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M Roach

Publications and source records attributed to M Roach.

At least 73 records · Page 4Linked to original sources

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer.

PURPOSE: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy. MATERIALS AND METHODS: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value > or = 1 ng/ml; or 2. a PSA value that rose > or = 0.5 ng/ml in < or = 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as 2/3(iPSA) + 10(GS-6), and high risk was defined as %rLN+ > or = 15%. Univariate and multivariate analyses were performed. RESULTS: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome. CONCLUSION: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.

Analysis of Variance↗

Failure patterns by prognostic group determined by recursive partitioning analysis (RPA) of 1547 patients on four radiation therapy oncology group (RTOG) studies in inoperable nonsmall-cell lung cancer (NSCLC).

PURPOSE: To identify groups of patients who might benefit from more aggressive systemic or local treatment, based on failure patterns when unresectable NSCLC was treated by radiation therapy (RT) alone. METHODS: From 4 RTOG trials, 1547 patients treated by RT alone were analyzed for patterns of first failure by RPA class defined by prognostic factors, including KPS, weight loss, nodal stage, pleural effusion, age and radiation therapy dose. All patients had NSCLC AJCC Stage II, IIIA, or IIIB, KPS > 50, with no previous RT or chemotherapy. Progressions in the primary (within irradiated fields), thorax (outside irradiated area, but within thorax), brain and distant metastasis other than brain were compared (2-sided) for each failure category by RPA. RESULTS: The RPA classes were 4 distinct subgroups that had significantly different median survivals of 12.6, 8.3, 6.3 and 3.3 months for Classes I, II, III and IV, respectively, (all groups, p = 0.0002). There were 583, 667, 249 and 48 patients in Classes I, II, III and IV, respectively. Primary failure was seen in 27%, 25%, 21% and 10% for Classes I, II, III, and IV, respectively (I vs. IV, p = 0.014; II vs. IV, p = 0.022). Distant metastasis, including brain metastasis, occurred at significantly higher rates among Classes I and II (58% and 54%) than in Classes III and IV (42% and 27%). A higher rate (58%) of death without an identifiable site of failure was found in Class IV than in Classes I, II and III (27%, 28% and 36%, respectively). CONCLUSIONS: The data suggest that physiologic compromise from the intrathoracic disease in Class IV patients is sufficient to cause death before specific sites of failure became evident. Clinical investigations using treatments directed at specific sites of failure could lead to improved outcome for Class I, II and, possibly, Class III patients. Inclusion of Class IV patients in clinical trials may obscure outcomes.

Aged↗

Centralized multiinstitutional postimplant analysis for interstitial prostate brachytherapy.

PURPOSE: To investigate the feasibility and utility of performing centralized postimplant analysis for transperineal interstitial permanent prostate brachytherapy (TIPPB) by conducting a pilot study that compares the results obtained from 125I implants conducted at five different institutions. METHODS AND MATERIALS: Dose-volume histogram (DVH) analysis was performed on 10 postimplant CT scans from each of five institutions. This analysis included the total implanted activity of 125I, ultrasound, and CT volumes of the prostate, target-volume ratios, dose homogeneity quantifiers, prostate dose coverage indices, and rectal doses. As a result of the uncertainty associated with the delineation of the prostatic boundaries on a CT scan, the contours were redrawn by a single, study center physician, and a repeat DVH analysis was performed. This provided the basis for comparison between institutions in terms of implant technique and quality. RESULTS: By comparing total activity to preimplant ultrasound volume we clearly demonstrated that differences exist in implant technique among these five institutions. The difficulty associated with determining glandular boundaries on CT scans was apparent, based upon the variability in prostate volumes drawn by the various investigators compared to those drawn by the study center physician. This made no difference, of course, in the TVR or homogeneity quantifiers that are independent of target location. Furthermore, this variability made surprisingly little difference in terms of dose coverage of the prostate gland. Rectal doses varied between institutions according to the various implant techniques. CONCLUSIONS: Centralized, outcome-based evaluation of transperineal interstitial permanent prostate brachytherapy is viable and appropriate. Such an approach could be reasonably used in the conduct of multiinstitutional trials used to study the efficacy of the procedure.

Brachytherapy↗

A three-field arc technique (3-FAT) for treating prostate cancer.

PURPOSE: We have previously designed two external beam radiotherapy techniques for treating prostate cancer. The seven-field, coplanar fixed beam technique resulted in dose distributions that were superior to other coplanar plans studied. The other technique using bilateral blocked arcs produced slightly higher doses to normal tissues but was far simpler to execute. We combined aspects of both these plans to produce a technique that was less complicated yet resulted in an improved dose distribution, i.e., to improve dose delivery to the clinical target volume (CTV) while minimizing doses to the rectum, bladder, and femoral heads. METHODS AND MATERIALS: Twenty patients, previously treated at the University of California, San Francisco (UCSF) with radiotherapy for adenocarcinoma of the prostate, were studied. Each patient was treated with an immobilizer, urethrogram, and a preplanning CT scan. A previously employed, seven-field, coplanar, fixed beam technique was compared with a newly designed three-field, arc technique (3-FAT). This 3-FAT was designed using two equally weighted rotational beams, with nonuniform blocks, beginning in the lateral gantry position and spanning anteriorly 35 degrees. The two beams became noncoplanar by turning the table 20 degrees, bringing the patient's feet toward the gantry (inferior oblique arcs). An anterior inferior oblique (AIO), angled 20 degrees to the inferior of anterior was included for 10% of the daily treatment. Dose-volume histograms (DVH) were used to evaluate doses to adjacent critical structures. The dose to each critical structure was averaged and tabulated for the 20 patients. In addition, we compared normalized doses to adjacent structures using 3-FAT and seven-coplanar, fixed beams vs. a technique using four noncoplanar, fixed beams. RESULTS: The three-field arc technique produced favorable dose distributions for the rectum, bladder, and femoral heads. Compared to the seven-field plan, employing the 3-FAT resulted in a 13% lower dose to 40% of the rectum, and 25% lower dose to 40% of the bladder. Compared to the four-field plan, employing the 3-FAT resulted in a 23% lower dose to 40% of the rectum, and 1% decrease in dose to 40% of the bladder. The three-field arc technique reduced the dose delivered to 40% of the femoral heads by approximately 45% when compared to the other techniques. Compared to other standard treatment techniques, the improvement in dose distribution was even greater. CONCLUSIONS: The 3-FAT represents a technical improvement in the treatment of cancer of the prostate and seminal vesicles by minimizing the dose delivered to adjacent critical structures. The 3-FAT can incorporate the advances of multileaf collimation and digitally reconstructed radiographs to deliver treatment with cost effectiveness and technological efficiency.

Adenocarcinoma↗

Sociodemographic analysis of patients in radiation therapy oncology group clinical trials.

PURPOSE: To assess the degree to which the sociodemographic characteristics of patients enrolled in Radiation Therapy Oncology Group (RTOG) clinical trails are representative of the general population. METHODS AND MATERIALS: Sociodemographic data were collected on 4016 patients entered in 33 open RTOG studies between July 1991 and June 1994. The data analyzed included educational attainment, age, gender, and race. For comparison, we obtained similar data from the U.S. Department of Census. We also compared our RTOG data with Surveillance Epidemiology and End Results (SEER) data for patients who received radiation therapy, to determine how RTOG patients compared with cancer patients in general, and with patients with cancers at sites typically treated with radiotherapy. RESULTS: Overall, the sociodemographic characteristics of patients entered in RTOG trials were similar to those of the Census data. We found that, in every age group of African-American men and at nearly every level of educational attainment, the proportion of RTOG trial participants mirrored the proportion in the census data. Significant differences were noted only in the youngest category of African-American men, where the RTOG accrues more in the lower educational categories and fewer with college experience. For African-American women, we found a similar pattern in every age group and at each level of educational attainment. As with men, RTOG trials accrued a considerably larger proportion of younger, less educated African-American women than the census reported. Using SEER for comparison, the RTOG enrolled proportionately more African-American men to trials all cancer sites combined, and for prostate and head and neck cancer. In head and neck trials, the RTOG enrolled nearly twice as many African-American men than would be predicted by SEER data. In lung cancer trials, RTOG underrepresented African-American men significantly; however, there was no difference for brain cancer trials. There were no racial differences in RTOG accrual and SEER incidence data for women on trials in brain, lung, and head and neck cancer. However, the RTOG trials accrued nearly twice the proportion of African-American women in cervical cancer trials and in all sites combined, compared to the SEER data. CONCLUSIONS: Comparisons with the U.S. Census and SEER show that African-Americans are proportionally well represented in cancer clinical trials conducted by the Radiation Therapy Oncology Group. The comparative analysis indicates that all educational levels in each age group of African-Americans generally mirror the U.S. Census, with one exception. The exception is a significant overrepresentation of less-educated African-Americans in the youngest age category. This exception is counter to the expectation that better-educated patients are more likely to enroll in trials. When compared with SEER data, the RTOG trials either parallel or overrepresent African-American men and women, with the only exception being in lung cancer, where men are underrepresented. These results show that, in comparison to the Census and SEER data, the RTOG has fulfilled its commitment to enroll African-American patients in its clinical trials.

Adult↗

Prostate-specific antigen levels are higher in African-American than in white patients in a multicenter registration study: results of RTOG 94-12.

PURPOSE: To compare serum prostate-specific antigen (PSA) levels in a national sample of African-American and white men with prostate cancer, and to attempt to explain any differences by using self-reported individual-level socioeconomic status adjustments. METHODS AND MATERIALS: During 4 1/2 months in 1994-95, 709 patients with nonmetastatic prostate cancer were enrolled in this prospective study; 17.5% were African-American and 82.5% were white. Information about clinical stage, tumor grade, pretreatment PSA, type of insurance, and educational and income status was obtained. Serum PSA levels were measured and racial differences were found; how the differences were influenced by other patient- or tumor-related factors and if the differences could be explained by socioeconomic status disparities were determined. In univariate analyses, factors associated with the mean PSA levels were studied; log-converted values were used to yield a normal distribution. Multivariate analyses were done on log-linear models for description of association patterns among various categorical variables; a perfectly fitted model should have a correlation value (CV) of 1.0. RESULTS: The mean PSA level was higher in African-Americans (14.68 ng/ml) than in whites (9.82 ng/ml) (p = 0.001). Clinical stage (p = 0.001), Gleason sum tumor grade (p = 0.0001), educational level (p = 0.001), and household income (p = 0.03) were also associated with mean PSA levels; age, type of biopsy, and insurance status were not. Disease stage (p = 0.0001), grade (p = 0.0001), education (p = 0.07), and income (p = 0.02) were all associated with PSA levels for whites, but none of these factors were important for African-Americans (all p values > 0.1). The best fitted log-linear model (CV = 0.99) contained PSA (< 10, 10-20, and > 20), Gleason sum grade (2-5, 6-7, and 8-10), race, and two interactions: PSA by race (p = 0.0012) and PSA by Gleason sum (p = 0.0001). Models replacing race for either income (CV = 0.82) or education (CV = 0.82) or both (CV = 0.78) did not fit as well. CONCLUSIONS: African-Americans with nonmetastatic prostate cancer have higher serum PSA levels at diagnosis than whites, implying a higher tumor cell burden. Individual-level household income, education, or insurance status alone or in combination account for racial differences, but only partially.

Analysis of Variance↗

Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial.

The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg(-1) day(-1) plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl(-1) for men and 14 g dl(-1) for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl(-1) for r-HuEPO-treated patients compared with 11.0 g dl(-1) for control subjects (P = 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl(-1) compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl(-1)). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and scheduling as well as the impact of r-HuEPO on clinical outcomes.

Anemia↗

Radiation therapy for the management of biopsy proved local recurrence after radical prostatectomy.

PURPOSE: We determine which clinical characteristics correlate with a successful outcome following external beam radiation for the management of biopsy proved, locally recurrent prostate cancer after radical prostatectomy. MATERIALS AND METHODS: The clinical records of 34 patients who were treated at our institution with external beam radiation for biopsy proved local disease recurrence after radical prostatectomy were reviewed. Mean followup was 77.9 months after radical prostatectomy and 38.3 months after radiotherapy. Preoperative, postoperative and pathological characteristics were examined for the ability to predict failure following radiotherapy. RESULTS: Of the 34 patients 9 (26%) exhibited persistently low and stable serum prostate specific antigen (PSA) (less than 0.5 ng./ml.), while 7 (21%) had an undetectable serum PSA (less than 0.1 ng./ml.) during followup. These 16 patients were considered to be successfully treated by radiation and in the remaining 18 (53%) radiation was considered to have failed. The likelihood of successful treatment at 3 years after radiotherapy for all patients was 48%. Preoperative PSA, PSA at first elevation, postoperative PSA velocity and pathological stage were not significant predictors of a successful outcome following radiation treatment. Patients with a serum PSA of 4 ng./ml. or less before receiving radiotherapy and those with a prostatectomy specimen Gleason score of 7 or less were significantly more likely to be successfully treated by radiotherapy. CONCLUSIONS: Radiation therapy is a viable treatment option for select patients with biopsy proved local disease recurrence following radical prostatectomy. The chance of achieving and maintaining a persistently low and stable or undetectable serum PSA is likely in those patients with a prostatectomy specimen Gleason score of 7 or less and a pre-radiation PSA of 4.0 ng./ml. or less. More effective treatment regimens are needed for those patients in whom radical prostatectomy fails.

Aged↗

Localization of the prostatic apex for radiotherapy treatment planning using urethroscopy.

PURPOSE: To assess the ability of computed tomography (CT) scans and retrograde urethrograms to accurately define the prostatic apex in the craniocaudad dimension, using urethroscopy as a reference. METHODS AND MATERIALS: Plain film radiographs of the pelvis were obtained in 15 patients with early-stage adenocarcinoma of the prostate, with the tip of a urethroscope held in place at the external sphincter, which most closely approximates the prostatic apex. The scope was then withdrawn, and a retrograde urethrogram was performed. Immediately afterwards, a CT scan of the pelvis was obtained. Because differential filling of the bladder and rectum affects the position of the prostatic apex, patients voided prior to rather than in between the three consecutive studies. RESULTS: The urethroscopy-defined prostatic apex was located 4 +/- 8 mm (mean +/- SD) superior to the CT-defined apex, 13 +/- 3 mm (mean +/- SD) superior to the urethrogram tip and 30 +/- 7 mm (mean +/- SD) superior to the ischial tuberosities. There was significant interobserver variability in the location of the prostatic apex as determined by CT scans. Placement of the inferior border of the radiation portals at the ischial tuberosities would have resulted in irradiation of > or = 20 mm bulbar urethra, as defined by the dye column of the retrograde urethrogram, in 6 out of 15 (40%) of the patients and irradiation of < 10 mm bulbar urethra in 2 out of 15 (13%) of the patients. CONCLUSION: Because the prostate blends inferiorly with the urogenital diaphragm, CT scans do not allow one to precisely localize the prostatic apex. Due to anatomic variability, the ischial tuberosities do not allow one to accurately localize the prostatic apex. Retrograde urethrograms provide helpful supplemental information regarding the position of the prostatic apex for radiotherapy treatment planning.

Endoscopy↗

Prostate volumes and organ movement defined by serial computerized tomographic scans during three-dimensional conformal radiotherapy.

The aim of this study was to assess changes in prostate volumes and organ movement during a course of external beam irradiation using serial computerized tomographic (CT) scans and three-dimensional treatment planning software. Ten consenting prostate cancer patients underwent repeat CT scans at biweekly intervals during the course of external beam irradiation. The spacing of 5 mm was used because this spacing mimics our clinical treatment approach. Prostate locations were determined by merging CT images using bony anatomy and comparing the differences in the prostate volumes, the edges (anterior, posterior, superior, inferior, and lateral) and centers of the prostate (EoP and CoP, respectively). Compared to the 10 initial treatment planning CT scans, the prostate volume determined by the repeat CT scans tended to be smaller (approximately 14%, P < 0.001). The prostate volumes determined by repeat CT scans tended to be stable with a mean volume of 86% (S.D. = 18%) of the initial CT. When assessed by changes in the EoP, superior movements appeared to be the most common source for concern for adequate coverage of the prostate, while inferior movement was not seen. When assessed by changes in CoP, movement of > or = 3 mm was noted in 47% of the studies in the superior direction, with the average displacement being approximately 2.0 mm. In this study, the prostate volume tended to be smaller 2 weeks after the start of radiotherapy. Moreover, the prostate volumes defined by the serial CT scans were less reproducible than expected. Superior displacement of the prostate is the most common and significant type of displacement, while inferior movement is least frequent when patients are simulated with their rectums empty. Because of the magnitude of daily setup errors, organ movement, and problems with reproducibility in target definition, additional field edge reductions do not appear to be warranted during the delivery of three-dimensional conformal radiotherapy. Efforts should be directed at improving our ability to reduce organ movement and accurately targeting the prostate.

Computer Simulation↗

Focal therapy for prostate cancer 1996: maximizing outcome.

OBJECTIVES: To summarize improvements in patient selection and the results of focal therapy for the management of localized prostate cancer. METHODS: A contemporary series of patients managed with wide surgical excision, radiation therapy (three-dimensional conformal radiation, interstitial radiation, and charged-particle or proton therapy), and cryo-therapy were reviewed. RESULTS: We used preoperative cancer grade, transrectal ultrasound, and serum prostate-specific antigen (PSA) in all patients, and cross-sectional imaging and bone scans in selected patients to allow for reasonably accurate cancer staging and selection of patients most likely to be cured by radical prostatectomy or radiation. In patients with extracapsular extension of prostate cancer, wide surgical excision and achievement of a clear surgical margin had therapeutic value. Newer radiation techniques resulted in a higher likelihood of prostate cancer control than previous techniques. Cryotherapy for patients with stages T1 through 3 prostate cancer was associated with a posttreatment undetectable PSA rate of 48% and a positive biopsy rate of 23%. CONCLUSIONS: Patients with organ-confined and, therefore, curable prostate cancer can be identified. Well-performed radical prostatectomy, radiation, and cryotherapy are alternative treatments for the management of localized prostate cancer.

Androgen Antagonists↗

Differences in drug prescribing patterns in elderly parkinsonian patients identified at hospital admission.

In the period July 1984 to June 1993 a total of 4541 admissions to a Department of Medicine for the Elderly were investigated. Approximately 9% of the total were diagnosed to have parkinsonism. Full drug histories together with the available demographic and clinical data were investigated in order to identify differences in the prescribing patterns in this group compared to those of non-parkinsonian patients admitted during this time frame. There was a statistically significant lower incidence among the parkinsonian group for the prescribing of all cardiovascular drug groups, anticoagulants, hypoglycaemics, bronchodilators, and corticosteroids compared with non-parkinsonian patients. In contrast, the incidence of hypnotics, laxatives, antidepressants and antipsychotics were significantly higher.

Aged↗

Neoadjuvant therapy prior to radiotherapy for clinically localized prostate cancer.

The optimal treatment for many unresectable solid tumors involves the combined use of chemotherapy and radiation. Retrospective and prospective randomized trials demonstrating a reduction in failure rates when neoadjuvant androgen suppression is combined with radiotherapy suggest that this is also likely to be true for prostate cancer. The absence of overlapping toxicities, the high response rates to androgen suppression, and the ease with which the prostate is included in radiotherapy portals makes the prostate an ideal site for chemoradiation. Since radiation and hormonally mediated apoptosis appear to be induced by different mechanisms their interaction may well be synergistic. Volumetric changes induced by hormonal suppression facilitate radioactive implantation in the prostate in men with large glands. This neoadjuvant approach also reduces the amount of normal tissue to be irradiated when used prior to 3-dimensional conformal radiotherapy while allowing higher doses to the tumor. It may be particularly important to use antiandrogens to block the 'intraprostatic flare' that may result from the testosterone surge induced by luteinizing hormone-releasing hormone in patients undergoing neoadjuvant (short course) androgen suppression. Men who are at particularly 'high risk' for biochemical failure when treated with radiotherapy alone should probably receive a 'longer' course of complete neoadjuvant and possibly adjuvant hormonal blockade, but the optimal duration and sequence of androgen suppression remain to be defined.

Androgen Antagonists↗