Omar M. Salazar

High dose radiation therapy in the treatment of malignant gliomas: final report.

Abstract One hundred patients with supratentorial malignant gliomas were prescribed to receive postoperative whole brain irradiation with doses ≥5000 rad; 41 had astrocytoma grade III and 59 had grade IV tumors. The median survival was 91 weeks for patients with grade III tumors and only 42 weeks for those with grade IV (p For patients with grade IV tumors the median survival was 30, 42 and 56 weeks respectively, these differences were significant (p The use of higher radiation doses was well tolerated; it did not compromise the quality of survival, and did not yield normal brain tissue necrosis. However, these doses did not seem to alter the total survival of patients, nor did they seem capable of sterilizing these tumors. Histopathological changes that were observed in normal brain tissue that was irradiated with 7000–8000 rad suggest that increasing total doses beyond this range might attain tumor sterilization, but could also lead to frank radiation necrosis in these patients.

Uterine sarcomas: natural history, treatment and prognosis.

Seventy‐three documented cases of uterine sarcoma were treated at the University of Rochester Strong Memorial Hospital from 1955 to 1975. Thirty‐three patients (45%) were treated with surgery only [S], 31 (43%) with surgery and radiation [S + R], and 9 (12%) with radiation alone [R]. A review of the literature with over 900 cases was also performed. Several important issues regarding these rare tumors are addressed, such as the prognosis of the several histologic variants, the role of radiation therapy in their management and what perhaps may constitute a comprehensive therapeutic approach. These tumors are characterized by local aggressiveness and early widespread dissemination. There are three main histologic varieties: mixed mesodermal sarcoma (MMS), leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS). Of the three, MMS was the most common, seen in 60% of the cases; LMS occurred in younger patients and tended to be localized to the uterine corpus (Stage I) in 80% of the instances. Tumor extent at diagnosis was the main prognosticator for survival in uterine sarcomas; patients with Stage I tumors had a significantly lower incidence of recurrences, as well as a better survival than patients with more advanced tumors. Stage‐by‐stage, there were no significant differences in survival among the pathologic variants. To ensure adequate staging, a surgical procedure is recommended first whenever possible. Adjuvant radiation therapy significantly improved disease controlability in the pelvis, although it may not have dramatically affected the final outcome. In addition to pelvic irradiation, some form of systemic therapy should be administered to decrease distant metastases.

Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors: Final radiation therapy oncology group report

This is the final analysis of Protocol #78–10 which explored increasing single‐doses of half‐body irradiation (HBI) in patients with multiple (symptomatic) osseous metastases. When given as palliation, HBI was found to relieve pain in 73% of the patients. In 20% of the patients the pain relief was complete; over two thirds of all patients achieved better than 50% pain relief. The HBI pain relief was dramatic with nearly 50% of all responding patients doing so within 48 hours and 80% within one week from HBI treatment. Furthermore, the pain relief was long‐lasting and continued without need of retreatment for at least 50% of the remaining patients life. These results compare favorably with those obtained by the Radiation Therapy Oncology Group (RTOG) using several conventional daily fractionated schemes on similar patients in a prior study (RTOG #74–02). HBI achieves pain relief sooner and with less evidence of pain recurrence in the irradiated area than conventionally treated patients. The most effective and safest of the HBI doses tested were 600 rad for the upper HBI and 800 rad for the lower or mid‐HBI. Increasing doses beyond these levels did not increase pain relief, duration of relief, or achieved a faster response; however, the increase in dose was associated with a definite increase in toxicity. Single‐dose HBI was well tolerated with no fatalities seen among 168 treated patients. A comprehensive premedication program has proven to decrease the acute radiation syndrome to very acceptable levels. There were excellent responses found in practically all tumors treated, but especially breast and prostate among which over 80% of all patients experienced pain relief, 30% in a complete fashion. Single‐dose HBI emerges as one of the safest, fastest, and more effective palliative tools for intractable cancer pain in modern radiation oncology. Cancer 58:29–39, 1986.

Systeniic (half-body) radiation therapy: Response and toxicity

Abstract Systemic (half-body) Radiation Therapy (SHBRT) was employed in 40 patients with advanced cancer. The upper half body was irradiated in 23 patients; the lower half was irradiated in 12 (6 of these also received radiation to the upper segment); 5 patients received radiation to the middle segment (abdomen and pelvis). All patients received a single dose of 800 rad delivered at low dose rates (30–40 rad/min) with a 10 MeV iincer accelerator. The “acute radiation syndrome” occurred mainly with irradiation of the upper half of the body; it consisted of nausea and vomiting, increases in temperature and pulse rate and a drop in blood pressure. The onset of this syndrome occurred shortly after the procedure and sometimes lasted for up to 10 hr. In the last 6 patients treated a comprehensive premedication program which includes the administration of glucocorticoids, antiemetics and adequate hydration has reduced these acute symptoms to a minimum. Irradiation of one half of the human body is hematologically safe; blood counts return to normal within 6–8 weeks after the procedure. The main limiting factor of upper body irradiation is pulmonary toxicity; single doses of 800 rad (uncorrected for lung transmission) may lead to a 10–20% incidence of fatal radiation pneumonitis. Caution is advocated and the total dose proposed at the present time is 600–700 rad corrected for long transmission; minimal pulmonary toxicity has been reported with this dose. Systemic radiation therapy given for pain palliation achieves its goal in over 8096 of all patients. This pain relief is complete in over 40% of the patients and occurs dramatically within the first 24–48 hr. Furthermore, this technique has proved effective in reducing large tumor collections for a limited period of time (average of 3 months); pathologic confirmation of severe radiation damage inflicted on tumor cells has been obtained. This report analyzes Phase I-II (toxicity-response) studies in patients with overt metastases and speculates on the potential uses of this therapeutic modality for occult deposits.

Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: A randomized phase III trial of the international atomic energy agency (IAEA)

Abstract Purpose: To find the fastest and most effective/efficient method to economically deliver fractionated half-body irradiation (HBI) for widespread (WS), symptomatic, metastatic bone cancer. Methods and Materials: A Phase III trial with 3 HBI arms: (Arm A) Control (15 Gy/5 fractions/5 days); (Arm B) Hyperfractionation (HF) (8 Gy/2 fractions/1 day); (Arm C) Accelerated HF (12 Gy/4 fractions/2 days). Six countries randomized 156 patients (all with WS bone metastases): 51, 56, and 49 patients to Arms A, B, and C, respectively. There were 72 (46%) breast, 50 (32%) prostate, 9 (6%) lung, and 25 (16%) miscellaneous primary tumors. Initial performance status (PS) was 1–2 in 101 (65%) and PS 3–4 in 55 (35%). The lower, upper, and middle halves of the body were treated 79, 68, and 9 times. Results: Pain relief was seen in 91% of patients (45% complete [CR] and 46% partial [PR]) within 3–8 days. Overall (OS), median (MST), and pain-free (PFS) survival was 174, 150, and 122 days. Breast tumors had a higher OS (279 days) than that of other primary tumors, but when analyzed by treatment, was not significantly different than prostate tumors in Arm A. No survival differences were found in patients with PS 1–2 vs. 3–4, CR vs. PR, bone with/without visceral metastases, or by the number of metastases ( 15 bone lesions). Quality of life (QOL) assessed by the percent of the remaining life free of pain was 71%; furthermore significant improvements in PS, pain, and narcotic scores were seen after HBI. Toxicity was very acceptable (41% none, 50% mild/moderate, 12% severe but transitory); more was seen with upper HBI. Conclusion: In terms of response, time to response, OS, MST, PFS, QOL, and toxicity, schedules for Arms A and C were similar for all but prostate primaries. Schedule for Arm B, which delivered the lowest biologic dose in the shortest time, had significantly worse results in pain relief, OS, MST, PFS, and QOL. Results indicate that, for most primary tumor types (except prostate), delivering two HBI daily doses of 3 Gy in 2 consecutive days is as effective as delivering a daily dose of 3 Gy for 5 consecutive days. Thus, this is a faster and much more convenient HBI schedule for the palliation of pain in widespread cancer.

Uterine sarcomas. Analysis of failures with special emphasis on the use of adjuvant radiation therapy

There were 47 failures among 73 verified cases of uterine sarcoma reported at the University of Rochester Tumor Registry from 1955 to 1975; they constitute the subject of this report. Of 33 patients initially treated with surgery only [S], 19 patients (58%) failed; 20 of 31 patients (65%) treated with surgery and radiation [S + R] failed; 8 of 9 patients (89%) treated by radiation alone [R] failed. According to pathology, failures occurred in 33 of 44 patients (75%) with mixed mesodermal sarcomas (MMS), 7 of 20 patients (35%) with leiomyosarcoma (LMS), 4 of 6 patients with endometrial stromal sarcomas (ESS), and 3 of 3 patients with other types of sarcoma. Once corrected by stage, there were no significant differences in failure rates, spread patterns or survival among these main histologic variants. Twenty of 41 patients (56%) with Stage I tumors failed with an average failure time of 32 months. Twenty‐seven of 32 patients (84%) with Stages II, III, and IV tumor failed; their average failure time was only 9 months. The mean failure time for both the patients treated with [S] and [S + R] was 22 months; for patients treated by [R] it was 3 months. Isolated pelvic failures constituted only 4% of all failures, failures both in the pelvis and in distant sites, 49%, and distant metastases, 47%. There was a marked decrease in pelvic failures in patients treated with [S + R] when compared to those who received [S]. Adjuvant radiation proved to increase tumor control in the pelvis but did not influence the final outcome because over 90% of all failures developed distant spread outside the pelvis. The most common distant failures were in the upper abdomen (mainly omentum and peritoneum) and in the lungs. Lung metastases alone was the only site of failure in 16% of the instances. A comprehensive treatment approach based on the spread and failure patterns will be proposed.

The state of the art toward defining the role of radiation therapy in the management of small cell bronchogenic carcinoma.

Abstract This review article discusses the “state of the art” in defining the role of radiotherapy in managing small cell bronchogenic carcinoma (SCBC). It reviews the history of therapeutic approaches to SCBC. Several issues of particular interest to limited disease are discussed. They are: local radiation therapy for limited disease, combined radiation therapy and chemotherapy in limited disease, combination chemotherapy alone for limited disease, and an overview of the treatment of limited disease. A section on extensive disease discusses the role of radiation therapy and chemotherapy, chemotherapy only for extensive disease, and an overview of the treatment of extensive disease. An additional section discusses the use of elective brain irradiation in small cell bronchogenic carcinoma.

THE MANAGEMENT OF CLINICAL STAGE I ENDOMETRIAL CARCINOMA

A retrospective analyses of 307 cases with clinical Stage I endometrial carcinoma was done in an attempt to determine the role of radiation therapy in the optimal treatment of this disease. A review of the modern literature with over 9000 cases served as a useful tool to corroborate inferences and conclusions. The present series has 155 patients (51%) treated with preoperative megavoltage external pelvic radiation with a variation in doses of less than 6%. Five‐year survival estimates (79%‐83%) in clinical Stage I endometrial carcinoma are similar among the several main treatment combination that are employed; they become a useless parameter for any comparison. The pelvic failure rate constitutes a more useful guideline in assessing the most adequate therapy. The pathologic grade of the tumor is the main prognosticator in endometrial carcinoma. Intimately related to the tumor grade is the depth of myometrial invasion of the carcinoma. The size of the uterus and/or its cavity carry less prognostic significance than traditionally thought. For grade I lesions, there is little error in diagnosis, few pelvic failures and excellent survival (96%); they could be approached with initial surgery and postoperative radiation reserved for selected patients. For grade 2 tumors, the error in diagnosis and the failure rate increases with an overall survival of 87%. For grade 3 tumors, the error in diagnosis and failure rates are quite high with a 5 year survival of only 70%. Preoperative radiation, especially external beam therapy, is suggested for grades 2 and 3 Stage I tumors. The use of this treatment modality yields only 3% pelvic failure and an overall 5 year survival of almost 90%.

Endometrial carcinoma: Analysis of failures with special emphasis on the use of initial preoperative external pelvic radiation

Abstract This paper analyzes in detail a total of 75 failures occurring among 364 patients with endometrial carcinoma. Approximately one half of all patients received preoperative external pelvic radiation for initial treatment. One-half of all failures occurred in the pelvis, the other half in distant sites. Failures in endometrial carcinoma are associated with a higher pathologic grade and clinical stage. An increase in grade and/or stage is associated with a higher incidence and depth of myometrial invasion and pelvic nodal involvement. The use of preoperative external pelvic radiation has eliminated vaginal recurrences in clinical Stages I and If and has reduced the overall incidence of pelvic failures to only 3%. Approximately one-third of patients with failures localized to the pelvis after initial surgery can be salvaged by the use of external pelvic radiation. Patients with distant metastases benefit significantly from therapy other than supportive measures.

Radiation therapy for tumors of the pineal region

Abstract This manuscript presents the results of treatment for 25 patients with tumors in the pineal region and related ectopic locations. Twenty two were treated with radiation therapy. Twelve patients died; autopsies were performed on 11 which allowed for a definition of the spread and failure patterns. A review of the literature with over 100 case studies was added to the present series in order to increase the significance of comparisons in failure rates by irradiated brain volumes and total doses delivered. The overall median survival for these patients was 10 years; at 5 years, 63% were alive and free of disease. The data suggests more than a 50% probability for tumors in these locations to extend by direct contiguity or by seeding along the third ventricle into adjacent supratentorial and infratentorial structures. The apparent tendency of some of these neoplasms to spread extensively within the cranium indicates the potential value of whole brain irradiation or at least the use of fields that are sufficiently large to encompass the entire ventricular system. In contrast, the low probability (≤5 10%) of metastasis to the spinal cord after adequate primary therapy does not indicate the routine use of elective spinal irradiation.