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II Trial of HDR-Brachytherapy Boosted Comprehensive IMRT for Intermediate-Risk Adenocarcinoma of the Prostate
Proceedings of the 49th Annual ASTRO Meeting
2286
Interstitial High Dose Rate (HDR) Brachytherapy + IMRT vs. HDR Monotherapy for Early Stage Prostate Cancer: A Report of 315 Cases
D. White1, R. J. Mark1,2, P. J. Anderson1, T. R. Neumann1, M. Nair1, S. Gurley1, R. S. Akins3 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 High Dose Rate (HDR) + External Beam Radiation Therapy (EBRT) technique has been reported with results comparing favorably to surgery, Low Dose Rate (LDR) brachytherapy ± EBRT, EBRT, and Intensity Modulated Radiation Therapy (IMRT). The role of supplemental EBRT in brachytherapy is controversial. We compare our results of HDR + IMRT vs. HDR monotherapy. Materials/Methods: Between 1997 and 2007, 315 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant. There were no Gleason Score or PSA exclusions. After discussion of treatment options, 109 patients elected HDR Implant + IMRT and 201 patients underwent HDR monotherapy. No patient received Hormonal Blockade. Median Gleason Score was 7 (range : 4 to 10). Median PSA was 9.8 (0.60 to 39.8). IMRT treatment volume included the prostate + seminal vesicles + 2 cm margin. Implant treatment volumes ranged from 42 cm3 to 196 cm3. In patients who received IMRT + HDR, 4500 cGy in 25 fractions was given via IMRT and 1650 cGy to 2000 cGy in 3 fractions via HDR. Our protocol for HDR alone, has called for two HDR Implants. 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: There was no significant difference between the treatment groups with respect to T-Stage, Gleason Score, and PSA. With a median follow-up of 78 months (range: 6 months to 132 months), the overall PSA disease free survival was 88.9% (280/315). In patients undergoing IMRT + HDR Implant, PSA disease free survival was 88.1% (96/109) vs. 89.3% (184/206) for patients undergoing HDR alone (p = 0.6). The 5 year actuarial survival was 86% for the group receiving IMRT + HDR vs. 89% with HDR monotherapy (log rank = 0.5). Urethral stricture requiring dilatation has developed in 3.8% (12/315) of patients. Urinary stress incontinence has occurred in 3.2% (10/315). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.2% (10/315) Grade 2. RTOG late rectal toxicities were: 0.3% (1/315) Grade 4, 0% Grade 3, 3.5% (11/315) Grade 2, and 4.1% (13/315) Grade 1. RTOG late rectal toxicity was higher in patients undergoing HDR + IMRT with 15.6% (17/109) of patients experiencing Grade 2 and 1 symptoms, vs. 3.4% (7/206) receiving HDR alone (p # 0.01). Conclusions: We have observed no significant difference in PSA disease free survival in patients undergoing HDR monotherapy vs. HDR + IMRT. Complications were similar, though RTOG Grade 1 and 2 late toxicity was higher in patients receiving HDR + IMRT. HDR monotherapy compares favorably to EBRT, LDR ± EBRT, and HDR + IMRT, both with regard to PSA disease free survival, and complications. With regard to implant technique, HDR brachytherapy 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, rectal complications may be reduced. Author Disclosure: D. White, None; R.J. Mark, None; P.J. Anderson, None; T.R. Neumann, None; M. Nair, None; S. Gurley, None; R.S. Akins, None.
2287
Phase I/II Trial of HDR-Brachytherapy Boosted Comprehensive IMRT for Intermediate-Risk Adenocarcinoma of the Prostate
M. Hagan, D. Todor, N. Dogan, Y. Wu, M. Anscher, D. Arthur Medical College of Virginia Hospitals, Richmond, VA Purpose/Objective(s): A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of IMRT delivered to the prostate, peri-prostatic soft-tissues and pelvic lymph nodes (PLN) combined with HDR-brachytherapy boosting of the prostate alone. Materials/Methods: From 2001 through 2006, 43 patients were treated on the phase I/II trial of HDR-brachytherapy boosted comprehensive IMRT for intermediate-risk adenocarcinoma of the prostate or its antecedent pilot study. Eligibility was limited to patients with T-stage # 2 b, PSA # 20 and Gleason score #7. Treatment was initialized with a single HDR fraction of 6 Gy, during which fiducial markers were placed in the prostate. Brachytherapy was followed by IMRT optimized to deliver in 28 fractions a Normalized Total Dose (NTD2 Gy) of 70 Gy to the prostate (plus a 5 mm margin) and the most proximal 2 cm of seminal vesicles. PLN received 50.4 Gy. The combined NTD2 Gy dose to the prostate was 80 Gy. Patients whose pre-treatment PSA was .10 ng/ml received short-term androgen ablation, consisting of 4 months of single-agent luprolide therapy. Results: All 43 patients completed treatment without Grade 3 toxicities. Acute grade 2 genitourinary toxicity (dysuria) occurred in fewer than 8% of patients. No acute grade 2 gastrointestinal toxicity was observed. Late toxicity was limited to transient grade 2 rectal bleeding observed in four patients (9%) after a median follow-up of 42 months. The median nadir PSA value was 0.2 ng/ml, with a range of 0.0–0.4 ng/ml. Ultrasound imaging of the prostate after 24 months revealed a median volume reduction of 56%(±2%). No biochemical failures have been observed. Conclusions: HDR-boosted IMRT is a safe, effective method for the delivery of 80 Gy to the prostate, while providing comprehensive treatment of the peri-prostatic soft tissues and PLN. The biologic response represented by the prostate volume reduction appears to be consistent with the dose delivered. Author Disclosure: M. Hagan, None; D. Todor, None; N. Dogan, None; Y. Wu, None; M. Anscher, None; D. Arthur, None.
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2286
Interstitial High Dose Rate (HDR) Brachytherapy + IMRT vs. HDR Monotherapy for Early Stage Prostate Cancer: A Report of 315 Cases
D. White1, R. J. Mark1,2, P. J. Anderson1, T. R. Neumann1, M. Nair1, S. Gurley1, R. S. Akins3 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 High Dose Rate (HDR) + External Beam Radiation Therapy (EBRT) technique has been reported with results comparing favorably to surgery, Low Dose Rate (LDR) brachytherapy ± EBRT, EBRT, and Intensity Modulated Radiation Therapy (IMRT). The role of supplemental EBRT in brachytherapy is controversial. We compare our results of HDR + IMRT vs. HDR monotherapy. Materials/Methods: Between 1997 and 2007, 315 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant. There were no Gleason Score or PSA exclusions. After discussion of treatment options, 109 patients elected HDR Implant + IMRT and 201 patients underwent HDR monotherapy. No patient received Hormonal Blockade. Median Gleason Score was 7 (range : 4 to 10). Median PSA was 9.8 (0.60 to 39.8). IMRT treatment volume included the prostate + seminal vesicles + 2 cm margin. Implant treatment volumes ranged from 42 cm3 to 196 cm3. In patients who received IMRT + HDR, 4500 cGy in 25 fractions was given via IMRT and 1650 cGy to 2000 cGy in 3 fractions via HDR. Our protocol for HDR alone, has called for two HDR Implants. 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: There was no significant difference between the treatment groups with respect to T-Stage, Gleason Score, and PSA. With a median follow-up of 78 months (range: 6 months to 132 months), the overall PSA disease free survival was 88.9% (280/315). In patients undergoing IMRT + HDR Implant, PSA disease free survival was 88.1% (96/109) vs. 89.3% (184/206) for patients undergoing HDR alone (p = 0.6). The 5 year actuarial survival was 86% for the group receiving IMRT + HDR vs. 89% with HDR monotherapy (log rank = 0.5). Urethral stricture requiring dilatation has developed in 3.8% (12/315) of patients. Urinary stress incontinence has occurred in 3.2% (10/315). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.2% (10/315) Grade 2. RTOG late rectal toxicities were: 0.3% (1/315) Grade 4, 0% Grade 3, 3.5% (11/315) Grade 2, and 4.1% (13/315) Grade 1. RTOG late rectal toxicity was higher in patients undergoing HDR + IMRT with 15.6% (17/109) of patients experiencing Grade 2 and 1 symptoms, vs. 3.4% (7/206) receiving HDR alone (p # 0.01). Conclusions: We have observed no significant difference in PSA disease free survival in patients undergoing HDR monotherapy vs. HDR + IMRT. Complications were similar, though RTOG Grade 1 and 2 late toxicity was higher in patients receiving HDR + IMRT. HDR monotherapy compares favorably to EBRT, LDR ± EBRT, and HDR + IMRT, both with regard to PSA disease free survival, and complications. With regard to implant technique, HDR brachytherapy 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, rectal complications may be reduced. Author Disclosure: D. White, None; R.J. Mark, None; P.J. Anderson, None; T.R. Neumann, None; M. Nair, None; S. Gurley, None; R.S. Akins, None.
2287
Phase I/II Trial of HDR-Brachytherapy Boosted Comprehensive IMRT for Intermediate-Risk Adenocarcinoma of the Prostate
M. Hagan, D. Todor, N. Dogan, Y. Wu, M. Anscher, D. Arthur Medical College of Virginia Hospitals, Richmond, VA Purpose/Objective(s): A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of IMRT delivered to the prostate, peri-prostatic soft-tissues and pelvic lymph nodes (PLN) combined with HDR-brachytherapy boosting of the prostate alone. Materials/Methods: From 2001 through 2006, 43 patients were treated on the phase I/II trial of HDR-brachytherapy boosted comprehensive IMRT for intermediate-risk adenocarcinoma of the prostate or its antecedent pilot study. Eligibility was limited to patients with T-stage # 2 b, PSA # 20 and Gleason score #7. Treatment was initialized with a single HDR fraction of 6 Gy, during which fiducial markers were placed in the prostate. Brachytherapy was followed by IMRT optimized to deliver in 28 fractions a Normalized Total Dose (NTD2 Gy) of 70 Gy to the prostate (plus a 5 mm margin) and the most proximal 2 cm of seminal vesicles. PLN received 50.4 Gy. The combined NTD2 Gy dose to the prostate was 80 Gy. Patients whose pre-treatment PSA was .10 ng/ml received short-term androgen ablation, consisting of 4 months of single-agent luprolide therapy. Results: All 43 patients completed treatment without Grade 3 toxicities. Acute grade 2 genitourinary toxicity (dysuria) occurred in fewer than 8% of patients. No acute grade 2 gastrointestinal toxicity was observed. Late toxicity was limited to transient grade 2 rectal bleeding observed in four patients (9%) after a median follow-up of 42 months. The median nadir PSA value was 0.2 ng/ml, with a range of 0.0–0.4 ng/ml. Ultrasound imaging of the prostate after 24 months revealed a median volume reduction of 56%(±2%). No biochemical failures have been observed. Conclusions: HDR-boosted IMRT is a safe, effective method for the delivery of 80 Gy to the prostate, while providing comprehensive treatment of the peri-prostatic soft tissues and PLN. The biologic response represented by the prostate volume reduction appears to be consistent with the dose delivered. Author Disclosure: M. Hagan, None; D. Todor, None; N. Dogan, None; Y. Wu, None; M. Anscher, None; D. Arthur, None.
S363