- Email: [email protected]
Five-year Biochemical Control Rates for Stereotactic Body Radiation Therapy for Organ-confined Prostate Cancer: A Multi-institutional Pooled Analysis
Volume 84 Number 3S Supplement 2012 Author Disclosure: J.M. Vainshtein: None. M. Schipper: None. M. Zalupski: None. T.S. Lawrence: None. R. Abrams: None. I.R. Francis: None. W. Leslie: None. E. Ben-Josef: None.
363 Toxicity and Dosimetric Parameters Related to Conventional Versus Dose-Escalated, Hypofractionated Radiation in Prostate Cancer H.D. Skinner, K.E. Hoffman, L.B. Levy, A.K. Lee, S.J. Frank, S. Choi, S.E. McGuire, T.J. Pugh, and D.A. Kuban; The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To compare long-term toxicity between the conventional and the dose-escalated, hypofractionated arms of a randomized trial and to establish the relationship of toxicity to dosimetric parameters. Materials/Methods: GI and GU toxicity were assessed using modified RTOG criteria for 204 men with low and intermediate-risk prostate cancer participating in a single institution, randomized trial of standard (CF: 75.6 Gy in 42 fx) versus hypofractionated (HF: 72 Gy in 30 fx) radiation. Dose volume histogram (DVH) parameters for rectum and bladder were obtained for all patients and were correlated with physician assessed toxicity. Results: Median follow-up for the entire study population was 5.8 years (0.4-9.8), with a median patient age of 67 (41-83). All patients in the CF arm met DVH parameters specified in the protocol (R70 Gy <20%, R60 <40%, and R40 <60%). For the HF arm, equivalent DVH parameters were generated based upon an a/b of 3 and 5.4. Overall rectal toxicity trended higher in the HF arm versus the CF arm (p Z 0.06). However, this was primarily due to increased grade 1 toxicity, with no significant difference found in grade 2 toxicity between arms (p Z 0.18). The incidence of both rectal (p Z 0.03) and GU (p Z 0.05) toxicity were less in patients treated later in the study. High dose rectal DVH parameters were correlated with rectal toxicity in the HF arm. Specifically, for a normal tissue a/b of 3, R62.2 16% (p Z 0.03) and R67.2 13% (p Z 0.02) or for an a/b of 5.4, R64.6 Gy 14% (p Z 0.03) and R70 10% (p Z 0.004) were significantly associated with rectal toxicity. In the CF arm, all bladder (B) DVH parameters were correlated with toxicity, while in the HF arm, B9.2 Gy 45% (p Z 0.02) and B18.5 31% (p Z 0.06) were associated with increased bladder toxicity. Conclusions: Although dose-escalated, hypofractionated radiation was associated with slightly higher overall toxicity, this was primarily due to low grade events. Moreover, toxicity decreased as physician experience using dose-escalated hypofractionated radiation increased. Several rectal and bladder DVH parameters associated with toxicity in the HF arm were defined for this regimen, as they have been previously for conventionally fractionated schemes. Author Disclosure: H.D. Skinner: None. K.E. Hoffman: None. L.B. Levy: None. A.K. Lee: None. S.J. Frank: None. S. Choi: None. S.E. McGuire: None. T.J. Pugh: None. D.A. Kuban: None.
364 Updated Results and Pattern of Failure in a Randomized Hypofractionation Trial for High-risk Prostate Cancer S. Arcangeli, L. Strigari, S. Gomellini, B. Saracino, M. Petrongari, P. Pinnaro`, V. Pinzi, and G. Arcangeli; IFO, Roma, Italy Purpose/Objective(s): To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high risk prostate cancer. Materials/Methods: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy/fraction in 8 weeks) versus hypofractionation (62 Gy at 3.1 Gy/fraction in 5 weeks) in combination with 9-month androgen deprivation therapy (ADT) on 168 patients with high risk prostate cancer. Freedom from biochemical (FFBF), local (LF) and distant failure (DF) were analyzed.
Oral Scientific Sessions S147 Results: In a median follow-up of 70 months, BF occurred in 35 (21%) of the 168 patients in the study. Of these 35 patients, LF was detected in 18 (51%) and DF in 22 (63%). The risk reduction by hypofractionation was significant in BF (10.3%), but not in LF and DF. Hypofractionation, with respect to conventional fractionation, determined only a non significant increase in the actuarial FFBF but no difference in LF and DF, when considering the entire group of patients. However, an increase of the 5-yr survival rates in all three endpoints, FFBF, LF and DF was observed in the subgroups of patients with an iPSA 20 ng/mL. In multivariate analysis, the type of fractionation, iPSA level, GS (4 + 3) and T-stage 2 c have been confirmed as independent prognostic factors for BF. High iPSA levels and GS (4 + 3) were also significantly associated with an increased risk of DF, while T-stage 2 c resulted in the only independent variable for LR. Conclusions: Our results confirm the isoeffectiveness of the two fractionation schedules employed in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of patients with iPSA 20 ng/mL. The a/b ratio should be more appropriately evaluated by LF results than BF results, at least in high-risk disease. Author Disclosure: S. Arcangeli: None. L. Strigari: None. S. Gomellini: None. B. Saracino: None. M. Petrongari: None. P. Pinnaro`: None. V. Pinzi: None. G. Arcangeli: None.
365 Five-year Biochemical Control Rates for Stereotactic Body Radiation Therapy for Organ-confined Prostate Cancer: A Multiinstitutional Pooled Analysis A. Katz,1 D. Freeman,2 J. Aronovitz,3 D. Fuller,4 G. Bolzicco,5 R. Meier,6 S. Collins,7 J. Wang,8 M. Steinberg,8 and C. King8; 1Flushing Radiation Oncology, Flushing, NY, 2Cyberknife Center of Tampa Bay, Tampa, FL, 3 Beth Israel Deaconess Medical Center, Boston, MA, 4Cyberknife Centers of San Diego, San Diego, CA, 5San Bortolo Hospital, Vicenza, Italy, 6 Swedish Medical Center, Seattle, WA, 7Georgetown University Hospital, Washington, DC, 8UCLA Medical Center, Los Angeles, CA Purpose/Objective(s): To report the 5-year biochemical relapse-free survival (bRFS) rates from a pooled multi-institutional dataset of a large number of localized prostate cancer patients treated with stereotactic body radiation therapy (SBRT). Materials/Methods: The outcome data from 1,101 patients with localized adenocarcinoma of the prostate were pooled from 8 institutions. Patients were treated between 2003 and 2011. The distribution by stage was 92% T1-2a and 8% T2b-3. The distribution by Gleason score (GS) was 72% Gleason 6, 20% Gleason 7 and 8% Gleason 8-10. The distribution by risk (NCCN) was 59% low, 30% intermediate and 11% highrisk. Median baseline PSA was 5.4 ng/mL; 88% of PSAs were <10 ng/ mL, 10% were 10-20 ng/mL and 2% were >20 ng/mL. All patients had SBRT as the radiotherapeutic modality. The median dose was 36.25 Gy (range, 35-40 Gy) delivered either with 4 or 5 fractions; this is equivalent to a range of 90-112 Gy in conventional fractionation, assuming an alpha/beta ratio of 1.5 Gy. In most cases, the PTV was the GTV expanded by 5 mm, 3 mm posteriorly; 2 mm of this was to account for errors in target definition and delivery. Androgen deprivation therapy was given to 146 (14%) patients. Biochemical relapse, defined as a rise >2 ng/mL above nadir, was determined in a total of 49 patients. Of the 49, 9 had resolution of the rise (i.e., the >2 ng/mL rise was a large bounce). However, outcome analyses were performed on all 49 cases; no cases were excluded. Results: The median follow-up for all 1,101 cases was 36 months (range 1 to 66 months). For all patients, the biochemical relapse-free actuarial survival (bRFS) rate at 5 years was 93%. The 5-year actuarial bRFS rates for Gleason score <6, Gleason score 7 and Gleason score >8 were 95%, 83%, and 78%, respectively (p Z 0.001). The 5-year actuarial bRFS rates for iPSA 4, iPSA 4-10, iPSA 10-20, and iPSA >20 were 96%, 94%, 82%, and 73%, respectively (p Z 0.001). The 5-year actuarial bRFS rates for low-, intermediate- and high-risk patients were 95%, 90%, and 80%, respectively (p < 0.001). No difference in bRFS was observed with the use of androgen deprivation (p Z 0.76). A PSA bounce of >0.20 ng/mL was
S148
International Journal of Radiation Oncology Biology Physics
observed in 16% of the patients at a median of 36 months (range 6-60 months). The median bounce magnitude was 0.505 ng/mL (range 0.2-5.29 ng/mL). For the 335 cases with a minimum of 4 years of follow-up (median 53 months), the 5-year bRFS rates for low-risk and intermediaterisk cases were 97% and 89%, respectively. Conclusions: With a large cohort of patients treated with stereotactic body radiation therapy, with a reasonably long follow-up period, excellent efficacy was demonstrated at 5 years. For high-risk cases, the results are preliminary, given the small number of cases treated. However, for low and intermediate risk cases, these results compare favorably with other modalities. These results support a low alpha beta ratio for prostate cancer. Author Disclosure: A. Katz: F. Honoraria; Accuray. D. Freeman: F. Honoraria; Accuray. J. Aronovitz: None. D. Fuller: None. G. Bolzicco: None. R. Meier: None. S. Collins: G. Consultant; Accuray. J. Wang: None. M. Steinberg: None. C. King: None.
been minimal. EPIC urinary, bowel and sexual function responses appear favorable compared to other radiation therapy modalities. Early PSA responses are promising. With further follow-up, this study will help determine whether SBRT provides a therapeutic gain in the treatment of organ-confined prostate cancer. Acknowledgment: This project was supported by NCT00643994 and a grant from Accuray Inc. Author Disclosure: R. Meier: None. I. Kaplan: None. A. Beckman: None. G. Henning: None. S. Woodhouse: None. S. Williamson: None. N. Mohideen: None. D. Herold: None. C. Cotrutz: D. Employment Other; Spouse employed by Accuray. M. Sanda: None.
366 Stereotactic Body Radiation Therapy for Intermediate-risk Organconfined Prostate Cancer: Interim Toxicity and Quality of Life Outcomes From a Multi-institutional Study R. Meier,1 I. Kaplan,2 A. Beckman,3 G. Henning,4 S. Woodhouse,5 S. Williamson,6 N. Mohideen,7 D. Herold,8 C. Cotrutz,1 and M. Sanda2; 1 Swedish Cancer Institute, Seattle, WA, 2Beth Israel Deaconess Medical Center, Boston, MA, 3Central Baptist Hospital, Lexington, KY, 4St. Joseph Mercy Hospital System, Ypsilanti, MI, 5Community Cancer Center, Normal, IL, 6Capital Health System, Trenton, NJ, 7Northwest Community Hospital, Arlington Heights, IL, 8Jupiter Medical Center, Jupiter, FL Purpose/Objective(s): A phase II prospective multi-center study was initiated in 2007 to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for organ-confined prostate cancer. The study included 21 institutions and completed accrual in 2011. We report an interim analysis of toxicities, quality of life (QOL) and early PSA outcomes of the intermediate-risk cohort. Materials/Methods: A total of 129 hormone-naı¨ve intermediate-risk patients (CS T1c-T2b, N0-x, M0-x, with either Gleason Z 7 and PSA <10 ng/mL, or Gleason 6 and PSA between 10 and 20) with biopsy proven adenocarcinoma of the prostate were enrolled. MR imaging was used to assist in target localization. All patients were treated with a non-isocentric robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy and seminal vesicles received 36.25 Gy. No patient had androgen deprivation therapy. Toxicities were assessed using CTCAE v3 criteria. QOL for urinary, bowel and sexual function were assessed using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire; patients with erections “Firm enough for intercourse” on question 9 were scored as potent. Biochemical failure was defined as a 2 ng/mL rise above nadir. Results: Median follow-up was 30 months (range 10-42 months). No acute grade 3+ toxicities were reported. Acute Grade 2 GU and GI toxicities occurred in 20% and 8.5% of patients, respectively. One patient required temporary catheter placement for acute urinary retention. Late Grade 2 GU and GI toxicities occurred in 10% and 2% of patients, respectively. One late Grade 3 GU toxicity (bladder neck injury 1 year after treatment) was reported. There were no other Grade 3-5 toxicities. Mean EPIC urinary and bowel scores fell at 1 month and returned to baseline by 24 months. At baseline 52% of patients were potent, declining to 35% at 24 months. Pre-treatment median PSA was 5.93 ng/mL, decreasing to 0.80, 0.38 and 0.20 ng/mL at 1, 2 and 3 years, respectively. One patient had a biochemical failure at 3 months follow-up due to a biopsy-proven nodal metastasis. No other biochemical failures have been observed, resulting in a 3-year Kaplan-Meier biochemical progression-free survival rate of 99.2%. Conclusions: In a multi-institutional study employing SBRT in intermediate-risk prostate cancer patients, serious acute and late toxicities have
367 Dose Escalation of 5-Fraction Radiation Therapy for Prostate Cancer: Quality of Life Comparison of 2 Prospective Trials H.C. Quon,1 D.A. Loblaw,2 P. Cheung,2 C.I. Tang,3 G. Pang,2 G. Morton,2 A. Mamedov,2 L. D’Alimonte,2 A. Deabreu,2 and R. Tirona2; 1Cancercare Manitoba, Winnipeg, MB, Canada, 2Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Calvary Mater Newcastle Hospital, Waratah, Australia Purpose/Objective(s): To compare the quality of life of two fivefraction radiation therapy schedules for the treatment of localized prostate cancer. Materials/Methods: Two sequential phase I/II studies of five-fraction radiation therapy for the treatment of low and intermediate risk prostate cancer have been conducted. In the first trial, patients received 35 Gy in 5 fractions, once per week over 29 days (Group 1). In the second trial, patients received 40 Gy in 5 fractions, once per week over 29 days (Group 2). Treatment was delivered to the prostate only with intensity modulated radiation therapy using daily image guidance with gold seed fiducials and a 4mm (Group 1) or 5 mm (Group 2) CTV-PTV margin. Quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) instrument in both trials at baseline and every 6 months. A clinically relevant change in EPIC score was defined as a decrease of >0.5 standard deviation of the baseline value. Results: Eighty-four patients have been treated in Group 1 with a median follow-up of 36 months. In Group 2, 30 patients have been treated with a median follow-up of 12 months. EPIC scores at 12 months were compared. There was a lower proportion of patients who experienced a clinically relevant decrease in bowel bother scores in Group 1 versus Group 2 (27.4 vs. 61.1%, p Z 0.01), respectively. However, there was no significant difference in proportion of patients reporting moderate to severe problems in overall bowel habits (7.3% vs. 11.1%, p Z 0.63). No significant differences were found in the proportion of patients with clinically relevant decreases in domain summary scores, which for Group 1 versus Group 2 were: urinary (36.9 vs. 27.8%, p Z 0.59), bowel (27.4 vs. 50.0%, p Z 0.09), sexual (35.0 vs. 35.3%, p Z 1.00), and hormonal (21.7 vs. 23.5%, p Z 1.00). Mean domain summary scores at 12 months are shown in the Table. Conclusions: Patients receiving an escalated dose of five-fraction radiation therapy had a greater risk of a clinically relevant decrease in bowel bother EPIC score. However, moderate to severe overall bowel problems were not significantly different. Most quality of life scores remained high in both groups.
Oral Scientific Abstract 367; Table dard deviation) at 12 months EPIC domain Urinary Bowel Sexual Hormonal
Mean EPIC summary scores (+/- stan-
Group 1 89.9 92.1 47.9 93.2
+/+/+/+/-
11.2 8.4 26.9 7.4
Group 2 84.0 85.5 43.0 87.8
+/+/+/+/-
18.4 15.5 23.8 14.7
363 Toxicity and Dosimetric Parameters Related to Conventional Versus Dose-Escalated, Hypofractionated Radiation in Prostate Cancer H.D. Skinner, K.E. Hoffman, L.B. Levy, A.K. Lee, S.J. Frank, S. Choi, S.E. McGuire, T.J. Pugh, and D.A. Kuban; The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To compare long-term toxicity between the conventional and the dose-escalated, hypofractionated arms of a randomized trial and to establish the relationship of toxicity to dosimetric parameters. Materials/Methods: GI and GU toxicity were assessed using modified RTOG criteria for 204 men with low and intermediate-risk prostate cancer participating in a single institution, randomized trial of standard (CF: 75.6 Gy in 42 fx) versus hypofractionated (HF: 72 Gy in 30 fx) radiation. Dose volume histogram (DVH) parameters for rectum and bladder were obtained for all patients and were correlated with physician assessed toxicity. Results: Median follow-up for the entire study population was 5.8 years (0.4-9.8), with a median patient age of 67 (41-83). All patients in the CF arm met DVH parameters specified in the protocol (R70 Gy <20%, R60 <40%, and R40 <60%). For the HF arm, equivalent DVH parameters were generated based upon an a/b of 3 and 5.4. Overall rectal toxicity trended higher in the HF arm versus the CF arm (p Z 0.06). However, this was primarily due to increased grade 1 toxicity, with no significant difference found in grade 2 toxicity between arms (p Z 0.18). The incidence of both rectal (p Z 0.03) and GU (p Z 0.05) toxicity were less in patients treated later in the study. High dose rectal DVH parameters were correlated with rectal toxicity in the HF arm. Specifically, for a normal tissue a/b of 3, R62.2 16% (p Z 0.03) and R67.2 13% (p Z 0.02) or for an a/b of 5.4, R64.6 Gy 14% (p Z 0.03) and R70 10% (p Z 0.004) were significantly associated with rectal toxicity. In the CF arm, all bladder (B) DVH parameters were correlated with toxicity, while in the HF arm, B9.2 Gy 45% (p Z 0.02) and B18.5 31% (p Z 0.06) were associated with increased bladder toxicity. Conclusions: Although dose-escalated, hypofractionated radiation was associated with slightly higher overall toxicity, this was primarily due to low grade events. Moreover, toxicity decreased as physician experience using dose-escalated hypofractionated radiation increased. Several rectal and bladder DVH parameters associated with toxicity in the HF arm were defined for this regimen, as they have been previously for conventionally fractionated schemes. Author Disclosure: H.D. Skinner: None. K.E. Hoffman: None. L.B. Levy: None. A.K. Lee: None. S.J. Frank: None. S. Choi: None. S.E. McGuire: None. T.J. Pugh: None. D.A. Kuban: None.
364 Updated Results and Pattern of Failure in a Randomized Hypofractionation Trial for High-risk Prostate Cancer S. Arcangeli, L. Strigari, S. Gomellini, B. Saracino, M. Petrongari, P. Pinnaro`, V. Pinzi, and G. Arcangeli; IFO, Roma, Italy Purpose/Objective(s): To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high risk prostate cancer. Materials/Methods: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy/fraction in 8 weeks) versus hypofractionation (62 Gy at 3.1 Gy/fraction in 5 weeks) in combination with 9-month androgen deprivation therapy (ADT) on 168 patients with high risk prostate cancer. Freedom from biochemical (FFBF), local (LF) and distant failure (DF) were analyzed.
Oral Scientific Sessions S147 Results: In a median follow-up of 70 months, BF occurred in 35 (21%) of the 168 patients in the study. Of these 35 patients, LF was detected in 18 (51%) and DF in 22 (63%). The risk reduction by hypofractionation was significant in BF (10.3%), but not in LF and DF. Hypofractionation, with respect to conventional fractionation, determined only a non significant increase in the actuarial FFBF but no difference in LF and DF, when considering the entire group of patients. However, an increase of the 5-yr survival rates in all three endpoints, FFBF, LF and DF was observed in the subgroups of patients with an iPSA 20 ng/mL. In multivariate analysis, the type of fractionation, iPSA level, GS (4 + 3) and T-stage 2 c have been confirmed as independent prognostic factors for BF. High iPSA levels and GS (4 + 3) were also significantly associated with an increased risk of DF, while T-stage 2 c resulted in the only independent variable for LR. Conclusions: Our results confirm the isoeffectiveness of the two fractionation schedules employed in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of patients with iPSA 20 ng/mL. The a/b ratio should be more appropriately evaluated by LF results than BF results, at least in high-risk disease. Author Disclosure: S. Arcangeli: None. L. Strigari: None. S. Gomellini: None. B. Saracino: None. M. Petrongari: None. P. Pinnaro`: None. V. Pinzi: None. G. Arcangeli: None.
365 Five-year Biochemical Control Rates for Stereotactic Body Radiation Therapy for Organ-confined Prostate Cancer: A Multiinstitutional Pooled Analysis A. Katz,1 D. Freeman,2 J. Aronovitz,3 D. Fuller,4 G. Bolzicco,5 R. Meier,6 S. Collins,7 J. Wang,8 M. Steinberg,8 and C. King8; 1Flushing Radiation Oncology, Flushing, NY, 2Cyberknife Center of Tampa Bay, Tampa, FL, 3 Beth Israel Deaconess Medical Center, Boston, MA, 4Cyberknife Centers of San Diego, San Diego, CA, 5San Bortolo Hospital, Vicenza, Italy, 6 Swedish Medical Center, Seattle, WA, 7Georgetown University Hospital, Washington, DC, 8UCLA Medical Center, Los Angeles, CA Purpose/Objective(s): To report the 5-year biochemical relapse-free survival (bRFS) rates from a pooled multi-institutional dataset of a large number of localized prostate cancer patients treated with stereotactic body radiation therapy (SBRT). Materials/Methods: The outcome data from 1,101 patients with localized adenocarcinoma of the prostate were pooled from 8 institutions. Patients were treated between 2003 and 2011. The distribution by stage was 92% T1-2a and 8% T2b-3. The distribution by Gleason score (GS) was 72% Gleason 6, 20% Gleason 7 and 8% Gleason 8-10. The distribution by risk (NCCN) was 59% low, 30% intermediate and 11% highrisk. Median baseline PSA was 5.4 ng/mL; 88% of PSAs were <10 ng/ mL, 10% were 10-20 ng/mL and 2% were >20 ng/mL. All patients had SBRT as the radiotherapeutic modality. The median dose was 36.25 Gy (range, 35-40 Gy) delivered either with 4 or 5 fractions; this is equivalent to a range of 90-112 Gy in conventional fractionation, assuming an alpha/beta ratio of 1.5 Gy. In most cases, the PTV was the GTV expanded by 5 mm, 3 mm posteriorly; 2 mm of this was to account for errors in target definition and delivery. Androgen deprivation therapy was given to 146 (14%) patients. Biochemical relapse, defined as a rise >2 ng/mL above nadir, was determined in a total of 49 patients. Of the 49, 9 had resolution of the rise (i.e., the >2 ng/mL rise was a large bounce). However, outcome analyses were performed on all 49 cases; no cases were excluded. Results: The median follow-up for all 1,101 cases was 36 months (range 1 to 66 months). For all patients, the biochemical relapse-free actuarial survival (bRFS) rate at 5 years was 93%. The 5-year actuarial bRFS rates for Gleason score <6, Gleason score 7 and Gleason score >8 were 95%, 83%, and 78%, respectively (p Z 0.001). The 5-year actuarial bRFS rates for iPSA 4, iPSA 4-10, iPSA 10-20, and iPSA >20 were 96%, 94%, 82%, and 73%, respectively (p Z 0.001). The 5-year actuarial bRFS rates for low-, intermediate- and high-risk patients were 95%, 90%, and 80%, respectively (p < 0.001). No difference in bRFS was observed with the use of androgen deprivation (p Z 0.76). A PSA bounce of >0.20 ng/mL was
S148
International Journal of Radiation Oncology Biology Physics
observed in 16% of the patients at a median of 36 months (range 6-60 months). The median bounce magnitude was 0.505 ng/mL (range 0.2-5.29 ng/mL). For the 335 cases with a minimum of 4 years of follow-up (median 53 months), the 5-year bRFS rates for low-risk and intermediaterisk cases were 97% and 89%, respectively. Conclusions: With a large cohort of patients treated with stereotactic body radiation therapy, with a reasonably long follow-up period, excellent efficacy was demonstrated at 5 years. For high-risk cases, the results are preliminary, given the small number of cases treated. However, for low and intermediate risk cases, these results compare favorably with other modalities. These results support a low alpha beta ratio for prostate cancer. Author Disclosure: A. Katz: F. Honoraria; Accuray. D. Freeman: F. Honoraria; Accuray. J. Aronovitz: None. D. Fuller: None. G. Bolzicco: None. R. Meier: None. S. Collins: G. Consultant; Accuray. J. Wang: None. M. Steinberg: None. C. King: None.
been minimal. EPIC urinary, bowel and sexual function responses appear favorable compared to other radiation therapy modalities. Early PSA responses are promising. With further follow-up, this study will help determine whether SBRT provides a therapeutic gain in the treatment of organ-confined prostate cancer. Acknowledgment: This project was supported by NCT00643994 and a grant from Accuray Inc. Author Disclosure: R. Meier: None. I. Kaplan: None. A. Beckman: None. G. Henning: None. S. Woodhouse: None. S. Williamson: None. N. Mohideen: None. D. Herold: None. C. Cotrutz: D. Employment Other; Spouse employed by Accuray. M. Sanda: None.
366 Stereotactic Body Radiation Therapy for Intermediate-risk Organconfined Prostate Cancer: Interim Toxicity and Quality of Life Outcomes From a Multi-institutional Study R. Meier,1 I. Kaplan,2 A. Beckman,3 G. Henning,4 S. Woodhouse,5 S. Williamson,6 N. Mohideen,7 D. Herold,8 C. Cotrutz,1 and M. Sanda2; 1 Swedish Cancer Institute, Seattle, WA, 2Beth Israel Deaconess Medical Center, Boston, MA, 3Central Baptist Hospital, Lexington, KY, 4St. Joseph Mercy Hospital System, Ypsilanti, MI, 5Community Cancer Center, Normal, IL, 6Capital Health System, Trenton, NJ, 7Northwest Community Hospital, Arlington Heights, IL, 8Jupiter Medical Center, Jupiter, FL Purpose/Objective(s): A phase II prospective multi-center study was initiated in 2007 to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for organ-confined prostate cancer. The study included 21 institutions and completed accrual in 2011. We report an interim analysis of toxicities, quality of life (QOL) and early PSA outcomes of the intermediate-risk cohort. Materials/Methods: A total of 129 hormone-naı¨ve intermediate-risk patients (CS T1c-T2b, N0-x, M0-x, with either Gleason Z 7 and PSA <10 ng/mL, or Gleason 6 and PSA between 10 and 20) with biopsy proven adenocarcinoma of the prostate were enrolled. MR imaging was used to assist in target localization. All patients were treated with a non-isocentric robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy and seminal vesicles received 36.25 Gy. No patient had androgen deprivation therapy. Toxicities were assessed using CTCAE v3 criteria. QOL for urinary, bowel and sexual function were assessed using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire; patients with erections “Firm enough for intercourse” on question 9 were scored as potent. Biochemical failure was defined as a 2 ng/mL rise above nadir. Results: Median follow-up was 30 months (range 10-42 months). No acute grade 3+ toxicities were reported. Acute Grade 2 GU and GI toxicities occurred in 20% and 8.5% of patients, respectively. One patient required temporary catheter placement for acute urinary retention. Late Grade 2 GU and GI toxicities occurred in 10% and 2% of patients, respectively. One late Grade 3 GU toxicity (bladder neck injury 1 year after treatment) was reported. There were no other Grade 3-5 toxicities. Mean EPIC urinary and bowel scores fell at 1 month and returned to baseline by 24 months. At baseline 52% of patients were potent, declining to 35% at 24 months. Pre-treatment median PSA was 5.93 ng/mL, decreasing to 0.80, 0.38 and 0.20 ng/mL at 1, 2 and 3 years, respectively. One patient had a biochemical failure at 3 months follow-up due to a biopsy-proven nodal metastasis. No other biochemical failures have been observed, resulting in a 3-year Kaplan-Meier biochemical progression-free survival rate of 99.2%. Conclusions: In a multi-institutional study employing SBRT in intermediate-risk prostate cancer patients, serious acute and late toxicities have
367 Dose Escalation of 5-Fraction Radiation Therapy for Prostate Cancer: Quality of Life Comparison of 2 Prospective Trials H.C. Quon,1 D.A. Loblaw,2 P. Cheung,2 C.I. Tang,3 G. Pang,2 G. Morton,2 A. Mamedov,2 L. D’Alimonte,2 A. Deabreu,2 and R. Tirona2; 1Cancercare Manitoba, Winnipeg, MB, Canada, 2Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Calvary Mater Newcastle Hospital, Waratah, Australia Purpose/Objective(s): To compare the quality of life of two fivefraction radiation therapy schedules for the treatment of localized prostate cancer. Materials/Methods: Two sequential phase I/II studies of five-fraction radiation therapy for the treatment of low and intermediate risk prostate cancer have been conducted. In the first trial, patients received 35 Gy in 5 fractions, once per week over 29 days (Group 1). In the second trial, patients received 40 Gy in 5 fractions, once per week over 29 days (Group 2). Treatment was delivered to the prostate only with intensity modulated radiation therapy using daily image guidance with gold seed fiducials and a 4mm (Group 1) or 5 mm (Group 2) CTV-PTV margin. Quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) instrument in both trials at baseline and every 6 months. A clinically relevant change in EPIC score was defined as a decrease of >0.5 standard deviation of the baseline value. Results: Eighty-four patients have been treated in Group 1 with a median follow-up of 36 months. In Group 2, 30 patients have been treated with a median follow-up of 12 months. EPIC scores at 12 months were compared. There was a lower proportion of patients who experienced a clinically relevant decrease in bowel bother scores in Group 1 versus Group 2 (27.4 vs. 61.1%, p Z 0.01), respectively. However, there was no significant difference in proportion of patients reporting moderate to severe problems in overall bowel habits (7.3% vs. 11.1%, p Z 0.63). No significant differences were found in the proportion of patients with clinically relevant decreases in domain summary scores, which for Group 1 versus Group 2 were: urinary (36.9 vs. 27.8%, p Z 0.59), bowel (27.4 vs. 50.0%, p Z 0.09), sexual (35.0 vs. 35.3%, p Z 1.00), and hormonal (21.7 vs. 23.5%, p Z 1.00). Mean domain summary scores at 12 months are shown in the Table. Conclusions: Patients receiving an escalated dose of five-fraction radiation therapy had a greater risk of a clinically relevant decrease in bowel bother EPIC score. However, moderate to severe overall bowel problems were not significantly different. Most quality of life scores remained high in both groups.
Oral Scientific Abstract 367; Table dard deviation) at 12 months EPIC domain Urinary Bowel Sexual Hormonal
Mean EPIC summary scores (+/- stan-
Group 1 89.9 92.1 47.9 93.2
+/+/+/+/-
11.2 8.4 26.9 7.4
Group 2 84.0 85.5 43.0 87.8
+/+/+/+/-
18.4 15.5 23.8 14.7