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965 Poster Change in histologic grade on repeat biopsy in untreated, low to intermediate grade, clinically localized prostate cancer
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and 8 in the second year), 1 patient (0.8%) grade 3 toxicity, and 37 (31.3%) grade 1 rectal toxicity. Age, prostate dosimetry, prostate volume and presence of diabetes were not statistically significant for rectal toxicity. Presence of cardiovascular disease was of borderline significance. Logistic regression shows that RV50, RV100, and RV150 values are not predictive of grade 2 or higher toxicity (p-values of 0.43, 0.96, and 0.62 respectively), However, Grade > 2 late toxicity was more common if VR50 is above 5.5 cc (<5.5 cc: 6% vs. >5.5 cc: 23%; p= .03). VR100 cutoff of 0.99cc (10% vs 22%; p=. 13) and VR150 cutoff of 0.09cc (9%vs 21%; p=. 12) are not statistically significant, Conclusions: Anterior rectal wall DVH is a practical method for recording rectal dosimetry post TPIP. Rectal VR50 can be used to predict late rectal toxicity, 963
Poster
Analysis and first report of the predictive value of the variseed real-time dosimetric optimization program (version 6.7) for permanent radioactive seed implantation (PSI) o f t h e prostate
A. Raben, H. Chert, A. Grebler, J. Geltzeiler, M. Geltzeiler, I. Keselman, S. Litvin, D. Simmons, J. Yang 1Monmouth Medical Center, Radiation Oncology, Long Branch, New Jer, sey, USA 2Monmouth Medical Center, Urology, Long Branch, New Jersey, USA Purpose: To evaluate predictive value of a commercially available real-time optimization program for permanent seed implant of the prostate, Materials and Methods:15 pts underwent PSt with iodine-125 sources using the VariSeed version 6.7 optimization system. On implant day (Day 0), Pts underwent US measurement from base to apex. Images and 1-125 source strength information were downloaded into the VariSeed station, in order to deliver 75% of the dose to the periphery and 25% to the central volume. Dosimetric goals placed on the prostate included: D90 > 144Gy and < 180Gy, V100of >95%,and dose constraintsonthe urethra (V150 <30%: 216 Gy to less than 30%) and anterior rectal wall (V110 < 1.5cc: 160 Gy). A dose > than 144 Gy to the prostate was allowed if Constraints to urethra and rectum were met. Seeds were localized and recorded. Dosimetric calculation was performed after initial peripheral loading to determine additional central loading pattern and seed placement. Dosimetric analysis was done after of the procedure, and at day 30 for comparison, Results:Initial dosimetry over-estimated the number of required 1-125 seeds by 10 to 15% to achieve a D90-144Gy in all pts. The mean gland volume was 37cc, Day 0 (Range 25 - 55) and 42cc(Range 32 - 63)on day 30. The gland size was larger in 13/15 (87%) cases, The mean Vl00 at day 0 was 97% (range: 85-100%), where 13/15 pts (87%) had > 95% of the gland covered by 144 Gy. At day 30, the mean V100 was 94% (range: 85-100%) with 7/15 (47%) pts showing 95% coverage of 144Gy. At day 0, the D90-144Gy range was achieved in 8/t5 pts(53%). 6/8 pts were above the Dg0 of 180Gy,and 1 pt slightly below 144Gy (139Gy). The mean D90 at day 0 was 176 Gy (Range: 139 to 205). At day 30, 8/15 (53%) pts were within range; however, the mean D90 dropped to 167Gy (Range 126 to 215Gy). The urethral constraint was achieved at day 0 in 14/15 (93%), with a mean V150 of 7%(Range 0 to 33%). However at day 30, 14/15 cases(93%), showed an increase of the V150 with a mean increase of 40% (Range 0 to 76%). Only 6/15 (40%) pts achieved a V150 < than 30% at day 30. The rectal wall constraint on day 0 was achieved in 13/15 pts (87%) with an mean V110 of 0.4 cc (range 0 to 2,6 cc), The mean at day 30 was 0.8 cc (range 0 to 2.1 cc), with 11/15 pts (73%) achieving the set constraint. Conclusion: Vari-Seed 6.7 did not maintain dose goals and constraints preset for the prostate and urethra, but was accurate for predicting rectal dose. 964
Poster
Early results o f a p h a s e 1 trial o f pelvic nodal irradiation In prostate cancer with intensity modulated radiotherapy (IMRT) J. Staffurth 1, D. Deamaley 1, H. McNair 1, D. Convery 2, E. Adams2, C. Clark2, J. Vaarkamp2, R, Huddart 1, S. Webb2, A. Horwich 1 1Royal Mars(fen NHS Trust, Radiotherapy, Surrey, United Kingdom 2Royal Marsden NHS Trust/Institute of Cancer Research, Physics, Surrey, United Kingdom introduction: Late bowel toxicity is the dose limiting side effect of pelvic radiotherapy. IMRT reduces bowel doses during PN irradiation and we are performing a Phase 1 trial escalating lymph node dose from 50-60 Gy in patients with advanced localized prostate cancer, who also receive adjuvant hormonal treatment. Methods: PTVl included the prostate and base of seminal vesicle, PTV2
Posters
remaining seminal vesicle and the hypogastric, obturator, pre-sacral, presciatic, internal and external lilac nodes, and PTV3 any involved PN. PTV1 received 70 Gy, PTV2 50 Gy and PTV3 55 Gy. The PTV2 and PTV3 doses will be escalated in 5 Gy increments in three cohorts. Inverse planning was performed with Corvus, Helax or Cadplan, Plans were delivered dynamically (Corvus and Cadplan) or by segmental MLC (Helax). Acute genitourinary (GU) and gastrointestinal (GI) RTOG toxicity has been recorded weekly during treatment. Late effects have been monitored with RTOG, LENT SOM, and FACT-P and UCLA prostate instruments. Acute effects are compared to a cohort of 30 patients with Iocalised prostate cancer treated to 74 Gy with conformal radiotherapy (3D-CRT). Results: Nineteen patients (median age 64 years (53-73)) have been treated. Median presenting PSA was 34.9 ng/ml (6.1-400). Thirteen men had T3 or T4 cancers, 8 with Gleason scores >7 and 6 had N1 disease. Average PTV1 median dose was 70 Gy, PTV2 51.1 Gy and PTV3 55 Gy. Volume of bowel irradiated to >50 Gy correlated with total volume of bowel (p
to intermediate grade, clinically localized prostate cancer Ft. Choo, V. Do, E. Bahk, L. Sugar, L. Klotz, C. Danjoux, G. Morton, G. DeBoer Toronto Sunnybrook Regional Cancer Centre, Radiation Oncology, Torchto, Canada Objective:To study the change of histologic grade of untreated, low to intermediate grade, clinically localized prostate adenocarcinoma (CLPA) over time on repeat biopsy. Materlats:A prospective single-arm cohort study has been in progress since November 1995, to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication for low to intermediate grade CLPA (T1 bT2c NOM0, Gleason score (GS) 7 or less, and PSA <15 ng/ml or less). Patients are managed with watchful observation alone as long as they do not meet the pre-defined criteria of disease progression. TRUS guided prostate biopsy is repeated at 12~18 months after enrolment to evaluate the change in GS. Possible associations of the change in GS with PSA doubling time and the baseline clinical parameters are explored with correlation analysis. Results:As of April 2001,67/161 (42%) eligible patients underwent re-biopsy of prostate. Re-biopsy was performed in 9 to 58 months after enrolment (median: 18). Median age is 70 years. The distribution of clinical stage, PSA at entry and initial GS is as follows: TI: T2 = 40:27, PSA < 5:5-9.9:10-14.9 = 23:34:10, initial GS 4:5:6:7:Gx = 2:13:37:14:1. Median PSA at entry is 7.6. Median follow-up is 29 months (range: 13-59). On repeat biopsy, GS was unchanged in 20 patients, upgraded in 20 and downgraded in 26 including 21 with no malignancy. Among patients with 2 or less positive cores on initial biopsy (n=43), 16 (37%) had no malignancy on re-biopsy. When there were 3 or greater positive cores on initial biopsy (n=19), only 2 (11%) had no malignancy on re-biopsy. In 5 patients who had TURP for the diagnosis of prostate cancer, 3 had no malignancy on re-biopsy. There was no statisticaily significant correlation between the change in GS and PSA doubling time or the baseline variables (age, initial PSA, clinical stage, and initial GS): Conclusion:In our cohort, there was no consistent upgrade of histologic grade on repeat biopsy at 9-58 months. This may be due to a short interval between the two biopsies, and/or the favorable clinical parameters of our cohorts which predict slow biological evolution over time. This observaUon is subject to the adequacy of biopsy sampling as well as intra- and interobserver variability of GS, The less the number of positive cores on initial biopsy, the higher the likelihood of being negative on the subsequent biopsy.
and 8 in the second year), 1 patient (0.8%) grade 3 toxicity, and 37 (31.3%) grade 1 rectal toxicity. Age, prostate dosimetry, prostate volume and presence of diabetes were not statistically significant for rectal toxicity. Presence of cardiovascular disease was of borderline significance. Logistic regression shows that RV50, RV100, and RV150 values are not predictive of grade 2 or higher toxicity (p-values of 0.43, 0.96, and 0.62 respectively), However, Grade > 2 late toxicity was more common if VR50 is above 5.5 cc (<5.5 cc: 6% vs. >5.5 cc: 23%; p= .03). VR100 cutoff of 0.99cc (10% vs 22%; p=. 13) and VR150 cutoff of 0.09cc (9%vs 21%; p=. 12) are not statistically significant, Conclusions: Anterior rectal wall DVH is a practical method for recording rectal dosimetry post TPIP. Rectal VR50 can be used to predict late rectal toxicity, 963
Poster
Analysis and first report of the predictive value of the variseed real-time dosimetric optimization program (version 6.7) for permanent radioactive seed implantation (PSI) o f t h e prostate
A. Raben, H. Chert, A. Grebler, J. Geltzeiler, M. Geltzeiler, I. Keselman, S. Litvin, D. Simmons, J. Yang 1Monmouth Medical Center, Radiation Oncology, Long Branch, New Jer, sey, USA 2Monmouth Medical Center, Urology, Long Branch, New Jersey, USA Purpose: To evaluate predictive value of a commercially available real-time optimization program for permanent seed implant of the prostate, Materials and Methods:15 pts underwent PSt with iodine-125 sources using the VariSeed version 6.7 optimization system. On implant day (Day 0), Pts underwent US measurement from base to apex. Images and 1-125 source strength information were downloaded into the VariSeed station, in order to deliver 75% of the dose to the periphery and 25% to the central volume. Dosimetric goals placed on the prostate included: D90 > 144Gy and < 180Gy, V100of >95%,and dose constraintsonthe urethra (V150 <30%: 216 Gy to less than 30%) and anterior rectal wall (V110 < 1.5cc: 160 Gy). A dose > than 144 Gy to the prostate was allowed if Constraints to urethra and rectum were met. Seeds were localized and recorded. Dosimetric calculation was performed after initial peripheral loading to determine additional central loading pattern and seed placement. Dosimetric analysis was done after of the procedure, and at day 30 for comparison, Results:Initial dosimetry over-estimated the number of required 1-125 seeds by 10 to 15% to achieve a D90-144Gy in all pts. The mean gland volume was 37cc, Day 0 (Range 25 - 55) and 42cc(Range 32 - 63)on day 30. The gland size was larger in 13/15 (87%) cases, The mean Vl00 at day 0 was 97% (range: 85-100%), where 13/15 pts (87%) had > 95% of the gland covered by 144 Gy. At day 30, the mean V100 was 94% (range: 85-100%) with 7/15 (47%) pts showing 95% coverage of 144Gy. At day 0, the D90-144Gy range was achieved in 8/t5 pts(53%). 6/8 pts were above the Dg0 of 180Gy,and 1 pt slightly below 144Gy (139Gy). The mean D90 at day 0 was 176 Gy (Range: 139 to 205). At day 30, 8/15 (53%) pts were within range; however, the mean D90 dropped to 167Gy (Range 126 to 215Gy). The urethral constraint was achieved at day 0 in 14/15 (93%), with a mean V150 of 7%(Range 0 to 33%). However at day 30, 14/15 cases(93%), showed an increase of the V150 with a mean increase of 40% (Range 0 to 76%). Only 6/15 (40%) pts achieved a V150 < than 30% at day 30. The rectal wall constraint on day 0 was achieved in 13/15 pts (87%) with an mean V110 of 0.4 cc (range 0 to 2,6 cc), The mean at day 30 was 0.8 cc (range 0 to 2.1 cc), with 11/15 pts (73%) achieving the set constraint. Conclusion: Vari-Seed 6.7 did not maintain dose goals and constraints preset for the prostate and urethra, but was accurate for predicting rectal dose. 964
Poster
Early results o f a p h a s e 1 trial o f pelvic nodal irradiation In prostate cancer with intensity modulated radiotherapy (IMRT) J. Staffurth 1, D. Deamaley 1, H. McNair 1, D. Convery 2, E. Adams2, C. Clark2, J. Vaarkamp2, R, Huddart 1, S. Webb2, A. Horwich 1 1Royal Mars(fen NHS Trust, Radiotherapy, Surrey, United Kingdom 2Royal Marsden NHS Trust/Institute of Cancer Research, Physics, Surrey, United Kingdom introduction: Late bowel toxicity is the dose limiting side effect of pelvic radiotherapy. IMRT reduces bowel doses during PN irradiation and we are performing a Phase 1 trial escalating lymph node dose from 50-60 Gy in patients with advanced localized prostate cancer, who also receive adjuvant hormonal treatment. Methods: PTVl included the prostate and base of seminal vesicle, PTV2
Posters
remaining seminal vesicle and the hypogastric, obturator, pre-sacral, presciatic, internal and external lilac nodes, and PTV3 any involved PN. PTV1 received 70 Gy, PTV2 50 Gy and PTV3 55 Gy. The PTV2 and PTV3 doses will be escalated in 5 Gy increments in three cohorts. Inverse planning was performed with Corvus, Helax or Cadplan, Plans were delivered dynamically (Corvus and Cadplan) or by segmental MLC (Helax). Acute genitourinary (GU) and gastrointestinal (GI) RTOG toxicity has been recorded weekly during treatment. Late effects have been monitored with RTOG, LENT SOM, and FACT-P and UCLA prostate instruments. Acute effects are compared to a cohort of 30 patients with Iocalised prostate cancer treated to 74 Gy with conformal radiotherapy (3D-CRT). Results: Nineteen patients (median age 64 years (53-73)) have been treated. Median presenting PSA was 34.9 ng/ml (6.1-400). Thirteen men had T3 or T4 cancers, 8 with Gleason scores >7 and 6 had N1 disease. Average PTV1 median dose was 70 Gy, PTV2 51.1 Gy and PTV3 55 Gy. Volume of bowel irradiated to >50 Gy correlated with total volume of bowel (p
to intermediate grade, clinically localized prostate cancer Ft. Choo, V. Do, E. Bahk, L. Sugar, L. Klotz, C. Danjoux, G. Morton, G. DeBoer Toronto Sunnybrook Regional Cancer Centre, Radiation Oncology, Torchto, Canada Objective:To study the change of histologic grade of untreated, low to intermediate grade, clinically localized prostate adenocarcinoma (CLPA) over time on repeat biopsy. Materlats:A prospective single-arm cohort study has been in progress since November 1995, to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication for low to intermediate grade CLPA (T1 bT2c NOM0, Gleason score (GS) 7 or less, and PSA <15 ng/ml or less). Patients are managed with watchful observation alone as long as they do not meet the pre-defined criteria of disease progression. TRUS guided prostate biopsy is repeated at 12~18 months after enrolment to evaluate the change in GS. Possible associations of the change in GS with PSA doubling time and the baseline clinical parameters are explored with correlation analysis. Results:As of April 2001,67/161 (42%) eligible patients underwent re-biopsy of prostate. Re-biopsy was performed in 9 to 58 months after enrolment (median: 18). Median age is 70 years. The distribution of clinical stage, PSA at entry and initial GS is as follows: TI: T2 = 40:27, PSA < 5:5-9.9:10-14.9 = 23:34:10, initial GS 4:5:6:7:Gx = 2:13:37:14:1. Median PSA at entry is 7.6. Median follow-up is 29 months (range: 13-59). On repeat biopsy, GS was unchanged in 20 patients, upgraded in 20 and downgraded in 26 including 21 with no malignancy. Among patients with 2 or less positive cores on initial biopsy (n=43), 16 (37%) had no malignancy on re-biopsy. When there were 3 or greater positive cores on initial biopsy (n=19), only 2 (11%) had no malignancy on re-biopsy. In 5 patients who had TURP for the diagnosis of prostate cancer, 3 had no malignancy on re-biopsy. There was no statisticaily significant correlation between the change in GS and PSA doubling time or the baseline variables (age, initial PSA, clinical stage, and initial GS): Conclusion:In our cohort, there was no consistent upgrade of histologic grade on repeat biopsy at 9-58 months. This may be due to a short interval between the two biopsies, and/or the favorable clinical parameters of our cohorts which predict slow biological evolution over time. This observaUon is subject to the adequacy of biopsy sampling as well as intra- and interobserver variability of GS, The less the number of positive cores on initial biopsy, the higher the likelihood of being negative on the subsequent biopsy.