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Biomedical subjects

W T Sause

Publications and source records attributed to W T Sause.

At least 73 records · Page 4Linked to original sources

Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group.

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.

Aged↗

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↗

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↗

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↗

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↗

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↗

Analysis of postoperative radiation therapy in stage I through III epithelial ovarian carcinoma.

A retrospective long-term analysis of the results of primary postoperative radiotherapy in 106 women with invasive epithelial ovarian carcinoma is presented. Forty-two women received open-field total abdominopelvic irradiation, and 64 received treatment by various subtotal abdominopelvic techniques. The mean follow-up of living patients in the two groups is 86 and 116 months, respectively. Women who had Federation International Gynecology and Oncology (FIGO) stages I through III-A with no postoperative residual disease, or less than 0.5-cm abdominal and/or less than 2-cm pelvic residual disease formed a favorable group in whom total abdominopelvic irradiation resulted in a 71% 10-year actuarial relapse-free survival rate compared with 40% for those treated by subtotal abdominopelvic techniques (P less than or equal to .0205). The survival improvement due to the total abdominopelvic technique in favorable patients became even more significant (P less than or equal to 0.003) after adjusting for differences in stage, grade, and postoperative residual disease volume (no, or favorable, gross). Increasing grade appeared to be associated with decreasing survival even among favorable patients treated with the optimal technique, although the differences did not approach statistical significance after adjusting for residual disease volume and stage. Surgical bowel complications were equivalent, 7.1% for total abdominopelvic v 8.1% for subtotal abdominopelvic techniques. The addition of intraperitoneal radioactive chromic phosphate increased the surgical bowel complication rate 33% over external pelvic irradiation alone without improving survival. Patients with unfavorable gross residual disease and/or FIGO stages III-B and IV were incurable by any radiation technique. Those with no, or favorable, gross residual tumor constitute a group in whom we believe open-field total abdominopelvic irradiation represents a potentially curative therapy modality.

Actuarial Analysis↗

Breast irradiation following silicone gel implants.

Little information is found in the literature regarding breast irradiation in patients with reconstructed or augmented breasts. From November 1970 to October 1984, we treated ten patients with silicone gel prostheses with external radiation for recurrent disease, or as primary therapy. All patients were treated with megavoltage equipment. Technique and doses varied with the clinical situation, but generally, patients received 5000 rad in five weeks to the breast or mound with opposed tangential fields. The majority of patients had excellent cosmetic results with minimal late skin changes and no fibrosis or contracture. We conclude that, with proper surgical and radiotherapeutic techniques, good cosmetic results can be obtained in these patients, without compromising their therapy.

Adult↗

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Adult↗

Evaluation of the response of unresectable carcinoid tumors to radiotherapy.

Sixteen patients with unresectable primary or metastatic carcinoid tumors were treated with radiotherapy. Objective responses (CR + PR) were documented in 4 of 16 patients (25%). The median survival of the responders was 46 months following radiotherapy, as compared to the 10-month median survival of the entire group of 16 patients. There were five additional patients who improved symptomatically or had minor responses. The seven patients who received the highest doses of radiotherapy (greater than 29 GY), to local or regional treatment ports, had the best response rate (43%). Many patients eventually had objective evidence of relapse or tumor progression within the radiotherapy port, in part reflecting the relatively low radiotherapy doses used in the treatment of the nine patients with abdominal carcinoids. One patient remains disease free at 103 months. Patients who exhibited the carcinoid syndrome appeared to respond less frequently to radiotherapy than patients who did not have ectopic hormone secretion, although the number of patients with ectopic hormone secretion was too small to establish this point in a definitive manner. The results of this study demonstrate that carcinoid tumors respond to moderate doses of radiotherapy in a manner similar to many other epithelial tumors.

Adult↗

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↗

Prostatic carcinoma: 5-year followup of patients with surgically staged disease undergoing extended field radiation.

We analyzed all patients who had undergone pre-radiation staging pelvic lympadenectomy from 1969 to 1979. Of 70 patients with a minimum followup of 5 years 33 had positive and 37 had negative nodes. Three of the 33 patients with positive lymph nodes were alive without disease at the time of our study, compared to 20 of 37 with negative lymph nodes. Our review suggests that extended field radiation has minimal or no impact on the natural history of prostatic carcinoma in patients with positive nodes. Patients with stages T1 and T2 lesions, and negative nodes do well with external beam therapy.

Carcinoma↗

Technical advances in radiation therapy.

Substantial advances have been made in radiation therapy. Many of these advances can be applied in most radiation therapy departments without expensive improvements in equipment. Changes in radiation fractionation, chemotherapeutic sensitization, intraoperative radiation, and interstitial implants can be performed with experience and improved physician training in most medium-sized departments. Advances that require investments in expensive equipment such as particle radiation and hyperthermia will need to be evaluated at designated treatment centers.

Brachytherapy↗

Large cell neuroendocrine tumors of the lung. Clinical significance and histopathologic definition.

Twenty-five cases of neuroendocrine tumors of lung, including bronchial carcinoids (eight), malignant (atypical) carcinoids (nine), and large cell undifferentiated carcinomas (LCAC) with neuroendocrine differentiation (eight) were analyzed. All carcinoids (BC) could be diagnosed by light microscopy; all patients with these tumors are alive without disease. Five of nine malignant carcinoids (MC) could be recognized histologically; four of nine were called LCAC and required electron microscopy for diagnosis. Survival correlated best with stage of diagnosis. High-grade neuroendocrine carcinomas (LCAC-NE) required electron microscopy for their diagnosis. Seven were LCAC histologically; one was diagnosed as malignant carcinoid (MC). Such tumors resemble small cell anaplastic carcinomas ultrastructurally and behaviorally. All eight patients with such high-grade tumors died of their disease; three of eight had no nodal metastases at the time of resection. This experience suggests it is clinically important to distinguish neuroendocrine neoplasms since behavior is predictable on the basis of morphology.

Adult↗

Dose response analysis of pediatric neuroblastoma to megavoltage radiation.

Children with neuroblastoma treated in Salt Lake City from 1966 through 1982 were analyzed in an attempt to develop guidelines for external beam radiation. Particular attention was addressed to time-dose relationships in those patients with residual disease post-resection (Stages II and III). Altogether, 76 patients were analyzed and survival rates were: Stage I--100%; Stage II--84%; Stage III--69.2%; Stage IV--14.3%; Stage IV-S--71.4%. Survival rates were correspondingly better in younger children and in infants. Indications for postoperative radiation therapy in this population were: unresectable or gross remaining tumor; residual tumor in neural foramina; tumor spill during surgery; positive regional lymph nodes or positive surgical margins. Local control was achieved in a majority of patients undergoing surgery and radiation for limited disease. In children younger than 1 year of age, no local failures were observed at doses above 1200 rad. In children between 1-2 years of age, no local failures were observed with doses as low as 1440 rad. In children older than 3 years, local failures were observed up to 4500 rad.

Adolescent↗

Testicular seminoma--analysis of radiation therapy for stage II disease.

Controversy exists regarding the extent of radiation to be delivered in patients with stage IIA testicular seminoma. We analyzed patients treated at our hospital radiation center through February 1981 in an attempt to evaluate the contribution of supradiaphragmatic radiation therapy in this disease. Six patients with stage IIA disease were not treated above the diaphragm and none failed, while 50 with stage I tumor in whom no lymphangiogram or computerized tomography scan was performed were treated below the diaphragm and none failed in the mediastinum or supraclavicular area. We agree with other investigators that radiation therapy above the diaphragm in patients with stage IIA testicular seminoma may be unnecessary.

Dysgerminoma↗