Try a new search

Format these results:

Searched for:

in-biosketch:true

person:zelefm01

Total Results:

484


Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy

Ashman, Jonathan B; Zelefsky, Michael J; Hunt, Margie S; Leibel, Steven A; Fuks, Zvi
PURPOSE/OBJECTIVE:To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS/METHODS:Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. RESULTS:Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. CONCLUSIONS:Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity.
PMID: 15913914
ISSN: 0360-3016
CID: 5527582

A measure of health-related quality of life among patients with localized prostate cancer: results from ongoing scale development

Befort, Christie A; Zelefsky, Michael J; Scardino, Peter T; Borrayo, Evelinn; Giesler, R Brian; Kattan, Michael W
BACKGROUND:We revised our prostate cancer-specific measure to better address the physiologic complications of the 3 major therapies for clinically localized prostate cancer and to assess the impact of symptoms on broader aspects of patient functioning. The study used a cross-sectional design, and participants completed the measure in a clinical setting. PATIENTS AND METHODS/METHODS:Participants underwent radical prostatectomy (n = 130), external beam radiation therapy (n = 120), or brachytherapy (n = 129). Their mean age was 66 years (standard deviation [SD], 8.2 years), and the median time since treatment was 12.36 months (mean, 21.7; SD, 25.4). Items were derived from previously validated instruments or developed based on the clinical experience of a multidisciplinary group of health professionals. RESULTS:The revised instrument included 46 items that formed 8 physiologic scales (2 urinary, 3 sexual, and 3 bowel function); 3 associated bother scales; and cancer worry, treatment regret, and treatment satisfaction scales. Correlations among scales provided evidence of convergent/divergent validity. Significant group differences were found using analysis of covariance (with time since treatment and age as covariates) on 6 of the 8 physiologic scales and on bowel bother and treatment satisfaction. CONCLUSION/CONCLUSIONS:The instrument provides a sensitive measure of physiologic differences across the 3 primary treatment groups and indicates that there are few differences across treatment groups on broader aspects of health-related quality of life. Further development of the measure is recommended.
PMID: 16197610
ISSN: 1540-0352
CID: 5527622

Methodology for biologically-based treatment planning for combined low-dose-rate (permanent implant) and high-dose-rate (fractionated) treatment of prostate cancer

Zaider, Marco; Zelefsky, Michael J; Cohen, Gilad N; Chui, Chen-Shou; Yorke, Ellen D; Ben-Porat, Leah; Happersett, Laura
PURPOSE/OBJECTIVE:The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. METHODS AND MATERIALS/METHODS:Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (alpha, beta, potential doubling time for prostate cancer cells [T(pot)], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. RESULTS:The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. CONCLUSIONS:We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.
PMID: 15708248
ISSN: 0360-3016
CID: 5527552

Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis

Horwitz, Eric M; Thames, Howard D; Kuban, Deborah A; Levy, Larry B; Kupelian, Patrick A; Martinez, Alvaro A; Michalski, Jeffrey M; Pisansky, Thomas M; Sandler, Howard M; Shipley, William U; Zelefsky, Michael J; Hanks, Gerald E; Zietman, Anthony L
PURPOSE/OBJECTIVE:Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. MATERIALS AND METHODS/METHODS:The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. RESULTS:The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). CONCLUSIONS:Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure.
PMID: 15711272
ISSN: 0022-5347
CID: 5527562

Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer

Zelefsky, Michael J; Ben-Porat, Leah; Scher, Howard I; Chan, Heather M; Fearn, Paul A; Fuks, Zvi Y; Leibel, Steven A; Venkatraman, E S
PURPOSE/OBJECTIVE:To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. MATERIALS AND METHODS/METHODS:A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. RESULTS:The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. CONCLUSION/CONCLUSIONS:In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
PMID: 15681527
ISSN: 0732-183x
CID: 5527542

Improved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: the combined experience of nine institutions in patients treated in 1994 and 1995

Kupelian, Patrick; Kuban, Deborah; Thames, Howard; Levy, Larry; Horwitz, Eric; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony
PURPOSE/OBJECTIVE:To study the radiation dose-response as determined by Kaplan-Meier prostate-specific antigen (PSA) disease-free survival (PSA-DFS) estimates in patients with stage T1-T2 prostate cancer treated within a 2-year period (1994-1995). METHODS:Nine institutions combined data on 4839 patients with stage T1 and T2 adenocarcinoma of the prostate who received > or =60 Gy external beam radiation therapy (RT) as sole treatment. No patient received neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. Of the 4839 patients, 1325 were treated in 1994 and 1995; 1061 were treated with <72 Gy and 264 with > or =72 Gy. The median RT doses for the <72 Gy and the > or =72 Gy groups were 68.4 Gy and 75.6 Gy, respectively. The median follow-up for the <72 Gy and the > or =72 Gy groups were 5.8 and 5.7 years, respectively. Risk groups, defined on the basis of T stage, pretherapy PSA level, and biopsy Gleason score (GS), were as follows: low risk--T1b, T1c, T2a, GS < or =6 and PSA < or =10 ng/mL; intermediate risk--T1b, T1c, T2a, GS < or =6 and PSA >10 ng/mL but < or =20 ng/mL or T2b, GS < or =6 and PSA < or =20 ng/mL or GS 7 and PSA < or =20 ng/mL; high risk--GS 8-10 or PSA >20 ng/mL. The endpoint for outcome analysis was PSA-DFS at 5 years after therapy using the American Society for Therapeutic Radiology and Oncology failure definition. RESULTS:Patients receiving > or =72 Gy had significantly more advanced cancers. The proportion of stage T2b/T2c cancers in the > or =72 Gy group was 42% compared with 32% in the <72 Gy group (p = 0.027). The mean pretherapy PSA was 11.4 ng/mL in the > or =72 Gy group compared with 10.7 ng/mL in the <72 Gy group (p = 0.001). The proportion of GS > or =8 cancers in the > or =72 Gy group was 9% compared with 7% in the <72 Gy group (p = 0.309). Overall, 15% of patients receiving <72 Gy had high-risk disease, compared with 22% of patients receiving > or =72 Gy (p = 0.034). The > or =72 Gy group had a greater number of follow-up PSA levels (mean 10.6/patient) compared with the <72 Gy group (mean 9.6/patient) (p = 0.007). For all 1325 patients, the 5- and 8-year PSA-DFS estimates were 64% and 62%, respectively. The 5-year PSA-DFS estimates for <72 Gy vs. > or =72 Gy were 63% vs. 69%, respectively (p = 0.046). Multivariate analysis for factors affecting PSA-DFS was performed for all cases using the following variables: pretherapy PSA (continuous), biopsy GS (continuous), stage (T1 vs. T2), radiation dose (continuous), and radiation technique (three-dimensional conformal vs. conventional). Pretreatment PSA (p < 0.001, chi-square 112.2), GS (p < 0.001, chi-square 12.8), radiation dose (p < 0.001, chi-square 13.5), and stage (p = 0.007, chi-square 7.2) were independent predictors of outcome. Radiotherapy technique was not (p = 0.50). CONCLUSION/CONCLUSIONS:Differences in PSA-DFS estimates observed in multiple retrospective series have been attributed to differences in follow-up duration between patients treated to conventional doses (longer follow-up intervals) and those treated to higher doses (shorter follow-up intervals). In this report, the median follow-up duration in the > or =72 Gy group was essentially identical to the <72 Gy group, because the study included a large number of patients treated consecutively during a narrow time range (1994-1995). With similar follow-up duration, higher than conventional radiotherapy doses were associated with improved PSA-DFS when controlled for the influence of pretreatment PSA levels, biopsy GS, and clinical T stage.
PMID: 15667961
ISSN: 0360-3016
CID: 5527532

Failure definition-dependent differences in outcome following radiation for localized prostate cancer: can one size fit all?

Kuban, Deborah; Thames, Howard; Levy, Larry; Horwitz, Eric; Kupelian, Patrick; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony
PURPOSE/OBJECTIVE:To compare long-term outcome using alternative failure definitions after external beam radiation for localized prostate cancer. METHODS AND MATERIALS/METHODS:Data from 4839 patients with stage T1b, T1c, and T2 adenocarcinoma of the prostate who were treated solely with external beam radiation between 1986 and 1995 at nine U.S. institutions were analyzed. Outcome using the following prostate-specific antigen (PSA) failure definitions was compared: (1) three consecutive PSA rises backdated (American Society for Therapeutic Radiology and Oncology [ASTRO]), (2) two PSA rises of at least 0.5 ng/mL each, backdated (0.5 x 2), (3) three consecutive PSA rises with failure recorded at the call date (ASTRO call date), (4) PSA > or =current PSA nadir + 2 ng/mL (Houston + 2), (5) PSA > or =current PSA nadir + 3 ng/mL (Houston + 3), (6) PSA >0.2 ng/mL, or (7) PSA >0.5 ng/mL. For definitions 3-7, the failure date was recorded as the date the criterion was met, without backdating. RESULTS:PSA disease-free survival (PSA-DFS) varied according to the failure definition used with differences of up to 13% with PSA rise definitions and up to 44% with absolute nadir value surgical-type definitions within the first 5 years post-therapy as compared with the ASTRO definition. PSA-DFS was 66%, 66%, 68%, 72%, 15%, and 25% at 5 years postradiation for definitions 2-7, respectively, vs. 59% for the ASTRO definition. Sensitivity and specificity of definitions 2, 4, and 5 were better than for the ASTRO definition, whereas, for definitions 6 and 7, the sensitivity was at least 90% but the specificity was only 9% and 26%, respectively. This analysis shows that the ASTRO definition does not overestimate outcome, particularly in the first 5 years after therapy, as compared with other definitions appropriate to irradiated patients. CONCLUSION/CONCLUSIONS:There are notable differences in both short- and long-term outcomes after definitive radiation for prostate cancer depending on the failure definition applied. Failure definitions must be tested objectively for sensitivity and specificity in predicting clinical outcome, and it is only in this manner that reasonable choices can be made. Although traditional surgical-type failure definitions do not seem applicable to patients treated with external beam radiation, further analysis of definitions across multiple therapeutic modalities is necessary to determine whether a universal failure definition might be feasible, at least for research and comparative purposes.
PMID: 15667960
ISSN: 0360-3016
CID: 5527522

Measurement of respiratory motion of the prostate in the prone and supine orientations using respiratory correlated computed tomography [Meeting Abstract]

Awunor, OA; Lovelock, MD; Ashman, JB; Mageras, GS; Zelefsky, MJ
ISI:000232083301351
ISSN: 0360-3016
CID: 5530142

The impact of MRI training on improvement of CT based post implant dosimetry: A six physician study [Meeting Abstract]

McLauphlin, PW; Narayana, V; Jackson, TR; Crook, JM; Lee, WR; Michalski, JM; Prestidge, BR; Zelefsky, MJ
ISI:000232083301079
ISSN: 0360-3016
CID: 5530132

Predictive factors for late genitourinary and gastrointestinal toxicity in patients with prostate cancer treated with adjuvant or salvage radiotherapy [Meeting Abstract]

Feng, M; Hanlon, AL; Pisansky, TM; Kuban, DA; Catton, C; Michalski, JM; Zelefsky, MJ; Kupelian, PA; Pollack, A; Kestin, LL; Valicenti, RK; DeWeese, TL
ISI:000232083300213
ISSN: 0360-3016
CID: 5530122