Biomedical subjects

Ming-Hui Chen

Publications and source records attributed to Ming-Hui Chen.

At least 19 recordsLinked to original sources

PubMed2007

Bayesian dynamic models for survival data with a cure fraction.

In this paper, we propose a new class of semi-parametric cure rate models. Specifically, we construct dynamic models for piecewise hazard functions over a finite partition of the time axis. Allowing the size of partition and the levels of baseline hazard to be random, our proposed models provide a great flexibility in controlling the degree of parametricity in the right tail of the survival distribution and the amount of correlations among the log-baseline hazard levels. Several properties of the proposed models are derived, and propriety of the implied posteriors with improper noninformative priors for regression coefficients based on the proposed models is established for the fixed partition of the time axis. In addition, an efficient reversible jump computational algorithm is developed for carrying out posterior computation. A real data set from a melanoma clinical trial is analyzed in detail to further demonstrate the proposed methodology.

Bayes Theorem↗

PubMed2006

Cancer-specific mortality after radiation therapy with short-course hormonal therapy or radical prostatectomy in men with localized, intermediate-risk to high-risk prostate cancer.

BACKGROUND: The presence of multiple determinants of aggressive cancer biology may impact prostate cancer-specific mortality (PCSM) rates compared with fewer factors. The authors estimated PCSM after radiation therapy with short-course androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with clinically localized, intermediate-risk to high-risk prostate cancer. METHODS: The study cohort included 3240 men treated from 1981 to 2002 with RT with 6 months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason score 7-10, or clinical tumor category T2b or T2c). Competing risks regression analyses were used to determine whether the number of risk factors present was associated with time to PCSM. RESULTS: Men with all 3 risk factors had significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of 9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1 or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95% CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of intermediate-risk to high-risk prostate cancer have significantly increased estimates of PCSM despite aggressive therapy compared with men with only 1 or 2 determinants. These men are appropriate candidates for enrollment onto randomized controlled trials evaluating the benefit of adding systemic therapies such as docetaxel to RT+AST or RP.

Aged↗

PubMed2006

Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.

AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.

Animals↗

PubMed2006

Prostate-specific antigen recurrence and mortality after conventional dose radiation therapy in select men with low-risk prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) were evaluated for men age >70 years receiving conventional dose external beam radiation therapy (RT). METHODS: Between January 1, 1989, and December 1, 2002, 358 men were treated with RT for localized prostate cancer at a Harvard Medical School Affiliate in Fall River, MA. Median age was 71.2 (range, 43.2-83.5) years and patients were followed for a median of 4.0 (range, 0.2-13.5) years. RESULTS: Univariable analysis demonstrated that increasing pretreatment PSA velocity was significantly associated with increasing pretreatment PSA (P < .0001), Gleason score (P = .0002), and shorter post-RT PSA doubling time (P = .0007) but not with clinical T-category (P = .09) or percent positive biopsies (P = .08). For the select cohort of men age >70 years with low-risk disease and a pretreatment PSA velocity < or =1.0 ng/mL per year, all deaths observed to date have been from nonprostate cancer etiologies. Whereas PSA recurrence in this group reached 43.3% by 7 years, due to the advanced age of the cohort and less aggressive biology, competing causes of mortality predominated as the cause of death despite PSA failure. CONCLUSIONS: In men age >70 years with low-risk prostate cancer and pretreatment PSA velocity < or =1.0 ng/mL/year, prostate cancer death was not observed despite a modest PSA recurrence rate.

Adult↗

PubMed2006

Six-month androgen suppression plus radiation therapy compared with radiation therapy alone for men with prostate cancer and a rapidly increasing pretreatment prostate-specific antigen level.

PURPOSE: We evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr. PATIENTS AND METHODS: The study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors. RESULTS: Despite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with RT. Treatment with RT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001). CONCLUSION: Treatment using 6 months of AST and RT compared with RT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM.

Aged↗

PubMed2006

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer.

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS: : A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS: : Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.

Aged↗

PubMed2006

Predictors of mortality after prostate-specific antigen failure.

PURPOSE: We identified factors associated with the length of survival after prostate-specific antigen (PSA) failure. METHODS AND MATERIALS: The study cohort comprised 81 of 206 men enrolled on a randomized trial evaluating external-beam radiation therapy (RT) with or without androgen suppression therapy (AST) and who experienced PSA failure. Salvage AST was administered at a PSA level of approximately 10 ng/mL as per protocol. Cox regression was used to determine factors associated with length of survival after PSA failure. RESULTS: A PSA DT (doubling time) <6 months (p = 0.04) and age at the time of PSA failure (p = 0.009) were significantly associated with length of survival. By 5 years, 35% and 65% of all-cause mortality was from prostate cancer in men whose age at PSA failure was 75 or higher vs. <75, respectively. Across all ages, 0%, 4%, as compared with 63% of men, were estimated to die of prostate cancer within 5 years after PSA failure if their PSA DT was >12, 6-12, or <6 months, respectively. CONCLUSIONS: Advanced age and a PSA DT <6 months at the time of PSA failure are associated with a significantly shorter survival.

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PubMed2006

Prostate-specific antigen velocity and survival for patients with hormone-refractory metastatic prostate carcinoma.

BACKGROUND: The authors investigated whether prostate-specific antigen (PSA) velocity was associated significantly with the time to death after randomization among patients with hormone-refractory metastatic prostate carcinoma (HRMPC) who were treated with cytotoxic, cytotatic, or combination therapy. METHODS: The study cohort included 213 men with HRMPC who were treated on 3 prospective, randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether there was a significant association between PSA velocity and the time to death after randomization, controlling for treatment and known prognostic factors. RESULTS: Increasing PSA velocity was associated significantly with shorter survival after randomization (P = 0.005) controlling for treatment and known prognostic factors. The adjusted hazard ratio for death was 1.8 (95% confidence interval [95% CI], 1.3-2.5; P = 0.0004) for men who had a PSA velocity > 0.0 ng/mL per month compared with men who had a PSA velocity < or = 0.0 ng/mL per month. Estimates of survival 2 years after randomization for these men were 16% (95% CI, 7-25%) and 44% (95% CI, 35-53%), respectively. CONCLUSIONS: PSA velocity was associated significantly with the length of survival among men with HRMPC who received cytotoxic, cytostatic, or combination therapy.

Adult↗

PubMed2006

Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality.

OBJECTIVES: To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. METHODS: From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray's P value. RESULTS: Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). CONCLUSIONS: Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community.

Adult↗

PubMed2006

Evidence to support a continued stage migration and decrease in prostate cancer specific mortality.

PURPOSE: We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. MATERIALS AND METHODS: Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. RESULTS: Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. CONCLUSIONS: During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease.

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PubMed2006

[Inhibitory effects of matrix metalloproteinase (MMP) inhibitor LY52 on expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3].

BACKGROUND & OBJECTIVE: Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 are associated with tumor progression, invasion, and metastasis. Using synthetic MMP inhibitors to block the proteolytic activity of these enzymes is a potential strategy of treating cancer. This study was to observe the inhibitory effects of LY52, a synthetic specific MMP inhibitor, on the expression of MMP-2 and MMP-9 and invasive ability of human ovarian carcinoma cell line SKOV3. METHODS: The inhibitory effect of LY52 on growth of SKOV3 cells was measured by MTT and clonogenic assays. The inhibitory effect of LY52 on the activity of gelatin was evaluated by spectrophotometry using succinylated gelatin as substrate. The inhibitory effect of LY52 on the expression of MMP-2 and MMP-9 was analyzed using SDS-PAGE zymography. The adhesive ability of SKOV3 cells to fibronectin (FN), laminin (LN), and matrigel was measured using MTT assay. The invasive ability of SKOV3 cells was assessed with a transwell cell culture chamber. RESULTS: LY52 had weak cytostatic effect on SKOV3 cells, the inhibitory rates were 10.54%-37.66% within 120 h incubation when the concentration was 10 microg/ml. LY52 inhibited gelatin degradation via suppressing the activities of gelatinases, the 50% inhibitory concentration (IC50) was 11.9 microg/ml. When treated with 0.1, 1, 10, 100, or 1,000 microg/ml LY52 for 24 h, the expression of MMP-2 in SKOV3 cells was suppressed by 10.66%-31.47%, and the expression of MMP-9 was suppressed by 22.56%-56.71%. When treated with LY52 for 1 h, the maximum inhibitory rates of adhesion of SKOV3 cells to FN, LN, and matrigel were 29.79%, 48.94%, and 50.92%, respectively. When treated with 0.1, 1, 10, 100, and 1,000 microg/ml LY52 for 24 h, the inhibitory rates of invasion of SKOV3 cells were 7.5%, 42.07%, 66.54%, 72.15%, and 82.84%, respectively. CONCLUSION: LY52 suppresses the invasion of SKOV3 cells via inhibiting the expression of MMP-2 and MMP-9.

Caffeic Acids↗

PubMed2006

Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix metalloproteinase-2, to suppress tumor invasion and metastasis.

LY52 is a caffeoyl pyrrolidine derivative designed to fit the S'1 active pocket of gelatinases that act in tumor invasion and metastasis. Herein, we examined the effects of LY52 on expression of matrix metalloproteinase (MMP)-2 expression in human breast cancer MDA-MB-231 cells and on in vitro invasion and in vivo metastasis. LY52 significantly blocked MMP-2 activity as evidenced by a decrease in the degradation of succinylated gelatin. Gelatin zymography analysis showed that LY52 (0.1-200 microg/ml) inhibited expression of active MMP-2 in concanavalin A-stimulated MDA-MB-231 cells. Inhibition of MMP-2 expression was also observed in tissue of tumor xenografts in mice that were orally administered LY52 (25 or 100 mg/kg). Furthermore, LY52 displayed an inhibitory effect on in vitro invasion of MDA-MB-231 cells and pulmonary metastasis of B16F10 murine melanoma cells in mice without significant toxic effects. These results suggest that LY52 is a potential MMP-2 inhibitor that may effectively suppress tumor invasion and metastasis.

Animals↗

PubMed2005

Toxicity and bioaccumulation of tributyltin and triphenyltin on oysters and rock shells collected from Taiwan maricuture area.

The present study was undertaken to evaluate the toxicity of tributyltin (TBT) on oysters (Crassostrea gigas) and bioaccumulation of TBT and triphenyltin (TPhT) on oysters and rock shells (Thais clavigera) from mariculture areas of Taiwan. When treated with concentrations of 0.08, 0.40, 2.00, 10.00 and 50.00 microg TBT/L, the 48-, 72-, 96- and 120-h LC50s of oysters were 44.6, 18.4, 17.9 and 14.3 microg TBT/L, respectively. In the bioaccumulation experiments, oysters and rock shells were exposed to various concentrations of organotins, i.e. A: control, B: 0.40 microg TBT/L, C: 0.40 microg TPhT/L, and D: 0.20 microg TBT/L + 0.20 microg TPhT/L. In general, TPhT was faster accumulated than TBT in both oysters and rock shells and oysters had a higher elimination capability than rock shells. Additionally, greater bioaccumulation and elimination rates had been observed in female oysters than males. To rock shells, the bioaccumulation rate of organotins in imposex females was greater than males and females.

Animals↗

PubMed2005

Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy.

PURPOSE: We evaluated predictors of prostate cancer-specific mortality (PCSM) after prostate-specific antigen (PSA) failure after radical prostatectomy (RP) or radiation therapy (RT). PATIENTS AND METHODS: A total of 1,159 men with clinically localized prostate cancer treated with RP (n = 498) or RT (n = 661) developed PSA failure, and they formed the study cohort. Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis, including post-treatment PSA doubling time (PSA-DT), Gleason score, and interval to PSA failure, could also predict time to PCSM after PSA failure. The cumulative incidence method was used to estimate PCSM after PSA failure. RESULTS: A post-RP PSA-DT of less than 3 months (hazard ratio [HR], 54.9; 95% CI, 16.7 to 180), a post-RT PSA-DT of less than 3 months (HR, 12.8; 95% CI, 7.0 to 23.1), and a biopsy Gleason score of 8 to 10 (HR, 6.1; 95% CI, 3.4 to 10.7) for patients treated with RT were significantly associated with PCSM. Post-RP estimated rates of PCSM 5 years after PSA failure were 31% (95% CI, 17% to 45%) v 1% (95% CI, 0% to 2%) for patients with PSA-DT of less than 3 months v > or = 3 months. Post-RT estimated rates of PCSM 5 years after PSA failure were 75% (95% CI, 59% to 92%) v 35% (95% CI, 24% to 47%) for patients with a biopsy Gleason score of > or = 8 v < or = 7, respectively, and PSA-DT of less than 3 months; these rates were 15% (95% CI, 0.8% to 28%) v 4% (95% CI, 1% to 6%), respectively, for patients with a PSA-DT > or = 3 months. CONCLUSION: Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score. These parameters may be useful in identifying patients for a randomized trial evaluating hormonal therapy with or without docetaxel.

Aged↗

PubMed2005

Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure.

PURPOSE: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA), we evaluated whether a PSA nadir of more than 0.2 ng/mL was significantly associated with prostate cancer-specific mortality (PCSM). PATIENTS AND METHODS: The study cohort comprised 747 men with rising PSA and negative bone scan after surgery (n = 486) or radiation therapy (n = 261) who were treated with AST. Cox regression was used to evaluate whether a significant association existed between the PSA nadir level after 8 months of AST and the time to PCSM, controlling for treatment and known prognostic factors. RESULTS: The post-AST PSA nadir (pCox < .0001), the pre-AST PSA doubling time (DT) (pCox = .002), PSA level (P = .0001), and Gleason eight to 10 cancers (pCox = .01) were significantly associated with time to PCSM. The adjusted hazard ratio for PCSM was 20 (95% CI, 7 to 61; pCox < .0001), for men with a PSA nadir of more than 0.2 ng/mL as compared with all others. A PSA DT of less than 3 months was observed in 30% (224 of 747) of the study cohort. Of the 28 observed prostate cancer deaths, 21 (75%) occurred in men whose PSA nadir was more than 0.2 ng/mL and who had a PSA DT of less than 3 months. CONCLUSION: A PSA nadir of more than 0.2 ng/mL after 8 months of AST given for postoperative or postradiation PSA failure is significantly associated with PCSM and is clinically significant because it accounted for 75% of the cancer deaths observed in this study.

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PubMed2005

Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure.

PURPOSE: We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. PATIENTS AND METHODS: A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression. RESULTS: A preoperative PSA velocity more than 2.0 ng/mL/yr (P = .001) and biopsy Gleason score 7 (P = .006) or 8 to 10 (P = .003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P = .005), a nonpalpable cancer (P = .001) with a Gleason score < or = 6 (P = .0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P = .03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. CONCLUSION: A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy.

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PubMed2005

Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy.

CONTEXT: Men with localized prostate cancer and a preoperative prostate-specific antigen (PSA) velocity greater than 2.0 ng/mL per year experience a 10-fold increase in prostate cancer-specific mortality despite surgery. OBJECTIVE: To assess whether a greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis was significantly associated with prostate cancer-specific mortality following radiation therapy (RT). DESIGN, SETTING, AND PATIENTS: Between January 1, 1989, and December 1, 2002, 358 men treated with RT for localized prostate cancer formed the study cohort (median age at treatment, 71.2 [range, 43.2-83.5] years). A Cox regression multivariable analysis was used to evaluate whether a PSA velocity greater than 2.0 ng/mL per year was significantly associated with prostate cancer-specific mortality and all-cause mortality after controlling for prognostic factors available at diagnosis. MAIN OUTCOME MEASURE: Time to prostate cancer-specific mortality for the 125 men with low-risk prostate cancer (clinical tumor category T1c or T2a and PSA level <10.0 ng/mL and Gleason score < or =6) and the 233 men with higher-risk disease, stratified by the PSA velocity. RESULTS: A PSA velocity greater than 2.0 ng/mL per year was significantly associated with a shorter time to prostate cancer-specific mortality (adjusted hazard ratio [HR], 12.0; 95% confidence interval [CI], 3.0-54.0; P = .001) and all-cause mortality (adjusted HR, 2.1; 95% CI, 1.3-3.6; P = .005) when compared with men whose PSA velocity was 2.0 ng/mL per year or less. Men presenting with low-risk disease and a PSA velocity greater than 2.0 ng/mL per year had a 7-year estimate of prostate cancer-specific mortality of 19% (95% CI, 2%-39%) compared with 0% for men whose PSA velocity was 2.0 ng/mL per year or less. The corresponding values for men with higher-risk disease were 24% (95% CI, 12%-37%) and 4% (95% CI, 0%-11%), respectively. CONCLUSIONS: A greater than 2.0-ng/mL increase in PSA level during the year prior to diagnosis is associated with a significantly higher risk of death due to prostate cancer following RT despite having low-risk disease. Such men who are planning to undergo RT and are in good health could be considered for RT combined with androgen suppression therapy because this approach improves survival in men with higher-risk disease.

Adult↗

PubMed2005

Acute gastrointestinal, genitourinary, and dermatological toxicity during dose-escalated 3D-conformal radiation therapy (3DCRT) using an intrarectal balloon for prostate gland localization and immobilization.

PURPOSE: We determined the acute gastrointestinal (GI), genitourinary (GU), and dermatologic (D) toxicity during dose-escalated three-dimensional conformal radiation therapy (3DCRT). A modified intrarectal balloon (Medrad) was used for prostate gland localization and immobilization. METHODS: Forty-six men with clinical category T1c to T3a, and at least one high-risk feature (PSA >10, Gleason > or =7, or MRI evidence of extracapsular extension or seminal vesical invasion) comprised the study cohort. Treatment consisted of hormonal therapy and 4-field 3DCRT using an intrarectal balloon for the initial 15 of 40 treatments. Planning treatment volume dose was 72 Gy (95% normalization). A Mantel-Haenzel Chi-square test compared the distribution of GU, GI, and D symptoms at baseline and at end of treatment (EOT). RESULTS: There was no significant difference between the 2 time points in the proportion of patients with bowel symptoms (p = 0.73), tenesmus (p = 0.27), nocturia (p = 1.00), or GU urgency (p = 0.40). However, there was a significant decrease in GU frequency (70% vs. 50%, p = 0.46) as a result of medical interventions and a significant increase in hemorrhoidal irritation (4% vs. 20%, p = 0.02) and anal cutaneous skin reaction (0% vs. 70%, p < 0.001). By 3 months after EOT compared to baseline, there was no significant difference in the proportion of patients experiencing hemorrhoidal bleeding (4% vs. 8%, p = 0.52), requiring intervention for hemorrhoidal symptoms (7% vs. 5%, p = 0.8), or experiencing persistent anal cutaneous skin reaction (0% vs. 3%, p = 0.31). CONCLUSION: Dose-escalated 3DCRT using an intrarectal balloon for prostate localization and immobilization was well tolerated. Acute GU, GI, and D symptoms resolved with standard dietary or medical interventions by the EOT or shortly thereafter.

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