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OC-25 HIGH-DOSE RATE AFTERLOADING BRACHYTHERAPY USING ONE OR TWO FRACTIONS FOR LOCALISED PROSTATE CANCER
S10
PROFFERED PAPERS: PROSTATE 1 OC-24 TEN-YEAR OUTCOMES FOR PATIENTS WITH GLEASON 8-10 TREATED WITH HIGH DOSE RATE BRACHYTHERAPY BOOST A. Martinez1, C. Shah2, N. Mohammed2, J. Demanes3, R. MartinezMonge4, H. Ye2, R. Galalae5 1 Michigan Healthcare Professionals, Radiation Oncology, Farmington Hills, USA 2 Beaumont Health System, Radiation Oncology, Royal Oak, USA 4 Universidad de Navarra, Radiation Oncology, Pamplona, Spain 5 Kiel University, Radiation Oncology, Kiel, Germany Purpose/Objective: To report long term multi-institutional outcomes for Gleason 8–10 prostate cancer patients treated with external beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy boost. Materials and Methods: Between 1987 and 2002, 483 patients with Gleason 8-10 disease were treated for localized prostate cancer at William Beaumont Hospital (WBH), the California Endocurietherapy Center (CET), Kiel University, and the Universidad de Navarra on four prospective HDR boost trials. Conformal EBRT was delivered to the pelvis (dose range 36 Gy–50.4 Gy) along with HDR boost for a combined biologic equivalent dose (BED) of 215–366 Gy (α/β=1.2). Conformal intensity modulated HDR-BT was planned and treatment was delivered using on-line trans-rectal ultrasound (TRUS) images at WBH. At CET, Kiel University, and Navarra University, HDR-BT treatment planning was CT based. Biochemical control (BC) was defined according to the Phoenix criteria (freedom from PSA rise of 2ng/ml above nadir). Results: Mean patient age was 68.4 years with mean initial PSA (iPSA) of 18.8 ng/ml. Mean follow-up was 6.1 years. 10-year outcomes were: biochemical control (BC) 53.5%, distant metastases (DM) 22.1%, clinical failure (CF) 25.6%, cause specific survival (CSS) 82.6% and overall survival (OS) 62.7%. Hormones were given in 69.9% of patients but did not significantly improve BC, DM, CSS, or OS. 10-year outcomes stratified by iPSA (<40 vs. >40 ng/ml) were improved for all outcomes with lower iPSA including BC (57.4% v. 10.3%, p<0.001), freedom from distant metastases (81.5% v. 43.4% (p<0.001), CSS (85.0% v. 59.1% (p<0.001), and OS (63.8% vs. 47.9%, p=0.02). Univariate analysis of biochemical control found tumor stage (OR 1.35, p<0.001), pre-treatment PSA (OR 1.03, p<0.001), and Gleason score (OR 1.69, p=0.05) to be associated with no association noted with hormonal therapy (p=0.94) and BED (0.34). Multivariate analysis confirmed tumor stage (p=0.03), pre-treatment PSA (p=0.02), and Gleason score (p=0.03) but not hormonal therapy (p=0.57) or BED (p=0.42). Table: 5 and 10-year outcomes for cases by No Pre-RT HT with Pre-RT HT 5-yr Outcome
10-yr outcome
No Pre- PreHT HT
No Pre-HT
pvalue
World Congress of Brachytherapy 2012 OC-25 HIGH-DOSE RATE AFTERLOADING BRACHYTHERAPY USING ONE OR TWO FRACTIONS FOR LOCALISED PROSTATE CANCER P. Hoskin1, A. Rojas1, P. Ostler1, R. Hughes1, R. Alonzi1, L. Bryant1, G. Lowe1 1 Mount Vernon Hospital, Cancer Centre, Northwood Middlesex, United Kingdom Purpose/Objective: to evaluate toxicity after high-dose-rate brachytherapy (HDR-BT) alone in localised prostate cancer. Materials/Methods: 134 sequential patients were treated with 26 Gy in 2 fractions (Group A; n= 110) or a single dose of 19 Gy (Group B; n = 24) HDR-BT alone. The D30% urethral dose constraints were < 28.5 Gy and < 20.8 Gy, respectively. Inclusion criteria were either MRI stage ≥ T2b, or Gleason score ≥ 7 with no metastases on isotope bone scan or pelvic MRI. Patients with previous TURP were excluded. Primary endpoints are early and late urinary and gastrointestinal toxicity, using the RTOG/EORTC scales and the International Prostate Symptom Score (IPSS). Patients were seen at 2, 4, and 12 weeks after implant,then at 6 monthly intervals. Prevalence of events was calculated and Chi-square tests used to test for significance. The secondary endpoint is biochemical relapse-free interval (bRFI), using the Phœnix definition (PAS nadir plus 2 µg/L), calculated using the Kaplan-Meier method. Results: Median follow-up for patients in Group A, in study for at least 6 months, is 18 months (n = 100); in Group B the maximum follow-up is 13.2 months. Median age is 69 years for both schedules. Patients had predominantly intermediate or high-risk disease: Group A 99%, Group B 92%. In both groups, 79% had neo-adjuvant and adjuvant androgen deprivation treatment. Table 1 shows prevalence of severe (grade 3 or worse) early and late urinary adverse events. Table 1. Percent prevalence of early and late Grade 3 or worse genito-urinary (GU) events, catheterization and IPSS ≥ 20 at the indicated follow-up times. (26 Gy = 110 patients;19 Gy = 24 patients) Early (weeks)
2
4
12
GU ≥3 26 Gy 19 Gy
6 0
2 0
1 0
Catheter 26 Gy 19 Gy
*6 22
6 17
4 11
6 8
19 11
12 10
7 6
6
12
18
24
GU ≥3 26 Gy
2
0
0
0
Catheter 26 Gy
3
0
0
0
IPSS ≥20 26 Gy
3
3
4
3
IPSS ≥20 26 Gy 19 Gy Late (months)
0
Pre-HT
Free DM
90.4%
87.3% 81.7%
75.6%
0.29
Free LR
93.1%
98.1% 85.3%
97.4%
0.001*
CSS
95.8%
94.0% 85.9%
80.9%
0.19
OS
85.7%
86.2% 63.1%
64.4%
0.89
Free CF
84.7%
86.4% 73.1%
75.1%
0.76
BC (PHOENIX)
66.7%
70.5% 51.7%
54.4%
0.38
Conclusions: Combination of HDR brachytherapy and EBRT provides high BED with high rates of disease control and improved outcomes for patients with Gleason 8-10 prostate cancer even with iPSA up to 40 ng/ml. Hormonal therapy did not improve the outcomes in this high BED cohort.
No significant difference was seen between dose groups. However the proportion of patients requiring catheterization was higher in Group B. Prevalence of IPSS ≥ 20 was similar in both arms and most patients had returned to baseline levels by 12 weeks. No early or late severe GI events (scores of 3 or 4) were seen. Late toxicity and bRFI are only evaluable in Group A. No grade 4 GU events have been observed during the first 24 months. At 6 months 3% of patients had an indwelling catheter (3/90) and 2% had Grade-3 GU morbidity. Between 12 to 24 months, no grade 3 events were seen and no patients required catheterization; 3% - 4% of patients had an IPSS ≥ 20. At 2 years 99% are free of biochemical recurrence.
World Congress of Brachytherapy 2012 Conclusions: The results indicate that large doses per fraction of high-dose-rate brachytherapy are feasible and early and late adverse events manageable. The incidence of severe early urinary events is similar in both groups but a higher proportion of patients required catheterization after 19 Gy HDR-BT, although the numbers in this group are small at present. This may reflect greater acute radiation effectsfrom the single dose although many cases are related to hæmaturia and clot retention. Biochemical control for locally advanced prostate cancer in patients treated with 26 Gy at 2 years is encouraging. OC-26 PROSTATE CANCER: SINGLE FRACTION HDR BOOST - 12.5GY OR 15GY WITH EXTERNAL BEAM RADIATION. A COMPARISON OF TOXICITY C. Arthur1, J. Malik1, R. Swindell1, P. Mandall1, A. Choudhury1, J. Logue1, J. Wylie1 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom Purpose/Objective: High Dose Rate (HDR) brachytherapy offers a highly conformal approach to radiotherapy delivery, enabling dose escalation in the treatment of prostate cancer. The potential to improve patient outcomes must be balanced against the risk of toxicity. An HDR boost of 12.5Gy or 15Gy was delivered prior to 37.5Gy in 15 fractions using 3D conformal external beam radiotherapy (EBRT), to patients with intermediate- and high-risk prostate cancer. We report results of acute and late toxicity associated with these HDR brachytherapy dose regimens. Materials and Methods: Data was collected prospectively on patients treated with HDR brachytherapy and EBRT between July 2008 and February 2011. Toxicity data was collected using IPSS and LENT-SOMA questionnaires which were completed at baseline and regular intervals thereafter. Results: 177 patients with histologically confirmed prostate adenocarcinoma received an HDR boost. The 1st cohort (95 patients) were treated from July 2008 - March 2010 and received 12.5Gy; a 2nd cohort (82 patients) received a 15Gy boost between April 2010 February 2011. Patients had intermediate or high risk disease; the majority (154 cases, (87%)) were staged as T2 or T3 disease with a median age of 67 years (range 57-77), median PSA was 16.0 ng/ml (0.29-102), median Gleason score 7 (6-10) and IPSS 8 (0-27). Dosimetric data was similar between the 2 treatment cohorts (12.5Gy and 15Gy respectively). The median V100 was 96.1% (range, 84.0 99.3) compared with 97.1% (range, 84.6 - 99.8), urethra D10 = 110.8% (range, 104.0-115.9) versus 111.4% (range, 104.7-114.9) and rectal D max 10.9Gy (range, 8.2-12.8) versus 13.2Gy (11.1-13.9). Median IPSS’ peaked 6 weeks following EBRT (12.5Gy = 9, 15Gy = 10), with no clinical difference between cohorts after 6 and 12 months. Urinary catheterisation was required by 17 patients (18%) who received 12.5 Gy (median duration = 7 days (range, 1-120)) and 6 patients (7%) in the 15 Gy cohort (median duration = 28 days (range, 2-50)). LENT-SOMA bladder/urethra mean scores peaked 6 weeks after EBRT (12.5Gy = 0.59, 15Gy = 0.73) with maximum scores ≥2 reported by 72% (12.5Gy) and 80% (15 Gy) of patients. Mean scores remained similar at 6 months (0.53 (12.5Gy), 0.62 (15Gy)) and 12 months ((0.57 (12.5Gy), 0.61 (15Gy)). LENT-SOMA rectum/bowel mean scores peaked after 6 months (0.37 and 0.40 respectively) with 51% (12.5Gy) and 72% (15Gy) of patients reporting maximum scores of ≥ 2. Mean scores were similar between the 2 groups after 12 months (12.5Gy = 0.33, 15Gy = 0.22). Conclusions: HDR dose escalation from 12.5Gy to 15Gy, in association with EBRT, was well tolerated with no clinically significant increase in acute and late toxicity observed between the treatment cohorts. The difference in catheterisation rates was attributed to a change in clinical practice. We conclude that the toxicity reported with the 15Gy regimen is acceptable in view of the level of dose escalation (BED1.5 = 265Gy).
S 11 OC-27 A DOSIMETRIC ANALYSIS OF RADIATION THERAPY ONCOLOGY GROUP (RTOG) 0321: THE IMPORTANCE OF URETHRAL DOSE I. Hsu1, D. Hunt2, W. Straube3, J. Pouliot1, A. Cunha1, D. Krishnamurthy1, H. Sandler4 1 UCSF Comprehensive Cancer Center, Radiation Oncology, San Francisco CA, USA 3 Washington University, Image-Guided Therapy Center, St. Louis MO, USA 4 Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center, Radiation Oncology, Los Angeles CA, USA Purpose/Objective: RTOG 0321 is the first and only cooperative group, prospective HDR prostate brachytherapy trial. It is also the only such trial with complete digital brachytherapy dosimetry data. This is a detailed descriptive report of the dosimetric parameters and an analysis of treatment toxicity. Materials and Methods: Patients were treated with external beam radiotherapy 45 Gy in 25 fractions and one HDR implant with a prescribed dose of 19 Gy in 2 fractions. Implants were done with TRUS guidance, using CT-compatible, non-metallic catheters. HDR planning was done on ≤ 3 mm-thick CT slices. Plans were then submitted to the Image-Guided Therapy Center (ITC). The 'mean DVH' of the PTV, implanted volume, and organs at risk (OAR) were subsequently calculated. This included the mean and standard deviation of the volume at ten-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), number of catheters/implant, and number of patients per institution were collected. Multivariate analysis and calculation of Hazard Ratios (HR) of all the variables against reported Grade > 2 (G2+) GU and GI adverse events (AE) were performed. Results: Dosimetry data were based on 122 eligible patients (129 enrolled) with complete data from 14 institutions. The mean (range) of PTV, implanted volume, catheters/implant, and patients/ institution were: 54 cc (19-130), 63 cc (26-147), 19 (13-29), and 9 (219), respectively. The mean (range) of %V100PTV, V80Bladder, V80Rectum, V120Urethra, COIN and HI were: 94% (87-99), 0.40cc (0-3.2), 0.15cc (01.1), 0.25cc (0-1.1), 0.75 (0.49-0.87), and 0.63 (0.39-0.85), respectively. There were too few G2+ GI AE for correlative analysis, thus the analysis was performed on the more common G2+ GU AE. There were 36 acute and 28 late G2+ GU AE. There were positive correlations between both acute and late G2+ GU AE and urethral dose at multiple dose levels. Positive correlations with late AE were also seen with PTV and implanted volume at high-dose levels (>150% of prescribed dose). A negative correlation was seen between HI and acute AE. Patients from institutions with a higher patient accrual rate had a lower rate of G2+ acute and late AE. Conclusions: Higher urethral dose, larger high dose volumes (hot spots) and lower dose homogeneity were associated with greater treatment-related toxicities. A mean DVH comparison at all dose levels should be used for quality control and future research comparison. OC-28 HDR PROSTATE BRACHYTHERAPY IN ANATOMICALLY UNSUITABLE CASES (<20CC, >50CC, PRIOR TURP)-UNCOMPROMISED RESULTS A. Peddada1, S. Jennings2, R. Biggers3, G. Gibbs4, E. Cohn5, A. Monroe1 1 Penrose Cancer Center, Radiation Oncology, Colorado Springs, USA 2 Colorado Springs Health Partners, Urology, Colorado Springs, USA 3 Pikes Peak Urology, Urology, Colorado Springs, USA 4 Penrose Cancer Center, Medical Physics, Colorado Springs, USA 5 Urology Associates, Urology, Colorado Springs, USA Purpose/Objective: We conducted a retrospective analysis of our single institution experience with HDR prostate brachytherapy with the aim of comparing differences in dosimetric parameters and toxicity between the anatomic high risk group, (i.e. patients with prostate glands <20cc, >50cc, or historyof prior TURP), and the remainder of our patients, the standard risk group. Materials and Methods: Between June 2001 and December 2011, 647 patients received HDR brachytherapy as a boost to external beam radiotherapy in the definitive management of localized prostate cancer.
PROFFERED PAPERS: PROSTATE 1 OC-24 TEN-YEAR OUTCOMES FOR PATIENTS WITH GLEASON 8-10 TREATED WITH HIGH DOSE RATE BRACHYTHERAPY BOOST A. Martinez1, C. Shah2, N. Mohammed2, J. Demanes3, R. MartinezMonge4, H. Ye2, R. Galalae5 1 Michigan Healthcare Professionals, Radiation Oncology, Farmington Hills, USA 2 Beaumont Health System, Radiation Oncology, Royal Oak, USA 4 Universidad de Navarra, Radiation Oncology, Pamplona, Spain 5 Kiel University, Radiation Oncology, Kiel, Germany Purpose/Objective: To report long term multi-institutional outcomes for Gleason 8–10 prostate cancer patients treated with external beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy boost. Materials and Methods: Between 1987 and 2002, 483 patients with Gleason 8-10 disease were treated for localized prostate cancer at William Beaumont Hospital (WBH), the California Endocurietherapy Center (CET), Kiel University, and the Universidad de Navarra on four prospective HDR boost trials. Conformal EBRT was delivered to the pelvis (dose range 36 Gy–50.4 Gy) along with HDR boost for a combined biologic equivalent dose (BED) of 215–366 Gy (α/β=1.2). Conformal intensity modulated HDR-BT was planned and treatment was delivered using on-line trans-rectal ultrasound (TRUS) images at WBH. At CET, Kiel University, and Navarra University, HDR-BT treatment planning was CT based. Biochemical control (BC) was defined according to the Phoenix criteria (freedom from PSA rise of 2ng/ml above nadir). Results: Mean patient age was 68.4 years with mean initial PSA (iPSA) of 18.8 ng/ml. Mean follow-up was 6.1 years. 10-year outcomes were: biochemical control (BC) 53.5%, distant metastases (DM) 22.1%, clinical failure (CF) 25.6%, cause specific survival (CSS) 82.6% and overall survival (OS) 62.7%. Hormones were given in 69.9% of patients but did not significantly improve BC, DM, CSS, or OS. 10-year outcomes stratified by iPSA (<40 vs. >40 ng/ml) were improved for all outcomes with lower iPSA including BC (57.4% v. 10.3%, p<0.001), freedom from distant metastases (81.5% v. 43.4% (p<0.001), CSS (85.0% v. 59.1% (p<0.001), and OS (63.8% vs. 47.9%, p=0.02). Univariate analysis of biochemical control found tumor stage (OR 1.35, p<0.001), pre-treatment PSA (OR 1.03, p<0.001), and Gleason score (OR 1.69, p=0.05) to be associated with no association noted with hormonal therapy (p=0.94) and BED (0.34). Multivariate analysis confirmed tumor stage (p=0.03), pre-treatment PSA (p=0.02), and Gleason score (p=0.03) but not hormonal therapy (p=0.57) or BED (p=0.42). Table: 5 and 10-year outcomes for cases by No Pre-RT HT with Pre-RT HT 5-yr Outcome
10-yr outcome
No Pre- PreHT HT
No Pre-HT
pvalue
World Congress of Brachytherapy 2012 OC-25 HIGH-DOSE RATE AFTERLOADING BRACHYTHERAPY USING ONE OR TWO FRACTIONS FOR LOCALISED PROSTATE CANCER P. Hoskin1, A. Rojas1, P. Ostler1, R. Hughes1, R. Alonzi1, L. Bryant1, G. Lowe1 1 Mount Vernon Hospital, Cancer Centre, Northwood Middlesex, United Kingdom Purpose/Objective: to evaluate toxicity after high-dose-rate brachytherapy (HDR-BT) alone in localised prostate cancer. Materials/Methods: 134 sequential patients were treated with 26 Gy in 2 fractions (Group A; n= 110) or a single dose of 19 Gy (Group B; n = 24) HDR-BT alone. The D30% urethral dose constraints were < 28.5 Gy and < 20.8 Gy, respectively. Inclusion criteria were either MRI stage ≥ T2b, or Gleason score ≥ 7 with no metastases on isotope bone scan or pelvic MRI. Patients with previous TURP were excluded. Primary endpoints are early and late urinary and gastrointestinal toxicity, using the RTOG/EORTC scales and the International Prostate Symptom Score (IPSS). Patients were seen at 2, 4, and 12 weeks after implant,then at 6 monthly intervals. Prevalence of events was calculated and Chi-square tests used to test for significance. The secondary endpoint is biochemical relapse-free interval (bRFI), using the Phœnix definition (PAS nadir plus 2 µg/L), calculated using the Kaplan-Meier method. Results: Median follow-up for patients in Group A, in study for at least 6 months, is 18 months (n = 100); in Group B the maximum follow-up is 13.2 months. Median age is 69 years for both schedules. Patients had predominantly intermediate or high-risk disease: Group A 99%, Group B 92%. In both groups, 79% had neo-adjuvant and adjuvant androgen deprivation treatment. Table 1 shows prevalence of severe (grade 3 or worse) early and late urinary adverse events. Table 1. Percent prevalence of early and late Grade 3 or worse genito-urinary (GU) events, catheterization and IPSS ≥ 20 at the indicated follow-up times. (26 Gy = 110 patients;19 Gy = 24 patients) Early (weeks)
2
4
12
GU ≥3 26 Gy 19 Gy
6 0
2 0
1 0
Catheter 26 Gy 19 Gy
*6 22
6 17
4 11
6 8
19 11
12 10
7 6
6
12
18
24
GU ≥3 26 Gy
2
0
0
0
Catheter 26 Gy
3
0
0
0
IPSS ≥20 26 Gy
3
3
4
3
IPSS ≥20 26 Gy 19 Gy Late (months)
0
Pre-HT
Free DM
90.4%
87.3% 81.7%
75.6%
0.29
Free LR
93.1%
98.1% 85.3%
97.4%
0.001*
CSS
95.8%
94.0% 85.9%
80.9%
0.19
OS
85.7%
86.2% 63.1%
64.4%
0.89
Free CF
84.7%
86.4% 73.1%
75.1%
0.76
BC (PHOENIX)
66.7%
70.5% 51.7%
54.4%
0.38
Conclusions: Combination of HDR brachytherapy and EBRT provides high BED with high rates of disease control and improved outcomes for patients with Gleason 8-10 prostate cancer even with iPSA up to 40 ng/ml. Hormonal therapy did not improve the outcomes in this high BED cohort.
No significant difference was seen between dose groups. However the proportion of patients requiring catheterization was higher in Group B. Prevalence of IPSS ≥ 20 was similar in both arms and most patients had returned to baseline levels by 12 weeks. No early or late severe GI events (scores of 3 or 4) were seen. Late toxicity and bRFI are only evaluable in Group A. No grade 4 GU events have been observed during the first 24 months. At 6 months 3% of patients had an indwelling catheter (3/90) and 2% had Grade-3 GU morbidity. Between 12 to 24 months, no grade 3 events were seen and no patients required catheterization; 3% - 4% of patients had an IPSS ≥ 20. At 2 years 99% are free of biochemical recurrence.
World Congress of Brachytherapy 2012 Conclusions: The results indicate that large doses per fraction of high-dose-rate brachytherapy are feasible and early and late adverse events manageable. The incidence of severe early urinary events is similar in both groups but a higher proportion of patients required catheterization after 19 Gy HDR-BT, although the numbers in this group are small at present. This may reflect greater acute radiation effectsfrom the single dose although many cases are related to hæmaturia and clot retention. Biochemical control for locally advanced prostate cancer in patients treated with 26 Gy at 2 years is encouraging. OC-26 PROSTATE CANCER: SINGLE FRACTION HDR BOOST - 12.5GY OR 15GY WITH EXTERNAL BEAM RADIATION. A COMPARISON OF TOXICITY C. Arthur1, J. Malik1, R. Swindell1, P. Mandall1, A. Choudhury1, J. Logue1, J. Wylie1 1 The Christie NHS Foundation Trust, Clinical Oncology, Manchester, United Kingdom Purpose/Objective: High Dose Rate (HDR) brachytherapy offers a highly conformal approach to radiotherapy delivery, enabling dose escalation in the treatment of prostate cancer. The potential to improve patient outcomes must be balanced against the risk of toxicity. An HDR boost of 12.5Gy or 15Gy was delivered prior to 37.5Gy in 15 fractions using 3D conformal external beam radiotherapy (EBRT), to patients with intermediate- and high-risk prostate cancer. We report results of acute and late toxicity associated with these HDR brachytherapy dose regimens. Materials and Methods: Data was collected prospectively on patients treated with HDR brachytherapy and EBRT between July 2008 and February 2011. Toxicity data was collected using IPSS and LENT-SOMA questionnaires which were completed at baseline and regular intervals thereafter. Results: 177 patients with histologically confirmed prostate adenocarcinoma received an HDR boost. The 1st cohort (95 patients) were treated from July 2008 - March 2010 and received 12.5Gy; a 2nd cohort (82 patients) received a 15Gy boost between April 2010 February 2011. Patients had intermediate or high risk disease; the majority (154 cases, (87%)) were staged as T2 or T3 disease with a median age of 67 years (range 57-77), median PSA was 16.0 ng/ml (0.29-102), median Gleason score 7 (6-10) and IPSS 8 (0-27). Dosimetric data was similar between the 2 treatment cohorts (12.5Gy and 15Gy respectively). The median V100 was 96.1% (range, 84.0 99.3) compared with 97.1% (range, 84.6 - 99.8), urethra D10 = 110.8% (range, 104.0-115.9) versus 111.4% (range, 104.7-114.9) and rectal D max 10.9Gy (range, 8.2-12.8) versus 13.2Gy (11.1-13.9). Median IPSS’ peaked 6 weeks following EBRT (12.5Gy = 9, 15Gy = 10), with no clinical difference between cohorts after 6 and 12 months. Urinary catheterisation was required by 17 patients (18%) who received 12.5 Gy (median duration = 7 days (range, 1-120)) and 6 patients (7%) in the 15 Gy cohort (median duration = 28 days (range, 2-50)). LENT-SOMA bladder/urethra mean scores peaked 6 weeks after EBRT (12.5Gy = 0.59, 15Gy = 0.73) with maximum scores ≥2 reported by 72% (12.5Gy) and 80% (15 Gy) of patients. Mean scores remained similar at 6 months (0.53 (12.5Gy), 0.62 (15Gy)) and 12 months ((0.57 (12.5Gy), 0.61 (15Gy)). LENT-SOMA rectum/bowel mean scores peaked after 6 months (0.37 and 0.40 respectively) with 51% (12.5Gy) and 72% (15Gy) of patients reporting maximum scores of ≥ 2. Mean scores were similar between the 2 groups after 12 months (12.5Gy = 0.33, 15Gy = 0.22). Conclusions: HDR dose escalation from 12.5Gy to 15Gy, in association with EBRT, was well tolerated with no clinically significant increase in acute and late toxicity observed between the treatment cohorts. The difference in catheterisation rates was attributed to a change in clinical practice. We conclude that the toxicity reported with the 15Gy regimen is acceptable in view of the level of dose escalation (BED1.5 = 265Gy).
S 11 OC-27 A DOSIMETRIC ANALYSIS OF RADIATION THERAPY ONCOLOGY GROUP (RTOG) 0321: THE IMPORTANCE OF URETHRAL DOSE I. Hsu1, D. Hunt2, W. Straube3, J. Pouliot1, A. Cunha1, D. Krishnamurthy1, H. Sandler4 1 UCSF Comprehensive Cancer Center, Radiation Oncology, San Francisco CA, USA 3 Washington University, Image-Guided Therapy Center, St. Louis MO, USA 4 Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center, Radiation Oncology, Los Angeles CA, USA Purpose/Objective: RTOG 0321 is the first and only cooperative group, prospective HDR prostate brachytherapy trial. It is also the only such trial with complete digital brachytherapy dosimetry data. This is a detailed descriptive report of the dosimetric parameters and an analysis of treatment toxicity. Materials and Methods: Patients were treated with external beam radiotherapy 45 Gy in 25 fractions and one HDR implant with a prescribed dose of 19 Gy in 2 fractions. Implants were done with TRUS guidance, using CT-compatible, non-metallic catheters. HDR planning was done on ≤ 3 mm-thick CT slices. Plans were then submitted to the Image-Guided Therapy Center (ITC). The 'mean DVH' of the PTV, implanted volume, and organs at risk (OAR) were subsequently calculated. This included the mean and standard deviation of the volume at ten-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), number of catheters/implant, and number of patients per institution were collected. Multivariate analysis and calculation of Hazard Ratios (HR) of all the variables against reported Grade > 2 (G2+) GU and GI adverse events (AE) were performed. Results: Dosimetry data were based on 122 eligible patients (129 enrolled) with complete data from 14 institutions. The mean (range) of PTV, implanted volume, catheters/implant, and patients/ institution were: 54 cc (19-130), 63 cc (26-147), 19 (13-29), and 9 (219), respectively. The mean (range) of %V100PTV, V80Bladder, V80Rectum, V120Urethra, COIN and HI were: 94% (87-99), 0.40cc (0-3.2), 0.15cc (01.1), 0.25cc (0-1.1), 0.75 (0.49-0.87), and 0.63 (0.39-0.85), respectively. There were too few G2+ GI AE for correlative analysis, thus the analysis was performed on the more common G2+ GU AE. There were 36 acute and 28 late G2+ GU AE. There were positive correlations between both acute and late G2+ GU AE and urethral dose at multiple dose levels. Positive correlations with late AE were also seen with PTV and implanted volume at high-dose levels (>150% of prescribed dose). A negative correlation was seen between HI and acute AE. Patients from institutions with a higher patient accrual rate had a lower rate of G2+ acute and late AE. Conclusions: Higher urethral dose, larger high dose volumes (hot spots) and lower dose homogeneity were associated with greater treatment-related toxicities. A mean DVH comparison at all dose levels should be used for quality control and future research comparison. OC-28 HDR PROSTATE BRACHYTHERAPY IN ANATOMICALLY UNSUITABLE CASES (<20CC, >50CC, PRIOR TURP)-UNCOMPROMISED RESULTS A. Peddada1, S. Jennings2, R. Biggers3, G. Gibbs4, E. Cohn5, A. Monroe1 1 Penrose Cancer Center, Radiation Oncology, Colorado Springs, USA 2 Colorado Springs Health Partners, Urology, Colorado Springs, USA 3 Pikes Peak Urology, Urology, Colorado Springs, USA 4 Penrose Cancer Center, Medical Physics, Colorado Springs, USA 5 Urology Associates, Urology, Colorado Springs, USA Purpose/Objective: We conducted a retrospective analysis of our single institution experience with HDR prostate brachytherapy with the aim of comparing differences in dosimetric parameters and toxicity between the anatomic high risk group, (i.e. patients with prostate glands <20cc, >50cc, or historyof prior TURP), and the remainder of our patients, the standard risk group. Materials and Methods: Between June 2001 and December 2011, 647 patients received HDR brachytherapy as a boost to external beam radiotherapy in the definitive management of localized prostate cancer.