- Email: [email protected]
Long-term Outcome for Very High Risk Prostate Cancer Treated with Permanent Interstitial Brachytherapy
Proceedings of the 53rd Annual ASTRO Meeting
2401
The Toxicity of Dose Escalated External Beam Radiation Therapy after Elective Pelvic Nodal Irradiation: Evaluating the Utility of the QUANTEC Rectal Dose Thresholds
R. G. Carlson, W. J. Morris, V. Moiseenko, S. Tyldesley, R. Kosztyla, J. Hamm, J. Hui, J. Jackson, H. Sahota, M. Liu BC Cancer Agency, Vancouver, BC, Canada Purpose/Objective(s): Elective pelvic nodal irradiation (EPNI) increases the volume of the rectum subjected to moderate doses (40-50Gy) of external beam radiation therapy (EBRT). Some evidence suggests that EPNI may reduce the tolerance of small rectal volumes to high doses (.65Gy). Using data derived from rectal DVHs this study evaluates the QUANTEC thresholds and the correlation between late rectal bleeding and dose in a cohort of uniformly treated patients. Materials/Methods: ASCENDE RT is a trial open to unfavorable risk patients with clinical stage #T3a and pretreatment PSA #40 ng/mL that combines androgen deprivation therapy (ADT; 12 months total, 8 months neoadjuvant) and EPNI with randomization to either a high dose 3D conformal EBRT boost (Arm 1) or a 125I brachytherapy boost (Arm 2). The study sample consists of all Arm 1 patients who completed treatment by Dec. 31, 2008 (N = 119). After removing identifiers, the planning CTs were copied and rectal contours were outlined on the CT images by 3 trained observers. To minimize bias, observers were blinded to the other contours as well as the rectal bleeding status of the subjects. By including the original contours, four independent rectal DVHs were acquired for each patient providing an N of 476 for analysis. Results: The median age of the cohort was 67 years. All but one individual received ADT as per protocol; 97% (N = 116) received radiotherapy by protocol (78 Gy in 39 fractions). The median follow up for the group was 59.4 months. There were 15 subjects with grade 2 rectal bleeding, three with grade 3, and none with $ grade 4. The 5 year K-M estimates are 16.5% for $ grade 2 and 2.8% $ grade 3. The mean time from the start of radiation to late grade 2+ rectal bleeding was 16.0 (± 15.1) months. The CT scans from 57 subjects have been contoured thus far (N = 228). The median and mean V70 were 29.0% and 30.2% (SD 3.7%) and for V75 were 16.7% and 17.1% (SD 2.3%). While there is minimal intra- and inter-observer variance in the high dose part of the rectal DVH, in the low/moderate dose region, we identify a relatively large total variance with an overlap index of 65%. The total variance consists of actual anatomic variation and errors in contouring; estimating their relative proportions should help define confidence intervals suitable for this region of the DVH. Conclusions: This study reveals non-uniform variance in rectal DVH where the variance is low in the high dose region and high in the low/moderate dose region. We submit that this pattern of non-uniform variance is intrinsic, making multiple blinded observers essential if investigators seek a valid and quantitative answer to the question: Does EPNI reduce the radio-tolerance of small rectal volumes to high doses and thereby increase the risk of rectal bleeding? Author Disclosure: R.G. Carlson: None. W.J. Morris: None. V. Moiseenko: None. S. Tyldesley: None. R. Kosztyla: None. J. Hamm: None. J. Hui: None. J. Jackson: None. H. Sahota: None. M. Liu: None.
2402
Long-term Outcome for Very High Risk Prostate Cancer Treated with Permanent Interstitial Brachytherapy
N. Bittner1, G. S. Merrick2, W. M. Butler2, R. W. Galbreath2, J. Lief2, E. Adamovich3, K. E. Wallner4 1 3
Tacoma Valley Radiation Oncology Center, Puyallup, WA, 2Schiffler Cancer Center/Wheeling Jesuit, Wheeling, WV, Department of Pathology, Wheeling Hospital, Wheeling, WV, 4Puget Sound Healthcare Corporation, Seattle, WA
Purpose/Objective(s): The management of high risk prostate cancer remains controversial. Despite cure rates of approximately 40% for high risk patients in the modern radical prostatectomy era, radical prostatectomy is being increasingly utilized in this patient population. In this study, we evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in very high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Materials/Methods: From April 1995 - June 2007, 131 patients underwent permanent interstitial brachytherapy for very high risk prostate cancer (Gleason score 10, Gleason score 8-9 with . 50% of the biopsies positive for malignancy, any Gleason score 8-9 with a PSA . 20ng/mL, any clinical stage T3 and any PSA . 40ng/mL). Median follow-up was 7.4 years. 120 patients (91.6%) received supplemental external beam radiation therapy and 100 (76.4%) received androgen deprivation therapy (ADT) with a median duration of 19.5 months (range 4-36 months). The median post implant day 0 D90 was 121.9% of prescription dose. bPFS was defined as a PSA # 0.40ng/mL after nadir. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastasis who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. Results: At 12 years, CSS, bPFS and OS were 90.3%, 86.3% and 60.5%. The median Gleason score was 8.0 with 110 patients (84.0%) diagnosed with Gleason score 8-10 histology. The mean pre-treatment PSA was 17.0. 73 patients (65.7%) presented with a pre-treatment PSA . 10ng/mL. The median time for biochemical and distant failure was 1.6 and 1.4 years. In contrast, the median time to death for biochemical and distant failure was 6.4 years vs. 3.9 years. In Cox regression analysis, CSS and bPFS were both closely related to percent positive biopsies and ADT duration. OS was most closely related to patient age and percent positive biopsies. Overall cause of death was a result of diseases of the heart in 18.5%, non prostate cancer in 8.6%, other causes in 7.4%, and prostate cancer in 8.3% of patients at 12 years. For biochemically controlled patients, the median post-treatment PSA was \ 0.02ng/mL. Conclusions: High quality brachytherapy results in favorable bPFS and CSS for patients with very high risk disease. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health in very high risk prostate cancer patients may positively impact overall survival. Author Disclosure: N. Bittner: None. G.S. Merrick: None. W.M. Butler: None. R.W. Galbreath: None. J. Lief: None. E. Adamovich: None. K.E. Wallner: None.
S403
2401
The Toxicity of Dose Escalated External Beam Radiation Therapy after Elective Pelvic Nodal Irradiation: Evaluating the Utility of the QUANTEC Rectal Dose Thresholds
R. G. Carlson, W. J. Morris, V. Moiseenko, S. Tyldesley, R. Kosztyla, J. Hamm, J. Hui, J. Jackson, H. Sahota, M. Liu BC Cancer Agency, Vancouver, BC, Canada Purpose/Objective(s): Elective pelvic nodal irradiation (EPNI) increases the volume of the rectum subjected to moderate doses (40-50Gy) of external beam radiation therapy (EBRT). Some evidence suggests that EPNI may reduce the tolerance of small rectal volumes to high doses (.65Gy). Using data derived from rectal DVHs this study evaluates the QUANTEC thresholds and the correlation between late rectal bleeding and dose in a cohort of uniformly treated patients. Materials/Methods: ASCENDE RT is a trial open to unfavorable risk patients with clinical stage #T3a and pretreatment PSA #40 ng/mL that combines androgen deprivation therapy (ADT; 12 months total, 8 months neoadjuvant) and EPNI with randomization to either a high dose 3D conformal EBRT boost (Arm 1) or a 125I brachytherapy boost (Arm 2). The study sample consists of all Arm 1 patients who completed treatment by Dec. 31, 2008 (N = 119). After removing identifiers, the planning CTs were copied and rectal contours were outlined on the CT images by 3 trained observers. To minimize bias, observers were blinded to the other contours as well as the rectal bleeding status of the subjects. By including the original contours, four independent rectal DVHs were acquired for each patient providing an N of 476 for analysis. Results: The median age of the cohort was 67 years. All but one individual received ADT as per protocol; 97% (N = 116) received radiotherapy by protocol (78 Gy in 39 fractions). The median follow up for the group was 59.4 months. There were 15 subjects with grade 2 rectal bleeding, three with grade 3, and none with $ grade 4. The 5 year K-M estimates are 16.5% for $ grade 2 and 2.8% $ grade 3. The mean time from the start of radiation to late grade 2+ rectal bleeding was 16.0 (± 15.1) months. The CT scans from 57 subjects have been contoured thus far (N = 228). The median and mean V70 were 29.0% and 30.2% (SD 3.7%) and for V75 were 16.7% and 17.1% (SD 2.3%). While there is minimal intra- and inter-observer variance in the high dose part of the rectal DVH, in the low/moderate dose region, we identify a relatively large total variance with an overlap index of 65%. The total variance consists of actual anatomic variation and errors in contouring; estimating their relative proportions should help define confidence intervals suitable for this region of the DVH. Conclusions: This study reveals non-uniform variance in rectal DVH where the variance is low in the high dose region and high in the low/moderate dose region. We submit that this pattern of non-uniform variance is intrinsic, making multiple blinded observers essential if investigators seek a valid and quantitative answer to the question: Does EPNI reduce the radio-tolerance of small rectal volumes to high doses and thereby increase the risk of rectal bleeding? Author Disclosure: R.G. Carlson: None. W.J. Morris: None. V. Moiseenko: None. S. Tyldesley: None. R. Kosztyla: None. J. Hamm: None. J. Hui: None. J. Jackson: None. H. Sahota: None. M. Liu: None.
2402
Long-term Outcome for Very High Risk Prostate Cancer Treated with Permanent Interstitial Brachytherapy
N. Bittner1, G. S. Merrick2, W. M. Butler2, R. W. Galbreath2, J. Lief2, E. Adamovich3, K. E. Wallner4 1 3
Tacoma Valley Radiation Oncology Center, Puyallup, WA, 2Schiffler Cancer Center/Wheeling Jesuit, Wheeling, WV, Department of Pathology, Wheeling Hospital, Wheeling, WV, 4Puget Sound Healthcare Corporation, Seattle, WA
Purpose/Objective(s): The management of high risk prostate cancer remains controversial. Despite cure rates of approximately 40% for high risk patients in the modern radical prostatectomy era, radical prostatectomy is being increasingly utilized in this patient population. In this study, we evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in very high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Materials/Methods: From April 1995 - June 2007, 131 patients underwent permanent interstitial brachytherapy for very high risk prostate cancer (Gleason score 10, Gleason score 8-9 with . 50% of the biopsies positive for malignancy, any Gleason score 8-9 with a PSA . 20ng/mL, any clinical stage T3 and any PSA . 40ng/mL). Median follow-up was 7.4 years. 120 patients (91.6%) received supplemental external beam radiation therapy and 100 (76.4%) received androgen deprivation therapy (ADT) with a median duration of 19.5 months (range 4-36 months). The median post implant day 0 D90 was 121.9% of prescription dose. bPFS was defined as a PSA # 0.40ng/mL after nadir. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastasis who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. Results: At 12 years, CSS, bPFS and OS were 90.3%, 86.3% and 60.5%. The median Gleason score was 8.0 with 110 patients (84.0%) diagnosed with Gleason score 8-10 histology. The mean pre-treatment PSA was 17.0. 73 patients (65.7%) presented with a pre-treatment PSA . 10ng/mL. The median time for biochemical and distant failure was 1.6 and 1.4 years. In contrast, the median time to death for biochemical and distant failure was 6.4 years vs. 3.9 years. In Cox regression analysis, CSS and bPFS were both closely related to percent positive biopsies and ADT duration. OS was most closely related to patient age and percent positive biopsies. Overall cause of death was a result of diseases of the heart in 18.5%, non prostate cancer in 8.6%, other causes in 7.4%, and prostate cancer in 8.3% of patients at 12 years. For biochemically controlled patients, the median post-treatment PSA was \ 0.02ng/mL. Conclusions: High quality brachytherapy results in favorable bPFS and CSS for patients with very high risk disease. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health in very high risk prostate cancer patients may positively impact overall survival. Author Disclosure: N. Bittner: None. G.S. Merrick: None. W.M. Butler: None. R.W. Galbreath: None. J. Lief: None. E. Adamovich: None. K.E. Wallner: None.
S403