- Email: [email protected]
4N0 Prostate Cancer
Proceedings of the 47th Annual ASTRO Meeting
related to toxicity from 5-FU. We also found large age and gender differences in the likelihood of developing methylated tumors and tumors with genomic instability (MSI). Conclusions: Genes regulating folate metabolism are likely to be responsible for the variation in response/toxicity to 5-FU chemotherapy. Molecular phenotypes of MSI and DNA Methylation are surrogates of genomic factors that relate to carcinogenesis and response to therapy. Folate is the sole contributor of methyl groups, hence changes in dietary folate predisposes individuals to the development of methylated tumors. A more detailed analysis of SNPs is underway incorporating 100s of genes using DNA array technology. We are also incorporating blood based testing in future prospective studies to evaluate the impact of genomic polymorphisms on patient response to treatment.
203
Preliminary Analysis of RTOG 9902: Increased Toxicity Observed with the Use of Adjuvant Chemotherapy
H.M. Sandler,1 M. DeSilvio,2 K. Pienta,1 E. Hug,3 A. Sucha,4 R. Rajan,5 K. Kerlin,6 J. Michalski,7 S. Rosenthal8 University of Michigan, Ann Arbor, MI, 2RTOG Statistical Center, Philadelphia, PA, 3Dartmouth-Hitchcock Medical Center, Lebanon, NH, 4Albert Einstein Medical Center, Philadelphia, PA, 5McGill University, Montreal, QC, Canada, 6Wayne Radiation Oncology, Goldsboro, NC, 7Washington University, St. Louis, MO, 8Radiological Associates, Sacramento, CA 1
Purpose/Objective: High risk, clinically localized prostate cancer (PCa) is generally treated with a combination of radiotherapy (RT) and long term, androgen ablation (LTAD). However, many patients (Pts) develop recurrence following therapy, ultimately with distant disease. Cytotoxic chemotherapy (CT) is beginning to have a larger clinical role in management of hormone refractory prostate cancer (HRPCa) and it was our hypothesis that adjuvant CT would improve the survival rate of high risk PCa when used in combination with RT and LTAD. Materials/Methods: Pts with PSA 20 –100 and Gleason score (GS) ⱖ7 or clinical stage ⱖT2 and GS ⱖ8 were randomized to androgen ablation for 8 weeks then RT and LTAD with or without four 21-day cycles of CT with oral estramustine 280 mg tid ⫻ 14 days, oral VP-16 50 mg/m2 in divided doses bid ⫻ 14 days, and paclitaxel 135 mg/m2 iv on day 2. Warfarin was originally given at 1 mg/day during CT, but, after thromboembolic (TE) toxicity was observed, the dosage was increased to keep the INR between 1.5 and 2.5. The RT consisted of 46.8 Gy to a small pelvic field (in order to minimize hematologic toxicity) followed by a boost to the prostate of 23.4 Gy for a total dose of 70.2 Gy. Results: This study opened on Jan 11, 2000 and closed on Oct 4, 2004 with a total of 397 Pts (of a planned 1440) entered. Pts had high risk features: 68% had GS 8 or greater, median PSA was 22.7 ng/mL, and 33% were cT3. 378 Pts have toxicity information available. 199 Pts were enrolled with less intense anticoagulation and 179 Pts were enrolled after the anticoagulation was intensified. After the warfarin was increased, toxicity information was carefully scrutinized and the rate of TE event was found to exceed the rate prospectively defined as the maximum allowable (2 TE events occurred among first 10 eligible and analyzable Pts). This information was reported to the DMC and patient accrual was suspended on Jul 30, 2004 and permanently closed to patient accrual on Oct 4, 2004 for patient safety. Overall, there were 34 Pts who experience at least one grade ⱖ4 events (2 grade 5) in the CT arm vs. 0 in the no-CT arm. Using Kaplan-Meier analysis and log rank testing, there were statistically significant increases in grade ⱖ3 GI, cardiovascular, and TE toxicities in the CT arm. In the CT arm, the 12 month cumulative estimate of cardiovascular toxicity was 12% and, for TE events, it was 10%. For those Pts who actually received CT, the 1-yr rate of TE toxicity was 16% with less intense anticoagulation and 8% with more intense anticoagulation. Conclusions: Increased toxicity was seen in the CT arm of RTOG 9902. Careful monitoring led to an appropriate halt in patient accrual. Despite the early stoppage due to toxicity, this trial of nearly 400 Pts is the largest prospective chemotherapyradiotherapy study in PCa and demonstrates that the RTOG can carry out CT trials in localized prostate cancer. Estramustine is associated with TE toxicity, which led to the early stoppage of this trial. Recent studies in HRPCa seem to indicate that this agent no longer needs to be a part of chemotherapy regimens for PCa. The RTOG will follow patients enrolled in this trial for outcome and longer term toxicity analysis. A successor trial (RTOG 0521) will be activated in high risk, localized PCa utilizing docetaxel without estramustine in order for further evaluate the hypothesis that adjuvant CT can improve survival in high risk, but clinically and radiographically non-metastatic PCa.
204
A Multi-Institutional Matched-Control Analysis of Adjuvant and Salvage Postoperative Radiation Therapy for pT3/4N0 Prostate Cancer
R.K. Valicenti,1 A.L. Hanlon,2 T.M. Pisansky,3 H.M. Sandler,4 D.A. Kuban,5 C. Catton,6 J.M. Michalski,7 M.J. Zelefsky,8 P.A. Kupelian,9 L.L. Kestin,10 T.L. DeWeese,11 A. Pollack12 1 Radiation Oncology, Jefferson Medical College, Philadelphia, PA, 2Biostatistics, Fox Chase Cancer Center, Philadelphia, PA, 3Radiation Oncology, Mayo Clinic, Rochester, MN, 4Radiation Oncology, University of Michigan, Ann Arbor, MI, 5 Radiation Oncology, M.D. Anderson Cancer Center, Houston, TX, 6Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 7Radiation Oncology, Washington University, St. Louis, MO, 8Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY, 9Radiation Oncology, Cleveland Clinic, Cleveland, OH, 10Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 11Radiation Oncology, Johns Hopkins University, Baltimore, MD, 12Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective: It is assumed that salvage postoperative radiation therapy (RT) and adjuvant RT after prostectomy lead to equivalent long-term tumor control for selected patients. To address this issue, we studied a group of prostate cancer patients undergoing adjuvant RT by comparing them with a matched control group of patients undergoing salvage RT after biochemical failure. Materials/Methods: In a multi-institutional database of 1699 postoperative patients, 316 patients undergoing radical prostatectomy were found to have pT3/4N0 prostate cancer, had undetectable prostatic specific antigen (PSA) in the immediate postoperative period, and complete preoperative, operative, and postoperative information. Seventy-two patients received adjuvant RT within 12 months of surgery. Two-hundred and fifty-seven underwent salvage RT after PSA failure (median pre-RT PSA ⫽ 0.6 ng/ml, range 0.2 to 10 ng/ml). From these two cohorts, we matched patients in 1:2 ratio according to preoperative PSA (⬍10 ng/ml vs. ⬎ 10 ng/ml), Gleason score (⬍7, 7, or ⬎7), seminal vesicle invasion (SVI), surgical margin status, and length of follow-up. A PSA rise above 0.2 ng/ml was considered treatment failure.
S123
S124
I. J. Radiation Oncology
● Biology ● Physics
Volume 63, Number 2, Supplement, 2005
Results: One hundred and seventy-four patients (58:116) were matched. The median follow-up time was 6 years from the time of surgery. After controlling for the prognostic factors by the matching, there was a significant improvement in long-term PSA control with early adjuvant RT vs. delayed salvage RT. The 5-year Kaplan-Meier freedom from PSA failure was 68% (95% confidence interval [CI]: 54% to 82%) after adjuvant RT as compared to 42% (95% CI: 32% to 52%) for those undergoing salvage RT at time of PSA failure (Log-Rank p⫽.0087). On multivariate analysis we found that salvage RT (Hazard Ratio⫽ 2.1, p⫽.0047), SVI, and Gleason score above 7 were independent predictors of increased biochemical failure (all p⬍0.01). Conclusions: Early postoperative adjuvant RT for pT3/4N0 prostate cancer significantly reduces the risk of long-term disease progression after radical prostatectomy as compared to delayed salvage RT. Its effect on overall survival awaits additional follow-up data.
205
A Multi-Institutional Phase I/II Trial of Dose-per-fraction Escalation for Localized Prostate Cancer
M.A. Ritter,1 R.J. Chappell,2 W.A. Tome,1 P.A. Kupelian3 Human Oncology, University of Wisconsin, Madison, WI, 2Biostatistics, University of Wisconsin, Madison, WI, 3Radiation Oncology, M.D. Anderson Cancer Center, Orlando, FL 1
Purpose/Objective: A lower indicated alpha/beta ratio for prostate cancer control than for rectal toxicity suggests that radiation hypofractionation (HFX) could increase the therapeutic ratio. We have undertaken a novel phase I/II clinical trial to assess the tolerability and efficacy of increasingly HFX’d regimens. The first level of this ongoing three-level, increasingly hypofractionated trial is complete. The trial design and initial results are presented. Materials/Methods: Three increasingly HFX’d levels were designed per LQ modeling to maintain approximately constant predicted late toxicity (assuming an alpha/beta of 3) relative to 76 Gy in 38 fractions. Novel aspects of the trial design include a fractions-per-week escalation (first 4, then 5) nested within each HFX level to limit possible acute and consequential rectal toxicities, as well as a prorated analysis of grade 2 rectal bleeding, the designated HFX escalation-limiting toxicity. The planned HFX levels I, II and III (and targeted accruals) are 64.7 Gy/ 22 fx of 2.94 Gy (50 pts), 58.08 Gy/ 16 fx of 3.63 Gy (50 pts) and 51.6 Gy/ 12 fx of 4.3 Gy (150 pts), respectively (table). These HFX schedules predict for tumor NTD doses (in 2 Gy fractions) equivalent to in excess of 80 Gy (see table), assuming a tumor alpha/beta ratio of 1.5. Tomotherapy or Linac-based IMRT with image guidance was used. Two institutions participated in completing level I accrual, with two additional academic institutions now joining to contribute to levels II and III accrual. Results: Level I accrual is complete with 50 patients. Toxicities were modest: The average IPSS score reached a maximum of 14/35 at 2 weeks post treatment, but then rapidly declined to about the pre-treatment baseline of 9. A 40% rate of acute grade 2 GU toxicity (based on alpha blockers use) during treatment declined to 12% by one year. Only minor grade I acute GI toxicities were seen during and shortly after treatment. Four vs. 5 treatments per week were equally well tolerated. Late rectal toxicities were also modest: The 50 patients (median follow-up 10 months) experienced a projected 9.6% rate of grade 2 GI toxicity (rectal bleeding) at two years, but no grade 3 toxicities. Interestingly, PSAs decreased with a median initial half-life of 1.3 months - about twice as rapidly as typical for standard fractionation. Conclusions: The first treatment level (22 fx of 2.94 Gy each) of a multi-institutional phase I/II prostate HFX trial has been completed with 50 patients accrued and with acceptable levels of acute and preliminary late toxicities were observed. Accrual to the next more HFXed level is underway with the ultimate goal of selecting a HFX regimen for phase III testing. Hypofractionation for prostate cancer is attractive for its potential therapeutic gain as well as its economic and logistic advantage.
206
Hypofractionated Intensity Modulated Radiotherapy (70 Gy at 2.5 Gy Per Fraction) for Localized Prostate Cancer: Long-Term Outcome Results
V.V. Thakkar,1 D. Khuntia,3 C.A. Reddy,1 E.A. Mahadevan,1 A. Klein,4 N. Chehade,5 P.A. Kupelian2 Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, OH, 2Department of Radiation Oncology, M.D. Anderson Cancer Center Orlando, Orlando, FL, 3Department of Human Oncology, University of Wisconsin, Madison, WI, 4Glickman Urologic Institute, The Cleveland Clinic, Cleveland, OH, 5Department of Urology, Kaiser Permanente, Cleveland, OH 1
Purpose/Objective: The aim of this study is to present our observations on relapse-free survival and toxicity on patients with long term follow-up after hypofractionated intensity modulated radiotherapy (HFRT) to a total of 70 Gy delivered at 2.5 Gy per fraction over 51⁄2 weeks. Materials/Methods: The study sample includes the first one hundred consecutive localized prostate cancer patients treated with HFRT at the Cleveland Clinic from 1998 to 1999. All patients had available pretreatment PSA levels (iPSA) and biopsy Gleason scores (GS). Treatment consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Delivery was performed with a Dynamic Multi-Leaf Collimator. A total of 70.0 Gy was prescribed for all patients at 2.5 Gy per fraction to be delivered in 28 fractions over 5 1⁄2 weeks. The location of the prostate gland was verified and adjusted daily with the BAT™ transabdominal ultrasound system. Thirty-six patients had low-risk disease, 30 had intermediate risk disease, and 34 had high risk disease. Fifty-one patients received hormonal therapy for 6 months in combination with
related to toxicity from 5-FU. We also found large age and gender differences in the likelihood of developing methylated tumors and tumors with genomic instability (MSI). Conclusions: Genes regulating folate metabolism are likely to be responsible for the variation in response/toxicity to 5-FU chemotherapy. Molecular phenotypes of MSI and DNA Methylation are surrogates of genomic factors that relate to carcinogenesis and response to therapy. Folate is the sole contributor of methyl groups, hence changes in dietary folate predisposes individuals to the development of methylated tumors. A more detailed analysis of SNPs is underway incorporating 100s of genes using DNA array technology. We are also incorporating blood based testing in future prospective studies to evaluate the impact of genomic polymorphisms on patient response to treatment.
203
Preliminary Analysis of RTOG 9902: Increased Toxicity Observed with the Use of Adjuvant Chemotherapy
H.M. Sandler,1 M. DeSilvio,2 K. Pienta,1 E. Hug,3 A. Sucha,4 R. Rajan,5 K. Kerlin,6 J. Michalski,7 S. Rosenthal8 University of Michigan, Ann Arbor, MI, 2RTOG Statistical Center, Philadelphia, PA, 3Dartmouth-Hitchcock Medical Center, Lebanon, NH, 4Albert Einstein Medical Center, Philadelphia, PA, 5McGill University, Montreal, QC, Canada, 6Wayne Radiation Oncology, Goldsboro, NC, 7Washington University, St. Louis, MO, 8Radiological Associates, Sacramento, CA 1
Purpose/Objective: High risk, clinically localized prostate cancer (PCa) is generally treated with a combination of radiotherapy (RT) and long term, androgen ablation (LTAD). However, many patients (Pts) develop recurrence following therapy, ultimately with distant disease. Cytotoxic chemotherapy (CT) is beginning to have a larger clinical role in management of hormone refractory prostate cancer (HRPCa) and it was our hypothesis that adjuvant CT would improve the survival rate of high risk PCa when used in combination with RT and LTAD. Materials/Methods: Pts with PSA 20 –100 and Gleason score (GS) ⱖ7 or clinical stage ⱖT2 and GS ⱖ8 were randomized to androgen ablation for 8 weeks then RT and LTAD with or without four 21-day cycles of CT with oral estramustine 280 mg tid ⫻ 14 days, oral VP-16 50 mg/m2 in divided doses bid ⫻ 14 days, and paclitaxel 135 mg/m2 iv on day 2. Warfarin was originally given at 1 mg/day during CT, but, after thromboembolic (TE) toxicity was observed, the dosage was increased to keep the INR between 1.5 and 2.5. The RT consisted of 46.8 Gy to a small pelvic field (in order to minimize hematologic toxicity) followed by a boost to the prostate of 23.4 Gy for a total dose of 70.2 Gy. Results: This study opened on Jan 11, 2000 and closed on Oct 4, 2004 with a total of 397 Pts (of a planned 1440) entered. Pts had high risk features: 68% had GS 8 or greater, median PSA was 22.7 ng/mL, and 33% were cT3. 378 Pts have toxicity information available. 199 Pts were enrolled with less intense anticoagulation and 179 Pts were enrolled after the anticoagulation was intensified. After the warfarin was increased, toxicity information was carefully scrutinized and the rate of TE event was found to exceed the rate prospectively defined as the maximum allowable (2 TE events occurred among first 10 eligible and analyzable Pts). This information was reported to the DMC and patient accrual was suspended on Jul 30, 2004 and permanently closed to patient accrual on Oct 4, 2004 for patient safety. Overall, there were 34 Pts who experience at least one grade ⱖ4 events (2 grade 5) in the CT arm vs. 0 in the no-CT arm. Using Kaplan-Meier analysis and log rank testing, there were statistically significant increases in grade ⱖ3 GI, cardiovascular, and TE toxicities in the CT arm. In the CT arm, the 12 month cumulative estimate of cardiovascular toxicity was 12% and, for TE events, it was 10%. For those Pts who actually received CT, the 1-yr rate of TE toxicity was 16% with less intense anticoagulation and 8% with more intense anticoagulation. Conclusions: Increased toxicity was seen in the CT arm of RTOG 9902. Careful monitoring led to an appropriate halt in patient accrual. Despite the early stoppage due to toxicity, this trial of nearly 400 Pts is the largest prospective chemotherapyradiotherapy study in PCa and demonstrates that the RTOG can carry out CT trials in localized prostate cancer. Estramustine is associated with TE toxicity, which led to the early stoppage of this trial. Recent studies in HRPCa seem to indicate that this agent no longer needs to be a part of chemotherapy regimens for PCa. The RTOG will follow patients enrolled in this trial for outcome and longer term toxicity analysis. A successor trial (RTOG 0521) will be activated in high risk, localized PCa utilizing docetaxel without estramustine in order for further evaluate the hypothesis that adjuvant CT can improve survival in high risk, but clinically and radiographically non-metastatic PCa.
204
A Multi-Institutional Matched-Control Analysis of Adjuvant and Salvage Postoperative Radiation Therapy for pT3/4N0 Prostate Cancer
R.K. Valicenti,1 A.L. Hanlon,2 T.M. Pisansky,3 H.M. Sandler,4 D.A. Kuban,5 C. Catton,6 J.M. Michalski,7 M.J. Zelefsky,8 P.A. Kupelian,9 L.L. Kestin,10 T.L. DeWeese,11 A. Pollack12 1 Radiation Oncology, Jefferson Medical College, Philadelphia, PA, 2Biostatistics, Fox Chase Cancer Center, Philadelphia, PA, 3Radiation Oncology, Mayo Clinic, Rochester, MN, 4Radiation Oncology, University of Michigan, Ann Arbor, MI, 5 Radiation Oncology, M.D. Anderson Cancer Center, Houston, TX, 6Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 7Radiation Oncology, Washington University, St. Louis, MO, 8Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY, 9Radiation Oncology, Cleveland Clinic, Cleveland, OH, 10Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 11Radiation Oncology, Johns Hopkins University, Baltimore, MD, 12Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective: It is assumed that salvage postoperative radiation therapy (RT) and adjuvant RT after prostectomy lead to equivalent long-term tumor control for selected patients. To address this issue, we studied a group of prostate cancer patients undergoing adjuvant RT by comparing them with a matched control group of patients undergoing salvage RT after biochemical failure. Materials/Methods: In a multi-institutional database of 1699 postoperative patients, 316 patients undergoing radical prostatectomy were found to have pT3/4N0 prostate cancer, had undetectable prostatic specific antigen (PSA) in the immediate postoperative period, and complete preoperative, operative, and postoperative information. Seventy-two patients received adjuvant RT within 12 months of surgery. Two-hundred and fifty-seven underwent salvage RT after PSA failure (median pre-RT PSA ⫽ 0.6 ng/ml, range 0.2 to 10 ng/ml). From these two cohorts, we matched patients in 1:2 ratio according to preoperative PSA (⬍10 ng/ml vs. ⬎ 10 ng/ml), Gleason score (⬍7, 7, or ⬎7), seminal vesicle invasion (SVI), surgical margin status, and length of follow-up. A PSA rise above 0.2 ng/ml was considered treatment failure.
S123
S124
I. J. Radiation Oncology
● Biology ● Physics
Volume 63, Number 2, Supplement, 2005
Results: One hundred and seventy-four patients (58:116) were matched. The median follow-up time was 6 years from the time of surgery. After controlling for the prognostic factors by the matching, there was a significant improvement in long-term PSA control with early adjuvant RT vs. delayed salvage RT. The 5-year Kaplan-Meier freedom from PSA failure was 68% (95% confidence interval [CI]: 54% to 82%) after adjuvant RT as compared to 42% (95% CI: 32% to 52%) for those undergoing salvage RT at time of PSA failure (Log-Rank p⫽.0087). On multivariate analysis we found that salvage RT (Hazard Ratio⫽ 2.1, p⫽.0047), SVI, and Gleason score above 7 were independent predictors of increased biochemical failure (all p⬍0.01). Conclusions: Early postoperative adjuvant RT for pT3/4N0 prostate cancer significantly reduces the risk of long-term disease progression after radical prostatectomy as compared to delayed salvage RT. Its effect on overall survival awaits additional follow-up data.
205
A Multi-Institutional Phase I/II Trial of Dose-per-fraction Escalation for Localized Prostate Cancer
M.A. Ritter,1 R.J. Chappell,2 W.A. Tome,1 P.A. Kupelian3 Human Oncology, University of Wisconsin, Madison, WI, 2Biostatistics, University of Wisconsin, Madison, WI, 3Radiation Oncology, M.D. Anderson Cancer Center, Orlando, FL 1
Purpose/Objective: A lower indicated alpha/beta ratio for prostate cancer control than for rectal toxicity suggests that radiation hypofractionation (HFX) could increase the therapeutic ratio. We have undertaken a novel phase I/II clinical trial to assess the tolerability and efficacy of increasingly HFX’d regimens. The first level of this ongoing three-level, increasingly hypofractionated trial is complete. The trial design and initial results are presented. Materials/Methods: Three increasingly HFX’d levels were designed per LQ modeling to maintain approximately constant predicted late toxicity (assuming an alpha/beta of 3) relative to 76 Gy in 38 fractions. Novel aspects of the trial design include a fractions-per-week escalation (first 4, then 5) nested within each HFX level to limit possible acute and consequential rectal toxicities, as well as a prorated analysis of grade 2 rectal bleeding, the designated HFX escalation-limiting toxicity. The planned HFX levels I, II and III (and targeted accruals) are 64.7 Gy/ 22 fx of 2.94 Gy (50 pts), 58.08 Gy/ 16 fx of 3.63 Gy (50 pts) and 51.6 Gy/ 12 fx of 4.3 Gy (150 pts), respectively (table). These HFX schedules predict for tumor NTD doses (in 2 Gy fractions) equivalent to in excess of 80 Gy (see table), assuming a tumor alpha/beta ratio of 1.5. Tomotherapy or Linac-based IMRT with image guidance was used. Two institutions participated in completing level I accrual, with two additional academic institutions now joining to contribute to levels II and III accrual. Results: Level I accrual is complete with 50 patients. Toxicities were modest: The average IPSS score reached a maximum of 14/35 at 2 weeks post treatment, but then rapidly declined to about the pre-treatment baseline of 9. A 40% rate of acute grade 2 GU toxicity (based on alpha blockers use) during treatment declined to 12% by one year. Only minor grade I acute GI toxicities were seen during and shortly after treatment. Four vs. 5 treatments per week were equally well tolerated. Late rectal toxicities were also modest: The 50 patients (median follow-up 10 months) experienced a projected 9.6% rate of grade 2 GI toxicity (rectal bleeding) at two years, but no grade 3 toxicities. Interestingly, PSAs decreased with a median initial half-life of 1.3 months - about twice as rapidly as typical for standard fractionation. Conclusions: The first treatment level (22 fx of 2.94 Gy each) of a multi-institutional phase I/II prostate HFX trial has been completed with 50 patients accrued and with acceptable levels of acute and preliminary late toxicities were observed. Accrual to the next more HFXed level is underway with the ultimate goal of selecting a HFX regimen for phase III testing. Hypofractionation for prostate cancer is attractive for its potential therapeutic gain as well as its economic and logistic advantage.
206
Hypofractionated Intensity Modulated Radiotherapy (70 Gy at 2.5 Gy Per Fraction) for Localized Prostate Cancer: Long-Term Outcome Results
V.V. Thakkar,1 D. Khuntia,3 C.A. Reddy,1 E.A. Mahadevan,1 A. Klein,4 N. Chehade,5 P.A. Kupelian2 Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, OH, 2Department of Radiation Oncology, M.D. Anderson Cancer Center Orlando, Orlando, FL, 3Department of Human Oncology, University of Wisconsin, Madison, WI, 4Glickman Urologic Institute, The Cleveland Clinic, Cleveland, OH, 5Department of Urology, Kaiser Permanente, Cleveland, OH 1
Purpose/Objective: The aim of this study is to present our observations on relapse-free survival and toxicity on patients with long term follow-up after hypofractionated intensity modulated radiotherapy (HFRT) to a total of 70 Gy delivered at 2.5 Gy per fraction over 51⁄2 weeks. Materials/Methods: The study sample includes the first one hundred consecutive localized prostate cancer patients treated with HFRT at the Cleveland Clinic from 1998 to 1999. All patients had available pretreatment PSA levels (iPSA) and biopsy Gleason scores (GS). Treatment consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Delivery was performed with a Dynamic Multi-Leaf Collimator. A total of 70.0 Gy was prescribed for all patients at 2.5 Gy per fraction to be delivered in 28 fractions over 5 1⁄2 weeks. The location of the prostate gland was verified and adjusted daily with the BAT™ transabdominal ultrasound system. Thirty-six patients had low-risk disease, 30 had intermediate risk disease, and 34 had high risk disease. Fifty-one patients received hormonal therapy for 6 months in combination with