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Toxicity and Dosimetric Parameters Related to Conventional Versus Dose-Escalated, Hypofractionated Radiation in Prostate Cancer
Oral Scientific Sessions S147
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.
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
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.
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