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Biomedical subjects

T E Moon

Publications and source records attributed to T E Moon.

At least 109 records · Page 6Linked to original sources

Histopathologic review of lymphoma cases from the Southwest Oncology Group.

Lymphoma Pathology Panel and Repository (LPPR) review of pathologic material from 354 patients registered on Southwest Oncology Group clinical trials substantiated the diagnosis of Hodgkin's disease (Lukes-Butler classification) in 175 (94%) of 186 cases and the diagnosis of non-Hodgkin's lymphoma (Rappaport classification) in 162 (96%) of 168 cases. However, complete agreement (type and subtype) between institutional and LPPR review diagnoses was found in only 66% of confirmed cases of Hodgkin's disease and in only 58% of confirmed cases of non-Hodgkin's lymphomas. In 26 (16%) of 160 cases of non-Hodgkin's lymphoma, the initial interpretation of pattern (nodular vs diffuse) differed: 20 (25%) of 81 nodular lymphomas had been thought to be diffuse and 6 (8%) of 79 diffuse lymphomas had been diagnosed as nodular. The frequency with which initial diagnoses were confirmed on LPPR review was highest for three subtypes of lymphoma: nodular sclerosis Hodgkin's disease (88%), diffuse histiocytic lymphoma (86%), and nodular lymphocytic lymphoma (78%); rates of confirmation for all other subtypes ranged from 13-50%. The results of this analysis emphasize the necessity of having pathologic review of all cases entered on major lymphoma studies so that comparability of cases can be assured and the results of those studies placed in proper perspective.

Hodgkin Disease↗

Dose response evaluation of adriamycin in human neoplasia.

Because patients treated with 60-90 mg/m2 every three to four weeks reach cardiotoxic doses of 550 mg/m2 within 36 weeks, prolonged treatment with Adriamycin is limited. The purpose of this study was to determine whether lower doses could be given over longer periods without loss of efficacy. Good risk patients treated with 75, 60, or 45 mg/m2 had remission rates of 25, 27, and 19%; poor risk patients treated with 50 and 25 mg/m2 had remission rates of 16 and 12% respectively. Although a dose response was identified, there were no statistically significant differences in remission rates, durations of remission, or toxicities in the dose schedules studied. Irreversible congestive heart failure occurred in five patients with cumulative doses of 240-390 mg/m2. Unless rapid remission induction is urgent, we recommend 60 mg/m2 X four doses and measurement of myocardial function if treatment is to continue.

Adult↗

Prognosis in children with metastatic rhabdomyosarcoma.

Distant metastases were documented in 83 of 161 children with rhabdomyosarcoma seen between 1953 and 1974. Of these, 31 had metastases at diagnosis (Group IV) and 7 were noted to have metastases only at autopsy. Only 6 are living with no evidence of disease activity at 6, 20, 77, 85, 105, and 112 months from time of metastasis. One child is living with disease at 98 months. Late deaths occurred in 2 at 31 and 41 months after metastasis. Sixty-four of the 66 deaths occurred within 24 months. The median durations of life after metastasis were less than 9 months in Groups I and II patients, less than 6 months in Group III patients, and about 12 months in 31 Group IV patients. The median time to metastasis in Groups I, II, and III patients was 9 months.

Adolescent↗

Curability of non-Hodgkin's lymphomas.

The relapse rates of patients with malignant lymphoma have been analyzed in relation to the number of patients in complete remission (CR) at yearly intervals after the onset of therapy. Several different patterns of relapse have been identified. Patients in CR from nodular poorly differentiated lymphocytic lymphoma have a low rate of recurrent disease (14%) during the first year of treatment but rates of relapse in succeeding years have not decreased. Patients with diffuse poorly differentiated lymphocytic lymphoma have a significantly higher relapse rate during the first year of treatment (33%). However, remission duration curves suggest that the risk of relapse is decreasing with time. Patients with diffuse histiocytic lymphoma, who initially have the greatest risk of disease recurrence (42%), subsequently showed a significant fall in their rate of relapse. As many as 50% of these patients who attain a CR may have been cured of their disease. An analysis of CR duration curves may be used to determine the effective doubling time of various malignant diseases and to estimate cure rates within a few years after the onset of therapy.

Cell Division↗

Combination intrathecal therapy for meningeal leukemia: two versus three drugs.

The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three-agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p=0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously of sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.

Brain Neoplasms↗

Nabilone: a potent antiemetic cannabinol with minimal euphoria.

Nabilone is a cannabinol derivative which has potent central antiemetic effects in animals. We observed that the drug significantly reduced the nausea and vomiting induced by cancer chemotherapy in 10 of 13 patients who were refractory to conventional antiemetics. A dose-response effect was apparent. The drug was generally well-tolerated, although it also had sedative effects. Additionally, dizziness, decreased coordination and postural hypotension were observed in some patients. Euphoric effects of the agent were minimal at antiemetic dosage levels.

Adolescent↗

Chemotherapy of non-Hodgkin's lymphoma: 10 years' experience in the Southwest Oncology Group.

The Southwest Oncology Group (SWOG) has completed five studies of high-dose intermittent combination chemotherapy for the management of advanced (stage III and IV) non-Hodgkin's lymphoma involving 1143 patients from May 1966 to September 1974. Lack of uniform histopathologic interpretation precludes precise analysis of these data. Although there has been little change in complete response duration over the years of this study, there has been an overall improvement in response rate and survival though there is no statistically significant improvement in the best overall survival when compared to the Stanford experience in stage III and IV disease (1960-71). The response rate and survival in diffuse histiocytic lymphoma have improved since the first study. There is definite evidence of a plateau in the survival curve beyond 2 years. The percentage of survival at which the plateau appears has increased over the years to 40% in the most recent studies, and the survival is suggestively better than the Stanford experience (P = 0.09). Over the years there has been a distinct improvement in response rate and survival of patients with nodular lymphocytic lymphoma, although the best SWOG survival is no different than the Stanford experience (P = 0.36).

Bleomycin↗

Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma.

Combination chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone) and HOP (Adrimycin, vincristine, and prednisone, was used as treatment for patients with pathologically staged, advanced non-Hodgkin's lymphoma. Among 204 evaluable patients treated on CHOP there were 71% complete remissions with 92% overall responses. Among the 216 evaluable patients on HOP there were 61% complete remissions and 88% responses. Complete remission rates among patients with histiocytic lymphoma were comparable to those of patients with lymphocytic disease. Patients with nodular lymphoma had higher rates of complete remission than their counterparts with diffuse lymphoma. This was noted with both CHOP (78% vs. 67%) and HOP (67% vs. 60%) induction therapy. Rapid responses were common, as more than 14% of complete remissions and 66% of overall responses were achieved with the first course of treatment. Patients in complete remission have been maintained with either cyclophosphamide, vincristine, and prednisone (COP) or arabinosyl cytosine, vincristine, and prednisone (OAP). After 1 year, 86% of patients on COP and 80% on OAP are projected to be free of disease.

Cyclophosphamide↗

IgM levels and IgM-mediated immune responses in patients with acute hepatitis A, acute hepatitis B and chronic HB antigenaemia.

Immunoglobulin M (IgM) levels and their relationship to isohaemagglutinins, febrile agglutinins, sheep cell agglutinins, and rheumatoid factor were measured in patients with acute hepatitis A, acute hepatitis B, chronic hepatitis B antigenaemia, and normal control populations. Significant IgM elevations were observed in both types of acute hepatitis, but not in chronic hepatitis B antigenaemia. There was no correlation of the IgM level with either the prevalence or titre of any IgM-mediated immune response studied. These data suggest that the IgM elevations in both types of hepatitis may reflect virus-specific IgM synthesis.

Agglutinins↗

Role of DTIC (NSC-45388) in the chemotherapy of sarcomas.

DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.

Clinical Trials as Topic↗

A statistical model of the dynamics of a mosquito vector (Culex tarsalis) population.

A model of the dynamics of a mosquito Culex tarsalis is derived that includes the life states through which the mosquito proceeds. Transition probabilities from one state (egg, larva, pupa and adult) to another are derived and they depend on the duration of stay and mortality in each state. A formula is derived for the expected number of mosquitoes alive at any time during the spring or summer. This formula depends on the number of eggs oviposited and the transition probabilities. Data are used to estimate the parameters and to illustrate the usefulness of this model in examining the effect of changes in mosquito survival on the dynamics of the population.

Animals↗

Familial clustering of hepatitis B surface antigen among Panamanian Indians.

Several authors have suggested that the host genome determines the occurrence of chronic HBS Ag (hepatitis B surface antigen). In attempts to evaluate this possibility, total infection rate and the combined frequencies of HBS Ag and antibody to HBS Ag and radioimmunoprecipitation to measure antibody to HBS Ag, we tested sera from 255 Panamanian Guaymi Indians. They represented 48 families and 32 living units. Clusters of chronically antigenemic individuals were found in families. Clusters of infection were not found in families or living units. Differences in family composition (age and sex) did not explain the increased occurrence of HGS Ag. These findings support the hypothesis that some humans have an inherited susceptibility to chronic infection with hepatitis B virus after exposure.

Adolescent↗

Clinical trials of cancer prevention agents: true versus observed prevention effect.

Important considerations in the design and conduct of cancer and other long-term prevention trials include intervention compliance and frequency of events during follow-up. Each of these can produce observed proportions of events for control and test groups that differ less than anticipated. Methods and approximate 'rules of thumb' are presented that relate power and sample size to the impact of compliance and latent intervention effect. Results are based upon specific modifications in well-known formulae that reflect long-term prevention trials. Data from an ongoing cancer prevention trial illustrate the methods. Compliance was estimated accurately using the low cost capsule count method.

Antineoplastic Agents↗

Design and analysis of the ESVEM Trial.

Inadequate understanding of the design and statistical approach of a clinical trial and the failure to recognize subjective aspects of the analysis often result in misinterpretation of trial results. This is exacerbated by the push to shorten publications and the wish for a simple message that summarizes the outcome of the trial. The purpose of this review is to critically review the design and statistical analyses of the results, to evaluate the assumptions underlying the statistical tests, and to examine the results of exploratory analysis on the interpretation of major findings of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. The trial was unusual because its primary objective was to compare testing methods instead of treatments. This necessitated using a subset of the original randomized groups for sensible analysis of the clinical question. Nevertheless, the two groups appeared to be well balanced. The absence of a difference in outcome could be verified by several analyses. In addition, confidence intervals were narrow, indicating the high precision and reliability of the findings. However, the comparison of antiarrhythmic drugs is problematic because the trial was not designed to address this issue. There were differences in the distribution of clinical characteristics between the groups who received different antiarrhythmic drugs. Nevertheless, using both univariate analyses and a variety of adjustments for important prognostic variables, treatment with sotalol appeared to be a significant predictor of reduced arrhythmia recurrence, and sotalol was consistently associated with a trend for nearly a 50% reduction in sudden death and all-cause mortality as compared with the other drugs administered in the trial. In conclusion, the ESVEM trial raises a number of interesting and instructive issues about clinical trial design and analysis.

Anti-Arrhythmia Agents↗