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High-dose Moderately Hypofractionated Tomotherapy for Localized Prostate Cancer: Promising 3-year Results
Proceedings of the 52nd Annual ASTRO Meeting sexual dysfunction. Analysis by baseline functional category is a useful means of predicting long-term QOL scores for an individual patient. Author Disclosure: J. Coen, None; J. Paly, None; A. Niemierko, None; A. Rodrigues, None; E. Weyman, None; W.U. Shipley, None; A.L. Zietman, None; J.A. Talcott, None.
2325
High-dose Moderately Hypofractionated Tomotherapy for Localized Prostate Cancer: Promising 3-year Results
N. Di Muzio1, C. Fiorino1, C. Cozzarini1, F. Alongi1, B. Pappalardi1, P. Mangili1, R. Valdagni2, G. Berardi1, R. Calandrino1, G. Guazzoni1 1
Research Institute S. Raffaele Hospital, Milan, Italy, 2Istituto Nazionale dei Tumori, Milan, Italy
Purpose/Objective(s): To report acute/late toxicity and early biochemical relapse-free survival (bRFS) results of the first 98 patients (pts), with a 1-year minimum follow-up, treated within a Phase I-II study with moderate hypofractionation by image-guided helical tomotherapy (HTT). Materials/Methods: Between January 2006 and March 2009, 98 pts (median age 73 years; range 56-89) underwent to simultaneous integrated boost radical radiation therapy with HTT (HiArtII). According to NCCN staging, 45 low risk, and 53 intermediatehigh risk pts received 71,4-74,2 Gy/28 fractions to the prostate gland respectively, while concomitantly delivering 65.5 Gy to the overlap between rectum and PTV and 51.8 Gy on pelvic lymph-nodes (only in intermediate-high risk pts). The median follow-up was 36 mos (range 12-50 mo); Hormonal therapy was prescribed to 74 patients (33 low and 41 intermediate-high risk pts). Late toxicities were evaluated and scored using the RTOG/EORTC scale. Biochemical relapses were defined according to the ASTRO definition. Results: The 3-year grade 3 GU toxicity rate was 4.5 % (±2.2%); three out of five events were stenosis requiring dilatation. No pts experienced G3 GI toxicity. The 3-year grade2-3 toxicity rate was 19.9% (±4.2%) and 8.7% (±3.0%) for GU and rectal toxicity respectively. 95/98 pts were evaluable for biochemical control: biochemical relapses were seen in only 3 pts and were all three associated to early (\20 months) bone metastatic progression. The 3-year bRFS rates were 100% and 94% for low and intermediate-high risk patients respectively. Late grade 2-3 GU toxicity was clearly correlated with acute toxicity (p = 0.001, log-rank test) with a 3-year late GU toxicity rate equal to 12.3% (±4.1%) and 40.1% (±10.0) for patients with acute grade 0-1 and grade 2-3 GU toxicity, respectively. Interestingly, the risk of late grade2-3 GU toxicity was similar in the two dose groups (71.4Gy without pelvic nodes vs. 74.2 with pelvic nodes: 17.8% vs. 21.3%, p = 0.69). Conclusions: This study shows excellent results with regard to 3-year late toxicity; in particular no G3 late rectal toxicity and a reduced rate of grade 3 GU toxicity was found up to now; late grade 2-3 GU toxicity seems to show a prevalently consequential component. Although most pts received also hormonal therapy, the early biochemical control results are very promising. Further follow-up is needed to assess definitive late toxicity and long-term biochemical control outcome. Author Disclosure: N. Di Muzio, None; C. Fiorino, None; C. Cozzarini, None; F. Alongi, None; B. Pappalardi, None; P. Mangili, None; R. Valdagni, None; G. Berardi, None; R. Calandrino, None; G. Guazzoni, None.
2326
Long-term Predictors of Biochemical and Distant Metastatic Failure following Post Prostatectomy Salvage Radiotherapy
A. Goenka1, J. J. Magsanoc2, X. Pei1, M. Schechter1, M. J. Zelefsky1 1
Memorial Sloan Kettering Cancer Center, New York, NY, 2St. Luke’s Medical Cener Quezon City, Quezon City, Philippines
Purpose/Objective(s): To determine long term clinical and pathological predictors of biochemical tumor control and distant metastases in prostate cancer patients receiving salvage radiation treatment (SRT) with 3D-CRT/IMRT. Materials/Methods: Between 1988 and 2006, 285 consecutive patients were treated at our institution with SRT after radical prostatectomy (RP). All patients had a detectable PSA prior to initiation of SRT. Two hundred fifteen patients (75%) had at least two consecutive increases in PSA and 201 (71%) had a post-prostatectomy PSA $0.2. The median pre-SRT PSA was 0.4 ng/ml. Pathologic characteristics included 68 patients (24%) with $ Gleason 8 disease, 114 (40%) with involved surgical margins, 152 (53%) with extracapsular extension (ECE), 66 (23%) with seminal vesicle involvement (SVI), and 55 (19%) with vascular invasion (VI). 92 patients (32%) had either radiographic or biopsy proven local recurrence (RBLR) pre SRT. 79 patients (28%) received androgen deprivation treatment (ADT) as a component of salvage treatment. The median RT dose was 7020 cGy (range: 5400-7800 cGy). Results: The overall 5-year and 7-year actuarial PSA relapse-free survival was 43% and 37%, and distant metastases free survival 84% and 76%. The median time from prostatectomy to biochemical failure was 19 months and from prostatectomy to SRT 31 months. Following completion of SRT, the median follow-up was 58 months (range: 2-221 months). Patients with positive surgical margins had a 47% 7-yr bPFS vs. 32% with negative margins, and those with pre-SRT PSA \0.6 ng/mL 42% vs. 31% with PSA $0.6 ng/ml. Patients with positive margins, combined with a pre-SRT PSA\0.6 ng/ml and post-prostatectomy PSA nadir of 0 had a 7-year bPFS of 55%. On multivariate analysis, VI (p \ 0.01), surgical margin status (p \ 0.01), and pre-salvage PSA $0.6 (p \ 0.01) were independent predictors of PSA relapse. The 7-year actuarial risk of distant metastases with RBLR was 38% vs. 19% without RBLR, and with Gleason score $ 8 42% vs. 13% with Gleason score \8. Patients with Gleason score \8 without RBLR had a 7-year DMFS of 89%. RBLR (p\0.01) and Gleason score $ 8 (p\0.01) were highly predictive of distant metastasis on multivariate analysis. ADT was not associated with improved distant metastases free survival (p = 0.20). Conclusions: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with a detectable PSA post-prostatectomy. Patients with Gleason score $8 or patients with evidence of radiographic or pathologic local failure prior to SRT have a significantly greater risk of distant metastasis. Improved systemic therapy regimens in conjunction with SRT are needed in particular for this latter high-risk cohort. Author Disclosure: A. Goenka, None; J.J. Magsanoc, None; X. Pei, None; M. Schechter, None; M.J. Zelefsky, None.
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2325
High-dose Moderately Hypofractionated Tomotherapy for Localized Prostate Cancer: Promising 3-year Results
N. Di Muzio1, C. Fiorino1, C. Cozzarini1, F. Alongi1, B. Pappalardi1, P. Mangili1, R. Valdagni2, G. Berardi1, R. Calandrino1, G. Guazzoni1 1
Research Institute S. Raffaele Hospital, Milan, Italy, 2Istituto Nazionale dei Tumori, Milan, Italy
Purpose/Objective(s): To report acute/late toxicity and early biochemical relapse-free survival (bRFS) results of the first 98 patients (pts), with a 1-year minimum follow-up, treated within a Phase I-II study with moderate hypofractionation by image-guided helical tomotherapy (HTT). Materials/Methods: Between January 2006 and March 2009, 98 pts (median age 73 years; range 56-89) underwent to simultaneous integrated boost radical radiation therapy with HTT (HiArtII). According to NCCN staging, 45 low risk, and 53 intermediatehigh risk pts received 71,4-74,2 Gy/28 fractions to the prostate gland respectively, while concomitantly delivering 65.5 Gy to the overlap between rectum and PTV and 51.8 Gy on pelvic lymph-nodes (only in intermediate-high risk pts). The median follow-up was 36 mos (range 12-50 mo); Hormonal therapy was prescribed to 74 patients (33 low and 41 intermediate-high risk pts). Late toxicities were evaluated and scored using the RTOG/EORTC scale. Biochemical relapses were defined according to the ASTRO definition. Results: The 3-year grade 3 GU toxicity rate was 4.5 % (±2.2%); three out of five events were stenosis requiring dilatation. No pts experienced G3 GI toxicity. The 3-year grade2-3 toxicity rate was 19.9% (±4.2%) and 8.7% (±3.0%) for GU and rectal toxicity respectively. 95/98 pts were evaluable for biochemical control: biochemical relapses were seen in only 3 pts and were all three associated to early (\20 months) bone metastatic progression. The 3-year bRFS rates were 100% and 94% for low and intermediate-high risk patients respectively. Late grade 2-3 GU toxicity was clearly correlated with acute toxicity (p = 0.001, log-rank test) with a 3-year late GU toxicity rate equal to 12.3% (±4.1%) and 40.1% (±10.0) for patients with acute grade 0-1 and grade 2-3 GU toxicity, respectively. Interestingly, the risk of late grade2-3 GU toxicity was similar in the two dose groups (71.4Gy without pelvic nodes vs. 74.2 with pelvic nodes: 17.8% vs. 21.3%, p = 0.69). Conclusions: This study shows excellent results with regard to 3-year late toxicity; in particular no G3 late rectal toxicity and a reduced rate of grade 3 GU toxicity was found up to now; late grade 2-3 GU toxicity seems to show a prevalently consequential component. Although most pts received also hormonal therapy, the early biochemical control results are very promising. Further follow-up is needed to assess definitive late toxicity and long-term biochemical control outcome. Author Disclosure: N. Di Muzio, None; C. Fiorino, None; C. Cozzarini, None; F. Alongi, None; B. Pappalardi, None; P. Mangili, None; R. Valdagni, None; G. Berardi, None; R. Calandrino, None; G. Guazzoni, None.
2326
Long-term Predictors of Biochemical and Distant Metastatic Failure following Post Prostatectomy Salvage Radiotherapy
A. Goenka1, J. J. Magsanoc2, X. Pei1, M. Schechter1, M. J. Zelefsky1 1
Memorial Sloan Kettering Cancer Center, New York, NY, 2St. Luke’s Medical Cener Quezon City, Quezon City, Philippines
Purpose/Objective(s): To determine long term clinical and pathological predictors of biochemical tumor control and distant metastases in prostate cancer patients receiving salvage radiation treatment (SRT) with 3D-CRT/IMRT. Materials/Methods: Between 1988 and 2006, 285 consecutive patients were treated at our institution with SRT after radical prostatectomy (RP). All patients had a detectable PSA prior to initiation of SRT. Two hundred fifteen patients (75%) had at least two consecutive increases in PSA and 201 (71%) had a post-prostatectomy PSA $0.2. The median pre-SRT PSA was 0.4 ng/ml. Pathologic characteristics included 68 patients (24%) with $ Gleason 8 disease, 114 (40%) with involved surgical margins, 152 (53%) with extracapsular extension (ECE), 66 (23%) with seminal vesicle involvement (SVI), and 55 (19%) with vascular invasion (VI). 92 patients (32%) had either radiographic or biopsy proven local recurrence (RBLR) pre SRT. 79 patients (28%) received androgen deprivation treatment (ADT) as a component of salvage treatment. The median RT dose was 7020 cGy (range: 5400-7800 cGy). Results: The overall 5-year and 7-year actuarial PSA relapse-free survival was 43% and 37%, and distant metastases free survival 84% and 76%. The median time from prostatectomy to biochemical failure was 19 months and from prostatectomy to SRT 31 months. Following completion of SRT, the median follow-up was 58 months (range: 2-221 months). Patients with positive surgical margins had a 47% 7-yr bPFS vs. 32% with negative margins, and those with pre-SRT PSA \0.6 ng/mL 42% vs. 31% with PSA $0.6 ng/ml. Patients with positive margins, combined with a pre-SRT PSA\0.6 ng/ml and post-prostatectomy PSA nadir of 0 had a 7-year bPFS of 55%. On multivariate analysis, VI (p \ 0.01), surgical margin status (p \ 0.01), and pre-salvage PSA $0.6 (p \ 0.01) were independent predictors of PSA relapse. The 7-year actuarial risk of distant metastases with RBLR was 38% vs. 19% without RBLR, and with Gleason score $ 8 42% vs. 13% with Gleason score \8. Patients with Gleason score \8 without RBLR had a 7-year DMFS of 89%. RBLR (p\0.01) and Gleason score $ 8 (p\0.01) were highly predictive of distant metastasis on multivariate analysis. ADT was not associated with improved distant metastases free survival (p = 0.20). Conclusions: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with a detectable PSA post-prostatectomy. Patients with Gleason score $8 or patients with evidence of radiographic or pathologic local failure prior to SRT have a significantly greater risk of distant metastasis. Improved systemic therapy regimens in conjunction with SRT are needed in particular for this latter high-risk cohort. Author Disclosure: A. Goenka, None; J.J. Magsanoc, None; X. Pei, None; M. Schechter, None; M.J. Zelefsky, None.
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