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Biomedical subjects

D Grignon

Publications and source records attributed to D Grignon.

At least 19 recordsLinked to original sources
PubMed2001

Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.

PURPOSE: To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. METHODS AND MATERIALS: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. RESULTS: As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival. CONCLUSION: In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Adenocarcinoma↗
PubMed2001

Role of eicosanoids in prostate cancer progression.

Metabolism of arachidonic acid through cyclooxygenase, lipoxygenase, or P450 epoxygenase pathways leads to the formation of various bioactive eicosanoids. In this review, we discuss alterations in expression pattern of eicosanoid-generating enzymes found during prostate tumor progression and expound upon their involvement in tumor cell proliferation, apoptosis, motility, and tumor angiogenesis. The expression of cyclooxygenase-2, 12-lipoxygenase, and 15-lipoxygenase-1 are up-regulated during prostate cancer progression. It has been demonstrated that inhibitors of cyclooxygenase-2, 5-lipoxygenase and 12-lipoxygenase cause tumor cell apoptosis, reduce tumor cell motility and invasiveness, or decrease tumor angiogenesis and growth. The eicosanoid product of 12-lipoxygenase, 12(S)-hydroeicosatetraenoic acid, is found to activate Erkl/2 kinases in LNCaP cells and PKCalpha in rat prostate AT2.1 tumor cells. Overexpression of 12-lipoxygenase and 15-lipoxygenase-1 in prostate cancer cells stimulate prostate tumor angiogenesis and growth, suggesting a facilitative role for 12-lipoxygenase and 15-lipoxygenase-1 in prostate tumor progression. The expression of 15-lipoxygenase-2 is found frequently to be lost during the initiation and progression of prostate tumors. 15(S)-hydroxyeicosatetraenoic acid, the product of 15-lipoxygenase-2, inhibits proliferation and causes apoptosis in human prostate cancer cells, suggesting an inhibitory role for 15-lipoxygenase-2 in prostate tumor progression. The regulation of prostate cancer progression by eicosanoids, in either positive or negative ways, provides an exciting possibility for management of this disease.

Apoptosis↗
PubMed2001

Biochemical recurrence after radical prostatectomy in black and white American men with a positive or negative family history of prostate cancer.

PURPOSE: We investigated the impact of a family history of prostate cancer on predicting biochemical recurrence in black and white American men. MATERIAL AND METHODS: Between January 1991 and December 1996, 910 men underwent radical retropubic prostatectomy for clinically localized prostate cancer, of whom 676 had data available on prostate cancer family history. Statistical analysis was performed to identify any correlation among the known predictors of biochemical outcome and family history in each race. RESULTS: Median followup was 34 months (range 2 to 103). We identified 355 (52%) and 321 (48%) white and black American men, respectively, for whom data were available on prostate cancer family history, including 177 (26%) with a positive and 499 (74%) with a negative history. Family history was positive in 94 black (29%) and 83 white (23%) men. No significant difference was noted in the incidence of familial prostate cancer in the 2 races (p = 0.10). In black men the biochemical failure rate was 32% and 26% in those with a positive and negative history (log rank test p = 0.51), while in white men the rate was 17% and 18%, respectively (log rank test p = 0.79). A family history positive for prostate cancer was not associated with biochemical failure in either race. CONCLUSIONS: Biochemical recurrence was not significantly worse in patients with a family history of prostate cancer than in those with nonfamilial disease in either race.

Black People↗
PubMed2001

Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy.

An inverse association has been observed between dietary intake of lycopene and the risk of prostate cancer. We investigated the effects of lycopene supplementation in patients with prostate cancer. Twenty-six men with newly diagnosed, clinically localized (14 T(1) and 12 T(2)) prostate cancer were randomly assigned to receive 15 mg of lycopene (n = 15) twice daily or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of differentiation and apoptosis were assessed by Western blot analysis on benign and malignant parts of the prostate gland. Prostatectomy specimens were entirely embedded, step-sectioned, and evaluated for pathological stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. Eleven (73%) subjects in the intervention group and two (18%) subjects in the control group had no involvement of surgical margins and/or extra-prostatic tissues with cancer (P = 0.02). Twelve (84%) subjects in the lycopene group and five (45%) subjects in the control group had tumors <4 ml in size (P = 0.22). Diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia was present in 10 (67%) subjects in the intervention group and in 11 (100%) subjects in the control group (P = 0.05). Plasma prostate-specific antigen levels decreased by 18% in the intervention group, whereas they increased by 14% in the control group (P = 0.25). Expression of connexin 43 in cancerous prostate tissue was 0.63 +/- 0.19 absorbance in the lycopene group compared with 0.25 +/- 0.08 in the control group (P = 0.13). Expression of bcl-2 and bax did not differ significantly between the two study groups. IGF-1 levels decreased in both groups (P = 0.0002 and P = 0.0003, respectively). The results suggest that lycopene supplementation may decrease the growth of prostate cancer. However, no firm conclusions can be drawn at this time because of the small sample size.

Administration, Oral↗
PubMed2000

Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential.

The involvement of 12-lipoxygenase (12-LOX) expression and function in tumor metastasis has been demonstrated in several murine tumor cell lines. In addition, 12-LOX expression was detected in human prostatic tumors and correlated to the clinical stage of disease. Here we provide data that human prostate cancer cell lines express the platelet-type isoform of 12-LOX at both the mRNA and protein levels, and immunohistochemistry revealed 12-LOX expression in human prostate tumors. The enzyme was localized to the plasma membrane, cytoplasmic organelles and nucleus in non-metastatic cells (PC-3 nm) and to the cytoskeleton and nucleus in metastatic cells (DU-145). After orthotopic/intraprostatic injection of tumor cells into SCID mice, the metastatic prostate carcinoma cells (DU-145) expressed 12-LOX at a significantly higher level compared with the non-metastatic counterparts, PC-3nm. The functional involvement of 12-LOX in the metastatic process was demonstrated when DU-145 cells were pretreated in vitro with the 12-LOX inhibitors N-benzyl-N-hydroxy-5-phenylpentamide (BHPP) or baicalein, the use of which significantly inhibited lung colonization. These data suggest a potential involvement of 12-LOX in the progression of human prostate cancer.

Animals↗
PubMed2000

Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials.

PURPOSE: To assess the impact of short-term and long-term androgen suppression on the disease-specific and overall survival of 2200 men treated with radiotherapy on one of 5 prospective randomized trials when stratified by prognostic risk groups. METHODS AND MATERIALS: Between 1975 and 1992, 2742 men were treated for clinically localized prostate cancer on one of 5 consecutive prospective Phase III randomized trials. Patients were selected for this analysis if they were deemed evaluable and eligible for the trial, and if follow-up information was available. For this analysis patients were stratified into four previously described prognostic risk groups: Group 1 patients had a Gleason score (GS) = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The median pretreatment prostate-specific antigen (PSA) was 25 ng/ml for the 434 evaluable patients for whom this information was available. The median follow-up times for patients treated on early studies exceeded 11 years, and for more recent studies 6 years. RESULTS: Risk group 2 patients with "bulky" or T3 disease appeared to have a disease-specific survival benefit at 8 years with the addition of 4 months of goserelin and flutamide. Group 3 and 4 patients were noted to have an approximately 20% higher survival at 8 years with the addition of long-term hormonal therapy (p < or =0.0004). CONCLUSIONS: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.

Androgen Antagonists↗
PubMed2000

Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials.

PURPOSE: Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS: Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS: By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS: Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.

Aged↗
PubMed2000

Prostate cancer biochemical recurrence stage for stage is more frequent among African-American than white men with locally advanced but not organ-confined disease.

OBJECTIVES: To determine whether outcome differences between African-American men (AAM) and white men with prostate cancer (PCa) will still be present if we control for stage in a large cohort of men. It is well established that AAM have a worse outcome from PCa than white men. METHODS: We examined 848 consecutive patients who underwent radical prostatectomy at Wayne State University, Karmanos Cancer Institute, between 1991 and 1995. The mean follow-up was 34 months (range 1.5 to 75). We included men with Gleason score 7 (4 + 3) with those men with Gleason score 8 to 10 for racial/ethnic comparisons. RESULTS: AAM and white men diagnosed with organ-confined PCa demonstrated similar prostate-specific antigen (PSA) levels, Gleason grade, and biochemical recurrence. However, AAM diagnosed with non-organ-confined disease demonstrated higher PSA levels and a higher incidence of recurrence than did white men with non-organ-confined disease. There was a trend toward AAM having a greater proportion of high-grade lesions than white men when PCa was not organ confined. The evidence suggests that the difference in recurrence among AAM versus white men is based on pretreatment PSA, grade, extracapsular extension, and positive surgical margins. Seminal vesicle invasion predicted a worse prognosis equally for both AAM and white men. CONCLUSIONS: A difference in biochemical recurrence was not detected between AAM and white men with organ-confined PCa after radical prostatectomy. PSA was higher in AAM than in white men with pathologically locally advanced PCa, and the biochemical recurrence was greater. AAM had a greater percentage of high Gleason grade lesions compared with white men, and this difference approached statistical significance. We hypothesize that AAM have a more rapid growth rate of PCa, which may be responsible for these clinical findings. Further investigations of the biology of PCa are needed to understand these findings.

Black or African American↗
PubMed2000

Survival advantage from higher-dose radiation therapy for clinically localized prostate cancer treated on the Radiation Therapy Oncology Group trials.

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P <.05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P <.05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.

Aged↗
PubMed2000

Should the age specific prostate specific antigen cutoff for prostate biopsy be higher for black than for white men older than 50 years?

PURPOSE: Investigators who have examined age specific reference ranges recommend a higher prostate specific antigen (PSA) cutoff for biopsy for black than for white men older than 50 years. We controlled for PSA to determine whether age specific reference range cutoffs for diagnosis defined by the Walter Reed Army Medical Center group (Walter Reed group) would improve the disproportionate prostate cancer prognosis between black and white men. MATERIALS AND METHODS: We studied 651 consecutive patients who underwent radical prostatectomy at Wayne State University between 1991 and 1995 with a mean followup of 34 months (range 1.5 to 75). Log rank tests were used to determine the homogeneity of survival functions between black and white men with similar PSA ranges, and between groups defined by age specific PSA reference ranges for each race. RESULTS: Disease stage and grade were similar or worse in black men for any PSA range, and biochemical disease-free survival was similar or worse within each range. Black men had a higher percentage of high grade prostate cancer than white men 60 to 69 years old who would not have undergone biopsy using the Walter Reed group proposed PSA cutoff. CONCLUSIONS: Black men have similar or worse prostate cancer severity and outcome than white men with similar PSA ranges. Using age specific reference ranges for the PSA test defined by the Walter Reed group, black men have worse outcome than white men after radical prostatectomy. Therefore, we recommend that the PSA cutoff for biopsy should not be higher for black men at any age range.

Black or African American↗
PubMed1999

Role of radical prostatectomy in patients with prostate cancer of high Gleason score.

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.

Adult↗
PubMed1999

Should African-American men be tested for prostate carcinoma at an earlier age than white men?

BACKGROUND: There have recently been challenges to testing high risk populations, i.e., African-American men younger than 50 years, for prostate carcinoma (PCa). The mortality rate of patients with PCa between ages 40 and 60 years is nearly 3 times greater among African-American men (AAM) compared with white men (WM). The literature in support of testing AAM at an earlier age than WM is sparse. Therefore, the authors present clinical and histologic data that support the testing of AAM at a younger age, utilizing data on patients with clinically localized PCa. METHODS: Examination of consecutive radical prostatectomy specimens from AAM and WM was performed from January 1991 to June 1996 among AAM and WM at Wayne State University, Harper Hospital, Detroit, Michigan. International, salvage prostatectomy, and neoadjuvant hormonal therapy patients were excluded, as were patients with lymph node metastasis. The authors examined biochemical recurrences of PCa in this cohort of men treated from January 1991 through December 1995. Univariate analysis of contingency tables was performed, using chi-squared-tests to assess the correlation between stage and race after stratification of patients by age group. Biochemical recurrence was analyzed using the Kaplan-Meier method and the log rank test. RESULTS: The authors examined radical prostatectomy specimens from 759 patients and biochemical recurrence outcome of 655 patients. AAM patients ages 50-69 years had higher prostate specific antigen levels, worse Gleason scores, more advanced stages of disease, and a higher recurrence rate. However, among men ages 70-79 years, there was no difference in these parameters between AAM and WM. Among men ages 40-49 years, a larger sample size is necessary to make meaningful comparisons. CONCLUSIONS: Data on the outcomes of men treated for clinically localized PCa demonstrated more advanced disease and more frequent recurrence among young AAM than among WM, young and of advanced age. These differences in disease severity and recurrence, in addition to the disproportionate mortality among young AAM, are strong evidence that AAM should be tested for PCa at an earlier age than WM.

Black or African American↗
PubMed1999

Long-term survival after radiotherapy alone: radiation therapy oncology group prostate cancer trials.

PURPOSE: We assess the relative importance of the several pretreatment characteristics in predicting death from prostate cancer in patients treated with curative intent with external beam radiotherapy alone. MATERIALS AND METHODS: Patients entered on 4 prospective phase III randomized trials conducted by the Radiation Therapy Oncology Group between 1975 and 1992 were selected for this analysis if they were deemed evaluable and eligible for the trial, they had received no hormonal therapy with initial treatment and followup information was available. A disease specific survival event was declared if death was certified as due to prostate cancer, complications of treatment or unknown causes with clinically active malignancy. Median followup for patients treated on early and late studies exceeded 11 and 6 years, respectively. RESULTS: Most of the patients (1,557) had tumors clinically staged as T3 (59%), and 87 (36%) with clinically staged T1-2 tumors had pathologically positive lymph nodes. On multivariate analysis Gleason score, clinical stage and nodal status were associated with a less favorable overall and disease specific survival, whereas others factors, such as age and race, were not. A Gleason score of 8 to 10 was associated with a high risk of dying of prostate cancer in the first 5 years (risk ratio 20.0, p = 0.0001). The 10-year disease specific survival for patients with a Gleason score of 2 to 5, 6 to 7 and 8 to 10 was 87, 75 and 44%, respectively, following radiotherapy. Based on published reports these rates were higher than expected with observation alone. CONCLUSIONS: In the first 10 years Gleason score was the single most important predictor of death. Gleason score should be incorporated into the current clinical staging system.

Aged↗