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Intensity Modulated Radiation Therapy as Salvage Option after Permanent Brachytherapy Failure in Prostate Cancer
I. J. Radiation Oncology d Biology d Physics
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Volume 72, Number 1, Supplement, 2008
0.758). The three variables found to be independent predictors of FDM were PSADT (\0.0001), GS (0.012), and the use of initial ADT (0.006). Conclusion: PSADT remains a significant predictor of clinical failure and CSS for men treated with 3DCRT or IMRT who fail according to the Phoenix definition. The immediate use of ADT in patients with PSADT \6 months demonstrates significant improvements in CSS, although the benefit is less apparent in patients with longer PSADT. These results further refine the role of PSADT in predicting which patients may benefit from ADT for PSA failure and which patients may be observed expectantly and spared the toxicity of ADT. Author Disclosure: E.M. Horwitz, None; K. Ruth, None; R.G. Uzzo, None; M.K. Buyyounouski, None; Y. Wong, None; D.Y.T. Chen, None; A. Pollack, None.
1051
Intensity Modulated Radiation Therapy as Salvage Option after Permanent Brachytherapy Failure in Prostate Cancer
J. L. F. da Silva, C. M. K. Haddad, S. A. Hanna, C. E. V. Abreu Hospital Sirio Libanes, Sao Paulo, Brazil Purpose/Objective(s): Permanent prostate brachytherapy (PB) is a treatment option for localized prostate cancer. However, the options are uncertain and literature is scarce when failure occurs. Based on the hypothesis that PB fails mainly due to erroneous case selection or inadequate dosimetry, patients with local recurrence without metastases could be salvaged by another local treatment like external-beam radiation therapy. The aims of this study are to analyze the toxicity profile and the outcomes of a sample of patients submitted to salvage intensity-modulated radiation therapy (IMRT) after PB failure. Materials/Methods: Between June of 1998 and February of 2008, data from 11 patients were retrospectively reviewed. They received salvage IMRT after PB failure, detected by PSA increase and confirmed by at least one biopsy. Brachytherapy prescribed dose was 144 Gy with iodine-125 for all patients. IMRT doses varied according to each case. Toxicity analysis was according to Common Toxicity Criteria version 2.0. Statistical analysis was performed with software StatXact version 8. Results: Median age at PB was 68 years (56-79) and at IMRT was 74 years (58-84). Median time for failure was 47 months (2894). Median delivered radiation dose at salvage IMRT was 68 Gy (60-74). Salvage IMRT led to an increase of maximum toxicities at any time observed during the follow-up: Gastrointestinal toxicity: from 1 grade I case after-PB to 3 grade I cases, 1 grade II case, and 1 grade III case. Three cases were confirmed by rectoscopy. Genitourinary: from 5 grade I cases and 1 grade II case after-PB to 7 grade II cases and 1 grade III case. Sexual dysfunction has not been changed: 10 potent patients before PB have maintained it after IMRT treatment. Urinary continence: 2 patients have become incontinent - 1 grade III with complete resolution after implantation of artificial sphincter and another 1 grade II. Median follow-up after PB was 100 months (76-121) and after IMRT was 48 months (11-84). Nine patients had no evidence of biochemical or clinical disease (81.8%) at the time of their last consultation. One patient had evidence of bone metastases 10 months later after IMRT and was under hormonal therapy. Another patient developed bone metastases 36 months after salvage treatment and died due to visceral involvement 84 months later. Conclusions: Re-irradiation of the prostate can be effective and feasible, offering encouraging biochemical control possibilities, at the cost of increase in late toxicity scores, as 2 cases with incontinence in the follow-up. More studies are necessary to clarify this strategy. Author Disclosure: J.L.F. da Silva, None; C.M.K. Haddad, None; S.A. Hanna, None; C.E.V. Abreu, None.
1052
Local Control Following Permanent Prostate Brachytherapy (PPB): Effect of High Biologic Effective Dose on Biopsy Results and Oncologic Outcomes
N. N. Stone, R. G. Stock, J. A. Cesaretti, P. Unger Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): To determine the factors that influence local control (LC) and systemic relapse in patients undergoing PBB. Materials/Methods: 584 of 2241 patients who had PBB from 1990-2005 agreed to ultrasound guided prostate biopsy (PB) 2 years post-implant. A minimum of 6 cores (range, 6-30) were taken and repeated yearly if the initial PB was positive. Patients with an initial negative biopsy had subsequent repeat PB if PSA failure occurred. All patients with Gleason score (GS) $7, clinical stage $T2b or PSA .10 ng/ml had SV biopsies and pelvic lymph node dissection (PLND) if positive. Treatments included I-125 (n = 363, 62.2%, prescription dose 160 Gy, TG43), Pd-103 (n = 114, 19.5%, 125 Gy, NIST99), or Pd-103 (100 Gy) combined with EBRT (45 Gy, n = 107, 18.5%). Patients with positive SV and negative PLND had implant to the prostate and proximal SVs followed by 45 Gy EBRT. Hormone therapy (HT) was used for 9 months in 142/183 (77.6%) of the high risk (HR) patients, for 6 months in 77/141 (54.6%) of the intermediate risk (IR) patients, and for 3 months in low risk (LR) patients with PV .50 cc (n = 61/260, 23.5%). All biopsy material was reviewed by an experienced pathologist and was reported as negative or positive. Radiation doses were determined by 30-day CT dosimetry and converted to the biologic effective dose (BED, a/b=2). PSA failure was determined using the Phoenix definition. Comparisons were made by Chi-square analysis and linear regression. Survival was determined by the Kaplan Meier method with proportions tested by log rank. Results: The median PSA was 7.1 ng/ml (range, 1-189) and the median follow-up was 7.1 years (range, 1-16). 48/584 (8.2%) had a persistent positive PB. Of the 21 with a positive SV, 1 (4.8%) remained positive. Positive PB by BED group were #150 Gy, 22/ 121 (18.2%), .150-200 Gy, 15/244 (6.1%), and .200 Gy, 6/193 (3.1%, p\0.001). Regression analyses revealed in LR BED (p = 0.019), in IR HT (p = 0.011) and BED (p = 0.040), and in HR BED (p = 0.004) as predictors of a positive PB. Biochemical freedom from failure (bFFF) at 7 years was 82.7%. bFFF by biopsy results were 84.7% for negative vs 59.2% for positive PB (p \ 0.001). Cox regression revealed GS (p = 0.003), PSA (p\0.001), BED (p = 0.017), and PB (p = 0.017) as significant predictors of bFFF. In LR BED (p = 0.038) and PB (p = 0.002), in IR BED (p = 0.003), and in HR GS (p = 0.006), PSA (p \ 0.001), and PB (p = 0.038) remained significant. There were 53 deaths (9.1%), of which 8 were due to prostate cancer. Cause-specific survival (CSS) at 7 years was 99.2% for negative vs 87.6% for positive PB (p \ 0.001).
S136
Volume 72, Number 1, Supplement, 2008
0.758). The three variables found to be independent predictors of FDM were PSADT (\0.0001), GS (0.012), and the use of initial ADT (0.006). Conclusion: PSADT remains a significant predictor of clinical failure and CSS for men treated with 3DCRT or IMRT who fail according to the Phoenix definition. The immediate use of ADT in patients with PSADT \6 months demonstrates significant improvements in CSS, although the benefit is less apparent in patients with longer PSADT. These results further refine the role of PSADT in predicting which patients may benefit from ADT for PSA failure and which patients may be observed expectantly and spared the toxicity of ADT. Author Disclosure: E.M. Horwitz, None; K. Ruth, None; R.G. Uzzo, None; M.K. Buyyounouski, None; Y. Wong, None; D.Y.T. Chen, None; A. Pollack, None.
1051
Intensity Modulated Radiation Therapy as Salvage Option after Permanent Brachytherapy Failure in Prostate Cancer
J. L. F. da Silva, C. M. K. Haddad, S. A. Hanna, C. E. V. Abreu Hospital Sirio Libanes, Sao Paulo, Brazil Purpose/Objective(s): Permanent prostate brachytherapy (PB) is a treatment option for localized prostate cancer. However, the options are uncertain and literature is scarce when failure occurs. Based on the hypothesis that PB fails mainly due to erroneous case selection or inadequate dosimetry, patients with local recurrence without metastases could be salvaged by another local treatment like external-beam radiation therapy. The aims of this study are to analyze the toxicity profile and the outcomes of a sample of patients submitted to salvage intensity-modulated radiation therapy (IMRT) after PB failure. Materials/Methods: Between June of 1998 and February of 2008, data from 11 patients were retrospectively reviewed. They received salvage IMRT after PB failure, detected by PSA increase and confirmed by at least one biopsy. Brachytherapy prescribed dose was 144 Gy with iodine-125 for all patients. IMRT doses varied according to each case. Toxicity analysis was according to Common Toxicity Criteria version 2.0. Statistical analysis was performed with software StatXact version 8. Results: Median age at PB was 68 years (56-79) and at IMRT was 74 years (58-84). Median time for failure was 47 months (2894). Median delivered radiation dose at salvage IMRT was 68 Gy (60-74). Salvage IMRT led to an increase of maximum toxicities at any time observed during the follow-up: Gastrointestinal toxicity: from 1 grade I case after-PB to 3 grade I cases, 1 grade II case, and 1 grade III case. Three cases were confirmed by rectoscopy. Genitourinary: from 5 grade I cases and 1 grade II case after-PB to 7 grade II cases and 1 grade III case. Sexual dysfunction has not been changed: 10 potent patients before PB have maintained it after IMRT treatment. Urinary continence: 2 patients have become incontinent - 1 grade III with complete resolution after implantation of artificial sphincter and another 1 grade II. Median follow-up after PB was 100 months (76-121) and after IMRT was 48 months (11-84). Nine patients had no evidence of biochemical or clinical disease (81.8%) at the time of their last consultation. One patient had evidence of bone metastases 10 months later after IMRT and was under hormonal therapy. Another patient developed bone metastases 36 months after salvage treatment and died due to visceral involvement 84 months later. Conclusions: Re-irradiation of the prostate can be effective and feasible, offering encouraging biochemical control possibilities, at the cost of increase in late toxicity scores, as 2 cases with incontinence in the follow-up. More studies are necessary to clarify this strategy. Author Disclosure: J.L.F. da Silva, None; C.M.K. Haddad, None; S.A. Hanna, None; C.E.V. Abreu, None.
1052
Local Control Following Permanent Prostate Brachytherapy (PPB): Effect of High Biologic Effective Dose on Biopsy Results and Oncologic Outcomes
N. N. Stone, R. G. Stock, J. A. Cesaretti, P. Unger Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): To determine the factors that influence local control (LC) and systemic relapse in patients undergoing PBB. Materials/Methods: 584 of 2241 patients who had PBB from 1990-2005 agreed to ultrasound guided prostate biopsy (PB) 2 years post-implant. A minimum of 6 cores (range, 6-30) were taken and repeated yearly if the initial PB was positive. Patients with an initial negative biopsy had subsequent repeat PB if PSA failure occurred. All patients with Gleason score (GS) $7, clinical stage $T2b or PSA .10 ng/ml had SV biopsies and pelvic lymph node dissection (PLND) if positive. Treatments included I-125 (n = 363, 62.2%, prescription dose 160 Gy, TG43), Pd-103 (n = 114, 19.5%, 125 Gy, NIST99), or Pd-103 (100 Gy) combined with EBRT (45 Gy, n = 107, 18.5%). Patients with positive SV and negative PLND had implant to the prostate and proximal SVs followed by 45 Gy EBRT. Hormone therapy (HT) was used for 9 months in 142/183 (77.6%) of the high risk (HR) patients, for 6 months in 77/141 (54.6%) of the intermediate risk (IR) patients, and for 3 months in low risk (LR) patients with PV .50 cc (n = 61/260, 23.5%). All biopsy material was reviewed by an experienced pathologist and was reported as negative or positive. Radiation doses were determined by 30-day CT dosimetry and converted to the biologic effective dose (BED, a/b=2). PSA failure was determined using the Phoenix definition. Comparisons were made by Chi-square analysis and linear regression. Survival was determined by the Kaplan Meier method with proportions tested by log rank. Results: The median PSA was 7.1 ng/ml (range, 1-189) and the median follow-up was 7.1 years (range, 1-16). 48/584 (8.2%) had a persistent positive PB. Of the 21 with a positive SV, 1 (4.8%) remained positive. Positive PB by BED group were #150 Gy, 22/ 121 (18.2%), .150-200 Gy, 15/244 (6.1%), and .200 Gy, 6/193 (3.1%, p\0.001). Regression analyses revealed in LR BED (p = 0.019), in IR HT (p = 0.011) and BED (p = 0.040), and in HR BED (p = 0.004) as predictors of a positive PB. Biochemical freedom from failure (bFFF) at 7 years was 82.7%. bFFF by biopsy results were 84.7% for negative vs 59.2% for positive PB (p \ 0.001). Cox regression revealed GS (p = 0.003), PSA (p\0.001), BED (p = 0.017), and PB (p = 0.017) as significant predictors of bFFF. In LR BED (p = 0.038) and PB (p = 0.002), in IR BED (p = 0.003), and in HR GS (p = 0.006), PSA (p \ 0.001), and PB (p = 0.038) remained significant. There were 53 deaths (9.1%), of which 8 were due to prostate cancer. Cause-specific survival (CSS) at 7 years was 99.2% for negative vs 87.6% for positive PB (p \ 0.001).