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Mark K Buyyounouski

Publications and source records attributed to Mark K Buyyounouski.

11 recordsLinked to original sources
PubMed2007

Prostate-specific antigen nadir within 12 months of prostate cancer radiotherapy predicts metastasis and death.

BACKGROUND: The nadir prostate-specific antigen (PSA) at 1 year (nPSA12) was investigated as an early estimate of biochemical and clinical outcome after radiotherapy (RT) alone for localized prostate cancer.METHODS.From May 1989 to November 1999, 1000 men received 3D conformal RT alone (median, 76 Gy) with minimum and median follow-up periods of 26 and 58 months, respectively, from the end of treatment. The calculation of PSA doubling time (PSADT) was possible in 657 patients. Multivariate analyses (MVAs) via Cox proportional hazards regression were used to determine the association of nPSA12 to biochemical failure (BF; ASTRO definition), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). Dichotomization of nPSA12 was optimized by evaluating the sequential model likelihood ratio and P-values.RESULTS.In MVA, nPSA12 as a continuous variable was independent of RT dose, T-stage, Gleason score, pretreatment initial PSA, age, and PSADT in predicting for BF, DM, CSM, and OM. Dichotomized nPSA12 (2 versus >2 ng/mL) was independently related to DM and CSM. Kaplan-Meier 10-year DM rates for nPSA12 2 versus >2 ng/mL were 4% versus 19% (P<.0001).CONCLUSIONS.nPSA12 is a strong independent predictor of outcome after RT alone for prostate cancer and should be useful in identifying patients at high risk for progression to metastasis and death.

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PubMed2006

Radiation dose and late failures in prostate cancer.

PURPOSE: To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone. METHODS: The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months. RESULTS: Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at < or =4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in < or =4 years. Radiation dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74-Gy group. In patients receiving > or =74 Gy, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree. CONCLUSION: The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.

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PubMed2005

Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial.

PURPOSE: The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. PATIENTS AND METHODS: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. RESULTS: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. CONCLUSION: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

Dose Fractionation, Radiation↗
PubMed2005

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.

PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.

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PubMed2005

Biochemical failure and the temporal kinetics of prostate-specific antigen after radiation therapy with androgen deprivation.

PURPOSE: The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF. METHODS AND MATERIALS: Between December 1, 1991 and April 30, 1998, 688 men with T1c-T3 NX/0 M0 prostate cancer received three-dimensional conformal RT alone (n = 586) or in combination with either short-term (STAD: 3 to 12 months, n = 82) or long-term (LTAD: 12 to 36 months, n = 20) AD. Follow-up, calculated from the end of all treatment, was >/=48 months. The mean posttreatment PSA was calculated in 3-month intervals. RESULTS: The median posttreatment clinical follow-up period was 76 months (range, 48-152 months). The posttreatment PSA values from the end of all treatment for the RT+STAD-BF group showed an initial period of rise followed by a period of decline at 30 months and then a continued rise again. The decline in the mean posttreatment PSA is explained in part by stabilization in PSA level after 3 consecutive rises. Nonbiochemical failures (NBF) after RT+STAD had a relatively constant mean PSA over time of approximately 0.5 ng/mL. Unlike the RT+STAD-NBF profile, the RT+LTAD-NBF profile rose continuously and steadily to a level approaching 1 ng/mL. The RT+LTAD-BF profile rose continuously but at a slower rate over time. Nine RT+STAD-NBF patients (22%) and 2 RT+LTAD-BF (29%) patients experienced 3 consecutive rises followed by a subsequent decline and stabilization of PSA compared to 10 RT-BF patients (5%). Redistributing these misclassified patients to their respective NBF groups changed the mean posttreatment PSA profiles as follows: The RT+LTAD-BF profile rose constantly and steadily with a doubling time of approximately 16 months, and the RT+LAD-NF initially rose to a value of approximately 0.5 ng/mL, then at 36 months began to decline. CONCLUSIONS: The temporal kinetics of posttreatment PSA after RT+AD and RT alone are different. The American Society of Therapeutic Radiation Oncology definition for biochemical failure overestimates BF in 20-30% after RT+AD compared to 5% after RT alone.

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PubMed2004

The radiation doses to erectile tissues defined with magnetic resonance imaging after intensity-modulated radiation therapy or iodine-125 brachytherapy.

PURPOSE: To report penile bulb (PB) and corporal bodies (CB) doses during intensity-modulated radiation therapy (IMRT) and permanent (125)I prostate implant alone (BT) for favorable, early stage, clinically localized prostate cancer using computed tomography (CT) and magnetic resonance imaging (MRI) to provide a basis for comparison as the initial report of a comprehensive project to develop erectile tissues sparing techniques. METHODS AND MATERIAL: Prostate, PB and CB volumes were defined by a fused CT/MRI simulation study performed before treatment in 29 IMRT patients and verification study performed 30 days postimplant in 15 BT patients. The median prescribed prostate dose for the IMRT and BT groups was 74 Gy and 145 Gy, respectively. Dose volume histograms (DVHs) were generated to determine the dose characteristics for the PB, CB, and prostate for each patient. D(90), V(100), and V(50) were used, where D(i) was defined as the dose that covers i% of the prostate volume and V(i) is the fractional volume of the prostate that receives i% of the prescribed dose. The Wilcoxon rank sum test was used to evaluate significance between the groups. RESULTS: The median PB D(90), V(100), and V(50) values were 17.5 Gy, 0%, and 31.9% for the IMRT group; and 52.5 Gy, 21.5%, and 89.7% for the BT group. The median CB D(90), V(100), and V(50) values were 7.3 Gy, 0%, and 0.9% for the IMRT group; and 26.9 Gy, 2.4%, and 20.1% for the BT group. The differences between the IMRT vs. BT V(100) values, but not V(50), were statistically significant for the PB (p = 0.001) and CB (p = 0.001). CONCLUSIONS: Radiation dose to the PB and CB is low with IMRT or BT. Magnetic resonance imaging is superior to CT for the imaging of erectile tissues. Intensity-modulated radiation therapy may offer further reductions in the doses received by the PB and CB; however, at what cost to prostate coverage and normal tissue sparing will be the subject of a follow-up study.

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PubMed2004

Intensity-modulated radiotherapy with MRI simulation to reduce doses received by erectile tissue during prostate cancer treatment.

PURPOSE: The radiation doses received by erectile tissue may contribute to erectile dysfunction after treatment of prostate cancer. This is the first description of the ability to limit the dose received by the penile bulb (PB) and corporal bodies (CB) using intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Twenty-three patients with palpation Stage T1c-T2bN0M0 prostate cancer received IMRT alone. The dose prescribed to the planning target volume was 74-78 Gy. All patients underwent CT and MRI simulation to define the target and normal structures. Three plans with identical beam arrangements and energy were generated for each patient, with varying dose constraints for the PB and CB: no dose constraint, intermediate-dose constraint (20 Gy and 15 Gy, respectively) and low-dose constraint (15 Gy and 7 Gy, respectively). All plans were normalized, such that 95% of the planning target volume received at least 100% of the prescribed dose. For each plan, the ability to meet prostate dose homogeneity criteria (PHC; prostate maximal dose </=120% prescribed dose) and rectal tolerance dose-volume histogram criteria (RTC; </=35% and </=17% of rectal volume received 40 Gy and 65 Gy, respectively) was determined. The D(90), V(50), and V(75) were determined for both PB and the CB, where D(i) was the dose received by i% of the target volume and V(i) was the target volume receiving i% of the prescribed dose. RESULTS: The median PB D(90), V(50), and V(75) for the plans with no dose, intermediate-dose, and low-dose constraints was 20.8 Gy, 33.8%, and 9.9%; 8.0 Gy, 1.7%, and 0%; and 7.1 Gy, 0.1%, and 0%, respectively. The median CB D(90), V(50), and V(75) for plans with no dose, intermediate-dose, and low-dose constraints was 10.2 Gy, 3.8%, and 0%; 6.0 Gy, 0%, and 0%; and 4.9 Gy, 0%, and 0%, respectively. Overall differences in the D(90), V(50), and V(75) among the groups were significant for both the PB and the CB (p <0.0001). All plans with no dose constraint met the PHC and RTC. Twenty plans with an intermediate-dose constraint met the PHC and 21 met the RTC. Eighteen plans with a low-dose constraint met the PHC and 19 met the RTC. No statistically significant difference was found in the number of beam segments for the three groups (median of 51, 55, and 53; p = 0.8). CONCLUSION: In the vast majority of cases, it is possible to limit the dose to erectile tissue with IMRT, usually by >/=50% without significantly compromising the PHC, RTC, or treatment duration. A Phase III randomized trial has been designed to test the clinical significance of the erectile tissue-sparing technique described here.

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PubMed2003

Positive prostate biopsy laterality and implications for staging.

OBJECTIVES: To examine the effect of including positive prostate biopsy information in palpation staging (2002 system) and the influence of this information on freedom from biochemical failure (bNED). Prostate biopsy laterality status (unilateral versus bilateral positive) is part of clinical staging using American Joint Commission on Cancer criteria, but is rarely used. METHODS: From April 1, 1989 to September 30, 1999, 1038 patients with palpable T1-T3Nx-0M0 prostate cancer were treated with three-dimensional conformal radiotherapy alone. Kaplan-Meier bNED curves were compared using the log-rank test. The Cox proportional hazards regression model of bNED was used for multivariate analysis. RESULTS: The median follow-up was 46 months. The proportion of patients with bilateral positive biopsies by palpation category T1c was 24%, by T2a was 17%, by T2b was 26%, by T2c was 65%, and by T3 was 53%. No statistically significant difference was noted in bNED on the basis of biopsy laterality status for the palpation T stages T1c, T2a, T2b, or T3. A statistically significant difference in the 5-year bNED in the T2c stage was found; those with unilateral positive biopsies fared worse (46% versus 74%, respectively, P = 0.04). CONCLUSIONS: Inclusion of positive biopsy laterality status into clinical staging causes stage migration without reflecting a change in outcome and should not be used.

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