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Biomedical subjects

J M Krall

Publications and source records attributed to J M Krall.

At least 37 records · Page 2Linked to original sources
PubMed1989

Hormonal cytoreduction in locally advanced carcinoma of the prostate treated with definitive radiotherapy: preliminary results of RTOG 83-07.

RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end-points of this study include tumor clearance rate, effect on serum testosterone, local-regional control, disease-free interval, and survival. Eligible patients were those with histologically confirmed locally advanced adenocarcinoma, clinical Stage B2 and C without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients with medical conditions potentially predisposing to cardiovascular (thromboembolic) sequelae of endocrine therapy were not eligible. Patients were stratified by clinical stage, histological grade, and nodal status and were randomized to receive either Megestrol 40 mg PO tid or Diethylstilbestrol 1 mg PO tid. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44 to 46 Gy, 1.8 to 2 Gy per day to the regional lymphatics followed by a boost to the prostate consisting of 20 to 25 Gy, 1.8 to 2 Gy per day to a total of 65 to 70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 197 were analyzable. Correlation of the incidence of drug related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs 7%) and fluid retention (21% vs 6%). The incidence of thromboembolic phenomena was comparable (8% vs 5% in the Megestrol arm). Although patients on the DES arm demonstrated a significantly greater median decrease in testosterone level, correlation of the treatment assigned to the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 3 years only 6.5% of the evaluable patients manifested evidence of local failure. The results of the study indicate comparable efficacy (using tumor clearance as an end-point) of DES and Megestrol. While DES appears more effective in suppressing testosterone it is also associated with a higher incidence of toxicity. The cytoreduction (using either DES, Megestrol, or an alternative regimen) concept remains to be tested in a Phase III study comparing it to radiotherapy alone.

Adenocarcinoma↗
PubMed1989

Analysis of independent variables affecting survival after recurrence of prostate cancer.

Two hundred and sixty-six patients developed recurrence after external beam radiation therapy for Stage B or C prostate cancer. The median survival from the time of recurrence was 30 months, the 5-year actuarial survival was 22% and the 8-year actuarial survival was 13%. The original stage influences survival after recurrence. Median survival is 35 months for Stage B and 27 months for Stage C. Five-year actuarial survivals are 31% for Stage B and 16% for Stage C. The site of recurrence (infield or metastatic) influences survival after recurrence. Median survival is 33 months for infield and 25 months for metastatic. Five-year actuarial survival is 30% for infield and 17% for metastatic. The time of recurrence influences survival after recurrence, comparing survival in patients recurring in the first year after treatment, to patients recurring in the second or later years after treatment. Median survival after recurrence is 14 months for those who recur in the first year, 32 months for those who recur later. Histologic grade influences survival after recurrence. Median survivals are 49 months for well differentiated, 31 months for moderately differentiated, and 23 months for poorly differentiated. Cox regression analysis indicates that original stage, site of recurrence (local vs. metastatic), time of recurrence after therapy, and histologic grade are all independent variables influencing survival after recurrence (p = less than .01). This study supports the aggressive treatment of prostate cancer to prevent recurrence and provides a means of estimating prognosis for patients who suffer a recurrence of their prostate cancer after treatment.

Humans↗
PubMed1989

Fast neutron radiotherapy in the treatment of locally advanced adenocarcinoma of the prostate. Clinical experience and future directions.

The major clinical experiences using fast neutrons for the treatment of locally advanced prostatic carcinomas are reviewed. In all trials to date, there is evidence that treatment regimens employing a component of fast neutrons achieve results that equal or surpass those obtainable with conventional megavoltage external beam irradiation for comparable groups of patients. Late complications of neutron treatment have not exceeded the complication rate expected by photon irradiation. The structure of the current Radiation Therapy Oncology Group phase III randomized trial comparing neutron and photon treatment of patients with stages B2, C, and D1 disease is discussed.

Adenocarcinoma↗
PubMed1988

Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06.

From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage A2 (occult disease with more than 3 positive chips and poorly differentiated tumor) and Stage B without clinical (lymphangiogram) or biopsy evidence of lymph node involvement. The patients were randomized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180-200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy. As of February, 1988, the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control, incidence of distant metastases, ned (no evidence of disease) survival and survival. The results of the study revealed no statistically significant benefit of elective pelvic irradiation.

Aged↗
PubMed1988

The outcome of treatment of 313 patients with T-1 (UICC) prostate cancer treated with external beam irradiation.

Three hundred and thirteen patients with UICC T-1 N-0 M-0 prostate cancer were treated with external beam irradiation in 1973 and 1974 or in 1978, and their outcome determined 3-10 years after treatment. Survival over the first 5 years was comparable to that expected for a group of age matched normal males (77% vs. 81%), but during the second 5-year interval, there was a decrease in survival below that expected (51% vs 62%), a reflection of death in patients who developed metastasis as a first recurrence (18%). Overall, 72% of patients were free of any recurrence at 5 years and, 88% free of infield recurrence. The development of metastatic recurrence was significantly related to grade; at 5 years 87% of grade I, 79% of grade II and 69% of grade III patients were free of metastasis. There was a trend for increased local recurrence with increasing grade, but it was not statistically significant. There was a dose/response relation for complications, and radiation doses above 6500 cGy are associated with an increase in complication from 6% to 11% (p = .09). Complications requiring hospitalization for evaluation or management occurred in 30 (10%) of 313 patients. There were no deaths from complications and less than 2% of patients required surgical correction of complications. External beam radiation offers the patient with early prostate cancer a favorable opportunity for cure without the morbidity of impotence, incontinence, and occasional death experienced following LND and radical prostatectomy. Lymph node dissection does not seem necessary for most patients with T-1 prostate cancer as the positive yield in those with Grades I and II cancers is less than the complications of the procedure, and extensive involvement can be detected by non-invasive means.

Adult↗
PubMed1987

Eight years experience with neutron radiotherapy in the treatment of stages C and D prostate cancer: updated results of the RTOG 7704 randomized clinical trial.

The records of 91 patients enrolled between June 1977 and April 1983 in the Radiation Therapy Oncology Group (RTOG) randomized study investigating fast neutron radiation therapy in the treatment of locally advanced prostate cancer were reviewed. Patients with stages C and D1 adenocarcinoma were randomized to receive either combined fast neutron and photon irradiation (mixed-beam) or conventional photon irradiation alone. Survival (actuarial) at eight years for the mixed-beam cohort was 63% vs 13% for the patients receiving photons alone (P = .01). Corresponding "determinental" survival rates, adjusted by exclusion of intercurrent deaths, were 82% and 54%, respectively (P = .02). Freedom from locally recurrent prostate cancer was 77% for mixed-beam patients and 31% for patients receiving photons alone (P less than .01). Analyses of outcomes accounting for all major prognostic determinants confirm the greater efficacy of mixed beam treatment with P less than .05 for survival, determinental survival, and local control.

Adenocarcinoma↗
PubMed1987

Prognostic significance of nodal involvement in locally advanced (stage C) carcinoma of prostate--RTOG experience.

A total of 500 patients with extracapsular extension (clinical Stage C) carcinoma of the prostate received definitive radiotherapy directed to the prostate and the regional lymphatics. Pretreatment evaluation of the regional lymphatics was optional and was done in 245 patients who underwent either staging laparotomy or lymphangiography. The remaining 255 patients had no nodal evaluation. In 72 of the node-evaluated patients there was evidence of spread to the pelvic lymphatics and in 173 patients lymph nodes were negative. The three populations (lymph nodes-not evaluated, lymph nodes-involved, and lymph nodes-not involved) were analyzed as to the distribution of the recognized prognostic variables and compared as to the study end points (locoregional failure, incidence of distant metastases, disease-free survival, and survival).

Carcinoma↗
PubMed1987

Radical prostatectomy or radiotherapy in carcinoma of prostate. The dilemma continues.

Evaluation of the efficacy of radical prostatectomy versus radiotherapy in carcinoma of the prostate has been compromised by the scarcity of data in comparable populations. A nationwide search was conducted to compile the available data on the use of radiotherapy in lymphadenectomy-staged patients. The assessed population consists of patients with tumor confined to the gland (Stages A2 and B), negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase level who received external beam radiotherapy with curative intent. To provide a broad spectrum of experiences, the search included patients from a large number of institutions including Stanford University, Washington University (St. Louis), those participating in the Radiation Therapy Oncology Group, and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients were identified. No selection criteria other than the aforementioned were applied. The patients were treated consecutively during the survey period. In sharp contradistinction to the reported results of the VA Uro-Oncology Group the analysis indicates a less than 10 per cent probability of progression within the first five years after completion of treatment. Nationwide, the outcome of radiotherapy-treated patients appears to be equivalent to the comparable surgically treated population.

Humans↗
PubMed1987

Prognostic factors in carcinoma of the prostate--analysis of RTOG study 75-06.

A total of 566 evaluable patients were accessioned to a phase III RTOG study of extended field irradiation in carcinoma of the prostate from 1976 to 1983. Eligible patients were those with locally advanced disease, either clinical Stage C or clinical Stage A2 or B with pelvic lymph node involvement. The treatment consisted of irradiation of the regional lymphatics followed by a boost to the prostate. The data have been analyzed extensively to identify variables of potential prognostic significance. The assessed factors include tumor size, clinical stage, the degree of histological differentiation, nodal status, serum acid phosphatase status, hormonal management status, age, and race. These factors have been assessed as to their interdependence and correlation with the clinical course (study endpoints) using univariate analyses and Cox's Regression model. Significant interdependence of tumor size and Gleason score and tumor size and acid phosphatase was identified. The population receiving hormonal management either prior to or during radiotherapy had a significantly higher proportion of high grade tumors. Correlation of the assessed variables and the study endpoints (local control, incidence of distant metastases, NED survival, survival) singled out the degree of histological differentiation as the most powerful prognostic factor for all the endpoints. Age proved a useful predictor of local control (younger patients failed at a significantly higher rate), as did tumor size. Elevation of serum acid phosphatase correlated well with the incidence of metastatic disease but was not a useful predictor of survival. Tumor size and hormonal management status correlated well with the incidence of metastatic disease but only when analyzed separately from other factors. Their prognostic value was absent when Cox regression analysis was applied. Nodal status did not correlate well with any of the study endpoints, indicating then that in patients with clinical Stage C disease, treated with definitive radiotherapy to the prostate and regional lymphatics, this parameter may have limited prognostic usefulness. Although patients who received concomitant hormonal management had a significantly higher proportion of high grade lesions, their clinical course fared favorably in comparison with the population not receiving concomitant hormonal management. This may indicate a beneficial effect of adjuvant hormonal treatment which needs to be tested in a prospective study.

Acid Phosphatase↗
PubMed1987

Correlation of radiotherapeutic parameters and treatment related morbidity in carcinoma of the prostate--analysis of RTOG study 75-06.

Treatment related morbidity, recorded in patients entered onto a RTOG phase III study (testing the value of periaortic irradiation in locally advanced carcinoma of the prostate), has been correlated with radiotherapeutic parameters to identify and quantify the relationship with treatment volumes, doses, and techniques. Between 1976 and 1983 a total of 526 analyzable cases were entered onto the study. The study design entailed randomization to either pelvic irradiation followed by a prostate boost or pelvic and periaortic irradiation followed by a prostate boost. Periaortic irradiation was not associated with a significantly increased incidence of bowel injuries manifested by diarrhea. No correlation between the total dose to the regional lymphatics (ranging from 4400 to 5100 cGy) and the incidence of bowel and bladder injuries could be established. Doses to the prostate in excess of 7000 cGy have not resulted in a significantly increased incidence of bladder injuries, but have been associated with a significant increase in the incidence of bowel injuries manifested by diarrhea. The techniques of pelvic irradiation did not seem to significantly influence the incidence of bowel or bladder complications. The technique of delivery of the prostatic boost did seem to influence the incidence of bowel injuries. This refers to the lateral boost technique and the perineal boost technique which have been associated with a higher incidence of diarrhea. All of the conclusions based on this analysis are applicable only to treatment volumes and dose ranges used in this study and to conventional fractionation of 180 to 200 cGy per day.

Cystitis↗
PubMed1987

Correlation of radiotherapeutic parameters and treatment related morbidity--analysis of RTOG Study 77-06.

The current report is an updated and detailed analysis of treatment related morbidity in RTOG 77-06, a Phase III randomized study comparing prostatic irradiation versus pelvic irradiation followed by a prostatic boost, in patients with Stage A2 and B carcinoma of the prostate without evidence of nodal involvement. A total of 453 analyzable cases were accrued from 1978 to 1983, when the study was closed. All cases of treatment related morbidity were classified as to severity (using a clinical severity grading system). The data were then correlated with a number of radiotherapeutic parameters including treatment volumes (fields), doses, and techniques. Overall, pelvic irradiation, compared to prostate irradiation only, was not associated with a significantly increased incidence of treatment related morbidity. Within the range of pelvic doses used in this study a significant dose effect could not be detected. Total doses to the prostate of more than 7000 cGy were associated with an increased risk of rectal bleeding. Certain treatment techniques, (AP/PA irradiation of the pelvic lymphatics) were associated with an increased incidence of bowel complications.

Humans↗
PubMed1987

A ten year follow-up of 682 patients treated for prostate cancer with radiation therapy in the United States.

This report extends the follow-up of patients studied in the Patterns of Care Survey of Prostate Cancer treated in the United States between 1973 and 1975 from a maximum of 5 years to a maximum of 10 years. Survival for 60 Stage A patients was the same as expected for their age distribution (83% at 5 years and 62% at 10 years). Survival for 312 Stage B patients was 73% at 5 years and 46% at 10 years and for 296 Stage C patients was 58% at 5 years and 38% at 10 years. Infield recurrence was determined by clinical means, at 5 years 97% of Stage A patients, 86% of Stage B patients, and 74% of Stage C patients were free of local recurrence. At 10 years 97% of Stage A patients, 74% of Stage B patients, and 69% of Stage C patients remained free of local recurrence. Patients with Stage B and C cancer who developed their first failure infield show a long-term survivorship after recurrence of 40% and 20% respectively. This is in contrast to Stage B and C patients who develop a first recurrence at a metastatic site where the rate of progress to death was slower in Stage B patients than for those with Stage C disease (mean survival 32 months versus 19 months), but eventually all are dead by 7 years after recurrence. Complications were infrequent, actuarial analysis shows 93% of patients free of serious complications at 5 years and 89% free at 10 years. There were 14 patients (2%) whose complications required surgical correction and 2 of the 682 patients died of complications.

Actuarial Analysis↗
PubMed1987

Correlation of pre-treatment transurethral resection and prognosis in patients with stage C carcinoma of the prostate treated with definitive radiotherapy--RTOG experience.

Four hundred and ninety-four patients with clinical Stage C carcinoma of the prostate, who were entered onto a phase III RTOG study, have been analyzed as to the potential effect of the pre-treatment transurethral resection (TUR) of the tumor. Treatment consisted of definitive irradiation to the prostate (6500-7000 cGy) and regional lymphatics (4500-5000 cGy). A total of 202 patients underwent pre-treatment TUR. This population was compared with the remaining 292 patients as to the rate of locoregional failure, incidence of distant metastases, disease-free survival, and survival. The TUR population fared significantly worse for all four end-points. To account for uneven distribution of recognized prognostic factors the results were then adjusted using stratified Mantel-Haenszel tests. The stratification process resulted in a reduced level of significance in the differences between the two populations. However, a trend toward a higher incidence of distant metastases could be observed within most strata. The trend was most pronounced in subpopulations characterized by Gleason score 6-7 and normal serum acid phosphatase (SAP). For the population characterized by Gleason score 6-10 and normal SAP, the differences in the incidence of distant metastases retained statistical significance. Whether these findings are secondary to tumor dissemination during TUR or are due to incompletely identified selection biases remains to be demonstrated in future (prospective) studies.

Clinical Trials as Topic↗
PubMed1987

Definitive radiotherapy in resectable (stage A2 and B) carcinoma of the prostate--results of a nationwide overview.

To evaluate the efficacy of definitive radiotherapy in a population of patients with carcinoma of the prostate who satisfy the customary selection criteria for radical prostatectomy, a nation-wide search was conducted. The assessed population consists of patients with clinical Stage A2 and B carcinoma of the prostate, negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase. The search included patients from Stanford University, Washington University in St. Louis, those participating in the Radiation Therapy Oncology Group and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients satisfying the selection criteria received definitive radiotherapy during the surveyed period. The end-point of analysis was the time to progression (distant metastases). The results of the analysis indicate a very low (less than 10%) probability of progression within the first 5 years after completion of treatment. Contrary to the recent report from the VA Uro-Oncology Group the study demonstrates a comparable outcome in radiotherapeutically and surgically treated patients.

Humans↗
PubMed1986

Extended field (periaortic) irradiation in carcinoma of the prostate--analysis of RTOG 75-06.

From 1976 to 1983 the Radiation Therapy Oncology Group conducted a study of extended field (periaortic) irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage C tumor with or without evidence of pelvic lymph node involvement and also those with Stage A-2 and B with evidence of pelvic lymph node involvement. The stratification criteria included histological grade, clinical stage, absence or presence of hormonal manipulation, and method of lymph node evaluation (lymphangiogram vs. laparotomy vs. no nodal evaluation). The patients were randomized to either receive pelvic irradiation followed by a boost to the prostate or pelvic and periaortic irradiation followed by a boost to the prostate. The prescribed daily dose was 180-200 rad to a total midplane dose to the regional lymphatics to 4000-4500 rad. The prostatic boost target volume was to receive additional 2000-2500 rad bringing the total dose to that area to a minimum of 6500 rad. A total of 523 analyzable patients have been accessioned to the protocol. Four hundred forty-eight of these are known to have received treatment per protocol. Median follow-up is 4 years and 3 months. The analyzable patients were evaluated for the incidence of distant metastases, NED survival and survival as a function of treatment arm. No statistically significant differences between the treatment arms could be documented. Similarly, no significant difference between treatment arms could be documented within a number of subpopulations such as those characterized by a particular grade, hormonal status, stage, age, acid phosphatase level, etc. The results of the study revealed no apparent benefit of elective periaortic irradiation in patients with detectable disease confined to the pelvis.

Aged↗
PubMed1985

Fast neutron radiotherapy for locally advanced prostate cancer: results of an RTOG randomized study.

Between June 1977 and April 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized study investigating fast neutron radiation therapy in the treatment of patients with locally advanced (Stage C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation therapy or fast neutron irradiation used in a mixed-beam treatment schedule (neutron/photon). A total of 91 analyzable patients were entered in the study; 78 of them were treated without major protocol deviations. The two treatment groups were balanced in regard to all major prognostic variables. Actuarial curves for "overall" survival, "determinantal" survival and local/regional control are presented both for the entire group of 91 patients and the 78 patients treated within protocol guidelines. The overall local/regional tumor recurrence rate is 7% for the mixed-beam treated group of patients and is 22% for the photon (X ray) treated group of patients. The difference is statistically significant at the p = 0.05 level. For the entire group of 91 evaluable patients, the 5-year "overall" survival rate is 62% for the mixed-beam-treated group and 35% for the photon-treated group. This difference is also statistically significant (p less than 0.05). However, this statistical significance is lost when the smaller number of patients treated strictly within protocol guidelines is considered. The significance is regained (p less than 0.02) when one looks at "determinantal" survival, which uses active cancer at time of death as the failure endpoint. This study demonstrates that a regional treatment modality, in this case mixed-beam irradiation, can influence both local/regional tumor control and survival in patients with locally-advanced adenocarcinoma of the prostate gland.

Adenocarcinoma↗
PubMed1985

Patterns of care studies: dose-response observations for local control of adenocarcinoma of the prostate.

Five hundred seventy-four patients with prostate cancer treated by external beam radiation therapy in the United States in 1973 to 1975 have been analyzed comparing radiation dose with in-field recurrence. Dose-response effects are observed for all cases (p = less than .05) and T-2 and T-3 tumors, but not for T-0, T-1 and T-4 tumors. For doses calculated at the center of the prostate, these observations suggest optimal control is obtained at no more than 6000 rad for T-0 and T-1 tumors; 6000-6500 rad for T-2 tumors; 6500-7000 rad for T-3 tumors; and that greater than 7000 rad is required only for T-4 tumors. The paraprostatic dose calculated at a point 4 cm lateral to the center of the prostate also shows a correlation of dose with infield failure for all cases (p = .01). Observations in individual T states suggest optimal control is obtained at no more than 6000 rad for T-0, T-1 and T-2 tumors, 6500-6999 rad for T-3 and greater than or equal to 7000 rad for T-4. These data suggest that for T-2 and T-3 cancers, extension in the periprostatic region must be treated. A comparison of central dose vs. stage indicates institutional policy rather than cancer volume determines the radiation dose used in treating prostate cancer. A change in institutional policies to treat with optimal doses as indicated by this study would result in an overall increase in local control and a decrease in complications.

Actuarial Analysis↗