increasing throughput which will have financial implications. PO-0681 REACHING PSA NADIR UNDER 0.35 NG/ML AFTER 2 YEARS FOLLOWING BRACHYTHERAPY PREDICTS BIOCHEMICAL CONTROL A. Guarneri1, A. Botticella1, F. Munoz1, M. Levis1, R. Ragona1, A. Filippi1, U. Ricardi1 1 S. Giovanni Battista Hospital-University of Torino, Radiation Oncology Unit, Torino, Italy
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Purpose/Objective: After definitive radiotherapy, prolonged time to radiation-induced prostate cancer cells death and normal PSAproducing epithelium make difficult to estabilish a PSA threshold for tumor control. To date, several reports have attempted to link PSA decrease after external beam radiotherapy and biochemical outcome, but PSA post-treatment kinetics after brachytherapy (BRT) is poorly defined. Purpose of this study is to determine the significance of the nadir PSA (nPSA) and of the time to nPSA (TnPSA) in predicting biochemical outcome in early-stage prostate adenocarcinoma patients after BRT. Materials and Methods: We retrospectively analyzed 113 early-stage prostate adenocarcinoma patients undergoing BRT with permanent implant of 125I as monotherapy. Exclusion criteria were: follow-up time <12 months and administration of any form of androgendeprivation therapy. Median age was 68 years. Median and mean pretreatment zenith PSA were 6.3 ng/mL (range: 1,5-11 ng/mL). Respectively, 74 (65.5%) and 31 (27.5%) patients were classified as low-risk and intermediate-risk according to D'Amico risk group stratification. In 8 patients (7%), risk group was not determinate due to a non-determinable Gleason Score. The ASTRO Phoenix definition (nadir + 2 ng/mL) was used to define PSA failure. Biochemical Disease-Free Survival (bDFS) was considered as endpoint. Survival functions were determined using Kaplan-Meier method and Cox regression with proportions tested with the log-rank test Results: With a median follow-up of 43.7 months (range, 12.4-107.9 months), 3- and 5-years bDFS were 95.8% and 89.1%, respectively. As the median nadir value in this population, a nPSA value of 0.35 ng/mL was selected as cut-off. Thirthy-seven (32.7%) patients reached their nPSA in less than 24 months, and 76 (67.3%) in more than 24 months. Out of 37 patients reaching nPSA within 24 months, 13 had a nPSA under the cut-off value of 0.35 ng/mL and 24 above. Nine biochemical relapses were recorded (9/37, 24.3%), eight of whom (88.9%) in the group with nPSA above 0.35 ng/mL (p=0.08). No other relapses were recorded in the 76 remaining patients. On multivariate analysis, a nPSA <0.35 ng/mL in a time interval >24 months was independently associated with enhanced bDFS (p=0.013 and p=0.038, respectively). Conclusions: Patients who attain a nPSA <0.35 ng/mL with a TnPSA >24 months were significantly more likely to experience freedom from biochemical failure. PO-0682 OUTCOMES FOLLOWING PERMANENT BRACHYTHERAPY IN JAPANESE PATIENTS WITH INTERMEDIATE-RISK PROSTATE CANCER N. Katayama1, M. Takemoto2, T. Ogata1, T. Waki1, K. Katsui1, K. Bekku3, R. Tanimoto3, S. Ebara3, Y. Nasu3, S. Kanazawa1 1 Okayama University Hospital, Radiology, Okayama, Japan 2 Japanese Red Cross Society Himeji Hospital, Radiology, Himeji, Japan 3 Okayama University Hospital, Urology, Okayama, Japan Purpose/Objective: Few reports of outcome following permanent prostate brachytherapy (PPB) in Japanese patients with intermediaterisk prostate cancer (PCa) are available. The 7 year experience of permanent brachytherapy monotherapy at a single centre for Japanese patients with intermediate-risk PCa is reported. Materials and Methods: From February 2004 to November 2011, 224 consecutive Japanese patients with clinically localized PCa classified as intermediate-risk based on National Comprehensive Cancer Network (NCCN) guidelines were treated with PPB. All patients were treated with iodine-125 seeds (prescription dose 144 Gy). No patient received supplemental external beam; 43.3% received neoadjuvant hormone therapy (NAHT). The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Biochemical recurrence (BCR) was analyzed by the Phoenix (nadir + 2 ng/ml) definition. Urinary and rectal morbidity was evaluated using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. The KaplanMeier method was used to calculate rates of BCR, disease specific survival (DSS), and overall survival (OS). The log-rank test was used for univariate analysis to compare BCR rates between patient subsets. Cox regression analysis was used for multivariate analysis. Results: The mean age was 66.9 (range, 50-78) years. Median followup was 48.2 months (range, 1.0-88.5 months). The 5-year biochemical BCR, DSS, and OS rates were 87.3%, 98.6%, and 96.3%, respectively. Grade 2 urinary and rectal toxicity was observed in 1.4% and 0.9%, respectively. No patients had greater than grade 2 toxicity. On univariate analysis, the Gleason score (GS) was a significant predicting factor for BCR (p = 0.003). Patients with GS 4+3 showed higher BCR rates than patients with GS 3+4 (p = 0.017), although patients with GS
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PO-0678 HYPOFRACTIONATION WITH ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER: RESULTS AT 8 YEARS M. Yassa1, B. Fortin1, M.A. Fortin2, C. Lambert3, T.V. Nguyen3, J.P. Bahary3 1 Maisonneuve-Rosemont Hospital, Radiation Oncology, Montréal, Canada 2 Cité de la Santé, Radiation Oncology, Laval, Canada 3 CHUM - Notre-Dame Hospital, Radiation Oncology, Montréal, Canada
Conclusions: Late radiation-induced toxicity, particularly urinary incontinence and rectal pain, has a significant impact on HRQoL. Based on this outcome we recommend the clinical practice to focus more on limiting the incidences of these toxicities in order to optimize patients' health realted quality of life. PO-0677 EXTERNAL BEAM PROSTATE RADIOTHERAPY: ANORECTAL TOXICITY AND THE INFLUENCE OF ENDORECTAL BALLOONS R. Smeenk1, W.P.M. Hopman2, M. Kunze-Busch1, A.L. Hoffmann3, P. van Kollenburg1, E.N.J.T. van Lin1, J.H.A.M. Kaanders1 1 Radboud University Nijmegen Medical Center, Department of Radiation Oncology, Nijmegen, The Netherlands 2 Radboud University Nijmegen Medical Center, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands 3 MAASTRO clinic, Department of Radiation Oncology, Maastricht, The Netherlands Purpose/Objective: to identify anatomic structures involved in the development of fecal incontinence-related complaints after prostate RT and to investigate dose-effect relations for these structures. Also, to investigate whether an endorectal balloon (ERB) reduces doses to these structures and subsequently anorectal toxicity. Materials and Methods: firstly, two planning studies were performed, both in primary RT (78 Gy) and after prostatectomy (70 Gy), to compare doses to the anal wall (Awall) and rectal wall (Rwall) separately with and without ERB. Secondly, anorectal manometry and barostat testing was performed after prostate RT, and functions were correlated to specific anorectal complaints (incontinence, urgency, and frequency) and dose parameters. Thirdly, individual pelvic floor muscles were delineated and doses to these muscles were compared between patients with and without specific complaints. Subsequently, dose-effect curves were constructed. Finally, interfraction and intrafraction prostate motion were compared between patients with ERB and without ERB using real-time electromagnetic tracking. Results: in primary prostate RT, ERBs reduce Awall mean dose by 12 Gy (3D-CRT) and 7.5 Gy (IMRT), and it is shown that the Awall can be delineated consistently with and without ERB. After prostatectomy, ERBs reduce anorectal doses, especially regarding Awall (6 Gy mean dose reduction). Function testing shows significantly reduced anal squeeze pressure and tolerated Rwall pressure in patients with incontinence and/or urgency; patients with frequency have a reduced rectal capacity and sensory function. Dosimetry shows associations between urgency and several anal and rectal parameters and between incontinence and some anal parameters. No dose parameters are associated with frequency. Further analysis shows that urgency is associated with doses to all investigated pelvic floor muscles; incontinence is associated with the puborectalis muscle (PRM) and external anal sphincter (EAS). Dose-effect curves led to the following constraints regarding mean doses to reduce the risk of urgency: ≤30 Gy (internal anal sphincter), ≤10 Gy (EAS), ≤50 Gy (PRM) and ≤40 Gy (levator ani muscles). Patients treated with ERB reported less incontinence and urgency and received significantly lower doses to Awall, Rwall and all pelvic floor muscles. Finally, real-time tracking showed that ERBs significantly reduce intrafraction motion, suggesting that a 5 mm PTV margin suffices to correct for this motion. Interfraction variation is not reduced by ERBs. Conclusions: specific fecal incontinence-related complaints seem to originate from different anatomic regions, which should be accounted for in RT planning. ERBs reduce Awall, Rwall and pelvic floor muscle doses. Also, they reduce intrafraction prostate motion. These findings suggest that ERBs may reduce late anorectal toxicity.
Purpose/Objective: With a low alpha/beta ratio, prostate cancer (PC) reacts as a late-responding tissue with a higher sensitivity to larger fractions. Hypofractionated radiation may therefore lead to a therapeutic gain with decreased short term side-effects. The long term side effects of such a fractionation remain unknown. Long term results of a combined treatment of hypofractionation and hormone therapy are also unknown. Materials and Methods: Between 2001 and 2002, 42 patients with intermediate-risk PC as defined by the RTOG 9910 protocol were recruited for this study (stage T1b-T4 & gleason 2-6 & PSA 10-100 ug/L; or stage T1b-T4 & gleason 7 & PSA < 20 ug/L; or stage T1b-T1c & gleason > 8 & PSA < 20 ug/L). Treatment consisted of one leuprolide injection (4 month depot) combined with one month of oral antiandrogen. 3D conformal radiation started 8 weeks after the leuprolide injection delivering 57 Gy in 19 daily fractions (biological equivalent to 72 Gy in 36 fractions using an alpha/beta ratio of 1.5 Gy) to the prostate and proximal seminal vesicles. Pelvic nodes were not treated. Prostate localisation using ultrasound was performed daily. Toxicity was scored according to the NCI-CTC version 2 Genitourinary (GU) and Gastrointestinal (GI) scale. Treatment failure was noted if there was clinical evidence of local or distant recurrence, if hormone therapy was started or if there was a biochemical failure (PSA nadir plus 2 ug/L). Results: Acute toxicity has previously been presented and is acceptable. With a median follow-up of 8.4 years, overall survival is 90%, disease-specific survival is 97% and biochemical disease free survival (DFS) is 73%. Based on current classifications, 76% of patients had 'true' intermediate-risk PC (stage T2b-T2c or gleason score of 7 or PSA of 10-20 ug/L), with an 8 year DFS of 79%. Of note, 90% of patients renormalized their testosterone levels post treatment and DFS was not impacted by testosterone levels post treatment. At last follow-up, 82% of patients were asymptomatic. No chronic toxicity ≥ grade 3 was observed. Five patients (13%) had chronic grade 2 GU toxicity requiring alpha blocker medication. No patient had chronic grade 1 GU toxicity. One patient had chronic grade 1 and another had grade 2 GI toxicity. Conclusions: Hypofractionated radiotherapy with combined androgen deprivation is safe and effective in intermediate-risk PC with no increased long term toxicity and good results after 8 years of followup. A current Canadian phase 3 trial (PROFIT trial) is comparing a similar fractionation to 78 Gy in 39 fractions but without androgen deprivation. With the growing evidence in the literature of the benefit from using a combination of hormone and radiation therapy for intermediate-risk prostate cancer patients, our treatment scheme should also be studied in a phase 3 trials PO-0679 OPTIMAL OUTCOME AFTER PERMANENT SEED PROSTATE BRACHYTHERAPY: THE TRIFECTA ANALYSIS 1 2 1 1 A. Tétreault-Laflamme , T. Zilli , G. Delouya , D. Taussky 1 Centre Hospitalier de l'Université de Montréal, Radiation Oncology, Montréal, Canada 2 Hopital Universitaire de Genève, Radiation Oncology, Genève, Switzerland Purpose/Objective: High rates of tumor control have been observed in patients with low- and intermediate-risk prostate cancers treated with permanent seed prostate brachytherapy (PB). While this remains the primary objective, current trends aim at limiting the treatmentrelated toxicities of PB. The purpose of this study was to assess in a combined analysis (Trifecta) the optimal outcome for patients treated with exclusive permanent seed PB, as defined by the likelihood of achieving disease control and preserve normal urinary and sexual functions. Materials and Methods: 384 patients with localized prostate cancer were treated with PB at our institution between 2005 and 2010. Excluding patients without erectile dysfunction (ED) not responding to medication (grade 3 from the Common Terminology Criteria for Adverse Events version 3.0, CTCAE v 3.0) and with a minimal follow-
ESTRO 31
up of one year, a total of 233 patients were considered for the analysis. All patients were implanted with 125I using an intraoperative, inverse planned PB technique at a dose of 144 Gy. Biochemical control (BC), genito-urinary (GU) and sexual toxicity rates were assessed. Patients with concurrent BC, no GU toxicity and preserved sexual potency at 1, 2, 3, and 4 years were classified in the Trifecta group. BC was defined as prostate-specific antigen (PSA) level lower than the preceding PSA and as a PSA ≤ 0,5ng/mL for years 1 and 2 and for years 3 and 4, respectively. Absence of GU toxicity was defined as an International Prostate Symptom Score (IPSS) of no more than three points higher than baseline score at 1 year and as the complete absence of GU toxicity (CTCAE v 3.0 grade 0) on years 2 to 4. Patients with Grade 0 to 2 ED (2 = medication necessary) were deemed as sexually potent. Multivariate analysis was performed to predict for Trifecta at 1, 2 and 3 years in 111 patients with complete data set on each point in time from years 1-3. Results: Trifecta endpoints were achieved in 70% (n=163), 47.4% (n=83), 48.1% (n=50) and 54.5% (n=30) of the patients on years 1 to 4 after PB, respectively. The BC rates were 100%, 76.2%, 64.6% and 75.4% at 1, 2, 3 and 4 years, respectively. The corresponding potency rates were 93.6%, 90%, 93.7% and 95.2%, while the rates of Grade 0 GU toxicity were 74.2%, 61%, 73.3% and 74.6%. In the multivariate analysis, prostate D90 (p=0.047) and V100 (p=0.021) on year 1, and age at year 2 (p=0.038) and 3 (p=0.032) were significant predictors of Trifecta. Conclusions: The Trifecta endpoints were achieved approximately in 50% of the patients in the time range varying from years 2 to 4 after PB. The most common reason excluding patients from the Trifecta group remained urinary toxicity. Although our criteria for Trifecta were very strict, results of this series were comparable with previous prostatectomy studies. PO-0680 DOSIMETRIC COMPARISON OF FORWARD PLANNED IMRT (F-IMRT), INVERSE PLANNED IMRT (I-IMRT) AND VMAT FOR PROSTATE CANCER M. Singhera1, E. Selvadurai1, G. Smythe1, A. Creak1, A. Horwich1, R. Huddart1, D. Dearnaley1 1 The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Academic Urology Unit, Sutton, United Kingdom Purpose/Objective: To perform a dosimetric analysis of f-IMRT,i-IMRT and VMAT for prostate cancer radiotherapy. Materials and Methods: CT datasets and contours of 8 prostate cancer patients randomised within the Conventional or Hypofrationated High dose intensity modulated radiotherapy (CHHiP) trial were used to create IMRT and VMAT plans using Pinnacle. These were compared to the clinical f-IMRT plans. Planning objectives for the planning target volumes (PTVs) and organs at risk (OARs) were as per the CHHiP protocol. f-IMRT plans were forward planned using 3 multi-segmented beams. iIMRT plans had 5 multi-segmented beams using the step and shoot technique. VMAT plans were produced using a single arc which rotated from 179-181 degrees at a 5 degree collimator angle with variable dose rate and control points at 0.4cm/degree. D2%, D98%, homogeneity index (HI), conformity index (CI) and mean dose to each PTV was analysed. We analysed dose as per CHHiP trial dose constraints and mean dose for the rectum and bladder, V60 for the urethral bulb and V50 for the bowel and femoral heads. Dosimetric analysis was done using the paired t-test. Results: There was no statistical difference in mean dose, HI and CI of the PTVs and dose to OARs between the 3 modalities. Mean monitor units (MUs) were 284 for f-IMRT, 334 for i-IMRT and 387 for VMAT. MUs were significantly higher for VMAT compared with i-IMRT (p=0.009) and for i-IMRT compared with f-IMRT (P=0.0005) Conclusions: f-IMRT planning techniques as used in the CHHiP trial provide comparative dosimetry to PTVs and OARs. Contrary to published data, we report increased MUs with VMAT. Further research into planning and treatment time is needed to ascertain whether VMAT provides a temporal advantage thus allowing for reduced intrafraction movement and increasing throughput which will have financial implications. PO-0681 REACHING PSA NADIR UNDER 0.35 NG/ML AFTER 2 YEARS FOLLOWING BRACHYTHERAPY PREDICTS BIOCHEMICAL CONTROL A. Guarneri1, A. Botticella1, F. Munoz1, M. Levis1, R. Ragona1, A. Filippi1, U. Ricardi1 1 S. Giovanni Battista Hospital-University of Torino, Radiation Oncology Unit, Torino, Italy
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Purpose/Objective: After definitive radiotherapy, prolonged time to radiation-induced prostate cancer cells death and normal PSAproducing epithelium make difficult to estabilish a PSA threshold for tumor control. To date, several reports have attempted to link PSA decrease after external beam radiotherapy and biochemical outcome, but PSA post-treatment kinetics after brachytherapy (BRT) is poorly defined. Purpose of this study is to determine the significance of the nadir PSA (nPSA) and of the time to nPSA (TnPSA) in predicting biochemical outcome in early-stage prostate adenocarcinoma patients after BRT. Materials and Methods: We retrospectively analyzed 113 early-stage prostate adenocarcinoma patients undergoing BRT with permanent implant of 125I as monotherapy. Exclusion criteria were: follow-up time <12 months and administration of any form of androgendeprivation therapy. Median age was 68 years. Median and mean pretreatment zenith PSA were 6.3 ng/mL (range: 1,5-11 ng/mL). Respectively, 74 (65.5%) and 31 (27.5%) patients were classified as low-risk and intermediate-risk according to D'Amico risk group stratification. In 8 patients (7%), risk group was not determinate due to a non-determinable Gleason Score. The ASTRO Phoenix definition (nadir + 2 ng/mL) was used to define PSA failure. Biochemical Disease-Free Survival (bDFS) was considered as endpoint. Survival functions were determined using Kaplan-Meier method and Cox regression with proportions tested with the log-rank test Results: With a median follow-up of 43.7 months (range, 12.4-107.9 months), 3- and 5-years bDFS were 95.8% and 89.1%, respectively. As the median nadir value in this population, a nPSA value of 0.35 ng/mL was selected as cut-off. Thirthy-seven (32.7%) patients reached their nPSA in less than 24 months, and 76 (67.3%) in more than 24 months. Out of 37 patients reaching nPSA within 24 months, 13 had a nPSA under the cut-off value of 0.35 ng/mL and 24 above. Nine biochemical relapses were recorded (9/37, 24.3%), eight of whom (88.9%) in the group with nPSA above 0.35 ng/mL (p=0.08). No other relapses were recorded in the 76 remaining patients. On multivariate analysis, a nPSA <0.35 ng/mL in a time interval >24 months was independently associated with enhanced bDFS (p=0.013 and p=0.038, respectively). Conclusions: Patients who attain a nPSA <0.35 ng/mL with a TnPSA >24 months were significantly more likely to experience freedom from biochemical failure. PO-0682 OUTCOMES FOLLOWING PERMANENT BRACHYTHERAPY IN JAPANESE PATIENTS WITH INTERMEDIATE-RISK PROSTATE CANCER N. Katayama1, M. Takemoto2, T. Ogata1, T. Waki1, K. Katsui1, K. Bekku3, R. Tanimoto3, S. Ebara3, Y. Nasu3, S. Kanazawa1 1 Okayama University Hospital, Radiology, Okayama, Japan 2 Japanese Red Cross Society Himeji Hospital, Radiology, Himeji, Japan 3 Okayama University Hospital, Urology, Okayama, Japan Purpose/Objective: Few reports of outcome following permanent prostate brachytherapy (PPB) in Japanese patients with intermediaterisk prostate cancer (PCa) are available. The 7 year experience of permanent brachytherapy monotherapy at a single centre for Japanese patients with intermediate-risk PCa is reported. Materials and Methods: From February 2004 to November 2011, 224 consecutive Japanese patients with clinically localized PCa classified as intermediate-risk based on National Comprehensive Cancer Network (NCCN) guidelines were treated with PPB. All patients were treated with iodine-125 seeds (prescription dose 144 Gy). No patient received supplemental external beam; 43.3% received neoadjuvant hormone therapy (NAHT). The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Biochemical recurrence (BCR) was analyzed by the Phoenix (nadir + 2 ng/ml) definition. Urinary and rectal morbidity was evaluated using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. The KaplanMeier method was used to calculate rates of BCR, disease specific survival (DSS), and overall survival (OS). The log-rank test was used for univariate analysis to compare BCR rates between patient subsets. Cox regression analysis was used for multivariate analysis. Results: The mean age was 66.9 (range, 50-78) years. Median followup was 48.2 months (range, 1.0-88.5 months). The 5-year biochemical BCR, DSS, and OS rates were 87.3%, 98.6%, and 96.3%, respectively. Grade 2 urinary and rectal toxicity was observed in 1.4% and 0.9%, respectively. No patients had greater than grade 2 toxicity. On univariate analysis, the Gleason score (GS) was a significant predicting factor for BCR (p = 0.003). Patients with GS 4+3 showed higher BCR rates than patients with GS 3+4 (p = 0.017), although patients with GS