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Body Mass Index and PSA Failure Following Brachytherapy for Localized Prostate Cancer
Proceedings of the 49th Annual ASTRO Meeting
2227
Interstitial High Dose Rate (HDR) Brachtherapy as Monotherapy for Early Stage Prostate Cancer: A Report of 206 Cases
R. J. Mark1,2, R. S. Akins3, P. J. Anderson1, T. R. Neumann1, M. Nair1, D. White1, S. Gurley1 1
Joe Arrington Cancer Center, Lubbock, TX, 2Texas Tech University, Lubbock, TX, 3University of Miami, Miami, FL
Purpose/Objective(s): Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) technique has been reported with results comparing favorably to surgery and External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial implant is combined with EBRT. There is little published data on HDR alone. We report our results with HDR alone. Materials/Methods: Between 1997 and 2007, 206 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant, under spinal anesthetic or local anesthetic. There were no Gleason Score or PSA exclusions. No patient received EBRT or Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes ranged from 41 cm3 to 196 cm3. Treatment volume included the prostate and seminal vesicles in all cases. Radiation Treatment planning was performed using CT Scanning and the Nucletron Plato Treatment Planning System. Our IRB protocol for HDR alone, has called for two HDR Implants, spaced 4 weeks apart. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12–16) were followed, and limited to #105% of the prescription dose. Results: With a median follow-up of 78 months (range: 6 months to 132 months), PSA disease free survival was 89.3% (184/206). Acute and chronic complications were uncommon. Urethral stricture requiring dilatation has developed in 5.3% (11/206) of patients. Urinary stress incontinence has occurred in 3.9% (8/206). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.9% (8/206) Grade 2. RTOG late rectal toxicities were: 0.5% (1/206) Grade 4, 0% Grade 3, 1.5% (3/206) Grade 2, and 1.9% (4/206) Grade 1. Conclusions: With a median follow-up of 78 months, results with HDR implant alone compare favorably to EBRT, LDR ± EBRT, and HDR + EBRT, both with regard to PSA disease free survival, and complications. HDR offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, bladder and rectal complications appear to be significantly reduced. Author Disclosure: R.J. Mark, None; R.S. Akins, None; P.J. Anderson, None; T.R. Neumann, None; M. Nair, None; D. White, None; S. Gurley, None.
2228
Association of Rectal Dosimetry and Toxicity With Body Mass Index After Permanent Brachytherapy for Low Risk Prostate Cancer
J. M. Crook, E. P. Saibishkumar, G. Pond, M. Aneja Princess Margaret Hospital, Toronto, ON, Canada Purpose/Objective(s): Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by inverse square law. We hypothesized that men with higher BMI will have a lower dose to rectal wall and less rectal toxicity after permanent prostate implant. Materials/Methods: Prospectively-collected data on rectal dosimetry/toxicity and body mass index of 366 patients who underwent 125I prostate implant was analyzed. All implants were done by a single experienced radiation oncologist. Rectal wall was contoured on all slices where seeds were seen. Post implant dosimetry used CT-MRI fusion on day 30 for all patients. The volume of rectal wall receiving the prescribed dose (RV100 in cc) and the dose to 1 cc of rectal wall (RD1cc) were reported for rectal dosimetry. Other factors evaluated for association with rectal dosimetry included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, prostate volume, prostate edema, and prostate dosimetry factors (D90 V100, V150). Rectal toxicity was reported as per RTOG criteria. All the above-mentioned factors as well as RV100 and RD1cc were analyzed for rectal toxicity. Pearson correlation coefficient and logistic regression were used for univariate and multivariate analysis respectively. Results: The BMI ranged from 15.9 to 46.8 (mean ± SD: 27.8 ± 4.2). The mean ± SD values for RV100 and RD1cc were 0.78 ± 0.47 cc and 128.2 ± 27.8 Gy respectively. There was significant negative association of BMI with RV100 (p = 0.006) and RD1cc (p = 0.003) on univariate analysis. The mean RV100 and RD1cc for men with higher BMI (.27.8) were lower compared to their counterparts (0.7 vs. 0.86 cc and 123.4 vs. 132.4 Gy respectively). On multivariate analysis for RV100 and RD1cc, BMI remained significant (p- values 0.002 and 0.003 respectively)) along with prostate volume and V150. This finding suggests that anatomic factors are important in rectal dosimetry in permanent implant for prostate cancer. Overall the incidence of RTOG acute rectal toxicity was 12% (grade 2: 1.3%) and chronic 6% (grade 2: 0.5%). No grade 3 toxicity occurred. None of the factors evaluated were predictive for rectal toxicity. Conclusions: Men with lower BMI receive significantly higher rectal wall dose compared to those with higher BMI. This did not, however, translate into higher rectal toxicity. Author Disclosure: J.M. Crook, None; E.P. Saibishkumar, None; G. Pond, None; M. Aneja, None.
2229
Body Mass Index and PSA Failure Following Brachytherapy for Localized Prostate Cancer
1
J. J. Coen , J. A. Efstathiou1, R. Y. Skowronski1, J. A. Grocela1, A. E. Hirsch2, A. L. Zietman1 1
Massachusetts General Hospital, Boston, MA, 2Boston Medical Center, Boston, MA
Purpose/Objective(s): Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT). We investigated whether BMI is associated with time to PSA failure in a cohort of men treated with permanent prostate brachytherapy for clinically localized prostate cancer.
S329
I. J. Radiation Oncology d Biology d Physics
S330
Volume 69, Number 3, Supplement, 2007
Patients/Methods: A retrospective analysis was conducted on 374 consecutive patients who underwent brachytherapy with or without supplemental EBRT and/or ADT for clinical stage T1c-T2c NX M0 prostate cancer between August 1996 and December 2001 and who had a minimum follow-up of 3 years. Forty-nine (13%) of these patients received supplemental EBRT and 131 (35%) received ADT, while 207 (55.4%) were treated with brachytherapy only. Height and weight data were available at baseline for 353 (94%) of the men. Cox regression analyses were performed to evaluate the relationship between BMI and time to PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, pre-implant PSA level, Gleason score, T-category, use of supplemental EBRT, and use of ADT. Results: Median age, PSA, and BMI at baseline were 66 (range 42–80) years, 5.7 (range 0.4–22.6) ng/ml, and 27.1 (range 18.2– 53.6) kg/m2, respectively. After a median follow-up of 6.0 (range 3.0–10.2) years, there were a total of 76 PSA failures. BMI was not associated with PSA failure. At 6-years, the PSA failure rate was 30.2% for men with BMI \ 25 kg/m2, 19.5% for men with BMI $25–\30, and 14.4% for men with BMI $30 (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, when using alternative definitions of PSA failure, and when excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure [adjusted HR 1.12, 95% CI 1.05– 1.20, p = 0.0006] (Table). Conclusions: Unlike following surgery or EBRT, a greater baseline BMI is not associated with higher PSA failure rates in men treated with brachytherapy for clinically localized prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy for obese patients. Table: Multivariate Analysis of PSA Failure using Nadir +2 Definition (n = 350) Covariate BMI (kg/m2) \25 $25–\30 $30 Baseline PSA (ng/ml), continuous Gleason score #6 7 8–10 Tumor category T1 T2 EBRT No Yes ADT No Yes Race Black Other
Adjusted HR [95% CI]
p-value
— 0.76 [0.45–1.29] 0.56 [0.29–1.10] 1.12 [1.05–1.20]
— 0.31 0.091 0.0006
— 1.64 [0.91–2.96] 0.94 [0.22–4.00]
— 0.099 0.93
— 0.81 [0.45–1.43]
— 0.46
— 1.12 [0.56–2.23]
— 0.75
— 1.11 [0.68–1.83]
— 0.68
— 0.49 [0.22–1.07]
— 0.073
Author Disclosure: J.J. Coen, None; J.A. Efstathiou, None; R.Y. Skowronski, None; J.A. Grocela, None; A.E. Hirsch, None; A.L. Zietman, None.
2230
The Effect of the Time Interval Between Brachytherapy and Post-implant Dosimetric Evaluation on Dosimetric Quality: Analysis of the Pro-qura Database
P. Grimm1, G. S. Merrick2, J. Blasko1, J. Sylvester1, Z. Allen2,3, W. Butler2, U. Chaudry2, M. Sitter1 1
Seattle Prostate Center, Seattle, WA, 2Schiffler Cancer Center, Wheeling, WV, 3Wheeling Jesuit University, Wheeling, WV
Purpose/Objective(s): To analyze the Pro-Qura database to evaluate the effect of time interval between brachytherapy and postimplant dosimetric evaluation on post-implant dosimetric quality. Materials/Methods: In the Pro-Qura database, 4,593 post plans from 57 institutions were stratified by the time interval between implant and post-implant CT scan. Post-implant CT evaluated at multiple intervals. This analysis was reinstituted to the 2,370 patients with day 0 and day 30 with post-implant dosimetry. I-125 was used in 1,755 patients and Pd-103 in 615. Post-implant dosimetry was performed in a standardized fashion by overlaying the pre-implant ultrasound and the post-implant CT scan. Criteria for implant adequacy included a D90 . 90% and a V100 . 80% for both isotopes. An adequate V150 was defined as \60% for I-125 and \75% for Pd-103. A D90 . 140% was deemed ‘‘too hot’’. Results: Day 0 dosimetric evaluation resulted in a mean V100 and D90 of 81.6% and 88.7% respectively. A V100 and D90 of 87.8% and 100.0% were reported for day 30 dosimetry (p \ 0.001). Day 0 dosimetric evaluation resulted in 26.9% of implants being ‘‘too cool’’ and 13.4% ‘‘too hot’’. In contrast, 20.1% of day 30 dosimetric evaluations were ‘‘too cool’’ and 16.1% ‘‘too hot’’. In terms of isotope, Pd-103 cases were more likely to be ‘‘too cool’’ while I-125 cases more likely to be ‘‘too hot’’. Conclusions: Post-implant dosimetry performed at day 30 results in statistically and clinically significant improvements in postimplant dosimetric parameters compared to day 0 dosimetry in community-based brachytherapy programs. The influence of timing is substantially greater for Pd-103 than I-125 implants. Author Disclosure: P. Grimm, None; G.S. Merrick, None; J. Blasko, None; J. Sylvester, None; Z. Allen, None; W. Butler, None; U. Chaudry, None; M. Sitter, None.
2227
Interstitial High Dose Rate (HDR) Brachtherapy as Monotherapy for Early Stage Prostate Cancer: A Report of 206 Cases
R. J. Mark1,2, R. S. Akins3, P. J. Anderson1, T. R. Neumann1, M. Nair1, D. White1, S. Gurley1 1
Joe Arrington Cancer Center, Lubbock, TX, 2Texas Tech University, Lubbock, TX, 3University of Miami, Miami, FL
Purpose/Objective(s): Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) technique has been reported with results comparing favorably to surgery and External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial implant is combined with EBRT. There is little published data on HDR alone. We report our results with HDR alone. Materials/Methods: Between 1997 and 2007, 206 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant, under spinal anesthetic or local anesthetic. There were no Gleason Score or PSA exclusions. No patient received EBRT or Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes ranged from 41 cm3 to 196 cm3. Treatment volume included the prostate and seminal vesicles in all cases. Radiation Treatment planning was performed using CT Scanning and the Nucletron Plato Treatment Planning System. Our IRB protocol for HDR alone, has called for two HDR Implants, spaced 4 weeks apart. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12–16) were followed, and limited to #105% of the prescription dose. Results: With a median follow-up of 78 months (range: 6 months to 132 months), PSA disease free survival was 89.3% (184/206). Acute and chronic complications were uncommon. Urethral stricture requiring dilatation has developed in 5.3% (11/206) of patients. Urinary stress incontinence has occurred in 3.9% (8/206). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.9% (8/206) Grade 2. RTOG late rectal toxicities were: 0.5% (1/206) Grade 4, 0% Grade 3, 1.5% (3/206) Grade 2, and 1.9% (4/206) Grade 1. Conclusions: With a median follow-up of 78 months, results with HDR implant alone compare favorably to EBRT, LDR ± EBRT, and HDR + EBRT, both with regard to PSA disease free survival, and complications. HDR offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, bladder and rectal complications appear to be significantly reduced. Author Disclosure: R.J. Mark, None; R.S. Akins, None; P.J. Anderson, None; T.R. Neumann, None; M. Nair, None; D. White, None; S. Gurley, None.
2228
Association of Rectal Dosimetry and Toxicity With Body Mass Index After Permanent Brachytherapy for Low Risk Prostate Cancer
J. M. Crook, E. P. Saibishkumar, G. Pond, M. Aneja Princess Margaret Hospital, Toronto, ON, Canada Purpose/Objective(s): Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by inverse square law. We hypothesized that men with higher BMI will have a lower dose to rectal wall and less rectal toxicity after permanent prostate implant. Materials/Methods: Prospectively-collected data on rectal dosimetry/toxicity and body mass index of 366 patients who underwent 125I prostate implant was analyzed. All implants were done by a single experienced radiation oncologist. Rectal wall was contoured on all slices where seeds were seen. Post implant dosimetry used CT-MRI fusion on day 30 for all patients. The volume of rectal wall receiving the prescribed dose (RV100 in cc) and the dose to 1 cc of rectal wall (RD1cc) were reported for rectal dosimetry. Other factors evaluated for association with rectal dosimetry included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, prostate volume, prostate edema, and prostate dosimetry factors (D90 V100, V150). Rectal toxicity was reported as per RTOG criteria. All the above-mentioned factors as well as RV100 and RD1cc were analyzed for rectal toxicity. Pearson correlation coefficient and logistic regression were used for univariate and multivariate analysis respectively. Results: The BMI ranged from 15.9 to 46.8 (mean ± SD: 27.8 ± 4.2). The mean ± SD values for RV100 and RD1cc were 0.78 ± 0.47 cc and 128.2 ± 27.8 Gy respectively. There was significant negative association of BMI with RV100 (p = 0.006) and RD1cc (p = 0.003) on univariate analysis. The mean RV100 and RD1cc for men with higher BMI (.27.8) were lower compared to their counterparts (0.7 vs. 0.86 cc and 123.4 vs. 132.4 Gy respectively). On multivariate analysis for RV100 and RD1cc, BMI remained significant (p- values 0.002 and 0.003 respectively)) along with prostate volume and V150. This finding suggests that anatomic factors are important in rectal dosimetry in permanent implant for prostate cancer. Overall the incidence of RTOG acute rectal toxicity was 12% (grade 2: 1.3%) and chronic 6% (grade 2: 0.5%). No grade 3 toxicity occurred. None of the factors evaluated were predictive for rectal toxicity. Conclusions: Men with lower BMI receive significantly higher rectal wall dose compared to those with higher BMI. This did not, however, translate into higher rectal toxicity. Author Disclosure: J.M. Crook, None; E.P. Saibishkumar, None; G. Pond, None; M. Aneja, None.
2229
Body Mass Index and PSA Failure Following Brachytherapy for Localized Prostate Cancer
1
J. J. Coen , J. A. Efstathiou1, R. Y. Skowronski1, J. A. Grocela1, A. E. Hirsch2, A. L. Zietman1 1
Massachusetts General Hospital, Boston, MA, 2Boston Medical Center, Boston, MA
Purpose/Objective(s): Greater body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure following radical prostatectomy and external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT). We investigated whether BMI is associated with time to PSA failure in a cohort of men treated with permanent prostate brachytherapy for clinically localized prostate cancer.
S329
I. J. Radiation Oncology d Biology d Physics
S330
Volume 69, Number 3, Supplement, 2007
Patients/Methods: A retrospective analysis was conducted on 374 consecutive patients who underwent brachytherapy with or without supplemental EBRT and/or ADT for clinical stage T1c-T2c NX M0 prostate cancer between August 1996 and December 2001 and who had a minimum follow-up of 3 years. Forty-nine (13%) of these patients received supplemental EBRT and 131 (35%) received ADT, while 207 (55.4%) were treated with brachytherapy only. Height and weight data were available at baseline for 353 (94%) of the men. Cox regression analyses were performed to evaluate the relationship between BMI and time to PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, pre-implant PSA level, Gleason score, T-category, use of supplemental EBRT, and use of ADT. Results: Median age, PSA, and BMI at baseline were 66 (range 42–80) years, 5.7 (range 0.4–22.6) ng/ml, and 27.1 (range 18.2– 53.6) kg/m2, respectively. After a median follow-up of 6.0 (range 3.0–10.2) years, there were a total of 76 PSA failures. BMI was not associated with PSA failure. At 6-years, the PSA failure rate was 30.2% for men with BMI \ 25 kg/m2, 19.5% for men with BMI $25–\30, and 14.4% for men with BMI $30 (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, when using alternative definitions of PSA failure, and when excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure [adjusted HR 1.12, 95% CI 1.05– 1.20, p = 0.0006] (Table). Conclusions: Unlike following surgery or EBRT, a greater baseline BMI is not associated with higher PSA failure rates in men treated with brachytherapy for clinically localized prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy for obese patients. Table: Multivariate Analysis of PSA Failure using Nadir +2 Definition (n = 350) Covariate BMI (kg/m2) \25 $25–\30 $30 Baseline PSA (ng/ml), continuous Gleason score #6 7 8–10 Tumor category T1 T2 EBRT No Yes ADT No Yes Race Black Other
Adjusted HR [95% CI]
p-value
— 0.76 [0.45–1.29] 0.56 [0.29–1.10] 1.12 [1.05–1.20]
— 0.31 0.091 0.0006
— 1.64 [0.91–2.96] 0.94 [0.22–4.00]
— 0.099 0.93
— 0.81 [0.45–1.43]
— 0.46
— 1.12 [0.56–2.23]
— 0.75
— 1.11 [0.68–1.83]
— 0.68
— 0.49 [0.22–1.07]
— 0.073
Author Disclosure: J.J. Coen, None; J.A. Efstathiou, None; R.Y. Skowronski, None; J.A. Grocela, None; A.E. Hirsch, None; A.L. Zietman, None.
2230
The Effect of the Time Interval Between Brachytherapy and Post-implant Dosimetric Evaluation on Dosimetric Quality: Analysis of the Pro-qura Database
P. Grimm1, G. S. Merrick2, J. Blasko1, J. Sylvester1, Z. Allen2,3, W. Butler2, U. Chaudry2, M. Sitter1 1
Seattle Prostate Center, Seattle, WA, 2Schiffler Cancer Center, Wheeling, WV, 3Wheeling Jesuit University, Wheeling, WV
Purpose/Objective(s): To analyze the Pro-Qura database to evaluate the effect of time interval between brachytherapy and postimplant dosimetric evaluation on post-implant dosimetric quality. Materials/Methods: In the Pro-Qura database, 4,593 post plans from 57 institutions were stratified by the time interval between implant and post-implant CT scan. Post-implant CT evaluated at multiple intervals. This analysis was reinstituted to the 2,370 patients with day 0 and day 30 with post-implant dosimetry. I-125 was used in 1,755 patients and Pd-103 in 615. Post-implant dosimetry was performed in a standardized fashion by overlaying the pre-implant ultrasound and the post-implant CT scan. Criteria for implant adequacy included a D90 . 90% and a V100 . 80% for both isotopes. An adequate V150 was defined as \60% for I-125 and \75% for Pd-103. A D90 . 140% was deemed ‘‘too hot’’. Results: Day 0 dosimetric evaluation resulted in a mean V100 and D90 of 81.6% and 88.7% respectively. A V100 and D90 of 87.8% and 100.0% were reported for day 30 dosimetry (p \ 0.001). Day 0 dosimetric evaluation resulted in 26.9% of implants being ‘‘too cool’’ and 13.4% ‘‘too hot’’. In contrast, 20.1% of day 30 dosimetric evaluations were ‘‘too cool’’ and 16.1% ‘‘too hot’’. In terms of isotope, Pd-103 cases were more likely to be ‘‘too cool’’ while I-125 cases more likely to be ‘‘too hot’’. Conclusions: Post-implant dosimetry performed at day 30 results in statistically and clinically significant improvements in postimplant dosimetric parameters compared to day 0 dosimetry in community-based brachytherapy programs. The influence of timing is substantially greater for Pd-103 than I-125 implants. Author Disclosure: P. Grimm, None; G.S. Merrick, None; J. Blasko, None; J. Sylvester, None; Z. Allen, None; W. Butler, None; U. Chaudry, None; M. Sitter, None.