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Mack Roach

Publications and source records attributed to Mack Roach.

At least 55 records · Page 3Linked to original sources
PubMed2004

Neoadjuvant hormonal therapy in men being treated with radiotherapy for localized prostate cancer.

Several prospective randomized trials have demonstrated that men with localized prostate cancer benefit from the use of short-term neoadjuvant hormonal therapy (NHT) in combination with external beam radiotherapy (EBRT). Seven randomized trials were summarized in 6 publications including patients treated with NHT in combination with EBRT on 1 or more arms. A total of 17 different arms were compared including radiotherapy alone (n = 3), and NHT and concurrent hormonal therapy (N&CHT) (n = 12) with or without short-term adjuvant hormonal therapy (SAHT) (n = 5) or long-term hormonal therapy (n = 1). Patients treated with EBRT alone had a worse outcome than those treated with NHT. Intermediate-risk patients treated with 2 to 3 months of NHT did as well as those treated with longer neoadjuvant therapy or SAHT. The preponderance of data supports the use of NHT in combination with EBRT in intermediate-risk patients.

Journal Article↗
PubMed2003

A zero PSA slope in posttreatment prostate-specific antigen supports cure of patients with long-term follow-up after external beam radiotherapy for localized prostate cancer.

PURPOSE: To determine whether the rate of change in prostate-specific antigen (PSA) in patients treated with external beam radiotherapy for localized prostate cancer improves our ability to define which patients are likely to be cured of their disease. METHODS AND MATERIALS: Patients treated between 1987 and 1995 at the University of California, San Francisco and the University of Michigan for localized prostate cancer with external beam radiotherapy and without hormonal ablation were evaluated for this study. The PSA slope was calculated for 199 patients who were disease free by the American Society for Therapeutic Radiology and Oncology consensus definition for at least 4 years and at last follow-up. Patients were categorized into groups defined by no increase, minimal increase, modest increase, and a definite increase in change in PSA level, corresponding to slopes of 0.0-0.1, >0.1-0.5, and >0.5 ng/mL/y, respectively. RESULTS: Fifty-four percent of the patients displayed a non-increasing PSA (Group 1), 23% had a minimal increase (Group 2), 17% had a modest increase (Group 3), and 6% had a definite increase (Group 4). Patients with a non-increasing PSA slope had a significantly longer time to nadir (median 47.8, 31.6, 29.9, and 23.3 months for Groups 1-4, respectively, p = 0.0001) and a lower median PSA nadir (median 0.30, 0.40, 0.55, and 1.00 ng/mL for Groups 1-4, respectively, p = 0.0006). CONCLUSION: On the basis of PSA kinetics, we believe that a group of patients can be defined who appear to be cured of localized prostate cancer (i.e., have a zero slope). These patients have a lower and later PSA nadir, as well as a more substantial proportional effect of external beam radiotherapy on their PSA level. Patients with a definite increase in PSA slope are erroneously labeled disease free by the American Society for Therapeutic Radiology and Oncology consensus definition.

Aged↗
PubMed2003

(Non)-migration of radiopaque markers used for on-line localization of the prostate with an electronic portal imaging device.

PURPOSE: Radiopaque gold markers can be implanted in the prostate to visualize its position on portal images during radiation therapy. This procedure assumes that the markers do not move within the prostate. In this work we test this assumptiom. METHODS AND MATERIALS: Three markers were implanted transrectally in the prostate of patients undergoing external radiation therapy. An orthogonal pair of portal images was acquired periodically throughout the course of radiation therapy with an a-Si electronic portal imaging device (EPID). The marker coordinates were determined, and the distances between the implanted markers were recorded. The distance time trend is used to evaluate the magnitude of marker migration. RESULTS: The average standard deviation (SD) of the distances between markers was 1.3 mm (range 0.44 to 3.04 mm). Three of the 11 patients show a SD larger than 2 mm. For these patients, all three distances show a simultaneous reduction with time, compatible with a shrinking of the prostate. All had been treated with neoadjuvant hormone therapy. For 1 of the 3 patients, this reduction in volume was confirmed with a repeat computed tomographic scan. CONCLUSION: None of the 33 markers studied migrated significantly. The implantation of three radiopaque gold markers enables accurate and precise on-line verification of the prostate position during external beam radiation therapy. The use of three markers provides a tool to monitor prostate position and volume changes that can occur over time due to hormone or radiation therapy.

Gold↗
PubMed2003

Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II.

PURPOSE: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. MATERIALS AND METHODS: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. RESULTS: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. CONCLUSIONS: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of >/= Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Adenocarcinoma↗
PubMed2003

Race and survival of men treated for prostate cancer on radiation therapy oncology group phase III randomized trials.

PURPOSE: We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials. MATERIALS AND METHODS: Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively. RESULTS: On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA. CONCLUSIONS: As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

Black or African American↗
PubMed2003

Serum prostate-specific antigen and survival after external beam radiotherapy for carcinoma of the prostate.

OBJECTIVES: To evaluate the significance of pretreatment prostate-specific antigen (pPSA) levels as a predictor of overall survival simultaneously with previously established prognostic factors. The pPSA level is a major predictor of treatment failure after radiotherapy and surgery, but to date has not been shown to predict survival. METHODS: This analysis was based on data from 927 patients with clinically localized prostate cancer treated with radiotherapy alone between 1987 and 1998. These patients were stratified into four prognostic risk groups, and multivariate analysis was used to determine the independent impact of pPSA level on PSA failure, progression-free survival (death from any cause after PSA failure), and overall survival (death from any cause). RESULTS: In a multivariate analysis simultaneously considering the prognostic risk group, a pPSA level greater than or equal to 20 ng/mL was associated with a higher risk of PSA failure and worse progression-free and overall survival. CONCLUSIONS: The pPSA level is an independent predictor of survival in patients initially treated with radiotherapy alone.

Adenocarcinoma↗
PubMed2003

The evolving role of pelvic radiation therapy.

Whole pelvic radiotherapy (WPRT) is controversial in the management of prostate cancer. The estimation of the risk of pelvic lymph node involvement in prostate cancer patients will identify those who will potentially benefit from WPRT. Nomograms and equations based on pretreatment prostate-specific antigen (PSA), Gleason score, and/or clinical stage allow clinicians to quickly estimate nodal risk. Most of the studies analyzing WPRT, including a randomized trial from the Radiation Therapy Oncology Group (RTOG), were conducted in the pre-PSA era and did not necessarily include patients at high risk for nodal involvement. The addition of hormonal therapy to WPRT has been shown in 4 major prospective randomized trials to improve survival for some subsets of patients. The preliminary results of RTOG 94-13 show the superiority of WPRT over prostate-only radiotherapy (PORT) in high-risk prostate cancer patients receiving hormonal therapy. For most other solid tumors, the regional lymph nodes are routinely treated by some modality, so it is not surprising that WPRT might benefit a subset of high-risk patients.

Androgen Antagonists↗
PubMed2003

Hormonal therapy and radiotherapy for localized prostate cancer: who, where and how long?

PURPOSE: The results from recent randomized trials were used to identify subpopulations of patients most likely to benefit from long versus short-term hormonal therapy with external beam radiotherapy. MATERIALS AND METHODS: Radiation Therapy Oncology Group study 9413 included 1,323 men with prostate cancer and a risk of lymph node involvement greater than 15%. In this study the hypotheses tested were that whole pelvis radiotherapy would improve progression-free survival (PFS) compared to prostate only radiotherapy and that neoadjuvant and concurrent hormone therapy (N&CHT) with radiotherapy would improve PFS compared to radiotherapy with adjuvant hormone therapy. The conclusions of this study were compared to other studies using long-term hormonal therapy. RESULTS: At a median followup of almost 5 years, when all 4 treatment arms from study 9413 were compared, the group receiving whole pelvis radiotherapy plus N&CHT had a significant PFS advantage (p = 0.008). CONCLUSIONS: Intermediate risk patients should receive N&CHT in combination with external beam radiotherapy while high risk patients require the addition of long-term adjuvant hormone therapy.

Adenocarcinoma↗
PubMed2003

Radiation medicine innovations for the new millenium.

PURPOSE OF THE STUDY: To review technological advances in the field of radiation oncology in the management of benign and malignant diseases. BASIC PROCEDURES: We reviewed major advances in the field of radiation oncology in the past decade with special emphasis on reduction of treatment related toxicities, and technological improvements in planning and delivery of radiation. Modalities reviewed include computerized three-dimensional conformal treatment planning, stereotactic radiosurgery, intensity-modulated radiation therapy, ultrasound-guided transperineal permanent brachytherapy of the prostate, and high-dose rate brachytherapy. MAIN FINDINGS: There have been major technological advances as evidenced by a decrease in treatment-related toxicities and better target definition resulting in higher local control rates. PRINCIPAL CONCLUSIONS: Significant improvements in technique and equipment have firmly positioned radiotherapy as major artillery in the fight against both benign and malignant diseases.

Brachytherapy↗
PubMed2002

Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10.

PURPOSE: To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT. METHODS AND MATERIALS: Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT. RESULTS: Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%. CONCLUSION: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.

Aged↗
PubMed2002

Interim report of toxicity from 3D conformal radiation therapy (3D-CRT) for prostate cancer on 3DOG/RTOG 9406, level III (79.2 Gy).

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406. METHODS AND MATERIALS: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI > or = 15%. For Group 1 patients, the planning target volume (PTV) margins were 5-10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV(1)) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV(2)). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of > or = 3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies. RESULTS: Acute tolerance to 79.2 Gy was excellent with no patients experiencing > or = Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4-4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of > or = 3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of > or = Grade 3 late effects for Group 1 (two cases) is significantly lower (p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (p = 0.0037) than the 12.1 cases expected. CONCLUSION: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.

Adult↗
PubMed2002

Interobserver variability leads to significant differences in quantifiers of prostate implant adequacy.

PURPOSE: To compare the prostate gland volumes and subsequent quantifiers of implant adequacy determined by five separate brachytherapists on postimplant CT images performed 1 day after prostate brachytherapy. METHODS AND MATERIALS: Ten consecutive patients underwent a CT scan 1 day after prostate brachytherapy, using 125I. Four experienced prostate brachytherapists were recruited to participate in this study in addition to the lead author. Each reviewer was asked to independently contour the prostate on sequential axial CT images for all 10 patients using a commercially available treatment planning system. Prostate volumes were calculated along with commonly reported quantifiers of implant adequacy (minimal dose received by 90% of the prostate gland [D(90)] and percentage of prostate volume receiving 100% of prescribed minimal peripheral dose [V(100)]). RESULTS: The mean prostate volume (SD) was significantly different according to the individual reviewers: Rev 1, 50.89 cm(3) (10.6); Rev 2, 55.42 cm(3) (15.79); Rev 3, 40.02 cm(3) (9.95); Rev 4, 56.70 cm(3) (12.16); and Rev 5, 44.52 cm(3) (10.95); p <0.0001. Significant differences were also observed for the mean V(100): Rev 1, 83.4% (5.5); Rev 2, 85.4% (7.6); Rev 3, 89.9% (5.4); Rev 4, 77.7% (6.3); and Rev 5, 81.5 (4.3); p <0.0001; and for the mean D(90), reported as the percentage of the prescription dose: Rev 1, 87.9 (8.9); Rev 2, 92.5 (15.4); Rev 3, 102.6 (16.7); Rev 4, 75.1 (11.3); and Rev 5, 81.4 (8.1); p <0.0001. Reproducibility was measured using the intraclass correlation coefficient (ICC). The reproducibility of the prostate volume was fair (ICC = 0.639) but was poor for the dosimetric quantifiers (V(100) ICC = 0.344 and D(90) ICC = 0.275). CONCLUSION: Significant interobserver differences in prostate volume defined on postimplant CT scans were observed. These differences led to significant differences in commonly used dosimetric quantifiers according to the individual reviewer. Until a greater degree of agreement among reviewers can be established, inferences concerning postimplant CT-based dosimetric analysis will be problematic at best. Additional efforts to increase interobserver agreement are required.

Brachytherapy↗
PubMed2002

The effect of beam energy and number of fields on photon-based IMRT for deep-seated targets.

PURPOSE: To examine the influence of energy and number of beams on nontarget dose when using intensity-modulated radiation therapy (IMRT) to treat deep-seated targets. METHODS AND MATERIALS: Ten patients with prostate cancer (36-226 cc) treated locally to 75.6 Gy were studied. IMRT plans were created for 6-, 10-, and 18-MV photons using 4, 6, 9, and 11 coplanar nonopposed fields. Plans, normalized to cover 95% of the target volume, were analyzed using: (a) conformity index (CI) at 105%, 100%, 95%, 90%, 80%, 70%, 50% of prescribed dose; (b) prescription isodose line (PI); (c) minimum dose to target (Tar(min)); (d) maximum dose to tissue (Tis(max)); (e) dose to rectum/bladder/penis bulb; (f) integral nontarget dose (ID). Because CI evaluates dose independent of location, tissue also was divided into "near region" (NR: 1-cm-thick shell surrounding target) and "far region" (FR: tissue minus NR) volumes that were evaluated at the same levels as CI. RESULTS: The target and sensitive structure metrics were the same for all plans. However, although there was little difference in NR volume exposed to dose, regardless of energy or number of fields, there was a significant increase in FR volume exposed to dose, at all levels, for low energy/few field plans compared to high energy/many fields (e.g., > 50 cc >or= 65 Gy). This effect disappeared with >or= 9 fields regardless of energy. CONCLUSION: With IMRT, the use of 6 MV photons with less than 9 fields may result in an increase in dose in regions distant from the target volume (e.g., near the skin surface), even though the CI and sensitive structure metrics may indicate good conformance of high dose to the target volume itself. The clinical significance of this increased dose distant from the target, in terms of complications, remains to be determined.

Humans↗
PubMed2002

Prostate-specific antigen in prostate cancer: a case study in the development of a tumor marker to monitor recurrence and assess response.

The serum marker known as prostate-specific antigen (PSA) has established itself as the most important tool for the early detection of prostate cancer. However, more recent data indicate that (post-treatment) PSA and PSA kinetics can be used to predict the outcome of a variety of therapeutic interventions including radical prostatectomy, radiation therapy, androgen deprivation, and treatment of hormone-refractory prostate cancer. PSA recurrence after radiation therapy is now accepted as a harbinger of developing metastatic disease. The American Society for Therapeutic Radiation Oncology (ASTRO) consensus definition is the most widely accepted definition of failure after radiation therapy. Rather than using a specific PSA cutoff, three consecutive PSA rises was felt to be a more reliable indicator of biochemical failure. The PSA nadir (the lowest PSA level achieved after therapeutic intervention) also appears to correlate with the likelihood of remaining disease-free. Similarly, a rapid doubling time is a significant predictor of developing distant metastases. The most appropriate definition for biochemical (PSA) failure following radical prostatectomy is usually considered to be a non-zero value. As is the case after radiotherapy, there appears to be a relationship between the rate of rise of the PSA and the risk of distant failure following radical prostatectomy. In patients with metastatic disease, multiple studies appear to indicate that a fall in PSA, however measured, appears to be predictive of improved outcome in prostate cancer patients treated with androgen deprivation. Multiple reports of trials in the treatment of hormone-refractory prostate cancer (HRPC) appear to substantiate the observation that patients who have a greater than 50% decline in PSA have an improved survival. Correlation of PSA declines with other markers of clinical benefit, including clinically significant "subjective" end points such as pain control, have strengthened the argument that a PSA decline can serve as an intermediate endpoint in clinical trials involving HRPC patients.

Humans↗