- Email: [email protected]
PO-0682 OUTCOMES FOLLOWING PERMANENT BRACHYTHERAPY IN JAPANESE PATIENTS WITH INTERMEDIATE-RISK PROSTATE CANCER
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
S265
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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3+4 was not a significant predicting factor for BCR in comparison with patients with GS 3+3 (p = 0.39). Multivariate analysis indicated that GS was significantly associated with BCR (p = 0.004), and initial prostate-specific antigen (PSA) level tended to be associated with BCR (p = 0.061), while age, prostate volume, T stage, NAHT, and dose irradiating 90% of the prostate volume (prostate D90) were insignificant. Conclusions: Our outcomes following PPB in Japanese patients with intermediate-risk PCa were in agreement with those of larger published series in Western patients. GS were significantly associated with BCR, and especially GS 4+3 carried a bad BCR prognosis. PO-0683 CBCT ADAPTIVE PROTOCOL TO REDUCE PTV-RECTUM INTERSECTION IN THE PROSTATE RADIOTHERAPY G. Mantello1, F. Cucciarelli1, L. Vicenzi1, F. Fenu1, S. Costantini1, M. Giacometti2, M. Valenti2, L. Fabbietti1, S. Maggi2, M. Cardinali1 1 Azienda Ospedaliero Universitaria Ospedali Riuniti, Dept Radiotherapy, Ancona, Italy 2 Azienda Ospedaliero Universitaria Ospedali Riuniti, Dept Physics, Ancona, Italy Purpose/Objective: To quantify dosimetric and clinical benefit of CBCT adaptive protocol by reducing PTV-rectum intersection in prostate 3DCRT. Materials and Methods: data of 162 patients (pts) treated with IGRT using Linac 21 EX Varian Medical System (with OBI) was analyzed. 112 pts (group 1) were treated on prostate and seminal vesicles following our already consolidated protocol of off-line adaptive re-planning (the first 5 CBCTs were used to personalize CTV-to-PTV margin). 51 pts (group 2) were instead treated on prostate only, where 3 implanted gold markers, were used to correct prostate position. The rectum was defined with the cranial border where it turns into the sigmoid colon and the caudal border to include the anus. A total dose of 74 Gy (group 1) and 78 Gy (group 2), 2 Gy per fraction was prescribed. Patients started treatment with a PTV margin of 1 cm, 5 mm posterior (pre-PTV). Definitive Plan (re-planning) was calculated on an adapted PTV (re-PTV) defined as the volume that represents the maximum excursions of the CTVs on the first 5 CBCTs in every patient. Dose constrains VR50 50, VR60 40, VR70 20, VR74 5-13 to the rectum were prescribed. Rectum volume intersected by selected dose constraints was calculated in the preplanning (DVH-pre) and in the final replanning (DVH-re). Reduction of PTV-rectum intersection volume (cc) was evaluated in both above groups of patients. Rectal toxicity was recorded and CTCAE vers. 4 scale was used to classify symptoms. For late toxicity patients with at least 6 months of follow up were evaluated. Mean and median follow up were 28 (range 6-62) and 23 months respectively. Results: In group1, mean pre-PTV was 250 cc (range 129-547), while mean re- PTV was 163 cc (74-338). In group 2, mean pre-PTV was 188 cc (96-276), while mean re-PTV was 108 cc (34-184). The advantages in terms of rectal volume sparing are reported in the table: Group 1 Dose volume
VR50 VR60 VR70 VR74
Preplanning rectum volume (%) cc 40 28 27 19 13 9 2 1.5
Group 2 Dose Preplanning volume rectum volume (%) cc VR50 38 24 VR60 27 17 VR70 17 11 VR74 9 6
Replanning rectum volume % cc 35 24 23 16 10 7 1.3 0.9 Replanning rectum volume % cc 31 20 22 14 12 8 5 3.4
Data from toxicity of these pts was very good. The reduction of replanning margin allowed a reduction of rectum volume intersected in the dose volumes and resulted in a low acute and late toxicity. In
the whole group the acute recorded toxicity was rectal pain (G1 in 3 pts, G3 in 1 pt), anal mucositis (G1 in 7 pts ), proctitis (G1 in 12 pts, G2 in 21 pts, G3 in 3 pts), while the late toxicity was anal mucositis (G1 in 1 pt ) and proctitis (G1 in 15 pts, G2 in 4 pts). Conclusions: CBCT Adaptive protocol was helpful to personalize and, in most cases, to reduce rectum-PTV intersection in the prostate radiotherapy. Consequently, toxicity results were very low, with few cases of G1-G2 acute and late rectal effects and only 4 cases of G3 acute toxicity and no G3 late toxicity. PO-0684 CONTINUOUS INTRA-FRACTION KV IMAGING: CORRELATION OF CONEBEAM CT RECTAL PARAMETERS WITH PROSTATE MOTION F. Hegi-Johnson1, J. Ng2, J. Booth1, P. Gaur1, A. Kneebone1, P. Keall3, T. Eade1 1 Royal North Shore Hospital, Department of Radiation Oncology, Sydney NSW, Australia 2 Sydney University, Institute of Medical Physics, Sydney NSW, Australia 3 Sydney University, Department of Medicine, Sydney NSW, Australia Purpose/Objective: Intra-fraction motion of the prostate is a welldocumented problem, which needs to be addressed particularly in hypofractionated protocols. Preliminary to the introduction of prostate stereotactic ablative body radiotherapy (SABR), we have developed a novel technique to measure continuous intra-fraction motion. This utilizes kV imaging technology available on most modern linear accelerators. We report the first clinical results and correlate intra-fractional prostate excursion with rectal parameters as assessed by pre-treatment cone-beam CT (CBCT) Materials and Methods: Continuous intra-fraction kV images (1) were acquired on 8 patients receiving volumetric modulated arc therapy (VMAT) radiotherapy for prostate cancer and the 3D position of the fiducial markers calculated. CBCT was acquired in 60 of these fractions and used to investigate potential predictors of intra-fraction motion. For this study significant motion was defined as > 3mm excursion from the isocentre. The rectum was split into upper and lower segments based on the pubic symphysis, and scans were scored as full or empty. The following parameters were analysed to assess their relationship to the intra-fraction motion observed: volume of rectal gas, rectal score and the presence of gas within the upper and lower rectum. Wilcoxon rank test was used to compare rectal volume and motion. Results: There were 15 fractions (25%) with motion > 3mm, and 7 (12%) fractions with motion >5mm. The upper rectum was full in 42 fractions (70%) and empty in 18 fractions (30%). A full upper rectum significantly predicted motion compared to an empty upper rectum (p=0.02), however there was no predictive value of an empty or full lower rectal volume (p=0.8). None of the other factors investigated had a significant effect on intra-fraction motion. Conclusions: Continuous intra-fraction kV imaging was successfully obtained during the treatment of 8 patients. This has enabled the novel use of CBCT data, which was acquired during treatment. In our study, the upper rectum status potentially identifies a cohort of patients who have minimal intra-fraction motion, and who may be suitable for SABR of the prostate. In these patients with a consistently empty upper rectum and minimal intra-fraction motion, margin reduction to 3 mm may be possible resulting in a potential reduction in toxicity, without comprising the accuracy of treatment delivery. Reference: 1. Poulsen PR, Cho B, Keall PJ. Real-time prostate trajectory estimation with a single imager in arc radiotherapy: a simulation study. Physics in medicine and biology 2009;54:4019. PO-0685 ACUTE TOXICITY OF PELVIC AND PROSTATE RADIATION FOR HIGH RISK PROSTATE CANCER: THE IMPACT OF IMRT AND BLADDER FILLING S. Jain1, P. Cheung1, A. Loblaw1, G. Morton1, C. Danjoux1, E. Szumacher1, W. Chu1, H. Chung1, D. Vesprini1, A. Sahgal1 1 Sunnybrook Health Sciences Centre, Radiation Oncology, Toronto, Canada Purpose/Objective: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. While studies show a clear dosimetric benefit to organs at risk, there is a lack of clinical data demonstrating reduced toxicity with the use of IMRT in this setting.
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
S265
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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3+4 was not a significant predicting factor for BCR in comparison with patients with GS 3+3 (p = 0.39). Multivariate analysis indicated that GS was significantly associated with BCR (p = 0.004), and initial prostate-specific antigen (PSA) level tended to be associated with BCR (p = 0.061), while age, prostate volume, T stage, NAHT, and dose irradiating 90% of the prostate volume (prostate D90) were insignificant. Conclusions: Our outcomes following PPB in Japanese patients with intermediate-risk PCa were in agreement with those of larger published series in Western patients. GS were significantly associated with BCR, and especially GS 4+3 carried a bad BCR prognosis. PO-0683 CBCT ADAPTIVE PROTOCOL TO REDUCE PTV-RECTUM INTERSECTION IN THE PROSTATE RADIOTHERAPY G. Mantello1, F. Cucciarelli1, L. Vicenzi1, F. Fenu1, S. Costantini1, M. Giacometti2, M. Valenti2, L. Fabbietti1, S. Maggi2, M. Cardinali1 1 Azienda Ospedaliero Universitaria Ospedali Riuniti, Dept Radiotherapy, Ancona, Italy 2 Azienda Ospedaliero Universitaria Ospedali Riuniti, Dept Physics, Ancona, Italy Purpose/Objective: To quantify dosimetric and clinical benefit of CBCT adaptive protocol by reducing PTV-rectum intersection in prostate 3DCRT. Materials and Methods: data of 162 patients (pts) treated with IGRT using Linac 21 EX Varian Medical System (with OBI) was analyzed. 112 pts (group 1) were treated on prostate and seminal vesicles following our already consolidated protocol of off-line adaptive re-planning (the first 5 CBCTs were used to personalize CTV-to-PTV margin). 51 pts (group 2) were instead treated on prostate only, where 3 implanted gold markers, were used to correct prostate position. The rectum was defined with the cranial border where it turns into the sigmoid colon and the caudal border to include the anus. A total dose of 74 Gy (group 1) and 78 Gy (group 2), 2 Gy per fraction was prescribed. Patients started treatment with a PTV margin of 1 cm, 5 mm posterior (pre-PTV). Definitive Plan (re-planning) was calculated on an adapted PTV (re-PTV) defined as the volume that represents the maximum excursions of the CTVs on the first 5 CBCTs in every patient. Dose constrains VR50 50, VR60 40, VR70 20, VR74 5-13 to the rectum were prescribed. Rectum volume intersected by selected dose constraints was calculated in the preplanning (DVH-pre) and in the final replanning (DVH-re). Reduction of PTV-rectum intersection volume (cc) was evaluated in both above groups of patients. Rectal toxicity was recorded and CTCAE vers. 4 scale was used to classify symptoms. For late toxicity patients with at least 6 months of follow up were evaluated. Mean and median follow up were 28 (range 6-62) and 23 months respectively. Results: In group1, mean pre-PTV was 250 cc (range 129-547), while mean re- PTV was 163 cc (74-338). In group 2, mean pre-PTV was 188 cc (96-276), while mean re-PTV was 108 cc (34-184). The advantages in terms of rectal volume sparing are reported in the table: Group 1 Dose volume
VR50 VR60 VR70 VR74
Preplanning rectum volume (%) cc 40 28 27 19 13 9 2 1.5
Group 2 Dose Preplanning volume rectum volume (%) cc VR50 38 24 VR60 27 17 VR70 17 11 VR74 9 6
Replanning rectum volume % cc 35 24 23 16 10 7 1.3 0.9 Replanning rectum volume % cc 31 20 22 14 12 8 5 3.4
Data from toxicity of these pts was very good. The reduction of replanning margin allowed a reduction of rectum volume intersected in the dose volumes and resulted in a low acute and late toxicity. In
the whole group the acute recorded toxicity was rectal pain (G1 in 3 pts, G3 in 1 pt), anal mucositis (G1 in 7 pts ), proctitis (G1 in 12 pts, G2 in 21 pts, G3 in 3 pts), while the late toxicity was anal mucositis (G1 in 1 pt ) and proctitis (G1 in 15 pts, G2 in 4 pts). Conclusions: CBCT Adaptive protocol was helpful to personalize and, in most cases, to reduce rectum-PTV intersection in the prostate radiotherapy. Consequently, toxicity results were very low, with few cases of G1-G2 acute and late rectal effects and only 4 cases of G3 acute toxicity and no G3 late toxicity. PO-0684 CONTINUOUS INTRA-FRACTION KV IMAGING: CORRELATION OF CONEBEAM CT RECTAL PARAMETERS WITH PROSTATE MOTION F. Hegi-Johnson1, J. Ng2, J. Booth1, P. Gaur1, A. Kneebone1, P. Keall3, T. Eade1 1 Royal North Shore Hospital, Department of Radiation Oncology, Sydney NSW, Australia 2 Sydney University, Institute of Medical Physics, Sydney NSW, Australia 3 Sydney University, Department of Medicine, Sydney NSW, Australia Purpose/Objective: Intra-fraction motion of the prostate is a welldocumented problem, which needs to be addressed particularly in hypofractionated protocols. Preliminary to the introduction of prostate stereotactic ablative body radiotherapy (SABR), we have developed a novel technique to measure continuous intra-fraction motion. This utilizes kV imaging technology available on most modern linear accelerators. We report the first clinical results and correlate intra-fractional prostate excursion with rectal parameters as assessed by pre-treatment cone-beam CT (CBCT) Materials and Methods: Continuous intra-fraction kV images (1) were acquired on 8 patients receiving volumetric modulated arc therapy (VMAT) radiotherapy for prostate cancer and the 3D position of the fiducial markers calculated. CBCT was acquired in 60 of these fractions and used to investigate potential predictors of intra-fraction motion. For this study significant motion was defined as > 3mm excursion from the isocentre. The rectum was split into upper and lower segments based on the pubic symphysis, and scans were scored as full or empty. The following parameters were analysed to assess their relationship to the intra-fraction motion observed: volume of rectal gas, rectal score and the presence of gas within the upper and lower rectum. Wilcoxon rank test was used to compare rectal volume and motion. Results: There were 15 fractions (25%) with motion > 3mm, and 7 (12%) fractions with motion >5mm. The upper rectum was full in 42 fractions (70%) and empty in 18 fractions (30%). A full upper rectum significantly predicted motion compared to an empty upper rectum (p=0.02), however there was no predictive value of an empty or full lower rectal volume (p=0.8). None of the other factors investigated had a significant effect on intra-fraction motion. Conclusions: Continuous intra-fraction kV imaging was successfully obtained during the treatment of 8 patients. This has enabled the novel use of CBCT data, which was acquired during treatment. In our study, the upper rectum status potentially identifies a cohort of patients who have minimal intra-fraction motion, and who may be suitable for SABR of the prostate. In these patients with a consistently empty upper rectum and minimal intra-fraction motion, margin reduction to 3 mm may be possible resulting in a potential reduction in toxicity, without comprising the accuracy of treatment delivery. Reference: 1. Poulsen PR, Cho B, Keall PJ. Real-time prostate trajectory estimation with a single imager in arc radiotherapy: a simulation study. Physics in medicine and biology 2009;54:4019. PO-0685 ACUTE TOXICITY OF PELVIC AND PROSTATE RADIATION FOR HIGH RISK PROSTATE CANCER: THE IMPACT OF IMRT AND BLADDER FILLING S. Jain1, P. Cheung1, A. Loblaw1, G. Morton1, C. Danjoux1, E. Szumacher1, W. Chu1, H. Chung1, D. Vesprini1, A. Sahgal1 1 Sunnybrook Health Sciences Centre, Radiation Oncology, Toronto, Canada Purpose/Objective: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. While studies show a clear dosimetric benefit to organs at risk, there is a lack of clinical data demonstrating reduced toxicity with the use of IMRT in this setting.