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Richard K Valicenti

Publications and source records attributed to Richard K Valicenti.

12 recordsLinked to original sources
PubMed2026

Participant Heterogeneity in the Prostate Cancer Biobank of the NRG: An Obstacle to Broadening the Reach of Precision Oncology.

PURPOSE: Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS: Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS: Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). CONCLUSION: White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

Aged↗
PubMed2006

Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: an analysis of Radiation Therapy Oncology Group Protocol 92-02.

PURPOSE: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. METHODS AND MATERIALS: We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS). RESULTS: After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (p(Cox) = 0.002), PSADT <6 months (p(Cox) < 0.001), PSADT <9 months (p(Cox) < 0.001), and PSADT <12 months (p(Cox) < 0.001) but not for PSADT <3 (p(Cox) = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (p(Cox)< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. CONCLUSIONS: Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT.

Adult↗
PubMed2004

Inverse treatment planning using volume-based objective functions.

The results of optimization of inverse treatment plans depend on a choice of the objective function. Even when the optimal solution for a given cost function can be obtained, a better solution may exist for a given clinical scenario and it could be obtained with a revised objective function. In the approach presented in this work mixed integer programming was used to introduce a new volume-based objective function, which allowed for minimization of the number of under- or overdosed voxels in selected structures. By selecting and prioritizing components of this function the user could drive the computations towards the desired solution. This optimization approach was tested using cases of patients treated for prostate and oropharyngeal cancer. Initial solutions were obtained based on minimization/maximization of the dose to critical structures and targets. Subsequently, the volume-based objective functions were used to locate solutions, which satisfied better clinical objectives particular to each of the cases. For prostate cases, these additional solutions offered further improvements in sparing of the rectum or the bladder. For oropharyngeal cases, families of solutions were obtained satisfying an intensity modulated radiation therapy protocol for this disease site, while offering significant improvement in the sparing of selected critical structures, e.g., parotid glands. An additional advantage of the present approach was in providing a convenient mechanism to test the feasibility of the dose-volume histogram constraints.

Algorithms↗
PubMed2004

Importance of margin extent as a predictor of outcome after adjuvant radiotherapy for Gleason score 7 pT3N0 prostate cancer.

PURPOSE: To evaluate, in Gleason score 7, pT3N0 prostate cancer patients with positive surgical margins, the predictors of progression-free survival and to identify a patient subgroup that would benefit from immediate adjuvant postoperative radiotherapy (ART). METHODS AND MATERIALS: Between November 1989 and August 1998, 76 men underwent radical prostatectomy and were found to have capsular penetration (pT3N0), surgical Gleason score 7, tumor present at the resection margin, and an undetectable postoperative prostate-specific antigen (PSA) level. All surgical specimens underwent whole-mount serial sectioning to determine the degree of margin positivity (focal vs. extensive). Of the 76 men, 45 underwent early ART (within 6 months with a median dose of 64.8 Gy), and 31 had no immediate treatment. We defined freedom from PSA failure (bNED) as the absence of two consecutive PSA rises >0.2 ng/mL. RESULTS: The median follow-up time was 5.1 years (range, 2-10 years). The ART and non-ART patients were similar with respect to preoperative PSA level, Gleason score (4 + 3 vs. 3 + 4), presence of seminal vesicle invasion, and margin extent. On univariate analysis, margin extent was predictive for improved bNED (5-year bNED rate of 92% vs. 58%, p = 0.010, for men with focal and extensive margins, respectively). Gleason score (4 + 3 vs. 3 + 4), seminal vesicle invasion, and ART were not statistically significant predictors. On multivariate analysis, the preoperative PSA level, margin extent, and ART were independent significant factors. In the group with extensive surgical margins, men receiving ART had a significantly greater 5-year bNED survival rate compared with the non-ART patients (73% vs. 31%, p = 0.004). CONCLUSION: These data suggest that the amount of microscopic residual tumor significantly affects bNED after radical prostatectomy for Gleason score 7, pT3N0 prostate cancer. In addition, men with pathologic evidence of microscopic local disease appear to benefit from early ART compared with untreated controls.

Aged↗
PubMed2004

Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV.

PURPOSE: This is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma. METHODS AND MATERIALS: A total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS: The average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up. CONCLUSION: Tolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.

Adenocarcinoma↗
PubMed2004

Long-term outcome of patients with prostate cancer and pathologic seminal vesicle invasion (pT3b): effect of adjuvant radiotherapy.

OBJECTIVES: To evaluate the long-term outcome of patients with prostate cancer who have pathologic seminal vesicle invasion without lymph node metastasis (pT3bN0M0) and compare management strategies. METHODS: From October 1987 to August of 1997, 43 men underwent radical prostatectomy at Thomas Jefferson University Hospital, had pT3bN0M0 disease, complete preoperative and postoperative prostate-specific antigen (PSA) data, and a minimum of 2 years of follow-up. Eighteen patients with undetectable postoperative PSA levels received adjuvant radiotherapy (RT) within 6 months of surgery. Twelve patients with undetectable PSA levels postoperatively were considered for salvage treatment at biochemical progression. Thirteen patients with persistently elevated PSA levels postoperatively underwent immediate salvage RT. We evaluated the prognostic factors for freedom from biochemical failure (bNED), distant metastasis (DM), disease-specific survival, and overall survival. RESULTS: The median follow-up time was 5.9 years (range 2 to 10). Patients who received adjuvant RT had significantly greater 5-year bNED survival than patients who did not (80% versus 8%, P <0.001) and increased freedom from DM that was of borderline significance (P = 0.05). The 5-year survival estimates for DM were 0% for the adjuvant RT versus 17% for the observed patient group. In patients with undetectable postoperative PSA levels, the preoperative PSA level was an independent prognostic factor for later disease progression. Patients with a preoperative PSA level of less than 20 ng/mL showed significantly greater 5-year bNED survival than those with a preoperative PSA level of 20 ng/mL or greater (56% versus 32%, P <0.05). The survival curves for risk of DM and death from prostate cancer for those two patient groups were not significantly different statistically. CONCLUSIONS: Although pathologic seminal vesicle invasion has been associated with poor prognosis and high DM risk, adjuvant RT may result in improved bNED survival in patients with undetectable PSA levels after radical prostatectomy. The effect on clinical outcome awaits additional follow-up.

Adenocarcinoma↗
PubMed2003

Use of neoadjuvant and adjuvant therapy to prevent or delay recurrence of prostate cancer in patients undergoing surgical treatment for prostate cancer.

There have been improvements in the outcome of patients with clinically localized prostate cancer treated by radical prostatectomy. However, some patients treated with radical prostatectomy will have clinical or biochemical progression. These men are at increased risk of dying of their disease. Identification of patients with adverse features at the time of radical prostatectomy may permit the use of additional multimodality therapies to improve outcomes. Whether this additional multimodality therapy should be administered in the neoadjuvant or adjuvant setting remains controversial. Further, whether a patient at increased risk for progression after radical prostatectomy requires additional therapy before the development of documented progression remains controversial. This article reviews the potential multimodality approaches to prevent or delay recurrence of prostate cancer in patients undergoing surgical treatment for prostate cancer.

Adenocarcinoma↗
PubMed2003

RTOG 94-06: is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity?

PURPOSE: This study determines the effect on toxicity of adding neoadjuvant hormonal therapy (NHT) to three-dimensional conformal radiation therapy (3D-CRT) in RTOG 94-06. METHODS AND MATERIALS: Between August 1994 and February 2000, 583 eligible prostate cancer patients enrolled on the first 3 dose levels of RTOG 94-06, a Phase I/II dose escalation 3D-CRT trial. Two hundred and seven men initiated hormonal therapy (HT) between 2 to 3 months before 3D-CRT, and completed all HT no longer than 3 months after radiotherapy. Thirty-three patients receiving longer-duration HT were excluded. The 547 patients were treated at dose level I (68.4 Gy), level II (73.8 Gy), or level III (79.2 Gy). All dose prescriptions were to the minimum isodose surface encompassing the planning target volume (dose levels I and II) or the clinical target volume (dose level III). Men were stratified into three risk groups according to their relative risk of seminal vesicle invasion: <15% (Group 1) vs. >15% (Group 2), or to T stage (T1, 2 vs. T3 tumors [Group 3]). In Group 2 patients, there was a clinical target volume reduction to treat only the prostate after delivery of 55.8 Gy to a planning target volume including the seminal vesicles. All HT consisted of a luteinizing hormone-releasing hormone agonist with or without a nonsteroidal anti-androgen. RESULTS: On univariate analysis, NHT significantly increased the likelihood of Grade 2 acute genitourinary (GU) complications (22% to 32%, p = 0.009). Hormonal therapy did not have a significant univariate effect on any other acute or late toxicity. On multivariate analysis, the percent of the bladder (< or =30% vs. >30%) receiving > or = the reference dose (68.4 Gy, 73.8 Gy, or 79.2 Gy) (p = 0.0009, relative risk = 2.07, confidence interval: 1.88-2.28) was a significant predictor of acute GU effects. Although NHT was not significant in itself, in the multivariate analysis its interaction with baseline urinary status was an important factor (p = 0.011, relative risk = 4.31, confidence interval: 1.68-5.29). CONCLUSION: Neoadjuvant HT did not show an independent effect on the risk of side effects after 3D-CRT in patients treated on RTOG 94-06. However, this combined modality therapy significantly increased the risk of acute GU effects compared to 3D-CRT alone in men with poor baseline urinary function.

Adenocarcinoma↗
PubMed2003

Radiation therapy after radical prostatectomy: a review of the issues and options.

The role of postoperative radiation therapy after radical prostatectomy is controversial. Radiation can be delivered as an adjuvant therapy in the immediate postoperative period for high-risk patients or as salvage therapy in the setting of a rising prostate-specific antigen. There are important issues that must be addressed when considering radiation therapy after prior prostatectomy. One issue is the determination of whether a patient has local disease amenable to salvage pelvic radiation or whether the patient has occult metastatic disease. In addition, the radiation oncologist must decide if an acceptable dose of radiation therapy can be administered safely to the prostate bed. There are no published randomized clinical trials on the topic of postprostatectomy radiation therapy, although several have completed accrual or are in progress. Based on the available literature, postoperative radiation is a safe option in the patient at high risk for local recurrence based on adverse pathology or clinical features (eg, extensive extracapsular disease, positive margins, high volume Gleason score >7, and so on). Administration of an adequate dose of prostate bed radiation (ie, >64 Gy) in men with these adverse prognostic features appears to effectively reduce prostate-specific antigen (PSA) recurrence rates. The protracted natural history of prostate cancer requires longer follow-up to determine if survival will be ultimately affected by adjuvant or salvage radiation therapy. Some urologists have advised a "wait and watch policy" for high-risk postprostatectomy patients. Administration of radiation therapy is done only if and when the PSA rises. However, data suggest this approach may have limited durability in high-risk prostate cancer and could reduce the likelihood of prolonged progression-free survival. This review summarizes published retrospective and prospective data to guide decision making in selecting appropriate candidates for postprostatectomy radiation therapy.

Clinical Trials as Topic↗
PubMed2002

Longitudinal comparison of sexual function after 3-dimensional conformal radiation therapy or prostate brachytherapy.

PURPOSE: The risk of erectile dysfunction can influence treatment decisions for localized prostate cancer. To estimate the risk from 2 popular radiotherapies we compared erectile function and overall satisfaction with sexual function after 3-dimensional (D) conformal radiation therapy and transperineal prostate brachytherapy. MATERIALS AND METHODS: A total of 128 patients with prostate cancer underwent 3-D conformal radiation therapy (median dose 70.2 Gy. to the planning target volume) and 60 underwent palladium transperineal prostate brachytherapy (median dose 90 or 115 Gy. to 80% of the prostate with or without external nonconformal beam radiation therapy. Of the 128 patients 47 (37%) also received a luteinizing hormone releasing hormone (LH-RH) agonist (3 to 4 months), whereas 26 (43%) of the 60 patients received external beam radiation therapy and LH-RH (8 to 9 months). We evaluated erectile function and overall satisfaction with questions from validated, self-administered questionnaires. Patients responded to the questions serially before any prostate cancer therapy and at regular followup visits thereafter. We used the time until a patient returned to baseline erectile function and overall satisfaction to compare treatment modalities. RESULTS: Median followup was 21 months. Of patients receiving 3-D conformal radiation therapy with or without LH-RH agonists 65% (95% CI 47% to 82%) and 67% (53% to 81%), respectively, returned to baseline overall satisfaction within 12 months after treatment versus 23% (9% to 50%) and 56% (38% to 75%) of the patients treated with transperineal prostate brachytherapy with or without external beam radiation therapy and LH-RH agonists, respectively. Reductions in overall satisfaction appeared to relate to changes in erectile function. CONCLUSIONS: These data suggest that in the absence of LH-RH agonist use 3-D conformal radiation therapy and transperineal prostate brachytherapy have a similar impact on erectile function and overall satisfaction. Differences observed in erectile function and overall satisfaction in the 2 groups of patients who received adjuvant LH-RH may be due to the different duration of therapy (3 versus 8 months). Longer followup will be needed to evaluate this hypothesis.

Aged↗