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Alan Pollack

Publications and source records attributed to Alan Pollack.

At least 55 records · Page 3Linked to original sources
PubMed2004

Short-term androgen deprivation and PSA doubling time: their association and relationship to disease progression after radiation therapy for prostate cancer.

PURPOSE: The goal of this study was to investigate the relationship between PSA doubling time (PSADT) and initial management of prostate cancer with short-term androgen deprivation (STAD) and the impact of these factors on disease progression after radiation therapy. METHODS AND MATERIALS: Between May 1989 and October 1998, 284 patients treated with 3D-CRT experienced biochemical failure (BF) as defined under the ASTRO consensus statement. All patients had sufficient follow-up data for PSADT calculations. Linear regression was used to assess predictors of PSADT among STAD, time to biochemical failure (TTBF), Gleason Score, tumor stage, dose, posttreatment PSA nadir, pretreatment PSA, and age. A composite covariate was created from the various combinations of factors found to be predictive of PSADT. The composite covariate was then included, along with PSADT and the factors previously mentioned, in proportional hazards modeling of freedom from distant metastasis (FDM), cause-specific survival (CSS), and overall survival (OS). RESULTS: Fifty-four (19%) patients developed distant metastasis, 20 (7%) died of prostate cancer, and 53 (19%) died of any cause. The median PSADT was 12 months. Predictors of a longer PSADT were TTBF >12 months, Gleason Score 2-6, and STAD. An ordinal composite covariate was created with eight levels on the basis of the magnitude of observed mean PSADT within the eight possible combinations of the three dichotomized predictors. The most significant predictor of higher FDM rates in Cox modeling was the composite covariate, followed by longer PSADT, STAD, lower PSA nadir, higher RT dose, and Gleason Score 2-6. Predictors of higher CSS rates were lower nadir, longer PSADT, T1/T2ab tumors, the composite covariate, and STAD. The most significant predictor of a higher OS rate was STAD, followed by longer PSADT, younger age at diagnosis, the composite covariate, lower nadir, and T1/T2ab tumors. CONCLUSIONS: Longer TTBF, Gleason Score 2-6 tumors, and STAD were predictive of longer PSADT. Even after adjusting for these factors in the capacity of their predictive properties for PSADT, STAD and observed PSADT continued to be significant independent predictors of FDM, CSS, and OS. STAD appears to have a pronounced impact on disease progression, probably the result partly of the prolongation of PSADT.

Aged↗
PubMed2004

Predictors of preferences and utilities in men treated with 3D-CRT for prostate cancer.

PURPOSE: To assess the preferences and utilities for prostate cancer health state scenarios of men treated with three-dimensional conformal radiotherapy and the predictors of treatment preferences. METHODS AND MATERIALS: The preferences and utilities for probabilistic health states of impotence and incontinence associated with prostate cancer therapies were elicited from prostate cancer registry participants using a modified time trade-off interview. Sociodemographic, disease, and treatment characteristics, as well as quality-of-life scores, were assessed to determine the predictors of preferences. RESULTS: Fifty-seven men treated with three-dimensional conformal radiotherapy completed the time trade-off interview. Of these men, 83% had Stage T1-T2 and 30% were receiving hormonal therapy. The utilities followed a linear trend with declining scores for increasing risk of poorer health states. Men showed an increased preference for health states associated with radiotherapy compared with surgery or hormonal therapy. Univariate predictors of preference included income and marital status. Multivariate predictors of preferences included more aggressive therapy and better prognostic indicators. Current quality-of-life scores in terms of global, sexual, or urinary function were poor predictors of preferences. CONCLUSION: Preference elicitation can assist in decision-making, and understanding the predictors of patient preferences can assist in identifying factors that may increase patient perceptions of poorer outcomes.

Aged↗
PubMed2004

Prostate cancer radiotherapy dose response: an update of the fox chase experience.

PURPOSE: The effectiveness of increasing radiotherapy dose for men with prostate cancer was evaluated with reference to prognostic groups as defined by pretreatment serum prostate specific antigen (PSA), Gleason score, T stage and perineural invasion. MATERIALS AND METHODS: There were 839 men treated between April 1989 and December 1997 with conformal radiotherapy alone. Cox multivariate analysis was used to establish important predictors of biochemical failure (BF) separately for patients with an initial pretreatment PSA (iPSA) of less than 10, 10 to 19.9, or 20 or greater ng/ml. Radiotherapy (RT) dose was evaluated as a continuous and categorical (dose groups of less than 72, 72 to 75.9 and 76 Gy or greater) variable. RESULTS: At a median 63-month followup multivariate analysis demonstrated that iPSA and radiotherapy (RP) dose were the most significant predictors of BF, followed by Gleason score and T stage. Perineural invasion was not an independent correlate of outcome. RT dose was significant in all iPSA groups (less than 10, 10 to 19.9 and 20 or greater ng/ml). Gleason score was significant when iPSA was less than 10 ng/ml. T stage was significant when iPSA was 20 ng/ml or greater and it was borderline when iPSA was 10 to 19.9 ng/ml (p = 0.08). Prognostic subgroups were derived from these results and tested for an effect of RT dose on univariate analysis. Radiation dose was not a correlate of BF in the most favorable (PSA less than 10 ng/ml and Gleason score 2 to 6) and the most unfavorable (PSA 20 ng/ml or greater and stage T3-T4) prognostic groups but it was otherwise an influential determinant of outcome. CONCLUSIONS: RT dose escalation to 76 Gy or greater improved patient outcome for all prognostic groups except those at the favorable and unfavorable extremes.

Adult↗
PubMed2003

Hazards of dose escalation in prostate cancer radiotherapy.

PURPOSE: To assess the benefit of escalating the dose in definitive prostate cancer radiotherapy vs. the associated risk of complications. MATERIALS AND METHODS: Between 1987 and 1999, 1087 patients with clinical Stage T1b-T3 adenocarcinoma of the prostate were definitively irradiated without hormonal therapy and had a pretreatment serum prostate-specific antigen (PSA) and Gleason score recorded. The median follow-up was 65 months. Doses ranged from 64 to 78 Gy, with the treatment techniques corresponding to the year of therapy and the prescribed dose. A total of 301 patients were treated on a randomized protocol to either 70 or 78 Gy. Also, 163 patients were treated with three-dimensional conformal therapy and had dose-volume histograms available for review. RESULTS: Tumor stage, grade, pretreatment PSA level, and radiation dose were all independent predictors of PSA disease-free survival (PSA-DFS) in multivariate analysis. The hazard rate for biochemical failure peaked at 1.5-3 years after radiotherapy. Although a statistically significant dose effect on PSA-DFS was found in the pretreatment PSA levels of those with both < or =10 ng/mL and >10 ng/mL, in those with a pretreatment PSA < or =10 ng/mL, the improvement in outcome was only seen going from a dose level of 64-66 Gy to 68-70 Gy with a 5-year PSA-DFS rate of 66% vs. 81% (p <0.0001). This was also confirmed by the data from the randomized patients who showed no difference in outcome whether treated to 70 Gy or 78 Gy. In patients with a pretreatment PSA level >10 ng/mL, a statistically significant improvement was found in disease-free outcome among the 64-66-Gy, 68-70-Gy, and 78-Gy levels. PSA-DFS was approximately 50% better at each higher dose level at 5 and 8 years after treatment. The dose had a statistically significant impact in both intermediate- and high-risk groups. Rectal morbidity was both dose and volume related. Although at 5 years after therapy, the Grade 2-3 rectal complication rate was twice as high for patients treated to 78 Gy than to 70 Gy, 26% vs. 12%, this risk could be markedly diminished by adhering to dose-volume constraints. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, although it appears that radiation-dose escalation may improve PSA-DF outcome, the price paid in treatment morbidity can be high without adequate attention to dose-volume constraints of normal tissue. Care must be taken to consider not only the hazard of tumor recurrence but also that of complications.

Adenocarcinoma↗
PubMed2003

A method for increased dose conformity and segment reduction for SMLC delivered IMRT treatment of the prostate.

PURPOSE: The focus of this work is to develop a practical planning method that results in increased dose conformity and reduced treatment time for segmental multileaf collimation (sMLC) based intensity-modulated radiation therapy (IMRT) delivery. METHODS AND MATERIALS: Additional regions for dose constraint are introduced within the normal tissue during the planning process by designing a series of concentric ellipsoids around the target. A dose gradient is then defined by assigning dose constraints to each concentric region. The technique was tested at two centers and data for 26 and 10 patients, respectively, are presented allowing for differences in treatment technique, beam energy, ellipsoid definition, and prescription dose. At both centers, a series of patients previously treated for prostate cancer with IMRT were selected, and comparisons were made between the original and new plans. RESULTS: While meeting target dose specifications and normal tissue constraints, the average number of beam directions decreased by 1.6 with a standard error (SE) of 0.1. The average time for delivery at center 1 decreased by 29.0% with an SE of 2.0%, decreasing from 17.5 min to 12.3 min. The average time for delivery at center 2 decreased by 29.9% with an SE of 3.8%, decreasing from 11 min to 7.7 min. The amount of nontarget tissue receiving D(100) decreased by 15.7% with an SE of 2.4%. Nontarget tissue receiving D(95), D(90), and D(50) decreased by 16.3, 15.1, and 19.5%, respectively, with SE values of approximately 2% at center 1. Corresponding values for D(100), D(95), D(90), and D(50) decreased by 13.5, 16.7, 17.1, and 5.1%, respectively, with SE values of less than 3% at center 2. CONCLUSION: By designating subsets of tissue as concentric regions around the target(s) and carefully defining each region's dose constraints, we have gained an increased measure of control over the region outside the target boundaries. This increased control manifests as two distinct endpoints that are beneficial to the IMRT process: increased dose conformity and decreased treatment time.

Algorithms↗
PubMed2003

Does short-term androgen deprivation substitute for radiation dose in the treatment of high-risk prostate cancer?

PURPOSE: Randomized trials have corroborated the clinical benefit of adding androgen deprivation (AD) to radiotherapy (RT) in the treatment of high-risk prostate cancer. Another competing strategy is to escalate the RT dose using three-dimensional conformal RT (3D-CRT). In this analysis, we asked whether the addition of short-term AD (STAD) ( 20 ng/mL, Gleason score 8-10, or T3-4) prostate cancer is an effective substitute for dose escalation. METHODS AND MATERIALS: Between March 1, 1990 and November 30, 1998, 296 high-risk prostate cancer patients were treated with 3D-CRT alone (n = 206) or in combination with STAD (n = 90). The patient characteristics were median age 68 years, median follow-up 58 months, pretreatment initial prostate-specific antigen 21.8 ng/mL, RT dose 75 Gy, STAD duration 3 months, and time off STAD 64 months. The impact of STAD with respect to dose was examined using univariate analysis for dose ranges of <75 Gy and >or=75 Gy. Stepwise Cox proportional hazards regression multivariate analysis was performed to determine independent correlates of freedom from biochemical failure (bNED), freedom from distant metastasis (FDM), and overall survival. In a separate matched-pair analysis (n = 44 per group), those treated to <75 Gy + STAD (Group A) were compared with those who received >or=75 Gy alone (Group B). RESULTS: On univariate analysis, the addition of STAD had no impact on bNED, FDM, or overall survival in either dose group. On multivariate analysis, initial prostate-specific antigen level, palpation T stage, and RT dose were significant correlates of bNED. For FDM and overall survival, the significant covariates were palpation T stage and Gleason score, respectively. Finally, in matched-pair analysis, the higher RT dose group had a significantly greater bNED rate at 5 years (Group A 35% vs. Group B 57%, p = 0.0190). CONCLUSION: Our data suggest that STAD, as used here (median 3 months), is not a substitute for RT dose in the treatment of high-risk prostate cancer. RT dose is an essential element in the treatment of high-risk prostate cancer.

Aged↗
PubMed2003

Dosimetric consequences of using a surrogate urethra to estimate urethral dose after brachytherapy for prostate cancer.

PURPOSE: To assess the accuracy and dosimetric consequences of defining a surrogate urethra at the geometric center of the prostate in postimplant CT scans. METHODS AND MATERIALS: Eighty postimplant CT scans were obtained with a Foley catheter in place at Day 0 and at 1 month for 40 patients who had undergone (125)I prostate brachytherapy. The percentage of urethral volume receiving at least 275% of the prescribed dose (uV(275)), uV(250), uV(200), uV(150), maximal dose received by 90% of urethral volume (uD(90)), uD(70), uD(30), and uD(1) were measured for the Foley catheter and surrogate urethra. The distance between the Foley catheter and surrogate urethra was measured at the base, middle, and apex of the prostate. RESULTS: A statistically significant difference was found in all the above-listed dosimetric parameters between the Foley catheter and surrogate urethra at Day 0 (p <or= 0.001). At 1 month, the uD(90), uD(70), and uD(1) remained significantly different between the Foley catheter and surrogate urethra (p <or= 0.05). The difference in the uV(275) (p = 0.055) and uV(150) (p = 0.059) between the Foley catheter and surrogate urethra showed a trend toward statistical significance at 1 month. The uV(250), uV(200), and uD(30) were greater for the surrogate urethra than for the Foley catheter at 1 month, but were not significantly different statistically. The mean distance between the Foley catheter and the surrogate urethra was greatest at the base (1.2 cm) in the vertical axis at Day 0 and decreased substantially to 0.87 cm at 1 month (p = 0.0004). CONCLUSION: Using a surrogate urethra at the geometric center of the prostate may significantly overestimate the urethral dose at Day 0 and certain dosimetric parameters at 1 month. An alternative position for a surrogate urethra accounting for the difference in the location of the Foley catheter near the base of the prostate at Day 0 and 1 month could be considered in future studies.

Brachytherapy↗
PubMed2003

Radiation therapy dose escalation for prostate cancer: a rationale for IMRT.

The response of prostate cancer to radiation was well-documented in the pre-PSA era. Large palpable tumors resolved within months of treatment with relatively modest radiation doses of 64-70 Gy. The use of PSA-based failure as an endpoint, however, has made it clear that cure rates were much lower than appreciated. While doses in this range are still widely used today, data from retrospective, sequential prospective and now randomized studies indicate that for patients with intermediate-to-high risk disease, doses above 70 Gy are associated with a significant reduction in biochemical failure. The use of 3D-conformal radiotherapy to escalate radiation dose has resulted in modest increases in rectal and bladder toxicity. The application of intensity modulated radiotherapy methods allows for greater sparing of the surrounding normal tissues and, hence, the potential to further escalate dose. The results of dose escalation, the ability of IMRT to reduce rectal and bladder exposure to high radiation doses and the use of new imaging methods to more accurately target the prostate are described.

Humans↗
PubMed2003

Biochemical failure as a determinant of distant metastasis and death in prostate cancer treated with radiotherapy.

PURPOSE: Biochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer. METHODS AND MATERIALS: A total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration. RESULTS: BF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships. CONCLUSION: BF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD.

Aged↗
PubMed2003

Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth.

PURPOSE: Androgen deprivation (AD) is frequently combined with radiotherapy (RT); however, the optimal sequence in vivo is currently unknown. Previous published work from our laboratory demonstrated that AD with RT was consistent with at least an additive, and possibly supra-additive, effect with the combined approach. We, therefore, performed additional experiments to elucidate the optimal sequence. METHODS AND MATERIALS: R3327-G Dunning rat prostate tumor cells were grown s.c. in the flanks of Copenhagen rats. Treatment was initiated when the tumor reached approximately 1 cm(3). Temporary AD was performed by a transscrotal orchiectomy followed 14 days later with androgen restoration using s.c. testosterone implants. RT was delivered using (60)Co to 7 Gy. Seven groups, including the controls, were analyzed: Group 1, sham control (Day 0: AD + testosterone); 2, AD control (Day 0: AD, Day 14: testosterone); 3, RT alone on Day 7 (Day 0: AD + testosterone, Day 7 RT); 4, RT alone on Day 3 (Day 0: AD + testosterone, Day 3: RT); 5, RT during AD (Day 0: AD, Day 7: RT, Day 14: testosterone); 6, RT before AD (Day 0: RT, Day 3: AD, Day 17: testosterone); and Group 7, RT after AD (Day 0: AD, Day 14: testosterone, Day 17: RT). The doubling times for tumor growth were calculated for the seven groups from the end of treatment plus 1 day. Differences in doubling time were assessed using analysis of variance, with pair-wise comparisons accomplished using post-hoc Bonferroni tests. RESULTS: An analysis of the differences in the tumor volume doubling time as measured from the end of treatment suggests that Groups 1 and 7 were statistically different from the other groups (p = 0.02). As expected, the sham control group had the shortest doubling time at 5.4 days and Group 7 (14 days of AD administered before RT) had the longest doubling time at 32.6 days. The findings were similar even after excluding an outlying doubling time of 85 days from Group 7 (p < 0.0001). To assess the effect of sequencing further, only Groups 5 through 7 (excluding the outlier) were compared in an analysis of variance with post-hoc Bonferroni tests. Group 7 (RT after AD) demonstrated a significantly longer doubling time than Groups 5 and 6 (p = 0.0024). CONCLUSION: The results suggest that neoadjuvant AD may result in prolonged suppression of tumor growth, even after testosterone replacement.

Animals↗
PubMed2003

The Gleason score shift: score four and seven years ago.

PURPOSE: There is some evidence that Gleason scores (GS) have shifted over time, although documentation of the extent to which this has occurred and its clinical significance is sparse. METHODS AND MATERIALS: Three types of analyses were performed to characterize the GS shift. First, the time-related changes in GS, T-stage category, and PSA for all 983 patients treated with conformal radiotherapy at our institution were examined between 1992 and 1997. Then a matched-pair analysis of patients treated without androgen deprivation was implemented. Patients were matched for grouped GS, grouped PSA, T category, and grouped radiation dose; 242 patients (Cohort 1) treated between 1992 and 1994 were compared to 242 patients treated between 1995 and 1997 (Cohort 2). Follow-up for each patient in Cohort 1 was truncated to match the length of follow-up for his counterpart in Cohort 2 (median follow-up 42 vs. 47 months). The ASTRO consensus definition of a rising PSA was used. Finally, the pathology slides of 106 patients treated with radiotherapy at another institution between 1987 and 1993 underwent a blind second review by one of the study pathologists (P.T.) in 1998. RESULTS: The percentages of prostate cancer patients treated with radiotherapy at our institution from 1992 to 1994 vs. 1995 to 1997 were GS 2-5: 49% vs. 16%, GS 6: 27% vs. 59%, GS 7: 20% vs. 19%, and GS > or =8: 8.3% vs. 6%. There was no clear difference in T category over time with 92-96% having T1-T2 disease. The percentage of patients with a PSA < or = 10 ng/mL rose rapidly from 35% in 1992 to 63% in 1994. In corroboration of these findings, the pathologic review of specimens from 106 patients at another institution yielded changes between the initial reading to the recent reading of 50% to 6% for GS 2-5, 22% to 31% for GS 6, 16% to 25% for GS 7, and 12% to 25% for GS 8-10 (p < 0.0001). From the matched-pair analysis, 5-year Kaplan-Meier bNED rates were 68% and 82% (p = 0.03) favoring Cohort 2. CONCLUSIONS: During the study period, pretreatment PSA values declined and T category remained stable; yet, GS increased. Upgrading of GS would be expected to lead to an improvement in outcome for all GS groups because of the Will Rogers effect, which explains in part the results of the matched-pair analysis. The GS shift confounds retrospective series spanning the 1990s.

Humans↗
PubMed2003

Experience of ultrasound-based daily prostate localization.

PURPOSE: The NOMOS (Sewickley, PA) B-mode Acquisition and Targeting System (BAT) ultrasound system provides a rapid means of correcting for interfraction prostate positional variation. In this investigation, we report our experience on the clinical issues relevant to the daily use of the BAT system and the analysis of combined setup error and organ motion for 3509 BAT alignment procedures in 147 consecutive patients treated with IMRT for prostate cancer. METHODS AND MATERIALS: After setup to external skin marks, therapists performed the BAT ultrasound alignment procedure before each IMRT treatment. In this study, a single physician (A.C.) reviewed all BAT images and classified image quality and accuracy of image alignment by the therapist. On a scale of 1-3, near-perfect image quality or alignment was given a 1, fair image quality or misalignment > or = 5 mm (likely within the PTV) was given a 2, and unacceptable image quality or misalignment >5 mm (potential to violate the PTV) was given a value of 3. The distribution of shifts made was analyzed in each dimension and for all patients. The time required to perform the BAT alignment was also assessed in 17 patients. RESULTS: Among the 3509 attempted BAT procedures, the image quality was judged to be poor or unacceptable in 5.1% (181). Of the remaining 3328 BAT images, with quality scores of 1-2, alignments were unacceptable (>5 mm misalignment as judged by the reviewing physician) in 3% (100). The mean shift in each direction, averaged over all patients, was 0.5-0.7 mm. Interfraction standard deviation (1 SD) of prostate position based on combined setup error and internal organ motion is 4.9 mm, 4.4 mm, and 2.8 mm in the anteroposterior (AP), superior-inferior (SI), and lateral (RL) dimensions, respectively. The distribution of the shifts was a near-random Gaussian-type in all three major axes, with greater variations in AP and SI directions. The percent of BAT procedures in which the shift was >5 mm was 28.6% in AP, 23% in SI, and 9% in RL directions. The average BAT procedure took extra 5 min out of a 20-min time slot in a typical eight-field IMRT treatment. CONCLUSIONS: The quality of the daily ultrasound images was deemed acceptable in 95%. Major alignment errors by therapists were only 3%. The BAT system is clinically effective and feasible in a matter of 5 min. Although the accuracy of the BAT was not addressed in this investigation, we found a significant percentage of large shifts being made from the initial alignment position.

Humans↗
PubMed2003

Is intraoperative nomogram-based overplanning of prostate implants necessary?

PURPOSE: Several investigators have described intraoperative planning of prostate implants based on a nomogram. The aim of this work was to investigate the adequacy of the nomogram in predicting the total activity necessary for optimal dosimetry. METHODS AND MATERIALS: Eighty CT-based postimplant treatment plans were performed for patients who underwent ultrasound guided I-125 permanent implants alone between April 2000 and March 2001. The cohort of 40 patients had early stage (T1-T2) prostatic carcinoma and pre-treatment prostate volumes of 19-50 cc. I-125 seeds (0.391 mCi/seed) were implanted to achieve a distribution of 75% of the activity peripherally and 25% centrally. The CT studies were obtained on the day of (CT1) and at 1 month (CT2) after implant. All patients were catheterized at CT1, and 28 patients were catheterized at CT2 to visualize the urethra. For each patient, the percentage difference (dA) between the total implanted and nomogram predicted activity for a known prostate volume was calculated. The V200 (volume receiving 200% of the prescribed dose), V150, V100, V90, D100 (maximum dose received by 100% of the volume), D90, and D80 were measured for the prostate at CT1 and CT2. For the urethra, V275, V250, V200, and V150 were evaluated, and V100 and V70 were evaluated for the rectum. The Pearson test was used to correlate the dosimetric parameters with dA. Linear regression was used to fit the correlation of the volume and dose parameters with dA. RESULTS: The median V100 at CT1 and CT2 was 91.8% and 94.2%, respectively. The Pearson test was significant for the prostate V100 and dA measured at CT1 (p = 0.005) but not at CT2 (p = 0.106). A similar correlation was found for the prostate D90 at CT1 (p = 0.002), but not at CT2 (p = 0.076). D100 (maximum dose received by 100% of volume) for prostate did not correlate with dA at CT1 (p = 0.094) and CT2 (p = 0.148). The volume of the prostate receiving higher doses (greater than 150% and 200% of the prescribed dose) correlated with dA. There were no significant correlations between V275, V250, V200, and V150 at CT1 and CT2 as a function of dA for the urethra. V100 and V70 for the rectum correlated significantly with dA; for V100, p = 0.041 at CT1 and p = 0.014 at CT2 and for V70, p = 0.041 at CT1 and p = 0.026 at CT2. A linear regression model fitted to the prostate data obtained from CT1 with the goal of achieving a V100 of 90% and D90 of 145 Gy suggests that no increase in the number of seeds may be warranted using intraoperative planning. The implants examined showed no concomitant increase of urethral doses with increase in activity relative to the nomogram, but showed an increase in the rectal doses for the same increase in activity. CONCLUSION: The doses evaluated at CT1 represent an underestimate, whereas those obtained at CT2 represent an overestimate of the actual delivered protracted permanent implant dose. Based on these results and consideration of the dynamic nature of the dose distribution, target coverage obtained with intraoperative planning using the nomogram predicted activity is consistent with published guidelines for a quality implant and critical structure doses are within tolerance.

Brachytherapy↗
PubMed2003

Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II.

PURPOSE: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. MATERIALS AND METHODS: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. RESULTS: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. CONCLUSIONS: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of >/= Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Adenocarcinoma↗
PubMed2003

Molecular markers of outcome after radiotherapy in patients with prostate carcinoma: Ki-67, bcl-2, bax, and bcl-x.

BACKGROUND: Abnormal expression of key proteins of the apoptotic pathway has been associated with poor prognosis, although there have been few studies of these correlations in patients with prostate carcinoma who are treated with radiotherapy. The current study examined the association between expression levels of Ki-67, bcl-2, bax, and bcl-x in pretreatment biopsy specimens and patient outcome after definitive radiotherapy alone. METHODS: Archival pretreatment prostate biopsy tumor tissue was retrieved from 106 patients with Stage T1-T3 prostate carcinoma who were treated at the University of Texas M. D. Anderson Cancer Center with external beam radiotherapy between 1987 and 1993. Expression levels of Ki-67 (MIB-1 staining; n = 106 patients), bcl-2 (n = 77 patients), bax (n = 70 patients), and bcl-x (both long and short splice variants; n = 72 patients) were determined by immunohistochemical staining. The Ki-67 labeling index (Ki67-LI) was available for all patients and was derived from the percentage of Ki-67 positive cells. Biochemical failure after radiotherapy was defined as three consecutive rises in prostate specific antigen level on follow-up. The median follow-up was 62 months. RESULTS: High Ki67-LI (> 3.5%) expression was observed in 33% of patients, overexpression of bcl-2 was observed in 16% of patients, altered bax expression was observed in 23% of patients, and altered bcl-x expression was observed in 53% of patients. There was no correlation found between the biomarkers. Kaplan-Meier survival estimates of freedom from biochemical failure (bNED) and the log-rank test revealed significantly lower rates in association with high Ki67-LI, positive bcl-2, and altered bax staining. No correlation was observed between bcl-x staining and bNED. Cox proportional hazards multivariate analysis confirmed that bcl-2 and bax were independent of pretreatment PSA level, Gleason score, disease stage, and Ki67-LI in predicting bNED. CONCLUSIONS: Abnormalities in the expression levels of bcl-2 and bax were associated with increased failure after patients were treated for prostate carcinoma with external beam radiotherapy. These biomarkers appeared to be useful in categorizing patient risk further, beyond Ki-67 staining and conventional clinical prognostic factors.

Biomarkers, Tumor↗