Michael L. Feldstein

Radiation and High-Dose Metronidazole in Supratentorial Glioblastomas

We used high-dose metronidazole, an in vitro and in vivo specific radiosensitizer of hypoxic cells, in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas. Thirty-six patients were stratified according to functional level and randomly allocated within two weeks of operation to one of two therapeutic groups: Group 1, radiation alone; and Group 2, radiation as in Group 1 but with high-dose metronidazole. We examined survival with the Kaplan-Meier probability plot and non-parametric tests. Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death (P = 0.02). This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant. Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors.

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.

Quality of life research in oncology. Past achievements and future priorities.

The status of quality of life research in oncology is assessed, and priorities for future research with regard to conceptual and theoretical developments, focus and content of research, research designs and practical strategies for research implementation, and transferring information to clinical practice and medical policy decision‐making are identified. There is general agreement that quality of life is a subjective and multidimensional construct, yet comprehensive theoretical models have not been developed and applied fully. We recommend that future research be based on conceptual models that explicate the interrelationships among quality of life domains throughout the stages of cancer care. These models, and the longitudinal research that follows from them, should attend specifically to cross‐class and cross‐cultural issues to avoid overgeneralization from theory and research that are based largely on the views of the majority culture. We encourage the inclusion of this theory‐based quality of life assessment as a standard component of clinical trials. Success in this endeavor will require additional standardization of quality of life measures for use across a range of cancer patient populations, including the development of age‐specific norms and instruments designed to assess the entire family system.

A randomized clinical trial of alprazolam versus progressive muscle relaxation in cancer patients with anxiety and depressive symptoms.

A randomized nonblinded study was performed in three cancer centers to test over a 10-day period the efficacy of (1) a triazolobenzodiazepine, alprazolam, 0.5 mg three times a day and (2) use of a behavioral technique in which patients were trained in progressive muscle relaxation at an initial session with a behavioral psychologist and then asked to listen at home to an audiotape of the session three times a day. Of 147 cancer patients who met entry levels of distress and completed the study, uncontrolled for site or disease stage, 70 were randomized to drug, 77 to relaxation. Four measures of anxiety and depression were used: Covi, Raskin, Affects Balance, and Symptoms Checklist-90 (SCL-90). Results showed that both treatment arms resulted in significant (P less than .001) decrease in observer and patient-reported anxious and depressed mood symptoms. Although both treatment arms were effective, patients receiving the drug showed a slightly more rapid decrease in anxiety and greater reduction of depressi...

Fundamental dilemmas of the randomized clinical trial process: results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators.

PURPOSEnWe studied oncologists attitudes and behavior with regard to their participation in randomized clinical trials.nnnMETHODSnWe surveyed the 1,737 physician members of the Eastern Cooperative Oncology Group (ECOG) using the Physician Orientation Profile (POP), a self-administered mailed questionnaire. A response rate of 86% was achieved (1,485 of 1,737); each physicians actual patient accrual was recorded.nnnRESULTSnAll respondents indicated that they had a systematic pattern of patient preselection for entry onto trials beyond the formal inclusion/exclusion trial criteria. Eighty-nine percent stated that improving patient quality of life rather than prolonging survival was more personally satisfying. Sixty-two percent did not enter a single patient during the 12-month period following the survey, while 10% entered 80% of all patients during that time. Physicians overestimated their accrual rate by a factor of 6. Eighty-three percent defined randomization and adherence to trial protocol as a serious challenge to their ability to make individualized treatment decisions.nnnCONCLUSIONnThis study raises questions regarding the following: (1) the perceived generalizability of trial findings, (2) the role of end points other than survival for clinical trials, (3) the consequences of physician overestimation of patient accrual, and (4) the impact of randomized trials on the behavior of clinicians. Further investigation into these critical issues will provide meaningful recommendations to enhance the future design, implementation, and conduct of randomized clinical trials in cancer.

The Relationship of Psychological Distress, Extent of Disease, and Performance Status in Patients With Lung Cancer

This study examined the association between two primary covariates, extent of disease (ED) and performance status rating (PSR), and the outcome of psychological distress in patients with small cell carcinoma of the lung. Patients were studied at the time of entry onto one of three Cancer and Leukemia Group B (CALGB) protocols: 7781 (N = 165) and 8083 (N = 139) for limited disease; and 7782 (N = 151) for extensive disease. Besides ED (limited versus extensive), a four‐point rating of PSR was obtained. Psychological distress was measured by the standardized Profile of Mood States (POMS). Gender, age, marital status, education, PSR, ED and two relevant interaction terms (PSR X ED; gender X ED) were analyzed using multiple linear and hierarchical regressions. Of the six main variables, gender and PSR had significant association with POMS total mood disturbance, a summary score for POMS emotional subscales, and most of the individual subscales. The PSR X ED interaction provided a rationale for testing a new regression model in which PSR and ED were combined into a single index of impairment. The final index resulted in five levels of physical impairment which bear an approximately linear relationship to increasing levels of distress (Overall regression, P < 0.001). These data suggest that PSR is an important factor in modelling POMS distress at both levels of ED, and that ED becomes an important factor with poorer performance status only.

A survey of psychotropic drug prescriptions in an oncology population

The present study examined the prescription practices concerning psychotropic drugs in 5 major oncology centers over a 6 month period. During the survey period 1579 patients were admitted to the collaborating institutions, and 51% of them were prescribed at least one psychotropic medication. Hypnotics were the most frequently prescribed drugs, accounting for 48% of total prescriptions, followed by anti‐psychotics at 26% and anti‐anxiety agents at 25%. Anti‐depressant drugs accounted for only 1% of psychotropic prescriptions. Analysis of prescription rationales revealed that 44% of the psychotropic prescriptions were written for sleep, while 25% were given for nausea and vomiting; approximately 17% were attributed to psychological distress, and 12% were associated with diagnostic medical procedures. The overall rate of prescription was approximately 2 psychotropic drugs per patient per admission, with only 2% of prescriptions resulting in chart‐documented side effects. At the level of individual compounds, 3 distinct drugs accounted for 72% of total prescriptions—flurazepam (33%), prochlorperazine (21%), and diazepam (17%).

The relative importance of estrogen receptor analysis as a prognostic factor for recurrence or response to chemotherapy in women with breast cancer

The value of estrogen receptor (ER) analysis in primary breast cancer samples as a potential prognostic factor was examined in three clinical situations: time to recurrence in patients with no therapy after mastectomy, failure of patients receiving adjuvant therapy, and response of advanced disease patients to cytotoxic chemotherapy. Other prognostic factors analyzed were menopausal and nodal status. In none of these clinical settings were we able to demonstrate the usefulness of ER status as a prognosticator of the disease course or its response to therapy.

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.