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Mack Roach

Publications and source records attributed to Mack Roach.

At least 19 recordsLinked to original sources

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↗

Staging for prostate cancer: time to incorporate pretreatment prostate-specific antigen and Gleason score?

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system for prostate cancer is based primarily based on clinical tumor (T) classification. In this article, the authors summarize arguments for incorporating additional pretreatment parameters and creating a new staging system for prostate cancer. METHODS: Men with localized prostate cancer who received treatment with external beam radiation alone were analyzed using the 1997 AJCC staging system compared with a system that included pretreatment prostate-specific antigen (pPSA) level and Gleason score (GS). Multivariate analyses using a Cox proportional-hazards model were carried out to evaluate T classification, GS, and pPSA as predictors of overall survival (OS), disease-specific survival (DSS), and freedom from PSA failure (FFPF). RESULTS.: Based on pretreatment characteristics in a series of contemporary patients, only 0.6% of patients were classified with AJCC stage I disease, 16.0% were classified with AJCC stage III disease, and 83.4% were classified with AJCC stage II disease. Multivariate analyses indicated the independent statistical significance of T classification, GS, and pPSA in predicting OS, DSS, and FFPF (model chi-square value, P < .0001 for each). Using these 3 predictors, subsets of patients who had similar outcomes were combined to provide examples of the insensitivity of the AJCC system for predicting outcomes. Incorporating pPSA and GS allowed the identification of differences in OS, DSS, and FFPF for subsets of patients with AJCC stage II disease (P < .0001, P = .005, and P < .0001, respectively). CONCLUSIONS: The current AJCC staging system does not divide contemporary patients with prostate cancer into prognostic subgroups and does not identify patients who have comparable biochemical control and survival. The AJCC staging system for prostate cancer should be changed to incorporate pPSA, GS, and risk stratification.

Antineoplastic Agents, Hormonal↗

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: the University of California-San Francisco experience.

PURPOSE: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-up time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs > or =1, and have subsequently been found to have distant metastases. CONCLUSIONS: Salvage HDR prostate brachytherapy appears to be feasible and effective.

Aged↗

Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer.

PURPOSE: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. METHODS AND MATERIALS: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated: 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. RESULTS: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V(45 Gy) = 98% and V(42.75 Gy) = 100%. Compared with WP 3DCRT, IMRT reduced bladder V(45 Gy) by 78%, rectum V(45 Gy) by 48%, and small bowel V(45 Gy) by 232 cm3. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V(45 Gy) by 90%, rectum V(45 Gy) by 54% and small bowel V(45 Gy) by 455 cm3 compared with EF 3DCRT. CONCLUSION: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.

Aged↗

Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether "mini-pelvis" (MP; defined as > or = 10 x 11 cm but < 11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms 1 and 2 of the study. METHODS AND MATERIALS: Eligible patients had a risk of lymph node (LN) involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and another group of 324 patients were randomized to receive PO RT + N&CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an "MP" field and the smaller a PO field. RESULTS: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. CONCLUSIONS: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.

Adult↗

Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.

In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

Androgen Antagonists↗

Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer.

PURPOSE: The Calypso 4D Localization System is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first human use of the system, to evaluate the localization accuracy of this technique compared with radiographic localization and to assess its ability to obtain real-time prostate-motion information. METHODS AND MATERIALS: Three transponders were implanted in each of 20 patients. Eleven eligible patients of the 20 patients participated in a study arm that compared radiographic triangulated transponder locations to electromagnetically recorded transponder locations. Transponders were tracked for 8-min periods. RESULTS: The implantations were all successful, with no major complications. Intertransponder distances were largely stable. Comparison of the patient localization on the basis of transponder locations as per the Calypso system with the radiographic transponder localization showed an average (+/-SD) 3D difference of 1.5 +/- 0.9 mm. Upon tracking during 8 min, 2 of the 11 patients showed significant organ motion (>1 cm), with some motion lasting longer that 1 min. CONCLUSION: Calypso transponders can be used as magnetic intraprostatic fiducials. Clinical evaluation of this novel 4D nonionizing electromagnetic localization system with transponders indicates a comparable localization accuracy to isocenter, (within 2 mm) compared with X-ray localization.

Electromagnetic Phenomena↗

Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level.

PURPOSE: To evaluate the metabolic response by comparing the time to resolution of spectroscopic abnormalities (TRSA) and the time to prostate-specific antigen level in low-risk prostate cancer patients after treatment with three-dimensional conformal external beam radiotherapy (3D-CRT) compared with permanent prostate implantation (PPI). Recent studies have suggested that the treatment of low-risk prostate cancer yields similar results for patients treated with 3D-CRT or PPI. METHODS AND MATERIALS: A total of 50 patients, 25 in each group, who had been treated with 3D-CRT or PPI, had undergone endorectal magnetic resonance spectroscopy imaging before and/or at varying times after therapy. The 3D-CRT patients had received radiation doses of > or =72 Gy compared with 144 Gy for the PPI patients. The spectra from all usable voxels were examined for detectable levels of metabolic signal, and the percentages of atrophic and cancerous voxels were tabulated. RESULTS: The median time to resolution of the spectroscopic abnormalities was 32.2 and 24.8 months and the time to the nadir prostate-specific antigen level was 52.4 and 38.0 months for the 3D-CRT and PPI patients, respectively. Of the 3D-CRT patients, 92% achieved negative endorectal magnetic resonance spectroscopy imaging findings, with 40% having complete metabolic atrophy. All 25 PPI patients had negative endorectal magnetic resonance spectroscopy imaging findings, with 60% achieving complete metabolic atrophy. CONCLUSION: The results of this study suggest that metabolic and biochemical responses of the prostate are more pronounced after PPI. Our results have not proved PPI is more effective at curing prostate cancer, but they have demonstrated that it may be more effective at destroying prostate metabolism.

Aged↗

Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG protocol 86-10.

PURPOSE: We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10. METHODS: [corrected] With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started. RESULTS: For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared to [corrected] those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started. CONCLUSION: [corrected] The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival.

Analysis of Variance↗

Radiotherapy in the management of common genitourinary malignancies.

A continued role for radiation therapy in the multidisciplinary management of genitourinary malignancies seems certain. Treatment outcomes continue to improve, accompanied by diminishing rates of toxicity. With continued technologic advances in the delivery of radiation, including the use of adaptive radiotherapy, the discovery and application of novel treatment agents, and the combined efforts of urologists, medical oncologists, and radiation oncologists, patients who have genitourinary malignancies have an excellent chance of cure.

Brachytherapy↗

Defining high risk prostate cancer with risk groups and nomograms: implications for designing clinical trials.

PURPOSE: Death from prostate cancer is usually preceded by metastases and it usually occurs in men with high risk disease who experienced biochemical failure with a short prostate specific antigen doubling time. We developed a model for determining disease specific survival in prostate cancer. MATERIALS AND METHODS: We used the model for defining high risk prostate cancer that was developed by the Radiation Therapy Oncology Group and combined it with the Kattan nomogram for predicting the risk of metastases. We selected 414 Radiation Therapy Oncology Group intermediate and high risk patients who were treated with external beam radiotherapy alone. Excluded were patients with low risk disease. The Kaplan-Meier product limit method was used to estimate the probability of freedom from biochemical failure, overall survival and disease specific survival. RESULTS: A significant difference was observed in freedom from biochemical failure, disease specific survival and overall survival among the 3 tertiles created by the nomogram using the cutoff points less than 8.5%, 8.5% to 15% and greater than 15% (p <0.001, 0.0002 and 0.0003, respectively). Only the risk of metastases using the categorized nomogram score (less than 8.5% and 8.5% to 15% vs greater than 15%), not preradiotherapy prostate specific antigen or Radiation Therapy Oncology Group risk (Radiation Therapy Oncology Group 2 vs 3), was a significant predictor of disease specific and overall survival for intermediate/high risk patients and intermediate/high risk with 15% or less risk for metastases. CONCLUSIONS: We combined a risk group stratification scheme for disease specific survival with a nomogram predicting the risk of metastases and created a model that may be useful for designing phase III trials with metastases and disease specific survival as study end points.

Clinical Trials as Topic↗

Megavoltage cone-beam CT: system description and clinical applications.

In this article, we describe a clinical mega-voltage cone-beam computed tomography (MV CBCT) system, present the image acquisition and patient setup procedure, discuss the positioning accuracy and image quality, and illustrate its potential use for image-guided radiation therapy (IGRT) through selected clinical examples. The MV CBCT system consists of a standard linear accelerator equipped with an amorphous-silicon flat panel electronic portal-imaging device adapted for mega-electron volt (MeV) photons. An integrated computer workspace provides automated acquisition of projection images, image reconstruction, CT to CBCT image registration, and couch shift calculation. The system demonstrates submillimeter localization precision and sufficient soft-tissue resolution to visualize structures such as the prostate. In our clinic, we have used the MV CBCT system to detect nonrigid spinal cord distortions, monitor tumor growth and shrinkage, and locate and position stationary tumors in the lung. MV CBCT has also greatly improved the delineation of structures in CT images that suffer from metal artifacts. MV CBCT has undergone significant development in the last few years. Current image quality has already proven sufficient for many IGRT applications. Moreover, we expect the range of clinical applications for MV CBCT to grow as imaging technology continues to improve.

Humans↗

Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.

OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG > or =19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

Androgen Antagonists↗

New techniques and management options for localized prostate cancer.

Prostate cancer is diagnosed in younger men who want treatment that does not compromise their quality of life, take time away from work, or cause worrisome side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, and third-generation cryotherapy are modifications of previously used techniques in the treatment of prostate cancer and are presented in this article. Although some or all of the outcomes might be expected to change in the future, the urologic surgeon is left to select an approach, presumably on the basis of the experience, level of training, and care pathways at his or her institution.

Journal Article↗

Prostate cancer progression after therapy of primary curative intent: a review of data from prostate-specific antigen era.

BACKGROUND: Radical prostatectomy and radiotherapy (RT), both radical therapies, are the standard treatments of curative intent for early prostate cancer. However, these therapies are not curative in all patients and, consequently, a substantial proportion of treated patients remain at risk of disease progression and/or cancer-related death. METHODS: This article presents contemporary data on the incidence of prostate-specific antigen (PSA) and clinical disease progression after primary therapy of curative intent in relation to commonly assessed pretreatment or pathologic disease characteristics. RESULTS: The data highlight the substantial risk of progression for certain patient groups, such as those with Gleason score 8-10, cT3 disease, lymph node metastases, and/or pretreatment PSA levels > 20 ng/mL. CONCLUSIONS: Improved and/or additional treatment options are needed for these patient groups.

Brachytherapy↗

Radiotherapy in the management of clinically localized prostate cancer: evolving standards, consensus, controversies and new directions.

Major advances have been made in the definitive use of various forms of radiotherapy (RT) in the management of clinically localized prostate cancer (PCa). Despite tremendous gains, the radiation oncology community continues to struggle with several key questions. In general, the areas of controversy pertain to how to improve the therapeutic ratio of RT. Specifically, key issues include dose escalation; the relative benefit of alternative forms of RT (ie, brachytherapy and protons); target localization; the use, timing, and duration of androgen deprivation; and the need for pelvic nodal irradiation. Multiple efforts have been made to address each of these issues; however, there is no consensus on how to resolve them. This review is an evidence-based critique of the available treatment approaches considered for the optimal use of radiotherapy as definitive management of clinically localized PCa.

Brachytherapy↗